Special Report: Psychedelics in Medicine Part 1: Psychedelics as a potential therapeutic option for psychiatric conditions

Section 1: Psychedelics as a potential therapeutic option for psychiatric conditions

Psychedelic drugs, such as lysergic acid diethylamide (LSD), was of interest to molecular psychiatry in the 1950s due to its considerable chemical similarity to serotonin (5-HT). In the context of a highly regulated system, the use of psychedelics in psychiatry is not necessarily novel, but a reemerging concept.[1] They are generally considered Schedule I controlled substances (psilocybin, DMT, MDMA),[2] which traditionally are considered to purport no medical value and high potential for abuse.[3]

Despite this, psychedelic drugs such as psilocybin, in particular, have recently received increased attention with potential to treat a range of conditions.[4] Through a better understanding of pharmacokinetics and 5-HT receptor subtypes, psilocybin has become known to have a significant impact on 5-HT2A, specifically in the cerebral cortex as a non-selective serotonin agonist.[5] This is believed to inhibit thalamic filtering via GABAergic projections, which permits cortical regions to receive more sensory information.[5,6,7] However, the claustrum, a subcortical nucleus expressing high 5-HT2A receptors and projecting glutamatergic inputs to the cerebral cortex, seems to also experience positive effects following psilocybin administration.[7] There is also ample evidence that psilocybin, for example, reduces amygdalar reactivity and improves responses originating in the prefrontal and orbitofrontal cortices.[8] Clinically speaking, the culmination of these findings have led to great excitement in the application of drugs such as psilocybin for the treatment of various psychiatric conditions. In terms of dosing, there is substantial convenience and reduction of costs in administering fixed doses. It has been found that body weight does not significantly impact effects and the benefits outweigh advantages of weight-adjusted dosing.[9]

Concerns do exist regarding treatment with psychedelic drugs, with some reporting that terms such as consciousness and spiritual are misused and poorly defined.[10] Further, one must be cautious with maintaining professional boundaries in the context of psychedelic drug treatment and therapy. The combination of these treatment modalities are currently viewed positively by many, such that conventional psychotherapy could be greatly enhanced through the use of psychedelic drugs[11], effects that span the range of psychedelics and result in greater effect sizes than trials of pharmacotherapy or psychotherapy alone.[12]  While much research remains regarding safety and efficacy, guidelines are in place that have resulted in very few persisting adverse reactions.[13] Areas of improvement include but are not limited to ethics, trial design, and unambiguously defining outcomes.[11] The current reality is that psychedelics demonstrate unique potential for the treatment of psychiatric conditions and are likely to become more widespread as research continues to explore this area.[14]

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