Background:
Posttraumatic stress disorder (PTSD) is a chronic and debilitating psychiatric condition with a lifetime prevalence of up to 8%, and substantially higher rates among veterans and survivors of repeated or severe trauma. PTSD frequently co-occurs with major depressive disorder, generalized anxiety, chronic pain syndromes, and severe sleep disturbances, leading to long-term functional impairment and reduced quality of life. A growing proportion of patients report using cannabis for emotional regulation, attenuation of intrusive memories, reduction of hyperarousal, and improvement in sleep. Experimental evidence suggests that cannabinoids may influence fear extinction, memory reconsolidation, and stress reactivity via CB1-mediated pathways. Yet robust clinical data, particularly long-term, real-world evidence, remain limited. Further clarification of the therapeutic role, safety, and optimal clinical integration of medical cannabis (MC) in chronic PTSD is therefore essential.

Methods:
We conducted a long-term, naturalistic evaluation of 280 adult patients (aged 18–77) with chronic PTSD authorized by the Ministry of Health to receive MC. These individuals were drawn from a larger cohort of 1,790 evaluated applicants. Follow-up occurred over a 10–12-year period with clinical reassessments every 6–12 months. Patients were categorized into: (1) “pure” PTSD (n = 35), (2) PTSD with comorbid depression (n = 74), and (3) PTSD with chronic pain (n = 171). Standardized measures included the Clinician-Administered PTSD Scale (CAPS), Quality of Life Scale (QoLS), and Clinical Global Impression–Improvement (CGI-I). Data on somatic comorbidity, pain intensity, sleep quality, and concurrent pharmacotherapy were periodically collected, allowing observation of longitudinal treatment patterns and medication changes.

Results:
More than half of the cohort were initially treated with psychotropic or analgesic medications. MC (GAP/GMP-certified) was supplied by licensed producers, with average daily doses of 1.5–2.5 g containing 15–25% total cannabinoids, predominantly THC with variable CBD content. Most patients relied on inhalation (smoking or vaporization), often supplemented by sublingual extracts for steadier symptom control. Significant improvements were observed in QoLS, CGI-I, and across all major PTSD symptom clusters. Patients consistently reported reductions in nightmares, intrusive memories, flashbacks, avoidance behaviors, emotional numbing, hypervigilance, irritability, exaggerated startle responses, and sleep-onset difficulties. Many described increased emotional flexibility, reduced reactivity, and improved day-to-day coping. Patients with comorbid depression or chronic pain demonstrated the largest clinical gains, including reduced pain levels, improved mood and motivation, enhanced sleep continuity, and meaningful improvements in social functioning, family relationships, and occupational performance. Severe dissociative symptoms (more common in women) and profound emotional numbing (more common in men) were less responsive and often required careful dose adjustments. A minority experienced dose-dependent cognitive effects, such as decreased concentration and/or short-term memory lapses. Many patients successfully reduced or discontinued opioids, sedatives, and antidepressants without destabilization. MC was generally well tolerated. Side effects were mild and transient, with no serious adverse events, psychiatric decompensations, or cases of pathological dependence or addiction observed. Twenty-one patients discontinued MC due to non-medical factors (cost, logistics), and 25 changed clinical settings without worsening of symptoms.

Discussion & Conclusions:
This long-term real-world study suggests that MC may provide clinically meaningful symptomatic relief and functional improvement in chronic PTSD, especially among those with comorbid depression or chronic pain—subgroups often resistant to standard treatment. Benefits included reductions in re-experiencing, avoidance, and hyperarousal symptoms, along with improved emotional regulation, sleep quality, social functioning, and overall quality of life. The favorable safety profile and reduced reliance on other psychotropic and analgesic medications further support its potential role as an adjunctive therapeutic option. However, given the non-randomized observational design, findings should be interpreted with caution. Variability in cannabis formulations, dosing patterns, individual sensitivity, and comorbidity burden may affect outcomes. Large, controlled clinical trials are needed to confirm these results and establish evidence-based guidelines for cannabinoid composition, dosing strategies, delivery methods, and integration of MC into comprehensive PTSD care.