Neural mechanisms underlying psilocybin’s therapeutic potential – the need for preclinical in vivo electrophysiology

Summary & key facts

This paper is a review of what scientists know so far about how psilocybin, the active ingredient in so-called magic mushrooms, affects the brain. The authors say psilocybin changes perception, emotion, and thought and likely acts on a brain system called the default mode network, especially parts called the prefrontal cortex and the hippocampus. Current brain imaging studies do not all agree on exactly how activity in those areas changes. The authors argue we need more lab studies that record electrical brain signals in living animals to see how whole brain networks and rhythms are altered. Those answers are important for understanding why psilocybin can have lasting psychological effects and for judging its promise as a tool for hard-to-treat depression and other conditions.

Key facts:

• This paper is a review, which means the authors summarized and analyzed many existing studies instead of running new experiments.
• Psilocybin changes perception, emotion, and thinking. It likely acts on the brain’s default mode network, a set of regions involved in self-focused thought and memory, especially the prefrontal cortex and the hippocampus.
• Different brain imaging studies have produced mixed and sometimes contradictory results about whether psilocybin increases or decreases activity in those brain regions.
• The authors recommend more preclinical studies that record electrical activity from neurons in living brains. This method is called in vivo electrophysiology and can track fast brain rhythms and how different parts of the brain sync up.
• Studying brain rhythms and synchrony could help explain how psilocybin produces strong and sometimes long-lasting changes in experience and mood.
• The review says understanding these neural mechanisms is crucial before we can reliably use psilocybin to help people with severe depression and other difficult-to-treat mental health problems, but it does not claim that psilocybin is already a proven treatment.

Abstract

Psilocybin is a naturally occurring psychedelic compound with profound perception-, emotion- and cognition-altering properties and great potential for treating brain disorders. However, the neural mechanisms mediating its effects require in-depth investigation as there is still much to learn about how psychedelic drugs produce their profound and long-lasting effects. In this review, we outline the current understanding of the neurophysiology of psilocybin's psychoactive properties, highlighting the need for additional preclinical studies to determine its effect on neural network dynamics. We first describe how psilocybin's effect on brain regions associated with the default-mode network (DMN), particularly the prefrontal cortex and hippocampus, likely plays a key role in mediating its consciousness-altering properties. We then outline the specific receptor and cell types involved and discuss contradictory evidence from neuroimaging studies regarding psilocybin's net effect on activity within these regions. We go on to argue that in vivo electrophysiology is ideally suited to provide a more holistic, neural network analysis approach to understand psilocybin's mode of action. Thus, we integrate information about the neural bases for oscillatory activity generation with the accumulating evidence about psychedelic drug effects on neural synchrony within DMN-associated areas. This approach will help to generate important questions for future preclinical and clinical studies. Answers to these questions are vital for determining the neural mechanisms mediating psilocybin's psychotherapeutic potential, which promises to improve outcomes for patients with severe depression and other difficulty to treat conditions.

Topics

Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Biological neural network Cognition Consciousness Default mode network Electrophysiology Hallucinogen Neuroimaging Neurophysiology Neuroscience Prefrontal cortex Psilocybin Psychiatry Psychology

Substances

Psilocybin

Conditions & symptoms

Depression Sadness or low mood