image: Plasticity-promoting mechanisms triggered by dimethyltryptamine (DMT) and β-carboline (BC). (A) DMT and BC-induced increase in cortical plasticity are linked to enhanced BDNF levels, although this might result from activation of different receptors. (B) Increased hippocampal plasticity and neurogenesis induced by DMT and BC rely on different molecular pathways. 5HT2A: serotonergic receptor 2A subtype; BC: β-carboline; BDNF: brain-derived neurotrophic factor;DMT: N,N-dimethyltryptamine; SIGMA1: sigma receptor subtype 1.
Credit: Rafael Guimarães dos Santos,
RIBEIRÃO PRETO, São Paulo, Brazil, 3 December 2024 - As interest in psychedelic medicine grows, researchers have synthesized a decade of evidence to understand how ayahuasca influences fear and anxiety in the brain. A new review published in Psychedelics consolidates findings from molecular studies, animal research, and human trials to create a clearer picture of how this traditional Amazonian brew affects emotional processing and memory systems.
The analysis, led by Lorena Terene Lopes Guerra and colleagues at the University of São Paulo, examines the growing body of evidence about ayahuasca's complex interactions with brain systems involved in emotional processing and memory, with particular focus on its effects through two distinct serotonin receptor systems.
"Understanding how signals coordinate the processes in cells, tissues, and organs is fundamental to grasping ayahuasca's potential therapeutic applications," explains Dr. Rafael Guimarães dos Santos, one of the review's authors. "By examining evidence across multiple levels - from receptor interactions to clinical outcomes - we can better understand how this traditional medicine might help treat anxiety and trauma-related disorders."
The review synthesizes evidence showing that ayahuasca's effects involve a delicate balance between two serotonin receptor types: 5-HT2A and 5-HT1A. This dual action appears crucial for understanding both the immediate effects of ayahuasca and its potential long-term therapeutic benefits.
Key findings from the reviewed literature include:
• Ayahuasca's main component, DMT, acts primarily through 5-HT2A receptors to influence emotional processing
• The brew's β-carboline compounds may work through different mechanisms to affect memory and anxiety
• Clinical studies suggest specific effects on fear extinction and emotional processing
• Brain imaging studies show ayahuasca modulates activity in regions crucial for emotional regulation
The synthesis of available evidence raises important questions about ayahuasca's therapeutic potential. Can the timing of ayahuasca administration be optimized for treating specific conditions? Might different preparations of ayahuasca be more effective for different therapeutic purposes? How do individual differences in receptor systems affect treatment outcomes?
Current evidence reviewed suggests ayahuasca might be particularly promising for treating PTSD and anxiety disorders. However, Dr. dos Santos emphasizes the need for more controlled clinical trials: "While the preclinical and observational evidence is encouraging, we need more rigorous clinical studies to understand the optimal therapeutic applications."
The review also examines safety considerations and the importance of controlled settings for therapeutic use, noting that ayahuasca's complex nature requires careful consideration of individual patient factors.
The full Genomic Press peer-reviewed article, titled “Effects of ayahuasca on fear and anxiety: cross-talk between 5HT1A and 5HT2A receptors,” is available on 03 December 2024 in Psychedelics. The article is freely available online at https://url.genomicpress.com/2p9dauta.
About Psychedelics - Psychedelics: The Journal of Psychedelic Pharmacology (ISSN: 2997-2671) is a peer-reviewed medical research journal published by Genomic Press, New York. Psychedelics is exclusively dedicated to the latest advancements in the realm of psychedelic substances and their potential therapeutic uses. We embrace the full spectrum of research, from fundamental investigations to cutting-edge clinical studies. Psychedelics welcomes diverse perspectives and contributions, advancing the understanding of psychedelic compounds.
Journal
Psychedelics
Method of Research
Literature review
Subject of Research
Animals
Article Title
Effects of ayahuasca on fear and anxiety: cross-talk between 5HT1A and 5HT2A receptors
Article Publication Date
3-Dec-2024
COI Statement
The authors declare no conflicts of interest. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The manuscript has been read and approved by all authors.