Headache Currents

Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science

Eric P. Baron DO,

Corresponding Author

Eric P. Baron DO

[email protected]

Department of Neurology, Center for Neurological Restoration - Headache and Chronic Pain Medicine, Cleveland Clinic Neurological Institute, Cleveland, OH, 44195 USA

Address all correspondence to E.P. Baron, 10524 Euclid Avenue, C21, Cleveland, OH, 44195, USA, email:[email protected]Search for more papers by this author

Eric P. Baron DO,

Corresponding Author

Eric P. Baron DO

[email protected]

Department of Neurology, Center for Neurological Restoration - Headache and Chronic Pain Medicine, Cleveland Clinic Neurological Institute, Cleveland, OH, 44195 USA

Address all correspondence to E.P. Baron, 10524 Euclid Avenue, C21, Cleveland, OH, 44195, USA, email:[email protected]Search for more papers by this author

First published: 27 August 2018

https://doi.org/10.1111/head.13345

Citations: 151

Conflict of Interest: None.

Read the full text

About

PDF

Tools

Share a link

Email
Facebook
Twitter
LinkedIn
Reddit
Wechat

Abstract

Background

Comprehensive literature reviews of historical perspectives and evidence supporting cannabis/cannabinoids in the treatment of pain, including migraine and headache, with associated neurobiological mechanisms of pain modulation have been well described. Most of the existing literature reports on the cannabinoids Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), or cannabis in general. There are many cannabis strains that vary widely in the composition of cannabinoids, terpenes, flavonoids, and other compounds. These components work synergistically to produce wide variations in benefits, side effects, and strain characteristics. Knowledge of the individual medicinal properties of the cannabinoids, terpenes, and flavonoids is necessary to cross-breed strains to obtain optimal standardized synergistic compositions. This will enable targeting individual symptoms and/or diseases, including migraine, headache, and pain.

Objective

Review the medical literature for the use of cannabis/cannabinoids in the treatment of migraine, headache, facial pain, and other chronic pain syndromes, and for supporting evidence of a potential role in combatting the opioid epidemic. Review the medical literature involving major and minor cannabinoids, primary and secondary terpenes, and flavonoids that underlie the synergistic entourage effects of cannabis. Summarize the individual medicinal benefits of these substances, including analgesic and anti-inflammatory properties.

Conclusion

There is accumulating evidence for various therapeutic benefits of cannabis/cannabinoids, especially in the treatment of pain, which may also apply to the treatment of migraine and headache. There is also supporting evidence that cannabis may assist in opioid detoxification and weaning, thus making it a potential weapon in battling the opioid epidemic. Cannabis science is a rapidly evolving medical sector and industry with increasingly regulated production standards. Further research is anticipated to optimize breeding of strain-specific synergistic ratios of cannabinoids, terpenes, and other phytochemicals for predictable user effects, characteristics, and improved symptom and disease-targeted therapies.

REFERENCES

1Robbins MS, Lipton RB. The epidemiology of primary headache disorders. Semin Neurol. 2010; 30: 107-119.
10.1055/s-0030-1249220
PubMedWeb of Science®Google Scholar
2GBD 2015 Neurological Disorders Collaborator Group. Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol. 2017; 16: 877-897.
10.1016/S1474-4422(17)30299-5
PubMedWeb of Science®Google Scholar
3Steiner TJ, Birbeck GL, Jensen RH, Katsarava Z, Stovner LJ, Martelletti P. Headache disorders are third cause of disability worldwide. J Headache Pain. 2015; 16: 58.
10.1186/s10194-015-0544-2
PubMedWeb of Science®Google Scholar
4Stewart WF, Ricci JA, Chee E, Morganstein D, Lipton R. Lost productive time and cost due to common pain conditions in the US workforce. JAMA. 2003; 290: 2443-2454.
10.1001/jama.290.18.2443
CASPubMedWeb of Science®Google Scholar
5Rice AS, Smith BH, Blyth FM. Pain and the global burden of disease. Pain. 2016; 157: 791-796.
10.1097/j.pain.0000000000000454
PubMedWeb of Science®Google Scholar
6Evers S, Afra J, Frese A, European Federation of Neurological Societies, et al. EFNS guideline on the drug treatment of migraine–revised report of an EFNS task force. Eur J Neurol. 2009; 16: 968-981.
10.1111/j.1468-1331.2009.02748.x
CASPubMedWeb of Science®Google Scholar
7Holland S, Silberstein SD, Freitag F, Dodick DW, Argoff C, Ashman E. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012; 78: 1346-1353.
10.1212/WNL.0b013e3182535d0c
CASPubMedWeb of Science®Google Scholar
8Diener HC, Limmroth V. Advances in pharmacological treatment of migraine. Expert Opin Investig Drugs. 2001; 10: 1831-1845.
10.1517/13543784.10.10.1831
CASPubMedWeb of Science®Google Scholar
9Ferrari MD, Goadsby PJ, Roon KI, Lipton RB. Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalalgia. 2002; 22: 633-658.
10.1046/j.1468-2982.2002.00404.x
CASPubMedWeb of Science®Google Scholar
10Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet. 2001; 358: 1668-1675.
10.1016/S0140-6736(01)06711-3
CASPubMedWeb of Science®Google Scholar
11Baron EP. Comprehensive review of medicinal marijuana, cannabinoids, and therapeutic implications in medicine and headache: What a long strange trip it's been …. Headache. 2015; 55: 885-916.
10.1111/head.12570
PubMedWeb of Science®Google Scholar
12Lochte BC, Beletsky A, Samuel NK, Grant I. The use of cannabis for headache disorders. Cannabis Cannabinoid Res. 2017; 2: 61-71.
10.1089/can.2016.0033
CASPubMedGoogle Scholar
13Russo E. Hemp for headache: an in-depth historical and scientific review of cannabis in migraine treatment. J Cannabis Ther. 2001; 1: 21-92.
10.1300/J175v01n02_04
Google Scholar
14Russo E. Cannabis for migraine treatment: the once and future prescription? An historical and scientific review. Pain. 1998; 76: 3-8.
10.1016/S0304-3959(98)00033-5
CASPubMedWeb of Science®Google Scholar
15Akerman S, Holland PR, Lasalandra MP, Goadsby PJ. Endocannabinoids in the brainstem modulate dural trigeminovascular nociceptive traffic via CB1 and “triptan” receptors: implications in migraine. J Neurosci. 2013; 33: 14869-14877.
10.1523/JNEUROSCI.0943-13.2013
CASPubMedWeb of Science®Google Scholar
16Akerman S, Holland PR, Goadsby PJ. Cannabinoid (CB1) receptor activation inhibits trigeminovascular neurons. J Pharmacol Exp Ther. 2007; 320: 64-71.
10.1124/jpet.106.106971
CASPubMedWeb of Science®Google Scholar
17Akerman S, Kaube H, Goadsby PJ. Anandamide is able to inhibit trigeminal neurons using an in vivo model of trigeminovascular-mediated nociception. J Pharmacol Exp Ther. 2004; 309: 56-63.
10.1124/jpet.103.059808
CASPubMedWeb of Science®Google Scholar
18Woodhams SG, Chapman V, Finn DP, Hohmann AG, Neugebauer V. The cannabinoid system and pain. Neuropharmacology. 2017; 124: 105-120.
10.1016/j.neuropharm.2017.06.015
CASPubMedWeb of Science®Google Scholar
19Woodhams SG, Sagar DR, Burston JJ, Chapman V. The role of the endocannabinoid system in pain. Handb Exp Pharmacol. 2015; 227: 119-143.
10.1007/978-3-662-46450-2_7
CASPubMedGoogle Scholar
20Ben-Shabat S, Fride E, Sheskin T, et al. An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol. 1998; 353: 23-31.
10.1016/S0014-2999(98)00392-6
CASPubMedWeb of Science®Google Scholar
21Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011; 163: 1344-1364.
10.1111/j.1476-5381.2011.01238.x
CASPubMedWeb of Science®Google Scholar
22Moulin D, Boulanger A, Clark AJ, Canadian Pain Society, et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag. 2014; 19: 328-335.
10.1155/2014/754693
PubMedWeb of Science®Google Scholar
23 Committee of the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids. The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press; 2017.

Google Scholar
24Hazekamp A, Heerdink ER. The prevalence and incidence of medicinal cannabis on prescription in The Netherlands. Eur J Clin Pharmacol. 2013; 69: 1575-1580.
10.1007/s00228-013-1503-y
PubMedWeb of Science®Google Scholar
25Ilgen MA, Bohnert K, Kleinberg F, et al. Characteristics of adults seeking medical marijuana certification. Drug Alcohol Depend. 2013; 132: 654-659.
10.1016/j.drugalcdep.2013.04.019
PubMedWeb of Science®Google Scholar
26 Medical Marijuana Registry Statistics. Colorado Department of Health and Environment. (Accessed December 1, 2017, at https://www.colorado.gov/pacific/cdphe/medicalmarijuana).

Google Scholar
27 Medical Cannabis Registry. Minnesota Department of Health. (Accessed December 1, 2017, at http://www.health.state.mn.us/topics/cannabis/registry.html).

Google Scholar
28 Medical cannabis patient registry program. Illinois Department of Public Health. (Accessed December 1, 2017, at http://www.dph.illinois.gov/topics-services/prevention-wellness/medical-cannabis).

Google Scholar
29 Medical cannabis program. Hawaii Department of Health. (Accessed December 1, 2017, at http://health.hawaii.gov/medicalcannabis/).

Google Scholar
30 Oregon Medical Marijuana Program Statistics. Oregon Health Authority. (Accessed December 1, 2017, at http://www.oregon.gov/oha/PH/DISEASESCONDITIONS/CHRONICDISEASE/MEDICALMARIJUANAPROGRAM/Pages/data.aspx).

Google Scholar
31 Medicinal Marijuana Program. State of New Jersey Department of Health. (Accessed December 1, 2017, at http://www.nj.gov/health/medicalmarijuana/).

Google Scholar
32 Medical Marijuana - Reports. Arizona Department of Health Services. (Accessed December 1, 2017, at http://www.azdhs.gov/licensing/medical-marijuana/index.php#reports).

Google Scholar
33 Medical Marijuana Patient Cardholder Registry Monthly Reports. Nevada Division of Public and Behavioral Health (DPBH). (Accessed December 1, 2017, at http://dpbh.nv.gov/Reg/MM-Patient-Cardholder-Registry/dta/Monthly_Reports/Medical_Marijuana_Cardholder_Registry_-_Monthly_Reports/).

Google Scholar
34 Michigan Medical Marihuana Act Statistical Reports. The Michigan Department of Licensing and Regulatory Affairs, Bureau of Medical Marihuana Regulation. (Accessed December 1, 2017; at http://www.michigan.gov/lara/0,4601,7-154-79571_82631-448788-,00.html).

Google Scholar
35Aggarwal SK. Cannabinergic pain medicine: a concise clinical primer and survey of randomized-controlled trial results. Clin J Pain. 2013; 29: 162-171.
10.1097/AJP.0b013e31824c5e4c
PubMedWeb of Science®Google Scholar
36Serrano A, Parsons LH. Endocannabinoid influence in drug reinforcement, dependence and addiction-related behaviors. Pharmacol Ther. 2011; 132: 215-241.
10.1016/j.pharmthera.2011.06.005
CASPubMedWeb of Science®Google Scholar
37Rodriguez de Fonseca F, Del Arco I, Bermudez-Silva FJ, Bilbao A, Cippitelli A, Navarro M. The endocannabinoid system: physiology and pharmacology. Alcohol Alcohol. 2005; 40: 2-14.
10.1093/alcalc/agh110
CASPubMedWeb of Science®Google Scholar
38Maccarrone M, Gasperi V, Catani MV, et al. The endocannabinoid system and its relevance for nutrition. Annu Rev Nutr. 2010; 30: 423-440.
10.1146/annurev.nutr.012809.104701
CASPubMedWeb of Science®Google Scholar
39Greco R, Gasperi V, Maccarrone M, Tassorelli C. The endocannabinoid system and migraine. Exp Neurol. 2010; 224: 85-91.
10.1016/j.expneurol.2010.03.029
CASPubMedWeb of Science®Google Scholar
40Howlett AC. Efficacy in CB1 receptor-mediated signal transduction. Br J Pharmacol. 2004; 142: 1209-1218.
10.1038/sj.bjp.0705881
CASPubMedWeb of Science®Google Scholar
41Mallat A, Teixeira-Clerc F, Deveaux V, Manin S, Lotersztajn S. The endocannabinoid system as a key mediator during liver diseases: new insights and therapeutic openings. Br J Pharmacol. 2011; 163: 1432-1440.
10.1111/j.1476-5381.2011.01397.x
CASPubMedWeb of Science®Google Scholar
42Galve-Roperh I, Rueda D, Gomez del Pulgar T, Velasco G, Guzman M. Mechanism of extracellular signal-regulated kinase activation by the CB(1) cannabinoid receptor. Mol Pharmacol. 2002; 62: 1385-1392.
10.1124/mol.62.6.1385
CASPubMedWeb of Science®Google Scholar
43Ryberg E, Larsson N, Sjogren S, et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. 2007; 152: 1092-1101.
10.1038/sj.bjp.0707460
CASPubMedWeb of Science®Google Scholar
44De Petrocellis L, Di Marzo V. An introduction to the endocannabinoid system: from the early to the latest concepts. Best Pract Res Clin Endocrinol Metab. 2009; 23: 1-15.
10.1016/j.beem.2008.10.013
CASPubMedWeb of Science®Google Scholar
45Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992; 258: 1946-1949.
10.1126/science.1470919
CASPubMedWeb of Science®Google Scholar
46Battista N, Di Tommaso M, Bari M, Maccarrone M. The endocannabinoid system: an overview. Front Behav Neurosci. 2012; 6: 9.
10.3389/fnbeh.2012.00009
CASPubMedWeb of Science®Google Scholar
47Di Marzo V, Piscitelli F, Mechoulam R. Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes. Handb Exp Pharmacol. 2011;(203): 75-104.
10.1007/978-3-642-17214-4_4
PubMedGoogle Scholar
48Di Marzo V, Petrocellis LD. Plant, synthetic, and endogenous cannabinoids in medicine. Annu Rev Med. 2006; 57: 553-574.
10.1146/annurev.med.57.011205.135648
CASPubMedWeb of Science®Google Scholar
49Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008; 153: 199-215.
10.1038/sj.bjp.0707442
CASPubMedWeb of Science®Google Scholar
50Guindon J, Hohmann AG. The endocannabinoid system and pain. CNS Neurol Disord Drug Targets. 2009; 8: 403-421.
10.2174/187152709789824660
CASPubMedWeb of Science®Google Scholar
51Guindon J, Beaulieu P. The role of the endogenous cannabinoid system in peripheral analgesia. Curr Mol Pharmacol. 2009; 2: 134-139.
10.2174/1874467210902010134
CASPubMedGoogle Scholar
52Kraft B. Is there any clinically relevant cannabinoid-induced analgesia?. Pharmacology. 2012; 89: 237-246.
10.1159/000337376
CASPubMedWeb of Science®Google Scholar
53Ramikie TS, Nyilas R, Bluett RJ, et al. Multiple mechanistically distinct modes of endocannabinoid mobilization at central amygdala glutamatergic synapses. Neuron. 2014; 81: 1111-1125.
10.1016/j.neuron.2014.01.012
CASPubMedWeb of Science®Google Scholar
54Grant I, Atkinson JH, Gouaux B, Wilsey B. Medical marijuana: clearing away the smoke. Open Neurol J. 2012; 6: 18-25.
10.2174/1874205X01206010018
PubMedGoogle Scholar
55Pertwee RG, Howlett AC, Abood ME, et al. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB(1) and CB(2). Pharmacol Rev. 2010; 62: 588-631.
10.1124/pr.110.003004
CASPubMedWeb of Science®Google Scholar
56Katona I, Freund TF. Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med. 2008; 14: 923-930.
10.1038/nm.f.1869
CASPubMedWeb of Science®Google Scholar
57Raichlen DA, Foster AD, Gerdeman GL, Seillier A, Giuffrida A. Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the 'runner's high'. J Exp Biol. 2012; 215: 1331-1336.
10.1242/jeb.063677
CASPubMedWeb of Science®Google Scholar
58Iversen L. Cannabis and the brain. Brain. 2003; 126: 1252-1270.
10.1093/brain/awg143
PubMedWeb of Science®Google Scholar
59Napchan U, Buse DC, Loder EW. The use of marijuana or synthetic cannabinoids for the treatment of headache. Headache. 2011; 51: 502-505.
10.1111/j.1526-4610.2011.01848.x
PubMedWeb of Science®Google Scholar
60Mackie K. Signaling via CNS cannabinoid receptors. Mol Cell Endocrinol. 2008; 286: S60-S65.
10.1016/j.mce.2008.01.022
CASPubMedWeb of Science®Google Scholar
61Klein TW, Cabral GA. Cannabinoid-induced immune suppression and modulation of antigen-presenting cells. J Neuroimmune Pharmacol. 2006; 1: 50-64.
10.1007/s11481-005-9007-x
PubMedWeb of Science®Google Scholar
62Koppel BS, Brust JC, Fife T, et al. Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014; 82: 1556-1563.
10.1212/WNL.0000000000000363
PubMedWeb of Science®Google Scholar
63Zhang HY, Gao M, Liu QR, et al. Cannabinoid CB2 receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice. Proc Natl Acad Sci U S A. 2014; 111: E5007-E5015.
10.1073/pnas.1413210111
CASPubMedWeb of Science®Google Scholar
64Zhang HY, Gao M, Shen H, et al. Expression of functional cannabinoid CB2 receptor in VTA dopamine neurons in rats. Addict Biol. 2017; 22: 752-765.
10.1111/adb.12367
CASPubMedWeb of Science®Google Scholar
65Noyes R, Jr, Baram DA. Cannabis analgesia. Compr Psychiatry. 1974; 15: 531-535.
10.1016/0010-440X(74)90008-X
PubMedWeb of Science®Google Scholar
66Schnelle M, Grotenhermen F, Reif M, Gorter RW. Results of a standardized survey on the medical use of cannabis products in the German-speaking area. Forsch Komplementarmed. 1999; 6: 28-36.
10.1159/000057154
PubMedWeb of Science®Google Scholar
67Mackenzie S. Remarks on the value of Indian hemp in the treatment of a certain type of headache. Br Med J. 1887; 1: 97-98.
10.1136/bmj.1.1359.97
Google Scholar
68Nunberg H, Kilmer B, Pacula RL, Burgdorf J. An analysis of applicants presenting to a medical marijuana specialty practice in California. J Drug Policy Anal. 2011; 4. www.ncbi.nlm.nih.

PubMedGoogle Scholar
69el-Mallakh RS. Marijuana and migraine. Headache. 1987; 27: 442-443.
10.1111/j.1526-4610.1987.hed2708442.x
CASPubMedWeb of Science®Google Scholar
70Grinspoon L, Bakalar JB. Marihuana: The Forbidden Medicine. New Haven, CT: Yale University; 1993.

Google Scholar
71Volfe Z, Dvilansky A, Nathan I. Cannabinoids block release of serotonin from platelets induced by plasma from migraine patients. Int J Clin Pharmacol Res. 1985; 5: 243-246.

CASPubMedWeb of Science®Google Scholar
72el-Mallakh RS. Migraine headaches and drug abuse. South Med J. 1989; 82: 805.
10.1097/00007611-198906000-00041
CASPubMedWeb of Science®Google Scholar
73Gorji A. Pharmacological treatment of headache using traditional Persian medicine. Trends Pharmacol Sci. 2003; 24: 331-334.
10.1016/S0165-6147(03)00164-0
CASPubMedWeb of Science®Google Scholar
74Rhyne DN, Anderson SL, Gedde M, Borgelt LM. Effects of medical marijuana on migraine headache frequency in an adult population. Pharmacotherapy. 2016; 36: 505-510.
10.1002/phar.1673
CASPubMedWeb of Science®Google Scholar
75Donovan M. On the physical and medicinal qualities of Indian hemp (Cannabis indica); with observations on the best mode of administration, and cases illustrative of its powers. Dublin J Med Sci. 1845; 26: 368-461.
10.1007/BF02971741
Google Scholar
76Reynolds JR. On some of the therapeutical uses of Indian hemp. Arch Med. 1868; 2: 154-160.

Google Scholar
77Waring EJ. Practical Therapeutics. Philadelphia: Lindsay & Blakiston; 1874.

Google Scholar
78Ringer S. A Handbook of Therapeutics. London: H.K. Lewis; 1886.

Google Scholar
79Hare HA. Clinical and physiological notes on the action of Cannabis indica. There Gaz. 1887; 11: 225-228.

Google Scholar
80Suckling C. On the therapeutic value of Indian hemp. Br Med J. 1891; 2: 11-12.

Google Scholar
81Mikuriya TH, Chronic Migraine Headache: five Cases Successfully Treated with Marinol and/or Illicit Cannabis. Berkeley, CA: Schaffer Library of Drug Policy; 1991.

Google Scholar
82Nicolodi M, Sandoval V, Terrine A, Therapeutic use of cannabinoids - Dose Finding, Effects, and Pilot Data of Effects in Chronic Migraine and Cluster Headache. Abstract presentation at 3rd Congress of the European Academy of Neurology (EAN), Amsterdam, 6/24/17.

Google Scholar
83Pini LA, Guerzoni S, Cainazzo MM, et al. Nabilone for the treatment of medication overuse headache: results of a preliminary double-blind, active-controlled, randomized trial. J Headache Pain. 2012; 13: 677-684.
10.1007/s10194-012-0490-1
CASPubMedWeb of Science®Google Scholar
84Robbins MS, Tarshish S, Solomon S, Grosberg BM. Cluster attacks responsive to recreational cannabis and dronabinol. Headache. 2009; 49: 914-916.
10.1111/j.1526-4610.2009.01344.x
PubMedWeb of Science®Google Scholar
85Leroux E, Taifas I, Valade D, Donnet A, Chagnon M, Ducros A. Use of cannabis among 139 cluster headache sufferers. Cephalalgia. 2013; 33: 208-213.
10.1177/0333102412468669
PubMedWeb of Science®Google Scholar
86Donnet A, Lanteri-Minet M, Guegan-Massardier E, Société Française d'Etude des Migraines et Céphalées (SFEMC), et al. Chronic cluster headache: a French clinical descriptive study. J Neurol Neurosurg Psychiatry. 2007; 78: 1354-1358.
10.1136/jnnp.2006.112037
CASPubMedWeb of Science®Google Scholar
87Evans RW, Ramadan NM. Are cannabis-based chemicals helpful in headache?. Headache. 2004; 44: 726-727.
10.1111/j.1526-4610.2004.04133C.x
PubMedWeb of Science®Google Scholar
88Consroe P, Musty R, Rein J, Tillery W, Pertwee R. The perceived effects of smoked cannabis on patients with multiple sclerosis. Eur Neurol. 1997; 38: 44-48.
10.1159/000112901
CASPubMedWeb of Science®Google Scholar
89A, Multicenter Randomized, Double-blind, Parallel-group, Placebo-controlled, Efficacy, Safety and Tolerability Study of Dronabinol MDI in the Acute Treatment of Migraine Headache. ClinicalTrials.gov Identifier: NCT00123201. Global Clinical Director Solvay Pharmaceuticals. (Accessed December 15, 2017, at https://clinicaltrials.gov/ct2/show/study/NCT00123201).

Google Scholar
90Bigal ME, Lipton RB. Overuse of acute migraine medications and migraine chronification. Curr Pain Headache Rep. 2009; 13: 301-307.
10.1007/s11916-009-0048-3
PubMedWeb of Science®Google Scholar
91Ware MA, Wang T, Shapiro S, et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMA J. 2010; 182: E694-E701.
10.1503/cmaj.091414
PubMedWeb of Science®Google Scholar
92Ellis RJ, Toperoff W, Vaida F, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 2009; 34: 672-680.
10.1038/npp.2008.120
CASPubMedWeb of Science®Google Scholar
93Wilsey B, Marcotte T, Tsodikov A, et al. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain. 2008; 9: 506-521.
10.1016/j.jpain.2007.12.010
CASPubMedWeb of Science®Google Scholar
94Abrams DI, Jay CA, Shade SB, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007; 68: 515-521.
10.1212/01.wnl.0000253187.66183.9c
CASPubMedWeb of Science®Google Scholar
95Corey-Bloom J, Wolfson T, Gamst A, et al. Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. CMA J. 2012; 184: 1143-1150.
10.1503/cmaj.110837
PubMedWeb of Science®Google Scholar
96Wallace M, Schulteis G, Atkinson JH, et al. Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers. Anesthesiology. 2007; 107: 785-796.
10.1097/01.anes.0000286986.92475.b7
PubMedWeb of Science®Google Scholar
97Greenwald MK, Stitzer ML. Antinociceptive, subjective and behavioral effects of smoked marijuana in humans. Drug Alcohol Depend. 2000; 59: 261-275.
10.1016/S0376-8716(99)00128-3
CASPubMedWeb of Science®Google Scholar
98Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain. 2013; 14: 136-148.
10.1016/j.jpain.2012.10.009
CASPubMedWeb of Science®Google Scholar
99Abrams DI, Couey P, Shade SB, Kelly ME, Benowitz NL. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011; 90: 844-851.
10.1038/clpt.2011.188
CASPubMedWeb of Science®Google Scholar
100Eisenberg E, Ogintz M, Almog S. The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: a phase 1a study. J Pain Palliat Care Pharmacother. 2014; 28: 216-225.
10.3109/15360288.2014.941130
PubMedGoogle Scholar
101Ware MA, Wang T, Shapiro S, Collet JP. COMPASS study team. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). J Pain. 2015; 16: 1233-1242.
10.1016/j.jpain.2015.07.014
PubMedWeb of Science®Google Scholar
102Fiz J, Duran M, Capella D, Carbonell J, Farre M. Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life. PLoS One. 2011; 6: e18440.
10.1371/journal.pone.0018440
CASPubMedWeb of Science®Google Scholar
103Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain. 2007; 133: 210-220.
10.1016/j.pain.2007.08.028
CASPubMedWeb of Science®Google Scholar
104Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology. 2005; 65: 812-819.
10.1212/01.wnl.0000176753.45410.8b
PubMedWeb of Science®Google Scholar
105Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford). 2006; 45: 50-52.
10.1093/rheumatology/kei183
CASPubMedWeb of Science®Google Scholar
106Serpell M, Ratcliffe S, Hovorka J, et al. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. Eur J Pain. 2014; 18: 999-1012.
10.1002/j.1532-2149.2013.00445.x
CASPubMedWeb of Science®Google Scholar
107Rog DJ, Nurmikko TJ, Young CA. Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clin Ther. 2007; 29: 2068-2079.
10.1016/j.clinthera.2007.09.013
CASPubMedWeb of Science®Google Scholar
108Wade DT, Makela PM, House H, Bateman C, Robson P. Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis. Mult Scler. 2006; 12: 639-645.
10.1177/1352458505070618
CASPubMedWeb of Science®Google Scholar
109Portenoy RK, Ganae-Motan ED, Allende S, et al. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain. 2012; 13: 438-449.
10.1016/j.jpain.2012.01.003
CASPubMedWeb of Science®Google Scholar
110Notcutt W, Price M, Miller R, et al. Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 'N of 1' studies. Anaesthesia. 2004; 59: 440-452.
10.1111/j.1365-2044.2004.03674.x
CASPubMedWeb of Science®Google Scholar
111Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003; 17: 21-29.
10.1191/0269215503cr581oa
PubMedWeb of Science®Google Scholar
112Berman JS, Symonds C, Birch R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 2004; 112: 299-306.
10.1016/j.pain.2004.09.013
PubMedWeb of Science®Google Scholar
113Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage. 2010; 39: 167-179.
10.1016/j.jpainsymman.2009.06.008
PubMedWeb of Science®Google Scholar
114Langford RM, Mares J, Novotna A, et al. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. J Neurol. 2013; 260: 984-997.
10.1007/s00415-012-6739-4
CASPubMedWeb of Science®Google Scholar
115Zajicek JP, Hobart JC, Slade A, Barnes D, Mattison PG. MUSEC Research Group. Multiple sclerosis and extract of cannabis: results of the MUSEC trial. J Neurol Neurosurg Psychiatry. 2012; 83: 1125-1132.
10.1136/jnnp-2012-302468
PubMedWeb of Science®Google Scholar
116Holdcroft A, Maze M, Dore C, Tebbs S, Thompson S. A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management. Anesthesiology. 2006; 104: 1040-1046.
10.1097/00000542-200605000-00021
CASPubMedWeb of Science®Google Scholar
117Zajicek J, Fox P, Sanders H, UK MS Research Group, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet. 2003; 362: 1517-1526.
10.1016/S0140-6736(03)14738-1
CASPubMedWeb of Science®Google Scholar
118Narang S, Gibson D, Wasan AD, et al. Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. J Pain. 2008; 9: 254-264.
10.1016/j.jpain.2007.10.018
CASPubMedWeb of Science®Google Scholar
119Svendsen KB, Jensen TS, Bach FW. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ. 2004; 329: 253.
10.1136/bmj.38149.566979.AE
CASPubMedWeb of Science®Google Scholar
120Svendsen KB, Jensen TS, Bach FW. Effect of the synthetic cannabinoid dronabinol on central pain in patients with multiple sclerosis–secondary publication. Ugeskr Laeger. 2005; 167: 2772-2774.

