When you’re under stress, your brain’s amygdala (a key emotional brain center) may release cannabinoid molecules*, activating the same brain receptors that THC** does, Northwestern Medicine researchers have discovered.

These endogenous (body’s own) feel-good cannabinoid molecules dampen incoming stress alarms from the hippocampus, a memory and emotion center in the brain, the researchers report in a study with mice, published Sept. 12 in the journal Cell Reports. 

Overcoming stress disorders: new drug development

Stress heightens risk for many psychiatric disorders. This new finding opens a new avenue for drug development to treat psychiatric disorders from conditions like generalized anxiety, major depression and post-traumatic stress disorder (PTSD), the researchers suggest.

“Understanding how the brain adapts to stress at the molecular, cellular and circuit level could provide critical insight into how stress is translated into mood disorders and may reveal novel therapeutic targets for the treatment of stress-related disorders,” said study author Dr. Sachi Patel, chair of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and a Northwestern Medicine psychiatrist.

“The endocannabinoid system is one of the leading signaling systems that has been identified as a prominent drug-development candidate for stress-related psychiatric disorders, Patel said.

Removing cannabinoid receptor decreases pleasure and ability to cope

When these scientists removed the target of these cannabinoids, the cannabinoid receptor type 1, it resulted in poorer ability to cope with stress and motivational deficits in the mice. Specifically, when the receptor target of these endogenous cannabinoids was removed at hippocampal-amygdala synapses, mice adopted more passive and immobile responses to stress and had a lower preference to drink a sweetened sucrose water after stress exposure.

This finding may relate to anhedonia (decrease in pleasure), often experienced by patients with stress-related disorders such as depression and PTSD.

“Determining whether increasing the levels of endogenous cannabinoids can be used as potential therapeutics for stress-related disorders is a next logical step from this study and our previous work,” said Patel. “Also, there are ongoing clinical trials in this area that may be able to answer this question in the near future.” 

* Cannabinoids are a class of biological compounds that bind to cannabinoid receptors. They are most frequently sourced from and associated with the plants of the Cannabis genus, including Cannabis sativa, Cannabis indica, and Cannabis ruderalis.

** THC (tetrahydrocannabinol) is the substance that’s primarily responsible for the effects of marijuana on a person’s mental state.

Citation: Kondev, V., Najeed, M., Yasmin, F., Morgan, A., Loomba, N., Johnson, K., … & Patel, S. Sept.12, 2023. Endocannabinoid Release at Ventral Hippocampal-Amygdala Synapses Regulates Stress-Induced Behavioral Adaptation. Cell Reports. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=433

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