Cannabinoid exposure and cocaine response

A rodent study suggests that cannabinoid exposure during adolescence may alter the brain’s response to cocaine. The endocannabinoid system modulates reward and cognitive processes in the brain and plays a central role in neurodevelopment. Cannabis use among adolescents has been associated with increased risk of subsequent cocaine use and thought to alter the brain’s response to cocaine and other addictive substances. Eric Kandel, Denise Kandel, Philippe Melas, and colleagues examined epigenetic responses, gene expression, and other biochemical changes in the brains of rats that resulted from cocaine exposure, with and without prior exposure to a synthetic cannabinoid. Prior exposure to cannabinoids resulted in an enhanced response to cocaine’s stimulatory effects in adolescent rats, but not adult rats. The enhanced behavioral response was associated with increased histone acetylation and reduced levels of the enzyme histone deacetylase 6 in the brain’s prefrontal cortex. Cannabinoid exposure also led to alterations in cocaine-induced gene expression patterns, alternative splicing events in genes related to neurotransmitter receptor membrane localization, and enhanced effects of cocaine on protein phosphorylation. The results suggest that cannabinoid exposure during adolescence alters the initial behavioral, molecular, and epigenetic responses to cocaine, potentially enhancing susceptibility to addiction in vulnerable individuals, according to the authors.

Article #19-20866: “Cannabinoid exposure in rat adolescence reprograms the initial behavioral, molecular, and epigenetic response to cocaine,” by Maria Scherma et al.

MEDIA CONTACT: Philippe A. Melas, Karolinska Institutet, Stockholm, SWEDEN; tel: +46-708-884405; e-mail:

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