PubMedGoogle Scholar
121Naef M, Curatolo M, Petersen-Felix S, Arendt-Nielsen L, Zbinden A, Brenneisen R. The analgesic effect of oral delta-9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions. Pain. 2003; 105: 79-88.
10.1016/S0304-3959(03)00163-5
CASPubMedWeb of Science®Google Scholar
122Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008; 9: 164-173.
10.1016/j.jpain.2007.09.002
CASPubMedWeb of Science®Google Scholar
123Wissel J, Haydn T, Muller J, et al. Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain: a double-blind placebo-controlled cross-over trial. J Neurol. 2006; 253: 1337-1341.
10.1007/s00415-006-0218-8
CASPubMedWeb of Science®Google Scholar
124Pinsger M, Schimetta W, Volc D, Hiermann E, Riederer F, Polz W. Benefits of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain–a randomized controlled trial. Wien Klin Wochenschr. 2006; 118: 327-335.
10.1007/s00508-006-0611-4
PubMedWeb of Science®Google Scholar
125Toth C, Mawani S, Brady S, et al. An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain. 2012; 153: 2073-2082.
10.1016/j.pain.2012.06.024
CASPubMedWeb of Science®Google Scholar
126Turcotte D, Doupe M, Torabi M, et al. Nabilone as an adjunctive to gabapentin for multiple sclerosis-induced neuropathic pain: a randomized controlled trial. Pain Med. 2015; 16: 149-159.
10.1111/pme.12569
CASPubMedWeb of Science®Google Scholar
127Noyes R, Jr, Brunk SF, Avery DA, Canter AC. The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Clin Pharmacol Ther. 1975; 18: 84-89.
10.1002/cpt197518184
PubMedWeb of Science®Google Scholar
128Noyes R, Jr, Brunk SF, Baram DA, Canter A. Analgesic effect of delta-9-tetrahydrocannabinol. J Clin Pharmacol. 1975; 15: 139-143.
10.1002/j.1552-4604.1975.tb02348.x
PubMedWeb of Science®Google Scholar
129Schley M, Legler A, Skopp G, Schmelz M, Konrad C, Rukwied R. Delta-9-THC based monotherapy in fibromyalgia patients on experimentally induced pain, axon reflex flare, and pain relief. Curr Med Res Opin. 2006; 22: 1269-1276.
10.1185/030079906X112651
CASPubMedWeb of Science®Google Scholar
130Maurer M, Henn V, Dittrich A, Hofmann A. Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double-blind trial. Eur Arch Psychiatry Clin Neurosci. 1990; 240: 1-4.
10.1007/BF02190083
CASPubMedWeb of Science®Google Scholar
131Staquet M, Gantt C, Machin D. Effect of a nitrogen analog of tetrahydrocannabinol on cancer pain. Clin Pharmacol Ther. 1978; 23: 397-401.
10.1002/cpt1978234397
CASPubMedWeb of Science®Google Scholar
132Salim K, Schneider U, Burstein S, Hoy L, Karst M. Pain measurements and side effect profile of the novel cannabinoid ajulemic acid. Neuropharmacology. 2005; 48: 1164-1171.
10.1016/j.neuropharm.2005.02.010
CASPubMedWeb of Science®Google Scholar
133Karst M, Wippermann S, Ahrens J. Role of cannabinoids in the treatment of pain and (painful) spasticity. Drugs. 2010; 70: 2409-2438.
10.2165/11585260-000000000-00000
CASPubMedWeb of Science®Google Scholar
134Martin-Sanchez E, Furukawa TA, Taylor J, Martin JL. Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med. 2009; 10: 1353-1368.
10.1111/j.1526-4637.2009.00703.x
PubMedWeb of Science®Google Scholar
135Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011; 72: 735-744.
10.1111/j.1365-2125.2011.03970.x
CASPubMedWeb of Science®Google Scholar
136Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. JAMA. 2003; 290: 1757-1762.
10.1001/jama.290.13.1757
CASPubMedWeb of Science®Google Scholar
137Wade DT, Makela P, Robson P, House H, Bateman C. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler. 2004; 10: 434-441.
10.1191/1352458504ms1082oa
CASPubMedWeb of Science®Google Scholar
138Frank B, Serpell MG, Hughes J, Matthews JN, Kapur D. Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ. 2008; 336: 199-201.
10.1136/bmj.39429.619653.80
CASPubMedWeb of Science®Google Scholar
139Lynch ME, Ware MA. Cannabinoids for the treatment of chronic non-cancer pain: An updated systematic review of randomized controlled trials. J Neuroimmune Pharmacol. 2015; 10: 293-301.
10.1007/s11481-015-9600-6
CASPubMedWeb of Science®Google Scholar
140Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: A systematic review and meta-analysis. JAMA. 2015; 313: 2456-2473.
10.1001/jama.2015.6358
CASPubMedWeb of Science®Google Scholar
141Hill KP. Medical marijuana for treatment of chronic pain and other medical and psychiatric problems: A clinical review. JAMA. 2015; 313: 2474-2483.
10.1001/jama.2015.6199
CASPubMedWeb of Science®Google Scholar
142Boychuk DG, Goddard G, Mauro G, Orellana MF. The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. J Oral Facial Pain Headache. 2015; 29: 7-14.
10.11607/ofph.1274
PubMedWeb of Science®Google Scholar
143Downing NS, Aminawung JA, Shah ND, Krumholz HM, Ross JS. Clinical trial evidence supporting FDA approval of novel therapeutic agents, 2005-2012. JAMA. 2014; 311: 368-377.
10.1001/jama.2013.282034
CASPubMedWeb of Science®Google Scholar
144Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod. 2012; 75: 311-335.
10.1021/np200906s
CASPubMedWeb of Science®Google Scholar
145Andre CM, Hausman JF, Guerriero G. Cannabis sativa: The plant of the thousand and one molecules. Front Plant Sci. 2016; 7: 19.
10.3389/fpls.2016.00019
PubMedWeb of Science®Google Scholar
146Lucas P, Walsh Z. Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients. Int J Drug Policy. 2017; 42: 30-35.
10.1016/j.drugpo.2017.01.011
PubMedWeb of Science®Google Scholar
147Lucas P, Walsh Z, Crosby K, et al. Substituting cannabis for prescription drugs, alcohol and other substances among medical cannabis patients: The impact of contextual factors. Drug Alcohol Rev. 2016; 35: 326-333.
10.1111/dar.12323
PubMedWeb of Science®Google Scholar
148Lucas P. Rationale for cannabis-based interventions in the opioid overdose crisis. Harm Reduct J. 2017; 14:58-017-0183-9.
10.1186/s12954-017-0183-9
PubMedWeb of Science®Google Scholar
149Nielsen S, Sabioni P, Trigo JM, et al. Opioid-sparing effect of cannabinoids: A systematic review and meta-analysis. Neuropsychopharmacology. 2017; 42: 1752-1765.
10.1038/npp.2017.51
CASPubMedWeb of Science®Google Scholar
150McGeeney BE. Cannabinoids and hallucinogens for headache. Headache. 2013; 53: 447-458.
10.1111/head.12025
PubMedWeb of Science®Google Scholar
151Bushlin I, Rozenfeld R, Devi LA. Cannabinoid-opioid interactions during neuropathic pain and analgesia. Curr Opin Pharmacol. 2010; 10: 80-86.
10.1016/j.coph.2009.09.009
CASPubMedWeb of Science®Google Scholar
152Parolaro D, Rubino T, Vigano D, Massi P, Guidali C, Realini N. Cellular mechanisms underlying the interaction between cannabinoid and opioid system. Curr Drug Targets. 2010; 11: 393-405.
10.2174/138945010790980367
CASPubMedWeb of Science®Google Scholar
153Welch SP, Stevens DL. Antinociceptive activity of intrathecally administered cannabinoids alone, and in combination with morphine, in mice. J Pharmacol Exp Ther. 1992; 262: 10-18.

CASPubMedWeb of Science®Google Scholar
154Pugh G, Jr, Smith PB, Dombrowski DS, Welch SP. The role of endogenous opioids in enhancing the antinociception produced by the combination of delta 9-tetrahydrocannabinol and morphine in the spinal cord. J Pharmacol Exp Ther. 1996; 279: 608-616.

CASPubMedWeb of Science®Google Scholar
155Smith FL, Cichewicz D, Martin ZL, Welch SP. The enhancement of morphine antinociception in mice by delta9-tetrahydrocannabinol. Pharmacol Biochem Behav. 1998; 60: 559-566.
10.1016/S0091-3057(98)00012-4
CASPubMedWeb of Science®Google Scholar
156Cichewicz DL, Welch SP, Smith FL. Enhancement of transdermal fentanyl and buprenorphine antinociception by transdermal delta9-tetrahydrocannabinol. Eur J Pharmacol. 2005; 525: 74-82.
10.1016/j.ejphar.2005.09.039
CASPubMedWeb of Science®Google Scholar
157Cichewicz DL, Martin ZL, Smith FL, Welch SP. Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification. J Pharmacol Exp Ther. 1999; 289: 859-867.

CASPubMedWeb of Science®Google Scholar
158Cichewicz DL. Synergistic interactions between cannabinoid and opioid analgesics. Life Sci. 2004; 74: 1317-1324.
10.1016/j.lfs.2003.09.038
CASPubMedWeb of Science®Google Scholar
159Cichewicz DL, McCarthy EA. Antinociceptive synergy between delta(9)-tetrahydrocannabinol and opioids after oral administration. J Pharmacol Exp Ther. 2003; 304: 1010-1015.
10.1124/jpet.102.045575
CASPubMedWeb of Science®Google Scholar
160Smith PA, Selley DE, Sim-Selley LJ, Welch SP. Low dose combination of morphine and delta9-tetrahydrocannabinol circumvents antinociceptive tolerance and apparent desensitization of receptors. Eur J Pharmacol. 2007; 571: 129-137.
10.1016/j.ejphar.2007.06.001
CASPubMedWeb of Science®Google Scholar
161Russo EB. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008; 4: 245-259.
10.2147/TCRM.S1928
CASPubMedWeb of Science®Google Scholar
162Manzanares J, Corchero J, Romero J, Fernandez-Ruiz JJ, Ramos JA, Fuentes JA. Chronic administration of cannabinoids regulates proenkephalin mRNA levels in selected regions of the rat brain. Brain Res Mol Brain Res. 1998; 55: 126-132.
10.1016/S0169-328X(97)00371-9
CASPubMedWeb of Science®Google Scholar
163Bachhuber MA, Saloner B, Cunningham CO, Barry CL. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Intern Med. 2014; 174: 1668-1673.
10.1001/jamainternmed.2014.4005
PubMedWeb of Science®Google Scholar
164Livingston MD, Barnett TE, Delcher C, Wagenaar AC. Recreational cannabis legalization and opioid-related deaths in Colorado, 2000-2015. Am J Public Health. 2017; 107: 1827-1829.
10.2105/AJPH.2017.304059
PubMedWeb of Science®Google Scholar
165Scavone JL, Sterling RC, Weinstein SP, Van Bockstaele EJ. Impact of cannabis use during stabilization on methadone maintenance treatment. Am J Addict. 2013; 22: 344-351.
10.1111/j.1521-0391.2013.12044.x
PubMedWeb of Science®Google Scholar
166Raby WN, Carpenter KM, Rothenberg J, et al. Intermittent marijuana use is associated with improved retention in naltrexone treatment for opiate-dependence. Am J Addict. 2009; 18: 301-308.
10.1080/10550490902927785
CASPubMedWeb of Science®Google Scholar
167Collen M. Prescribing cannabis for harm reduction. Harm Reduct J. 2012; 9: 1.
10.1186/1477-7517-9-1
PubMedWeb of Science®Google Scholar
168Haroutounian S, Ratz Y, Ginosar Y, et al. The effect of medicinal cannabis on pain and quality-of-life outcomes in chronic pain: A prospective open-label study. Clin J Pain. 2016; 32: 1036-1043.
10.1097/AJP.0000000000000364
PubMedWeb of Science®Google Scholar
169Boehnke KF, Litinas E, Clauw DJ. Medical cannabis use is associated with decreased opiate medication use in a retrospective cross-sectional survey of patients with chronic pain. J Pain. 2016; 17: 739-744.
10.1016/j.jpain.2016.03.002
PubMedWeb of Science®Google Scholar
170Leizer C, Ribnicky D, Poulev A, Dushenkov S, Raskin I. The composition of hemp seed oil and its potential as an important source of nutrition. J Nutraceutical Funct Med Food. 2000; 2: 35-54.
10.1300/J133v02n04_04
Google Scholar
171Ross SA, Mehmedic Z, Murphy TP, Elsohly MA. GC-MS analysis of the total delta9-THC content of both drug- and fiber-type cannabis seeds. J Anal Toxicol. 2000; 24: 715-717.
10.1093/jat/24.8.715
CASPubMedWeb of Science®Google Scholar
172Elsohly MA, Slade D. Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci. 2005; 78: 539-548.
10.1016/j.lfs.2005.09.011
CASPubMedWeb of Science®Google Scholar
173 174. Marcu JP. An overview of major and minor phytocannabinoids. In: V Preedy, ed. Neuropathology of Drug Addictions and Substance Misuse, Volume 1: Foundations of Understanding, Tobacco, Alcohol, Cannabinoids and Opioids. London: Academic Press; 2016: 672-678.

Google Scholar
174O'Sullivan SE, Kendall DA, Randall MD. Time-dependent vascular effects of Endocannabinoids mediated by peroxisome proliferator-activated receptor gamma (PPARgamma). PPAR Res. 2009; 2009: 1.
10.1155/2009/425289
Web of Science®Google Scholar
175O'Sullivan SE, Kendall DA. Cannabinoid activation of peroxisome proliferator-activated receptors: potential for modulation of inflammatory disease. Immunobiology. 2010; 215: 611-616.
10.1016/j.imbio.2009.09.007
CASPubMedWeb of Science®Google Scholar
176De Petrocellis L, Orlando P, Moriello AS, et al. Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. Acta Physiol (Oxf). 2012; 204: 255-266.
10.1111/j.1748-1716.2011.02338.x
CASPubMedWeb of Science®Google Scholar
177De Petrocellis L, Vellani V, Schiano-Moriello A, et al. Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J Pharmacol Exp Ther. 2008; 325: 1007-1015.
10.1124/jpet.107.134809
CASPubMedWeb of Science®Google Scholar
178De Petrocellis L, Di Marzo V. Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: focus on G-protein-coupled receptors and transient receptor potential channels. J Neuroimmune Pharmacol. 2010; 5: 103-121.
10.1007/s11481-009-9177-z
PubMedWeb of Science®Google Scholar
179De Petrocellis L, Ligresti A, Moriello AS, et al. Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol. 2011; 163: 1479-1494.
10.1111/j.1476-5381.2010.01166.x
CASPubMedWeb of Science®Google Scholar
180Barann M, Molderings G, Brüss M, Bönisch H, Urban BW, Göthert M. Direct inhibition by cannabinoids of human 5-HT3A receptors: probable involvement of an allosteric modulatory site. Br J Pharmacol. 2002; 137: 589-596.
10.1038/sj.bjp.0704829
CASPubMedWeb of Science®Google Scholar
181Hejazi N, Zhou C, Oz M, Sun H, Ye JH, Zhang L. Delta9-tetrahydrocannabinol and endogenous cannabinoid anandamide directly potentiate the function of glycine receptors. Mol Pharmacol. 2006; 69: 991-997.
10.1124/mol.105.019174
CASPubMedWeb of Science®Google Scholar
182McHugh D, Page J, Dunn E, Bradshaw HB. Delta(9) -Tetrahydrocannabinol and N-arachidonyl glycine are full agonists at GPR18 receptors and induce migration in human endometrial HEC-1B cells. Br J Pharmacol. 2012; 165: 2414-2424.
10.1111/j.1476-5381.2011.01497.x
CASPubMedWeb of Science®Google Scholar
183Pertwee RG. Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists. Curr Med Chem. 2010; 17: 1360-1381.
10.2174/092986710790980050
CASPubMedWeb of Science®Google Scholar
184Hajos N, Ledent C, Freund TF. Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. Neuroscience. 2001; 106: 1-4.
10.1189/jlb.0405216
CASPubMedGoogle Scholar
185Govaerts SJ, Hermans E, Lambert DM. Comparison of cannabinoid ligands affinities and efficacies in murine tissues and in transfected cells expressing human recombinant cannabinoid receptors. Eur J Pharm Sci. 2004; 23: 233-243.
10.1016/j.ejps.2004.07.013
CASPubMedWeb of Science®Google Scholar
186Nicolodi M, Volpe AR, Sicuteri F. Fibromyalgia and headache. Failure of serotonergic analgesia and N-methyl-D-aspartate-mediated neuronal plasticity: their common clues. Cephalalgia. 1998; 18: 41-44.
10.1177/0333102498018S2111
PubMedWeb of Science®Google Scholar
187Hampson AJ, Grimaldi M, Axelrod J, Wink D. Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci U S A. 1998; 95: 8268-8273.
10.1073/pnas.95.14.8268
CASPubMedWeb of Science®Google Scholar
188Hampson AJ, Bornheim LM, Scanziani M, et al. Dual effects of anandamide on NMDA receptor-mediated responses and neurotransmission. J Neurochem. 1998; 70: 671-676.
10.1046/j.1471-4159.1998.70020671.x
CASPubMedWeb of Science®Google Scholar
189Hampson AJ, Grimaldi M, Lolic M, Wink D, Rosenthal R, Axelrod J. Neuroprotective antioxidants from marijuana. Ann N Y Acad Sci. 2000; 899: 274-282.
10.1111/j.1749-6632.2000.tb06193.x
CASPubMedWeb of Science®Google Scholar
190Wilkinson JD, Kendall DA, Ralevic V. Delta 9-tetrahydrocannabinol inhibits electrically-evoked CGRP release and capsaicin-sensitive sensory neurogenic vasodilatation in the rat mesenteric arterial bed.. Br J Pharmacol. 2007; 152: 709-716.
10.1038/sj.bjp.0707448
CASPubMedWeb of Science®Google Scholar
191Li J, Daughters RS, Bullis C, et al. The cannabinoid receptor agonist WIN 55,212-2 mesylate blocks the development of hyperalgesia produced by capsaicin in rats. Pain. 1999; 81: 25-33.
10.1016/S0304-3959(98)00263-2
CASPubMedWeb of Science®Google Scholar
192Brown AJ. Novel cannabinoid receptors. Br J Pharmacol. 2007; 152: 567-575.
10.1038/sj.bjp.0707481
CASPubMedWeb of Science®Google Scholar
193Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci. 2009; 30: 515-527.
10.1016/j.tips.2009.07.006
CASPubMedWeb of Science®Google Scholar
194Rahn EJ, Hohmann AG. Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside. Neurotherapeutics. 2009; 6: 713-737.
10.1016/j.nurt.2009.08.002
CASPubMedWeb of Science®Google Scholar
195Pacher P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006; 58: 389-462.
10.1124/pr.58.3.2
CASPubMedWeb of Science®Google Scholar
196Srivastava MD, Srivastava BI, Brouhard B. Delta9 tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells. Immunopharmacology. 1998; 40: 179-185.
10.1016/S0162-3109(98)00041-1
CASPubMedWeb of Science®Google Scholar
197Kozela E, Pietr M, Juknat A, Rimmerman N, Levy R, Vogel Z. Cannabinoids Delta(9)-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-kappaB and interferon-beta/STAT proinflammatory pathways in BV-2 microglial cells. J Biol Chem. 2010; 285: 1616-1626.
10.1074/jbc.M109.069294
CASPubMedWeb of Science®Google Scholar
198Barrie N, Manolios N. The endocannabinoid system in pain and inflammation: Its relevance to rheumatic disease. Eur J Rheumatol. 2017; 4: 210-218.
10.5152/eurjrheum.2017.17025
PubMedWeb of Science®Google Scholar
199Ruhaak LR, Felth J, Karlsson PC, Rafter JJ, Verpoorte R, Bohlin L. Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol Pharm Bull. 2011; 34: 774-778.
10.1248/bpb.34.774
CASPubMedWeb of Science®Google Scholar
200Martin BR, Compton DR, Thomas BF, et al. Behavioral, biochemical, and molecular modeling evaluations of cannabinoid analogs. Pharmacol Biochem Behav. 1991; 40: 471-478.
10.1016/0091-3057(91)90349-7
CASPubMedWeb of Science®Google Scholar
201Martin BR, Lichtman AH. Cannabinoid transmission and pain perception. Neurobiol Dis. 1998; 5: 447-461.
10.1006/nbdi.1998.0218
CASPubMedWeb of Science®Google Scholar
202DeLong GT, Wolf CE, Poklis A, Lichtman AH. Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Delta(9)-tetrahydrocannabinol. Drug Alcohol Depend. 2010; 112: 126-133.
10.1016/j.drugalcdep.2010.05.019
CASPubMedWeb of Science®Google Scholar
203Zygmunt PM, Andersson DA, Hogestatt ED. Delta 9-tetrahydrocannabinol and cannabinol activate capsaicin-sensitive sensory nerves via a CB1 and CB2 cannabinoid receptor-independent mechanism. J Neurosci. 2002; 22: 4720-4727.
10.1523/JNEUROSCI.22-11-04720.2002
CASPubMedWeb of Science®Google Scholar
204Manzanares J, Julian M, Carrascosa A. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol. 2006; 4: 239-257.
10.2174/157015906778019527
CASPubMedWeb of Science®Google Scholar
205Burston JJ, Sagar DR, Shao P, et al. Cannabinoid CB2 receptors regulate central sensitization and pain responses associated with osteoarthritis of the knee joint. PLoS One. 2013; 8: e80440.
10.1371/journal.pone.0080440
PubMedWeb of Science®Google Scholar
206Gui H, Liu X, Wang ZW, He DY, Su DF, Dai SM. Expression of cannabinoid receptor 2 and its inhibitory effects on synovial fibroblasts in rheumatoid arthritis. Rheumatology (Oxford). 2014; 53: 802-809.
10.1093/rheumatology/ket447
CASPubMedWeb of Science®Google Scholar
207Clayton N, Marshall FH, Bountra C, O'Shaughnessy CT. CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain. Pain. 2002; 96: 253-260.
10.1016/S0304-3959(01)00454-7
CASPubMedWeb of Science®Google Scholar
208Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009; 1: 1333-1349.
10.4155/fmc.09.93
CASPubMedWeb of Science®Google Scholar
209Jensen B, Chen J, Furnish T, Wallace M. Medical marijuana and chronic pain: A review of basic science and clinical evidence. Curr Pain Headache Rep. 2015; 19: 50.
10.1007/s11916-015-0524-x
PubMedWeb of Science®Google Scholar
210Weber J, Schley M, Casutt M, et al. Tetrahydrocannabinol (Delta 9-THC) treatment in chronic central neuropathic pain and fibromyalgia patients: Results of a Multicenter Survey. Anesthesiol Res Pract. 2009; 2009: 1.
10.1155/2009/827290
Google Scholar
211Weber M, Goldman B, Truniger S. Tetrahydrocannabinol (THC) for cramps in amyotrophic lateral sclerosis: A randomised, double-blind crossover trial. J Neurol Neurosurg Psychiatry. 2010; 81: 1135-1140.
10.1136/jnnp.2009.200642
CASPubMedWeb of Science®Google Scholar
212Smith PB, Martin BR. Spinal mechanisms of delta 9-tetrahydrocannabinol-induced analgesia. Brain Res. 1992; 578: 8-12.
10.1016/0006-8993(92)90222-U
CASPubMedWeb of Science®Google Scholar
213Smith FL, Fujimori K, Lowe J, Welch SP. Characterization of delta9-tetrahydrocannabinol and anandamide antinociception in nonarthritic and arthritic rats. Pharmacol Biochem Behav. 1998; 60: 183-191.
10.1016/S0091-3057(97)00583-2
CASPubMedWeb of Science®Google Scholar
214Walker JM, Huang SM. Cannabinoid analgesia. Pharmacol Ther. 2002; 95: 127-135.
10.1016/S0163-7258(02)00252-8
CASPubMedWeb of Science®Google Scholar
215Walker JM, Strangman NM, Huang SM. Cannabinoids and pain. Pain Res Manag. 2001; 6: 74-79.
10.1155/2001/413641
CASPubMedGoogle Scholar
216Walker JM, Hohmann AG, Martin WJ, Strangman NM, Huang SM, Tsou K. The neurobiology of cannabinoid analgesia. Life Sci. 1999; 65: 665-673.
10.1016/S0024-3205(99)00289-1
CASPubMedWeb of Science®Google Scholar
217Evans FJ. Cannabinoids: the separation of central from peripheral effects on a structural basis. Planta Med. 1991; 57: S60-S67.
10.1055/s-2006-960231
CASWeb of Science®Google Scholar
218Fine PG, Rosenfeld MJ. The endocannabinoid system, cannabinoids, and pain. Rambam Maimonides Med J. 2013; 4: e0022.
10.5041/RMMJ.10129
PubMedGoogle Scholar
219Welch SP. Blockade of cannabinoid-induced antinociception by norbinaltorphimine, but not N,N-diallyl-tyrosine-Aib-phenylalanine-leucine, ICI 174,864 or naloxone in mice. J Pharmacol Exp Ther. 1993; 265: 633-640.

CASPubMedWeb of Science®Google Scholar
220Wallace MS, Marcotte TD, Umlauf A, Gouaux B, Atkinson JH. Efficacy of inhaled cannabis on painful diabetic neuropathy. J Pain. 2015; 16: 616-627.
10.1016/j.jpain.2015.03.008
CASPubMedWeb of Science®Google Scholar
221Serpell MG, Notcutt W, Collin C. Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis. J Neurol. 2013; 260: 285-295.
10.1007/s00415-012-6634-z
PubMedWeb of Science®Google Scholar
222Notcutt W, Langford R, Davies P, Ratcliffe S, Potts R. A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex(R) (nabiximols). Mult Scler. 2012; 18: 219-228.
10.1177/1352458511419700
CASPubMedWeb of Science®Google Scholar
223Johnson JR, Lossignol D, Burnell-Nugent M, Fallon MT. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. J Pain Symptom Manage. 2013; 46: 207-218.
10.1016/j.jpainsymman.2012.07.014
CASPubMedWeb of Science®Google Scholar
224Zajicek JP, Sanders HP, Wright DE, et al. Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. J Neurol Neurosurg Psychiatry. 2005; 76: 1664-1669.
10.1136/jnnp.2005.070136
CASPubMedWeb of Science®Google Scholar
225Zajicek JP, Apostu VI. Role of cannabinoids in multiple sclerosis. CNS Drugs. 2011; 25: 187-201.
10.2165/11539000-000000000-00000
CASPubMedWeb of Science®Google Scholar
226Vaney C, Heinzel-Gutenbrunner M, Jobin P, et al. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study. Mult Scler. 2004; 10: 417-424.
10.1191/1352458504ms1048oa
CASPubMedWeb of Science®Google Scholar
227Collin C, Davies P, Mutiboko IK, Ratcliffe S. Sativex Spasticity in MS Study Group. Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur J Neurol. 2007; 14: 290-296.
10.1111/j.1468-1331.2006.01639.x
CASPubMedWeb of Science®Google Scholar
228Collin C, Ehler E, Waberzinek G, et al. A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurol Res. 2010; 32: 451-459.
10.1179/016164109X12590518685660
CASPubMedWeb of Science®Google Scholar
229Syed YY, McKeage K, Scott LJ. Delta-9-tetrahydrocannabinol/cannabidiol (Sativex(R)): a review of its use in patients with moderate to severe spasticity due to multiple sclerosis. Drugs. 2014; 74: 563-578.
10.1007/s40265-014-0197-5
CASPubMedWeb of Science®Google Scholar
230Lakhan SE, Rowland M. Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. BMC Neurol. 2009; 9: 59.
10.1186/1471-2377-9-59
CASPubMedWeb of Science®Google Scholar
231Barnes MP. Sativex: clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain. Expert Opin Pharmacother. 2006; 7: 607-615.
10.1517/14656566.7.5.607
CASPubMedWeb of Science®Google Scholar
232 GW Pharmaceuticals. Sativex Product Monograph; 2010.

Google Scholar
233Sallan SE, Zinberg NE, Frei E. 3rd., Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med. 1975; 293: 795-797.
10.1056/NEJM197510162931603
CASPubMedWeb of Science®Google Scholar
234Sallan SE, Cronin C, Zelen M, Zinberg NE. Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. N Engl J Med. 1980; 302: 135-138.
10.1056/NEJM198001173020302
CASPubMedWeb of Science®Google Scholar
235Vinciguerra V, Moore T, Brennan E. Inhalation marijuana as an antiemetic for cancer chemotherapy. N Y State J Med. 1988; 88: 525-527.

CASPubMedWeb of Science®Google Scholar
236Carey MP, Burish TG, Brenner DE. Delta-9-tetrahydrocannabinol in cancer chemotherapy: research problems and issues. Ann Intern Med. 1983; 99: 106-114.
10.7326/0003-4819-99-1-106
CASPubMedWeb of Science®Google Scholar
237Lucas VS, Jr, Laszlo J. delta 9-Tetrahydrocannabinol for refractory vomiting induced by cancer chemotherapy. JAMA. 1980; 243: 1241-1243.
10.1001/jama.1980.03300380021014
PubMedWeb of Science®Google Scholar
238Frytak S, Moertel CG, O'Fallon JR, et al. Delta-9-tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy. A comparison with prochlorperazine and a placebo. Ann Intern Med. 1979; 91: 825-830.
10.7326/0003-4819-91-6-825
CASPubMedWeb of Science®Google Scholar
239Ungerleider JT, Andrysiak T, Fairbanks L, Goodnight J, Sarna G, Jamison K. Cannabis and cancer chemotherapy: a comparison of oral delta-9-THC and prochlorperazine. Cancer. 1982; 50: 636-645.
10.1002/1097-0142(19820815)50:4<636::AID-CNCR2820500404>3.0.CO;2-4
CASPubMedWeb of Science®Google Scholar
240Orr LE, McKernan JF, Bloome B. Antiemetic effect of tetrahydrocannabinol. Compared with placebo and prochlorperazine in chemotherapy-associated nausea and emesis. Arch Intern Med. 1980; 140: 1431-1433.
10.1001/archinte.1980.00330220019010
CASPubMedGoogle Scholar
241Orr LE, McKernan JF. Antiemetic effect of delta 9-tetrahydrocannabinol in chemotherapy-associated nausea and emesis as compared to placebo and compazine. J Clin Pharmacol. 1981; 21: 76S-80S.
10.1002/j.1552-4604.1981.tb02578.x
CASPubMedWeb of Science®Google Scholar
242Levitt M, Wilson A, Bowman D, et al. Physiologic observations in a controlled clinical trial of the antiemetic effectiveness of 5, 10, and 15 mg of delta 9-tetrahydrocannabinol in cancer chemotherapy. Ophthalmologic implications. J Clin Pharmacol. 1981; 21: 103S-109S.
10.1002/j.1552-4604.1981.tb02583.x
CASPubMedWeb of Science®Google Scholar
243McCabe M, Smith FP, Macdonald JS, Woolley PV, Goldberg D, Schein PS. Efficacy of tetrahydrocannabinol in patients refractory to standard antiemetic therapy. Invest New Drugs. 1988; 6: 243-246.
10.1007/BF00175407
CASPubMedWeb of Science®Google Scholar
244Niiranen A, Mattson K. A cross-over comparison of nabilone and prochlorperazine for emesis induced by cancer chemotherapy. Am J Clin Oncol. 1985; 8: 336-340.
10.1097/00000421-198508000-00013
CASPubMedWeb of Science®Google Scholar
245Herman TS, Einhorn LH, Jones SE, et al. Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy. N Engl J Med. 1979; 300: 1295-1297.
10.1056/NEJM197906073002302
CASPubMedWeb of Science®Google Scholar
246Vincent BJ, McQuiston DJ, Einhorn LH, Nagy CM, Brames MJ. Review of cannabinoids and their antiemetic effectiveness. Drugs. 1983; 25(Suppl 1): 52-62.
10.2165/00003495-198300251-00006
PubMedWeb of Science®Google Scholar
247Einhorn L. Nabilone: an effective antiemetic agent in patients receiving cancer chemotherapy. Cancer Treat Rev. 1982; 9: 55-61.
10.1016/S0305-7372(82)80037-6
PubMedWeb of Science®Google Scholar
248Einhorn LH, Nagy C, Furnas B, Williams SD. Nabilone: an effective antiemetic in patients receiving cancer chemotherapy. J Clin Pharmacol. 1981; 21: 64S-69S.
10.1002/j.1552-4604.1981.tb02576.x
CASPubMedWeb of Science®Google Scholar
249Ahmedzai S, Carlyle DL, Calder IT, Moran F. Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy. Br J Cancer. 1983; 48: 657-663.
10.1038/bjc.1983.247
CASPubMedWeb of Science®Google Scholar
250Garb S, Beers AL, Bograd M. Two-pronged study of tetrahydrocannabinol (THC) prevention of vomiting for cancer chemotherapy. IRCS Med. Sci. 1980; 8: 203-204.

