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10 cannabis patient care | vol. 2 no. 4 cannapatientcare.com research focus Overview of the Research on Cannabis for PTSD B Y R U T H F I S H E R T HE DIAGNOSTIC AND Statistical Manual of Men- tal Disorders, Fifth Edition (DSM-5) characterizes post-traumatic stress disorder (PTSD) as a disorder related to trauma or stress, associated with "expo- sure to actual or threatened death, serious injury or sexual vi- olation." There are four proposed diagnostic clusters of symp- toms from which PTSD victims suffer (1): Re-experiencing . . . spontaneous memories of the trau- matic event, recurrent dreams related to it, flashbacks or other intense or prolonged psychological distress. Avoidance . . . [of] distressing memories, thoughts, feelings or external reminders of the event. Negative cognitions and mood represents myriad feel- ings, from a persistent and distorted sense of blame of self or others, to estrangement from others or markedly dimin- ished interest in activities, to an inability to remember key aspects of the event. Finally, arousal is marked by aggressive, reckless, or self-destructive behavior, sleep disturbances, hyper-vigi- lance, or related problems. PTSD researcher George Fraser notes that while PTSD is generally associated with experiences by those in the mili- tary, "the majority" of those who actually suffer from PTSD ex- perienced trauma related to physical or sexual abuse, traffic accidents, natural disasters, or interpersonal violence (2). Prevalence Estimates of the lifetime prevalence of PTSD cluster between 8% to 10%, where prevalence is estimated to be higher in women than in men (2–5). Furthermore, PTSD is estimated to be more prevalent than other anxiety disorders such as panic disorder, obsessive compulsive disorder, and generalized anxiety disorder (2). Comorbidities PTSD is associated with several comorbid conditions, including depression, anxiety, psychosis, and substance use disorders (4,6). Current Treatments PTSD is currently treated with a combination of any of a varie- ty of psychotherapies (for example, prolonged exposure ther- apy, cognitive processing therapy, and extinction learning) and medications (for example, selective serotonin reuptake inhibitors [SSRIs], serotonin/norepinephrine reuptake inhib- itors [SNRIs], antiadrenergic agents, and second-generation antipsychotics) (4,6–8). Unfortunately, however, current treat- ments are not very effective and adherence is low, generally leading victims to suffer significant impairments in long-term quality of life (2,3,6,9). Origin In a nutshell, "PTSD is a psychiatric condition that develops as an aberrant adaptation to a traumatic event" (10). Moreover, "the diversity of the symptoms such as flashbacks, nightmares, hyperarousal, avoidance, numbing, anxiety, anger, impulsivity, or aggression suggests the involvement of multiple neurotrans- mitter systems" (3). Indeed, a group of Johns Hopkins and NYU researchers described the origins of PTSD as involving many neurotransmitter systems, including: the noradrenergic, seroto- nergic, endogenous cannabinoid, opioid, hypothalamic-pituitary adrenal (HPA) axis, and glutamate systems (9). Researchers have thus established that PTSD involves the endocannabinoid system (ECS) directly, and it involves many other neurotransmitter systems that, in turn, are moderat- ed by the ECS. Given the centrality of the ECS in the emer- gence of PTSD, it makes sense that people who suffer from PTSD have been found to have low levels of ECS activity; that is, their ECSs are malfunctioning. Taken together, these two findings, the centrality of the ECS in modulating symptoms of PTSD and the diminished levels of ECS activity, suggest that enhancing ECS tone—such as by using cannabis—may very well help address symptoms of PTSD (4,8,11,12). Cannabis Mechanisms of Action for Addressing Symptoms of PTSD The major symptoms of PTSD include fear and hypervigilance, flashbacks, sleep disorders, stress and anxiety, and depres- sion. Let's consider each of these major symptoms of PTSD, each symptom's emergence in the body, the role the ECS plays in this origin, and thus how cannabis may be expected to address that symptom. Fear and Hypervigilance Individuals who develop PTSD generally experience a trau- matic event within a certain context—that is, in the presence of certain sights, sounds, or smells—and then they develop