Summary: Researchers investigated the efficacy of dronabinol, a plant-derived tetrahydrocannabinol (THC) formulation, in treating trauma-related nightmares in patients with post-traumatic stress disorder (PTSD).
The trial demonstrated a statistically significant reduction in nightmare burden among participants receiving dronabinol compared to placebo. Over a third of dronabinol-treated patients reported complete resolution of nightmares by week ten, while an additional 21% experienced a reduction of at least 50%.
The compound specifically mitigated nocturnal trauma re-experiencing without inducing severe adverse events, withdrawal symptoms, or dependence, though mild-to-moderate side effects such as dizziness and headache were observed.
Key Facts
- Quantifiable Nightmare Burden Reduction: On an 8-point severity scale, nightmare burden in the dronabinol cohort decreased by an average of 3.7 points, compared to a 2.2-point reduction in the placebo group.
- High Rate of Complete Remission: More than 33% of patients receiving dronabinol reported complete cessation of trauma-related nightmares after ten weeks of nightly administration.
- Meaningful Clinical Improvement: An additional 21% of dronabinol-treated participants experienced at least a 50% reduction in nightmare burden, with roughly 83% (five out of six) reporting marked overall health improvement.
- Symptom Specificity: Dronabinol selectively targeted nightmare severity and sleep disruption; overall PTSD severity and co-occurring depressive symptoms did not demonstrate significant secondary changes.
- Safety & Tolerability Profile: No severe adverse events or withdrawal symptoms were recorded following treatment discontinuation. Mild-to-moderate side effects included dizziness, headache, and increased appetite.
Source: Charite
Drastic or even life-threatening events can have lingering effects, like an echo. This is referred to as post-traumatic stress disorder (PTSD). The brain is unable to process these overwhelming experiences and stores the memories in such a way that they cannot be consciously controlled. They resurface again and again. Also at night, when people with PTSD relive the trauma over and over again until they wake up – usually in a state of panic.
Antidepressants or blood pressure-lowering medications are commonly used to provide relief, among other treatments, but these are only partially effective and usually do not help relieving the nightmares. A medication specifically for treating trauma-related nightmares has not yet been approved in Germany.
Prof. Stefan Röpke conducts research on trauma-related disorders at the Department of Psychiatry and Neurosciences on the Benjamin Franklin Campus of Charité. In their search for new treatment approaches and avenues, he and his team, along with other partners, focused on the principal psychoactive compound of the cannabis plant: tetrahydrocannabinol, or THC for short. This active ingredient, also known for its psychoactive effects, interacts with the body’s endocannabinoid system, which is involved in regulating sleep, stress, and the processing of emotional memories.
Stefan Röpke explains: “There is evidence suggesting that during REM sleep – the intense dream phases in which the brain processes experiences and regulates emotions – THC reduces dream activity and thereby alleviates nocturnal stress responses.”
A cannabinoid specifically targeting nightmares
Cannabis-based medications are already finding use in pain management, typically when standard treatments prove insufficient or patients cannot tolerate them. In Germany, this has been possible since the so-called “Cannabis for medical purposes” law took effect in 2017. Since then, it has become easier to use plant-derived or synthetically produced cannabinoids for medical and medical-scientific purposes.
For their current study the researchers selected a form of THC derived directly from the cannabis plant in the form of drops – the prescription medication Dronabinol. The aim was to determine whether this approach could alleviate nightmares associated with PTSD and whether its use is safe in this context.
More than 170 patients with post-traumatic stress disorder and frequent, intense nightmares participated in the study. For a ten week period, they received either the medication or an identical-looking, cannabis-flavored placebo every evening before bedtime. Neither the healthcare providers nor the participants knew who was receiving which treatment – the gold standard of medical research, a so-called double-blind, placebo-controlled study.
By the end of the study period, nightmares had decreased to a significantly greater extent in the Dronabinol group than in the placebo group. On a scale of zero to eight points, the nightmare burden decreased by an average of 3.7 points, compared to only 2.2 points in the placebo group – a difference that is clearly noticeable to those affected.
“More than a third of the patients treated with Dronabinol reported that they no longer experienced any nightmares after ten weeks. Another 21 percent reported that their nightmare burden had been at least halved,” as Stefan Röpke stated. “And about five out of six patients in the dronabinol group felt their health had markedly improved.”