Web of Science®Google Scholar
251Lane M, Smith FE, Sullivan RA, Plasse TF. Dronabinol and prochlorperazine alone and in combination as antiemetic agents for cancer chemotherapy. Am J Clin Oncol. 1990; 13: 480-484.
10.1097/00000421-199012000-00006
CASPubMedWeb of Science®Google Scholar
252Lane M, Vogel CL, Ferguson J, et al. Dronabinol and prochlorperazine in combination for treatment of cancer chemotherapy-induced nausea and vomiting. J Pain Symptom Manage. 1991; 6: 352-359.
10.1016/0885-3924(91)90026-Z
CASPubMedWeb of Science®Google Scholar
253Plasse TF, Gorter RW, Krasnow SH, Lane M, Shepard KV, Wadleigh RG. Recent clinical experience with dronabinol. Pharmacol Biochem Behav. 1991; 40: 695-700.
10.1016/0091-3057(91)90385-F
CASPubMedWeb of Science®Google Scholar
254Cunningham D, Forrest GJ, Soukop M, Gilchrist NL, Calder IT, McArdle CS. Nabilone and prochlorperazine: a useful combination for emesis induced by cytotoxic drugs. Br Med J (Clin Res Ed). 1985; 291: 864-865.
10.1136/bmj.291.6499.864
CASPubMedWeb of Science®Google Scholar
255Gonzalez-Rosales F, Walsh D. Intractable nausea and vomiting due to gastrointestinal mucosal metastases relieved by tetrahydrocannabinol (dronabinol). J Pain Symptom Manage. 1997; 14: 311-314.
10.1016/S0885-3924(97)00229-7
CASPubMedWeb of Science®Google Scholar
256Chang AE, Shiling DJ, Stillman RC, et al. Delta-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate. A prospective, randomized evaluation. Ann Intern Med. 1979; 91: 819-824.
10.7326/0003-4819-91-6-819
CASPubMedWeb of Science®Google Scholar
257Staquet M, Bron D, Rozencweig M, Kenis Y. Clinical studies with a THC analog (BRL-4664) in the prevention of cisplatin-induced vomiting. J Clin Pharmacol. 1981; 21: 60S-63S.
10.1002/j.1552-4604.1981.tb02575.x
CASPubMedWeb of Science®Google Scholar
258Sharkey KA, Darmani NA, Parker LA. Regulation of nausea and vomiting by cannabinoids and the endocannabinoid system. Eur J Pharmacol. 2014; 722: 134-146.
10.1016/j.ejphar.2013.09.068
CASPubMedWeb of Science®Google Scholar
259Parker LA, Rock EM, Limebeer CL. Regulation of nausea and vomiting by cannabinoids. Br J Pharmacol. 2011; 163: 1411-1422.
10.1111/j.1476-5381.2010.01176.x
CASPubMedWeb of Science®Google Scholar
260Tramer MR, Carroll D, Campbell FA, Reynolds DJ, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ. 2001; 323: 16-21.
10.1136/bmj.323.7303.16
CASPubMedGoogle Scholar
261Sutton IR, Daeninck P. Cannabinoids in the management of intractable chemotherapy-induced nausea and vomiting and cancer-related pain. J Support Oncol. 2006; 4: 531-535.

CASPubMedGoogle Scholar
262Pisanti S, Malfitano AM, Grimaldi C, et al. Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents. Best Pract Res Clin Endocrinol Metab. 2009; 23: 117-131.
10.1016/j.beem.2009.02.001
CASPubMedWeb of Science®Google Scholar
263Gurley RJ, Aranow R, Katz M. Medicinal marijuana: a comprehensive review. J Psychoactive Drugs. 1998; 30: 137-147.
10.1080/02791072.1998.10399683
CASPubMedWeb of Science®Google Scholar
264Tortorice PV, O'Connell MB. Management of chemotherapy-induced nausea and vomiting. Pharmacotherapy. 1990; 10: 129-145.
10.1002/j.1875-9114.1990.tb02560.x
CASPubMedWeb of Science®Google Scholar
265Cunningham D, Bradley CJ, Forrest GJ, et al. A randomized trial of oral nabilone and prochlorperazine compared to intravenous metoclopramide and dexamethasone in the treatment of nausea and vomiting induced by chemotherapy regimens containing cisplatin or cisplatin analogues. Eur J Cancer Clin Oncol. 1988; 24: 685-689.
10.1016/0277-5379(88)90300-8
CASPubMedWeb of Science®Google Scholar
266Soderpalm AH, Schuster A, de Wit H. Antiemetic efficacy of smoked marijuana: subjective and behavioral effects on nausea induced by syrup of ipecac. Pharmacol Biochem Behav. 2001; 69: 343-350.
10.1016/S0091-3057(01)00533-0
CASPubMedWeb of Science®Google Scholar
267Machado Rocha FC, Stefano SC, De Cassia Haiek R, Rosa Oliveira LM, Da Silveira DX. Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur J Cancer Care (Engl). 2008; 17: 431-443.
10.1111/j.1365-2354.2008.00917.x
CASPubMedWeb of Science®Google Scholar
268Musty R, Rossi R. Effects of smoked cannabis and oral delta-9-tetrahydrocannabinol on nausea and emesis after cancer chemotherapy: A review of state clinical trials. J Cannabis Therapeutics. 2001; 1: 29-42.
10.1300/J175v01n01_03
CASGoogle Scholar
269Meiri E, Jhangiani H, Vredenburgh JJ, et al. Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin. 2007; 23: 533-543.
10.1185/030079907X167525
CASPubMedWeb of Science®Google Scholar
270Ekert H, Waters KD, Jurk IH, Mobilia J, Loughnan P. Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol. Med J Aust. 1979; 2: 657-659.
10.5694/j.1326-5377.1979.tb127271.x
CASPubMedWeb of Science®Google Scholar
271Pertwee RG. Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities. Philos Trans R Soc Lond B Biol Sci. 2012; 367: 3353-3363.
10.1098/rstb.2011.0381
CASPubMedWeb of Science®Google Scholar
272Rock EM, Connolly C, Limebeer CL, Parker LA. Effect of combined oral doses of Delta(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models. Psychopharmacology (Berl). 2016; 233: 3353-3360.
10.1007/s00213-016-4378-7
CASPubMedWeb of Science®Google Scholar
273Green ST, Nathwani D, Goldberg DJ, Kennedy DH. Nabilone as effective therapy for intractable nausea and vomiting in AIDS. Br J Clin Pharmacol. 1989; 28: 494-495.
10.1111/j.1365-2125.1989.tb03533.x
CASPubMedWeb of Science®Google Scholar
274Chan HS, Correia JA, MacLeod SM. Nabilone versus prochlorperazine for control of cancer chemotherapy-induced emesis in children: a double-blind, crossover trial. Pediatrics. 1987; 79: 946-952.

CASPubMedWeb of Science®Google Scholar
275Dalzell AM, Bartlett H, Lilleyman JS. Nabilone: an alternative antiemetic for cancer chemotherapy. Arch Dis Child. 1986; 61: 502-505.
10.1136/adc.61.5.502
CASPubMedWeb of Science®Google Scholar
276Abrahamov A, Abrahamov A, Mechoulam R. An efficient new cannabinoid antiemetic in pediatric oncology. Life Sci. 1995; 56: 2097-2102.
10.1016/0024-3205(95)00194-B
CASPubMedWeb of Science®Google Scholar
277 Abbott Products Inc. Marinol Product Monograph; 2010.

Google Scholar
278 Valeant Canada. Cesamet Product Monograph; 2009.

Google Scholar
279Notcutt WG, Price M, Chapman G. Clinical experience with nabilone for chronic pain. Pharm Sci. 1997; 3: 551-555.
10.1111/j.2042-7158.1997.tb00493.x
CASGoogle Scholar
280Hamann W, di Vadi PP. Analgesic effect of the cannabinoid analogue nabilone is not mediated by opioid receptors. Lancet. 1999; 353: 560.
10.1016/S0140-6736(98)05429-4
CASPubMedWeb of Science®Google Scholar
281Berlach DM, Shir Y, Ware MA. Experience with the synthetic cannabinoid nabilone in chronic noncancer pain. Pain Med. 2006; 7: 25-29.
10.1111/j.1526-4637.2006.00085.x
PubMedWeb of Science®Google Scholar
282Martyn CN, Illis LS, Thom J. Nabilone in the treatment of multiple sclerosis. Lancet. 1995; 345: 579.
10.1016/S0140-6736(95)90485-9
CASPubMedWeb of Science®Google Scholar
283Hampson AJ, Axelrod J, Grimaldi M, Cannabinoids as antioxidants and neuroprotectants. U.S. Patent #6,630,507. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6630507.PN.&OS=PN/6630507&RS=PN/6630507. 2003.

Google Scholar
284Sanchez AJ, Garcia-Merino A. Neuroprotective agents: cannabinoids. Clin Immunol. 2012; 142: 57-67.
10.1016/j.clim.2011.02.010
CASPubMedWeb of Science®Google Scholar
285van der Stelt M, Veldhuis WB, Bär PR, Veldink GA, Vliegenthart JF, Nicolay K. Neuroprotection by Delta9-tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity. J Neurosci. 2001; 21: 6475-6479.
10.1523/JNEUROSCI.21-17-06475.2001
PubMedWeb of Science®Google Scholar
286van der Stelt M, Di Marzo V. Cannabinoid receptors and their role in neuroprotection. Neuromolecular Med. 2005; 7: 37-50.
10.1385/NMM:7:1-2:037
PubMedWeb of Science®Google Scholar
287Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease. Int J Geriatr Psychiatry. 1997; 12: 913-919.
10.1002/(SICI)1099-1166(199709)12:9<913::AID-GPS663>3.0.CO;2-D
CASPubMedWeb of Science®Google Scholar
288Eubanks LM, Rogers CJ, Beuscher AE, 4th, et al. A molecular link between the active component of marijuana and Alzheimer's disease pathology. Mol Pharm. 2006; 3: 773-777.
10.1021/mp060066m
CASPubMedWeb of Science®Google Scholar
289Cao C, Li Y, Liu H, et al. The potential therapeutic effects of THC on Alzheimer's disease. J Alzheimers Dis. 2014; 42: 973-984.
10.3233/JAD-140093
CASPubMedWeb of Science®Google Scholar
290Passmore MJ. The cannabinoid receptor agonist nabilone for the treatment of dementia-related agitation. Int J Geriatr Psychiatry. 2008; 23: 116-117.
10.1002/gps.1828
PubMedWeb of Science®Google Scholar
291Walther S, Mahlberg R, Eichmann U, Kunz D. Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia. Psychopharmacology (Berl). 2006; 185: 524-528.
10.1007/s00213-006-0343-1
CASPubMedWeb of Science®Google Scholar
292Carter GT, Abood ME, Aggarwal SK, Weiss MD. Cannabis and amyotrophic lateral sclerosis: hypothetical and practical applications, and a call for clinical trials. Am J Hosp Palliat Care. 2010; 27: 347-356.
10.1177/1049909110369531
PubMedWeb of Science®Google Scholar
293Amtmann D, Weydt P, Johnson KL, Jensen MP, Carter GT. Survey of cannabis use in patients with amyotrophic lateral sclerosis. Am J Hosp Palliat Care. 2004; 21: 95-104.
10.1177/104990910402100206
PubMedGoogle Scholar
294Bilsland LG, Dick JR, Pryce G, et al. Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in SOD1 mice. FASEB J. 2006; 20: 1003-1005.
10.1096/fj.05-4743fje
CASPubMedWeb of Science®Google Scholar
295Raman C, McAllister SD, Rizvi G, Patel SG, Moore DH, Abood ME. Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004; 5: 33-39.
10.1080/14660820310016813
CASPubMedWeb of Science®Google Scholar
296Gelinas DF, Miller RG, Abood M. Pilot Study of safety and tolerability of delta 9-THC (Marinol) treatment for ALS. Amyotroph Lateral Scler Other Motor Neuron Disord. 2002; 3: 23-24.

PubMedWeb of Science®Google Scholar
297Buccellato E, Carretta D, Utan A, et al. Acute and chronic cannabinoid extracts administration affects motor function in a CREAE model of multiple sclerosis. J Ethnopharmacol. 2011; 133: 1033-1038.
10.1016/j.jep.2010.11.035
CASPubMedWeb of Science®Google Scholar
298Ungerleider JT, Andyrsiak T, Fairbanks L, Ellison GW, Myers LW. Delta-9-THC in the treatment of spasticity associated with multiple sclerosis. Adv Alcohol Subst Abuse. 1987; 7: 39-50.
10.1300/J251v07n01_04
CASPubMedGoogle Scholar
299Brenneisen R, Egli A, Elsohly MA, Henn V, Spiess Y. The effect of orally and rectally administered delta 9-tetrahydrocannabinol on spasticity: a pilot study with 2 patients. Int J Clin Pharmacol Ther. 1996; 34: 446-452.

CASPubMedWeb of Science®Google Scholar
300Kurz R, Blass K. Use of dronabinol (delta-9-THC) in autism: A prospective single-case-study with an early infantile autistic child. Cannabinoids. 2010; 5: 4-6.

Google Scholar
301Foldy C, Malenka RC, Sudhof TC. Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling. Neuron. 2013; 78: 498-509.
10.1016/j.neuron.2013.02.036
CASPubMedWeb of Science®Google Scholar
302Hadland SE, Knight JR, Harris SK. Medical marijuana: review of the science and implications for developmental-behavioral pediatric practice. J Dev Behav Pediatr. 2015; 36: 115-123.
10.1097/DBP.0000000000000129
PubMedWeb of Science®Google Scholar
303Siniscalco D, Sapone A, Giordano C, et al. Cannabinoid receptor type 2, but not type 1, is up-regulated in peripheral blood mononuclear cells of children affected by autistic disorders. J Autism Dev Disord. 2013; 43: 2686-2695.
10.1007/s10803-013-1824-9
PubMedWeb of Science®Google Scholar
304Bou Khalil R. Would some cannabinoids ameliorate symptoms of autism?. Eur Child Adolesc Psychiatry. 2012; 21: 237-238.
10.1007/s00787-012-0255-z
PubMedWeb of Science®Google Scholar
305Moldzio R, Pacher T, Krewenka C, et al. Effects of cannabinoids Delta(9)-tetrahydrocannabinol, Delta(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures. Phytomedicine. 2012; 19: 819-824.
10.1016/j.phymed.2012.04.002
CASPubMedWeb of Science®Google Scholar
306Zeissler ML, Eastwood J, McCorry K, Hanemann CO, Zajicek JP, Carroll CB. Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis. Oncotarget. 2016; 7: 46603-46614.
10.18632/oncotarget.10314
PubMedGoogle Scholar
307Zeissler ML, Eastwood J, Hanemann CO, Zajicek J, Carroll C. Δ9–Tetrahydrocannabinol is protective through PPARTγ dependent mitochondrial biogenesis in a cell culture model of Parkinson's Disease. J Neurol Neurosurg Psychiatry. 2013; 84: e2.58.
10.1136/jnnp-2013-306573.150
Web of Science®Google Scholar
308Lotan I, Treves TA, Roditi Y, Djaldetti R. Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study. Clin Neuropharmacol. 2014; 37: 41-44.
10.1097/WNF.0000000000000016
PubMedWeb of Science®Google Scholar
309Carroll CB, Zeissler ML, Hanemann CO, Zajicek JP. Delta(9)-tetrahydrocannabinol (Delta(9)-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson's disease. Neuropathol Appl Neurobiol. 2012; 38: 535-547.
10.1111/j.1365-2990.2011.01248.x
CASPubMedWeb of Science®Google Scholar
310Stampanoni Bassi M, Sancesario A, Morace R, Centonze D, Iezzi E. Cannabinoids in Parkinson's Disease. Cannabis Cannabinoid Res. 2017; 2: 21-29.
10.1089/can.2017.0002
PubMedGoogle Scholar
311Sieradzan KA, Fox SH, Hill M, Dick JP, Crossman AR, Brotchie JM. Cannabinoids reduce levodopa-induced dyskinesia in Parkinson's disease: a pilot study. Neurology. 2001; 57: 2108-2111.
10.1212/WNL.57.11.2108
CASPubMedWeb of Science®Google Scholar
312Muller-Vahl KR, Kolbe H, Schneider U, Emrich HM. Cannabis in movement disorders. Forsch Komplementarmed. 1999; 6(Suppl 3): 23-27.
10.1159/000057153
PubMedWeb of Science®Google Scholar
313Muller-Vahl KR, Schneider U, Kolbe H, Emrich HM. Treatment of Tourette's syndrome with delta-9-tetrahydrocannabinol. Am J Psychiatry. 1999; 156: 495.
10.1176/ajp.156.3.495
CASPubMedWeb of Science®Google Scholar
314Müller-Vahl KR, Koblenz A, Jöbges M, Kolbe H, Emrich HM, Schneider U. Influence of treatment of Tourette syndrome with delta9-tetrahydrocannabinol (delta9-THC) on neuropsychological performance. Pharmacopsychiatry. 2001; 34: 19-24.
10.1055/s-2001-15191
CASPubMedWeb of Science®Google Scholar
315Muller-Vahl KR, Schneider U, Koblenz A, et al. Treatment of Tourette's syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial. Pharmacopsychiatry. 2002; 35: 57-61.
10.1055/s-2002-25028
CASPubMedWeb of Science®Google Scholar
316Muller-Vahl KR. Cannabinoids reduce symptoms of Tourette's syndrome. Expert Opin Pharmacother. 2003; 4: 1717-1725.
10.1517/14656566.4.10.1717
PubMedWeb of Science®Google Scholar
317Muller-Vahl KR, Schneider U, Prevedel H, et al. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. J Clin Psychiatry. 2003; 64: 459-465.
10.4088/JCP.v64n0417
CASPubMedWeb of Science®Google Scholar
318Muller-Vahl KR, Prevedel H, Theloe K, Kolbe H, Emrich HM, Schneider U. Treatment of Tourette syndrome with delta-9-tetrahydrocannabinol (delta 9-THC): no influence on neuropsychological performance. Neuropsychopharmacology. 2003; 28: 384-388.
10.1038/sj.npp.1300047
CASPubMedWeb of Science®Google Scholar
319Curtis A, Rickards H. Nabilone could treat chorea and irritability in Huntington's disease. J Neuropsychiatry Clin Neurosci. 2006; 18: 553-554.
10.1176/jnp.2006.18.4.553
PubMedWeb of Science®Google Scholar
320Curtis A, Mitchell I, Patel S, Ives N, Rickards H. A pilot study using nabilone for symptomatic treatment in Huntington's disease. Mov Disord. 2009; 24: 2254-2259.
10.1002/mds.22809
CASPubMedWeb of Science®Google Scholar
321Blazquez C, Chiarlone A, Sagredo O, et al. Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease. Brain. 2011; 134: 119-136.
10.1093/brain/awq278
PubMedWeb of Science®Google Scholar
322El-Alfy AT, Ivey K, Robinson K, et al. Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacol Biochem Behav. 2010; 95: 434-442.
10.1016/j.pbb.2010.03.004
CASPubMedWeb of Science®Google Scholar
323Denson TF, Earleywine M. Decreased depression in marijuana users. Addict Behav. 2006; 31: 738-742.
10.1016/j.addbeh.2005.05.052
PubMedWeb of Science®Google Scholar
324Bossong MG, van Hell HH, Jager G, Kahn RS, Ramsey NF, Jansma JM. The endocannabinoid system and emotional processing: a pharmacological fMRI study with 9-tetrahydrocannabinol. Eur Neuropsychopharmacol. 2013; 23: 1687-1697.
10.1016/j.euroneuro.2013.06.009
CASPubMedWeb of Science®Google Scholar
325Betthauser K, Pilz J, Vollmer LE. Use and effects of cannabinoids in military veterans with posttraumatic stress disorder. Am J Health Syst Pharm. 2015; 72: 1279-1284.
10.2146/ajhp140523
PubMedWeb of Science®Google Scholar
326Greer GR, Grob CS, Halberstadt AL. PTSD symptom reports of patients evaluated for the New Mexico Medical Cannabis Program. J Psychoactive Drugs. 2014; 46: 73-77.
10.1080/02791072.2013.873843
PubMedWeb of Science®Google Scholar
327Passie T, Emrich HM, Karst M, Brandt SD, Halpern JH. Mitigation of post-traumatic stress symptoms by Cannabis resin: a review of the clinical and neurobiological evidence. Drug Test Anal. 2012; 4: 649-659.
10.1002/dta.1377
CASPubMedWeb of Science®Google Scholar
328Fraser GA. The use of a synthetic cannabinoid in the management of treatment-resistant nightmares in posttraumatic stress disorder (PTSD). CNS Neurosci Ther. 2009; 15: 84-88.
10.1111/j.1755-5949.2008.00071.x
PubMedWeb of Science®Google Scholar
329Roitman P, Mechoulam R, Cooper-Kazaz R, Shalev A. Preliminary, open-label, pilot study of add-on oral delta(9)-tetrahydrocannabinol in chronic post-traumatic stress disorder. Clin Drug Investig. 2014; 34: 587-591.
10.1007/s40261-014-0212-3
CASPubMedWeb of Science®Google Scholar
330Kohli DR, Li Y, Khasabov SG, et al. Pain-related behaviors and neurochemical alterations in mice expressing sickle hemoglobin: modulation by cannabinoids. Blood. 2010; 116: 456-465.
10.1182/blood-2010-01-260372
CASPubMedWeb of Science®Google Scholar
331Signorelli AA, Ribeiro SB, Moraes-Souza H, et al. Pain measurement as part of primary healthcare of adult patients with sickle cell disease. Rev Bras Hematol Hemoter. 2013; 35: 272-277.
10.5581/1516-8484.20130075
PubMedGoogle Scholar
332Lopez-Rodriguez AB, Siopi E, Finn DP, et al. CB1 and CB2 cannabinoid receptor antagonists prevent minocycline-induced neuroprotection following traumatic brain injury in mice. Cereb Cortex. 2015; 25: 35-45.
10.1093/cercor/bht202
PubMedWeb of Science®Google Scholar
333Nguyen BM, Kim D, Bricker S, et al. Effect of marijuana use on outcomes in traumatic brain injury. Am Surg. 2014; 80: 979-983.
10.1177/000313481408001015
PubMedWeb of Science®Google Scholar
334Akirav I. Targeting the endocannabinoid system to treat haunting traumatic memories. Front Behav Neurosci. 2013; 7: 124.
10.3389/fnbeh.2013.00124
PubMedWeb of Science®Google Scholar
335Fitton AG, Pertwee RG. Changes in body temperature and oxygen consumption rate of conscious mice produced by intrahypothalamic and intracerebroventricular injections of delta 9-tetrahydrocannabinol. Br J Pharmacol. 1982; 75: 409-414.
10.1111/j.1476-5381.1982.tb08802.x
CASPubMedWeb of Science®Google Scholar
336Malone DT, Taylor DA. Modulation of delta9-tetrahydrocannabinol-induced hypothermia by fluoxetine in the rat. Br J Pharmacol. 1998; 124: 1419-1424.
10.1038/sj.bjp.0701980
CASPubMedWeb of Science®Google Scholar
337Compton DR, Aceto MD, Lowe J, Martin BR. In vivo characterization of a specific cannabinoid receptor antagonist (SR141716A): inhibition of delta 9-tetrahydrocannabinol-induced responses and apparent agonist activity. JPharmacol Exp Ther. 1996; 277: 586-594.

CASPubMedWeb of Science®Google Scholar
338Compton DR, Johnson MR, Melvin LS, Martin BR. Pharmacological profile of a series of bicyclic cannabinoid analogs: classification as cannabimimetic agents. J Pharmacol Exp Ther. 1992; 260: 201-209.

CASPubMedWeb of Science®Google Scholar
339Fennessy MR, Taylor DA. The effect of delta9-tetrahydrocannabinol on body temperature and brain amine concentrations in the rat at differnt ambient temperatures. Br J Pharmacol. 1977; 60: 65-71.
10.1111/j.1476-5381.1977.tb16748.x
CASPubMedWeb of Science®Google Scholar
340Douthwaite AH. Choice of drugs in the treatment of duodenal ulcer. Br Med J. 1947; 2: 43-47.
10.1136/bmj.2.4514.43
CASPubMedWeb of Science®Google Scholar
341Andries A, Frystyk J, Flyvbjerg A, Stoving RK. Dronabinol in severe, enduring anorexia nervosa: a randomized controlled trial. Int J Eat Disord. 2014; 47: 18-23.
10.1002/eat.22173
CASPubMedWeb of Science®Google Scholar
342Cota D, Marsicano G, Lutz B, et al. Endogenous cannabinoid system as a modulator of food intake. Int J Obes Relat Metab Disord. 2003; 27: 289-301.
10.1038/sj.ijo.0802250
CASPubMedWeb of Science®Google Scholar
343Beal JE, Olson R, Laubenstein L, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage. 1995; 10: 89-97.
10.1016/0885-3924(94)00117-4
CASPubMedWeb of Science®Google Scholar
344Beal JE, Olson R, Lefkowitz L, et al. Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia. JPain Symptom Manage. 1997; 14: 7-14.
10.1016/S0885-3924(97)00038-9
CASPubMedWeb of Science®Google Scholar
345Nauck F, Klaschik E. Cannabinoids in the treatment of the cachexia-anorexia syndrome in palliative care patients. Schmerz. 2004; 18: 197-202.
10.1007/s00482-003-0277-z
CASPubMedWeb of Science®Google Scholar
346Nelson K, Walsh D, Deeter P, Sheehan F. A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. JPalliat Care. 1994; 10: 14-18.
10.1177/082585979401000105
CASPubMedGoogle Scholar
347Mattes RD, Engelman K, Shaw LM, Elsohly MA. Cannabinoids and appetite stimulation. Pharmacol Biochem Behav. 1994; 49: 187-195.
10.1016/0091-3057(94)90475-8
CASPubMedWeb of Science®Google Scholar
348Regelson W, Butler JR, Schultz J, Delta-9-THC as an effective antidepressant and appetite stimulating agent in advanced cancer patients. In: Int Conf Pharmacol Cannabis. Savannah: Raven; 1974.

Google Scholar
349Regelson W, Butler JR, Schulz J, Delta-9-tetracannabinol as an effective antidepressant and appetite-stimulating agent in advanced cancer patients. In: MC Braude, S Szara, eds. The Pharmacology of Marijuana. New York: Raven Press; 1976: 763-775.

Google Scholar
350Voth EA, Schwartz RH. Medicinal applications of delta-9-tetrahydrocannabinol and marijuana. Ann Intern Med. 1997; 126: 791-798.
10.7326/0003-4819-126-10-199705150-00008
CASPubMedWeb of Science®Google Scholar
351Gorter R, Seefried M, Volberding P. Dronabinol effects on weight in patients with HIV infection. Aids. 1992; 6: 127.
10.1097/00002030-199201000-00018
CASPubMedWeb of Science®Google Scholar
352Gorter RW. Cancer cachexia and cannabinoids. Forsch Komplementarmed. 1999; 6(Suppl 3): 21-22.

PubMedWeb of Science®Google Scholar
353Gorter RW. Experiences with dronabinol (delta-tetrahydrocannabinol) in oncological patients with anorexia-cachexia syndrome. Illustration of clinical problems and therapy based on 2 case reports. Schmerz. 2004; 18: S31-S33.

PubMedWeb of Science®Google Scholar
354Brisbois TD, de Kock IH, Watanabe SM, et al. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Ann Oncol. 2011; 22: 2086-2093.
10.1093/annonc/mdq727
CASPubMedWeb of Science®Google Scholar
355Ravikoff Allegretti J, Courtwright A, Lucci M, Korzenik JR, Levine J. Marijuana use patterns among patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013; 19: 2809-2814.
10.1097/01.MIB.0000435851.94391.37
PubMedWeb of Science®Google Scholar
356Weiss A, Friedenberg F. Patterns of cannabis use in patients with Inflammatory Bowel Disease: A population based analysis. Drug Alcohol Depend. 2015; 156: 84-89.
10.1016/j.drugalcdep.2015.08.035
PubMedWeb of Science®Google Scholar
357Naftali T, Bar-Lev Schleider L, Dotan I, Lansky EP, Sklerovsky Benjaminov F, Konikoff FM. Cannabis induces a clinical response in patients with Crohn's disease: a prospective placebo-controlled study. Clin Gastroenterol Hepatol. 2013; 11: 1276-1280.e1.
10.1016/j.cgh.2013.04.034
CASPubMedWeb of Science®Google Scholar
358Naftali T, Lev LB, Yablecovitch D, Yablekovitz D, Half E, Konikoff FM. Treatment of Crohn's disease with cannabis: an observational study. Isr Med Assoc J. 2011; 13: 455-458.

