THCV Increased Brain Responses to Both Rewarding and Unpleasant Food Stimuli

Within-subject, double-blind, placebo-controlled design with 20 healthy volunteers. Each participant received 10mg THCV and placebo on separate occasions in randomized order. fMRI measured neural responses to rewarding stimuli (sight/flavor of chocolate) and aversive stimuli (picture of moldy strawberries/unpleasant strawberry taste).

Rimonabant, the first CB1 antagonist for obesity, was withdrawn due to psychiatric side effects including depression and suicidality. THCV is a neutral CB1 antagonist (not an inverse agonist like rimonabant) and shows a different neural profile that might reduce appetite without causing depression, offering a potentially safer approach to cannabinoid-based obesity treatment.

The distinction between neutral antagonists and inverse agonists at CB1 receptors has important clinical implications. This is the first human study demonstrating that THCV, a natural cannabis compound, modulates food reward and aversion neurocircuitry differently from rimonabant, supporting its potential as a safer anti-obesity agent.

Only a single dose was tested in 20 healthy volunteers. The study measured neural responses, not actual eating behavior or weight loss. Long-term effects are unknown. The lack of subjective rating differences, despite brain activation changes, raises questions about the functional significance of the findings.