The newly christened Translational Psychedelic Research (TrPR) Program is launching a unique multidisciplinary network of scientists and healthcare providers who work together to research psychedelic-assisted therapies.
The TrPR Program, which is based at UCSF, is distinguishing itself from other university research groups through its distinctively inclusive approach to psychedelic medicine. Members of the TrPR network study psychedelic therapies that may benefit patients with conditions considered higher risk or overlooked by other researchers in the field, such as bipolar disorder, Parkinson’s and back pain.
TrPR includes investigators from both clinical and research disciplines based at medical centers from the San Francisco Bay Area to Seattle, says Dr. Joshua Woolley Associate Professor of Psychiatry at the UCSF Weill Institute for Neurosciences and Director of the Translational Psychedelic Research Program.
“I think our unifying goals are to understand if these treatments work, who they work for and how they work,” says Woolley.
Dr. Ellen Bradley, associate director of TrPR, says the program’s interdisciplinary team includes different perspectives that will help strengthen the research. “It’s kind of ever evolving,” says Bradley. “We’re really lucky we have a group that spans multiple medical specialties.”
The TrPR Program includes researchers with expertise in psychology, neurology, epidemiology, animal science, molecular science, even primary care and nursing. “It’s really exciting,” says Bradley. “I think it gives us a great advantage of how to design some of the studies and answer some really interesting questions.”
The TrPR team is reaching out to other programs and institutions. Bradley says that she is excited to see the UCSF Neuroscape neuroscience center begin to research psychedelic therapies and hopes to work with these investigators on future studies. Woolley says he has been talking with Neuroscape Director of Psychedelics Division, Robin Carhart-Harris, about possible collaborative projects.
“What brings everyone together is the motivation to really deepen our understanding of how psychedelic compounds impact the body and to figure out how psychedelic therapies can help patients living with a wide range of health issues,” says Bradley. “There’s just a ton of science to be done in this space, so the more folks who can roll up their sleeves and jump in, the better!”
A Pivotal Study on AIDS Survivors
Some members of TrPR were investigators in a pivotal study published in late 2020 that examined the effectiveness of psilocybin-assisted group therapy for demoralized older long-term AIDS survivors. The open-label safety and feasibility pilot study, which laid the groundwork for TrPR, looked at grief, guilt, and loss of purpose and meaning among participants, says Woolley.
The study focused on gay men who had been diagnosed with AIDS before 1996. “The people were older than many of the other trials, and there was more variability of severity of illness,” says Woolley. “It was more naturalistic.”
According to Woolley, there were a number of reasons to integrate group therapy into the study of older AIDS survivors. It was a more time and cost efficient way to integrate talk therapy, but it also followed indigenous practices in which people use psychedelics in a group setting. “There might be power in that, a group of people going through it together,” says Woolley. “They could talk about that experience with each other.”
Woolley notes that participants in studies at John Hopkins University investigating psychedelic-assisted therapies had wanted to talk to other participants in the same study. “In a Prozac study, that never happened,” says Woolley.
The study of AIDS survivors gave Woolley and his team significant momentum in the psychedelic research space. The TrPR Program is currently working with the Usona Institute on a clinical trial to study the medical and safety effects of psilocybin on patients with Major Depressive Disorder (MDD). This Phase 2 clinical trial is also taking place at seven other sites across the U.S.
The Usona clinical trial may be the highest profile investigation the TrPR Program has in progress, but the team is also pursuing other cutting edge research. According to Woolley, an upcoming open-label study of psilocybin for depression in bipolar II disorder is a strong example of the program’s philosophy toward working with patients with different risk profiles.
“One thing we are doing that is a little different than other groups is working on populations that are a little bit higher risk,” says Woolley.
Studying Psilocybin Treatment for Bipolar Disorder
Bipolar II disorder is a mental health condition which includes both depression and mania. According to Woolley, depression sometimes has a larger impact on people with bipolar disorder than the episodes of mania.
Psilocybin has been shown in studies to be a promising antidepressant. But Woolley notes that there are concerns about possible negative effects if psilocybin is used to treat people with bipolar disorder because of its potential effect on mania. Accordingly, people with bipolar disorder, as well as people with relatives who have bipolar disorder, have been excluded from modern psilocybin studies.
After completing a survey study to address these questions, the TrPR team concluded that while there are cases of bad outcomes from people with bipolar depression using psilocybin, these outcomes are limited to just a few cases over decades, says Woolley.
The mixed-methods study, which included a survey of about 600 people with bipolar disorder who used psychedelic mushrooms, was conducted in collaboration with Dr. Erin Michalak of the University of British Columbia’s Department of Psychiatry. The survey was followed by interviews with participants to obtain more qualitative information. The TrPR team even combed through relevant subforums on Reddit for anecdotal accounts.
“That community driven aspect is key,” says Bradley. “We’re not just doing a top-down, academic study. We’re trying to combine our team of specialists, but also rely on how people are already using these substances in the community.”
Bradley notes that the members of the TrPR team are well positioned to examine how psilocybin is presently used for self-medication and include this information while researching its therapeutic applications. “These treatments are not formalized in our healthcare system, but people are using these treatments out in the world,” says Bradley. “People are figuring out what works for them, what’s safe for them. That’s really, really important to listen to. It’s valuable to integrate those perspectives.”