PubMedWeb of Science®Google Scholar
359Hong J, Nandiwada V, Jones V, et al. CB1 cannabinoid receptor agonist inhibits matrix metalloproteinase activity in spinal cord injury: A possible mechanism of improved recovery. Neurosci Lett. 2015; 597: 19-24.
10.1016/j.neulet.2015.04.016
CASPubMedWeb of Science®Google Scholar
360Kwiatkoski M, Guimaraes FS, Del-Bel E. Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury. Neurotox Res. 2012; 21: 271-280.
10.1007/s12640-011-9273-8
CASPubMedWeb of Science®Google Scholar
361Arevalo-Martin A, Garcia-Ovejero D, Sierra-Palomares Y, et al. Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery. PLoS One. 2012; 7: e49057.
10.1371/journal.pone.0049057
CASPubMedWeb of Science®Google Scholar
362Kavia RB, De Ridder D, Constantinescu CS, Stott CG, Fowler CJ. Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Mult Scler. 2010; 16: 1349-1359.
10.1177/1352458510378020
CASPubMedWeb of Science®Google Scholar
363Turner CE, Elsohly MA, Boeren EG. Constituents of Cannabis sativa L. XVII. A review of the natural constituents. J Nat Prod. 1980; 43: 169-234.
10.1021/np50008a001
CASPubMedWeb of Science®Google Scholar
364Borgelt LM, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy. 2013; 33: 195-209.
10.1002/phar.1187
CASPubMedWeb of Science®Google Scholar
365Petro DJ, Ellenberger C Jr. Treatment of human spasticity with delta 9-tetrahydrocannabinol. J Clin Pharmacol. 1981; 21: 413S-416S.
10.1002/j.1552-4604.1981.tb02621.x
CASPubMedWeb of Science®Google Scholar
366Hagenbach U, Luz S, Ghafoor N, et al. The treatment of spasticity with Delta9-tetrahydrocannabinol in persons with spinal cord injury. Spinal Cord. 2007; 45: 551-562.
10.1038/sj.sc.3101982
CASPubMedWeb of Science®Google Scholar
367Appendino G, Gibbons S, Giana A, et al. Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. J Nat Prod. 2008; 71: 1427-1430.
10.1021/np8002673
CASPubMedWeb of Science®Google Scholar
368Ligresti A, Moriello AS, Starowicz K, et al. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J Pharmacol Exp Ther. 2006; 318: 1375-1387.
10.1124/jpet.106.105247
CASPubMedWeb of Science®Google Scholar
369Scott KA, Dalgleish AG, Liu WM. Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration. Int J Oncol. 2017; 51: 369-377.
10.3892/ijo.2017.4022
CASPubMedWeb of Science®Google Scholar
370Salazar M, Carracedo A, Salanueva IJ, et al. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest. 2009; 119: 1359-1372.
10.1172/JCI37948
CASPubMedWeb of Science®Google Scholar
371Liu WM, Scott KA, Shamash J, Joel S, Powles TB. Enhancing the in vitro cytotoxic activity of Delta9-tetrahydrocannabinol in leukemic cells through a combinatorial approach. Leuk Lymphoma. 2008; 49: 1800.
10.1080/10428190802239188
CASPubMedWeb of Science®Google Scholar
372Powles T, te Poele R, Shamash J, et al. Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway. Blood. 2005; 105: 1214-1221.
10.1182/blood-2004-03-1182
CASPubMedWeb of Science®Google Scholar
373Caffarel MM, Sarrio D, Palacios J, Guzman M, Sanchez C. Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res. 2006; 66: 6615-6621.
10.1158/0008-5472.CAN-05-4566
CASPubMedWeb of Science®Google Scholar
374Caffarel MM, Moreno-Bueno G, Cerutti C, et al. JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008; 27: 5033-5044.
10.1038/onc.2008.145
CASPubMedWeb of Science®Google Scholar
375Caffarel MM, Andradas C, Mira E, et al. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. Mol Cancer. 2010; 9: 196.
10.1186/1476-4598-9-196
CASPubMedWeb of Science®Google Scholar
376Greenhough A, Patsos HA, Williams AC, Paraskeva C. The cannabinoid delta(9)-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells. Int J Cancer. 2007; 121: 2172-2180.
10.1002/ijc.22917
CASPubMedWeb of Science®Google Scholar
377Preet A, Ganju RK, Groopman JE. Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene. 2008; 27: 339-346.
10.1038/sj.onc.1210641
CASPubMedWeb of Science®Google Scholar
378Guzman M, Duarte MJ, Blazquez C, et al. A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br J Cancer. 2006; 95: 197-203.
10.1038/sj.bjc.6603236
CASPubMedWeb of Science®Google Scholar
379Marcu JP, Christian RT, Lau D, et al. Cannabidiol enhances the inhibitory effects of delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol Cancer Ther. 2010; 9: 180-189.
10.1158/1535-7163.MCT-09-0407
CASPubMedWeb of Science®Google Scholar
380Norooznezhad AH, Norooznezhad F. Cannabinoids: Possible agents for treatment of psoriasis via suppression of angiogenesis and inflammation. Med Hypotheses. 2017; 99: 15-18.
10.1016/j.mehy.2016.12.003
CASPubMedWeb of Science®Google Scholar
381Wilkinson JD, Williamson EM. Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. J Dermatol Sci. 2007; 45: 87-92.
10.1016/j.jdermsci.2006.10.009
CASPubMedWeb of Science®Google Scholar
382Williams SJ, Hartley JP, Graham JD. Bronchodilator effect of delta1-tetrahydrocannabinol administered by aerosol of asthmatic patients. Thorax. 1976; 31: 720-723.
10.1136/thx.31.6.720
CASPubMedWeb of Science®Google Scholar
383Abboud RT, Sanders HD. Effect of oral administration of delta-tetrahydrocannabinol on airway mechanics in normal and asthmatic subjects. Chest. 1976; 70: 480-485.
10.1378/chest.70.4.480
CASPubMedWeb of Science®Google Scholar
384Hartley JP, Nogrady SG, Seaton A. Bronchodilator effect of delta1-tetrahydrocannabinol. Br J Clin Pharmacol. 1978; 5: 523-525.
10.1111/j.1365-2125.1978.tb01667.x
CASPubMedWeb of Science®Google Scholar
385Rajavashisth TB, Shaheen M, Norris KC, et al. Decreased prevalence of diabetes in marijuana users: cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) III. BMJ Open. 2012; 2: e000494.
10.1136/bmjopen-2011-000494
PubMedWeb of Science®Google Scholar
386Le Foll B, Trigo JM, Sharkey KA, Le Strat Y. Cannabis and Delta9-tetrahydrocannabinol (THC) for weight loss?. Med Hypotheses. 2013; 80: 564-567.
10.1016/j.mehy.2013.01.019
CASPubMedWeb of Science®Google Scholar
387Hepler RS, Frank IR. Marihuana smoking and intraocular pressure. Jama. 1971; 217: 1392.
10.1001/jama.1971.03190100074024
CASPubMedWeb of Science®Google Scholar
388Colasanti BK. Ocular hypotensive effect of marihuana cannabinoids: correlate of central action or separate phenomenon?. J Ocul Pharmacol. 1986; 2: 295-304.
10.1089/jop.1986.2.295
CASPubMedGoogle Scholar
389Tomida I, Azuara-Blanco A, House H, Flint M, Pertwee RG, Robson PJ. Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study. J Glaucoma. 2006; 15: 349-353.
10.1097/01.ijg.0000212260.04488.60
PubMedWeb of Science®Google Scholar
390Tomida I, Pertwee RG, Azuara-Blanco A. Cannabinoids and glaucoma. Br J Ophthalmol. 2004; 88: 708-713.
10.1136/bjo.2003.032250
CASPubMedWeb of Science®Google Scholar
391Green K. Marijuana smoking vs cannabinoids for glaucoma therapy. Arch Ophthalmol. 1998; 116: 1433-1437.
10.1001/archopht.116.11.1433
CASPubMedWeb of Science®Google Scholar
392Green K, Wynn H, Bowman KA. A comparison of topical cannabinoids on intraocular pressure. Exp Eye Res. 1978; 27: 239-246.
10.1016/0014-4835(78)90092-1
CASPubMedWeb of Science®Google Scholar
393Merritt JC, Perry DD, Russell DN, Jones BF. Topical delta 9-tetrahydrocannabinol and aqueous dynamics in glaucoma. J Clin Pharmacol. 1981; 21: 467S-71S.
10.1002/j.1552-4604.1981.tb02626.x
CASPubMedWeb of Science®Google Scholar
394Maor D, Treves T, Korczyn AD. Lack of effect of cannabinoids on carbonic anhydrase. J Neural Transm. 1980; 49: 205-206.
10.1007/BF01245226
CASPubMedWeb of Science®Google Scholar
395Merritt JC, Olsen JL, Armstrong JR, McKinnon SM. Topical delta 9-tetrahydrocannabinol in hypertensive glaucomas. J Pharm Pharmacol. 1981; 33: 40-41.
10.1111/j.2042-7158.1981.tb13699.x
CASPubMedWeb of Science®Google Scholar
396Flach AJ. Delta-9-tetrahydrocannabinol (THC) in the treatment of end-stage open-angle glaucoma. Trans Am Ophthalmol Soc. 2002; 100: 215-222. discussion 222-4.

PubMedGoogle Scholar
397Wan MJ, Daniel S, Kassam F, et al. Survey of complementary and alternative medicine use in glaucoma patients. J Glaucoma. 2012; 21: 79-82.

PubMedWeb of Science®Google Scholar
398Merritt JC, Crawford WJ, Alexander PC, Anduze AL, Gelbart SS. Effect of marihuana on intraocular and blood pressure in glaucoma. Ophthalmology. 1980; 87: 222-228.
10.1016/S0161-6420(80)35258-5
CASPubMedWeb of Science®Google Scholar
399Zhan GL, Camras CB, Palmberg PF, Toris CB. Effects of marijuana on aqueous humor dynamics in a glaucoma patient. J Glaucoma. 2005; 14: 175-177.
10.1097/01.ijg.0000151882.07232.1d
PubMedWeb of Science®Google Scholar
400Neff GW, O'Brien CB, Reddy KR, et al. Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease. Am J Gastroenterol. 2002; 97: 2117-2119.
10.1111/j.1572-0241.2002.05852.x
PubMedWeb of Science®Google Scholar
401 Cannabidiol (CBD) Pre-Review Report. World Health Organization: Expert Committee on Drug Dependence. (Accessed December 20, 2017, at http://www.who.int/medicines/access/controlled-substances/5.2_CBD.pdf).

Google Scholar
402 “Prohibited List: January 2018”. The World Anti-Doping Code International Standard. World Anti-Doping Agency (WADA). (Accessed 4/23, 2018, at https://www.wada-ama.org/sites/default/files/prohibited_list_2018_en.pdf).

Google Scholar
403Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol. 2007; 150: 613-623.
10.1038/sj.bjp.0707133
CASPubMedWeb of Science®Google Scholar
404Russo E, Guy GW. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses. 2006; 66: 234-246.
10.1016/j.mehy.2005.08.026
CASPubMedWeb of Science®Google Scholar
405Murillo-Rodriguez E, Millan-Aldaco D, Palomero-Rivero M, Mechoulam R, Drucker CR. Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats. FEBS Lett. 2006; 580: 4337-4345.
10.1016/j.febslet.2006.04.102
CASPubMedWeb of Science®Google Scholar
406Nicholson AN, Turner C, Stone BM, Robson PJ. Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. J Clin Psychopharmacol. 2004; 24: 305-313.
10.1097/01.jcp.0000125688.05091.8f
CASPubMedWeb of Science®Google Scholar
407Zuardi AW, Hallak JE, Crippa JA. Interaction between cannabidiol (CBD) and (9)-tetrahydrocannabinol (THC): influence of administration interval and dose ratio between the cannabinoids. Psychopharmacology (Berl). 2012; 219: 247-249.
10.1007/s00213-011-2495-x
CASPubMedWeb of Science®Google Scholar
408Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berl). 1982; 76: 245-250.
10.1007/BF00432554
CASPubMedWeb of Science®Google Scholar
409Zuardi AW, Finkelfarb E, Bueno OF, Musty RE, Karniol IG. Characteristics of the stimulus produced by the mixture of cannabidiol with delta 9-tetrahydrocannabinol. Arch Int Pharmacodyn Ther. 1981; 249: 137-146.

CASPubMedWeb of Science®Google Scholar
410Wright MJ, Jr, Vandewater SA, Taffe MA. Cannabidiol attenuates deficits of visuospatial associative memory induced by Delta(9) tetrahydrocannabinol. Br J Pharmacol. 2013; 170: 1365-1373.
10.1111/bph.12199
CASPubMedWeb of Science®Google Scholar
411Zuardi AW. Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev Bras Psiquiatr. 2008; 30: 271-280.
10.1590/S1516-44462008000300015
PubMedWeb of Science®Google Scholar
412Bisogno T, Hanus L, De Petrocellis L, et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. 2001; 134: 845-852.
10.1038/sj.bjp.0704327
CASPubMedWeb of Science®Google Scholar
413Ahrens J, Demir R, Leuwer M, et al. The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-Beta glycine receptor function. Pharmacology. 2009; 83: 217-222.
10.1159/000201556
CASPubMedWeb of Science®Google Scholar
414Qin N, Neeper MP, Liu Y, Hutchinson TL, Lubin ML, Flores CM. TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J Neurosci. 2008; 28: 6231-6238.
10.1523/JNEUROSCI.0504-08.2008
CASPubMedWeb of Science®Google Scholar
415Ross HR, Napier I, Connor M. Inhibition of recombinant human T-type calcium channels by Delta9-tetrahydrocannabinol and cannabidiol. J Biol Chem. 2008; 283: 16124-16134.
10.1074/jbc.M707104200
CASPubMedWeb of Science®Google Scholar
416Jenny M, Santer E, Pirich E, Schennach H, Fuchs D. Delta9-tetrahydrocannabinol and cannabidiol modulate mitogen-induced tryptophan degradation and neopterin formation in peripheral blood mononuclear cells in vitro. J Neuroimmunol. 2009; 207: 75-82.
10.1016/j.jneuroim.2008.12.004
CASPubMedWeb of Science®Google Scholar
417Evans AT, Formukong E, Evans FJ. Activation of phospholipase A2 by cannabinoids. Lack of correlation with CNS effects. FEBS Lett. 1987; 211: 119-122.
10.1016/0014-5793(87)81420-5
CASPubMedWeb of Science®Google Scholar
418Mechoulam R, Parker LA, Gallily R. Cannabidiol: an overview of some pharmacological aspects. J Clin Pharmacol. 2002; 42: 11S-19S.
10.1002/j.1552-4604.2002.tb05998.x
CASPubMedWeb of Science®Google Scholar
419Pagano E, Capasso R, Piscitelli F, et al. An orally active cannabis extract with high content in cannabidiol attenuates chemically-induced intestinal inflammation and hypermotility in the mouse. Front Pharmacol. 2016; 7: 341.
10.3389/fphar.2016.00341
PubMedWeb of Science®Google Scholar
420Mechoulam R, Peters M, Murillo-Rodriguez E, Hanus LO. Cannabidiol–recent advances. Chem Biodivers. 2007; 4: 1678-1692.
10.1002/cbdv.200790147
CASPubMedWeb of Science®Google Scholar
421Malfait AM, Gallily R, Sumariwalla PF, et al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci U S A. 2000; 97: 9561-9566.
10.1073/pnas.160105897
CASPubMedWeb of Science®Google Scholar
422Formukong EA, Evans AT, Evans FJ. Analgesic and antiinflammatory activity of constituents of Cannabis sativa L. Inflammation. 1988; 12: 361-371.
10.1007/BF00915771
CASPubMedWeb of Science®Google Scholar
423Formukong EA, Evans AT, Evans FJ. The medicinal uses of cannabis and its constituents. Phytother Res. 1989; 3: 219-231.
10.1002/ptr.2650030602
CASWeb of Science®Google Scholar
424Costa B, Trovato AE, Comelli F, Giagnoni G, Colleoni M. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur J Pharmacol. 2007; 556: 75-83.
10.1016/j.ejphar.2006.11.006
CASPubMedWeb of Science®Google Scholar
425Costa B, Colleoni M, Conti S, et al. Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn Schmiedebergs Arch Pharmacol. 2004; 369: 294-299.
10.1007/s00210-004-0871-3
CASPubMedWeb of Science®Google Scholar
426Booz GW. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic Biol Med. 2011; 51: 1054-1061.
10.1016/j.freeradbiomed.2011.01.007
CASPubMedWeb of Science®Google Scholar
427McHugh D, Tanner C, Mechoulam R, Pertwee RG, Ross RA. Inhibition of human neutrophil chemotaxis by endogenous cannabinoids and phytocannabinoids: evidence for a site distinct from CB1 and CB2. Mol Pharmacol. 2007; 73: 441-450.
10.1124/mol.107.041863
PubMedWeb of Science®Google Scholar
428Zhornitsky S, Potvin S. Cannabidiol in humans-the quest for therapeutic targets. Pharmaceuticals (Basel). 2012; 5: 529-552.
10.3390/ph5050529
CASPubMedGoogle Scholar
429Ribeiro A, Almeida VI, Costola-de-Souza C, et al. Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury. Immunopharmacol Immunotoxicol. 2015; 37: 35-41.
10.3109/08923973.2014.976794
CASPubMedWeb of Science®Google Scholar
430Ribeiro A, Ferraz-de-Paula V, Pinheiro ML, et al. Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor. Eur J Pharmacol. 2012; 678: 78-85.
10.1016/j.ejphar.2011.12.043
CASPubMedWeb of Science®Google Scholar
431Kozela E, Lev N, Kaushansky N, et al. Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL/6 mice. Br J Pharmacol. 2011; 163: 1507-1519.
10.1111/j.1476-5381.2011.01379.x
CASPubMedWeb of Science®Google Scholar
432Mecha M, Feliu A, Inigo PM, Mestre L, Carrillo-Salinas FJ, Guaza C. Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors. Neurobiol Dis. 2013; 59: 141-150.
10.1016/j.nbd.2013.06.016
CASPubMedWeb of Science®Google Scholar
433Mecha M, Torrao AS, Mestre L, Carrillo-Salinas FJ, Mechoulam R, Guaza C. Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress. Cell Death Dis. 2012; 3: e331.
10.1038/cddis.2012.71
CASPubMedWeb of Science®Google Scholar
434Comelli F, Bettoni I, Colleoni M, Giagnoni G, Costa B. Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress. Phytother Res. 2009; 23: 1678-1684.
10.1002/ptr.2806
CASPubMedWeb of Science®Google Scholar
435Comelli F, Giagnoni G, Bettoni I, Colleoni M, Costa B. Antihyperalgesic effect of a Cannabis sativa extract in a rat model of neuropathic pain: mechanisms involved. Phytother Res. 2008; 22: 1017-1024.
10.1002/ptr.2401
CASPubMedWeb of Science®Google Scholar
436Howard J, Anie KA, Holdcroft A, Korn S, Davies SC. Cannabis use in sickle cell disease: a questionnaire study. Br J Haematol. 2005; 131: 123-128.
10.1111/j.1365-2141.2005.05723.x
CASPubMedWeb of Science®Google Scholar
437Maione S, Piscitelli F, Gatta L, et al. Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action. Br J Pharmacol. 2011; 162: 584-596.
10.1111/j.1476-5381.2010.01063.x
CASPubMedWeb of Science®Google Scholar
438Williamson EM, Evans FJ. Cannabinoids in clinical practice. Drugs. 2000; 60: 1303-1314.
10.2165/00003495-200060060-00005
CASPubMedWeb of Science®Google Scholar
439Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res. 2005; 30: 1037-1043.
10.1007/s11064-005-6978-1
CASPubMedWeb of Science®Google Scholar
440Drysdale AJ, Ryan D, Pertwee RG, Platt B. Cannabidiol-induced intracellular Ca2+ elevations in hippocampal cells. Neuropharmacology. 2006; 50: 621-631.
10.1016/j.neuropharm.2005.11.008
CASPubMedWeb of Science®Google Scholar
441Ryan D, Drysdale AJ, Lafourcade C, Pertwee RG, Platt B. Cannabidiol targets mitochondria to regulate intracellular Ca2+ levels. J Neurosci. 2009; 29: 2053-2063.
10.1523/JNEUROSCI.4212-08.2009
CASPubMedWeb of Science®Google Scholar
442Carrier EJ, Auchampach JA, Hillard CJ. Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci U S A. 2006; 103: 7895-7900.
10.1073/pnas.0511232103
CASPubMedWeb of Science®Google Scholar
443O'Sullivan SE, Sun Y, Bennett AJ, Randall MD, Kendall DA. Time-dependent vascular actions of cannabidiol in the rat aorta. Eur J Pharmacol. 2009; 612: 61-68.
10.1016/j.ejphar.2009.03.010
CASPubMedWeb of Science®Google Scholar
444Takeda S, Usami N, Yamamoto I, Watanabe K. Cannabidiol-2',6'-dimethyl ether, a cannabidiol derivative, is a highly potent and selective 15-lipoxygenase inhibitor. Drug Metab Dispos. 2009; 37: 1733-1737.
10.1124/dmd.109.026930
CASPubMedWeb of Science®Google Scholar
445Walter L, Franklin A, Witting A, et al. Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci. 2003; 23: 1398-1405.
10.1523/JNEUROSCI.23-04-01398.2003
CASPubMedWeb of Science®Google Scholar
446Pisanti S, Malfitano AM, Ciaglia E, et al. Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacol Ther. 2017; 175: 133-150.
10.1016/j.pharmthera.2017.02.041
CASPubMedWeb of Science®Google Scholar
447Devinsky O, Cross JH, Laux L, Cannabidiol in Dravet Syndrome Study Group, et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017; 376: 2011-2020.
10.1056/NEJMoa1611618
CASPubMedWeb of Science®Google Scholar
448Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016; 15: 270-278.
10.1016/S1474-4422(15)00379-8
CASPubMedWeb of Science®Google Scholar
449Devinsky O, Cilio MR, Cross H, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014; 55: 791-802.
10.1111/epi.12631
CASPubMedWeb of Science®Google Scholar
450De Caro C, Leo A, Citraro R, et al. The potential role of cannabinoids in epilepsy treatment. Expert Rev Neurother. 2017; 17: 1069-1079.
10.1080/14737175.2017.1373019
PubMedWeb of Science®Google Scholar
451O'Connell BK, Gloss D, Devinsky O. Cannabinoids in treatment-resistant epilepsy: A review. Epilepsy Behav. 2017; 70: 341-348.
10.1016/j.yebeh.2016.11.012
PubMedWeb of Science®Google Scholar
452Crippa JA, Crippa AC, Hallak JE, Martin-Santos R, Zuardi AW. Delta9-THC intoxication by cannabidiol-enriched cannabis extract in two children with refractory epilepsy: Full remission after switching to purified cannabidiol. Front Pharmacol. 2016; 7: 359.
10.3389/fphar.2016.00359
PubMedWeb of Science®Google Scholar
453Hess EJ, Moody KA, Geffrey AL, et al. Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex. Epilepsia. 2016; 57: 1617-1624.
10.1111/epi.13499
CASPubMedWeb of Science®Google Scholar
454Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015; 56: 1246-1251.
10.1111/epi.13060
CASPubMedWeb of Science®Google Scholar
455Carlini EA, Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol. 1981; 21: 417S-427S.
10.1002/j.1552-4604.1981.tb02622.x
CASPubMedWeb of Science®Google Scholar
456Jones NA, Hill AJ, Smith I, et al. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. J Pharmacol Exp Ther. 2010; 332: 569-577.
10.1124/jpet.109.159145
CASPubMedWeb of Science®Google Scholar
457Friedman D, Sirven JI. Historical perspective on the medical use of cannabis for epilepsy: Ancient times to the 1980s. Epilepsy Behav. 2017; 70: 298-301.
10.1016/j.yebeh.2016.11.033
PubMedWeb of Science®Google Scholar
458Friedman D, Devinsky O. Cannabinoids in the treatment of epilepsy. N Engl J Med. 2015; 373: 1048-1058.
10.1056/NEJMra1407304
CASPubMedWeb of Science®Google Scholar
459Katona I. Cannabis and endocannabinoid signaling in epilepsy. Handb Exp Pharmacol. 2015; 231: 285-316.
10.1007/978-3-319-20825-1_10
CASPubMedGoogle Scholar
460Rosenberg EC, Tsien RW, Whalley BJ, Devinsky O. Cannabinoids and epilepsy. Neurotherapeutics. 2015; 12: 747-768.
10.1007/s13311-015-0375-5
CASPubMedWeb of Science®Google Scholar
461Rosenberg EC, Patra PH, Whalley BJ. Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection. Epilepsy Behav. 2017; 70: 319-327.
10.1016/j.yebeh.2016.11.006
PubMedWeb of Science®Google Scholar
462Hofmann ME, Frazier CJ. Marijuana, endocannabinoids, and epilepsy: potential and challenges for improved therapeutic intervention. Exp Neurol. 2013; 244: 43-50.
10.1016/j.expneurol.2011.11.047
CASPubMedWeb of Science®Google Scholar
463Karler R, Cely W, Turkanis SA. The anticonvulsant activity of cannabidiol and cannabinol. Life Sci. 1973; 13: 1527-1531.
10.1016/0024-3205(73)90141-0
CASPubMedWeb of Science®Google Scholar
464Blair RE, Deshpande LS, DeLorenzo RJ. Cannabinoids: is there a potential treatment role in epilepsy?. Expert Opin Pharmacother. 2015; 16: 1911-1914.
10.1517/14656566.2015.1074181
CASPubMedWeb of Science®Google Scholar
465Szaflarski JP, Bebin EM. Cannabis, cannabidiol, and epilepsy–from receptors to clinical response. Epilepsy Behav. 2014; 41: 277-282.
10.1016/j.yebeh.2014.08.135
PubMedWeb of Science®Google Scholar
466Porter BE, Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav. 2013; 29: 574-577.
10.1016/j.yebeh.2013.08.037
PubMedWeb of Science®Google Scholar
467Hussain SA, Zhou R, Jacobson C, et al. Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy Behav. 2015; 47: 138-141.
10.1016/j.yebeh.2015.04.009
PubMedWeb of Science®Google Scholar
468Cunha JM, Carlini EA, Pereira AE, et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology. 1980; 21: 175-185.
10.1159/000137430
CASPubMedWeb of Science®Google Scholar
469Karler R, Turkanis SA. Subacute cannabinoid treatment: anticonvulsant activity and withdrawal excitability in mice. Br J Pharmacol. 1980; 68: 479-484.
10.1111/j.1476-5381.1980.tb14562.x
CASPubMedWeb of Science®Google Scholar
470Karler R, Turkanis SA. The cannabinoids as potential antiepileptics. J Clin Pharmacol. 1981; 21: 437S-48S.
10.1002/j.1552-4604.1981.tb02624.x
CASPubMedWeb of Science®Google Scholar
471Consroe P, Martin A, Singh V. Antiepileptic potential of cannabidiol analogs. J Clin Pharmacol. 1981; 21: 428S-436S.
10.1002/j.1552-4604.1981.tb02623.x
CASPubMedWeb of Science®Google Scholar
472Chiu P, Olsen DM, Borys HK, Karler R, Turkanis SA. The influence of cannabidiol and delta 9-tetrahydrocannabinol on cobalt epilepsy in rats. Epilepsia. 1979; 20: 365-375.
10.1111/j.1528-1157.1979.tb04816.x
CASPubMedWeb of Science®Google Scholar
473Esposito G, Scuderi C, Valenza M, et al. Cannabidiol reduces Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement. PLoS One. 2011; 6: e28668-8.
10.1371/journal.pone.0028668
CASPubMedWeb of Science®Google Scholar
474Esposito G, Scuderi C, Savani C, et al. Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression. Br J Pharmacol. 2007; 151: 1272-1279.
10.1038/sj.bjp.0707337
CASPubMedWeb of Science®Google Scholar
475Esposito G, De Filippis D, Carnuccio R, Izzo AA, Iuvone T. The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells. J Mol Med (Berl). 2006; 84: 253-258.
10.1007/s00109-005-0025-1
CASPubMedWeb of Science®Google Scholar
476Esposito G, De Filippis D, Maiuri MC, De Stefano D, Carnuccio R, Iuvone T. Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement. Neurosci Lett. 2006; 399: 91-95.
10.1016/j.neulet.2006.01.047
CASPubMedWeb of Science®Google Scholar
477Watt G, Karl T. In vivo evidence for therapeutic properties of cannabidiol (CBD) for Alzheimer's disease. Front Pharmacol. 2017; 8: 20.
10.3389/fphar.2017.00020
PubMedWeb of Science®Google Scholar
478Hayakawa K, Mishima K, Nozako M, et al. Delayed treatment with cannabidiol has a cerebroprotective action via a cannabinoid receptor-independent myeloperoxidase-inhibiting mechanism. J Neurochem. 2007; 102: 1488-1496.
10.1111/j.1471-4159.2007.04565.x
CASPubMedWeb of Science®Google Scholar
479Martin-Moreno AM, Reigada D, Ramirez BG, et al. Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer's disease. Mol Pharmacol. 2011; 79: 964-973.
10.1124/mol.111.071290
CASPubMedWeb of Science®Google Scholar
480Scuderi C, Steardo L, Esposito G. Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of beta amyloid expression in SHSY5YAPP+ cells through PPARgamma involvement. Phytother Res. 2014; 28: 1007-1013.
10.1002/ptr.5095
CASPubMedWeb of Science®Google Scholar
481Cheng D, Spiro AS, Jenner AM, Garner B, Karl T. Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer's disease transgenic mice. J Alzheimers Dis. 2014; 42: 1383-1396.
10.3233/JAD-140921
CASPubMedWeb of Science®Google Scholar
482Cheng D, Low JK, Logge W, Garner B, Karl T. Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1E9 mice. Psychopharmacology (Berl). 2014; 231: 3009-3017.
10.1007/s00213-014-3478-5
CASPubMedWeb of Science®Google Scholar
483Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML. Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci. 2005; 25: 1904-1913.
10.1523/JNEUROSCI.4540-04.2005
CASPubMedWeb of Science®Google Scholar
484Iuvone T, Esposito G, Esposito R, Santamaria R, Di Rosa M, Izzo AA. Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. J Neurochem. 2004; 89: 134-141.
10.1111/j.1471-4159.2003.02327.x
CASPubMedWeb of Science®Google Scholar
485Iuvone T, Esposito G, De Filippis D, Scuderi C, Steardo L. Cannabidiol: a promising drug for neurodegenerative disorders?. CNS Neurosci Ther. 2009; 15: 65-75.
10.1111/j.1755-5949.2008.00065.x
CASPubMedWeb of Science®Google Scholar
486Campbell VA, Gowran A. Alzheimer's disease; taking the edge off with cannabinoids?. Br J Pharmacol. 2007; 152: 655-662.
10.1038/sj.bjp.0707446
CASPubMedWeb of Science®Google Scholar
487da Silva VK, de Freitas BS, da Silva Dornelles A, et al. Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: implications for neuroprotection. Mol Neurobiol. 2014; 49: 222-233.
10.1007/s12035-013-8514-7
CASPubMedWeb of Science®Google Scholar
488Fernandez-Ruiz J, Sagredo O, Pazos MR, et al. Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?. Br J Clin Pharmacol. 2013; 75: 323-333.
10.1111/j.1365-2125.2012.04341.x
CASPubMedWeb of Science®Google Scholar
489Santos NA, Martins NM, Sisti FM, et al. The neuroprotection of cannabidiol against MPP(+)-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson's disease. Toxicol in Vitro. 2015; 30: 231-240.
10.1016/j.tiv.2015.11.004
CASPubMedWeb of Science®Google Scholar
490Lastres-Becker I, Molina-Holgado F, Ramos JA, Mechoulam R, Fernandez-Ruiz J. Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: relevance to Parkinson's disease. Neurobiol Dis. 2005; 19: 96-107.
10.1016/j.nbd.2004.11.009
CASPubMedWeb of Science®Google Scholar
491Chagas MH, Zuardi AW, Tumas V, et al. Effects of cannabidiol in the treatment of patients with Parkinson's disease: an exploratory double-blind trial. J Psychopharmacol. 2014; 28: 1088-1098.
10.1177/0269881114550355
CASPubMedWeb of Science®Google Scholar
492Chagas MH, Eckeli AL, Zuardi AW, et al. Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's disease patients: a case series. J Clin Pharm Ther. 2014; 39: 564-566.
10.1111/jcpt.12179
CASPubMedWeb of Science®Google Scholar
493Zuardi AW, Crippa JA, Hallak JE, et al. Cannabidiol for the treatment of psychosis in Parkinson's disease. J Psychopharmacol. 2009; 23: 979-983.
10.1177/0269881108096519
CASPubMedWeb of Science®Google Scholar
494Campos AC, Fogaca MV, Sonego AB, Guimaraes FS. Cannabidiol, neuroprotection and neuropsychiatric disorders. Pharmacol Res. 2016; 112: 119-127.
10.1016/j.phrs.2016.01.033
CASPubMedWeb of Science®Google Scholar
495Garcia-Arencibia M, Garcia C, Fernandez-Ruiz J. Cannabinoids and Parkinson's disease. CNS Neurol Disord Drug Targets. 2009; 8: 432-439.
10.2174/187152709789824642
CASPubMedWeb of Science®Google Scholar
496García-Arencibia M, González S, de Lago E, Ramos JA, Mechoulam R, Fernández-Ruiz J. Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson's disease: importance of antioxidant and cannabinoid receptor-independent properties. Brain Res. 2007; 1134: 162-170.
10.1016/j.brainres.2006.11.063
CASPubMedWeb of Science®Google Scholar
497Fernandez-Ruiz J, Moreno-Martet M, Rodriguez-Cueto C, et al. Prospects for cannabinoid therapies in basal ganglia disorders. Br J Pharmacol. 2011; 163: 1365-1378.
10.1111/j.1476-5381.2011.01365.x
CASPubMedWeb of Science®Google Scholar
498Kozela E, Juknat A, Gao F, Kaushansky N, Coppola G, Vogel Z. Pathways and gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells. J Neuroinflammation. 2016; 13: 136.
10.1186/s12974-016-0603-x
PubMedWeb of Science®Google Scholar
499Kozela E, Juknat A, Kaushansky N, Ben-Nun A, Coppola G, Vogel Z. Cannabidiol, a non-psychoactive cannabinoid, leads to EGR2-dependent anergy in activated encephalitogenic T cells. J Neuroinflammation. 2015; 12: 52.
10.1186/s12974-015-0273-0
PubMedWeb of Science®Google Scholar
500Kozela E, Juknat A, Kaushansky N, Rimmerman N, Ben-Nun A, Vogel Z. Cannabinoids decrease the Th17 inflammatory autoimmune phenotype. J Neuroimmune Pharmacol. 2013; 8: 1265-1276.
10.1007/s11481-013-9493-1
PubMedWeb of Science®Google Scholar
501Giacoppo S, Pollastro F, Grassi G, Bramanti P, Mazzon E. Target regulation of PI3K/Akt/mTOR pathway by cannabidiol in treatment of experimental multiple sclerosis. Fitoterapia. 2017; 116: 77-84.
10.1016/j.fitote.2016.11.010
CASPubMedWeb of Science®Google Scholar
502Giacoppo S, Soundara Rajan T, Galuppo M, et al. Purified Cannabidiol, the main non-psychotropic component of Cannabis sativa, alone, counteracts neuronal apoptosis in experimental multiple sclerosis. Eur Rev Med Pharmacol Sci. 2015; 19: 4906-4919.

