A Phase II randomized trial published in Nature Medicine found that oral dronabinol significantly reduced PTSD-related nightmares compared with placebo over 10 weeks.
Written By: Mayuresh Salvi, PharmD
Reviewed By: Pharmacally Editorial Team
Oral dronabinol significantly reduced the frequency and intensity of trauma-related nightmares in adults with post-traumatic stress disorder (PTSD) compared with placebo in a multicenter randomized controlled trial published in Nature Medicine. The Phase II study, led by researchers at Charité Universitätsmedizin Berlin in collaboration with multiple clinical centers and Bionorica SE, met its primary endpoint and provides randomized clinical evidence supporting further evaluation of dronabinol (BX-1) for PTSD-associated nightmares, although longer-term efficacy and safety remain to be established.
PTSD-Related Nightmares Continue to Pose a Major Treatment Challenge
Nightmares are among the hallmark symptoms of PTSD and contribute substantially to chronic sleep disturbance, emotional distress, impaired daily functioning, and reduced quality of life. Although trauma-focused psychotherapy and antidepressants remain the cornerstone of PTSD treatment, pharmacological options specifically targeting recurrent nightmares have produced inconsistent results, leaving a considerable unmet clinical need.
Dronabinol (BX-1) is a synthetic formulation of Δ9-tetrahydrocannabinol (THC). Researchers investigated the therapy because the endocannabinoid system plays an important role in regulating fear extinction, emotional memory, stress responses, and sleep, making it a potential therapeutic target for persistent PTSD-related nightmares.
Multicenter Phase II Trial Evaluated Oral Dronabinol
The multicenter, double-blind, randomized, placebo-controlled Phase II trial (NCT04448808) enrolled 171 adults aged 18 to 65 years with PTSD and recurrent trauma-related nightmares. Participants were randomly assigned to receive oral dronabinol (2.5–15 mg) or placebo once daily before bedtime for 10 weeks, with 87 patients allocated to the dronabinol group and 84 to the placebo group. The mean participant age was 37.9 ± 12.8 years, and 79.3% were women.
The primary endpoint was the change from baseline to Week 10 in the Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) B2 score, which measures nightmare frequency and intensity. Secondary assessments evaluated overall PTSD symptoms, sleep-related outcomes, depressive symptoms, and safety.
Dronabinol Demonstrated Significant Improvement in Nightmare Severity
The trial met its primary efficacy endpoint.
At Week 10, participants receiving dronabinol experienced a significantly greater reduction in CAPS-IV B2 scores than those receiving placebo, with a between-group difference of −1.50 points (95% confidence interval, −2.28 to −0.71; P < 0.001).
The treatment effect corresponded to a Cohen’s d of 0.65, indicating a moderate effect size. These findings showed that oral dronabinol significantly reduced both the frequency and intensity of PTSD-related nightmares compared with placebo during the 10-week treatment period.
Safety Findings Support Further Evaluation
Adverse events occurred in 78 patients (89.7%) receiving dronabinol compared with 64 patients (77.1%) receiving placebo. Treatment discontinuation due to adverse events remained uncommon, occurring in five patients (5.7%) in the dronabinol group and six patients (7.2%) in the placebo group.
Serious adverse events were reported in seven patients (8.0%) receiving dronabinol, whereas no serious adverse events occurred in the placebo group. The investigators concluded that while dronabinol reduced PTSD-related nightmares, additional studies are needed to better define its long-term efficacy and safety.
Clinical Significance
The study adds randomized clinical evidence supporting dronabinol as a potential treatment for PTSD-related nightmares, an area where effective pharmacological options remain limited. By demonstrating statistically significant reductions in nightmare frequency and intensity in a rigorously conducted randomized controlled trial, the findings support continued investigation of cannabinoid-based therapy for this challenging symptom.
Researcher Perspective
The investigators concluded that oral dronabinol significantly reduced the frequency and intensity of PTSD-related nightmares compared with placebo over 10 weeks of treatment. They also emphasized that longer-term studies are required to determine the durability of treatment response and further characterize the long-term safety profile.
What This Means and What Comes Next
The publication of this multicenter randomized controlled trial provides important clinical evidence supporting dronabinol for PTSD-related nightmares. While the study demonstrated significant short-term improvements in nightmare frequency and intensity, further studies with longer follow-up will be needed to confirm sustained efficacy, better characterize long-term safety, and define the role of dronabinol in the management of PTSD-related sleep disturbances.
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About the Writer
Mayuresh Sunil Salvi (Linkedin) is a PharmD professional and healthcare writer with a strong interest in pharmacovigilance, drug safety, and emerging medical research. He is passionate about exploring new drug discoveries, clinical research, and advances in evidence-based medicine. His interests also include ward rounds, prescription audits, and treatment analysis to support rational pharmacotherapy and improved patient care.