Dronabinol, a pharmaceutical form of Tetrahydrocannabinol (THC) delivered as oil drops, was safe and effective for reducing nightmares related to posttraumatic stress disorder (PTSD), new research suggested.

In a multicenter, double-blind trial of nearly 200 patients with PTSD, participants who received 2.5-15 mg of dronabinol once daily for 10 weeks had significantly greater reductions in nightmare frequency and intensity compared to those who received matching placebo.

The treatment group also reported more adverse events (AEs), but the percentage of AE-related treatment discontinuations was lower than placebo.

“More than a third of patients treated with dronabinol reported that they no longer experienced any nightmares after 10 weeks,” lead study author Stefan Röpke, Department of Psychiatry and Neurosciences, Campus Benjamin Franklin, Charité–Universitätsmedizin Berlin, Berlin, Germany, said in a release.

Another 21% reported that their nightmare burden had been halved and about five out of six members reported that their health had “markedly improved,” Röpke added.

The findings were published online on August 5 in Nature Medicine.

A Hallmark of PTSD

PTSD prevalence is significantly higher in women than in men. Nightmares are common with the disorder, affecting between 50% and 70% of patients.

However, medications for this condition are limited, the investigators noted. Selective serotonin and serotonin-norepinephrine reuptake inhibitors have shown efficacy in PTSD itself but not in related nightmares. Although small studies have shown benefit for these nightmares from the alpha1-adrenergic antagonist prazosin, larger trials have not been positive.

Attention has been increasingly turning toward cannabinoids as a possible treatment option.

“Altered endocannabinoid signaling has been observed in patients with PTSD,” the investigators wrote, adding that this patient population often reports using cannabis for self-medication for better sleep and other indications.

The current study focused on dronabinol, a formulation of TCH delivered as drops. THC is the principal psychoactive compound of the cannabis plant.

The double-blind trial included 171 adults aged 18-65 years (mean age, 37.9 ± 12.8 years; 79.3% women) with PTSD and recurrent nightmares (> 2 per week) screened at four medical centers in Germany from 2020 to 2025. All were randomly assigned to receive either dronabinol at a dose of 2.5 mg-15 mg (n = 87) or matching placebo (n = 84) once nightly 1 hour before bedtime for 10 weeks. Both treatments were administered as oil drops on a spoon.

The primary outcome was change at week 10 in B2 item scores for nightmare frequency and intensity on the Clinician-Administered PTSD Scale for diagnostic and statistical manual of mental disorders-IV (CAPS-IV). Secondary endpoints included other efficacy and safety outcomes.

‘Appropriately Powered’ Evidence?

Results showed that the dronabinol group had greater change in nightmare frequency and intensity from baseline to week 10 on CAPS-IV B2 scores than the placebo group (-3.66 vs -2.17; P < .001).

Those receiving dronabinol also had greater overall improvement on the Patient Global Impression of Change (odds ratio, 4.66; P < .001).

In additional analyses of 145 patents at week 10, response rates were 57.9% vs 29% in the dronabinol vs placebo groups (P < .001), and remission rates were 36.8% vs 14.5%. The active treatment group also had greater improvements on the Pittsburgh Sleep Quality Index-Addendum (P < .001) and patient-reported PTSD symptom scores (P = .006).

AEs were reported in 89.7% of the treatment group vs 77.1% of the placebo group, with serious AEs occurring in 8% vs 0%.

Discontinuation of treatment because of AEs occurred in 5.7% of the active treatment group vs 7.2% of the placebo group. The AEs that occurred more often in the dronabinol group vs placebo group were dry mouth (9.2% vs 1.2%) and SARS-CoV-2 infection (12.6% vs 2.4%).

“These findings extend preliminary open-label and retrospective studies and provide evidence from an appropriately powered randomized controlled trial that cannabinoid receptor agonists improve PTSD-related nightmares,” the researchers wrote.

However, “long-term efficacy and safety require further evaluation,” they added.

The study was funded by Bionorica SE. Disclosure information for the study investigators is available in the original study publication.