Cannabis sativa L. has been used therapeutically for thousands of years.1
It was well known that the plant had psychotropic effects, inducing a “high.” However, the cause of those effects was not understood until recently. Research into the effects of the plant led to the discovery of cannabinoids, which can now be separated into 3 primary classes: phytocannabinoids, endocannabinoids, and synthetic cannabinoids.
Phytocannabinoids consist of >100 naturally occurring compounds found in Cannabis sativa L, the cannabis plant with a chemical structure related to endocannabinoids1,2
Endocannabinoids are compounds produced by the body that target cannabinoid receptors, such as CB1 and CB21
Synthetic cannabinoids are cannabinoids produced in a laboratory to structurally or functionally mimic the effects of endocannabinoids or phytocannabinoids1
This site is based on current cannabinoid research, peer-reviewed journal articles, and information from leading investigators and medical experts.
References: 1. Grotenhermen F. Cannabinoids and the endocannabinoid system. Cannabinoids. 2006;1:10-14. 2. ElSohly M, Gul W. Constituents of Cannabis sativa. In: Pertwee RG, ed. Handbook of Cannabis. Oxford, UK: Oxford University Press; 2014:3-22.
Best characterized phytocannabinoids1*
Recently, scientists have gained a greater understanding of different cannabinoids, such as THC (Δ9-tetrahydrocannabinol) and CBD (cannabidiol), and their potential therapeutic benefits.
Tetrahydrocannabinol (THC), most commonly delta 9, is the by-product of heating THCA
A major cannabinoid derived from cannabis or synthesized1,5,6
Primarily responsible for marijuana’s psychotropic properties5,6
Recreational and therapeutic uses: FDA-approved synthetic and analogue products such as Marinol.com and Syndros.com are indicated for nausea and vomiting related to chemotherapy and anorexia associated with AIDS
Tetrahydrocannabivarin, a lesser known cannabinoid, produced from tetrahydrocannabidivaric acid (THCVA)
Studies in rodent models of Parkinson’s disease, as well as insulin sensitivity (a model of diabetes)10,11
Under investigation for potential use in type 2 diabetes12
Cannabidolic acid (CBDA) is how CBD occurs in the plant
Testing of CBDA in rodent models illustrate that CBDA works on the serotonin receptor (specifically 5-HT1A) to prevent vomiting and suppress nausea and anxiety39,40
Cannabidiol (CBD), the by-product of heating CBDA
One of the major cannabinoids derived or synthesized from cannabis1
CBD has very low affinity for cannabinoid receptors CB1 and so is lacking euphoric side effects13
Under investigation for anticonvulsant properties, as a potential treatment for schizophrenia, as well as other conditions14-17
EPIDIOLEX is a specific formulation approved for specific epilepsies
Cannabidivarin (CBDV), a lesser known cannabinoid, produced from cannabidivaric acid (CBVA)
Studies in rodent models of epilepsy and autism spectrum disorder17,18
Under investigation for potential anticonvulsant properties
No clinical data are available
Tetrahydrocannabinolic acid A (how THC occurs in the cannabis plant)
Limited study in rodents in nausea4
Not currently under investigation
Phytocannabinoid Research and Discovery
Over 100 naturally occurring compounds are found in the cannabis plant, the best characterized of which are described above.1*
Phytocannabinoids such as THC, CBD, and cannabinol (CBN) were identified first and isolated from the plant. Then, in 1988, while scientists were investigating how THC exerted its effects, the endocannabinoid system was discovered within the body.
The discovery of this endogenous system has led to exploration of how cannabinoids, including both the plant molecules and synthetic versions developed in laboratories, might be used for therapeutic purposes.
Researchers are continuing to investigate the therapeutic potential of phytocannabinoids, while also exploring the development of synthetic cannabinoids that mimic their effects.2 Compounds that are researched and developed may focus on a single type of cannabinoid or may combine more than one type of cannabinoid.3
Do you know what causes
the marijuana "high"?
Do you know what causes the marijuana “high”?
This is largely attributed to a cannabinoid called THC, or Δ9-tetrahydrocannabinol. THC is a major phytocannabinoid that can be found in the cannabis plant and binds to the cannabinoid receptor primarily responsible for this psychotropic effect (CB1).1,2
*Level of evidence required to reference clinical data is phase 3 trials, which are randomized and controlled (randomized controlled trial: RCT). Adequate human studies are required for the FDA to evaluate safety and efficacy of a potential medicine. This content reflects studies known as of January 2018.
