Research into the role of the endocannabinoid system in anxiety

How can soldiers and civilians experiencing PTSD best be treated, and can medicinal cannabis play a role in this? The Brain Research and Innovation Centre of the Military Mental Healthcare has been dealing with this question for some time and researcher Nadia Leen has obtained her PhD for several substudies. Nadia currently works for Bedrocan and will contribute to research into gender differences in the acute effects of the products Bedrocan® and Bediol®.

Studies have long shown that the endocannabinoid system, the mechanism in the human body that regulates stress, among other things, plays an important role in fear extinction. Childhood trauma can also permanently disrupt the endocannabinoid system. However, forty per cent of patients with anxiety-related disorders do not respond to standard treatments such as cognitive behavioural therapy. An alternative treatment could be medicinal cannabis. In this specific case, treatment with CBD, because it would have an acute anxiolytic effect and stimulate fear extinction. CBD (cannabidiol) is a component of the cannabis plant that affects the endocannabinoid system after ingestion. Anandamide is one of the body’s own cannabinoid that is broken down less quickly after CBD use. Anandamide controls all kinds of processes in the human body.


Anandamide has an anxiolytic effect and plays an important role in extinguishing fear. Nadia Leen: “In our study, we wanted to know whether the level of Anandamide in blood plasma was associated with treatment success in veterans with PTSD. We thought: the higher the level, the better they respond to treatment because increased Anandamide levels are related to better fear extinction. However, the blood samples showed that there was no difference between healthy people and veterans.” Was that a disappointment? Nadia: “Yes, it certainly was, because we thought that Anandamide levels would be lower in veterans and that they would therefore benefit from boosting these levels. In fact, it was the opposite. Some veterans actually had increased Anandamide levels, which was associated with anxiety symptoms.”

Research team - Nadia Leen
Nadia Leen


Post-traumatic stress disorder (PTSD) is a trauma and stressor-related disorder that has a disruptive impact on family life, work, and can lead to general social exclusion. Isolation and PTSD can result in self-destructive behaviour, such as excessive use of alcohol or drug abuse. PTSD occurs after a traumatic event. The patient experiences nightmares and lifelike memories (flashbacks). Treatment often consists of a combination of medication, such as antidepressants, and cognitive behavioural therapy.

There is limited clinical data to support the prescription of medicinal cannabis for PTSD. Medical cannabis (oil, or floss) can be tried as a complementary therapy, in low doses (microdosing) and in combination with physical and psychological therapies.

Endocannabinoid system

“It seems, but that is purely hypothetical, that the endocannabinoid system will adapt to the long-term high levels of Anandamide after a while” Nadia continues, “which means that if the stress level is too high, the system becomes overactive and can no longer regulate the levels properly. We actually still have a lot to learn about the precise mechanism of action of the endocannabinoid system.”

Follow-up research has now started and Nadia is hopeful: “The endocannabinoid system is a promising candidate in understanding and treating anxiety, stress and trauma. I am therefore pleased that the Brain Research and Innovation Centre is continuing clinical research into the effects of CBD (cannabidiol) in veterans with an anxiety disorder and/or PTSD. Hopefully, it will contribute to reducing the burden that military personnel and veterans in particular experience in their daily lives due to PTSD.” The follow-up research is being conducted by PhD candidate Remco van Zijderveld.

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