Study identifies unexpected interplay between cannabis, cocaine exposure

It is often heard that an individual's initial response to a drug can have a large impact on whether they continue to use it or not. Hence, the new findings have suggested that early cannabis use makes young brains more sensitive to the first exposure to cocaine.

Reported in the Proceedings of the National Academy of Sciences, the study led by scientists at Columbia University and the University of Cagliari in Italy suggested that early use of cannabis may enhance the first experience with cocaine and lead to continued use among vulnerable individuals.

"We know from human epidemiological studies that individuals who abuse cocaine have a history of early cannabis use," said epidemiologist Denise Kandel, PhD, who is a professor of Sociomedical Sciences in Psychiatry at Columbia's Vagelos College of Physicians and Surgeons and co-senior author of today's paper.

"Our study in rats is the first to map the detailed molecular and epigenetic mechsms by which cocaine interacts with brains already exposed to cannabinoids, providing much-needed clarity to the biological mechsms that may increase the risk for drug abuse and addiction," added co-author and Nobel laureate Eric Kandel, MD, codirector of Columbia's Mortimer B. Zuckerman Mind Brain Behavior Institute and Senior Investigator of the Howard Hughes Medical Institute.

The research group examined the behavioral, molecular and epigenetic changes that occur when both adolescent and adult rats are first exposed to WIN, a synthetic cannabinoid with psychoactive properties similar to those of THC found in cannabis, and then are subsequently exposed to cocaine.

"We found that adolescent rats that had been pre-exposed to WIN had an enhanced reaction to their initial exposure to cocaine. Notably, we observed this effect in adolescent but not in adult rats," said Dr. Melas, who is now a junior researcher in the Department of Clinical Neuroscience at the Karolinska Institutet in Sweden.

Upon further examination, the team found that, when preceded by a history of psychoactive cannabinoid use in adolescence, exposure to cocaine sets off a battery of unique molecular reactions in the rat brain. These reactions included not only changes in the aforementioned glutamate receptors but also key epigenetic modifications. Epigenetic modifications are distinct, in that they affect the way genes are switched on or off but do not affect the sequence of the genes themselves.

The epigenetic effects of cannabinoids were found to be specific to adolescents and to target the brain's prefrontal cortex. The prefrontal cortex, which plays a role in various executive functions, including long-term planning and self-control, is one of the last regions of the brain to reach maturity, a fact that has long been linked to adolescents' propensity for risky behavior.

Moreover, aberrant prefrontal cortex activity is often observed in patients suffering from addiction. Efforts to enhance the function of the prefrontal cortex are currently being evaluated in the treatment of addiction through the use of brain stimulation and other methodologies.

"Our findings suggest that exposure to psychoactive cannabinoids during adolescence primes the mals' prefrontal cortex, so that it responds differently to cocaine compared to mals who had been given cocaine without having previously experienced cannabis," said Dr. Melas.

These results in rats offer important clues to the biological mechsms that may underlie the way that different classes of drugs can reinforce each other in humans.

( With inputs from ANI )

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