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The Bright Side of Psychedelics: Latest Advances and Challenges in Neuropharmacology

Summary

Researchers are rediscovering psychedelic compounds from traditional plants and fungi as potential treatments for mental health conditions and addiction. These substances work by interacting with brain chemistry, particularly serotonin systems, to reduce symptoms of depression, anxiety, and drug cravings. Recent clinical studies show promising results, especially for treating opioid addiction with single doses that can produce lasting improvements. However, more rigorous clinical trials are needed to fully understand how these compounds work and to establish safe, effective therapeutic protocols.

Background

Psychedelic molecules have been used historically in shamanic practices and have recently emerged as potential therapeutic agents for psychiatric disorders. Despite governmental restrictions in recent decades, there is growing interest in psychedelic-assisted psychotherapy (PAP) as an alternative strategy in response to the limited efficacy of current psychiatric medications.

Objective

This review aims to summarize the ethnobotanical uses and pharmacological mechanisms of major psychedelic plants and their active ingredients, including ibogaine, mescaline, N,N-dimethyltryptamine, psilocin, and lysergic acid diethylamide. The review presents structural and computational studies of receptor binding and discusses recent clinical studies evaluating efficacy in treating psychiatric disorders.

Results

The review identifies multiple mechanisms of action for psychedelics including serotonin receptor agonism, monoamine transporter inhibition, and neurotrophic factor modulation. Clinical studies demonstrate promising results for substance use disorders, depression, anxiety, and PTSD, with single-dose ibogaine treatments showing sustained effects for opioid addiction and epidemiological studies supporting therapeutic benefits of mescaline.

Conclusion

Psychedelics demonstrate significant therapeutic potential, particularly for substance use disorders and mood-related psychiatric conditions, though rigorous clinical trials are needed. The complex mechanisms of action involving multiple receptor systems and neurotrophic pathways require further investigation to optimize therapeutic applications and safety profiles.
  • Published in:International Journal of Molecular Sciences,
  • Study Type:Review,
  • Source: PMID: 36674849, DOI: 10.3390/ijms24021329
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