FDA Clears Phase 2 Trial of Cannabis in PTSD

The FDA has given clearance for a phase 2 study to begin that will test smoked cannabis in veterans with post-traumatic stress disorder (PTSD). The study will enroll 320 veterans suffering from moderate-to-severe PTSD who have previously used cannabis. Investigations will assess the safety of real-world use of inhalation THC dried cannabis flower compared with placebo cannabis.

Sue Sisley, M.D.

“Our veterans are in dire need of treatments that can ease their challenging symptoms of PTSD. In my own practice, veteran patients have shared how smoking cannabis helped them manage their PTSD symptoms more than traditional pharmaceuticals. Suicide among Veterans is an urgent public health crisis, but it’s solvable if we invest in researching new treatments for life-threatening health conditions like PTSD,” Sue Sisley, M.D., principal investigator and president of SRI Foundation, said in a news release.

PTSD significant concern among military personnel. Although about 6% of U.S. adults are diagnosed with PTSD, more than 23% for military service members experience post-traumatic stress disorder. Combat and previous mental health issues can contribute to veterans experiencing symptoms of PTSD.

Research has suggested that THC acts on receptors in the brain involved in memory and fear and could reduce inflammation.

The trial, MJP2, is funded by the Michigan Veteran Marijuana Research Grant Program and is being conducted by Multidisciplinary Association for Psychedelic Studies (MAPS), a research and educational organization focused on the study of psychedelics and marijuana.

The FDA had initially placed on partial clinical hold by on the trial in 2021, and in August 2024, MAPS filed a Formal Dispute Resolution Request (FDRR). Allison Coker, Ph.D., director of Cannabis Research at MAPS, said the company has resolved the issues raised by the agency.

One key issue was allowing study participants to self-titrate dosing of smoked cannabis with a high THC potency that corresponds to what is commercially available in states that permit its use. After discussions with the FDA, MAPS is able to proceed with self-titration of the cannabis during the trial.

The FDA also no longer objects to vaporization as a delivery method. The agency is, however, requiring additional information on the device to assess its safety before the study can begin.

A previous pilot crossover study, MJP1, assessed three inhaled cannabis treatments (high THC, high cannabidiol, THC+cannabidiol) compared with placebo in 76 veterans with chronic PTSD. The study found that all three types of treatment were able to improve PTSD symptoms, anxiety, depression, and sleep quality. But the effect of inhaled cannabis on PTSD symptoms, the primary endpoint of reduction in CAPS-5 total score, was not statistically significantly different from placebo. The CAPS-5 is a clinician-administered scale that assesses overall PTSD symptoms.

The most common adverse events from the MJP1 study were throat irritation, anxiety, cough, headache, nausea and paranoia. In the study, 11.2% of patients discontinued because of adverse events.

The new study, MJP2, will have a parallel design and study inhaled high THC-potency compared with placebo. In the previous study, high potency THC was the most effective in relieving PTSD symptoms. The dose was selected to align with what is currently available commercially in states that allow medical and recreational use.

According to the protocol, participants will have access to a mobile app to enter information and data. Patients with chronic obstructive pulmonary disease or asthma will be excluded from the study to mitigate risk of respiratory adverse events. Regular use of inhaled cannabis has been shown in some studies to be associated with increased chronic bronchitis, coughing and wheezing.