No dependence or severe side effects
According to the studies, the cannabinoid had a specific effect on nightmares and sleep, but not on all PTSD symptoms. Moreover, the severity of the post-traumatic stress disorder and any accompanying depression did not change conclusively.
Nevertheless, the majority of participants experienced significant relief, as the tormenting nightly re-experiencing of the traumatic event was interrupted, allowing for restful sleep. Taking the medication did not cause any severe side effects; however, the researchers observed moderate and mild side effects such as dizziness, headache, or increased appetite more frequently.
The study team did not observe any withdrawal symptoms after the end of the study period and the discontinuation of the evening doses. In the next steps going forward, the researchers now aim to determine whether taking the cannabinoid is also effective and safe over the long term, or whether a tolerance effect develops over time.
Funding: The research was initiated and led by Charité; researchers from the Psychiatric University Clinic of the Charité at St. Hedwig Hospital, the University Medical Center Hamburg-Eppendorf, and the Central Institute for Mental Health in Mannheim were also involved. The work was supported by the company Bionorica SE.
Key Questions Answered:
A: Conventional treatments such as antidepressants or blood pressure medications primarily target generalized daytime anxiety, mood dysregulation, or peripheral sympathetic tone. They do not directly regulate the specific neural circuits within the endocannabinoid system that govern REM sleep dream intensity, emotional memory reconsolidation, and central nocturnal stress responses.
A: THC interacts directly with the body’s endocannabinoid system, which modulates emotional memory processing, stress, and sleep architecture. During intense REM sleep phases, when the brain processes emotional experiences, THC reduces overall dream activity and dampens hyperactive limbic responses, thereby preventing the nightly surge of anxiety that triggers traumatic nightmares.
A: The study team observed no withdrawal symptoms following the discontinuation of the nightly dronabinol doses at the end of the ten-week period. While the treatment proved safe and non-addictive within this timeframe, future studies aim to evaluate whether long-term use across several months or years maintains efficacy or leads to drug tolerance
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this psychopharmacology and PTSD research news
Author: Markus Heggen
Source: Charité
Contact: Markus Heggen – Charité
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Dronabinol for nightmares in post-traumatic stress disorder: a randomized controlled trial” by Stefan Roepke, Nikola Schoofs, Kathlen Priebe, Felix Wuelfing, Kristina Meyer, Astrid Gieselmann, Katharina Stieglbauer, Milagros Galve, Sarah Biedermann, Jürgen Gallinat, Ingo Schäfer, Christian Schmahl, Jenny Zähringer, Robert Roehle, Erin D. Sprünken, Tim Friede, Stefan M. Gold, Tolou Maslahati, Christian Otte & Stefanie Koglin. Nature Medicine
DOI:10.1038/s41591-026-04546-9
Abstract
Dronabinol for nightmares in post-traumatic stress disorder: a randomized controlled trial
Nightmares are a hallmark of post-traumatic stress disorder (PTSD), yet pharmacological treatments remain limited. Here we conducted a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of dronabinol (BX-1; Δ9-tetrahydrocannabinol (THC)) for PTSD-related nightmares.
Adults with PTSD and recurrent nightmares were randomly assigned to receive dronabinol (2.5–15 mg) or placebo, once daily before bedtime, for 10 weeks. The primary endpoint was change from baseline to week 10 in the Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) B2 item assessing nightmare frequency and intensity.
A total of 171 patients underwent randomization (mean age, 37.9 ± 12.8 years; 79.3% female), with 87 assigned to dronabinol and 84 to placebo. At week 10, reduction in CAPS-IV B2 scores was significantly greater with dronabinol than with placebo (between-group difference −1.50; 95% confidence interval −2.28 to −0.71; Cohen’s d = 0.65; P < 0.001).
Adverse events occurred in 78 patients (89.7%) receiving dronabinol and 64 (77.1%) receiving placebo. Treatment discontinuation due to adverse events occurred in five (5.7%) and six (7.2%) patients, respectively. Serious adverse events occurred in seven patients (8.0%) receiving dronabinol and in none receiving placebo.
This trial provides evidence that dronabinol reduces the frequency and intensity of PTSD-related nightmares, although long-term efficacy and safety require further evaluation.
ClinicalTrials.gov: NCT04448808.
