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

BACKGROUND AND PURPOSE:

Both types of cannabinoid receptors – CB₁ and CB₂ – regulate brain functions relating to addictive drug-induced reward and relapse. CB₁receptor 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 CB₁antagonist/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 behavior following forced abstinence, nicotine-triggered reinstatement of nicotine-seeking behavior, acquisition of nicotine-induced conditioned place preference, anxiety-like behavior 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 behavior 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.

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