Chocolate, Cannabis, and Borderline Personality Disorder

The consequence of too little cannabis-like molecules in the brain.

Posted Sep 18, 2020

This story begins, as all good stories should, with a discussion of chocolate and your brain.

The cocoa plant and your brain both make a chemical called anandamide. Scientists have not yet discovered why. Does anandamide contribute to the pleasure of eating chocolate? Similarly, scientists know very little about the function of anandamide in the brain. It is one of the two most common cannabis-like molecules in your brain (there at least five others whose function remains a complete mystery).

THC from the cannabis plant acts analogous to anandamide in the human brain; they both bind to the same cannabinoid (or CB) receptors that are densely scattered throughout the brain. Anyone who has ingested or inhaled THC will not be surprised to learn that one of the major functions of anandamide is to control mood by acting within a brain region called the amygdala. Animal studies, and a few small studies using human subjects, have demonstrated that the amygdala is very active when we are angry or aggressive. Scientists have hypothesized that anandamide, acting within the amygdala, may normally be responsible for reducing feelings of anger and aggression. Smoking the marijuana plant simply enhances the normal function of anandamide to reduce feelings of anger and anxiety

A recent study (see below) investigated this hypothesis by examining whether people diagnosed with Borderline Personality Disorder (BPD), who are angry and aggressive much of the time, have lower levels of anandamide in their brain. BPD is a rather common mental condition that afflicts 10 percent of psychiatric outpatients and 20 percent of psychiatric inpatients. BPD presents with hostility and anger often leading to physical aggression. Forty percent of BPD patients take three or more psychotropic medications concurrently; some take much more. There are currently no FDA-approved medications for the treatment of BPD.

Patients with BPD may have abnormal activity within their amygdala. Activity within the amygdala is partially controlled by the prefrontal cortex. You might remember the Vulcans from the old "Star Trek" TV show. Vulcans had near-complete control over their aggression possibly because their prefrontal cortex was highly evolved. Several imaging studies of the brains of patients with BPD have discovered that the neural link between the prefrontal cortex and the amygdala does not function correctly. The consequence is that the signals from their prefrontal cortex are not sufficient to dampen down the amygdala-induced aggressive emotions. Vulcans probably did not suffer from BPD.

The cause of the failed signaling from the prefrontal cortex may be due to a failure of the brain to control the level of anandamide. The problem is that the level of anandamide is too low and, as a consequence, activity in the amygdala is too high. Why are the levels so low and why does this happen in the brains of people with BPD?

The answer to this question requires consideration of a gene mutation on chromosome number 1. The gene codes for the production of an enzyme called FAAH. FAAH metabolizes anandamide. The mutation is quite simple; it involves a transversion of a single cytosine to an adenine. The consequence is not so simple; patients with BPD have too much FAAH in their brain leading to very low levels of anandamide floating around in their brain. The low level of anandamide has a significant psychiatric consequence. The level of FAAH in both the prefrontal cortex and the amygdala of BPD patients correlated with the level of their hostility.

Thus, a chemical found in chocolate that is also made by our brain may get metabolized too quickly due to a simple gene mutation, leading to anger and aggression. It is a nice story but I should caution that it is still too soon to claim that we now understand how the brain’s endogenous marijuana system functions in BPD or any other psychiatric disorder. 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, such as Borderline Personality Disorder.

References

Kolla N.J. et al (2020) Elevated fatty acid amide hydrolase in the prefrontal cortex of borderline personality disorder: a [11-C]CURB positron emission tomography study. Neuropsychopharmacology, 45:1834–1841; https://doi.org/10.1038/s41386-020-0731-y