Δ8-Tetrahydrocannabivarin has potent anti-nicotine effects in several rodent models of nicotine dependence

Abstract

Background and Purpose: Both types of cannabinoid receptors—CB1 and CB2—regulate brain functions relating to addictive drug-induced reward and relapse. CB1 receptor antagonists and CB2 receptor agonists have anti-addiction efficacy, in animal models, against a broad range of addictive drugs. Δ9-Tetrahydrocannabivarin (Δ9-THCV)—a cannabis constituent—acts as a CB1 antagonist and a CB2 agonist. Δ8-Tetrahydrocannabivarin (Δ8-THCV) is a Δ9-THCV analogue with similar combined CB1 antagonist/CB2 agonist properties. Experimental Approach: We tested Δ8-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: Δ8-THCV significantly attenuated intravenous nicotine self-administration and both cue-induced and nicotine-induced relapse to nicotine-seeking behaviour in rats. Δ8-THCV also significantly attenuated nicotine-induced conditioned place preference and nicotine withdrawal in mice. Conclusions and Implications: We conclude that Δ8-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.