CASPubMedWeb of Science®Google Scholar
503Sagredo O, Pazos MR, Satta V, Ramos JA, Pertwee RG, Fernández-Ruiz J. Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington's disease. J Neurosci Res. 2011; 89: 1509-1518.
10.1002/jnr.22682
CASPubMedWeb of Science®Google Scholar
504Sagredo O, Ramos JA, Decio A, Mechoulam R, Fernandez-Ruiz J. Cannabidiol reduced the striatal atrophy caused 3-nitropropionic acid in vivo by mechanisms independent of the activation of cannabinoid, vanilloid TRPV1 and adenosine A2A receptors. Eur J Neurosci. 2007; 26: 843-851.
10.1111/j.1460-9568.2007.05717.x
CASPubMedWeb of Science®Google Scholar
505Consroe P, Laguna J, Allender J, et al. Controlled clinical trial of cannabidiol in Huntington's disease. Pharmacol Biochem Behav. 1991; 40: 701-708.
10.1016/0091-3057(91)90386-G
CASPubMedWeb of Science®Google Scholar
506Weydt P, Hong S, Witting A, Möller T, Stella N, Kliot M. Cannabinol delays symptom onset in SOD1 (G93A) transgenic mice without affecting survival. Amyotroph Lateral Scler Other Motor Neuron Disord. 2005; 6: 182-184.
10.1080/14660820510030149
CASPubMedWeb of Science®Google Scholar
507Resstel LBM, Tavares RF, Lisboa SFS, Joca SRL, Corrêa FMA, Guimarães FS. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br J Pharmacol. 2009; 156: 181-188.
10.1111/j.1476-5381.2008.00046.x
CASPubMedWeb of Science®Google Scholar
508Soares V. d P, Campos AC, Bortoli V. C d, Zangrossi H, Guimarães FS, Zuardi AW. Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors. Behav Brain Res. 2010; 213: 225-229.
10.1016/j.bbr.2010.05.004
CASPubMedWeb of Science®Google Scholar
509Campos AC, Fogaca MV, Scarante FF, et al. Plastic and neuroprotective mechanisms involved in the therapeutic effects of cannabidiol in psychiatric disorders. Front Pharmacol. 2017; 8: 269.
10.3389/fphar.2017.00269
PubMedWeb of Science®Google Scholar
510Schier A, Ribeiro N, Coutinho D, et al. Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa. CNS Neurol Disord Drug Targets. 2014; 13: 953-960.
10.2174/1871527313666140612114838
PubMedWeb of Science®Google Scholar
511Lemos JI, Resstel LB, Guimaraes FS. Involvement of the prelimbic prefrontal cortex on cannabidiol-induced attenuation of contextual conditioned fear in rats. Behav Brain Res. 2010; 207: 105-111.
10.1016/j.bbr.2009.09.045
CASPubMedWeb of Science®Google Scholar
512Almeida V, Levin R, Peres FF, et al. Cannabidiol exhibits anxiolytic but not antipsychotic property evaluated in the social interaction test. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 41: 30-35.
10.1016/j.pnpbp.2012.10.024
CASPubMedWeb of Science®Google Scholar
513Moreira FA, Wotjak CT. Cannabinoids and anxiety. Curr Top Behav Neurosci. 2010; 2: 429-450.
10.1007/7854_2009_16
PubMedWeb of Science®Google Scholar
514Moreira FA, Aguiar DC, Guimaraes FS. Anxiolytic-like effect of cannabidiol in the rat Vogel conflict test. Prog Neuropsychopharmacol Biol Psychiatry. 2006; 30: 1466-1471.
10.1016/j.pnpbp.2006.06.004
CASPubMedWeb of Science®Google Scholar
515Moreira FA, Grieb M, Lutz B. Central side-effects of therapies based on CB1 cannabinoid receptor agonists and antagonists: focus on anxiety and depression. Best Pract Res Clin Endocrinol Metab. 2009; 23: 133-144.
10.1016/j.beem.2008.09.003
CASPubMedWeb of Science®Google Scholar
516Schier AR, Ribeiro NP, Silva AC, et al. Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug. Rev Bras Psiquiatr. 2012; 34(Suppl 1): S104-S110.
10.1016/S1516-4446(12)70057-0
PubMedWeb of Science®Google Scholar
517Bergamaschi MM, Queiroz RH, Chagas MH, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology. 2011; 36: 1219-1226.
10.1038/npp.2011.6
CASPubMedWeb of Science®Google Scholar
518Marinho AL, Vila-Verde C, Fogaca MV, Guimaraes FS. Effects of intra-infralimbic prefrontal cortex injections of cannabidiol in the modulation of emotional behaviors in rats: contribution of 5HT(1)A receptors and stressful experiences. Behav Brain Res. 2015; 286: 49-56.
10.1016/j.bbr.2015.02.023
CASPubMedWeb of Science®Google Scholar
519Hsiao YT, Yi PL, Li CL, Chang FC. Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats. Neuropharmacology. 2012; 62: 373-384.
10.1016/j.neuropharm.2011.08.013
CASPubMedWeb of Science®Google Scholar
520Patel S, Hill MN, Cheer JF, Wotjak CT, Holmes A. The endocannabinoid system as a target for novel anxiolytic drugs. Neurosci Biobehav Rev. 2017; 76: 56-66.
10.1016/j.neubiorev.2016.12.033
CASPubMedWeb of Science®Google Scholar
521Blessing EM, Steenkamp MM, Manzanares J, Marmar CR. Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics. 2015; 12: 825-836.
10.1007/s13311-015-0387-1
CASPubMedWeb of Science®Google Scholar
522Crippa JA, Derenusson GN, Ferrari TB, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J Psychopharmacol. 2011; 25: 121-130.
10.1177/0269881110379283
CASPubMedWeb of Science®Google Scholar
523Crippa JA, Zuardi AW, Hallak JE. Therapeutical use of the cannabinoids in psychiatry. Rev Bras Psiquiatr. 2010; 32: S56-S66.

PubMedWeb of Science®Google Scholar
524Campos AC, Ferreira FR, Guimaraes FS. Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors. J Psychiatr Res. 2012; 46: 1501-1510.
10.1016/j.jpsychires.2012.08.012
PubMedWeb of Science®Google Scholar
525Crippa JA, Zuardi AW, Martin-Santos R, et al. Cannabis and anxiety: a critical review of the evidence. Hum Psychopharmacol. 2009; 24: 515-523.
10.1002/hup.1048
CASPubMedWeb of Science®Google Scholar
526Trezza V, Campolongo P. The endocannabinoid system as a possible target to treat both the cognitive and emotional features of post-traumatic stress disorder (PTSD). Front Behav Neurosci. 2013; 7: 100.
10.3389/fnbeh.2013.00100
PubMedWeb of Science®Google Scholar
527Campos AC, Ortega Z, Palazuelos J, et al. The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system. Int J Neuropsychopharmacol. 2013; 16: 1407-1419.
10.1017/S1461145712001502
CASPubMedWeb of Science®Google Scholar
528Zanelati TV, Biojone C, Moreira FA, Guimaraes FS, Joca SR. Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors. Br J Pharmacol. 2010; 159: 122-128.
10.1111/j.1476-5381.2009.00521.x
CASPubMedWeb of Science®Google Scholar
529Linge R, Jimenez-Sanchez L, Campa L, et al. Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors. Neuropharmacology. 2016; 103: 16-26.
10.1016/j.neuropharm.2015.12.017
CASPubMedWeb of Science®Google Scholar
530Shoval G, Shbiro L, Hershkovitz L, et al. Prohedonic effect of cannabidiol in a rat model of depression. Neuropsychobiology. 2016; 73: 123-129.
10.1159/000443890
CASPubMedWeb of Science®Google Scholar
531Consroe P, Sandyk R, Snider SR. Open label evaluation of cannabidiol in dystonic movement disorders. Int J Neurosci. 1986; 30: 277-282.
10.3109/00207458608985678
CASPubMedWeb of Science®Google Scholar
532Sandyk R, Snider SR, Consroe P, Elias SM. Cannabidiol in dystonic movement disorders. Psychiatry Res. 1986; 18: 291.
10.1016/0165-1781(86)90117-4
CASPubMedWeb of Science®Google Scholar
533Snider SR, Consroe P. Treatment of Meige's syndrome with cannabidiol. Neurology. 1984; 34: 147.

Google Scholar
534Crippa JA, Hallak JE, Abilio VC, de Lacerda AL, Zuardi AW. Cannabidiol and sodium nitroprusside: two novel neuromodulatory pharmacological interventions to treat and prevent psychosis. CNS Neurol Disord Drug Targets. 2015; 14: 970-978.
10.2174/1871527314666150909113930
CASPubMedWeb of Science®Google Scholar
535McGuire P, Robson P, Cubala WJ, et al. Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: A multicenter randomized controlled trial. Am J Psychiatry. 2018; 175: 225-231.
10.1176/appi.ajp.2017.17030325
PubMedWeb of Science®Google Scholar
536Hahn B. The potential of cannabidiol treatment for cannabis users with recent-onset psychosis. Schizophr Bull. 2018; 44: 46-53.
10.1093/schbul/sbx105
PubMedWeb of Science®Google Scholar
537Renard J, Norris C, Rushlow W, Laviolette SR. Neuronal and molecular effects of cannabidiol on the mesolimbic dopamine system: Implications for novel schizophrenia treatments. Neurosci Biobehav Rev. 2017; 75: 157-165.
10.1016/j.neubiorev.2017.02.006
CASPubMedWeb of Science®Google Scholar
538Rohleder C, Muller JK, Lange B, Leweke FM. Cannabidiol as a potential new type of an antipsychotic. A critical review of the evidence. Front Pharmacol. 2016; 7: 422.
10.3389/fphar.2016.00422
CASPubMedWeb of Science®Google Scholar
539Fakhoury M. Could cannabidiol be used as an alternative to antipsychotics? J Psychiatr Res. 2016; 80: 14-21.
10.1016/j.jpsychires.2016.05.013
PubMedWeb of Science®Google Scholar
540Gomes FV, Llorente R, Del Bel EA, Viveros M-P, López-Gallardo M, Guimarães FS. Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol. Schizophr Res. 2015; 164: 155-163.
10.1016/j.schres.2015.01.015
PubMedWeb of Science®Google Scholar
541Zuardi AW, Crippa JA, Hallak JE, et al. A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation. Curr Pharm Des. 2012; 18: 5131-5140.
10.2174/138161212802884681
CASPubMedWeb of Science®Google Scholar
542Zuardi AW, Crippa JA, Hallak JE, Moreira FA, Guimaraes FS. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res. 2006; 39: 421-429.
10.1590/S0100-879X2006000400001
CASPubMedWeb of Science®Google Scholar
543Zuardi AW, Morais SL, Guimaraes FS, Mechoulam R. Antipsychotic effect of cannabidiol. J Clin Psychiatry. 1995; 56: 485-486.

CASPubMedWeb of Science®Google Scholar
544Schubart CD, Sommer IE, Fusar-Poli P, de Witte L, Kahn RS, Boks MP. Cannabidiol as a potential treatment for psychosis. Eur Neuropsychopharmacol. 2014; 24: 51-64.
10.1016/j.euroneuro.2013.11.002
CASPubMedWeb of Science®Google Scholar
545Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012; 2: e94.
10.1038/tp.2012.15
CASPubMedWeb of Science®Google Scholar
546Mohammed N, Ceprian M, Jimenez L, Pazos MR, Martinez-Orgado J. Neuroprotective effects of cannabidiol in hypoxic ischemic insult. The therapeutic window in newborn mice. CNS Neurol Disord Drug Targets. 2017; 16: 102-108.
10.2174/1871527315666160927110305
CASPubMedWeb of Science®Google Scholar
547Mishima K, Hayakawa K, Abe K, et al. Cannabidiol prevents cerebral infarction via a serotonergic 5-hydroxytryptamine1A receptor-dependent mechanism. Stroke. 2005; 36: 1071-1082.
10.1161/01.STR.0000163083.59201.34
CASPubMedWeb of Science®Google Scholar
548Lafuente H, Pazos MR, Alvarez A, et al. Effects of cannabidiol and hypothermia on short-term brain damage in new-born piglets after acute hypoxia-ischemia. Front Neurosci. 2016; 10: 323.
10.3389/fnins.2016.00323
PubMedWeb of Science®Google Scholar
549Lafuente H, Alvarez FJ, Pazos MR, et al. Cannabidiol reduces brain damage and improves functional recovery after acute hypoxia-ischemia in newborn pigs. Pediatr Res. 2011; 70: 272-277.
10.1203/PDR.0b013e3182276b11
CASPubMedWeb of Science®Google Scholar
550Hayakawa K, Mishima K, Fujiwara M. Therapeutic potential of non-psychotropic cannabidiol in ischemic stroke. Pharmaceuticals (Basel). 2010; 3: 2197-2212.
10.3390/ph3072197
CASPubMedGoogle Scholar
551Hayakawa K, Irie K, Sano K, et al. Therapeutic time window of cannabidiol treatment on delayed ischemic damage via high-mobility group box1-inhibiting mechanism. Biol Pharm Bull. 2009; 32: 1538-1544.
10.1248/bpb.32.1538
CASPubMedWeb of Science®Google Scholar
552Pazos MR, Mohammed N, Lafuente H, et al. Mechanisms of cannabidiol neuroprotection in hypoxic-ischemic newborn pigs: role of 5HT(1A) and CB2 receptors. Neuropharmacology. 2013; 71: 282-291.
10.1016/j.neuropharm.2013.03.027
CASPubMedWeb of Science®Google Scholar
553Pazos MR, Cinquina V, Gomez A, et al. Cannabidiol administration after hypoxia-ischemia to newborn rats reduces long-term brain injury and restores neurobehavioral function. Neuropharmacology. 2012; 63: 776-783.
10.1016/j.neuropharm.2012.05.034
CASPubMedWeb of Science®Google Scholar
554Ruiz-Valdepeñas L, Martínez-Orgado JA, Benito C, Millán Á, Tolón RM, Romero J. Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study. J Neuroinflammation. 2011; 8: 5.
10.1186/1742-2094-8-5
CASPubMedWeb of Science®Google Scholar
555Castillo A, Tolon MR, Fernandez-Ruiz J, Romero J, Martinez-Orgado J. The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic-ischemic brain damage in mice is mediated by CB(2) and adenosine receptors. Neurobiol Dis. 2010; 37: 434-440.
10.1016/j.nbd.2009.10.023
CASPubMedWeb of Science®Google Scholar
556Mechoulam R, Shohami E. Endocannabinoids and traumatic brain injury. Mol Neurobiol. 2007; 36: 68-74.
10.1007/s12035-007-8008-6
CASPubMedWeb of Science®Google Scholar
557Mechoulam R, Spatz M, Shohami E. Endocannabinoids and neuroprotection. Sci STKE. 2002; 2002: re5.
10.1126/stke.2002.129.re5
CASPubMedGoogle Scholar
558Shohami E, Cohen-Yeshurun A, Magid L, Algali M, Mechoulam R. Endocannabinoids and traumatic brain injury. Br J Pharmacol. 2011; 163: 1402-1410.
10.1111/j.1476-5381.2011.01343.x
CASPubMedWeb of Science®Google Scholar
559Parolaro D, Massi P. Cannabinoids as potential new therapy for the treatment of gliomas. Expert Rev Neurother. 2008; 8: 37-49.
10.1586/14737175.8.1.37
CASPubMedGoogle Scholar
560Allister SDM, Chan C, Taft RJ, et al. Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells. J Neurooncol. 2005; 74: 31-40.
10.1007/s11060-004-5950-2
PubMedWeb of Science®Google Scholar
561McAllister SD, Murase R, Christian RT, et al. Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. Breast Cancer Res Treat. 2011; 129: 37-47.
10.1007/s10549-010-1177-4
CASPubMedWeb of Science®Google Scholar
562Shrivastava A, Kuzontkoski PM, Groopman JE, Prasad A. Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Mol Cancer Ther. 2011; 10: 1161-1172.
10.1158/1535-7163.MCT-10-1100
CASPubMedWeb of Science®Google Scholar
563Pisanti S, Bifulco M. Endocannabinoid system modulation in cancer biology and therapy. Pharmacol Res. 2009; 60: 107-116.
10.1016/j.phrs.2009.03.011
CASPubMedWeb of Science®Google Scholar
564Pisanti S, Picardi P, D'Alessandro A, Laezza C, Bifulco M. The endocannabinoid signaling system in cancer. Trends Pharmacol Sci. 2013; 34: 273-282.
10.1016/j.tips.2013.03.003
CASPubMedWeb of Science®Google Scholar
565Scott KA, Dennis JL, Dalgleish AG, Liu WM. Inhibiting heat shock proteins can potentiate the cytotoxic effect of cannabidiol in human glioma cells. Anticancer Res. 2015; 35: 5827-5837.

CASPubMedWeb of Science®Google Scholar
566Scott KA, Shah S, Dalgleish AG, Liu WM. Enhancing the activity of cannabidiol and other cannabinoids in vitro through modifications to drug combinations and treatment schedules. Anticancer Res. 2013; 33: 4373-4380.

CASPubMedWeb of Science®Google Scholar
567Ramer R, Merkord J, Rohde H, Hinz B. Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1. Biochem Pharmacol. 2010; 79: 955-966.
10.1016/j.bcp.2009.11.007
CASPubMedWeb of Science®Google Scholar
568Ramer R, Rohde A, Merkord J, Rohde H, Hinz B. Decrease of plasminogen activator inhibitor-1 may contribute to the anti-invasive action of cannabidiol on human lung cancer cells. Pharm Res. 2010; 27: 2162-2174.
10.1007/s11095-010-0219-2
CASPubMedWeb of Science®Google Scholar
569Ramer R, Bublitz K, Freimuth N, et al. Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1. FASEB J. 2012; 26: 1535-1548.
10.1096/fj.11-198184
CASPubMedWeb of Science®Google Scholar
570Ramer R, Heinemann K, Merkord J, et al. COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells. Mol Cancer Ther. 2013; 12: 69-82.
10.1158/1535-7163.MCT-12-0335
CASPubMedWeb of Science®Google Scholar
571Ramer R, Fischer S, Haustein M, Manda K, Hinz B. Cannabinoids inhibit angiogenic capacities of endothelial cells via release of tissue inhibitor of matrix metalloproteinases-1 from lung cancer cells. Biochem Pharmacol. 2014; 91: 202-216.
10.1016/j.bcp.2014.06.017
CASPubMedWeb of Science®Google Scholar
572Ramer R, Hinz B. New insights into antimetastatic and antiangiogenic effects of cannabinoids. Int Rev Cell Mol Biol. 2015; 314: 43-116.
10.1016/bs.ircmb.2014.10.005
CASPubMedWeb of Science®Google Scholar
573Ramer R, Hinz B. Cannabinoids as anticancer drugs. Adv Pharmacol. 2017; 80: 397-436.
10.1016/bs.apha.2017.04.002
CASPubMedGoogle Scholar
574Rocha FC, Dos Santos Junior JG, Stefano SC, da Silveira DX. Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas. J Neurooncol. 2014; 116: 11-24.
10.1007/s11060-013-1277-1
CASPubMedWeb of Science®Google Scholar
575McAllister SD, Christian RT, Horowitz MP, Garcia A, Desprez PY. Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. Mol Cancer Ther. 2007; 6: 2921-2927.
10.1158/1535-7163.MCT-07-0371
CASPubMedWeb of Science®Google Scholar
576Orellana-Serradell O, Poblete CE, Sanchez C, et al. Proapoptotic effect of endocannabinoids in prostate cancer cells. Oncol Rep. 2015; 33: 1599-1608.
10.3892/or.2015.3746
CASPubMedWeb of Science®Google Scholar
577Nabissi M, Morelli MB, Santoni M, Santoni G. Triggering of the TRPV2 channel by cannabidiol sensitizes glioblastoma cells to cytotoxic chemotherapeutic agents. Carcinogenesis. 2013; 34: 48-57.
10.1093/carcin/bgs328
CASPubMedWeb of Science®Google Scholar
578McKallip RJ, Jia W, Schlomer J, Warren JW, Nagarkatti PS, Nagarkatti M. Cannabidiol-induced apoptosis in human leukemia cells: A novel role of cannabidiol in the regulation of p22phox and Nox4 expression. Mol Pharmacol. 2006; 70: 897-908.
10.1124/mol.106.023937
CASPubMedWeb of Science®Google Scholar
579Massi P, Vaccani A, Ceruti S, Colombo A, Abbracchio MP, Parolaro D. Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. J Pharmacol Exp Ther. 2004; 308: 838-845.
10.1124/jpet.103.061002
CASPubMedWeb of Science®Google Scholar
580Solinas M, Massi P, Cinquina V, et al. Cannabidiol, a non-psychoactive cannabinoid compound, inhibits proliferation and invasion in U87-MG and T98G glioma cells through a multitarget effect. PLoS One. 2013; 8: e76918-e76919.
10.1371/journal.pone.0076918
CASPubMedWeb of Science®Google Scholar
581Massi P, Solinas M, Cinquina V, Parolaro D. Cannabidiol as potential anticancer drug. Br J Clin Pharmacol. 2013; 75: 303-312.
10.1111/j.1365-2125.2012.04298.x
CASPubMedWeb of Science®Google Scholar
582Romano B, Borrelli F, Pagano E, Cascio MG, Pertwee RG, Izzo AA. Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol. Phytomedicine. 2014; 21: 631-639.
10.1016/j.phymed.2013.11.006
CASPubMedWeb of Science®Google Scholar
583Yeshurun M, Shpilberg O, Herscovici C, et al. Cannabidiol for the prevention of graft-versus-host-disease after allogeneic hematopoietic cell transplantation: Results of a phase II study. Biol Blood Marrow Transplant. 2015; 21: 1770-1775.
10.1016/j.bbmt.2015.05.018
CASPubMedWeb of Science®Google Scholar
584Dirikoc S, Priola SA, Marella M, Zsurger N, Chabry J. Nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity. J Neurosci. 2007; 27: 9537-9544.
10.1523/JNEUROSCI.1942-07.2007
CASPubMedWeb of Science®Google Scholar
585De Filippis D, Esposito G, Cirillo C, et al. Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis. PLoS One. 2011; 6: e28159.
10.1371/journal.pone.0028159
PubMedWeb of Science®Google Scholar
586Sacerdote P, Martucci C, Vaccani A, et al. The nonpsychoactive component of marijuana cannabidiol modulates chemotaxis and IL-10 and IL-12 production of murine macrophages both in vivo and in vitro. J Neuroimmunol. 2005; 159: 97-105.
10.1016/j.jneuroim.2004.10.003
CASPubMedWeb of Science®Google Scholar
587Couch DG, Tasker C, Theophilidou E, Lund JN, O'Sullivan SE. Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon. Clin Sci (Lond). 2017; 131: 2611-2626.
10.1042/CS20171288
CASPubMedWeb of Science®Google Scholar
588Esposito G, Filippis DD, Cirillo C, et al. Cannabidiol in inflammatory bowel diseases: a brief overview. Phytother Res. 2013; 27: 633-636.
10.1002/ptr.4781
CASPubMedWeb of Science®Google Scholar
589Parker LA, Mechoulam R, Schlievert C. Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats. Neuroreport. 2002; 13: 567-570.
10.1097/00001756-200204160-00006
CASPubMedWeb of Science®Google Scholar
590Rock EM, Limebeer CL, Mechoulam R, Parker LA, Cannabidiol (the non-psychoactive component of cannabis) may act as a 5-HT1A auto-receptor agonist to reduce toxin-induced nausea and vomiting. Proceedings 19th Annual Symposium on the Cannabinoids. International Cannabinoid Research Society. 2009; 29.

Google Scholar
591Rock EM, Limebeer CL, Mechoulam R, Piomelli D, Parker LA. The effect of cannabidiol and URB597 on conditioned gaping (a model of nausea) elicited by a lithium-paired context in the rat. Psychopharmacology (Berl). 2008; 196: 389-395.
10.1007/s00213-007-0970-1
CASPubMedWeb of Science®Google Scholar
592Farrimond JA, Whalley BJ, Williams CM. Cannabinol and cannabidiol exert opposing effects on rat feeding patterns. Psychopharmacology (Berl). 2012; 223: 117-129.
10.1007/s00213-012-2697-x
CASPubMedWeb of Science®Google Scholar
593Ignatowska-Jankowska B, Jankowski MM, Swiergiel AH. Cannabidiol decreases body weight gain in rats: involvement of CB2 receptors. Neurosci Lett. 2011; 490: 82-84.
10.1016/j.neulet.2010.12.031
CASPubMedWeb of Science®Google Scholar
594Silvestri C, Paris D, Martella A, et al. Two non-psychoactive cannabinoids reduce intracellular lipid levels and inhibit hepatosteatosis. J Hepatol. 2015; 62: 1382-1390.
10.1016/j.jhep.2015.01.001
CASPubMedWeb of Science®Google Scholar
595Scutt A, Williamson EM. Cannabinoids stimulate fibroblastic colony formation by bone marrow cells indirectly via CB2 receptors. Calcif Tissue Int. 2007; 80: 50-59.
10.1007/s00223-006-0171-7
CASPubMedWeb of Science®Google Scholar
596Napimoga MH, Benatti BB, Lima FO, et al. Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats. Int Immunopharmacol. 2009; 9: 216-222.
10.1016/j.intimp.2008.11.010
CASPubMedWeb of Science®Google Scholar
597Bab I, Zimmer A, Melamed E. Cannabinoids and the skeleton: from marijuana to reversal of bone loss. Ann Med. 2009; 41: 560-567.
10.1080/07853890903121025
CASPubMedWeb of Science®Google Scholar
598Kogan NM, Melamed E, Wasserman E, et al. Cannabidiol, a major non-psychotropic cannabis constituent enhances fracture healing and stimulates lysyl hydroxylase activity in osteoblasts. J Bone Miner Res. 2015; 30: 1905-1913.
10.1002/jbmr.2513
CASPubMedWeb of Science®Google Scholar
599Magen I, Avraham Y, Ackerman Z, Vorobiev L, Mechoulam R, Berry EM. Cannabidiol ameliorates cognitive and motor impairments in bile-duct ligated mice via 5-HT1A receptor activation. Br J Pharmacol. 2010; 159: 950-957.
10.1111/j.1476-5381.2009.00589.x
CASPubMedWeb of Science®Google Scholar
600Magen I, Avraham Y, Ackerman Z, Vorobiev L, Mechoulam R, Berry EM. Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation. J Hepatol. 2009; 51: 528-534.
10.1016/j.jhep.2009.04.021
CASPubMedWeb of Science®Google Scholar
601Avraham Y, Grigoriadis N, Poutahidis T, et al. Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice. Br J Pharmacol. 2011; 162: 1650-1658.
10.1111/j.1476-5381.2010.01179.x
CASPubMedWeb of Science®Google Scholar
602Lim MP, Devi LA, Rozenfeld R. Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis. Cell Death Dis. 2011; 2: e170.
10.1038/cddis.2011.52
CASPubMedWeb of Science®Google Scholar
603Mukhopadhyay P, Rajesh M, Horvath B, et al. Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death. Free Radic Biol Med. 2011; 50: 1368-1381.
10.1016/j.freeradbiomed.2011.02.021
CASPubMedWeb of Science®Google Scholar
604Sultan SR, Millar SA, England TJ, O'Sullivan SE. A systematic review and meta-analysis of the haemodynamic effects of cannabidiol. Front Pharmacol. 2017; 8: 81.
10.3389/fphar.2017.00081
PubMedWeb of Science®Google Scholar
605Jadoon KA, Tan GD, O'Sullivan SE. A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study. J CI Insight. 2017; 2.

Google Scholar
606Stanley CP, Hind WH, O'Sullivan SE. Is the cardiovascular system a therapeutic target for cannabidiol? Br J Clin Pharmacol. 2013; 75: 313-322.
10.1111/j.1365-2125.2012.04351.x
CASPubMedWeb of Science®Google Scholar
607Stanley CP, Hind WH, Tufarelli C, O'Sullivan SE. Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB1 activation. Cardiovasc Res. 2015; 107: 568-578.
10.1093/cvr/cvv179
CASPubMedWeb of Science®Google Scholar
608Durst R, Danenberg H, Gallily R, et al. Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury. Am J Physiol Heart Circ Physiol. 2007; 293: H3602-H3607.
10.1152/ajpheart.00098.2007
CASPubMedWeb of Science®Google Scholar
609Rajesh M, Mukhopadhyay P, Batkai S, et al. Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. J Am Coll Cardiol. 2010; 56: 2115-2125.
10.1016/j.jacc.2010.07.033
CASPubMedWeb of Science®Google Scholar
610Weiss L, Zeira M, Reich S, et al. Cannabidiol arrests onset of autoimmune diabetes in NOD mice. Neuropharmacology. 2008; 54: 244-249.
10.1016/j.neuropharm.2007.06.029
CASPubMedWeb of Science®Google Scholar
611Weiss L, Zeira M, Reich S, et al. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity. 2006; 39: 143-151.
10.1080/08916930500356674
CASPubMedWeb of Science®Google Scholar
612Rajesh M, Mukhopadhyay P, Batkai S, et al. Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption. Am J Physiol Heart Circ Physiol. 2007; 293: H610-H619.
10.1152/ajpheart.00236.2007
CASPubMedWeb of Science®Google Scholar
613El-Remessy AB, Al-Shabrawey M, Khalifa Y, Tsai NT, Caldwell RB, Liou GI. Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes. Am J Pathol. 2006; 168: 235-244.
10.2353/ajpath.2006.050500
CASPubMedWeb of Science®Google Scholar
614Takeda S, Misawa K, Yamamoto I, Watanabe K. Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis. Drug Metab Dispos. 2008; 36: 1917-1921.
10.1124/dmd.108.020909
CASPubMedWeb of Science®Google Scholar
615Takeda S, Okazaki H, Kohro-Ikeda E, et al. DNA microarray analysis of genes in highly metastatic 4T1E/M3 murine breast cancer cells following exposure to cannabidiolic acid. Fundam Toxicol Sci. 2015; 2: 89-94.
10.2131/fts.2.89
CASGoogle Scholar
616Takeda S, Okajima S, Miyoshi H, et al. Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration. Toxicol Lett. 2012; 214: 314-319.
10.1016/j.toxlet.2012.08.029
CASPubMedWeb of Science®Google Scholar
617Bolognini D, Rock EM, Cluny NL, et al. Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation. Br J Pharmacol. 2013; 168: 1456-1470.
10.1111/bph.12043
CASPubMedWeb of Science®Google Scholar
618Rock EM, Kopstick RL, Limebeer CL, Parker LA. Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus. Br J Pharmacol. 2013; 170: 641-648.
10.1111/bph.12316
CASPubMedWeb of Science®Google Scholar
619Sirikantaramas S, Taura F, Tanaka Y, Ishikawa Y, Morimoto S, Shoyama Y. Tetrahydrocannabinolic acid synthase, the enzyme controlling marijuana psychoactivity, is secreted into the storage cavity of the glandular trichomes. Plant Cell Physiol. 2005; 46: 1578-1582.
10.1093/pcp/pci166
CASPubMedWeb of Science®Google Scholar
620De Petrocellis L, Ligresti A, Schiano Moriello A, et al. Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms. Br J Pharmacol. 2013; 168: 79-102.
10.1111/j.1476-5381.2012.02027.x
PubMedWeb of Science®Google Scholar
621Musty RE, Karniol IG, Shirikawa I, Takahashi RN, Knobel E, Interactions of delta-9-tetrahydrocannabinol and cannabinol in man. In: MC Braude, S Szara, eds. The Pharmacology of Marihuana, Vol 2. New York: Raven Press; 1976: 559-563.

