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Cited by 521

The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.

Are cannabidiol and Δ9‐tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review

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McPartland, John M, Duncan, Marnie, Di Marzo, Vincenzo, Pertwee, Roger G·2015·British Journal of Pharmacology
DOI 10.1111/bph.12944
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Abstract

Based upon evidence that the therapeutic properties ofCannabis preparations are not solely dependent upon the presence of Δ 9‐tetrahydrocannabinol (THC), pharmacological studies have been recently carried out with other plant cannabinoids (phytocannabinoids), particularly cannabidiol (CBD) and Δ 9‐tetrahydrocannabivarin (THCV). Results from some of these studies have fostered the view that CBD and THCV modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first‐generation CB1 receptor inverse agonists, such as rimonabant. Here, we review in vitro and ex vivo mechanistic studies of CBD and THCV, and synthesize data from these studies in a meta‐analysis. Synthesized data regarding mechanisms are then used to interpret results from recent pre‐clinical animal studies and clinical trials. The evidence indicates that CBD and THCV are not rimonabant‐like in their action and thus appear very unlikely to produce unwanted CNS effects. They exhibit markedly disparate pharmacological profiles particularly at CB1 receptors:CBD is a very low‐affinity CB1 ligand that can nevertheless affect CB1 receptor activity in vivo in an indirect manner, while THCV is a high‐affinity CB1 receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 receptor antagonism.THCV has also high affinity for CB2 receptors and signals as a partial agonist, differing from both CBD and rimonabant. These cannabinoids illustrate how in vitro mechanistic studies do not always predict in vivo pharmacology and underlie the necessity of testing compounds in vivo before drawing any conclusion on their functional activity at a given target.

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Metadata

Authors
McPartland, J. M., Duncan, M., Di Marzo, V., & Pertwee, R. G.
Venue
British Journal of Pharmacology
Publisher
Wiley
Published
2015-01-08
Volume
172
Issue
3
Pages
737-753
ISSN
  • 0007-1188 (ISSN-L)
  • 1476-5381
DOI
10.1111/bph.12944
OpenAlex
W2101643484
Cited by
521
References
25
FWCI
5.78
Type
journal article
Language
en
Open access
bronze
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)

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