A THC pill cut PTSD nightmares in a 171-person trial

Nightmares are not a complication of post-traumatic stress disorder. They are part of the definition of it, listed among the ways the trauma keeps returning.

The drug options for them are thin. A multicenter trial published in Nature Medicine tested a new one on 171 adults: a pill containing the main psychoactive compound in cannabis, taken nightly for ten weeks.

The nightmares improved. The count of serious side effects moved the other way: seven on the drug, none on placebo.

Why nightmares are the target

Post-traumatic stress disorder (PTSD) is a mental health disorder that some people develop after they experience or see a traumatic event.

It is usually described in four groups of symptoms: re-experiencing symptoms, when something reminds you of the trauma and you feel that fear again; avoidance symptoms, when you try to avoid situations or people that trigger memories; arousal and reactivity symptoms, which may cause you to be jittery or be on the lookout; and cognition and mood symptoms, which are negative changes in beliefs and feelings.

Nightmares are listed as a re-experiencing symptom, alongside flashbacks. They are the trauma re-running while a person is asleep and unable to use any of the coping strategies therapy teaches.

The treatment gap is what motivated this trial. The main treatments for PTSD are talk therapy, medicines, or both, with medicines including antidepressants and options to help with sleep problems and nightmares. The researchers put it more bluntly: nightmares are a hallmark of post-traumatic stress disorder (PTSD), yet pharmacological treatments remain limited.

What dronabinol is, and is not

Dronabinol is delta-9-tetrahydrocannabinol, or THC, manufactured as a pharmaceutical and swallowed as a capsule at a measured dose.

That distinction carries most of the weight in how this result should be read. Two THC drugs are approved in the US, for chemotherapy sickness and for weight loss in AIDS (acquired immunodeficiency syndrome). In the official wording: these drugs treat nausea caused by chemotherapy and increase appetite in patients who have severe weight loss from AIDS. Nightmares are not on that list.

It is also not the same as using cannabis. Short-term effects of cannabis include altered senses, such as seeing brighter colors and trouble with thinking, problem-solving, and memory, and after using marijuana for a while, it is possible to get addicted to it.

A fixed nightly dose of one compound, taken under trial supervision, is a different exposure from a plant with variable content taken at will.

How the PTSD nightmares trial was run

The design is the strongest thing about this study. It was a multicenter, double-blind, randomized, placebo-controlled trial, which is the arrangement that makes a result about the drug rather than about expectation.

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. A total of 171 patients underwent randomization (mean age, 37.9 years; 79.3% female), with 87 assigned to dronabinol and 84 to placebo.

The outcome was specific rather than general. The primary endpoint was change from baseline to week 10 in the Clinician-Administered PTSD Scale B2 item assessing nightmare frequency and intensity. One item, rated by a clinician, measuring the thing the drug was meant to fix.

What the PTSD nightmares scores did

At week 10, the reduction in nightmare scores was significantly greater with dronabinol than with placebo, by 1.50 points on that item.

The effect size is the more useful number for a reader. Cohen’s d = 0.65 is a moderate effect, meaning the average person on the drug did better than roughly three quarters of the people on placebo. In a symptom with few treatments, moderate is worth having.

The authors’ own claim stays within that. This trial provides evidence that dronabinol reduces the frequency and intensity of PTSD-related nightmares.

The dronabinol side effect count

Adverse events were common everywhere. Adverse events occurred in 78 patients (89.7%) receiving dronabinol and 64 (77.1%) receiving placebo, which is close to everybody in both arms and normal in a trial that asks about symptoms weekly.

Dropping out was not the problem either. Treatment discontinuation due to adverse events occurred in five (5.7%) and six (7.2%) patients, respectively. Slightly more people quit the placebo.

Then the line that matters. Serious adverse events occurred in seven patients (8.0%) receiving dronabinol and in none receiving placebo.

Seven against zero, in 171 people over ten weeks. In absolute terms it is a handful of events; as a ratio it is one arm to none. The abstract does not say what those events were, and that is the single most important gap in what is currently public.

What 171 people cannot settle about dronabinol

The authors say it themselves: long-term efficacy and safety require further evaluation.

Ten weeks is short for a chronic condition, and THC is a drug where tolerance and dependence develop over months rather than weeks. Nothing here speaks to what happens at a year, or on stopping.

The participants were 79.3% female with a mean age of 37.9, which does not match the PTSD population most people picture and does match a large part of the real one.

The paper is paywalled, so the authors’ own limitations section was not available for this piece.

What this changes for someone with PTSD

Not the treatment on offer today. Dronabinol is not approved for nightmares anywhere, and this is one trial.

What it changes is the direction of research on a symptom that has been under-served. A moderate effect in a properly blinded, placebo-controlled, multicenter trial is a real result, and it justifies the larger and longer study that would establish whether the safety signal is noise.

The thing not to take from it is that cannabis treats nightmares. A measured nightly dose of one compound in a supervised trial is not the same intervention, and the trial did not test the alternative.