A medication containing tetrahydrocannabinol (THC) significantly reduced the frequency and intensity of nightmares among patients with post-traumatic stress disorder (PTSD), according to a randomized clinical trial published in Nature.

The study, published August 5, was conducted by researchers from Charité – Universitätsmedizin Berlin, University Medical Center Hamburg-Eppendorf, the Central Institute of Mental Health in Mannheim and other German institutions.

Researchers enrolled 171 adults with PTSD and recurring nightmares in the multicenter, double-blind, placebo-controlled trial. Participants had an average age of 37.9, and 79.3% were female.

Participants were randomly assigned to receive either dronabinol, a prescription medication containing THC, or a placebo each evening before bed for 10 weeks. Dronabinol doses ranged from 2.5 milligrams to 15 milligrams, with 87 patients assigned to the dronabinol group and 84 assigned to the placebo group.

The researchers measured nightmare frequency and intensity using an eight-point section of the Clinician-Administered PTSD Scale. By week 10, nightmare scores had declined by an average of 3.7 points among participants receiving dronabinol, compared with 2.2 points among those receiving a placebo.

The 1.5-point difference between the groups was statistically significant, researchers reported, with a moderate-to-large effect size.

More than one-third of patients receiving dronabinol reported experiencing no nightmares by the end of the treatment period. Another 21% experienced a reduction of at least 50% in their nightmare burden, while approximately five out of six said their overall health had noticeably improved.

Researchers said the treatment appeared to specifically affect nightmares and sleep rather than PTSD more broadly. Overall PTSD severity and accompanying symptoms of depression did not conclusively improve compared with placebo.

THC interacts with the body’s endocannabinoid system, which helps regulate sleep, stress and the processing of emotional memories. The researchers said evidence suggests THC may reduce dream activity during rapid eye movement sleep, potentially decreasing the nighttime stress responses associated with traumatic memories.

Adverse events were reported by 89.7% of patients receiving dronabinol and 77.1% of those receiving placebo. Mild or moderate effects such as dizziness, headaches and increased appetite occurred more frequently in the dronabinol group.

Five patients receiving dronabinol, or 5.7%, discontinued treatment because of adverse events, compared with six patients, or 7.2%, in the placebo group. Although the paper recorded serious adverse events among seven dronabinol recipients and none among placebo recipients, Charité said the medication did not cause any severe side effects. Researchers also reported finding no evidence of withdrawal symptoms after treatment ended.

The researchers said the results provide evidence that dronabinol can reduce the frequency and intensity of PTSD-related nightmares, but additional studies are needed to determine whether the benefits and safety are maintained over longer treatment periods and whether patients develop tolerance.

The investigator-initiated trial was supported by an unrestricted grant from Bionorica SE, which also supplied the study medication. According to the study, the company had no role in designing or conducting the trial, analyzing or interpreting the results, or preparing the manuscript.