Bedtime THC eased persistent PTSD nightmares

Clinical takeaway: Consider bedtime dronabinol for persistent post-traumatic stress disorder nightmares as a symptom-specific treatment, not a stand-alone therapy.

A patient may be receiving stable treatment for post-traumatic stress disorder (PTSD) and still dread sleep because the same trauma returns night after night. In that setting, the nightmares themselves may need treatment in their own right. The 2023 Department of Veterans Affairs and Department of Defense guideline addresses nightmares separately, suggesting prazosin for PTSD-associated nightmares while recommending against cannabis or cannabis derivatives for PTSD overall. Prazosin remains a reasonable option, but mixed efficacy and BP-lowering effects can limit its use.

Dronabinol, a prescription form of delta-9-tetrahydrocannabinol (THC), is not FDA-approved for PTSD, making its use for nightmares off-label. Against that backdrop, investigators conducted a 10-week, multicenter, double-blind, randomized, placebo-controlled trial comparing bedtime dronabinol with placebo rather than prazosin in 171 adults aged 18 to 65 with PTSD and at least two nightmares per week.

In the primary analysis, nightmare burden fell by 3.66 points with dronabinol and 2.17 points with placebo at week 10, an adjusted difference of 1.50 points on the 8-point scale. Among the 145 participants with observed week-10 data, 57.9% of those receiving dronabinol had at least a 50% reduction in nightmare burden, and 36.8% had complete nightmare remission. The corresponding placebo rates were 29.0% and 14.5%.

Dronabinol did not clearly improve clinician-rated overall PTSD or depression. Adverse events were more common with dronabinol, but discontinuation due to adverse events was similar between groups.

Investigators titrated bedtime dronabinol oil from 2.5 mg to 15 mg during the first four weeks, stopping when nightmares remitted or further increases were not tolerated. Participants then continued their individualized dose for six weeks while maintaining stable background medication. The primary endpoint was change in clinician-rated nightmare frequency and intensity on an 8-point scale at week 10.

Longer trials should compare dronabinol directly with prazosin and determine whether nightmare relief persists, tolerance develops, or safety changes with continued nightly use.

Stefan Röpke, professor in the Department of Psychiatry and Neurosciences at Charité in Berlin, said existing evidence suggests that during rapid eye movement sleep, “THC reduces dream activity and thereby alleviates nocturnal stress responses.”

Source: Roepke S, et al (2026 Aug 5). Nat Med. Dronabinol for nightmares in post-traumatic stress disorder: a randomized controlled trial