Researchers to test psychedelic drugs as treatments for depression, PTSD and more

Psychedelic drugs—often associated with 1960s counterculture—are attracting newfound attention from physicians and neuroscientists who are studying their potential to help people suffering from an assortment of behavioral health problems.

University of New Mexico Health Sciences researchers are at the forefront of several new studies to evaluate the use of drugs like psilocybin, ketamine and MDMA to treat depression, opioid use disorder, methamphetamine addiction and PTSD.

Two new psilocybin-related studies are getting underway, said Larry Leeman, MD, MPH, a professor in the Departments of Family & Community Medicine in the UNM School of Medicine, who also serves as medical director for UNM's Milagro Program.

RECONNECT is a Phase II multi-center study of RE104—a novel compound that's related to psilocybin—for postpartum depression, which affects about 13% of new mothers. "The exciting thing about this one is it has the potential to quickly reverse postpartum depression," Leeman said.

Some participants in the double-blind placebo-controlled study will receive a one-time injection of the short-acting drug, whose psychedelic effects peak at about 2.5 hours, he said.

"I have an interest because it might be useful in cases where a shorter experience might be more useful," Leeman said.

While some people experiencing postpartum depression have a pre-existing mood disorder, many experience it only as an outcome of pregnancy, and might need just one treatment session to recover, he said. Psilocybin has been shown to have an effect on major depression within a few days, which may be particularly beneficial for mothers whose postpartum depression may be affecting maternal-infant bonding. It can only be used for people who are not breastfeeding, however.

RE104 is also being explored for treating patients with life-threatening cancer diagnoses who are experiencing depression and anxiety, he said. Leeman expects UNM will probably participate in that study, starting in 2025.

The other new study, dubbed uAspire, is a Phase III randomized, double-blind multicenter project assessing the potential benefits of psilocybin, the active ingredient in so-called "magic mushrooms," for major depressive disorder.

UNM's portion of the study is planned for 15–20 participants, Leeman said. Earlier studies have found that psilocybin trips coupled with therapy can help people rapidly reframe their traumatic memories and alleviate their distress.

The study is designed so that everyone who enters it can eventually receive psilocybin, he said. "This is an issue with randomized controlled trials, especially if you take people that are in emotional pain," he said.

Study participants who desperately hope a trial medication will alleviate their distress may actually feel worse if they receive an inactive placebo. "It's like a negative placebo—a nocebo," Leeman said.

UAspire will follow participants for 54 months, randomizing some participants to 25 mg of psilocybin—a moderate-to-high dose—while others will receive a smaller 5 mg dose or an inactive placebo.

"In six weeks, you get re-scored for depression, and if you meet the criteria then, without anyone knowing what you got in the randomized portion, you become able to be re-dosed in the open label session for a total of four times in the next year," he said.

"It's a really pragmatic trial," Leeman said. "Even if you do your session and don't feel like you have the active drug, you know that in six weeks, if you're still depressed, you'll receive the 25 mg psilocybin dose. I think this will minimize the likelihood of their depression worsening if they believe they did not receive psilocybin."

The new studies join Leeman's existing research project to study whether therapy coupled with MDMA—better known as "Ecstasy" or "Molly"—can help postpartum mothers with opioid-use disorder overcome their addictions. The hope is that MDMA sessions facilitated by trained therapists will alleviate the PTSD symptoms that often drive illicit drug use, Leeman said.

The studies are carried out at the Interdisciplinary Substance Use and Brain Injury Center (ISUBI), adjacent to Pete & Nancy Domenici Hall on UNM's North Campus, he said. ISUBI can accommodate overnight stays for MDMA-assisted therapy and day-long stays for other psychedelic therapy studies, enabling studies requiring that patients be observed for a period following their treatment to be in a safe, supportive setting.

UNM Health Sciences psychedelic research dates back to the early 1990s, when Rick Strassman, MD, an associate professor in the Department of Psychiatry & Behavioral Sciences, studied psilocybin and DMT—the active ingredient in ayahuasca, Leeman said.

More recently, UNM researchers, including Snehal Bhatt, MD, professor of Psychiatry and chief of the Division of Addictions Psychiatry, played a major role in a widely reported 2022 study reporting that psilocybin-assisted therapy helped people overcome alcohol use disorder.

Now, Bhatt is taking part in the KMD (Ketamine for Methamphetamine Dependence) study, a multi-site evaluation of ketamine as a treatment for methamphetamine addiction. Ketamine is an anesthetic whose dissociative properties have sometimes led to its abuse as a recreational drug, but it has also been found to rapidly alleviate depression symptoms.

The safety and efficacy study, run through the National Institute on Drug Abuse (NIDA) Clinical Trials Network, involves four sites and seeks to enroll 30 participants at each location over two years, Bhatt said.

"Methamphetamine, in particular, is posing a huge public health challenge," he said. "Here in New Mexico and around the country the rates are just going up." At the moment there are few effective treatments for methamphetamine addiction, he said, but there is hope that ketamine might be a game-changer.

"Some artificial intelligence algorithms that NIDA used actually showed that ketamine is one of the more promising treatment approaches," Bhatt said. "One of the big priorities at NIDA is co-occurring depression, because you do see that a very high proportion of people using methamphetamine have depression."

Some participants will undergo two 40-minute infusions of ketamine per week for three weeks, then one per week in week four and week six. The others will receive similar infusions of an active placebo called midazolam, a sedative and anesthetic. Participants will be followed for 12 weeks and submit urine samples to reveal whether they had used methamphetamine, he said.

"The primary endpoint is looking at reductions in methamphetamine use within weeks five and six—that maintenance infusion period at the end of the active treatment," Bhatt said. "We'll also be tracking meth use all the way up to week 12. That's part of the secondary outcome, to see if the effects persist or if they wash away."

Study participants will be recruited from both UNM and community treatment clinics. "We want to make it available to our patients," he said. "It's going to be one of those big, all-hands-on-deck outreach efforts to make those connections, and if someone's interested, really get them enrolled in a timely way."

Provided by University of New Mexico