David Olson is the founding director of the newly launched Institute for Psychedelics and Neurotherapeutics at the University of California, Davis. Olson spoke with Erin about the prospect of developing next-generation non-hallucinogenic versions of drugs like psilocybin to treat brain disorders like depression, post-traumatic stress disorder and addiction and the regulatory barriers his research is up against. The interview is edited for length and clarity. Psychedelics startups and research centers seem to be popping up everywhere. What makes yours unique? Psychedelics are remarkable compounds in that they have profound effects on the brain. What the institute wants to do is understand the molecular and circuit-level mechanisms that allow psychedelics to do what they do and then reverse translate that to produce better, safer and more effective therapeutics that can be more widely accessible to a greater patient population. Several years ago, we had the idea that maybe we could separate the subjective effects of psychedelics from some of their beneficial effects on neuroplasticity and their antidepressant-like effects. We call those types of next-generation compounds nonhallucinogenic psychoplastogens. We believe those might be more scalable alternatives [to hallucinogenic psychedelics] that could be take-home therapies. By making molecules that are safe enough that you can take them home and put them in your medicine cabinet, you might be able to reach a larger patient population. You’re studying psychedelics and their analogues as potential treatments for depression, PTSD and addiction. Can you explain how that works? All of those disorders share a very interesting commonality. If you look at the part of the brain called the prefrontal cortex, if you look at the neurons in that brain region, they tend to look atrophied — their branches are retracted, their synapses have been pruned away. That’s really important because that brain region communicates with other brain regions that control fear, motivation, reward and cognition. The hypothesis for many years has been that if you can find a compound that can regrow those atrophied neurons, you can have a very broadly efficacious therapeutic. When we started studying psychedelics, we were looking for these plasticity-promoting compounds. And in 2018, we published a paper showing that they were really, really good at this. The other thing I want to emphasize is that cortical atrophy lies at the heart of many brain disorders. Right now, we’re focused on neuropsychiatry, but we’re moving in the direction of neurodegeneration — think Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia. There’s a lot of potential to actually reverse some of this — we think — some of the atrophying before the cells die. Controlled substances are notoriously difficult to research. Have regulatory barriers affected your research? In order to be able to work with these compounds, you have to be willing to do a lot of paperwork. You have to get licenses from both the federal and state governments. That has drastically limited the number of investigators that can be involved in this type of work. But at the end of the day, aren’t these substances controlled for a reason? They’re powerful substances that impact the brain. They need to be respected as such. But we also need to be able to understand how they do what they do if we’re ever going to fully understand how the brain works. I’ll give you a pretty shocking example. It’s easier for me to study the effects of cocaine than psilocybin. There’s less red tape, it’s cheaper, more efficient, I could do it quickly. That doesn’t make a whole lot of sense to me.
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