The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin.
R G Pertwee
British Journal of Pharmacology January 2008 DOI: 10.1038/sj.bjp.0707442 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Cannabis CBD |
| Key findings | The review reports that delta9-THC is a CB1/CB2 partial agonist whose effects depend on receptor expression and endogenous cannabinoid tone; CBD acts as a potent antagonist at CB1/CB2 in cell and tissue models, possibly explaining inhibition of immune cell migration; and delta9-THCV is a potent CB2 partial agonist in vitro but a CB1 antagonist in CB1-expressing tissues, acting in vivo as a CB1 antagonist or, at higher doses, an agonist. |
Abstract
Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, (-)-trans-delta9-tetrahydrocannabinol (delta9-THC), (-)-cannabidiol (CBD) and (-)-trans-delta9-tetrahydrocannabivarin (delta9-THCV), interact with cannabinoid CB1 and CB2 receptors. Delta9-THC, the main psychotropic constituent of cannabis, is a CB1 and CB2 receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by the expression level and signalling efficiency of cannabinoid receptors and by ongoing endogenous cannabinoid release. CBD displays unexpectedly high potency as an antagonist of CB1/CB2 receptor agonists in CB1- and CB2-expressing cells or tissues, the manner with which it interacts with CB2 receptors providing a possible explanation for its ability to inhibit evoked immune cell migration. Delta9-THCV behaves as a potent CB2 receptor partial agonist in vitro. In contrast, it antagonizes cannabinoid receptor agonists in CB1-expressing tissues. This it does with relatively high potency and in a manner that is both tissue and ligand dependent. Delta9-THCV also interacts with CB1 receptors when administered in vivo, behaving either as a CB1 antagonist or, at higher doses, as a CB1 receptor agonist. Brief mention is also made in this review, first of the production by delta9-THC of pharmacodynamic tolerance, second of current knowledge about the extent to which delta9-THC, CBD and delta9-THCV interact with pharmacological targets other than CB1 or CB2 receptors, and third of actual and potential therapeutic applications for each of these cannabinoids.
Comparable studies
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Citations in the library
Cited by 129
- Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history. Journal of Ethnopharmacology December 5, 2018
- Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Journal of Psychopharmacology October 5, 2012
- Beyond THC: The New Generation of Cannabinoid Designer Drugs Frontiers in Behavioral Neuroscience 2011
- Traditional marijuana, high‐potency cannabis and synthetic cannabinoids: increasing risk for psychosis World Psychiatry September 22, 2016
- Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Current Pharmaceutical Design September 12, 2012
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Cites 6
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