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. Δ9‐Tetrahydrocannabivarin (Δ9‐THCV)—a cannabis constituent—acts as a CB 1 antagonist and a CB 2 agonist. Δ8‐Tetrahydrocannabivarin (Δ8‐THCV) is a Δ9‐THCV analogue with similar combined CB 1 antagonist/CB 2 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.