The endocannabinoid system (ECS) intersects profoundly with addiction. Cannabinoid receptors—both type 1 (CB1) and type 2 (CB2)—help regulate the body’s dopamine reward system. This translates to effects on drug reward, abstinence, and relapse. Specifically, CB1 antagonists (receptor blockers) and CB2 agonists (receptor activators) may help curb addiction. With this in mind, scientists [1] recently investigated the power of Δ8‐tetrahydrocannabinivarin (Δ8-THCV) to help kick nicotine dependence to the curb.
Δ8‐Tetrahydrocannabinivarin (Δ8-THCV) is the more stable synthetic analogue of Δ9-THCV, often referred to as THCV. Like its natural counterpart, Δ8-THCV is a CB1 antagonist and a CB2 agonist. This makes it an ideal minor cannabinoid to target addiction pathways.
Although THCV is non-intoxicating and safe, and many humans are addicted to nicotine, the researchers turned to animal models for the study. They found that “Δ8‐THCV may have therapeutic potential for the treatment of nicotine dependence.”
After getting rats addicted to nicotine, the researchers measured how Δ8-THCV affects:
- Nicotine self-administration
- Nicotine seeking
- Behavior after forced abstinence
- Conditioned place preference (preference for the environment where nicotine was administered)
- Somatic withdrawal signs
- Hyperalgesia (sensitivity to pain) from withdrawal
The findings were generally positive across domains and often significant. Self-administration of nicotine decreased significantly at 10 mg Δ8-THCV/kg body weight but not at 3 mg/kg. After a 14-day “drug holiday,” 20 mg/kg was able to reduce nicotine seeking (a marker of relapse) by 90%. Higher doses were sometimes more effective (i.e., dose-dependent responses); 20 mg/kg was more effective than 10 mg/kg at reducing nicotine seeking in response to a cue (in this case, lights and a tone).
That said, 0.3 mg/kg “significantly ameliorated” anxiety-like behavior from nicotine withdrawal. The same relatively small dose “robustly ameliorated” somatic withdrawal symptoms (e.g., tremors, head shakes, jumps, curls, etc.). It also inhibited conditioned place preference and reversed the hyperalgesia associated with nicotine withdrawal.
How these results translate to humans is unclear (which is among the key arguments against animal testing). Ultimately, the researchers conclude, “THCVs may constitute a safe and [non-intoxicating] class of potential anti‐addiction, anti‐craving, and anti-relapse pharmacotherapies.” [1]
Reference:
1- Xi ZX, Muldoon P, Wang XF, et al. Δ8-Tetrahydrocannabivarin has potent anti-nicotine effects in several rodent models of nicotine dependence. Br J Pharmacol. 2019;176(24):4773-4784. doi:10.1111/bph.14844. [Impact Factor: 8.739; Times Cited: 2 (Semantic Scholar)]
