Exploring psychedelics: Understanding variability in treatment responses

(Press-News.org) WASHINGTON — Psychedelic compounds such as psilocybin, a substance found in various mushroom species, are garnering more research support as novel treatments for psychiatric disorders, but questions remain concerning who they may help the most. The findings will be presented on Tuesday, November 14, 1–2 p.m. at Neuroscience 2023, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.

Psychiatric disorders, including phobias, post-traumatic stress disorder (PTSD), depression, and substance use disorder, represent a major public health issue. Current behavioral and pharmacological treatments have limited efficacy for some individuals. Researchers are looking to novel therapeutic approaches, including the use of psychedelic compounds. Interest in psychedelic treatments is growing; the US Food and Drug Administration has recently given breakthrough drug status to some psychedelic compounds for the treatment of depression and PTSD. However, the underlying biological mechanisms of these substances — and which patients and conditions could benefit from them — are still largely unknown. Researchers are working with animal models to answer questions about the therapeutic actions of psychedelic compounds.

New findings show that:

Psilocybin treatment had opposite effects on fear extinction learning in male and female rats (Phillip Zoladz, Ohio Northern University) Psychedelics including psilocybin and DMT may have different effects on fear learning dependent on dose and sex in mice (John Razidlo, University of Wisconsin, Madison) Psilocybin treatment reduced signs of physical withdrawal in a mouse model of nicotine addiction (Belle Buzzi, Virginia Commonwealth University) “Studies suggest that certain psychedelic compounds show promise for treating a range of psychiatric disorders,” says Frederick Barrett, director of the Johns Hopkins Center for Psychedelic and Consciousness, who studies the mechanisms underlying the effects of psychedelic drugs. “The research presented today is crucial in understanding what factors may influence the efficacy of these compounds, including sex, dose, and timing of administration.”

This research was supported by national funding agencies including the National Institutes of Health and private funding organizations. Find out more about social behavior and the brain on BrainFacts.org.

Tuesday, November 14, 2023

1–2 p.m. EST

Walter E. Washington Convention Center, Room 202B

Psychedelic Drugs Press Conference Summary

Research in animal models suggests that the effects of psychedelic compounds may be influenced by sex, dose, and other factors. Research in rats shows that psilocybin treatment can reduce physical symptoms of nicotine withdrawal. Low-dose psilocybin sex-dependently enhances fear extinction in adult rats
Phillip Zoladz, p-zoladz@onu.edu, Abstract PSTR162.03

Fear-related psychological disorders such as phobias and post-traumatic stress disorder are associated with excessive responses to fear memories. Researchers treated rats with the psychedelic compound psilocybin after training them to associate a sound with a fear-inducing stimulus. Male rats learned that the tone no longer predicted the foot shock more quickly when treated with psilocybin. Conversely, female rats were slower to learn that the tone did not predict a shock when treated with the psychedelic. The findings suggest that the ability of psilocybin to aid in behavioral therapies for fear-related psychological disorders may depend on the sex of the individual. Differential modulation of threat assessment by psilocybin and DMT
John Razidlo, jrazidlo@wisc.edu, Abstract PSTR162.02

The psychedelic compounds psilocybin and N,N-dimethyltryptamine (DMT) have been shown to exert rapid antidepressant effects, though the underlying mechanisms are not fully understood. Researchers showed that psilocybin did not change the rate of fear learning or extinction of learned fear in mice. Male mice that received psilocybin showed reduced contextual fear reinstatement when compared to female mice that received psilocybin. Mice treated with DMT showed impaired learning of fear extinction once the threat had been removed. More research is needed to understand any time, dose, and sex-dependent effects of psychedelics, as well as their effects on fear-associated learning. The effect of the psychedelic psilocybin on nicotine dependence behaviors in preclinical models
Belle Buzzi, buzzib@vcu.edu, Abstract PSTR105.08

In a mouse model of nicotine dependence, animals that received psilocybin upon cessation of nicotine showed a reduction in signs of physical withdrawal. In mice that were genetically modified to not express the serotonin 2A receptor, which is important for the subjective effects of psychedelics, psilocybin did not reduce nicotine withdrawal symptoms.  The mice were also less sensitive to the rewarding effects of nicotine. Results suggest that psychedelics such as psilocybin may be effective as a potential smoking cessation therapy, and that the serotonin 2A receptor is important for this effect.

###

The Society for Neuroscience (SfN) is an organization of nearly 35,000 basic scientists and clinicians who study the brain and the nervous system.

END