CBD Prevented Social Avoidance and Increased Cocaine Vulnerability Caused by Repeated Social Stress in Mice

CBD (30 or 60 mg/kg) given during intermittent social defeat prevented social interaction deficits and the potentiation of cocaine conditioned place preference that normally follows stress exposure. CBD did not prevent anxiety-like effects. Gene expression analysis revealed that social defeat reduced expression of serotonin transporter, CRF, POMC, and cannabinoid receptors, and CBD reversed these reductions.

Male mice received CBD (30 or 60 mg/kg) and were exposed to four episodes of social defeat on postnatal days 47-56. Behavioral tests assessed social interaction, anxiety, and cocaine reward. Gene expression of serotonin transporter (dorsal raphe), CRF (paraventricular nucleus), POMC (arcuate nucleus), and glucocorticoid/cannabinoid receptors (hippocampus) was measured after the last defeat episode.

Social stress is a major risk factor for both mood disorders and substance use disorders in humans. This study shows that CBD given during the stress exposure period can prevent two key consequences: social withdrawal (relevant to depression/PTSD) and increased vulnerability to addictive drugs, while identifying the brain systems involved.

The co-occurrence of PTSD/depression and substance use disorders is one of the biggest challenges in mental health treatment. If CBD can prevent both the mood and addiction-vulnerability consequences of social stress, it could represent a fundamentally new approach to treating or preventing these commonly co-occurring conditions.

Male mice only; female responses may differ. Social defeat in mice is an approximation of human social stress. CBD doses were relatively high and may not translate directly to human dosing. Only cocaine reward was tested; other drugs may respond differently.