Google Scholar
622Karniol IG, Shirakawa I, Takahashi RN, Knobel E, Musty RE. Effects of delta9-tetrahydrocannabinol and cannabinol in man. Pharmacology. 1975; 13: 502-512.
10.1159/000136944
CASPubMedWeb of Science®Google Scholar
623Yoshida H, Usami N, Ohishi Y, Watanabe K, Yamamoto I, Yoshimura H. Synthesis and pharmacological effects in mice of halogenated cannabinol derivatives. Chem Pharm Bull (Tokyo). 1995; 43: 335-337.
10.1248/cpb.43.335
CASPubMedWeb of Science®Google Scholar
624Usami N, Kobana K, Yoshida H, et al. Synthesis and pharmacological activities in mice of halogenated delta 9-tetrahydrocannabinol derivatives. Chem Pharm Bull (Tokyo). 1998; 46: 1462-1467.
10.1248/cpb.46.1462
CASPubMedWeb of Science®Google Scholar
625Takahashi RN, Karniol IG. Pharmacologic interaction between cannabinol and delta9-tetrahydrocannabinol. Psychopharmacologia. 1975; 41: 277-284.
10.1007/BF00428937
CASPubMedWeb of Science®Google Scholar
626Croxford JL, Yamamura T. Cannabinoids and the immune system: potential for the treatment of inflammatory diseases? J Neuroimmunol. 2005; 166: 3-18.
10.1016/j.jneuroim.2005.04.023
CASPubMedWeb of Science®Google Scholar
627Idris AI, Sophocleous A, Landao-Bassonga E, van't Hof RJ, Ralston SH. Regulation of bone mass, osteoclast function, and ovariectomy-induced bone loss by the type 2 cannabinoid receptor. Endocrinology. 2008; 149: 5619-5626.
10.1210/en.2008-0150
CASPubMedWeb of Science®Google Scholar
628Idris AI, van 't Hof RJ, Greig IR, et al. Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nat Med. 2005; 11: 774-779.
10.1038/nm1255
CASPubMedWeb of Science®Google Scholar
629Ofek O, Karsak M, Leclerc N, et al. Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc Natl Acad Sci U S A. 2006; 103: 696-701.
10.1073/pnas.0504187103
CASPubMedWeb of Science®Google Scholar
630Colasanti BK, Craig CR, Allara RD. Intraocular pressure, ocular toxicity and neurotoxicity after administration of cannabinol or cannabigerol. Exp Eye Res. 1984; 39: 251-259.
10.1016/0014-4835(84)90013-7
CASPubMedWeb of Science®Google Scholar
631Cascio MG, Gauson LA, Stevenson LA, Ross RA, Pertwee RG. Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. Br J Pharmacol. 2010; 159: 129-141.
10.1111/j.1476-5381.2009.00515.x
CASPubMedWeb of Science®Google Scholar
632Banerjee SP, Snyder SH, Mechoulam R. Cannabinoids: influence on neurotransmitter uptake in rat brain synaptosomes. J Pharmacol Exp Ther. 1975; 194: 74-81.

CASPubMedWeb of Science®Google Scholar
633Musty R, Deyo R. A cannabigerol extract alters behavioral despair in an animal model of depression. Proceedings June 26; Symposium on the Cannabinoids. Int Cannabinoid Res Soc. 2006; 32.

Google Scholar
634Valdeolivas S, Navarrete C, Cantarero I, Bellido ML, Muñoz E, Sagredo O. Neuroprotective properties of cannabigerol in Huntington's disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice. Neurotherapeutics. 2015; 12: 185-199.
10.1007/s13311-014-0304-z
CASPubMedWeb of Science®Google Scholar
635Brierley DI, Samuels J, Duncan M, Whalley BJ, Williams CM. Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats. Psychopharmacology (Berl). 2016; 233: 3603-3613.
10.1007/s00213-016-4397-4
CASPubMedWeb of Science®Google Scholar
636Eisohly HN, Turner CE, Clark AM, Eisohly MA. Synthesis and antimicrobial activities of certain cannabichromene and cannabigerol related compounds. J Pharm Sci. 1982; 71: 1319-1323.
10.1002/jps.2600711204
CASPubMedWeb of Science®Google Scholar
637Borrelli F, Fasolino I, Romano B, et al. Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease. Biochem Pharmacol. 2013; 85: 1306-1316.
10.1016/j.bcp.2013.01.017
CASPubMedWeb of Science®Google Scholar
638Baek SH, Kim YO, Kwag JS, Choi KE, Jung WY, Han DS. Boron trifluoride etherate on silica-A modified Lewis acid reagent (VII). Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells. Arch Pharm Res. 1998; 21: 353-356.
10.1007/BF02975301
CASPubMedWeb of Science®Google Scholar
639Borrelli F, Pagano E, Romano B, et al. Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid. Carcinogenesis. 2014; 35: 2787-2797.
10.1093/carcin/bgu205
CASPubMedWeb of Science®Google Scholar
640Colasanti BK. A comparison of the ocular and central effects of delta 9-tetrahydrocannabinol and cannabigerol. J Ocul Pharmacol. 1990; 6: 259-269.
10.1089/jop.1990.6.259
CASPubMedGoogle Scholar
641Mukerji G, Yiangou Y, Corcoran SL, et al. Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations. BMC Urol. 2006; 6.
10.1186/1471-2490-6-6
Google Scholar
642Pagano E, Montanaro V, D, Girolamo A, Pistone A, et al. Effect of non-psychotropic plant-derived cannabinoids on bladder contractility: Focus on cannabigerol. Nat Prod Commun. 2015; 10: 1009-1012.
10.1177/1934578X1501000653
PubMedWeb of Science®Google Scholar
643Pertwee RG. Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications. Proc Nutr Soc. 2014; 73: 96-105.
10.1017/S0029665113003649
CASPubMedWeb of Science®Google Scholar
644Davis WM, Hatoum NS. Neurobehavioral actions of cannabichromene and interactions with delta 9-tetrahydrocannabinol. Gen Pharmacol. 1983; 14: 247-252.
10.1016/0306-3623(83)90004-6
CASPubMedWeb of Science®Google Scholar
645Turner CE, Elsohly MA. Biological activity of cannabichromene, its homologs and isomers. J Clin Pharmacol. 1981; 21: 283S-291S.
10.1002/j.1552-4604.1981.tb02606.x
CASPubMedWeb of Science®Google Scholar
646Wirth PW, Watson ES, ElSohly M, Turner CE, Murphy JC. Anti-inflammatory properties of cannabichromene. Life Sci. 1980; 26: 1991-1995.
10.1016/0024-3205(80)90631-1
CASPubMedWeb of Science®Google Scholar
647Deyo R, Musty R, A cannabichromene (CBC) extract alters behavioral despair on the mouse tail suspension test of depression. Proceedings 2003 Symposium on the Cannabinoids. International Cannabinoid Research Society. 2003; 146.

Google Scholar
648Shinjyo N, Di Marzo V. The effect of cannabichromene on adult neural stem/progenitor cells. Neurochem Int. 2013; 63: 432-437.
10.1016/j.neuint.2013.08.002
CASPubMedWeb of Science®Google Scholar
649Izzo AA, Capasso R, Aviello G, et al. Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice. Br J Pharmacol. 2012; 166: 1444-1460.
10.1111/j.1476-5381.2012.01879.x
CASPubMedWeb of Science®Google Scholar
650Hatoum NS, Davis WM, Elsohly MA, Turner CE. Cannabichromene and delta 9-tetrahydrocannabinol: interactions relative to lethality, hypothermia and hexobarbital hypnosis. Gen Pharmacol. 1981; 12: 357-362.
10.1016/0306-3623(81)90090-2
CASPubMedWeb of Science®Google Scholar
651Thomas A, Stevenson LA, Wease KN, et al. Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist. Br J Pharmacol. 2005; 146: 917-926.
10.1038/sj.bjp.0706414
CASPubMedWeb of Science®Google Scholar
652Dennis I, Whalley BJ, Stephens GJ. Effects of Delta9-tetrahydrocannabivarin on [35S]GTPgammaS binding in mouse brain cerebellum and piriform cortex membranes. Br J Pharmacol. 2008; 154: 1349-1358.
10.1038/bjp.2008.190
CASPubMedWeb of Science®Google Scholar
653Ma YL, Weston SE, Whalley BJ, Stephens GJ. The phytocannabinoid Delta(9)-tetrahydrocannabivarin modulates inhibitory neurotransmission in the cerebellum. Br J Pharmacol. 2008; 154: 204-215.
10.1038/bjp.2008.57
CASPubMedWeb of Science®Google Scholar
654Hill AJ, Weston SE, Jones NA, et al. Δ⁹Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats. Epilepsia. 2010; 51: 1522-1532.
10.1111/j.1528-1167.2010.02523.x
CASPubMedWeb of Science®Google Scholar
655Pertwee RG, Thomas A, Stevenson LA, et al. The psychoactive plant cannabinoid, Delta9-tetrahydrocannabinol, is antagonized by Delta8- and Delta9-tetrahydrocannabivarin in mice in vivo. Br J Pharmacol. 2007; 150: 586-594.
10.1038/sj.bjp.0707124
CASPubMedWeb of Science®Google Scholar
656Bolognini D, Costa B, Maione S, et al. The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice. Br J Pharmacol. 2010; 160: 677-687.
10.1111/j.1476-5381.2010.00756.x
CASPubMedWeb of Science®Google Scholar
657Riedel G, Fadda P, McKillop-Smith S, Pertwee RG, Platt B, Robinson L. Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice. Br J Pharmacol. 2009; 156: 1154-1166.
10.1111/j.1476-5381.2008.00107.x
CASPubMedWeb of Science®Google Scholar
658Cawthorne MA, Wargent E, Zaibi M, Stott C, Wright S. The CB1 antagonist, delta-9-tetrahydrocannabivarin (THCV) has anti-oebesity activity in dietary-induced obese (DIO) mice. Proceedings 17th Annual Symposium on the Cannabinoids. Int Cannabinoid Res Soc. 2007; 141.

Google Scholar
659Robinson L, Fadda P, McKillop-Smith S, Fratta W, Pertwee RG, Riedel G, Phytocannabinoid induced anorexic behavior in fasted and non-fasted mice. IACM Fourth Conference on Cannabinoids in Medicine; 2007.

Google Scholar
660Wargent ET, Zaibi MS, Silvestri C, et al. The cannabinoid Delta(9)-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutr Diabetes. 2013; 3: e68.
10.1038/nutd.2013.9
CASPubMedWeb of Science®Google Scholar
661Buchbauer G, Bohusch R, Biological activities of essential oils: An update. In: K Husnu Can Baser, G Buchbauer, eds. Handbook of Essential Oils: Science, Technology, and Applications. 2nd Edition. Boca Raton, FL: CRC Press; 2015: 281-322.
10.1201/b19393-11
Google Scholar
662Strano G. The Chemistry of Aromatherapeutic Oils. Crows Nest NSW, Australia: Allen & Unwin; 2005.

Google Scholar
663Smith N, Transdermal Cannabinoid Patch, U.S. Patent No. 20,150,297,556. 2015.

Google Scholar
664McPartland JM, Russo EB. Cannabis and Cannabis Extracts: greater than. The sum of their parts? J Cannabis Therapeut. 2001; 1: 103-132.
10.1300/J175v01n03_08
CASGoogle Scholar
665Paduch R, Kandefer-Szerszen M, Trytek M, Fiedurek J. Terpenes: substances useful in human healthcare. Arch Immunol Ther Exp (Warsz). 2007; 55: 315-327.
10.1007/s00005-007-0039-1
CASPubMedWeb of Science®Google Scholar
666Klauke AL, Racz I, Pradier B, et al. The cannabinoid CB(2) receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. Eur Neuropsychopharmacol. 2014; 24: 608-620.
10.1016/j.euroneuro.2013.10.008
CASPubMedWeb of Science®Google Scholar
667Passos GF, Fernandes ES, da Cunha FM, et al. Anti-inflammatory and anti-allergic properties of the essential oil and active compounds from Cordia verbenacea. J Ethnopharmacol. 2007; 110: 323-333.
10.1016/j.jep.2006.09.032
CASPubMedWeb of Science®Google Scholar
668Rogerio AP, Andrade EL, Leite DF, Figueiredo CP, Calixto JB. Preventive and therapeutic anti-inflammatory properties of the sesquiterpene alpha-humulene in experimental airways allergic inflammation. Br J Pharmacol. 2009; 158: 1074-1087.
10.1111/j.1476-5381.2009.00177.x
CASPubMedWeb of Science®Google Scholar
669Medeiros R, Passos GF, Vitor CE, et al. Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw. Br J Pharmacol. 2007; 151: 618-627.
10.1038/sj.bjp.0707270
CASPubMedWeb of Science®Google Scholar
670Horvath B, Mukhopadhyay P, Kechrid M, et al. β-Caryophyllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid 2 receptor-dependent manner. Free Radic Biol Med. 2012; 52: 1325-1333.
10.1016/j.freeradbiomed.2012.01.014
CASPubMedWeb of Science®Google Scholar
671Ghelardini C, Galeotti N, Di Cesare Mannelli L, Mazzanti G, Bartolini A. Local anaesthetic activity of beta-caryophyllene. Farmaco. 2001; 56: 387-389.
10.1016/S0014-827X(01)01092-8
CASPubMedWeb of Science®Google Scholar
672Gertsch J, Leonti M, Raduner S, et al. Beta-caryophyllene is a dietary cannabinoid. Proc Natl Acad Sci U S A. 2008; 105: 9099-9104.
10.1073/pnas.0803601105
CASPubMedWeb of Science®Google Scholar
673Calleja MA, Vieites JM, Montero-Meléndez T, et al. The antioxidant effect of beta-caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation. Br J Nutr. 2013; 109: 394-401.
10.1017/S0007114512001298
CASPubMedWeb of Science®Google Scholar
674Pant A, Mishra V, Saikia SK, et al. Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans. Exp Gerontol. 2014; 57: 81-95.
10.1016/j.exger.2014.05.007
CASPubMedWeb of Science®Google Scholar
675Legault J, Pichette A. Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel. J Pharm Pharmacol. 2007; 59: 1643-1647.
10.1211/jpp.59.12.0005
CASPubMedWeb of Science®Google Scholar
676Legault J, Dahl W, Debiton E, Pichette A, Madelmont JC. Antitumor activity of balsam fir oil: production of reactive oxygen species induced by alpha-humulene as possible mechanism of action. Planta Med. 2003; 69: 402-407.
10.1055/s-2003-39695
CASPubMedWeb of Science®Google Scholar
677Kim C, Cho SK, Kim KD, et al. β-Caryophyllene oxide potentiates TNF-α-induced apoptosis and inhibits invasion through down-modulation of NF-κB-regulated gene products. Apoptosis. 2014; 19: 708-718.
10.1007/s10495-013-0957-9
CASPubMedWeb of Science®Google Scholar
678Lampronti I, Saab AM, Gambari R. Antiproliferative activity of essential oils derived from plants belonging to the Magnoliophyta division. Int J Oncol. 2006; 29: 989-995.

CASPubMedWeb of Science®Google Scholar
679Singh B, Sharma RA. Plant terpenes: defense responses, phylogenetic analysis, regulation and clinical applications. 3 Biotech. 2015; 5: 129-151.
10.1007/s13205-014-0220-2
PubMedWeb of Science®Google Scholar
680Tambe Y, Tsujiuchi H, Honda G, Ikeshiro Y, Tanaka S. Gastric cytoprotection of the non-steroidal anti-inflammatory sesquiterpene, beta-caryophyllene. Planta Med. 1996; 62: 469-470.
10.1055/s-2006-957942
CASPubMedWeb of Science®Google Scholar
681Basile AC, Sertie JA, Freitas PC, Zanini AC. Anti-inflammatory activity of oleoresin from Brazilian Copaifera. J Ethnopharmacol. 1988; 22: 101-109.
10.1016/0378-8741(88)90235-8
CASPubMedWeb of Science®Google Scholar
682Ozturk A, Ozbek H. The anti-inflammatory activity of Eugenia caryophyllata essential oil: an animal model of anti-inflammatory activity. Eur J Gen Med. 2005; 2: 159-163.
10.29333/ejgm/82334
CASGoogle Scholar
683Apel MA, Lima ME, Sobral M, et al. Anti-inflammatory activity of essential oil from leaves of Myrciaria tenella and Calycorectes sellowianus. Pharm Biol. 2010; 48: 433-438.
10.3109/13880200903164386
CASPubMedWeb of Science®Google Scholar
684Pichette A, Larouche PL, Lebrun M, Legault J. Composition and antibacterial activity of Abies balsamea essential oil. Phytother Res. 2006; 20: 371-373.
10.1002/ptr.1863
CASPubMedWeb of Science®Google Scholar
685Campbell WE, Gammon DW, Smith P, Abrahams M, Purves TD. Composition and antimalarial activity in vitro of the essential oil of Tetradenia riparia. Planta Med. 1997; 63: 270-272.
10.1055/s-2006-957672
CASPubMedWeb of Science®Google Scholar
686Bento AF, Marcon R, Dutra RC, et al. β-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPAR-γ pathway. Am J Pathol. 2011; 178: 1153-1166.
10.1016/j.ajpath.2010.11.052
CASPubMedWeb of Science®Google Scholar
687Karsak M, Gaffal E, Date R, et al. Attenuation of allergic contact dermatitis through the endocannabinoid system. Science. 2007; 316: 1494-1497.
10.1126/science.1142265
CASPubMedWeb of Science®Google Scholar
688Al Mansouri S, Ojha S, Al Maamari E, Al Ameri M, Nurulain SM, Bahi A. The cannabinoid receptor 2 agonist, beta-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice. Pharmacol Biochem Behav. 2014; 124: 260-268.
10.1016/j.pbb.2014.06.025
CASPubMedWeb of Science®Google Scholar
689Gertsch J. Anti-inflammatory cannabinoids in diet: Towards a better understanding of CB(2) receptor action?. Commun Integr Biol. 2008; 1: 26-28.
10.4161/cib.1.1.6568
CASPubMedGoogle Scholar
690Bahi A, Al Mansouri S, Al Memari E, Al Ameri M, Nurulain SM, Ojha S. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice. Physiol Behav. 2014; 135: 119-124.
10.1016/j.physbeh.2014.06.003
CASPubMedWeb of Science®Google Scholar
691Xi ZX, Peng XQ, Li X, et al. Brain cannabinoid CB(2) receptors modulate cocaine's actions in mice. Nat Neurosci. 2011; 14: 1160-1166.
10.1038/nn.2874
CASPubMedWeb of Science®Google Scholar
692Guo K, Mou X, Huang J, Xiong N, Li H. Trans-caryophyllene suppresses hypoxia-induced neuroinflammatory responses by inhibiting NF-kappaB activation in microglia. J Mol Neurosci. 2014; 54: 41-48.
10.1007/s12031-014-0243-5
CASPubMedWeb of Science®Google Scholar
693Zheng X, Sun T, Wang X. Activation of type 2 cannabinoid receptors (CB2R) promotes fatty acid oxidation through the SIRT1/PGC-1alpha pathway. Biochem Biophys Res Commun. 2013; 436: 377-381.
10.1016/j.bbrc.2013.05.108
CASPubMedWeb of Science®Google Scholar
694Van Cleemput M, Cattoor K, De Bosscher K, Haegeman G, De Keukeleire D, Heyerick A. Hop (Humulus lupulus)-derived bitter acids as multipotent bioactive compounds. J Nat Prod. 2009; 72: 1220-1230.
10.1021/np800740m
CASPubMedWeb of Science®Google Scholar
695Lorenzetti BB, Souza GE, Sarti SJ, Santos Filho D, Ferreira SH. Myrcene mimics the peripheral analgesic activity of lemongrass tea. J Ethnopharmacol. 1991; 34: 43-48.
10.1016/0378-8741(91)90187-I
CASPubMedWeb of Science®Google Scholar
696Rao VS, Menezes AM, Viana GS. Effect of myrcene on nociception in mice. J Pharm Pharmacol. 1990; 42: 877-878.
10.1111/j.2042-7158.1990.tb07046.x
CASPubMedWeb of Science®Google Scholar
697do Vale TG, Furtado EC, Santos JG, Jr, Viana GS. Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) n.e. Brown. Phytomedicine. 2002; 9: 709-714.
10.1078/094471102321621304
CASPubMedWeb of Science®Google Scholar
698Bisset NG, Wichtl M. Herbal Drugs and Phytopharmaceuticals: A Handbook for Practice on a Scientific Basis, 3rd edn. Boca Raton, FL: Medpharm Scientific Publishers: Stuttgart; CRC Press; 2004.

Google Scholar
699De-Oliveira AC, Ribeiro-Pinto LF, Paumgartten JR. In vitro inhibition of CYP2B1 monooxygenase by beta-myrcene and other monoterpenoid compounds. Toxicol Lett. 1997; 92: 39-46.
10.1016/S0378-4274(97)00034-9
CASPubMedWeb of Science®Google Scholar
700Souza MC, Siani AC, Ramos MF, Menezes-de-Lima OJ, Henriques MG. Evaluation of anti-inflammatory activity of essential oils from two Asteraceae species. Pharmazie. 2003; 58: 582-586.

CASPubMedWeb of Science®Google Scholar
701Rufino AT, Ribeiro M, Sousa C, et al. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. Eur J Pharmacol. 2015; 750: 141-150.
10.1016/j.ejphar.2015.01.018
CASPubMedWeb of Science®Google Scholar
702 National Toxicology Program. NTP technical report on the toxicology and carcinogenesis studies of beta-myrcene (CAS No. 123-35-3) in F344/N rats and B6C3F1 mice (Gavage studies). Natl Toxicol Program Tech Rep Ser. 2010;(557): 1-163.

Google Scholar
703Noma Y, Asakawa Y, Biotransformation of monoterpenoids by microorganisms, insects, and mammals. In: KHC Baser, G Buchbauer, eds. Handbook of Essential Oils: Science, Technology, and Applications. Boca Raton, FL: CRC Press; 2010: 585-736.

Google Scholar
704Wang W, Wu N, Zu YG, Fu YJ. Antioxidative activity of Rosmarinus officinalis L. essential oil compared to its main components. Food Chem. 2008; 108: 1019-1022.
10.1016/j.foodchem.2007.11.046
CASPubMedWeb of Science®Google Scholar
705Aydin E, Türkez H, Geyikoğlu F. Antioxidative, anticancer and genotoxic properties of α-pinene on N2a neuroblastoma cells. Biologia. 2013; 68: 1004-1009.
10.2478/s11756-013-0230-2
CASWeb of Science®Google Scholar
706Kim MJ, Yang KW, Kim SS, et al. Chemical composition and anti-inflammation activity of essential oils from Citrus unshiu flower. Nat Prod Commun. 2014; 9: 727-730.

CASPubMedGoogle Scholar
707Bais S, Abrol N, Prashar Y, Kumari R. Modulatory effect of standardised amentoflavone isolated from Juniperus communis L. agianst Freund's adjuvant induced arthritis in rats (histopathological and X Ray anaysis). Biomed Pharmacother. 2017; 86: 381-392.
10.1016/j.biopha.2016.12.027
CASPubMedWeb of Science®Google Scholar
708Rufino AT, Ribeiro M, Judas F, et al. Anti-inflammatory and chondroprotective activity of (+)-alpha-pinene: structural and enantiomeric selectivity. J Nat Prod. 2014; 77: 264-269.
10.1021/np400828x
CASPubMedWeb of Science®Google Scholar
709Neves A, Rosa S, Goncalves J, et al. Screening of five essential oils for identification of potential inhibitors of IL-1-induced Nf-kappaB activation and NO production in human chondrocytes: characterization of the inhibitory activity of alpha-pinene. Planta Med. 2010; 76: 303-308.
10.1055/s-0029-1186085
CASPubMedWeb of Science®Google Scholar
710Gil ML, Jimenez J, Ocete MA, Zarzuelo A, Cabo MM. Comparative study of different essential oils of Bupleurum gibraltaricum Lamarck. Pharmazie. 1989; 44: 284-287.

CASPubMedWeb of Science®Google Scholar
711Bae GS, Park KC, Choi SB, et al. Protective effects of alpha-pinene in mice with cerulein-induced acute pancreatitis. Life Sci. 2012; 91: 866-871.
10.1016/j.lfs.2012.08.035
CASPubMedWeb of Science®Google Scholar
712Him A, Ozbek H, Turel I, Oner AC. Antinociceptive activity of α-pinene and fenchone. Pharmacol Online. 2008; 3: 363-369.

Google Scholar
713Kennedy DO, Dodd FL, Robertson BC, et al. Monoterpenoid extract of sage (Salvia lavandulaefolia) with cholinesterase inhibiting properties improves cognitive performance and mood in healthy adults. J Psychopharmacol. 2011; 25: 1088-1100.
10.1177/0269881110385594
CASPubMedWeb of Science®Google Scholar
714Miyazawa M, Yamafuji C. Inhibition of acetylcholinesterase activity by bicyclic monoterpenoids. J Agric Food Chem. 2005; 53: 1765-1768.
10.1021/jf040019b
CASPubMedWeb of Science®Google Scholar
715Perry NS, Houghton PJ, Theobald A, Jenner P, Perry EK. In-vitro inhibition of human erythrocyte acetylcholinesterase by salvia lavandulaefolia essential oil and constituent terpenes. J Pharm Pharmacol. 2000; 52: 895-902.
10.1211/0022357001774598
CASPubMedWeb of Science®Google Scholar
716Damien Dorman HJ, Figueiredo AC, Barroso JG, Deans SG. In vitro evaluation of antioxidant activity of essential oils and their components. Flavour and Fragrance Journal. 2000; 15: 12-16.
10.1002/(SICI)1099-1026(200001/02)15:1<12::AID-FFJ858>3.0.CO;2-V
Web of Science®Google Scholar
717Wang W, Li N, Luo M, Zu Y, Efferth T. Antibacterial activity and anticancer activity of Rosmarinus officinalis L. essential oil compared to that of its main components. Molecules. 2012; 17: 2704-2713.
10.3390/molecules17032704
CASPubMedWeb of Science®Google Scholar
718Griffiths ET, Bociek SM, Harries PC, Jeffcoat R, Sissons DJ, Trudgill PW. Bacterial metabolism of alpha-pinene: pathway from alpha-pinene oxide to acyclic metabolites in Nocardia sp. strain P18.3. J Bacteriol. 1987; 169: 4972-4979.
10.1128/jb.169.11.4972-4979.1987
CASPubMedWeb of Science®Google Scholar
719Rivas da Silva AC, Lopes PM, Barros de Azevedo MM, Costa DC, Alviano CS, Alviano DS. Biological activities of alpha-pinene and beta-pinene enantiomers. Molecules. 2012; 17: 6305-6316.
10.3390/molecules17066305
CASPubMedWeb of Science®Google Scholar
720Nissen L, Zatta A, Stefanini I, et al. Characterization and antimicrobial activity of essential oils of industrial hemp varieties (Cannabis sativa L.). Fitoterapia. 2010; 81: 413-419.
10.1016/j.fitote.2009.11.010
CASPubMedWeb of Science®Google Scholar
721Glisic S, Milojevic S, Dimitrijevic S, Orlovic A, Skala D. Antimicrobial activity of the essential oil and different fractions of Juniperus communis L. and a comparison with some commercial antibiotics. J Serb Chem Soc. 2007; 72: 311-320.
10.2298/JSC0704311G
CASWeb of Science®Google Scholar
722Leite AM, Lima EO, Souza EL, Diniz MFFM, Trajano VN, Medeiros IA. Inhibitory effect of β-pinene, α-pinene and eugenol on the growth of potential infectious endocarditis causing Gram-positive bacteria. Braz J Pharm Sci. 2007; 43: 121-126.

