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 CB2agonist. 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 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.

 

Texto original: https://www.ncbi.nlm.nih.gov/pubmed/31454413/