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What Happens When Your Brain’s Marijuana System Fails?

The psychiatric consequences of making too much or too little endocannabinoid.

If you are reading this blog you are likely aware that your brain possesses its own family of marijuana-like molecules. Science has not yet determined the role of these molecules in normal brain function. They clearly influence feeding behaviors and mood. One way to determine what else this endogenous marijuana system is doing is to investigate what happens when it appears to fail. Clinical studies have reported that your endogenous cannabis system has an important role in the function of a brain region called the basal ganglia. The basal ganglia region has many diverse functions that are often related to movement.

A recent study found that patients with Tourette syndrome showed a significant elevation in the concentration of the two most prevalent endogenous cannabinoids and their principle metabolites. Tourette syndrome is a neurodevelopmental disorder characterized by motor and vocal tics as well as psychological comorbidities such as attention-deficit/hyperactivity, obsessive-compulsive disorder, depression and anxiety. All of these symptoms have been linked, at least partially, to dysfunction of dopamine within the basal ganglia. The authors of this study concluded that these psychiatric conditions might also be due to an imbalance in the level of endogenous cannabinoid neurotransmitters. For example, they discovered that increased levels of one endogenous cannabinoid, called 2-AG, correlated significantly with the severity of the attention-deficit/hyperactivity.

These findings support the idea that dopamine function within the basal ganglia is directly controlled by the endogenous cannabinoid system. Why might this idea be true? In the past, drugs that target dopamine function have been used to control motor and vocal tics associated with Tourette syndrome, attention-deficit disorder, obsessive-compulsive disorder, depression and anxiety.

In contrast to patients with Tourette syndrome, people who suffer with either migraines or posttraumatic stress disorder may have too little activity in their brain’s endogenous marijuana system. This may explain why smoking marijuana is claimed to reduce headache pain severity by almost half. These patients may be simply providing their nervous system with a necessary level of cannabinoids.

It is too soon to claim that we now understand how the brain’s endogenous marijuana system functions in these disorders. There are numerous alternative explanations for the changes in cannabinoid neurotransmitters that have been observed. However, as more information accumulates it might one day be possible to design effective marijuana-like drugs for a variety of human disorders of the brain.

© Gary L. Wenk, Ph.D. is a Distinguished Professor of Neuroscience & Molecular Virology, Immunology and Medical Genetics at the Ohio State University and Medical Center and author of Your Brain on Food, 3rd Edition, 2019 and The Brain: What Everyone Needs to Know, 2017 (Oxford University Press)


Kirsten R. Müller-Vahl et al (2020) Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette syndrome. Neuropsychopharmacology (2020) 45:1323–1329;