Cannabis in the management of PTSD : a systematic review,
Yasir Rehman, Amreen Saini, Sarina Huang, Emma Sood, Ravneet Gill and Sezgi
AIMS Neuroscience, 2021, 8, (3), 414-434.
Doi : 10.3934/Neuroscience.2021022
Introduction : Existing reviews exploring cannabis effectiveness have numerous limitations including narrow search strategies. We systematically explored cannabis effects on PTSD symptoms, quality of life (QOL), and return to work (RTW). We also investigated harm outcomes such as adverse effects and dropouts due to adverse effects, inefficacy, and all-cause dropout rates.
Methods : Our search in MEDLINE, EMBASE, PsycInfo, CINAHL, Web of Science, CENTRAL, and PubMed databases, yielded 1 eligible RCT and 10 observational studies (n = 4672). Risk of bias (RoB) was assessed with the Cochrane risk of bias tool and ROBINS-I. Results: Evidence from the included studies was mainly based on non-randomized studies with no comparators. Results from unpooled, high RoB studies showed that cannabis was associated with a reduction in overall PTSD symptoms and improved QOL. Dry mouth, headaches, and psychoactive effects such as agitation and euphoria were the commonly reported adverse effects. In most studies, cannabis was well tolerated, but small proportions of patients experienced a worsening of PTSD symptoms.
Conclusion : Evidence in the current study primarily stems from low quality and high RoB observational studies. Further RCTs investigating cannabis effects on PTSD treatment should be conducted with larger sample sizes and explore a broader range of patient-important outcomes.
Keywords : PTSD; cannabis; THC; nabilone; symptoms reduction; functional improvement;
systematic review; meta-analysis; cannabinoid
Posttraumatic stress disorder (PTSD) results from experiencing or witnessing an emotionally traumatic event that is perceived to present a threat to the life or physical integrity of oneself or others [1,2]. PTSD affects approximately 8 to 9% of individuals in their lifetime and is over represented in the veteran population [3,4]. PTSD manifests primarily as symptoms in cognition when trauma is re-experienced through intrusive memories, flashbacks, and/or nightmares; active avoidance of external and internal reminders of the trauma; intensified mood and emotional states such as depression, anxiety, psychological instability, impulsivity, and hyperarousal; and changes in social abilities in both personal and interpersonal functioning [2,5].
PTSD is primarily treated by various psychotherapies and non-pharmacological interventions such as cognitive-behavioral therapy , exposure therapy [7,8], support therapies, biofeedback , and eye movement desensitization and reprocessing . Additionally, various pharmacological interventions such as selective serotonin reuptake inhibitors (SSRIs) [11,12], serotonin-norepinephrine reuptake inhibitors (SNRIs) , and tricyclic antidepressants  aim to re-establish the balance of neurotransmitters to mitigate the symptoms. In recent years, medicinal cannabis has been increasingly used in conjunction with current psychotherapies and/or pharmacological interventions as a potentially more effective way of managing PTSD [14–16]. Brain morphometric studies on PTSD patients have shown alterations in the activities of the amygdala (fear conditioning), prefrontal cortex (emotional regulation), and hippocampus (memory consolidation) , as well as dysregulation of the hypothalamic-pituitary axis , which is associated with abnormal levels of neurotransmitters such as norepinephrine and serotonin. Collectively, the structural and chemical changes  contribute to disturbances in behavioral neurology and manifest as impulsivity, sleep disruptions, nightmares, and
flashbacks. Cannabidiol, an active ingredient in cannabis, increases serotonin  and dopamine levels in the midbrain. This results in lower stress levels and better patient coping, ultimately reducing remission rates [14,16,20].
Current systematic reviews [21–25] exploring the effectiveness of cannabis in treating PTSD patients have key limitations such as language restrictions [21–25], literature searches developed from few databases [21–25], small sample sizes, and a narrow range of outcome focuses. Most systematic reviews focus on beneficial outcomes of cannabis intervention but do not report harm outcomes. In order to understand the scope of any treatment, consideration of both its benefits and potential risks is vital so that both patients and healthcare providers can establish realistic expectations and make informed decisions [26,27]. The objectives of this systematic review were to assess the effectiveness of cannabis on PTSD, quality of life, social function, return to work, and harm effects such as adverse effects and dropout rates, and to critically appraise the existing literature investigating the effects of cannabis in the management of PTSD.