One treatment each of two psychedelic drugs lowered depression and anxiety and improved cognitive functioning in a sample of U.S. special operations forces veterans who sought care at a clinic in Mexico, according to a new analysis of the participants' charts.

The treatment included a combination of ibogaine hydrochloride, derived from the West African shrub iboga, and 5-MeO-DMT, a psychedelic substance secreted by the Colorado River toad. Both are designated as Schedule I drugs under the U.S. Controlled Substances Act.

In addition to relieving symptoms of post-traumatic stress disorder (PTSD), the combined treatment also alleviated cognitive impairment linked to traumatic brain injury—which stood out to the researchers from The Ohio State University who led the chart-review analysis. Many special operations forces veterans seeking treatment for complex psychiatric symptoms do not respond to more traditional therapies.

The study is published in the American Journal of Drug and Alcohol Abuse.

"What sets this group apart from some other veterans and civilians is that often, they are exposed to repeated traumatic events as a routine part of their jobs. This build-up of exposure to these difficulties seems to produce a cluster of challenges that include traumatic brain injury, which we know in and of itself predisposes people to mental health problems," said lead author Alan Davis, associate professor and director of the Center for Psychedelic Drug Research and Education (CPDRE) in Ohio State's College of Social Work.

"So the fact that we saw that there were improvements in cognitive functioning linked to brain injury were probably the most striking results, because that's something we didn't predict and it's very new and novel in terms of how psychedelics might help in so many different domains."

Most of the veterans attending the clinic retreat program had been on active duty after 9/11 and reported seeking care for memory problems, brain injury, depression, anxiety, PTSD, sleep problems, anger and fatigue. Head injuries were reported by 86% of attendees, most of whom attributed memory problems, irritability, disordered sleep and ringing in the ears to those long-ago head traumas.

Eighty-six veterans completed pre-treatment questionnaires assessing a range of mental health symptoms as well as satisfaction with life, anger levels and suicidality. Each attendee received a single oral ibogaine hydrochloride dose, and on a separate day, at least three incremental inhalation doses adding up to 50 milligrams of 5-MeO-DMT, also commonly called Five or Bufo. Preparation and reflection sessions preceded and followed each treatment.

Overall, participants reported large improvements in self-reported PTSD symptoms, depression, anxiety, insomnia severity and anger, as well as a significant increase in satisfaction with life, from pre-treatment to the one-month follow-up, and sustained benefits at the three- and six-month follow-ups. Additional reported improvements that continued for six months included reductions in disability and post-concussive symptoms, and very large increases in psychological flexibility and cognitive functioning.

Davis said the improved cognitive functioning warrants more research into whether better thinking results from lowered mental health symptoms or biological changes to signaling in the brain, or a mixture of both types of effects. The researchers also noted that changes to psychological flexibility—one's capacity to act in ways that are consistent with their values regardless of whatever internal or external experience they might have—have been found in previous research to be connected to insightful and mystical psychedelic experiences.

"I think we're seeing a similar picture emerging here where the more one is psychologically flexible, the more likely it is that one's mental health symptoms will be reduced or ameliorated," Davis said.

Most attendees also reported moderate to strong desirable changes across a range of attitudes, behaviours and relationships. One month after treatment, almost half reported the psychedelic experience was the most spiritually significant (48.6%) or psychologically insightful (42.9%) of their lives, and 17.1% called it the most difficult or challenging experience in their life.

Davis and colleagues took a conservative approach to analyzing outcome data, building in an assumption that attendees who didn't complete all of the follow-up surveys may not have gotten the relief they had hoped for from the treatment. However they said finding that a population of veterans with complicated trauma histories can benefit from psychedelic therapy supports the importance of continuing to test psychedelic-assisted therapies in U.S. clinical trials.

Psilocybin-assisted therapy is currently being studied at Ohio State for the treatment of PTSD among military veterans.

Co-authors of the study include Yitong Xin and Nathan Sepeda of Ohio State and Lynnette Averill of Baylor College of Medicine and the U.S. Department of Veterans Affairs.