Our brains and bodies are incredible.  We have an entire system in place for utilizing a swath of naturally occuring endocannabinoids (eCBs).  It is no surprise that administration of a cannabinoid like cannabidiol, aka CBD, can help regulate brain function.  Research provides a number of findings about CBD’s anxiolytic potential.  More appealing, compare CBD to traditional, extremely habit forming and side-effect laden anxiety treatments, CBD treatment produces little to no side effects.  Notably, treatment can also be stopped without the potentially devastating withdrawal symptoms attributed to traditional anti-anxiety medications.  The homeopathic manner by which CBD treats the symptoms of anxiety is truly remarkable.

In the brain, CBD works to combat anxiety through a variety of pathways.  The most effective actions are the ones that take place at the: CB1r, 5-HT1a, and TRVP-1 receptors.  In this three part series, we explore in depth how CBD interaction with each receptor combats specific sources of anxiety.  Beginning with indirect activation of the CB1r receptor through FAAH inhibition.

Part 1: CB1R Receptors  – Learned Fear, Anxiety & PTSD

Indirect activation through FAAH inhibition

Our body’s endocannabinoid system serves many purposes, one of which is helping to regulate emotional behavior.   CBDs effectiveness is due to its ability to increase anandamide (AEA) levels which increase CB1r activity.  It does so by signaling for the inhibition of the FAAH enzyme which limits the anandamide levels the body needs to maintain homeostasis. High levels of FAAH mean low levels of AEA since FAAH works to control AEA production.  Surprisingly, unlike THC, CBD itself does not interact directly with the CB1r receptor, which is why there is no high with CBD treatment of any kind.  Instead, it allows for AEA to interact with the receptor on its behalf.

“The environment shapes people’s actions”

-B. F. Skinner-

Healthy mental and emotional balance includes maintaining a degree of “synaptic plasticity” – or the ability to continually learn at the synapse level from our emotional responses in both classical and fear conditioning situations.  Trauma can upset this natural plasticity which promotes fear in the brain.  This interrupts the normal requests for CB1r activation as the fear pathway now needs the brain’s resources.  PTSD sufferers show an excess of CB1r receptors desiring activation with notably low available AEA to do so.


High FAAH – High Anxiety

Interestingly enough, there is a genetic variation which links higher FAAH levels to poor fear response and slower trauma recovery.  Those with low FAAH levels, and therefore more AEA endocannabinoids, generally respond much better to fearful stimuli, navigate stress with level heads, and recover with expectant ease.  However, those with higher levels of FAAH clinically fare worse in the same traumatic situations. CBD allows individuals to be synaptically plastic so they can “go with the flow” better.  Thus, reducing stress and allowing for a cool, calm response like someone with naturally low FAAH levels.

With this new plasticity, CB1r activation sends a signal to the learned fear-stress network in the hippocampus and amygdala that we are not afraid any longer.  This delicate process towards rebalancing all starts with CBD decreasing FAAH.  This then increases AEA which then activates the CB1R receptor to tell the body, everything is ok.  Proven effective in clinical models, CBD for fear, anxiety and PTSD is a hopeful alternative for many suffering from anxieties crippling effects.  Furthermore, CBD administration lacks addictive qualities or side effects like pharmacological anxiolytics. Complex as one system is, indirect CB1r activation by FAAH inhibition is just one way that CBD works to combat anxiety.