Cannabis for PTSD
Post-traumatic stress disorder (PTSD) takes a significant toll on the physical, mental, and emotional health of patients and remains difficult to treat, with 1 out of 3 people who develop PTSD never recovering.  An estimated 8.2% of people in the United States have PTSD, with incidence higher in “at risk” populations such as veterans, the underprivileged, and women. [1, 2]
Treatments for PTSD thus far have been “opportunistic,” meaning that PTSD is currently treated with drugs developed for other conditions that have been observed to have benefit for PTSD as well.  As a result, patients are often prescribed a combination of medications to address symptoms that can include SSRIs, MAOIs, tricyclic antidepressants, antiadrenergic agents, anticonvulsants, sedatives, and/or antipsychotics.  These conventional treatments are often met with limited efficacy and considerable adverse effects.
The endocannabinoid system (ECS) and phytocannabinoids (e.g. THC and CBD) present a promising avenue for the treatment of PTSD. Rather than targeting neurotransmitter systems and their agonists, cannabinoids target the underlying neurobiological processes that lead to imbalances in these neurotransmitter systems, helping to return them to a state of homeostasis.  As we learn more about PTSD, the ECS, and cannabinoid medicine, we may discover that there is actually evidence underlying the common practice of self-medication with cannabis seen in the PTSD population. 
“It has been suggested that pharmacologic treatments in psychiatry have been overly reliant on neurotransmitter systems and their agonists. In the last several decades, advances in psychopharmacology have reduced adverse reactions but have failed to lead to major disease improvement. The endocannabinoid system may shed new light on the physiologic basis of psychiatric diseases, leading to new and more effective treatments.” 
-Raphael Mechoulam, Pioneer in Endocannabinoid Research
PTSD and the Brain: Symptoms and Mechanisms
PTSD involves an imbalance in the brain’s chemicals along with disruptions of normal neuroanatomy. The lack of homeostasis creates a dysregulation of immune, autonomic, hormonal, and cardiovascular functions.  PTSD can also be considered a memory disorder, with overactive, vivid recall combined with the inability to integrate or forget traumatic memories. The endocannabinoid system is intimately involved with not only the ability to forget painful, damaging memories, but with fear conditioning as well.
CB1 receptors are distributed throughout the brain, and appear in abundance through the areas of the brain implicated in fear, memory, and PTSD. These areas include the amygdala, hippocampus, hypothalamic-pituitary-adrenal axis (HPA), and prefrontal cortex. [2, 3] Studies have shown that the brains of individuals with PTSD have 20% more CB1 receptor availability as well as lower levels of anandamide. This imbalance may be part of the root mechanism of PTSD. 
Cannabinoids as a Treatment for PTSD
In general, the endocannabinoid system maintains homeostasis in the brain, and PTSD appears to be related to an imbalance in the ECS. While there is still much to learn about treating PTSD with cannabinoids, evidence exists showing that cannabinoids can be effective at relieving the symptoms of PTSD.
Memory Extinction: A commonly cited adverse effect of cannabis is impaired memory, however in PTSD this may be a desired outcome. During the process of forgetting, endocannabinoid levels and CB1 activation are elevated. Blockage of CB1 receptors have been shown to cause difficulty in forgetting aversive memories and hypersensitivity to stress.  If there is a deficit of endocannabinoids (as there is in PTSD), introducing phytocannabinoids may be helpful to re-activate CB1 receptors, aiding in the process of forgetting.
Anxiolytic (Anti-Anxiety): THC has been shown to have a significant effect on amygdala reactivity to threatening stimuli.  A functional MRI neuro-imaging study showed that THC reduced amygdala reactivity to threatening stimuli and had an effect similar to lorazepam.  Regular doses of THC also appear to induce hippocampal growth and development as well as the maintenance of homeostasis in the HPA, contributing to anxiolytic and antidepressant effects. [2, 5]
Antidepressant: THC, CBD, and CBC have been shown to exert antidepressant effects. Stimulation of cannabinoid receptors enhances stress-coping mechanisms and increases serotonin activity. 
Improved Sleep: Nabilone, a synthetic version of THC, has been shown to reduce treatment-resistant nightmares in PTSD patients. 72% of patients who received nabilone experienced either cessation of nightmares or a significant reduction in nightmare intensity. 
THC can have unwanted psychoactive effects for some patients, but if CBD is present those side effects may not be as troubling. Cannabis strains or preparations containing CBD in addition to THC may prevent undesired psychoactive effects sometimes caused by THC-rich cannabis medicines that lack CBD. CBD also improves endocannabinoid tone by inhibiting the FAAH enzyme that breaks down the helpful endocannabinoid anandamide. Brazilian scientists report that CBD reduces anxiety in animal models by binding directly to the 5HT1A serotonin receptor. Activating this receptor confers an anxiolytic and antidepressant effect. 
Addiction or Medicine?
Adults with PTSD are three times more likely to be dependent on cannabis than those without PTSD.  In the past, this has been seen as comorbidity; PTSD with the added complication of substance dependence. As the promise of targeting the ECS in PTSD treatment and the potential benefits of cannabinoids are discovered, what was previously considered cannabis dependence could be reframed as a legitimate treatment option. Still, it is important to recognize that cannabis dependence and adverse effects are real concerns that can be mitigated by clinician screening and monitoring of patients.
- Trezza V and Campolongo P. The Endocannabinoid System as a Possible Target to Treat Both the Cognitive and Emotional Features of Post-Traumatic Stress Disorder (PTSD). Frontiers in Behavioral Neuroscience. 09 August 2013 doi: 10.3389/fnbeh.2013.00100
- Krumm BA. Cannabis for Posttraumatic Stress Disorder: A Neurobiological Approach to Treatment. The Nurse Practitioner. Vol. 41, No. 1 2016.
- Numeister A, et al. Elevated Brain Cannabinoid CB1 Receptor Availability in Posttraumatic Stress Disorder: A Positron Emission Tomography Study. Mol Psychiatry. 2013 September ; 18(9): 1034–1040. doi:10.1038/mp.2013.61.
- Mikuriya T. Cannabis Eases Post-Traumatic Stress. O’Shaughnessy’s. Spring 2006 11-12.
- Passie T, et al. Mitigation of Post-Traumatic Stress Symptoms by Cannabis Resin: A Review of the Clinical and Neurobiological Evidence. Drug Testing and Analysis. 3 May 2012. DOI 10.1002/dta.137
- Zanelati TV, Biojone C, et al. Antidepressant-Like Effects of Cannabidol in Mice: Possible Involvement of 5-HT1A Receptors. British Journal of Pharmacology (2010), 159, 122–128
- Spagnolo PA, et al. FAAH Gene Variation Moderates Stress Response and Symtpom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence. Alcohol Clin Exp Res. 2016 Nov;40(11):2426-2434. doi: 10.1111/acer.13210. Epub 2016 Sep 26.
- Rezinik I. Medical Cannabis Use in Post-Traumatic Stress Disorder: A Naturalistic Observational Study. Abstract presented at the Cannabinoid Conference 2011, 8-10 September, Bonn, Germany.
- Bonn-Miller MO, et al. Posttraumatic Stress Symptom Severity and Marijuana Use Coping Motives: A Test of the Mediating Role of Non-Judgmental Acceptance Within a Trauma-Exposed Community Sample. Mindfulness (2010) 1:98–106. DOI 10.1007/s12671-010-0013-6