The mixed-methods study is informing upcoming research investigating the use of psilocybin on depression in bipolar II disorder, conducted by the TrPR team in collaboration with Dr. David Gard, director of the Motivation and Emotion Research Lab at San Francisco State University. Safeguards will include overnight observation of participants, a support person who sees participants daily and investigators checking on them routinely in a controlled environment.
“This has never been tried before, and there is some risk, but we think the potential for benefits is very high,” says Woolley. Bradely adds that the TrPR team is committed to seeking therapies for a broad range of people with mental health conditions. “We can’t just cherry pick the people who are the most healthy,” says Bradley. “We want to see people that are at risk potentially, but also could really benefit.”
Seeking Therapies For Higher Risk Groups
Another example of TrPR’s commitment to researching treatments for higher risk groups is the upcoming open-label trial of psilocybin for treating depression and anxiety in patients with Parkinson’s disease. This study is being conducted in collaboration with Dr. Jill Ostrem, medical director and division chief of the UCSF Movement Disorders and Neuromodulation Center.
As with people suffering from bipolar disorder, those with Parkinson’s can also experience a decreased quality of life. They are impacted by depression and anxiety more than one might realize, says Bradley. “I spend my time working with patients who have Parkinson’s,” says Bradley. “We don’t have great treatments for these patients, and a lot of them are suffering and frustrated by that.”
The TrPR Parkinson’s research will also be carefully monitored, with overnight observation and participants receiving a low test dose before getting a full dose. “It’ll be a small, open-label pilot, and it will involve quite a few precautions,” adds Bradley. “Something really important is a serial assessment of [participants’] motor symptoms to make sure there are no negative effects there.”
Another unexpected clinical trial launched by TrPR is a study of psilocybin as a possible treatment for lower back pain. “This population is not a particularly high risk population, but it is a novel population,” says Woolley.
According to Woolley, chronic lower back pain is a condition without a fully effective treatment for how people experience this pain. The study will look at how psilocybin might change the relationship between patients and their discomfort rather than seeking to reduce the pain itself. “We’re agnostic as to its effects on the intensity of the pain, but we’re hoping that will go down as well,” says Woolley.
Woolley says that Dr. Boris Heifets at the Stanford University School of Medicine Heifets Lab and Michael Silver, principal investigator at the Visual Neuroscience laboratory at the University of California, Berkeley, are close collaborators on the pain study.
“The pain study is really exciting because the development of chronic pain is not well understood,” says Bradley. “It’s physical, it’s emotional, it’s both of these things rolled together.”
Bradley notes that while psilocybin shows promise as a therapy that could potentially rewire neurocircuitry that’s gone awry, there are still many biomechanical questions that must be answered. The back pain study will give the TrPR Program the ability to look at the condition from a variety of perspectives, from psychological to molecular.
The bipolar II disorder, Parkinson’s and chronic back pain studies have all received UCSF Institutional Review Board (IRB) approval, which is required by the FDA to review and monitor biomedical research involving human subjects, says Woolley. He says these studies are expected to begin in the spring or summer of 2021.
An Inclusive Approach To Funders and Volunteers
The most significant financial support for the TrPR Program is a $2 million donation from a donor who wishes to remain anonymous, says Woolley. TrPR also received an additional $1 million in funding from Usona for its participation in the Institute’s psilocybin trial.
The TrPR team is presently in talks with academic and industry partners for future financing, says Woolley. As the academic study of psychedelics is still relatively new, he says these investigations do not get the types of government funding that other forms of medical research receive. Some of the funding for TrPR comes from smaller contributions from individual donors.
One individual donor to TrPR is Cassie Nielsen, who contributed funds and volunteered to assist the program by creating a database of researchers investigating psychedelics. Nielsen is a Talent Partner at VMG Partners, a private equity firm focused on consumer products. “He created an environment where I, as a random outsider, could join,” says Nielsen of Woolley. “It felt like I could have a voice in his room.”
Nielsen says she began her own personal research into psychedelic-assisted medical therapies because she has a family member who battles alcoholism. She began investigating podcasts, books and conferences on the subject until she found an article about Woolley and his team. “I reached out cold and said, I’m not sure how I can be supportive or if there’s ways I can volunteer with what you’re doing,” says Nielsen.
At first, Nielsen says the TrPR team was surprised that someone outside of the research or medical community was interested in volunteering, but they were happy to accept her support. Nielsen in turn says she was surprised and delighted. That was two years ago, and Nielsen is still helping to support the TrPR Program. In addition to helping create a database of researchers, she has also offered suggestions on how the team can present job descriptions and broaden the program’s exposure.
“I believe in [Woolley] and his team. He’s built an incredible team around him,” says Nielsen. “He gives his folks a lot of autonomy. He’s receptive to their ways of thinking.”
Nielsen has contributed $15,000 in unrestricted donations to the TrPR Program – $5,000 in 2019 and $10,000 in 2020 – and she expects her contributions to increase. Nielsen says she is encouraged that medical research into psychedelic-assisted therapies is increasingly visible.
Efforts to decriminalize psychedelics are also having a positive impact on access to these therapies by veterans, people of color and other underserved communities that have medical conditions psychedelic-assisted therapies could treat, says Nielsen. From her perspective, the inclusivity of TrPR is another sign of progress.
This story has been updated.
Main image: Nicki Adams