Cannabinoid Treatment for PTSD

PTSD is a psychiatric disorder of significant prevalence and morbidity. In the overall population, more than two thirds of individuals may experience a serious traumatic event at some point in their lifetime [1].

PTSD refers to the development of a cluster of characteristic symptoms that follow exposure to an extreme traumatic stressor and which appears to involve aberrant memory processing and impaired adaptation to changed environmental conditions. Sleep disturbance also occurs in up to 90% of cases. Patients with PTSD are also at risk for other psychological disorders, including but not limited to generalized anxiety disorder, major depressive disorder, and substance use disorder as well as physical problems including chronic pain, hypertension, and asthma.

Pre-clinical and human experimental studies suggest a role for certain cannabinoids in alleviating post-traumatic stress disorder (PTSD)-like symptoms [2]. However, while limited evidence from short-term clinical studies suggests a potential for oral THC and nabilone to decrease certain symptoms of PTSD, there are no long-term clinical studies for these preparations or any clinical studies of smoked/vapourized cannabis for PTSD [3].

Studies in humans have shown that individuals with PTSD have lower circulating endocannabinoid concentrations and an upregulation of brain CB1 receptors [4] - [5]. Limited evidence from observational studies suggests an association between herbal cannabis use and persistent/high levels of PTSD symptom severity over time.

There is limited evidence to suggest an association between PTSD and Cannabis Use Disorder. However, data from the National Comorbidity Study in USA (NCS) has also shown that adults suffering from PTSD were three times more likely to have a diagnosis of cannabis dependence compared to those without PTSD [6]. This may suggest a link with the self medication theory of addictions.

A double-blind, placebo-controlled, within-subject clinical study of 16 healthy volunteers looking at the effects of THC on amygdala reactivity to threat found that a 7.5 mg dose of dronabinol (vs. placebo) was associated with a significant reduction in amygdala reactivity to social signals of threat, but did not affect activity in primary visual and motor cortices. These findings are consistent with evidence suggesting that, at least at low doses, THC may have an anxiolytic effect in central mechanisms of fear behaviours [7].

References

[1] Trezza V, Campolongo P. The endocannabinoid system as a possible target to treat both the cognitive and emotional features of post-traumatic stress disorder (PTSD). Front Behav Neurosci 2013 Aug 9;7:100.

[2] Betthauser K, Pilz J, Vollmer LE. Use and effects of cannabinoids in military veterans with posttraumatic stress disorder. Am J Health Syst Pharm 2015 Aug 1;72(15):1279-84.

[3] Yarnell S. The use of medicinal marijuana for posttraumatic stress disorder: A review of the current literature. Prim Care Companion CNS Disord 2015 May 7;17(3):10.4088/PCC.15r01786. eCollection 2015.

[4] Hill MN, Patel S. Translational evidence for the involvement of the endocannabinoid system in stress-related psychiatric illnesses. Biol Mood Anxiety Disord 2013 Oct 22;3(1):19,5380-3-19.

[5] Hillard CJ. Stress regulates endocannabinoid-CB1 receptor signaling. Semin Immunol 2014 Oct;26(5):380-8.

[6] Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the national comorbidity survey. Arch Gen Psychiatry 1995 Dec;52(12):1048-60.

[7] Phan KL, Angstadt M, Golden J, Onyewuenyi I, Popovska A, de Wit H. Cannabinoid modulation of amygdala reactivity to social signals of threat in humans. J Neurosci 2008 Mar 5;28(10):2313-9.