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Journal of Psychiatric Practice Sep 2023There has been a burgeoning interest in psychedelics among the public, state legislatures, psychiatrists and other clinical providers, and within the research community.... (Review)
Review
There has been a burgeoning interest in psychedelics among the public, state legislatures, psychiatrists and other clinical providers, and within the research community. Increasing numbers of studies evaluating psychedelics for depression, anxiety, posttraumatic stress disorder, and substance use disorders have been conducted or are underway. While discussing psychedelics in general, the focus of this paper is on psilocybin and its mechanism, how it exerts a psychedelic effect, dosing, and a review of the treatment studies of psilocybin, which were primarily for treatment-resistant depression and cancer-related anxiety. Future directions and potential limitations of studying and regulating psilocybin and other psychedelics are also discussed.
Topics: Humans; Anxiety; Anxiety Disorders; Depressive Disorder, Treatment-Resistant; Hallucinogens; Psilocybin
PubMed: 37678363
DOI: 10.1097/PRA.0000000000000729 -
Biological Psychiatry. Cognitive... May 2024Clinical trials of psychedelic compounds like psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltrptamine (DMT) have forced a reconsideration of how nondrug... (Review)
Review
Clinical trials of psychedelic compounds like psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltrptamine (DMT) have forced a reconsideration of how nondrug factors, such as participant expectations, are measured and controlled in mental health research. As doses of these profoundly psychoactive substances increase, so does the difficulty in concealing the treatment condition in the classic double-blind, placebo-controlled trial design. As widespread public enthusiasm for the promise of psychedelic therapy grows, so do questions regarding whether and how much trial results are biased by positive expectancy. First, we review the key concepts related to expectancy and its measurement. Then, we review expectancy effects that have been reported in both micro- and macrodose psychedelic trials from the modern era. Finally, we consider expectancy as a discrete physiological process that can be independent of, or even interact with, the drug effect. Expectancy effects can be harnessed to improve treatment outcomes and can also be actively managed in controlled studies to enhance the rigor and generalizability of future psychedelic trials.
Topics: Humans; Hallucinogens; Clinical Trials as Topic; Anticipation, Psychological; Placebo Effect
PubMed: 38387698
DOI: 10.1016/j.bpsc.2024.02.004 -
Current Pain and Headache Reports Sep 2023This review presents the existing literature of and a framework for how psychedelic drugs might be applied as therapeutic agents in episodic migraine. (Review)
Review
PURPOSE OF REVIEW
This review presents the existing literature of and a framework for how psychedelic drugs might be applied as therapeutic agents in episodic migraine.
RECENT FINDINGS
The therapeutic effects of psychedelics in headache disorders have been reported for decades and controlled investigations are now beginning. In the first and only clinical trial of a psychedelic drug in migraine, the single administration of low-dose psilocybin reduced weekly migraine days and pain intensity for the following 2 weeks in episodic subjects. These transitional effects, along with abortive effects in two subjects and additional findings in cluster headache, offer insight into the potential medicinal use of this and other psychedelic drugs in episodic migraine. The existing evidence supports the continued investigation of psilocybin and other psychedelics as transitional treatments in episodic migraine. Acute and preventive effects also exist, but the risks may outweigh benefits with these applications. Future research of psychedelics in episodic migraine should be tailored for this condition and not modeled after protocols used in other medical or psychiatric conditions.
Topics: Humans; Hallucinogens; Psilocybin; Migraine Disorders; Mental Disorders; Cluster Headache
PubMed: 37540398
DOI: 10.1007/s11916-023-01145-y -
Psychoanalytic Review Dec 2023The psychoanalytic journey and the psilocybin journey both reveal unconscious dynamics. In this article a psychoanalyst discusses his own psilocybin journey....
The psychoanalytic journey and the psilocybin journey both reveal unconscious dynamics. In this article a psychoanalyst discusses his own psilocybin journey. Similarities and differences between these journeys are discussed. Possibilities are offered for a dialogue in which psilocybin may contribute to psychoanalytic understanding and psychoanalysis may contribute to the understanding of psychedelic sessions. Patients may benefit from this cross-fertilization.
