Psychedelic drugs, often associated with 1960s counterculture, are attracting newfound attention from physicians and neuroscientists studying their potential to help people suffering from various behavioral health problems.
University of New Mexico Health Sciences researchers are at the forefront of several new studies evaluating 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. He also serves as medical director for UNM’s Milagro Program.
“The exciting thing about [RE104] is it has the potential to quickly reverse postpartum depression,” Leeman said.
RECONNECT is a Phase 2 multi-center study of RE104 – a novel compound related to psilocybin – for postpartum depression, which affects about 13 percent 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 1/2 hours. “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. Psilocybin has been shown to affect 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.
RE104 is also being explored for treating patients with life-threatening cancer diagnoses who are experiencing depression and anxiety. Leeman expects UNM will probably participate in that study starting in 2025.
The other new study, dubbed uAspire, is a Phase 3 randomized double-blind multicenter project assessing the potential benefits of psilocybin for major depressive disorder. UNM’s portion of the study is planned for 15-20 participants. 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. “This is an issue with randomized controlled trials 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 weeks, 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 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.”
The new studies join Leeman’s existing research project studying whether therapy coupled with MDMA can help postpartum mothers with opioid use disorder overcome their addictions. The hope is that MDMA sessions facilitated by trained therapists will alleviate PTSD symptoms that often drive illicit drug use.
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. ISUBI can accommodate overnight stays for MDMA-assisted therapy and day-long stays for other psychedelic therapy studies enabling studies requiring patient observation following treatment to occur in a safe setting.
UNM Health Sciences' psychedelic research dates back to the early 1990s when Rick Strassman studied psilocybin and DMT – ayahuasca's active ingredient.
More recently Snehal Bhatt played a major role in a widely reported 2022 study reporting that psilocybin-assisted therapy helped people overcome alcohol use disorder.
Now Bhatt participates in KMD (Ketamine for Methamphetamine Dependence), evaluating ketamine as treatment for methamphetamine addiction through NIDA Clinical Trials Network involving four sites seeking to enroll 30 participants each over two years.
“Methamphetamine poses huge public health challenges here in New Mexico and around the country; rates are going up.” At present there are few effective treatments but there is hope ketamine might be game-changing.
“Some artificial intelligence algorithms NIDA used showed ketamine as promising treatment approaches.” One priority at NIDA is co-occurring depression since high proportions using methamphetamine have depression.
Participants undergo two weekly infusions over three weeks then weekly during week four-six followed by midazolam sedative-anesthetic infusions monitored over twelve weeks submitting urine samples revealing methamphetamine usage.
“The primary endpoint looks at reductions within weeks five-six maintenance infusion period tracking usage up till week twelve secondary outcomes persist/wash away.”
Participants recruited from both UNM/community clinics aiming timely enrollment outreach efforts connecting interested parties enrolled timely way.
People interested participating Reconnect/uAspire/MAT-POD contact reconnect@salud.unm.edu/uaspire@salud.unm.edu/matpod@salud.unm.edu eligibility details respectively.
