How Chronic Stress Affects Your Endocannabinoid System


Chronic stress can physically change your brain, disrupt your natural cannabinoid system and cause long-term anxiety, depression & PTSD symptoms.

For decades, researching cannabinoids was shunned as unprofitable “hippie science.” But now, the stigma around cannabis is lifting and mainstream neuroscientists are focused on studying the human endocannabinoid system.

Our body makes two natural cananbinoids:  anadamide and 2-AG. These “endocannabinoids” powerfully affect our mood, sleep, relaxation, memory and perception by interacting with CB1 & CB2 receptors in the brain & immune system.

The cannabinoid system can also be stimulated by ingesting plant-based “phytocannabinoids” like THC & CBD.

Here’s my interpretation of recent scientific studies:

Stress & Anxiety

Endocannabinoids regulate GABA & glutamate transmission [R, R].  GABA promotes relaxation & too much glutamate causes anxiety.

Severe stress releases endocannabinoids in the amygdala [R].

Stress hormones cause the rapid breakdown of anandamide in the amygdala to promote anxiety [R].

Blocking the breakdown of anadamide reverses the stress-induced anxiety state [R].

CBD moderately blocks the breakdown of anadamide in humans. CBD treatment caused a significant increase in serum anandamide levels [R].

Chronic stress causes a downregulation or loss of CB1 receptors in almost every part of the brain and lower anadamide levels, which increases stress response & anxiety [R].

The downshift in endocannabinoid-CB1 signaling and may be responsible for the negative effects of stress [R].

Mild chronic stress changes endocannabinoid-controlled nerve signaling and function in the hipocampus [R].

CBD may modulate endocannabinoids and interacting neurotransmitter systems to alleviate anxiety [R].



Chronic stress can downregulate the endocananbinoid system in the reward center of the brain leading to depression-like behaviors [R].

Stress can cause brain inflammation, leading to depression. Stimulating the CB2 receptors prevented the stress-induced increase in inflammatory cytokines [R].

The decreased CB1 signaling in animals with depression is reversed with Prozac [R].

Anandamide boosters & CB1 receptor stimulants have similar effects as antidepressants [R].

Suicide victims with mood disorders were more likely to have abnormal CB1 function [R].

Abused children with abnormal CB1 genes were more likely to suffer depression as adults [R].

The CB2 cannabinoid receptor (CB2R) gene is associated with depression & chronic stress increases the risk [R].

Chronic THC use may downregulate CB1 receptors and cause depression [R].


Cannabinoids make the sleep cycle less sensitive to changes in light. Endocannabinoids may modulate the circadian rhythm. [R]

Fear, “Bad” Memories & PTSD

The endocannabinoid system controls the “letting go” of bad memories [R].

Decreasing CB1 receptor activity can block fear extinction [R].

Blocking the enzyme that breaks down endocananbinoids facilitates long-term fear extinction [R].

Blocking the breakdown of anadamide causes more CB1 receptor activation in the dorsal hippocampus, inhibiting the formation of fearful memories [R].

When subjected to stress, CBD-treated animals had increased generalized fear, inhibited memory extinction and increased fear memory. This suggests caution when using CBD for anxiety treatment [R].

CBD disrupts the consolidation of fear memories [R].

CBD can alter important aspects of negative memories and promote significant improvements in PTSD symptoms [R].


3 thoughts on “How Chronic Stress Affects Your Endocannabinoid System”

  1. What you basically say is that the damage is permanent, which is very interesting and fearful.

    Have you researched into oxygen chamber treatments?
    Have you researched or tried MDMA assisted therapy for trauma and chronic stress?
    Are you practicing mindfulness and in particular body scan?

    1. Studies I’ve read suggest that certain changes in the CB receptors can heal & normalize after time. But I know of people who experienced chronic stress & seemed to experience PTSD-like effects in the limbic brain & cannabinoid systems (e.g., hypervigilance, ahedonia) persisted for YEARS afterwards… the stressor was removed but the symptoms did not resolve with basic supplements, therapy / self-help, rest and relaxation type interventions.

      My friend tried hyperbaric oxygen but didn’t report any breakthrough effects. I have researched MDMA but prefer natural supplements to stronger chemical drugs.’

      My intuition is that the cannabinoid-replacement (like CBD) and/or cannabis-assisted therapy might be the most effective route to healing certain types of trauma.

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