The Classical Psychedelic Psilocybin Reduces Nicotine Withdrawal: Initial Mechanisms

Authors

Belle Buzzi, Virginia Commonwealth University

Original Publication Date

2024

Document Type

Presentation

Comments

10th Annual VCU 3MT® Competition, held on October 4, 2024.

Abstract

This presentation explores the potential of psilocybin, a classical psychedelic, as a treatment for nicotine addiction. The research uses mouse models to examine psilocybin’s effects on nicotine withdrawal, a key factor in relapse. Findings show that psilocybin reduces withdrawal symptoms to control levels, an effect dependent on activation of the serotonin 2A receptor. These results suggest psilocybin may offer a novel therapeutic approach for smoking cessation, with future studies aimed at identifying brain regions and reward-related mechanisms involved.

Transcription

Next, we have Belle Buzzi. She's studying the classical psychedelic psilocybin reduces nicotine withdrawal initial mechanisms. She's in the School of Medicine, and her advisor is Dr. M. Imad Damaj. How many people know someone addicted to nicotine? Wow. Well, believe it or not, smoking still remains the leading cause of preventable disability, disease, and death in the United States, with half a million people dying each year due to a smoking-related illness. And while we do have treatments available, they lack efficacy, especially when it comes to long-term abstinence. So we need a new treatment. Studies suggest that psychedelics may actually be that new treatment option. And so an example of psychedelic is like LSD, psilocybin, or magic mushrooms, and DMT. A small study at Johns Hopkins found that 80% of their heavy smoker participants remain abstinent at a six-month follow-up following psilocybin. And while this is great, we do have questions that remain, such as what's happening or what's the mechanism that's underlying this therapeutic effect. We also want to understand what properties of nicotine are being targeted by psilocybin. And so what we did is we look at a mouse model of nicotine withdrawal and try to see what effect psilocybin has on that. The reason we look at withdrawal is because it's highly correlated to craving and eventual relapse. 75% of smokers eventually relapse a week later due to these withdrawal signs. So it's important to understand and to target. What we found is that mice chronically given nicotine show robust withdrawal signs, as you can see in the top. However, those mice that were also given psilocybin showed a complete reduction in withdrawal signs down to control levels. The next thing we want to understand is what's the mechanism behind this. To do this, we looked at a genetically altered mouse in which it did not express the serotonin 2A receptor, as you can see here. What we know about this receptor is that all classical psychedelics bind to it. We also know that activation of this receptor is important for the hallucinations or the trip. But what we don't know is whether activation of this receptor is what explains these therapeutic effects. So we repeated this withdrawal paradigm in the serotonin 2A knockout mice, and what we found is here. We found that psilocybin no longer reduced withdrawal signs, telling us that this receptor indeed plays a role in the therapeutic effects we see. In the future, we want to hone in on brain regions that are also involved in this attenuation. We also want to look at reward. So we know that psilocybin reduces withdrawal, but we want to know, does it affect the rewarding or the feel-good properties of nicotine? In conclusion, psychedelics may be the next treatment option to help the millions of smokers today. Thank you. Thank you.

Rights

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