Psilocybin — the psychedelic component in “magic mushrooms” — is one of multiple psychoactive substances currently researched at the University of Wisconsin-Madison Transdisciplinary Center for Research in Psychoactive Substances (TCRPS). While psychedelics have been utilized by indigenous communities throughout history, academic and scientific studies of these compounds reemerged after many government-funded studies on LSD were shut down in the 1970s and 1980s.
Psychoactive substances — the director of the center, Dr. Paul Hutson’s term of choice — refers to a general class of drugs that have hallucinogenic and non-hallucinogenic effects. Psychoactive substances may have a wide range of direct applications, such as treatment for mental health disorders such as PTSD, OCD or depression as well as in the treatment of substance abuse disorder and addiction. Hutson, a researcher in the UW Madison School of Pharmacy, was drawn to the field of psychoactive substances research through his work in cancer research and palliative care.
“The data from one dose of psilocybin seems to suggest that there is a substantial benefit for many persons with depression, at least as good as from SSRIs like Prozac, with fewer side effects,” Hutson said. “Not everybody improves — it's not a magic bullet, but it does have a substantial response rate.”
The goal of the center is to foster education and research around these areas and cultivate collaborations across campus and within Wisconsin communities, according to Hutson.
“We are trying to reach across the campus in a rather unique way, so we have four academic centers in this space … the College of Letters and Sciences, CALS, Asian Studies, Latin American and Caribbean studies, the School of Human Ecology and the School of Nursing,” Hutson said.
The center currently has five active clinical studies and two studies awaiting activation in psychedelic research. Dr. Randall Brown and Dr. Christopher Nicholas both serve as members of the center’s executive committee and co-principal investigators in several of the clinical studies.
A recent study from the NYU Center for Psychedelic Medicine has shown that psilocybin and psychotherapy contributed to an 83% reduction in heaving drinking. Similar research at Johns Hopkins indicated that psychedelics can help longtime smokers quit. Past studies at UW-Madison argued for the now standard dose of psilocybin, and also supported evidence from other groups that improve symptoms of depression and anxiety when administered after appropriate preparation and in a controlled setting. Similarly, MDMA has been shown to provide improved response rates when combined with psychotherapy for PTSD treatment in a controlled setting.
Perhaps most interestingly, researchers at the TCRPS are studying whether individuals need to remember their psychedelic “trip” in order to have transformative effects. In other words, does the psychedelic itself allow a mind-altering therapeutic benefit, or are hallucinogenic “trips” themselves necessary? By administering psilocybin with physician-administered doses of midazolam, a drug that is intended to block the memory of the psychedelic trip, researchers should soon have a greater understanding of the role of memory in psychedelic experiences, according to Nicholas.
“If [patients] don't remember their experience, but still show improvement on measures of well being and behavior change, then we can say, well, some part of the way psychedelics works is through the psychopharmacology and not just the subjective personal meaning that they get from them,” Nicholas said.
In order to participate in psilocybin studies, patients must be medically cleared before the psychedelic experience to ensure safety. In preparation for the experience, “facilitators,” trained individuals who administer the drugs and attend to the participants, build rapport and trust with the participant. EEGs and MRIs are used to measure brain activity during and after some sessions. Dosing sessions last several hours to a day. Directly after and often weeks later, patients are debriefed and the impact of their experience is discussed.
One of the difficulties in conducting psychedelic research is the personnel time and uptake for each patient and participant. According to Nicholas and Brown, two facilitators spend approximately 40 hours with each participant across the entirety of the study — meaning 80 hours of personnel costs per participant. While this is a considerable financial cost, this amount of time is to ensure safety, even though it does require a significant commitment from the participant.
“Speaking to recruitment, yes, we absolutely want to improve and optimize our ability to bring in a diverse representation of participants across all important demographics,” Nicholas said. “We want to find out how generalizable this work really can be clinically and how many people this work can really be an appropriate treatment for.”
Psychedelics are used in three predominant ways: recreationally, for spiritual traditions and for research in FDA and DEA accepted clinical studies. Hutson believes that understanding all uses of the drugs helps inform future medical and legal classifications.
“We've got these three groups, all of whom at this point feel that there is a substantial benefit from psychedelics,” Hutson said. “If we are to get this to the FDA for approval, the FDA is going to be aware of the sacramental uses of psychedelics, they are going to be aware of the recreational use of psychedelics, but they are going to require well controlled clinical studies to support any request for psilocybin to be approved as a new drug and rescheduled from a Schedule I drug to something more accessible.”
Schedule I drugs are characterized by having high potential for abuse, with little to no medical purposes. Research at the UW-Madison TCRPS is slowly starting to disprove both aspects of the Schedule I classification. Hutson believes the FDA medical approval for MDMA as a treatment for PTSD and psilocybin as treatment for depression will occur either in 2024 or 2025.
While there has been national attention surrounding the decriminalization and legalization of psychedelic drugs, Oregon remains the only state with a proposal to make psychedelics legal under supervision starting in 2023. When medically legal, the high costs to access psychedelics clinically may exacerbate inequalities in healthcare.
“We have high hopes for these medicines becoming integrated with mainstream health care. I think we have a lot to learn and work to do by way of informing what that looks like to ensure equitable access [and] to ensure that, for example, public insurances might cover therapies that have demonstrated benefit for particular conditions,” Brown said.
As the use of psychedelics expands, the qualifications necessary to facilitate and prescribe psychedelics have also come into question.
“There's still a lot of questions on what would be the required training to work with these substances both as a prescriber and someone who would [facilitate] these compounds therapeutically,” Nicholas said. “Oregon has developed their own criteria for what that is going to look like from a [legalization and] decriminalization standpoint. But the credentialing and licensure criteria that would be required is still very much unknown.”
The TCRPS started an online graduate program last school year within the UW Madison School of Pharmacy — the Master of Science in Psychoactive Pharmaceutical Investigation — to help educate future leaders and facilitators in the field. Brown and Nicholas also encourage undergraduate students with an interest in the center’s research to get involved.
“We're hoping that psychedelic research can be an opportunity for students to get involved to help with studies, look at data or come up with questions that they may have,” Nicholas said. “We care about doing this in an academic institution. We want to make sure that this involves trainees at all different levels.”
Noe Goldhaber is a staff writer for the Daily Cardinal specializing in campus and state news reporting.