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What Is the Future of Psychedelic Treatments?

Hopes and concerns from the front lines of psychedelic research.

The following interview with neuropharmacologist and pharmacist Cody Wenthur addresses some developments in psychedelic treatments and modern society. Dr. Wenthur's research lab is dedicated to multidisciplinary, translational approaches aimed at improving treatment for psychiatric illnesses, particularly substance use disorders and major depressive disorder.

In 2021, we are in the midst of what some commentators are calling a "psychedelic renaissance." To begin with, where do you fit within the current moment?

I’m currently a primary investigator and assistant professor at the University of Wisconsin, where I have been fortunate enough to join a large, transdisciplinary, group of scientists and scholars actively engaged in the study of psychedelics. The expertise within this group ranges from ecological to psychosocial, from historical to transcendental, but my own research role is focused on connecting molecular effects with functional behavioral outcomes.

In tandem with this research effort, I am also extremely excited to debut as the director of our Master’s degree option in Psychoactive Pharmaceutical Investigation, which will start its first class in Fall 2021.

What's the nature of your work at present and how are you attempting to improve mental health?

Starting from my earliest clinical and scientific training up to the present day, my research interests have long focused on understanding how the actions of psychoactive small molecules can lead to profound, long-term changes in behavior. Unfortunately, some of our most obvious examples of this phenomenon, such as the development of substance use disorders, are incredibly damaging to both mental and physical health. My lab’s major projects are thus centered on developing approaches that can mitigate or reverse the effects of harmful learned and habitual behaviors.

On one hand, this includes the use and development of "vaccination" approaches that prevent psychoactive small molecules from engaging with their targets in the brain, and on the other hand, includes the application of compounds like psychedelics that seem to open up a window of neuronal plasticity.

Considering psychedelics specifically, we are currently using a combination of pre-clinical and human studies to understand how physiological effects, such as cortisol release, and psychological effects, such as altered perception and meaning, act to modify the magnitude and duration of psychedelic-induced behavioral changes. As someone whose introduction to laboratory science traversed through investigation of serotonin signaling before continuing on to glutamate effects on learning, I continue to be especially interested in our ongoing projects that look at how and where the mechanisms of rapidly acting antidepressants from entirely different classes, such as psilocybin and ketamine, may overlap or converge.

Psychedelic science and medicine seem to be advancing on several fronts. What are you watching closely?

There are fascinating developments occurring across the board, but I’m particularly intrigued by studies that assess the intersections and impacts of the obviously altered conscious experiences versus the hidden molecular effects promoted by psychedelic compounds. Recent progress in identifying psychedelic analogues that promote neuronal plasticity, but don’t appear to induce altered states of perception, seems likely to result in especially useful tools for addressing whether experiencing particular types of phenomenological content are essential to support long-term change.

I also remain interested in following how the psychedelic-assisted psychotherapy model inspires additional approaches that combine the induction of neuroplasticity with proven non-pharmacologic therapies that provide improved cognitive and behavioral coping strategies. As psychedelic-assisted psychotherapies continue to be assessed across more and more traditional categories of psychiatric illness, it will likewise be intriguing to see whether this overall approach is broadly beneficial, particularly as it might serve to support their use as cross-cutting neuroscientific tools that would help inform the development of more physiologically-driven and reproducible diagnostic approaches in mental healthcare.

What are some of the current problems or challenges in psychedelic science and medicine?

The psychedelics working group at UW-Madison and I gave a lot of recent thought to this exact question as we worked through how our new master’s program could meet the ongoing needs of the field.

One critical challenge we quickly identified was to ensure that psychedelic science maintains the highest possible level of objectivity and integrity throughout its current growth phase. As the field expands beyond academic research settings into the broader pharmaceutical industry, there will be a continuing need for researchers that have been trained to understand the unique scientific, regulatory, sociocultural, and ethical considerations required to carry out high-quality studies in this space.

In one immediately relevant example, new participants in the field need to have an in-depth understanding of how psychedelic-enhanced meaning effects may influence trial design, especially as altered outcome expectations of clinical trial participants may emerge in response to the reports of "unprecedented" effects that are making their way into the public consciousness.

Another serious challenge is the field’s scientific and ethical duty to increase focus on historical and current sociocultural issues surrounding diversity, equity, and inclusion in the psychoactive pharmaceutical research space. Psychedelic-assisted psychotherapy studies to date have not been representative of broader U.S. demographics, and contributions of researchers, scholars, and stewards of traditional knowledge from underrepresented communities have often been minimized.

To give another example of how this broad concern is immediately relevant to the field at large, since self-identity can intersect with both participant mindset and receptivity to the treatment setting, this lack of diversity and inability to easily measure its effects directly risks the development of insufficiently generalizable protocols for widespread and equitable clinical use in the event of regulatory approval.

To address this challenge, I believe the field needs increased educational coverage and awareness of these issues, more engagement with community-partners and focus on health equity studies, and focused opportunities that promote the entry and success of individual researchers that have underrepresented backgrounds, and our research and education programs continue to work toward dedicated support on each of these fronts.

Thanks so much for your time, Cody!

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