Jeffrey Nicol ’25 admits his interest in psychedelic medicine and research, piqued during his undergraduate years in neurobiology, may still be viewed as on the fringe of science because of the psychedelic counterculture in the 1960s. But in the past 10 years or so interest in using psychedelic assisted therapy in psychiatry has accelerated along with research findings published in respected journals such as Nature Medicine and JAMA Psychiatry, among others.
Listening to podcasts about mental health while at University of California, Berkeley, Nicol became aware of emerging data on the resurgence of psychedelic science, “the data was striking, the stories were moving, and the science was exciting,” he recalls. Wanting to learn more, he “read every piece of literature I could get my hands on and soaked up the available information about this.
“I was convinced that this science would significantly alter the psychiatric landscape over the course of my career, and I wanted to be part of it as it unfolded.”
After graduating from Berkeley, and while applying to medical school, Nicol joined a research group at University of California, San Francisco, spending a gap year working on a Phase 3 trial of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for treatment of patients with post-traumatic stress disorder (PTSD).
He was hooked.
When he arrived at Geisel School of Medicine, Nicol sought out and began working with Wilder Doucette, MD, an assistant professor of psychiatry, who engages in pre-clinical work with psychedelics in rodent models. They are exploring pairing psychedelics with external brain stimulation techniques.
“We aren’t proposing psychedelics as a replacement for everyone in psychotherapy, but more as an alternative entry point into this treatment space,” Nicol says.
Exactly how psychedelics work is complicated and still being explored, but existing data supports the benefit of pairing psychedelics with proven therapies for people with diagnoses of depression, anxiety, or PTSD.
“Psychedelics are both anti-inflammatory and affect brain connectivity by freeing established networks and increasing information flow with a lot of crosstalk resulting in powerful suggestive experiences, often referred to as mystical,” Nicol explains. “Studies found that higher degrees of mystical experiences are correlated with increased therapeutic benefit when it comes to psychedelic assisted psychotherapy.”
Initially, the effect of psychedelics was thought to last only several hours during the time patients experience the drug, but data indicates the effects can last up to one year after a few therapeutic sessions—with smoking cessation and alcohol use disorders for example.
“In psychiatry, some psychiatric diseases are thought to be connected to maladaptive circuitry. If that circuitry can be changed, it may be able to get people out of depression thought spirals, anxiety spirals, and PTSD symptomology,” Nicol says.
“There are different theories of why this is helpful—a combination of the neuropharmacology of what is going on in the brain along with the subjective experience a person is having when under the influence.”
The psychedelics used in these studies, Nicol notes, are serotonergic, such as LSD and psilocybin, and produce a potent neuroplasticity inducing effect, meaning new cell growth in the brain. In this malleable state, neurons forming new connections are primed to grow and existing connections can change.
“All of your neurons are ready to make new connections and in the acute setting there are changes in your thinking and in your brain processing,” he says. “Without this plasticity, your brain would settle from that high energy state into the pathways of your normal brain state.
“But in this heightened state, some people have insights, realizations, and changes in their thinking. The theory is if your brain settles in this state maybe some of the circuitry responsible for depression or anxiety may be altered and reform around a new way of thinking that is less maladaptive. Our proposition is that by introducing this external stimulus of psychotherapy helps guide that unique brain state from point A to point B.”
While the data at this point is undeniable, it needs further study. Though Nicol says there are caveats that are important to acknowledge. One is that these are difficult substances with which to do a blind trial. Normally in clinical trials, the gold standard is a double-blind trial where neither the participants nor researchers know which participants are receiving the drug or placebo. But with a psychedelic it becomes immediately apparent an hour into the session.
“Again, the exact mechanisms of action are still being worked out,” Nicol says, “but I do think psychedelic therapeutics combined with proven psychiatric therapy can produce long-lasting benefits.”
Nicol discussed research on the benefits of psychedelic therapeutics during his medical student grand rounds presentation—The Therapeutic Potential of Psychedelics: Theories of Action and Future Directions.