Data that have been published in peer-reviewed journals can be found at PubMed.
Clinical trial information can be found at ClinicalTrials.gov.
AIDS=acquired immunodeficiency syndrome.
References: 1. ElSohly M, Gul W. Constituents of Cannabis sativa. In: Pertwee RG, ed. Handbook of Cannabis. Oxford, UK: Oxford University Press; 2014:3-22. 2. Grotenhermen F. Cannabinoids and the endocannabinoid system. Cannabinoids. 2006;1:10-14.
3. Sativex [package insert]. Berkshire, United Kingdom: GW Pharma Ltd; 2015. 4. Rock 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. 5. Pertwee RG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol. 2006;147:S163-S171. 6. Pertwee RG, Cascio MG. Known pharmacological actions of delta-9-tetrahydrocannabinol and of four other chemical constituents of cannabis that activate cannabinoid receptors. In: Pertwee RG, ed. Handbook of Cannabis. Oxford, UK: Oxford University Press; 2014:115-136. 7. Marinol [package insert]. North Chicago, IL: AbbVie Inc; 2017. 8. Cesamet [package insert]. Somerset, NJ: Meda Pharmaceuticals Inc; 2013. 9. Syndros [package insert]. Chandler, AZ: Insys Therapeutics, Inc; 2017. 10. Garcia C, Palomo-Garo C, Garcia-Arencibia M, Ramos JA, Pertwee RG, Fernandez-Ruiz J. Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ9-THCV in animal models of Parkinson’s disease. Br J Pharmacol. 2011;163:1495-1506. 11. Wargent ET, Zaibi MS, Hislop DC, et al. The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutr Diabetes. 2013;3,e68;doi:10.1038/nutd.2013.9. 12. Jadoon KA, Ratcliffe SH, Barrett DA, et al. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot study. Diabetes Care. 2016;39:1777-1786. 13. Amada N, Yamasaki Y, Williams CM, Whalley BJ. Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression. Peer J. 2013;e214; doi:10.7717/peerj.214. 14. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376:2011-2020. 15. Devinsky 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. 16. McGuire P, Robson P, Cubala WJ, et al. Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial. Am J Psychiatry. 2017; doi:10.1176/appi.ajp.2017.17030325. 17. Cascio MG, Pertwee RG. Known pharmacological actions of nine nonpsychotropic phytocannabinoids. In: Pertwee RG, ed. Handbook of Cannabis. Oxford, UK: Oxford University Press; 2014:137-156. 18. Iannotti FA, Hill CL, Leo A, et al. Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chem Neurosci. 2014;5:1131-1141.
References: 1. Russo EB. Current therapeutic cannabis controversies and clinical trial design issues. Front Pharmacol. 2016;14(7):1-19.
2. Russo EB. Cannabidiol claims and misconceptions. Trends Pharmacol Sci. 2017;38:198-201.
3. NIDA. Poster presented at Annual Meeting of American Epilepsy Society; December 1–5, 2017; Washington, DC. 4. World Health Organization website. http://www.who.int/features/qa/cannabidiol/en/. Accessed May 10, 2018.
The role of the endocannabinoid system
Endocannabinoids are compounds produced by the body that impact biological processes.1
The endocannabinoid system can impact a person’s physiological processes, including3:
- Pain and inflammation
- Feeding and energy regulation
- Learning and memory
- Emotion regulation
Endocannabinoids identified so far include:
- Anandamide (AEA)
- 2-arachidonoylglycerol (2-AG)
- N-arachidonoyl dopamine (NADA)
- Noladin ether (2-arachidonyl glyceryl ether)
These neuroregulatory molecules bind to cannabinoid receptors (such as CB1 and CB2) that have been found within the central nervous system, reproductive organs, skin, and digestive tract.1,2
This system can impact a person’s physiological processes, including pain and inflammation, feeding and energy regulation, learning and memory, and emotion regulation.3
Did you know that not all cannabinoids target the same receptors?
Did you know that not all cannabinoids target the same receptors?
CBD has very low affinity for CB1 and so it lacks euphoric side effects.1,2
References: 1. Grotenhermen F. Cannabinoids and the endocannabinoid system. Cannabinoids. 2006;1:10-14. 2. Oddi S, Maccarrone M. Phytocannabinoids and skin disorders. In: Pertwee RG, ed. Handbook of Cannabis. Oxford, UK: Oxford University Press; 2014:582-600.
3. Lichtman AH, Blankman JL, Cravatt BF. Endocannabinoid overload. Mol Pharmacol. 2010;78:993-995.