CBD Reduces Cocaine Use in Female Mice — But Dose Matters a Lot

In female mice, 10 mg/kg CBD attenuated cocaine self-administration acquisition by altering reward and cognitive markers in the mesocorticolimbic pathway. Conversely, 20 mg/kg increased cocaine consumption after punishment but reduced cocaine-seeking upon re-exposure to punishment cues and upregulated Htr1a (serotonin receptor) in the prefrontal cortex. Male mice showed no effects after punishment.

Female (and parallel male) mice received CBD at 10 or 20 mg/kg before intravenous cocaine self-administration testing. CBD's pharmacological profile was evaluated on anxiety-like and cognitive tasks. Effects on reward, cognitive, and serotonergic markers in the mesocorticolimbic pathway were assessed.

Cocaine use disorder has no approved medications, and women progress faster to addiction with worse outcomes. Finding that CBD modulates cocaine behavior in females specifically could open a sex-specific treatment approach.

The dramatic sex difference — CBD affecting cocaine behavior in females but not males — adds to growing evidence that addiction and its treatments work differently by sex. One-size-fits-all approaches to addiction treatment may be missing opportunities.

Mouse model with intravenous self-administration — different from human cocaine use patterns. Only two CBD doses tested. Sex differences observed in one paradigm (punishment) may not extend to others. Short-term study cannot address chronic treatment effects.