Study: CBD May Reduce Social Withdrawal and Cocaine Vulnerability Caused by Stress

Researchers from the University of Valencia, University of Zaragoza and University of Heidelberg used an intermittent social defeat (ISD) model, where adolescent male mice were exposed to aggressive encounters. ISD increased social avoidance, anxiety-like behavior, and made mice more likely to prefer a cocaine-associated environment in adulthood. It also altered the expression of genes linked to serotonin signaling, the endocannabinoid system, and the stress-regulating hypothalamus-pituitary-adrenal (HPA) axis. When CBD was administered before each stress episode, it prevented the social interaction deficits and the increased cocaine preference seen in stressed mice, though it did not reduce anxiety-like behavior. CBD also reversed most ISD-related changes in gene expression, including reductions in serotonin transporter (5-HTT), cannabinoid receptors (CB1R and CB2R), corticotropin-releasing factor (CRF), and proopiomelanocortin (POMC). However, effects varied by dose, and CBD did not reverse the stress-induced increase in glucocorticoid receptor expression.

The findings suggest CBD could help reduce social withdrawal and lower vulnerability to cocaine addiction following stress exposure, potentially through its effects on serotonin, endocannabinoid, and stress-response systems. While these preclinical results are promising, the authors note that human trials with people who have cocaine use disorder have so far shown limited benefits, highlighting the need for further research.