How cannabis and cannabis-based drugs harm the brain

August 13, 2018

A new study led by Ana Sebastião, group leader at Instituto de Medicina Molecular João Lobo Antunes and Professor of Faculdade de Medicina of Universidade de Lisboa (iMM, FMUL; Portugal) and her team in collaboration with researchers from the University of Lancaster (UK), shows that the long-term use of either cannabis or cannabis-based drugs impairs memory. The study now published in the Journal of Neurochemistry* reveals the implications for both recreational users and people who use the drug to combat epilepsy, multiple sclerosis and chronic pain.

Through the legalisation in several countries of cannabis or cannabis-based drugs, there is an increased number of long-term users and more potent varieties are available for recreational users. It is already known that heavy, regular cannabis use increases the risk of developing mental health problems including psychosis and schizophrenia. However, there is still little understanding of the potential negative side effects of long-term cannabinoid exposure.

Now, the research group led by Ana Sebastião in collaboration with Neil Dawson and his team at Lancaster University studied the effects of a specific cannabinoid drug (named WIN 55,212-2) and found that mice exposed for long-term to the drug had "significant memory impairments" and could not even discriminate between a familiar and novel object. Also, brain imaging studies showed that the drug impairs function in key brain regions involved in learning and memory. Moreover, the long-term exposure to the drug impairs the ability of brain regions involved in learning and memory to communicate with each other, suggesting that this underlies the negative effects of the drug on memory.

"Importantly, our work clearly shows that prolonged cannabinoid intake, when not used for medical reasons, does have a negative impact in brain function and memory. It is important to understand that the same medicine may re-establish an equilibrium under certain diseased conditions, such as in epilepsy or multiple sclerosis, but could cause marked imbalances in healthy individuals. As for all medicines, cannabinoid-based therapies have not only beneficial disease-related actions, but also negative side effects", says Ana Sebastião. A previous study from the same team has showed that acute exposure to cannabinoids results in recognition memory deficits, an effect that can be prevented by the use of a drug of the family of caffeine. "These results are very important for the development of pharmacological strategies aiming to decrease cognitive side effects of currently used cannabinoid-based therapies, which proved effective against several nervous system disorders", explains Ana Sebastião.

"This work offers valuable new insight into the way in which long-term cannabinoid exposure negatively impacts on the brain. Understanding these mechanisms is central to understanding how long-term cannabinoid exposure increases the risk of developing mental health issues and memory problems; only its understanding will allow to mitigate them", says Neil Dawson.
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The research was conducted at iMM, Faculdade de Medicina of the Universidade de Lisboa and University of Lancaster as part of the SynaNET project funded by the Horizon 2020, European Commission .

*Mouro, F.M., Ribeiro, J.A., Sebastião, A.M., Dawson, N. (2018) Chronic, intermittent treatment with a cannabinoid receptor agonist impairs recognition memory and brain network functional connectivity. J Neurochem. [Epub ahead of print] doi: 10.1111/jnc.14549.

Instituto de Medicina Molecular

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