CASGoogle Scholar
723Kose EO, Deniz IG, Sarikurkcu C, Aktas O, Yavuz M. Chemical composition, antimicrobial and antioxidant activities of the essential oils of Sideritis erythrantha Boiss. and Heldr. (var. erythrantha and var. cedretorum P.H. Davis) endemic in Turkey. Food Chem Toxicol. 2010; 48: 2960-2965.
10.1016/j.fct.2010.07.033
CASPubMedWeb of Science®Google Scholar
724Ozek G, Demirci F, Ozek T, et al. Gas chromatographic-mass spectrometric analysis of volatiles obtained by four different techniques from Salvia rosifolia Sm., and evaluation for biological activity. J Chromatogr A. 2010; 1217: 741-748.
10.1016/j.chroma.2009.11.086
CASPubMedWeb of Science®Google Scholar
725Falk AA, Hagberg MT, Lof AE, Wigaeus-Hjelm EM, Wang ZP. Uptake, distribution and elimination of alpha-pinene in man after exposure by inhalation. Scand J Work Environ Health. 1990; 16: 372-378.
10.5271/sjweh.1771
CASPubMedWeb of Science®Google Scholar
726Astani A, Reichling J, Schnitzler P. Comparative study on the antiviral activity of selected monoterpenes derived from essential oils. Phytother Res. 2010; 24: 673-679.
10.1002/ptr.2955
CASPubMedWeb of Science®Google Scholar
727Yang Z, Wu N, Zu Y, Fu Y. Comparative anti-infectious bronchitis virus (IBV) activity of (-)-pinene: effect on nucleocapsid (N) protein. Molecules. 2011; 16: 1044-1054.
10.3390/molecules16021044
CASPubMedWeb of Science®Google Scholar
728Loizzo MR, Saab AM, Tundis R, et al. Phytochemical analysis and in vitro antiviral activities of the essential oils of seven Lebanon species. Chem Biodivers. 2008; 5: 461-470.
10.1002/cbdv.200890045
CASPubMedWeb of Science®Google Scholar
729Nerio LS, Olivero-Verbel J, Stashenko E. Repellent activity of essential oils: a review. Bioresour Technol. 2010; 101: 372-378.
10.1016/j.biortech.2009.07.048
CASPubMedWeb of Science®Google Scholar
730Kusuhara M, Urakami K, Masuda Y, et al. Fragrant environment with alpha-pinene decreases tumor growth in mice. Biomed Res. 2012; 33: 57-61.
10.2220/biomedres.33.57
CASPubMedWeb of Science®Google Scholar
731Chen WQ, Xu B, Mao JW, et al. Inhibitory effects of alpha-pinene on hepatoma carcinoma cell proliferation. Asian Pac J Cancer Prev. 2014; 15: 3293-3297.
10.7314/APJCP.2014.15.7.3293
PubMedGoogle Scholar
732Fernandes ES, Passos GF, Medeiros R, et al. Anti-inflammatory effects of compounds alpha-humulene and (-)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. Eur J Pharmacol. 2007; 569: 228-236.
10.1016/j.ejphar.2007.04.059
CASPubMedWeb of Science®Google Scholar
733Chaves JS, Leal PC, Pianowisky L, Calixto JB. Pharmacokinetics and tissue distribution of the sesquiterpene alpha-humulene in mice. Planta Med. 2008; 74: 1678-1683.
10.1055/s-0028-1088307
CASPubMedWeb of Science®Google Scholar
734Tundis R, Loizzo MR, Bonesi M, et al. In vitro cytotoxic effects of Senecio stabianus Lacaita (Asteraceae) on human cancer cell lines. Nat Prod Res. 2009; 23: 1707-1718.
10.1080/14786410802194151
CASPubMedWeb of Science®Google Scholar
735Govindarajan M, Rajeswary M, Arivoli S, Tennyson S, Benelli G. Larvicidal and repellent potential of Zingiber nimmonii (J. Graham) Dalzell (Zingiberaceae) essential oil: an eco-friendly tool against malaria, dengue, and lymphatic filariasis mosquito vectors?. Parasitol Res. 2016; 115: 1807-1816.
10.1007/s00436-016-4920-x
PubMedWeb of Science®Google Scholar
736Satsu H, Matsuda T, Toshimitsu T, et al. Regulation of interleukin-8 secretion in human intestinal epithelial Caco-2 cells by alpha-humulene. Biofactors. 2004; 21: 137-139.
10.1002/biof.552210127
CASPubMedWeb of Science®Google Scholar
737Peana AT, D'Aquila PS, Chessa ML, Moretti MD, Serra G, Pippia P. (-)-Linalool produces antinociception in two experimental models of pain. Eur J Pharmacol. 2003; 460: 37-41.
10.1016/S0014-2999(02)02856-X
CASPubMedWeb of Science®Google Scholar
738Peana AT, D'Aquila PS, Panin F, Serra G, Pippia P, Moretti MD. Anti-inflammatory activity of linalool and linalyl acetate constituents of essential oils. Phytomedicine. 2002; 9: 721-726.
10.1078/094471102321621322
CASPubMedWeb of Science®Google Scholar
739Peana AT, Marzocco S, Popolo A, Pinto A. (-)-Linalool inhibits in vitro NO formation: Probable involvement in the antinociceptive activity of this monoterpene compound. Life Sci. 2006; 78: 719-723.
10.1016/j.lfs.2005.05.065
CASPubMedWeb of Science®Google Scholar
740Nakamura A, Fujiwara S, Matsumoto I, Abe K. Stress repression in restrained rats by (R)-(-)-linalool inhalation and gene expression profiling of their whole blood cells. J Agric Food Chem. 2009; 57: 5480-5485.
10.1021/jf900420g
CASPubMedWeb of Science®Google Scholar
741Russo EB. Handbook of Psychotropic Herbs: A Scientific Analysis of Herbal Remedies for Psychiatric Conditions. Binghamton, NY: Haworth Press; 2001.

Google Scholar
742Cline M, Taylor JE, Flores J, Bracken S, McCall S, Ceremuga TE. Investigation of the anxiolytic effects of linalool, a lavender extract, in the male Sprague-Dawley rat. AANA J. 2008; 76: 47-52.

PubMedGoogle Scholar
743Cheng BH, Sheen LY, Chang ST. Evaluation of anxiolytic potency of essential oil and S-(+)-linalool from Cinnamomum osmophloeum ct. linalool leaves in mice. J Tradit Complement Med 2014. 2015; 5: 27-34.
10.1016/j.jtcme.2014.10.007
PubMedWeb of Science®Google Scholar
744Buchbauer G, Jirovetz L, Jager W, Dietrich H, Plank C. Aromatherapy: evidence for sedative effects of the essential oil of lavender after inhalation. Z Naturforsch C. 1991; 46: 1067-1072.
10.1515/znc-1991-11-1223
CASPubMedWeb of Science®Google Scholar
745Jirovetz L, Buchbauer G, Jager W, Woidich A, Nikiforov A. Analysis of fragrance compounds in blood samples of mice by gas chromatography, mass spectrometry, GC/FTIR and GC/AES after inhalation of sandalwood oil. Biomed Chromatogr. 1992; 6: 133-134.
10.1002/bmc.1130060307
CASPubMedWeb of Science®Google Scholar
746Buchbauer G, Jirovetz L, Jager W, Plank C, Dietrich H. Fragrance compounds and essential oils with sedative effects upon inhalation. J Pharm Sci. 1993; 82: 660-664.
10.1002/jps.2600820623
CASPubMedWeb of Science®Google Scholar
747do Socorro S Rosa Mdo S, Mendonca-Filho RR, Bizzo HR, et al. Antileishmanial activity of a linalool-rich essential oil from Croton cajucara. Antimicrob Agents Chemother. 2003; 47: 1895-1901.
10.1128/AAC.47.6.1895-1901.2003
PubMedWeb of Science®Google Scholar
748Rodrigues Goulart H, Kimura EA, Peres VJ, Couto AS, Aquino Duarte FA, Katzin AM. Terpenes arrest parasite development and inhibit biosynthesis of isoprenoids in Plasmodium falciparum. Antimicrob Agents Chemother. 2004; 48: 2502-2509.
10.1128/AAC.48.7.2502-2509.2004
CASPubMedWeb of Science®Google Scholar
749de Sousa DP, Nobrega FF, Santos CC, de Almeida RN. Anticonvulsant activity of the linalool enantiomers and racemate: investigation of chiral influence. Nat Prod Commun. 2010; 5: 1847-1851.
10.1177/1934578X1000501201
PubMedWeb of Science®Google Scholar
750Elisabetsky E, Marschner J, Souza DO. Effects of Linalool on glutamatergic system in the rat cerebral cortex. Neurochem Res. 1995; 20: 461-465.
10.1007/BF00973103
CASPubMedWeb of Science®Google Scholar
751Ismail M. Central properties and chemical composition of Ocimum basilicum essential oil. Pharm Biol. 2006; 44: 619-626.
10.1080/13880200600897544
CASWeb of Science®Google Scholar
752Silva Brum LF, Emanuelli T, Souza DO, Elisabetsky E. Effects of linalool on glutamate release and uptake in mouse cortical synaptosomes. Neurochem Res. 2001; 26: 191-194.
10.1023/A:1010904214482
CASPubMedWeb of Science®Google Scholar
753Nunes DS, Linck VM, da Silva AL, Figueiro M, Elisabetsky E, Psychopharmacology of essential oils. In: KHC Baser, G Buchbauer, eds. Handbook of Essential Oils: Science, Technology, and Applications. Boca Raton, FL: CRC Press, 2010: 297-314.

Google Scholar
754Baschieri A, Ajvazi MD, Tonfack JLF, Valgimigli L, Amorati R. Explaining the antioxidant activity of some common non-phenolic components of essential oils. Food Chem. 2017; 232: 656-663.
10.1016/j.foodchem.2017.04.036
CASPubMedWeb of Science®Google Scholar
755Re L, Barocci S, Sonnino S, et al. Linalool modifies the nicotinic receptor-ion channel kinetics at the mouse neuromuscular junction. Pharmacol Res. 2000; 42: 177-182.
10.1006/phrs.2000.0671
CASPubMedWeb of Science®Google Scholar
756Ghelardini C, Galeotti N, Salvatore G, Mazzanti G. Local anaesthetic activity of the essential oil of Lavandula angustifolia. Planta Med. 1999; 65: 700-703.
10.1055/s-1999-14045
CASPubMedWeb of Science®Google Scholar
757Peana AT, Rubattu P, Piga GG, et al. Involvement of adenosine A1 and A2A receptors in (-)-linalool-induced antinociception. Life Sci. 2006; 78: 2471-2474.
10.1016/j.lfs.2005.10.025
CASPubMedWeb of Science®Google Scholar
758Batista PA, Werner MF, Oliveira EC, et al. Evidence for the involvement of ionotropic glutamatergic receptors on the antinociceptive effect of (-)-linalool in mice. Neurosci Lett. 2008; 440: 299-303.
10.1016/j.neulet.2008.05.092
CASPubMedWeb of Science®Google Scholar
759Kim JT, Ren CJ, Fielding GA, et al. Treatment with lavender aromatherapy in the post-anesthesia care unit reduces opioid requirements of morbidly obese patients undergoing laparoscopic adjustable gastric banding. Obes Surg. 2007; 17: 920-925.
10.1007/s11695-007-9170-7
PubMedWeb of Science®Google Scholar
760Hirota R, Roger NN, Nakamura H, Song HS, Sawamura M, Suganuma N. Anti-inflammatory effects of limonene from yuzu (Citrus junos Tanaka) essential oil on eosinophils. J Food Sci. 2010; 75: H87-H92.
10.1111/j.1750-3841.2010.01541.x
CASPubMedWeb of Science®Google Scholar
761Chaudhary SC, Siddiqui MS, Athar M, Alam MS. D-Limonene modulates inflammation, oxidative stress and Ras-ERK pathway to inhibit murine skin tumorigenesis. Hum Exp Toxicol. 2012; 31: 798-811.
10.1177/0960327111434948
CASPubMedWeb of Science®Google Scholar
762d'Alessio PA, Ostan R, Bisson J-F, Schulzke JD, Ursini MV, Béné MC. Oral administration of d-limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans. Life Sci. 2013; 92: 1151-1156.
10.1016/j.lfs.2013.04.013
CASPubMedWeb of Science®Google Scholar
763Piccinelli AC, Santos JA, Konkiewitz EC, et al. Antihyperalgesic and antidepressive actions of (R)-(+)-limonene, alpha-phellandrene, and essential oil from Schinus terebinthifolius fruits in a neuropathic pain model. Nutr Neurosci. 2015; 18: 217-224.
10.1179/1476830514Y.0000000119
CASPubMedWeb of Science®Google Scholar
764Singh P, Shukla R, Prakash B, et al. Chemical profile, antifungal, antiaflatoxigenic and antioxidant activity of Citrus maxima Burm. and Citrus sinensis (L.) Osbeck essential oils and their cyclic monoterpene, DL-limonene. Food Chem Toxicol. 2010; 48: 1734-1740.
10.1016/j.fct.2010.04.001
CASPubMedWeb of Science®Google Scholar
765Choi HS, Song HS, Ukeda H, Sawamura M. Radical-scavenging activities of citrus essential oils and their components: detection using 1,1-diphenyl-2-picrylhydrazyl. J Agric Food Chem. 2000; 48: 4156-4161.
10.1021/jf000227d
CASPubMedWeb of Science®Google Scholar
766Komori T, Fujiwara R, Tanida M, Nomura J, Yokoyama MM. Effects of citrus fragrance on immune function and depressive states. Neuroimmunomodulation. 1995; 2: 174-180.
10.1159/000096889
CASPubMedWeb of Science®Google Scholar
767Crowell PL, Gould MN. Chemoprevention and therapy of cancer by d-limonene. Crit Rev Oncog. 1994; 5: 1-22.
10.1615/CritRevOncog.v5.i1.10
CASPubMedWeb of Science®Google Scholar
768Rabi T, Bishayee A. d -Limonene sensitizes docetaxel-induced cytotoxicity in human prostate cancer cells: Generation of reactive oxygen species and induction of apoptosis. J Carcinog. 2009; 8: 9.
10.4103/1477-3163.51368
CASPubMedGoogle Scholar
769Vigushin DM, Poon GK, Boddy A, et al. Phase I and pharmacokinetic study of D-limonene in patients with advanced cancer. Cancer Research Campaign Phase I/II Clinical Trials Committee. Cancer Chemother Pharmacol. 1998; 42: 111-117.
10.1007/s002800050793
CASPubMedWeb of Science®Google Scholar
770da Fonseca CO, Simao M, Lins IR, Caetano RO, Futuro D, Quirico-Santos T. Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma. J Cancer Res Clin Oncol. 2011; 137: 287-293.
10.1007/s00432-010-0873-0
CASPubMedWeb of Science®Google Scholar
771Kim SS, Baik JS, Oh TH, Yoon WJ, Lee NH, Hyun CG. Biological activities of Korean Citrus obovoides and Citrus natsudaidai essential oils against acne-inducing bacteria. Biosci Biotechnol Biochem. 2008; 72: 2507-2513.
10.1271/bbb.70388
CASPubMedWeb of Science®Google Scholar
772Sanguinetti M, Posteraro B, Romano L, et al. In vitro activity of Citrus bergamia (bergamot) oil against clinical isolates of dermatophytes. J Antimicrob Chemother. 2007; 59: 305-308.
10.1093/jac/dkl473
CASPubMedWeb of Science®Google Scholar
773Harris B. Phytotherapeutic uses of essential oils. In: KHC Baser, G Buchbauer, eds. Handbook of Essential Oils: Science, Technology, and Applications. Boca Raton, FL: CRC Press; 2010: 315-352.

Google Scholar
774de Almeida AA, Costa JP, de Carvalho RB, de Sousa DP, de Freitas RM. Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its anxiolytic-like action. Brain Res. 2012; 1448: 56-62.
10.1016/j.brainres.2012.01.070
CASPubMedWeb of Science®Google Scholar
775Carvalho-Freitas MI, Costa M. Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L. Biol Pharm Bull. 2002; 25: 1629-1633.
10.1248/bpb.25.1629
CASPubMedWeb of Science®Google Scholar
776Pultrini A. d M, Galindo LA, Costa M. Effects of the essential oil from Citrus aurantium L. in experimental anxiety models in mice. Life Sci. 2006; 78: 1720-1725.
10.1016/j.lfs.2005.08.004
CASPubMedWeb of Science®Google Scholar
777Saiyudthong S, Marsden CA. Acute effects of bergamot oil on anxiety-related behaviour and corticosterone level in rats. Phytother Res. 2011; 25: 858-862.
10.1002/ptr.3325
CASPubMedWeb of Science®Google Scholar
778Pimenta FC, Alves MF, Pimenta MB, et al. Anxiolytic effect of Citrus aurantium L. on patients with chronic myeloid leukemia. Phytother Res. 2016; 30: 613-617.
10.1002/ptr.5566
CASPubMedWeb of Science®Google Scholar
779Komiya M, Takeuchi T, Harada E. Lemon oil vapor causes an anti-stress effect via modulating the 5-HT and DA activities in mice. Behav Brain Res. 2006; 172: 240-249.
10.1016/j.bbr.2006.05.006
CASPubMedWeb of Science®Google Scholar
780Turkez H, Aydin E, Geyikoglu F, Cetin D. Genotoxic and oxidative damage potentials in human lymphocytes after exposure to terpinolene in vitro. Cytotechnology. 2015; 67: 409-418.
10.1007/s10616-014-9698-z
CASPubMedWeb of Science®Google Scholar
781Aydin E, Türkez H, Taşdemir S. Anticancer and antioxidant properties of terpinolene in rat brain cells. Arh Hig Rada Toksikol. 2013; 64: 415-424.
10.2478/10004-1254-64-2013-2365
CASPubMedWeb of Science®Google Scholar
782Eftekhar F, Yousefzadi M, Azizian D, Sonboli A, Salehi P. Essential oil composition and antimicrobial activity of Diplotaenia damavandica. Z Naturforsch C. 2005; 60: 821-825.
10.1515/znc-2005-11-1202
CASPubMedGoogle Scholar
783Shafagha A, Shafaghatlonbar M. Antimicrobial activity and chemical constituents of the essential oils from flower, leaf and stem of Gypsophila bicolor from Iran. Nat Prod Commun. 2011; 6: 275-276.

PubMedWeb of Science®Google Scholar
784Okumura N, Yoshida H, Nishimura Y, Kitagishi Y, Matsuda S. Terpinolene, a component of herbal sage, downregulates AKT1 expression in K562 cells. Oncol Lett. 2012; 3: 321-324.
10.3892/ol.2011.491
CASPubMedWeb of Science®Google Scholar
785Ito K, Ito M. The sedative effect of inhaled terpinolene in mice and its structure-activity relationships. J Nat Med. 2013; 67: 833-837.
10.1007/s11418-012-0732-1
CASPubMedWeb of Science®Google Scholar
786Chang KS, Shin EH, Park C, Ahn YJ. Contact and fumigant toxicity of Cyperus rotundus steam distillate constituents and related compounds to insecticide-susceptible and -resistant Blattella germanica. J Med Entomol. 2012; 49: 631-639.
10.1603/ME11060
CASPubMedWeb of Science®Google Scholar
787Graßmann J, Hippeli S, Spitzenberger R, Elstner EF. The monoterpene terpinolene from the oil of Pinus mugo L. in concert with alpha-tocopherol and beta-carotene effectively prevents oxidation of LDL. Phytomedicine. 2005; 12: 416-423.
10.1016/j.phymed.2003.10.005
CASPubMedWeb of Science®Google Scholar
788Oliveira MG, Brito RG, Santos PL, et al. α-Terpineol, a monoterpene alcohol, complexed with β-cyclodextrin exerts antihyperalgesic effect in animal model for fibromyalgia aided with docking study. Chem Biol Interact. 2016; 254: 54-62.
10.1016/j.cbi.2016.05.029
CASPubMedWeb of Science®Google Scholar
789Held S, Schieberle P, Somoza V. Characterization of alpha-terpineol as an anti-inflammatory component of orange juice by in vitro studies using oral buccal cells. J Agric Food Chem. 2007; 55: 8040-8046.
10.1021/jf071691m
CASPubMedWeb of Science®Google Scholar
790Brand C, Ferrante A, Prager RH, et al. The water-soluble components of the essential oil of Melaleuca alternifolia (tea tree oil) suppress the production of superoxide by human monocytes, but not neutrophils, activated in vitro. Inflamm Res. 2001; 50: 213-219.
10.1007/s000110050746
CASPubMedWeb of Science®Google Scholar
791Burits M, Bucar F. Antioxidant activity of Nigella sativa essential oil. Phytother Res. 2000; 14: 323-328.
10.1002/1099-1573(200008)14:5<323::AID-PTR621>3.0.CO;2-Q
CASPubMedWeb of Science®Google Scholar
792Hassan SB, Gali-Muhtasib H, Goransson H, Larsson R. Alpha terpineol: a potential anticancer agent which acts through suppressing NF-kappaB signalling. Anticancer Res. 2010; 1911-1919.

PubMedWeb of Science®Google Scholar
793Park SN, Lim YK, Freire MO, Cho E, Jin D, Kook JK. Antimicrobial effect of linalool and alpha-terpineol against periodontopathic and cariogenic bacteria. Anaerobe. 2012; 18: 369-372.
10.1016/j.anaerobe.2012.04.001
CASPubMedWeb of Science®Google Scholar
794Zengin H, Baysal AH. Antibacterial and antioxidant activity of essential oil terpenes against pathogenic and spoilage-forming bacteria and cell structure-activity relationships evaluated by SEM microscopy. Molecules. 2014; 19: 17773-17798.
10.3390/molecules191117773
PubMedWeb of Science®Google Scholar
795Hammer KA, Carson CF, Riley TV. Antifungal activity of the components of Melaleuca alternifolia (tea tree) oil. J Appl Microbiol. 2003; 95: 853-860.
10.1046/j.1365-2672.2003.02059.x
CASPubMedWeb of Science®Google Scholar
796Williams AC, Barry BW. Terpenes and the lipid-protein-partitioning theory of skin penetration enhancement. Pharm Res. 1991; 08: 17-24.
10.1023/A:1015813803205
CASGoogle Scholar
797Zhu W, Liu X, Wang Y, Tong Y, Hu Y. Discovery of a novel series of alpha-terpineol derivatives as promising anti-asthmatic agents: Their design, synthesis, and biological evaluation. Eur J Med Chem. 2018; 143: 419-425.
10.1016/j.ejmech.2017.07.068
CASPubMedWeb of Science®Google Scholar
798Ribeiro TP, Porto DL, Menezes CP, et al. Unravelling the cardiovascular effects induced by alpha-terpineol: a role for the nitric oxide-cGMP pathway. Clin Exp Pharmacol Physiol. 2010; 37: 811-816.
10.1111/j.1440-1681.2010.05383.x
CASPubMedWeb of Science®Google Scholar
799Golfakhrabadi F, Khanavi M, Ostad SN, et al. Biological activities and composition of ferulago carduchorum essential oil. J Arthropod Borne Dis. 2014; 9: 104-115.

PubMedWeb of Science®Google Scholar
800Shafaghat A. Antibacterial activity and composition of essential oils from flower, leaf and stem of Chaerophyllum macropodum Boiss from Iran. Nat Prod Commun. 2009; 4: 861-864.

CASPubMedWeb of Science®Google Scholar
801Tsoyi K, Jang HJ, Lee YS, et al. (+)-Nootkatone and (+)-valencene from rhizomes of Cyperus rotundus increase survival rates in septic mice due to heme oxygenase-1 induction. J Ethnopharmacol. 2011; 137: 1311-1317.
10.1016/j.jep.2011.07.062
CASPubMedWeb of Science®Google Scholar
802Panella NA, Dolan MC, Karchesy JJ, et al. Use of novel compounds for pest control: insecticidal and acaricidal activity of essential oil components from heartwood of Alaska yellow cedar. J Med Entomol. 2005; 42: 352-358.
10.1093/jmedent/42.3.352
CASPubMedWeb of Science®Google Scholar
803Dietrich G, Dolan MC, Peralta-Cruz J, et al. Repellent activity of fractioned compounds from Chamaecyparis nootkatensis essential oil against nymphal Ixodes scapularis (Acari: Ixodidae). J Med Entomol. 2006; 43: 957-961.
10.1603/0022-2585(2006)43[957:RAOFCF]2.0.CO;2
CASPubMedWeb of Science®Google Scholar
804Santos PL, Araujo AA, Quintans JS, et al. Preparation, characterization, and pharmacological activity of Cymbopogon winterianus Jowitt ex Bor (Poaceae) leaf essential oil of beta-cyclodextrin inclusion complexes. Evid Based Complement Alternat Med. 2015; 2015: 502454.
10.1155/2015/502454
PubMedGoogle Scholar
805Marcuzzi A, Pontillo A, De Leo L, et al. Natural isoprenoids are able to reduce inflammation in a mouse model of mevalonate kinase deficiency. Pediatr Res. 2008; 64: 177-182.
10.1203/PDR.0b013e3181761870
CASPubMedWeb of Science®Google Scholar
806Tiwari M, Kakkar P. Plant derived antioxidants - Geraniol and camphene protect rat alveolar macrophages against t-BHP induced oxidative stress. Toxicol in Vitro. 2009; 23: 295-301.
10.1016/j.tiv.2008.12.014
CASPubMedWeb of Science®Google Scholar
807Godwin DA, Michniak BB. Influence of drug lipophilicity on terpenes as transdermal penetration enhancers. Drug Dev Ind Pharm. 1999; 25: 905-915.
10.1081/DDC-100102251
CASPubMedWeb of Science®Google Scholar
808Thapa D, Losa R, Zweifel B, Wallace RJ. Sensitivity of pathogenic and commensal bacteria from the human colon to essential oils. Microbiology. 2012; 158: 2870-2877.
10.1099/mic.0.061127-0
CASPubMedWeb of Science®Google Scholar
809Miladinovic DL, Ilic BS, Kocic BD, Ciric VM, Nikolic DM. Antibacterial investigation of thyme essential oil and its main constituents in combination with tetracycline. J Med Food. 2015; 18: 935-937.
10.1089/jmf.2014.0132
CASPubMedWeb of Science®Google Scholar
810Solorzano-Santos F, Miranda-Novales MG. Essential oils from aromatic herbs as antimicrobial agents. Curr Opin Biotechnol. 2012; 23: 136-141.
10.1016/j.copbio.2011.08.005
CASPubMedWeb of Science®Google Scholar
811Leite MC, de Brito Bezerra AP, de Sousa JP, de Oliveira Lima E. Investigating the antifungal activity and mechanism(s) of geraniol against Candida albicans strains. Med Mycol. 2015; 53: 275-284.
10.1093/mmy/myu078
CASPubMedWeb of Science®Google Scholar
812Juarez ZN, Bach H, Sanchez-Arreola E, Bach H, Hernandez LR. Protective antifungal activity of essential oils extracted from Buddleja perfoliata and Pelargonium graveolens against fungi isolated from stored grains. J Appl Microbiol. 2016; 120: 1264-1270.
10.1111/jam.13092
CASPubMedWeb of Science®Google Scholar
813Kpoviessi S, Bero J, Agbani P, et al. Chemical composition, cytotoxicity and in vitro antitrypanosomal and antiplasmodial activity of the essential oils of four Cymbopogon species from Benin. J Ethnopharmacol. 2014; 151: 652-659.
10.1016/j.jep.2013.11.027
CASPubMedWeb of Science®Google Scholar
814Maurya AK, Singh M, Dubey V, Srivastava S, Luqman S, Bawankule DU. Alpha-(-)-bisabolol reduces pro-inflammatory cytokine production and ameliorates skin inflammation. Curr Pharm Biotechnol. 2014; 15: 173-181.
10.2174/1389201015666140528152946
CASPubMedWeb of Science®Google Scholar
815Nurulain S, Prytkova T, Sultan AM, et al. Inhibitory actions of bisabolol on alpha7-nicotinic acetylcholine receptors. Neuroscience. 2015; 306: 91-99.
10.1016/j.neuroscience.2015.08.019
CASPubMedWeb of Science®Google Scholar
816Cavalieri E, Rigo A, Bonifacio M, et al. Pro-apoptotic activity of alpha-bisabolol in preclinical models of primary human acute leukemia cells. J Transl Med. 2011; 9: 45.
10.1186/1479-5876-9-45
CASPubMedWeb of Science®Google Scholar
817Cavalieri E, Mariotto S, Fabrizi C, et al. alpha-Bisabolol, a nontoxic natural compound, strongly induces apoptosis in glioma cells. Biochem Biophys Res Commun. 2004; 315: 589-594.
10.1016/j.bbrc.2004.01.088
CASPubMedWeb of Science®Google Scholar
818Costarelli L, Malavolta M, Giacconi R, et al. In vivo effect of alpha-bisabolol, a nontoxic sesquiterpene alcohol, on the induction of spontaneous mammary tumors in HER-2/neu transgenic mice. Oncol Res 2010. 18: 409-418.
10.3727/096504010X12671222663557
CASPubMedWeb of Science®Google Scholar
819Darra E, Abdel-Azeim S, Manara A, et al. Insight into the apoptosis-inducing action of alpha-bisabolol towards malignant tumor cells: involvement of lipid rafts and Bid. Arch Biochem Biophys. 2008; 476: 113-123.
10.1016/j.abb.2008.02.004
CASPubMedWeb of Science®Google Scholar
820Gomes-Carneiro MR, Dias DM, De-Oliveira AC, Paumgartten FJ. Evaluation of mutagenic and antimutagenic activities of alpha-bisabolol in the Salmonella/microsome assay. Mutat Res. 2005; 585: 105-112.
10.1016/j.mrgentox.2005.04.007
CASPubMedWeb of Science®Google Scholar
821Al Mansoori M, Al Shamri N, Al Kendi N, Al Jaberi M, Sheikh A, Amir N, Nalin N, et al. Bisabolol ameliorates cisplatin-induced nephrotoxicity in rats. Hamdan Med J. 2015; 8: 77-78.

Google Scholar
822Corpas-López V, Morillas-Márquez F, Navarro-Moll MC, Merino-Espinosa G, Díaz-Sáez V, Martín-Sánchez J. Martin-Sanchez J. (-)-alpha-bisabolol, a promising oral compound for the treatment of visceral leishmaniasis. J Nat Prod. 2015; 78: 1202-1207.
10.1021/np5008697
CASPubMedWeb of Science®Google Scholar
823Kurekci C, Padmanabha J, Bishop-Hurley SL, Hassan E, Al Jassim RA, McSweeney CS. Antimicrobial activity of essential oils and five terpenoid compounds against Campylobacter jejuni in pure and mixed culture experiments. Int J Food Microbiol. 2013; 166: 450-7.
10.1016/j.ijfoodmicro.2013.08.014
CASPubMedWeb of Science®Google Scholar
824Brehm-Stecher BF, Johnson EA. Sensitization of Staphylococcus aureus and Escherichia coli to antibiotics by the sesquiterpenoids nerolidol, farnesol, bisabolol, and apritone. Antimicrob Agents Chemother. 2003; 47: 3357-3360.
10.1128/AAC.47.10.3357-3360.2003
CASPubMedWeb of Science®Google Scholar
825Binet L, Binet P, Miocque M, Roux M, Bernier A. Reserches sur les proprietes pharmcodynamiques (action sedative et action spasmolytique) de quelques alcools terpeniques aliphatiques. Ann Pharm Fr. 1972; 30: 611-616.

CASPubMedWeb of Science®Google Scholar
826Arruda DC, D'Alexandri FL, Katzin AM, Uliana SR. Antileishmanial activity of the terpene nerolidol. Antimicrob Agents Chemother. 2005; 49: 1679-1687.
10.1128/AAC.49.5.1679-1687.2005
CASPubMedWeb of Science®Google Scholar
827AbouLaila M, Sivakumar T, Yokoyama N, Igarashi I. Inhibitory effect of terpene nerolidol on the growth of Babesia parasites. Parasitol Int. 2010; 59: 278-282.
10.1016/j.parint.2010.02.006
CASPubMedWeb of Science®Google Scholar
828Langenheim JH. Higher plant terpenoids: A phytocentric overview of their ecological roles. J Chem Ecol. 1994; 20: 1223-1280.
10.1007/BF02059809
CASPubMedWeb of Science®Google Scholar
829Lee SJ, Han JI, Lee GS, et al. Antifungal effect of eugenol and nerolidol against Microsporum gypseum in a guinea pig model. Biol Pharm Bull. 2007; 30: 184-188.
10.1248/bpb.30.184
CASPubMedWeb of Science®Google Scholar
830Lopes NP, Kato MJ, Andrade EH, et al. Antimalarial use of volatile oil from leaves of Virola surinamensis (Rol.) Warb. by Waiapi Amazon Indians. J Ethnopharmacol. 1999; 67: 313-319.
10.1016/S0378-8741(99)00072-0
CASPubMedWeb of Science®Google Scholar
831Wattenberg LW. Inhibition of azoxymethane-induced neoplasia of the large bowel by 3-hydroxy-3,7,11-trimethyl-1,6,10-dodecatriene (nerolidol). Carcinogenesis. 1991; 12: 151-152.
10.1093/carcin/12.1.151
CASPubMedWeb of Science®Google Scholar
832Cornwell PA, Barry BW. Sesquiterpene components of volatile oils as skin penetration enhancers for the hydrophilic permeant 5-fluorouracil. J Pharm Pharmacol. 1994; 46: 261-269.
10.1111/j.2042-7158.1994.tb03791.x
CASPubMedWeb of Science®Google Scholar
833Chavan MJ, Wakte PS, Shinde DB. Analgesic and anti-inflammatory activity of Caryophyllene oxide from Annona squamosa L. bark. Phytomedicine. 2010; 17: 149-151.
10.1016/j.phymed.2009.05.016
CASPubMedWeb of Science®Google Scholar
834Yang D, Michel L, Chaumont JP, Millet-Clerc J. Use of caryophyllene oxide as an antifungal agent in an in vitro experimental model of onychomycosis. Mycopathologia. 1999; 148: 79-82.
10.1023/A:1007178924408
CASPubMedWeb of Science®Google Scholar
835Bettarini F, Borgonovi GE, Fiorani T, et al. Antiparasitic compounds from East African plants: Isolation and biological activity of anonaine, matricarianol, canthin-6-one and caryophyllene oxide. Insect Sci Appl. 1993; 14: 93-99.

