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Clinical trials using psilocybin-, ketamine-, and MDMA-assisted psychotherapy have demonstrated striking long-term improvements in addiction, anxiety and depressive symptoms, and posttraumatic stress disorder. Despite evidence of broad therapeutic potential, there remain gaps in our knowledge of their ...

Clinical trials using psilocybin-, ketamine-, and MDMA-assisted psychotherapy have demonstrated striking long-term improvements in addiction, anxiety and depressive symptoms, and posttraumatic stress disorder. Despite evidence of broad therapeutic potential, there remain gaps in our knowledge of their mechanisms of action. Most of the benefits reported in clinical trials to date result from one to three doses of a psychedelic compound which produces an altered state of consciousness (ASC). Many hypotheses center around the ASC and how that might produce profound psychic changes. However, there is a large movement underway to capture the benefits of psychedelics by using doses which are subthreshold for ASC, or by exploring and engineering non-psychoactive analogues. Early data suggests some long-term benefits of chronic microdosing regimens, as well as newly engineered psychedelic analogues; however, more recent results question whether the benefits of microdosing might be due to an expectancy bias. How much of the clinical benefit of these agents is a result of ASC and how much is pharmacologically separable? What constitutes an ASC? In this Research Topic, we will explore the mechanisms of psychedelic drugs in the context of the altered states of consciousness induced by the drugs, and how that relates to the therapeutic effect of these agents.

We wish to explore several key and interrelated questions:
1) What are the cellular and system level changes that are induced by psychedelics,
2) What is the altered state of consciousness that arises with psychedelics,
3) How central is the ASC to the therapeutic effects of psychedelics, and
4) What benefits, if any, can be derived from non-ASC psychedelic administration, via either microdosing or the use of non-psychoactive analogues?

We are interested in both clinical and pre-clinical (animal) data that would illuminate any of these questions. We seek papers that will address mechanisms of action of psychedelic agents. We are interested in both acute and lasting cellular and network descriptions of neural changes produced by psychedelic agents, as well as perceptual and behavioral changes which accompany dosing with psychedelic agents. We are particularly interested in the tryptaminergic agents (e.g. LSD, psilocybin/psilocin, dimethyltryptamine, and related analogs) and phenethylamines (e.g. MDMA). We are open also to papers on other putative hallucinogens like dissociative and hypnotic drugs in cases where there appears to be therapeutic potential that is associated with an ASC.

We will seek a variety of paper types, including Original Research, Hypothesis and Theory, and Conceptual Analysis, as well as Systematic Reviews and Mini Reviews (see https://www.frontiersin.org/journals/neuroscience#article-types for descriptions of the article types).

Matthew McMurray has received a research grant from PsyBio Therapeutics, Inc. and is a member of the scientific advisory board for PsyBio Therapeutics, Inc.

Keywords: Psychedelics, altered state of consciousness, clinical, preclinical, mechanism of action, cellular, systems


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