Topics: Humans; Psilocybin; Psychoanalysis; Psychotherapists; Ego
PubMed: 38117518
DOI: 10.1521/prev.2023.110.4.457 -
Lakartidningen Apr 2024In the last 20 years there has been an increased interest in research on psychedelic compounds for treatment of psychiatric conditions such as depression, anxiety and... (Review)
Review
In the last 20 years there has been an increased interest in research on psychedelic compounds for treatment of psychiatric conditions such as depression, anxiety and substance use disorders. Despite existing treatments being efficacious for many patients, this is not the case for up to a third of the patients with depression. Additionally, treatments are often long and associated with side effects. This review focuses on the psychedelic compound psilocybin, a serotonin-2A-receptor agonist that has been seen to reduce depression and anxiety in patients after administration of only a single dose, with effects lasting several weeks. Recent findings from phase II studies suggest that psilocybin treatment for depression is safe and efficacious. A phase III study is currently recruiting. Whether psychedelics will become a part of standard healthcare remains to be seen, but findings do give rise to cautious optimism.
Topics: Humans; Hallucinogens; Psilocybin; Anxiety Disorders; Psychiatry
PubMed: 38572715
DOI: No ID Found -
Journal of Psychopharmacology (Oxford,... Sep 2023Hallucinogenic mushrooms have been used in religious and cultural ceremonies for centuries. Of late, psilocybin, the psychoactive compound in hallucinogenic mushrooms,... (Review)
Review
Hallucinogenic mushrooms have been used in religious and cultural ceremonies for centuries. Of late, psilocybin, the psychoactive compound in hallucinogenic mushrooms, has received increased public interest as a novel drug for treating mood and substance use disorders (SUDs). In addition, in recent years, some states in the United States have legalized psilocybin for medical and recreational use. Given this, clinicians need to understand the potential benefits and risks related to using psilocybin for therapeutic purposes so that they can accurately advise patients. This expert narrative review summarizes the scientific basis and clinical evidence on the safety and efficacy of psilocybin-assisted therapy for treating psychiatric disorders and SUDs. The results of this review are structured as a more extensive discussion about psilocybin's history, putative mechanisms of action, and recent legislative changes to its legal status. There is modest evidence of psilocybin-assisted therapy for treating depression and anxiety disorders. In addition, early data suggest that psilocybin-assisted therapy may effectively reduce harmful drinking in patients with alcohol use disorders. The evidence further suggests psilocybin, when administered under supervision (psilocybin-assisted therapy), the side effects experienced are mild and transient. The occurrence of severe adverse events following psilocybin administration is uncommon. Still, a recent clinical trial found that individuals in the psilocybin arm had increased suicidal ideations and non-suicidal self-injurious behaviors. Given this, further investigation into the safety and efficacy of psilocybin-assisted therapy is warranted to determine which patient subgroups are most likely to benefit and which are most likely to experience adverse outcomes related to its use.
Topics: Humans; Psilocybin; Alcoholism; Hallucinogens; Affect; Anxiety Disorders
PubMed: 37650489
DOI: 10.1177/02698811231190858 -
MMW Fortschritte Der Medizin Oct 2023
Topics: Humans; Psilocybin; Depression
PubMed: 37758991
DOI: 10.1007/s15006-023-3025-6 -
The Annals of Pharmacotherapy Oct 2023The objective of this systematic review is to determine the tolerability and safety of psilocybin in a variety of psychiatric and substance-dependence conditions. (Review)
Review
OBJECTIVE
The objective of this systematic review is to determine the tolerability and safety of psilocybin in a variety of psychiatric and substance-dependence conditions.
DATA SOURCES
A systematic review was conducted using Embase, PubMed, Cochrane Central, and Web of Science through September 2023 using the following terminology: "psilocybin" AND "mental-disease" OR "substance-dependence" AND "disease-therapy," in addition to other synonymous key words.
