Post-traumatic stress disorder (PTSD) is a relatively common psychiatric condition with a lifetime prevalence of 6.1% in the United States.1 PTSD often presents in clusters of symptoms, including the re-experiencing of traumatic events through intrusive memories and nightmares, avoidance of certain distressing factors, and alterations in mood, level of arousal, and cognition. Psychotherapy is the established first-line treatment for PTSD, and various psychiatric medications are also typically employed. The development of additional treatment agents is important because current medications, including selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, antiadrenergic agents, and second-generation antipsychotics, have questionable efficacy and often carry significant undesirable side-effect profiles.
Although the pathophysiology of PTSD has not yet been definitively described, a number of factors are suspected to contribute to the development of this disorder. One hypothesis relates PTSD to dysregulated memory retrieval through the process of reconsolidation and impaired extinction of aversive memories.2 The endogenous cannabinoid system has been shown to play an important role in the process of aversive memory extinction through the activity of central CB1 receptors.3 Two cannabinoid receptors are known to exist in the human body: CB1 and CB2 receptors. CB1 receptors are located mainly in the brain and modulate neurotransmitter release in a manner that prevents excessive neuronal activity, thus calming and decreasing anxiety. CB1 receptors also have a role in reducing pain, inflammation, regulating movement and posture control, and regulating sensory perception, memory, and cognitive function.
Cannabidiol (CBD) is known to have multiple physiologic mechanisms of action, including 5-HT1A serotonergic agonism, adenosine and opioid receptor modulation, activation of the endogenous endocannabinoid system, antagonism at GPR55 receptors, and activation of transient receptor potential channels.4,5 CBD’s activity at 5-HT1A receptors may drive its neuroprotective, antidepressive, and anxiolytic benefits, although the mechanism of action by which CBD decreases anxiety is still unclear.6 CBD was shown to be helpful for decreasing anxiety through a simulated public speaking test at doses of 300–600 mg in single-dose studies.7–9 Other studies suggest that lower doses of 10 mg/kg have a more anxiolytic effect than higher doses of 100 mg/kg in rats.10
Of particular interest to this study is the effect of CBD on the endogenous cannabinoid system. CBD has minimal affinity for CB1 and CB2 receptors,11 but it does indirectly cause activation of CB1 receptors by increasing the availability of endogenous endocannabinoids. Anandamide is an endogenous cannabinoid that acts as a partial agonist at CB1 receptors. It is metabolically deactivated by the enzyme fatty acid amide hydrolase (FAAH). CBD has been shown in some studies to inhibit FAAH, thus increasing the availability of anandamide and causing activation of the endocannabinoid system.12 Studies in rodent models have shown that pharmacologic activation of the endocannabinoid system through CB1-receptor agonist agents leads to decreased behavioral response to aversive memories in rodent models through the inhibition of memory reconsolidation and enhanced extinction.13–15 This early research suggests that agents such as CBD that cause indirect activation of the endocannabinoid system may have utility in the treatment of PTSD.
Current evidence regarding the use of CBD for PTSD in humans is minimal. One case report showed that administration of 12–37 mg of oral CBD daily was associated with a reduction in anxiety symptoms and sleep disturbances in a 10-year-old patient with PTSD due to sexual trauma.16 Another study showed that 32 mg of inhaled CBD resulted in consolidation of aversive memory extinction and attenuation of explicit fearful responding in healthy human subjects.17 See Bittencourt and Takahashi18 for a recent comprehensive review of pre-clinical and clinical studies regarding the relationship of CBD to PTSD. To date, no clinical trial evaluating the effectiveness of CBD in reducing symptoms of PTSD in humans has been completed.
The hypothesis of this study was that patients with DSM-5-diagnosed PTSD who were administered CBD along with routine psychiatric care would show a decrease in PTSD-specific symptomatology. This hypothesis was based on prior rodent and limited human studies that suggest that (1) CBD may cause decreased response to and increased extinction of aversive memories, and that (2) CBD may have an anxiolytic effect, which, in turn, would have therapeutic value in patients with PTSD. To this end, we conducted a retrospective file review of adult patients with PTSD who were treated with CBD as part of standard psychiatric care in an outpatient clinic. The goal of this review was to examine the tolerability of CBD and its effectiveness in PTSD symptom reduction.