Why THC Causes Anxiety in Veterans With PTSD

A study funded by the Dutch Ministry of Defense analyzed endocannabinoid levels in veterans with post-traumatic stress disorder. ECS tone was neutral in participants and THC conversely contributed to anxiety, a symptom of PTSD, in resting veterans. However, only relaxed participants were tested in the study. No veteran was under stress during the study. And since the endocannabinoid system that responds to THC works on demand, the method, according to the study, serves as a dramatic limitation.

Endocannabinoid levels increase in women after exercise. However, the surge is short-lived as the ECS quickly returns to normal. Long-term changes in the ECS do not occur in patients with PTSD. In the short term, the system could still shift as needed after loads, which has not been tested in recent Dutch research.

ECS and physical trauma

In a previous observational study, veterans with traumatic brain injury were much more likely to seek cannabis than those without physical trauma to the brain. The study, conducted by the Marcus Brain Institute, found no benefit from major cannabinoids. But the study of veterans with TBI, published earlier this year, left out the endocannabinoid system. dr Brandon Utter, who led the study with a PharmD, agreed with this author. The omission of the mere mention of endocannabinoids limited their observational study of cannabis search among veterans with TBI.

Inflammation, but also certain genetic predispositions, can lead to a form of deprivation known as clinical endocannabinoid deficiency. And while there are various causes and contributors that lead to ECS withdrawal. The theory was originally based on endocannabinoid levels found in the spinal fluid of migraine sufferers. However, to obtain this fluid, a clinician must puncture the patient’s spine. Of course, like any medical professional, a MD would hesitate before employing such an invasive strategy.

Non-invasive human endocannabinoid collection

Scientists from the latest Dutch study collected blood samples. More specifically, plasma was used to analyze endocannabinoid levels in 54 veterans with PTSD. Endocannabinoids were not disturbed in the patients. In fact, according to the study, increases in the endocannabinoid known as 2-AG made anxiety worse.

Unique biases and functions exist between each of the internal (endo) and external (exo) cannabinoids. That being said, 2-AG and THC both torment CB receptors. To better manage anxiety symptoms compared to THC alone, moderating the ECS with cannabinoids like CBG could benefit veterans with PTSD. But again, the veterans were not tested under duress, and minor cannabinoids were omitted from the study.

Turning fear on and off

Many targets of THC and ECS increase or decrease anxiety, depending on the target, environment, and person. Two main targets for modulating anxiety are the neurotransmitters GABA and glutamate.

The overall effect of THC and 2-AG on these neurotransmitters depends on unique phases in the CB1 receptor. Biphasic potential can result in endocannabinoids and phytocannabinoids having unique effects on anxiety, despite both substances targeting the same receptor.

Another important target for anxiety is acetylcholine (ACH), which can increase concentration. THC reduces focus by inhibiting ACH, which can reduce anxiety. When it comes to ACH and ECS, however, the idea applies more.

Block the leak before adding more to the synapse

Inflammation following physical trauma to the head leads to rapid breakdown of endocannabinoids. Enzymes that help break down endocannabinoids can be blocked to provide relief. But adding more 2-AG is not beneficial when enzymes are actively chewing up any endocannabinoids that are being introduced into the synapse. It’s like trying to fill a leaky bucket by increasing the water flow without doing anything to fix the actual leak.

An inhibitor of 2-AG degradation increases ACH receptors (M2 and M4). However, this effect was not reproduced by a cannabinoid receptor agonist. And CBD probably won’t be able to increase the receptor either. And M4 knockout has been shown to cause fear. This means that THC and 2-AG can contribute to anxiety by turning down an acetylcholine. CBG, on the other hand, balances the effects on ACH by protecting 2-AG through MAG-1 enzyme inhibition.

Let us know your thoughts on the benefits or issues of using THC to treat PTSD in the comments. Do you think medicinal cannabis with or without THC has a future in PTSD therapy for veterans if the right chemovar, full-spectrum hash, or smaller cannabinoids can be offered?

Sources

1. Leen NA, de Weijer AD, van Rooij SJH, Kennis M, Baas JMP, Geuze E. The role of the endocannabinoids 2-AG and anandamide in clinical symptoms and treatment outcomes in veterans with PTSD. Chronic Stress (Thousand Oaks). 2022;6:24705470221107290. Published June 9, 2022. doi:10.1177/24705470221107290
2. Brandon Utter, PharmD, C. Alan Anderson, MD, Christopher M. Filley, MD, James P. Kelly, MD, Catharine Johnston-Brooks, PhD, David B. Arciniegas, MD, Cannabis Use in a Cohort of US Military Veterans Who Seek Health Care With Persistent Symptoms After Mild Traumatic Brain Injury: Preliminary Observations, Military Medicine, 2022;, usac011