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Endocannabinoids May Defend the Body When It's Being Threatened

Changes in blood levels suggest that the body is preparing itself for trauma.

Key points

  • Plasma endocannabinoid levels increase in response to threats.
  • Increasing blood levels of endocannabinoids are a defensive response that contributes to a reduction in the experience of pain.
  • Endocannabinoids may also interfere with consolidation of memories associated with the threat experience.

Scientists are trying to determine the potential clinical benefits of medical marijuana. In the process, we are discovering how our endogenous cannabis neurotransmitters, the endocannabinoids, function. (My laboratory has studied the actions of cannabis on brain and body inflammation.) The endocannabinoid system includes two well-known transmitters (there are at least five others that are not well studied): AEA, also known as anandamide (found in chocolate), and 2-AG.

Recent evidence suggests that pharmacological manipulation of the endocannabinoid system may reduce anxiety and stress. Studies on humans and rodents suggest that enhancing the endocannabinoid system dampens our response to threat. The same approach has been considered for people suffering from exaggerated threat responses after traumatic experiences. To understand the nature of exaggerated threat response and to develop effective drug therapies, scientists need to know more about how the endogenous cannabis system in humans responds to threats. Do they help us to better remember the threat in order to avoid future events or do they help us to forget the trauma?

New Study on Plasma Endocannabinoids and Threats

A recent study investigated in humans whether plasma endocannabinoid levels are affected by the acquisition of threats. The study monitored plasma concentration of AEA and 2-AG before and after a threat experience in 44 men. This experience was combined with functional magnetic resonance imaging (fMRI) scanning of the brain.

The study found an increase in the blood level of AEA during the acquisition of the threat. The 2-AG levels changed in association with the individual’s expression of fear. Neural activity in the amygdala (a brain region responsible for processing and remembering fear responses) was associated with the increase in AEA concentration during acquisition of the threat. Neural activity in the hippocampus (a brain region critical for remembering the threat experience) and amygdala increased in association with increasing blood levels of AEA and 2-AG. Plasma levels of AEA started increasing as soon as the threat appeared.

Preparing for Attack and Forgetting Trauma

The authors speculated that the response of the endocannabinoid system is part of a normal physiological function to prepare the body for attack and potential injury. The enhancement of circulating AEA may also buffer strongly negative emotional responses and help the brain to forget traumatic experience associated with the threat. Treatment with cannabis might therefore be an effective way to reduce symptoms associated with posttraumatic stress disorder (PTSD). Overall, the increasing blood levels of endocannabinoids are a defensive response that contributes to a reduction in the experience of pain that might be a consequence of the threat.

Counterproductive Effects

Sometimes the effects of these endocannabinoids can be counterproductive. For example, one recent study in humans reported that higher 2-AG concentrations after a traumatic experience predicted greater symptoms of depression six months later. Taken together, these studies suggest that threat-induced changes in the release of endocannabinoids into the blood may have both short-term and long-term impacts on recovery from negative experiences and future behaviors.


Weisser, S., Mueller, M., Rauh, J. et al. (2022) Acquisition of threat responses are associated with elevated plasma concentration of endocannabinoids in male humans. Neuropsychopharmacol 47:1931–1938.

Wenk GL (2019) Your Brain on Food, 3rd Ed (Oxford University Press).