CASWeb of Science®Google Scholar
836Lin WY, Kuo YH, Chang YL, et al. Anti-platelet aggregation and chemical constituents from the rhizome of Gynura japonica. Planta Med. 2003; 69: 757-764.
10.1055/s-2003-42796
CASPubMedWeb of Science®Google Scholar
837Bang MH, Choi SY, Jang TO, et al. Phytol, SSADH inhibitory diterpenoid of Lactuca sativa. Arch Pharm Res. 2002; 25: 643-646.
10.1007/BF02976937
CASPubMedWeb of Science®Google Scholar
838Arnhold T, Elmazar MM, Nau H. Prevention of vitamin A teratogenesis by phytol or phytanic acid results from reduced metabolism of retinol to the teratogenic metabolite, all-trans-retinoic acid. Toxicol Sci. 2002; 66: 274-282.
10.1093/toxsci/66.2.274
CASPubMedWeb of Science®Google Scholar
839Stockman R. The physiological action of borneol. A contribution to the pharmacology of the camphor group. J Physiol. 1888; 9: 65-91.
10.1113/jphysiol.1888.sp000276
CASPubMedGoogle Scholar
840Park TJ, Park YS, Lee TG, Ha H, Kim KT. Inhibition of acetylcholine-mediated effects by borneol. Biochem Pharmacol. 2003; 65: 83-90.
10.1016/S0006-2952(02)01444-2
CASPubMedWeb of Science®Google Scholar
841Ehrnhofer-Ressler MM, Fricke K, Pignitter M, et al. Identification of 1,8-cineole, borneol, camphor, and thujone as anti-inflammatory compounds in a Salvia officinalis L. infusion using human gingival fibroblasts. J Agric Food Chem. 2013; 61: 3451-3459.
10.1021/jf305472t
CASPubMedWeb of Science®Google Scholar
842Almeida JR, Souza GR, Silva JC, et al. Borneol, a bicyclic monoterpene alcohol, reduces nociceptive behavior and inflammatory response in mice. ScientificWorldJournal. 2013; 2013: 1.

Google Scholar
843Adams JD, Wang X. Control of pain with topical plant medicines. Asian Pac J Trop Biomed. 2015; 5: 268-273.
10.1016/S2221-1691(15)30342-7
Google Scholar
844Jiang J, Shen YY, Li J, Lin YH, Luo CX, Zhu DY. (+)-Borneol alleviates mechanical hyperalgesia in models of chronic inflammatory and neuropathic pain in mice. Eur J Pharmacol. 2015; 757: 53-58.
10.1016/j.ejphar.2015.03.056
CASPubMedWeb of Science®Google Scholar
845Guangchi J, Shenghua Y, Xujun F. School of Pharmacy, West China University of Medical Sciences Chdngdu 610041. Anti-inflammatory effect of borneol and isoborneol. West China J Pharmaceutical Sci. 1990; 3.

Google Scholar
846Benelli G, Bedini S, Flamini G, et al. Mediterranean essential oils as effective weapons against the West Nile vector Culex pipiens and the Echinostoma intermediate host Physella acuta: what happens around? An acute toxicity survey on non-target mayflies. Parasitol Res. 2015; 114: 1011-1021.
10.1007/s00436-014-4267-0
PubMedWeb of Science®Google Scholar
847Dai JP, Chen J, Bei YF, Han BX, Wang S. Influence of borneol on primary mice oral fibroblasts: a penetration enhancer may be used in oral submucous fibrosis. J Oral Pathol Med. 2009; 38: 276-281.
10.1111/j.1600-0714.2008.00738.x
CASPubMedWeb of Science®Google Scholar
848Barreto RS, Quintans JS, Barreto AS, et al. Improvement of wound tissue repair by chitosan films containing (-)-borneol, a bicyclic monoterpene alcohol, in rats. Int Wound J. 2016; 13: 799-808.
10.1111/iwj.12385
PubMedWeb of Science®Google Scholar
849Yang CB, Pei WJ, Zhao J, Cheng YY, Zheng XH, Rong JH. Bornyl caffeate induces apoptosis in human breast cancer MCF-7 cells via the ROS- and JNK-mediated pathways. Acta Pharmacol Sin. 2014; 35: 113-123.
10.1038/aps.2013.162
CASPubMedWeb of Science®Google Scholar
850Chen J, Li L, Su J, Chen T. Natural borneol enhances bisdemethoxycurcumin-induced cell cycle arrest in the G2/M phase through up-regulation of intracellular ROS in HepG2 cells. Food Funct. 2015; 6: 740-748.
10.1039/C4FO00807C
CASPubMedWeb of Science®Google Scholar
851Su J, Lai H, Chen J, et al. Natural borneol, a monoterpenoid compound, potentiates selenocystine-induced apoptosis in human hepatocellular carcinoma cells by enhancement of cellular uptake and activation of ROS-mediated DNA damage. PLoS One. 2013; 8: e63502-11.
10.1371/journal.pone.0063502
CASPubMedWeb of Science®Google Scholar
852Zhang L, Han L, Qin J, Lu W, Wang J. The use of borneol as an enhancer for targeting aprotinin-conjugated PEG-PLGA nanoparticles to the brain. Pharm Res. 2013; 30: 2560-2572.
10.1007/s11095-013-1055-y
CASPubMedWeb of Science®Google Scholar
853Li YH, Sun XP, Zhang YQ, Wang NS. The antithrombotic effect of borneol related to its anticoagulant property. Am J Chin Med. 2008; 36: 719-727.
10.1142/S0192415X08006181
CASPubMedWeb of Science®Google Scholar
854Wu HY, Tang Y, Gao LY, et al. The synergetic effect of edaravone and borneol in the rat model of ischemic stroke. Eur J Pharmacol. 2014; 740: 522-531.
10.1016/j.ejphar.2014.06.035
CASPubMedWeb of Science®Google Scholar
855Jeong JG, Kim YS, Min YK, Kim SH. Low concentration of 3-carene stimulates the differentiation of mouse osteoblastic MC3T3-E1 subclone 4 cells. Phytother Res. 2008; 22: 18-22.
10.1002/ptr.2247
CASPubMedWeb of Science®Google Scholar
856Kweka EJ, Nyindo M, Mosha F, Silva AG. Insecticidal activity of the essential oil from fruits and seeds of Schinus terebinthifolia Raddi against African malaria vectors. Parasit Vectors. 2011; 4: 129.
10.1186/1756-3305-4-129
PubMedWeb of Science®Google Scholar
857Silva AG, Almeida DL, Ronchi SN, et al. The essential oil of Brazilian pepper, Schinus terebinthifolia Raddi in larval control of Stegomyia aegypti (Linnaeus, 1762). Parasit Vectors. 2010; 3: 79.
10.1186/1756-3305-3-79
PubMedWeb of Science®Google Scholar
858Nzira L, Per M, Peter F, Claus B. Lippia javanica (Burm F) Spreng: its general constituents and bioactivity on mosquitoes. Trop Biomed. 2009; 26: 85-91.

CASPubMedWeb of Science®Google Scholar
859Ramalho TR, Oliveira MT, Lima AL, Bezerra-Santos CR, Piuvezam MR. Gamma-terpinene modulates acute inflammatory response in mice. Planta Med. 2015; 81: 1248-1254.
10.1055/s-0035-1546169
CASPubMedWeb of Science®Google Scholar
860Rudback J, Bergstrom MA, Borje A, Nilsson U, Karlberg AT. alpha-Terpinene, an antioxidant in tea tree oil, autoxidizes rapidly to skin allergens on air exposure. Chem Res Toxicol. 2012; 25: 713-721.
10.1021/tx200486f
CASPubMedWeb of Science®Google Scholar
861Quintans-Junior L, Moreira JC, Pasquali MA, et al. Antinociceptive activity and redox profile of the monoterpenes (+)-Camphene, p-Cymene, and geranyl acetate in experimental models. ISRN Toxicol. 2013; 2013: 1.
10.1155/2013/459530
Google Scholar
862Marei GIK, Abdel Rasoul MA, Abdelgaleil SAM. Comparative antifungal activities and biochemical effects of monoterpenes on plant pathogenic fungi. Pestic Biochem Physiol. 2012; 103: 56-61.
10.1016/j.pestbp.2012.03.004
CASWeb of Science®Google Scholar
863Vallianou I, Peroulis N, Pantazis P, Hadzopoulou-Cladaras M. Camphene, a plant-derived monoterpene, reduces plasma cholesterol and triglycerides in hyperlipidemic rats independently of HMG-CoA reductase activity. PLoS One. 2011; 6: e20516-11.
10.1371/journal.pone.0020516
CASPubMedWeb of Science®Google Scholar
864Ali B, Al-Wabel NA, Shams S, Ahamad A, Khan SA, Anwar F. Essential oils used in aromatherapy: A systemic review. Asian Pac J Trop Biomed. 2015; 5: 601-611.
10.1016/j.apjtb.2015.05.007
Google Scholar
865Valente J, Zuzarte M, Goncalves MJ, et al. Antifungal, antioxidant and anti-inflammatory activities of Oenanthe crocata L. essential oil. Food Chem Toxicol. 2013; 62: 349-354.
10.1016/j.fct.2013.08.083
CASPubMedWeb of Science®Google Scholar
866Moss M, Oliver L. Plasma 1,8-cineole correlates with cognitive performance following exposure to rosemary essential oil aroma. Ther Adv Psychopharmacol. 2012; 2: 103-113.
10.1177/2045125312436573
CASPubMedGoogle Scholar
867Khan A, Vaibhav K, Javed H, et al. 1,8-cineole (eucalyptol) mitigates inflammation in amyloid Beta toxicated PC12 cells: relevance to Alzheimer's disease. Neurochem Res. 2014; 39: 344-352.
10.1007/s11064-013-1231-9
CASPubMedWeb of Science®Google Scholar
868Cho KH. 1,8-Cineole protected human lipoproteins from modification by oxidation and glycation and exhibited serum lipid-lowering and anti-inflammatory activity in zebrafish. BMB Rep. 2012; 45: 565-570.
10.5483/BMBRep.2012.45.10.044
CASPubMedWeb of Science®Google Scholar
869Santos FA, Rao VS. Antiinflammatory and antinociceptive effects of 1,8-cineole a terpenoid oxide present in many plant essential oils. Phytother Res. 2000; 14: 240-244.
10.1002/1099-1573(200006)14:4<240::AID-PTR573>3.0.CO;2-X
CASPubMedWeb of Science®Google Scholar
870Juergens UR. Anti-inflammatory properties of the monoterpene 1.8-cineole: current evidence for co-medication in inflammatory airway diseases. Drug Res (Stuttg). 2014; 64: 638-646.
10.1055/s-0034-1372609
CASPubMedGoogle Scholar
871Worth H, Schacher C, Dethlefsen U. Concomitant therapy with Cineole (Eucalyptole) reduces exacerbations in COPD: a placebo-controlled double-blind trial. Respir Res. 2009; 10: 69.
10.1186/1465-9921-10-69
CASPubMedWeb of Science®Google Scholar
872Worth H, Dethlefsen U. Patients with asthma benefit from concomitant therapy with cineole: a placebo-controlled, double-blind trial. J Asthma. 2012; 49: 849-853.
10.3109/02770903.2012.717657
CASPubMedWeb of Science®Google Scholar
873Juergens UR, Engelen T, Racké K, Stöber M, Gillissen A, Vetter H. Inhibitory activity of 1,8-cineol (eucalyptol) on cytokine production in cultured human lymphocytes and monocytes. Pulm Pharmacol Ther. 2004; 17: 281-287.
10.1016/j.pupt.2004.06.002
CASPubMedWeb of Science®Google Scholar
874Juergens UR, Dethlefsen U, Steinkamp G, Gillissen A, Repges R, Vetter H. Anti-inflammatory activity of 1.8-cineol (eucalyptol) in bronchial asthma: a double-blind placebo-controlled trial. Respir Med. 2003; 97: 250-256.
10.1053/rmed.2003.1432
CASPubMedWeb of Science®Google Scholar
875Santos FA, Silva RM, Campos AR, De Araújo RP, Lima Júnior RCP, Rao VSN. 1,8-cineole (eucalyptol), a monoterpene oxide attenuates the colonic damage in rats on acute TNBS-colitis. Food Chem Toxicol. 2004; 42: 579-584.
10.1016/j.fct.2003.11.001
CASPubMedWeb of Science®Google Scholar
876Lima PR, de Melo TS, Carvalho KM, et al. 1,8-cineole (eucalyptol) ameliorates cerulein-induced acute pancreatitis via modulation of cytokines, oxidative stress and NF-kappaB activity in mice. Life Sci. 2013; 92: 1195-1201.
10.1016/j.lfs.2013.05.009
CASPubMedWeb of Science®Google Scholar
877Kehrl W, Sonnemann U, Dethlefsen U. Therapy for acute nonpurulent rhinosinusitis with cineole: results of a double-blind, randomized, placebo-controlled trial. Laryngoscope. 2004; 114: 738-742.
10.1097/00005537-200404000-00027
PubMedWeb of Science®Google Scholar
878Burrow A, Eccles R, Jones AS. The effects of camphor, eucalyptus and menthol vapour on nasal resistance to airflow and nasal sensation. Acta Otolaryngol. 1983; 96: 157-161.
10.3109/00016488309132886
CASPubMedWeb of Science®Google Scholar
879Morcia C, Malnati M, Terzi V. In vitro antifungal activity of terpinen-4-ol, eugenol, carvone, 1,8-cineole (eucalyptol) and thymol against mycotoxigenic plant pathogens. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2011; 29: 1-22.
10.1080/19440049.2011.643458
PubMedWeb of Science®Google Scholar
880Ramsewak RS, Nair MG, Stommel M, Selanders L. In vitro antagonistic activity of monoterpenes and their mixtures against 'toe nail fungus' pathogens. Phytother Res. 2003; 17: 376-379.
10.1002/ptr.1164
CASPubMedWeb of Science®Google Scholar
881Moteki H, Hibasami H, Yamada Y, Katsuzaki H, Imai K, Komiya T. Specific induction of apoptosis by 1,8-cineole in two human leukemia cell lines, but not a in human stomach cancer cell line. Oncol Rep. 2002; 9: 757-760.

CASPubMedWeb of Science®Google Scholar
882Murata S, Shiragami R, Kosugi C, et al. Antitumor effect of 1, 8-cineole against colon cancer. Oncol Rep. 2013; 30: 2647-2652.
10.3892/or.2013.2763
CASPubMedWeb of Science®Google Scholar
883Chehregani A, Atri M, Yousefi S, Albooyeh Z, Mohsenzadeh F. Essential oil variation in the populations of Artemisia spicigera from northwest of Iran: chemical composition and antibacterial activity. Pharm Biol. 2013; 51: 246-252.
10.3109/13880209.2012.717631
CASPubMedWeb of Science®Google Scholar
884Ramos Alvarenga RF, Wan B, Inui T, Franzblau SG, Pauli GF, Jaki BU. Airborne antituberculosis activity of Eucalyptus citriodora essential oil. J Nat Prod. 2014; 77: 603-610.
10.1021/np400872m
CASPubMedWeb of Science®Google Scholar
885Conti B, Flamini G, Cioni PL, Ceccarini L, Macchia M, Benelli G. Mosquitocidal essential oils: are they safe against non-target aquatic organisms? Parasitol Res. 2014; 113: 251-259.
10.1007/s00436-013-3651-5
PubMedWeb of Science®Google Scholar
886Wang Y, You CX, Wang CF, et al. Chemical constituents and insecticidal activities of the essential oil from Amomum tsaoko against two stored-product insects. J Oleo Sci. 2014; 63: 1019-1026.
10.5650/jos.ess14087
CASPubMedWeb of Science®Google Scholar
887Rodenak Kladniew B, Polo M, Montero Villegas S, Galle M, Crespo R, García de Bravo M. Synergistic antiproliferative and anticholesterogenic effects of linalool, 1,8-cineole, and simvastatin on human cell lines. Chem Biol Interact. 2014; 214: 57-68.
10.1016/j.cbi.2014.02.013
CASPubMedWeb of Science®Google Scholar
888Choudhary MI, Batool I, Atif M, Hussain S, Atta-Ur-Rahman. Microbial transformation of (-)-guaiol and antibacterial activity of its transformed products. J Nat Prod. 2007; 70: 849-852.
10.1021/np068052a
CASPubMedWeb of Science®Google Scholar
889Liu T, Wang CJ, Xie HQ, Mu Q. Guaiol–a naturally occurring insecticidal sesquiterpene. Nat Prod Commun. 2013; 8: 1353-1354.

CASPubMedWeb of Science®Google Scholar
890Tian LL, Zhou Z, Zhang Q, et al. Protective effect of (+/-) isoborneol against 6-OHDA-induced apoptosis in SH-SY5Y cells. Cell Physiol Biochem. 2007; 20: 1019-1032.
10.1159/000110682
CASPubMedGoogle Scholar
891de Cassia da Silveira E, Sa R, Andrade LN, de Sousa DP. A review on anti-inflammatory activity of monoterpenes. Molecules. 2013; 18: 1227-1254.
10.3390/molecules18011227
PubMedWeb of Science®Google Scholar
892Stojanović G, Palić I, Ursić-Janković J. Composition and antimicrobial activity of the essential oil of Micromeria cristata and Micromeria juliana. Flavour Fragrance J. 2006; 21: 77-79.
10.1002/ffj.1507
CASWeb of Science®Google Scholar
893Armaka M, Papanikolaou E, Sivropoulou A, Arsenakis M. Antiviral properties of isoborneol, a potent inhibitor of herpes simplex virus type 1. Antiviral Res. 1999; 43: 79-92.
10.1016/S0166-3542(99)00036-4
CASPubMedWeb of Science®Google Scholar
894Alsemari A, Alkhodairy F, Aldakan A, et al. The selective cytotoxic anti-cancer properties and proteomic analysis of Trigonella Foenum-Graecum. BMC Complement Altern Med. 2014; 14: 114.
10.1186/1472-6882-14-114
PubMedWeb of Science®Google Scholar
895Al-Daghri NM, Alokail MS, Alkharfy KM, et al. Fenugreek extract as an inducer of cellular death via autophagy in human T lymphoma Jurkat cells. BMC Complement Altern Med. 2012; 12: 202.
10.1186/1472-6882-12-202
PubMedWeb of Science®Google Scholar
896Nibret E, Wink M. Trypanocidal and antileukaemic effects of the essential oils of Hagenia abyssinica, Leonotis ocymifolia, Moringa stenopetala, and their main individual constituents. Phytomedicine. 2010; 17: 911-920.
10.1016/j.phymed.2010.02.009
CASPubMedWeb of Science®Google Scholar
897Al-Rahmah AN, Mostafa AA, Abdelb-Megeed A, Yakout SM, Hussein SA. Fungicidal activities of certain methanolic plant extracts against tomato phytopathogenic fungi. Afr J Microbiol Res. 2013; 7: 517-524.

Google Scholar
898Kakarla S, Ganjewala D. Antimicrobial activity of essential oils of four lemongrass (Cymbopogon flexuosus Steud) varieties. Med Aromat Plant Sci Biotechnol. 2009; 3: 107-109.

Google Scholar
899Asghari G, Jalali M, Sadoughi E. Antimicrobial activity and chemical composition of essential oil from the seeds of Artemisia aucheri Boiss. Jundishapur J Nat Pharm Prod. 2012; 7: 11-15.
10.5812/jjnpp.3530
PubMedGoogle Scholar
900Gonçalves MJ, Cruz MT, Tavares AC, et al. Composition and biological activity of the essential oil from Thapsia minor, a new source of geranyl acetate. Ind Crops Prod. 2012; 35: 166-171.
10.1016/j.indcrop.2011.06.030
CASWeb of Science®Google Scholar
901Guleria S, Tiku AK, Koul A, Gupta S, Singh G, Razdan VK. Antioxidant and antimicrobial properties of the essential oil and extracts of Zanthoxylum alatum grown in north-western Himalaya. ScientificWorldJournal. 2013; 2013: 1.
10.1155/2013/790580
Google Scholar
902Lee HJ, Hyun EA, Yoon WJ, et al. In vitro anti-inflammatory and anti-oxidative effects of Cinnamomum camphora extracts. J Ethnopharmacol. 2006; 103: 208-216.
10.1016/j.jep.2005.08.009
PubMedWeb of Science®Google Scholar
903Burkhart CG, Burkhart HR. Contact irritant dermatitis and anti-pruritic agents: the need to address the itch. J Drugs Dermatol. 2003; 2: 143-146.

PubMedGoogle Scholar
904Cohen M, Wolfe R, Mai T, Lewis D. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. J Rheumatol. 2003; 30: 523-528.

CASPubMedWeb of Science®Google Scholar
905Xu H, Blair NT, Clapham DE. Camphor activates and strongly desensitizes the transient receptor potential vanilloid subtype 1 channel in a vanilloid-independent mechanism. J Neurosci. 2005; 25: 8924-8937.
10.1523/JNEUROSCI.2574-05.2005
CASPubMedWeb of Science®Google Scholar
906Mahboubi M, Kazempour N. The antimicrobial activity of essential oil from Perovskia abrotanoides Karel and its main components. Indian J Pharm Sci. 2009; 71: 343-347.
10.4103/0250-474X.56016
CASPubMedWeb of Science®Google Scholar
907Peier AM, Moqrich A, Hergarden AC, et al. A TRP channel that senses cold stimuli and menthol. Cell. 2002; 108: 705-715.
10.1016/S0092-8674(02)00652-9
CASPubMedWeb of Science®Google Scholar
908Galeotti N, Di Cesare Mannelli L, Mazzanti G, Bartolini A, Ghelardini C. Menthol: a natural analgesic compound. Neurosci Lett. 2002; 322: 145-148.
10.1016/S0304-3940(01)02527-7
CASPubMedWeb of Science®Google Scholar
909Pan R, Tian Y, Gao R, et al. Central mechanisms of menthol-induced analgesia. J Pharmacol Exp Ther. 2012; 343: 661-672.
10.1124/jpet.112.196717
CASPubMedWeb of Science®Google Scholar
910Kamatou GP, Vermaak I, Viljoen AM, Lawrence BM. Menthol: a simple monoterpene with remarkable biological properties. Phytochemistry. 2013; 96: 15-25.
10.1016/j.phytochem.2013.08.005
CASPubMedWeb of Science®Google Scholar
911Silva MI, Moura BA, Neto MR, et al. Gastroprotective activity of isopulegol on experimentally induced gastric lesions in mice: investigation of possible mechanisms of action. Naunyn Schmiedebergs Arch Pharmacol. 2009; 380: 233-245.
10.1007/s00210-009-0429-5
CASPubMedWeb of Science®Google Scholar
912Silva MI, de Aquino Neto MR, Teixeira Neto PF, et al. Central nervous system activity of acute administration of isopulegol in mice. Pharmacol Biochem Behav. 2007; 88: 141-147.
10.1016/j.pbb.2007.07.015
CASPubMedWeb of Science®Google Scholar
913Silva MI, Silva MA, de Aquino Neto MR, et al. Effects of isopulegol on pentylenetetrazol-induced convulsions in mice: possible involvement of GABAergic system and antioxidant activity. Fitoterapia. 2009; 80: 506-513.
10.1016/j.fitote.2009.06.011
CASPubMedWeb of Science®Google Scholar
914Bonjardim LR, Cunha ES, Guimaraes AG, et al. Evaluation of the anti-inflammatory and antinociceptive properties of p-cymene in mice. Z Naturforsch C. 2012; 67: 15-21.
10.5560/ZNC.2012.67c0015
CASPubMedWeb of Science®Google Scholar
915de Santana MF, Guimaraes AG, Chaves DO, et al. The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: Evidence for the involvement of opioid system and cytokines. Pharm Biol. 2015; 53: 1583-1590.
10.3109/13880209.2014.993040
PubMedWeb of Science®Google Scholar
916Kisko G, Roller S. Carvacrol and p-cymene inactivate Escherichia coli O157:H7 in apple juice. BMC Microbiol. 2005; 5: 36.
10.1186/1471-2180-5-36
CASPubMedWeb of Science®Google Scholar
917Segvic Klaric M, Kosalec I, Mastelic J, Pieckova E, Pepeljnak S. Antifungal activity of thyme (Thymus vulgaris L.) essential oil and thymol against moulds from damp dwellings. Lett Appl Microbiol. 2007; 44: 36-42.
10.1111/j.1472-765X.2006.02032.x
CASPubMedWeb of Science®Google Scholar
918Chen L, Zhao L, Zhang C, Lan Z. Protective effect of p-cymene on lipopolysaccharide-induced acute lung injury in mice. Inflammation. 2014; 37: 358-364.
10.1007/s10753-013-9747-3
CASPubMedWeb of Science®Google Scholar
919Rabbani SI, Devi K, Khanam S, Zahra N. Citral, a component of lemongrass oil inhibits the clastogenic effect of nickel chloride in mouse micronucleus test system. Pak J Pharm Sci. 2006; 19: 108-113.

CASPubMedGoogle Scholar
920Onawunmi GO. Evaluation of the antimicrobial activity of citral. Lett Appl Microbiol. 1989; 9: 105-108.
10.1111/j.1472-765X.1989.tb00301.x
CASWeb of Science®Google Scholar
921Sadraei H, Ghannadi A, Malekshahi K. Relaxant effect of essential oil of Melissa officinalis and citral on rat ileum contractions. Fitoterapia. 2003; 74: 445-452.
10.1016/S0367-326X(03)00109-6
CASPubMedWeb of Science®Google Scholar
922Zhuang SR, Chen SL, Tsai JH, et al. Effect of citronellol and the Chinese medical herb complex on cellular immunity of cancer patients receiving chemotherapy/radiotherapy. Phytother Res. 2009; 23: 785-790.
10.1002/ptr.2623
CASPubMedWeb of Science®Google Scholar
923Brito RG, Guimaraes AG, Quintans JS, et al. Citronellol, a monoterpene alcohol, reduces nociceptive and inflammatory activities in rodents. J Nat Med. 2012; 66: 637-644.
10.1007/s11418-012-0632-4
CASPubMedWeb of Science®Google Scholar
924Bastos JF, Moreira IJ, Ribeiro TP, et al. Hypotensive and vasorelaxant effects of citronellol, a monoterpene alcohol, in rats. Basic Clin Pharmacol Toxicol. 2010; 106: 331-337.
10.1111/j.1742-7843.2009.00492.x
CASPubMedWeb of Science®Google Scholar
925Lopez-Romero JC, Gonzalez-Rios H, Borges A, Simoes M. Antibacterial effects and mode of action of selected essential oils components against Escherichia coli and Staphylococcus aureus. Evid Based Complement Alternat Med. 2015; 2015: 795435.
10.1155/2015/795435
PubMedWeb of Science®Google Scholar
926Pereira FdE O, Mendes JM, Lima IO, Mota KS, Oliveira WA, Lima Ede O. Antifungal activity of geraniol and citronellol, two monoterpenes alcohols, against Trichophyton rubrum involves inhibition of ergosterol biosynthesis. Pharm Biol. 2015; 53: 228-234.
10.3109/13880209.2014.913299
CASPubMedWeb of Science®Google Scholar
927Flores-Sanchez IJ, Verpoorte R. Secondary metabolism in cannabis. Phytochem. Rev. 2008; 7: 615-639.
10.1007/s11101-008-9094-4
CASGoogle Scholar
928Arts IC, Hollman PC. Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr. 2005; 81: 317S-25S.
10.1093/ajcn/81.1.317S
CASPubMedWeb of Science®Google Scholar
929Andre CM, Larondelle Y, Evers D. Dietary antioxidants and oxidative stress from a human and plant perspective: A review. Curr Nutr Food Sci. 2010; 6: 2-12.
10.2174/157340110790909563
CASGoogle Scholar
930Murti K, Panchal MA, Gajera V, Solanki J. Pharmacological properties of matricaria recutita: a review. Pharmcognosy. 2012; 3: 348-351.

Google Scholar
931Gerritsen ME, Carley WW, Ranges GE, et al. Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression. Am J Pathol. 1995; 147: 278-292.

CASPubMedWeb of Science®Google Scholar
932Werz O, Seegers J, Schaible AM, et al. Cannflavins from hemp sprouts, a novel cannabinoid-free hemp food product, target microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase. PharmaNutrition. 2014; 2: 53-60.
10.1016/j.phanu.2014.05.001
CASGoogle Scholar
933Barrett ML, Scutt AM, Evans FJ. Cannflavin A and B, prenylated flavones from Cannabis sativa L. Experientia. 1986; 42: 452-453.
10.1007/BF02118655
CASPubMedWeb of Science®Google Scholar
934Gomez MA, Saenz MT, Garcia MD, Fernandez MA. Study of the topical anti-inflammatory activity of Achillea ageratum on chronic and acute inflammation models. Z Naturforsch C. 1999; 54: 937-941.
10.1515/znc-1999-1113
CASPubMedWeb of Science®Google Scholar
935Fischedick JT, Hazekamp A, Erkelens T, Choi YH, Verpoorte R. Metabolic fingerprinting of Cannabis sativa L., cannabinoids and terpenoids for chemotaxonomic and drug standardization purposes. Phytochemistry. 2010; 71: 2058-2073.
10.1016/j.phytochem.2010.10.001
CASPubMedWeb of Science®Google Scholar
936Hillig KW. A chemotaxonomic analysis of terpenoid variation in Cannabis. Biochem Syst Ecol. 2004; 32: 875-891.
10.1016/j.bse.2004.04.004
CASWeb of Science®Google Scholar
937Hillig KW, Mahlberg PG. A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae). Am J Bot. 2004; 91: 966-975.
10.3732/ajb.91.6.966
CASPubMedWeb of Science®Google Scholar
938Sawler J, Stout JM, Gardner KM, et al. The genetic structure of marijuana and hemp. PLoS One. 2015; 10: e0133292.
10.1371/journal.pone.0133292
PubMedWeb of Science®Google Scholar
939Baron EP, Lucas P, Eades J, Hogue O. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort. J Headache Pain. 2018; 19: 1-28.
10.1186/s10194-018-0862-2
PubMedWeb of Science®Google Scholar
940Casano S, Grassi G, Martini V, Michelozzi M. Variations in terpene profiles of different strains of Cannabis sativa L. Acta Hortic. 2011; 925: 115-121.
10.17660/ActaHortic.2011.925.15
Web of Science®Google Scholar
941Liu RH. Health-promoting components of fruits and vegetables in the diet. Adv Nutr. 2013; 4: 384S-92S.
10.3945/an.112.003517
CASPubMedWeb of Science®Google Scholar

Citing Literature

Volume58, Issue7

July/August 2018

Pages 1139-1186

Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science

Abstract

Background

Objective

Conclusion

REFERENCES

Citing Literature

References

Information

RESOURCES

PUBLICATION INFO

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science

Abstract

Background

Objective

Conclusion

REFERENCES

Citing Literature

References

Related

Information

RESOURCES

PUBLICATION INFO