STUDY SELECTION AND DATA EXTRACTION
Literature reporting acute effects and safety data following the use of psilocybin as the pharmacologic intervention in a clinical trial in adult patients with a psychiatric or substance-dependence condition were included. Following the application of inclusion and exclusion criteria, 16 studies were ultimately included in this review.
DATA SYNTHESIS
The most common treatment-emergent adverse effects reported were transient nausea and headache. Transient anxiety was reported as a frequent psychiatric effect, and 3 participants received a benzodiazepine for refractory anxiety during the psilocybin session. Psilocybin demonstrated modest increases in blood pressure and heart rate, and 1 participant received an antihypertensive for sustained hypertension during the psilocybin session. No cases of psilocybin-induced psychosis or Hallucinogen Persisting Perception Disorder were reported.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Treatment resistance remains a concern for psychiatric patients and novel therapies are needed to help alleviate the burden of morbidity and mortality. Psilocybin demonstrates promising acute and long-term safety that may allow for its use in psychiatric or substance-dependence conditions as an alternative to standards of care or in treatment-resistant patients.
CONCLUSIONS
Psilocybin has demonstrated tolerability and safety in recent literature that has investigated its therapeutic potential in a variety of psychiatric or substance-dependence conditions.
PubMed: 37902038
DOI: 10.1177/10600280231205645 -
The Journal of Clinical Psychiatry Aug 2023Despite their legality, alcohol and tobacco both have a well-documented potential for misuse and elevate users' likelihood for disease. Dependence on alcohol also...
Despite their legality, alcohol and tobacco both have a well-documented potential for misuse and elevate users' likelihood for disease. Dependence on alcohol also contributes to opioid overdoses, which claim 130 lives every day. Although awareness of the opioid epidemic is rising broadly among health care professionals, a majority of Americans still do not receive adequate, FDA-approved medications for their addiction. Effective medications are available for alcohol use disorder and medications for opioid use disorder have validated benefits that justify their use. In recent years, psychedelic compounds have attracted interest among scientists for their potential to alter mood and cognition in beneficial manners. Already, some evidence supports the use of psilocybin in alleviating symptoms of depression and anxiety; psychedelic compounds also have potential as alcohol use disorder treatments and may help reduce symptoms tied to opioid withdrawal. Because substance use disorders can culminate in death, a comprehensive, integrated, public health approach to the treatment of people with substance use disorders is essential.
Topics: Humans; Hallucinogens; Alcoholism; Addiction Medicine; Psilocybin; Opioid-Related Disorders; Ethanol
PubMed: 37555675
DOI: No ID Found -
BioRxiv : the Preprint Server For... Sep 2023Psychedelic drugs like lysergic acid diethylamide (LSD) and psilocybin have emerged as potentially transformative therapeutics for many neuropsychiatric diseases,...
Psychedelic drugs like lysergic acid diethylamide (LSD) and psilocybin have emerged as potentially transformative therapeutics for many neuropsychiatric diseases, including depression, anxiety, post-traumatic stress disorder, migraine, and cluster headaches. LSD and psilocybin exert their psychedelic effects via activation of the 5-hydroxytryptamine 2A receptor (HTR2A). Here we provide a suite of engineered mice useful for clarifying the role of HTR2A and HTR2A-expressing neurons in psychedelic drug actions. We first generated -EGFP-CT-IRES-CreERT2 mice (CT:C-terminus) to independently identify both HTR2A-EGFP-CT receptors and HTR2A-containing cells thereby providing a detailed anatomical map of HTR2A and identifying cell types that express HTR2A. We also generated a humanized mouse line and an additional constitutive -Cre mouse line. Psychedelics induced a variety of known behavioral changes in our mice validating their utility for behavioral studies. Finally, electrophysiology studies revealed that extracellular 5-HT elicited a HTR2A-mediated robust increase in firing of genetically-identified pyramidal neurons--consistent with a plasma membrane localization and mode of action. These mouse lines represent invaluable tools for elucidating the molecular, cellular, pharmacological, physiological, behavioral, and other actions of psychedelic drugs .
PubMed: 37808655
DOI: 10.1101/2023.09.25.559347