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Δ 8 ‐Tetrahydrocannabivarin has potent anti‐nicotine effects in several rodent models of nicotine dependence
Author(s) -
Xi ZhengXiong,
Muldoon Pretal,
Wang XiaoFei,
Bi GuoHua,
Damaj M. Imad,
Lichtman Aron H.,
Pertwee Roger G.,
Gardner Eliot L.
Publication year - 2019
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14844
Subject(s) - nicotine , conditioned place preference , pharmacology , nicotine withdrawal , addiction , self administration , agonist , alkaloid , cannabinoid receptor , antagonist , abstinence , psychology , medicine , receptor , chemistry , morphine , neuroscience , psychiatry , stereochemistry
Background and Purpose Both types of cannabinoid receptors—CB 1 and CB 2 —regulate brain functions relating to addictive drug‐induced reward and relapse. CB 1 receptor antagonists and CB 2 receptor agonists have anti‐addiction efficacy, in animal models, against a broad range of addictive drugs. Δ 9 ‐Tetrahydrocannabivarin (Δ 9 ‐THCV)—a cannabis constituent—acts as a CB 1 antagonist and a CB 2 agonist. Δ 8 ‐Tetrahydrocannabivarin (Δ 8 ‐THCV) is a Δ 9 ‐THCV analogue with similar combined CB 1 antagonist/CB 2 agonist properties. Experimental Approach We tested Δ 8 ‐THCV in seven different rodent models relevant to nicotine dependence—nicotine self‐administration, cue‐triggered nicotine‐seeking behaviour following forced abstinence, nicotine‐triggered reinstatement of nicotine‐seeking behaviour, acquisition of nicotine‐induced conditioned place preference, anxiety‐like behaviour induced by nicotine withdrawal, somatic withdrawal signs induced by nicotine withdrawal, and hyperalgesia induced by nicotine withdrawal. Key Results Δ 8 ‐THCV significantly attenuated intravenous nicotine self‐administration and both cue‐induced and nicotine‐induced relapse to nicotine‐seeking behaviour in rats. Δ 8 ‐THCV also significantly attenuated nicotine‐induced conditioned place preference and nicotine withdrawal in mice. Conclusions and Implications We conclude that Δ 8 ‐THCV may have therapeutic potential for the treatment of nicotine dependence. We also suggest that tetrahydrocannabivarins should be tested for possible anti‐addiction efficacy in a broader range of preclinical animal models, against other addictive drugs, and eventually in humans.