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• Smoking cannabis boosts brains' sensitivity to cocaine, US researchers report
• Young rats exposed to cannabis had 'enhanced reaction' to cocaine exposure
• In young humans cannabis abuse can enhance experiences with a different drug 

Cannabis is a gateway drug that gives users a heightened sensitivity to harder illegal substances like cocaine, a new study suggests.

US researchers found adolescent rats that had been pre-exposed to cannabis had an enhanced reaction to their first exposure to cocaine.

Exposure to psychoactive cannabinoids during adolescence was found to 'prime' the animal's prefrontal cortex in the brain.  

If applied to humans, the study suggests smoking a lot of weed as a teenager makes people more sensitive to cocaine and can lead to continued use and addiction. 

Cannabis abuse during adolescence can enhance a person's initial positive experience with a different drug, such as cocaine, leading to sustained use.

Cannabinoid exposure in rat adolescence reprograms the initial behavioral, molecular, and epigenetic response to cocaine

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The Science – Significance - The endocannabinoid system has a modulatory role in brain reward and cognitive processes. It has been hypothesized that repeated interference with endocannabinoid signaling (e.g., through abuse of cannabis or synthetic cannabinoids) can remodel the adolescent brain and make it respond differently to more addictive substances, such as cocaine. In the present study, we demonstrate that a history of synthetic cannabinoid exposure in adolescent animals results in distinct molecular and epigenetic changes following initial exposure to cocaine. These changes were pronounced in the prefrontal cortex and associated with an enhanced response to cocaine’s stimulatory effects. The prefrontal cortex is a brain region that still undergoes maturation in adolescence and its dysfunction contributes to the development of addictions.

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Abstract 

Cannabis is the third most used psychoactive substance worldwide. The legal status of cannabis is changing in many Western countries, while we have very limited knowledge of the public health impact of cannabis-related harms. There is a need for a summary of the evidence of harms and risks attributed to cannabis use, in order to inform the definition of cannabis risky use. We have conducted a systematic review of systematic reviews, aiming to define cannabis- related harms. We included systematic reviews published until July 2018 from six different databases and following the PRISMA guidelines. To assess study quality we applied the AMSTAR 2 tool. A total of 44 systematic reviews, including 1,053 different studies, were eligible for inclusion. 

Harm was categorized in three dimensions: mental health, somatic harm and physical injury (including mortality). 

Evidence shows a clear association between cannabis use and psychosis, affective disorders, anxiety, sleep disorders, cognitive failures, respiratory adverse events, cancer, cardiovascular outcomes, and gastrointestinal disorders. 

Moreover, cannabis use is a risk factor for motor vehicle collision, suicidal behavior and partner and child violence. Cannabis use is a risk factor for several medical conditions and negative social consequences. There is still little data on the dose-dependency of these effects; evidence that is essential in order to define, from a public health perspective, what can be considered risky use of cannabis. 

This definition should be based on quantitative and qualitative criteria that informs and permits the evaluation of current approaches to a regulated cannabis market.

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Soaring rates of vaping among young people and associated problems have resulted in great urgency and important challenges for policymakers. Despite the urgency, policies should be evidence-based and thoughtfully designed. They require effective, collaborative, and well-funded enforcement by federal and state governments. Policymakers should aim to reduce vaping among young people while maintaining avenues to help smokers quit. Finally, policies should be forward-thinking, since the e-cigarette market is rapidly changing and e-cigarette companies can be more agile than regulators.

Published March 25, 2020, at NEJM.org. DOI:  10.1056/NEJMp1917065   

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