The Potential Role of Serotonergic Hallucinogens in Depression Treatment

Abstract

Due to an increasing number of depression diagnoses and limited effective treatments, researchers continue to explore novel therapeutic strategies for this disorder. Recently, interest has revolved around the use of serotonergic psychedelics to reduce the symptoms of depression. In this systematic review, we summarize the currently available knowledge on the safety and efficacy of psychedelic substances for the treatment of depression. A literature search of the PubMed/MEDLINE database identified 14 clinical trials from the last 10 years that examined the use of psilocybin, MDMA, DMT, or LSD for the treatment of depression symptoms. Some psychedelics, especially psilocybin, demonstrated an ability to reduce depressive symptoms as measured by several psychological scales, which was often sustained for months after the last psychedelic session. Moreover, one study revealed that psilocybin has comparable efficacy to escitalopram in the treatment of depression. None of the studies reported any serious adverse events associated with psychedelic administration. The reviewed studies suggest that psychedelics have great potential in depression therapy and, after addressing and overcoming the current study limitations, may be used as a novel method of treating depression in the future.

The clinical pharmacology and potential therapeutic applications of 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeO‐DMT)

“…A growing body of research is demonstrating the efficacy of psychedelic drugs such as psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) in treating a variety of different psychiatric disorders, including treatment‐resistant depression, PTSD, substance use disorder, and anxiety‐related disorders (Vollenweider & Preller, 2020; Psiuk et al, 2021). However, systematic evidence of the therapeutic utility of 5‐MeO‐DMT is currently limited to anecdotal reports and observational studies in self‐selected healthy and clinical populations, who are using the drug in a natural environment (Lancelotta & Davis, 2020).…”

“…Improvements in mood in healthy volunteers and alleviation of psychiatric symptom severity in certain clinical populations after ingestion of 5‐MeO‐DMT are similar to results of observational and clinical studies assessing the therapeutic potential of the classic psychedelics psilocybin, LSD, and ayahuasca. As reviewed elsewhere (Vollenweider & Preller, 2020; Psiuk et al, 2021; Romeo et al, 2021) there is now a wealth of research demonstrating the safety of classic psychedelics, and a growing body of clinical work demonstrating their immediate and long‐lasting therapeutic efficacy. Thus, because of the apparent similar therapeutic profile as well as the extensive research behind the classic psychedelics, one may ask why investigations into 5‐MeO‐DMT are of interest.…”

Is Use of Psychedelic Drugs a Risk or Protective Factor for Late-Life Cognitive Decline?

“…Neurotransmitters are chemicals that communicate signals between neurons and from neurons to muscles ( The University of Queensland, 2017 ) and are essential for maintaining homeostasis and adequate brain functioning. Psychedelics, also called serotonergic hallucinogens, are non-addictive substances that affect the central nervous system by acting as agonists on serotonin (5-HT2A, 5-HT1A, and 5-HT2C) receptors ( Psiuk et al, 2021 ). Serotonin (5-HT) is a key neurotransmitter that affects mood, emotion, sexuality, breathing, stress, addiction, sleep, and digestion ( Watson, 2021 ).…”

Systematic Characterization of LSD metabolites inC. elegansby ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry

“…In addition to LSD, other serotonergic psychedelics, such as psilocybin, mescaline and dimethyltryptamine, have also shown positive and promising results, since, unlike traditional antidepressants, such as monoamine oxidase inhibitors and selective serotonin reuptake inhibitors, they act as full or partial serotonin 5-HT2A receptor agonists. [10,11,12,13,14].…”