About this Research Topic

Background

Psychedelic medicine has re-emerged as an exciting field of research over the past five to ten years, following several decades in the political – and medical - wilderness. Psilocybin, a naturally occurring prototype of the so-called “classic psychedelics”, has played a prominent role as the drug of choice in recent clinical trials investigating psychedelic-assisted psychotherapy for the treatment of a range of mental health conditions, and more fundamental research into brain function and consciousness.

In a strategic sense, the current wave of psychedelic research commenced with psilocybin mainly because it was relatively obscure, and hence lacked the sociopolitical baggage of the far more potent and widely known psychedelic, LSD. Psilocybin also had the perceived advantages of being a natural product with negligible toxicity, relatively short duration of action, and a lower potential for adverse psychological effects in therapeutic contexts.

However, psilocybin is but one of scores of compounds belonging to two chemical classes – phenethylamines and tryptamines, along with the related class of ergolines - that act as agonists of the serotonin (5-HT2A/2C) receptors responsible for the phenomenological and possibly therapeutic effects of classic psychedelics, plus numerous other serotonergic agonists that do not elicit psychedelic effects but nonetheless show promise as pharmacotherapeutic agents.

While psilocybin has proved to be an excellent “gateway psychedelic” to clinical research, there is clear potential to be explored among the many existing alternatives - legacy psychedelics such as mescaline, N,N-DMT and 5-MeO-DMT, and analogues created by eminent medicinal chemists, neuropharmacologists, and others in the latter half of the last century - along with the suite of entirely novel compounds emerging more recently through the efforts of a new generation of academics and a burgeoning community of small biotech enterprises.

Psychedelic science is possibly unique in bringing together the diverse fields of medicinal chemistry and pharmaceutical science, neuroscience, and psychological medicine in a therapeutically promising – not to mention fascinating – area of research.

Our sense is that the time is now ripe for broad-scale academic discussion of the intrinsic interest and therapeutic potential of the vast range of psychedelics Beyond Psilocybin and, hopefully, some early research outcomes in the area.

The goals of this Research Topic are as follows:

1. To present an overarching view of alternative/legacy and novel serotonergic psychedelics, particularly in the context of therapeutic applications. It should span the pharmacological characterization of alternative/legacy and novel classic psychedelics, and the exploration of novel and/or unexpected targets of psychedelic compounds.
2. Pre-clinical and clinical findings that investigate the (potential) clinical utility of alternative/legacy and novel serotonergic psychedelics.
3. Review articles on alternative/legacy psychedelics and their clinical potential would round out this Special Topic. These reviews should not only span known classic psychedelics but also discuss how new knowledge (arising from structure-activity relationship studies on serotonergic compounds) may help to optimize the clinical utility of these drugs.

Specific themes we would like to address include:

• SAR and structure-based development of novel serotonergic psychedelics
• Pharmacological characterization of alternative/legacy and novel psychedelics
• Mechanisms of action of alternative/legacy and novel 5-HT2A/2C serotonergic compounds
• Pre-clinical studies of alternative/legacy and novel psychedelics that investigate their mechanisms of action and therapeutic potential
• Medicinal chemistry and pharmacology of novel “non-psychedelic” psychoplastogens, and perspectives on their potential medical applications
• Pre-clinical and clinical studies on psilocybin, LSD, and analogues/congeners that might inform development of novel classic psychedelics
• Broader perspectives on potential clinical applications of novel psychedelics, including the clinical strengths and limitations of psilocybin and the scope to address these issues
• Perspectives on the current direction(s) of psychedelic medical research, particularly in the context of legacy versus novel compounds.

Dr. Jacqueline von Salm is a Co-Founder, share holder and patent holder of Psilera, Inc. The other Topic Editors declare no competing interests with regard to the Research Topic subject.

Keywords: psilocybin, psychedelics, Tryptamines, Mescaline, Psychoplastogens, Psychedelic-assisted psychotherapy

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