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Scientific Reports Feb 2024Do psychedelics affect sexual functioning postacutely? Anecdotal and qualitative evidence suggests they do, but this has never been formally tested. While sexual...
Do psychedelics affect sexual functioning postacutely? Anecdotal and qualitative evidence suggests they do, but this has never been formally tested. While sexual functioning and satisfaction are generally regarded as an important aspect of human wellbeing, sexual dysfunction is a common symptom of mental health disorders. It is also a common side effect of selective serotonin reuptake inhibitors (SSRIs), a first line treatment for depression. The aim of the present paper was to investigate the post-acute effects of psychedelics on self-reported sexual functioning, combining data from two independent studies, one large and naturalistic and the other a smaller but controlled clinical trial. Naturalistic use of psychedelics was associated with improvements in several facets of sexual functioning and satisfaction, including improved pleasure and communication during sex, satisfaction with one's partner and physical appearance. Convergent results were found in a controlled trial of psilocybin therapy versus an SSRI, escitalopram, for depression. In this trial, patients treated with psilocybin reported positive changes in sexual functioning after treatment, while patients treated with escitalopram did not. Despite focusing on different populations and settings, this is the first research study to quantitively investigate the effects of psychedelics on sexual functioning. Results imply a potential positive effect on post-acute sexual functioning and highlight the need for more research on this.
Topics: Humans; Hallucinogens; Sexual Behavior; Psilocybin; Escitalopram; Selective Serotonin Reuptake Inhibitors
PubMed: 38326446
DOI: 10.1038/s41598-023-49817-4 -
Scientific Reports Feb 2024This pilot study investigated psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder (AUD). Participants... (Randomized Controlled Trial)
Randomized Controlled Trial
This pilot study investigated psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder (AUD). Participants were recruited from a phase II, randomized, double-blind, placebo-controlled clinical trial investigating psilocybin-assisted therapy (PAT) for the treatment of AUD (NCT02061293). Eleven adult patients completed task-based blood oxygen dependent functional magnetic resonance imaging (fMRI) approximately 3 days before and 2 days after receiving 25 mg of psilocybin (n = 5) or 50 mg of diphenhydramine (n = 6). Visual alcohol and emotionally valanced (positive, negative, or neutral) stimuli were presented in block design. Across both alcohol and emotional cues, psilocybin increased activity in the medial and lateral prefrontal cortex (PFC) and left caudate, and decreased activity in the insular, motor, temporal, parietal, and occipital cortices, and cerebellum. Unique to negative cues, psilocybin increased supramarginal gyrus activity; unique to positive cues, psilocybin increased right hippocampus activity and decreased left hippocampus activity. Greater PFC and caudate engagement and concomitant insula, motor, and cerebellar disengagement suggests enhanced goal-directed action, improved emotional regulation, and diminished craving. The robust changes in brain activity observed in this pilot study warrant larger neuroimaging studies to elucidate neural mechanisms of PAT.Trial registration: NCT02061293.
Topics: Adult; Humans; Alcoholism; Psilocybin; Pilot Projects; Magnetic Resonance Imaging; Brain; Cues; Ethanol
PubMed: 38326432
DOI: 10.1038/s41598-024-52967-8 -
Scientific Reports Feb 2024Psilocybin, a serotonergic psychedelic, is being increasingly researched in clinical studies for the treatment of psychiatric disorders. The relatively lengthy duration...
Psilocybin, a serotonergic psychedelic, is being increasingly researched in clinical studies for the treatment of psychiatric disorders. The relatively lengthy duration of oral psilocybin's acute effects (4-6 h) may have pragmatic and cost-effectiveness limitations. Here, we explored the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT), a closely related, but faster-acting psychedelic intervention, on mental health outcomes in healthy volunteers. Data is reported from two separate analyses: (1) A comparison of mental health-related variables 1 week after 7, 14, 18, and 20 mg of IV DMT versus IV saline placebo (n = 13) and, (2) A prospective dataset assessing effects before versus 2 weeks after 20 mg of IV DMT (n = 17). Mental health outcomes included measures of depression severity (QIDS-SR16), trait anxiety (STAI-T), Neuroticism (NEO-FFI), wellbeing (WHO-5), meaning in life (MLQ), optimism (LOT-R), and gratitude (GQ-6). In both the prospective and placebo-controlled datasets, significant improvements in scores of depression were found 1-2 weeks after DMT administration. Significant reductions in trait Neuroticism were only found for the placebo-controlled sample. Finally, changes in depression and trait anxiety correlated with acute peak experiences (assessed via 'Oceanic Boundlessness'). While the use of two separate cohorts in pooled analysis limits the generalizability of these correlational findings, these results suggest that DMT may reduce depressive symptomatology by inducing peak experiences. The short half-life of IV DMT and its potential for flexible dosing via controlled infusions makes it an appealing candidate for psychedelic medicine. Further research in clinical samples is needed to corroborate the therapeutic potential of DMT.
Topics: Humans; N,N-Dimethyltryptamine; Hallucinogens; Psilocybin; Healthy Volunteers; Prospective Studies; Outcome Assessment, Health Care
PubMed: 38326357
DOI: 10.1038/s41598-024-53363-y -
Scientific Reports Feb 2024Psilocybin is the most researched classic psychedelic for Treatment-Resistant Depression (TRD). While optimizing set and setting are considered essential for efficacy... (Randomized Controlled Trial)
Randomized Controlled Trial
Psilocybin is the most researched classic psychedelic for Treatment-Resistant Depression (TRD). While optimizing set and setting are considered essential for efficacy and safety, patient perspectives on these aspects have rarely been investigated. To address this knowledge gap, the current paper explored the experiences of 11 TRD patients (8 women, 3 men) participating in a double-blind randomized clinical trial with a single session of oral (1, 10 or 25 mg) psilocybin treatment. After qualitative analysis, three major themes were identified: (1) challenges with trust-building and expectation management; (2) navigating the experience; and (3) the need for a more comprehensive treatment. Subthemes of the first theme include a general distrust in mental healthcare, trust in study therapists, limited time for preparation, and managing expectations. The second theme included the following subthemes: trusting to surrender, profound and overwhelming experiences, and music as a guide. The third theme addressed a desire for multiple psilocybin sessions, and challenges with sensemaking. Patients' perspectives provided important insights into potential optimization of psilocybin treatment of TRD, including individualized preparation, investment in trust-building, offering additional psilocybin sessions, providing access to sustained (psycho)therapy with trusted therapists, and personalizing treatment approaches, which may also enhance real-world adaption of these treatments.
Topics: Male; Humans; Female; Psilocybin; Depression; Hallucinogens; Music; Depressive Disorder, Treatment-Resistant
PubMed: 38316896
DOI: 10.1038/s41598-024-53188-9 -
Saudi Medical Journal Feb 2024
Topics: Adult; Humans; Hallucinogens; Psilocybin; Depression; Neoplasms
PubMed: 38309742
DOI: No ID Found -
Biological Psychiatry. Cognitive... May 2024Psychedelic compounds, including psilocybin, LSD (lysergic acid diethylamide), DMT (N,N -dimethyltryptamine), and 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), all of... (Review)
Review Comparative Study
Psychedelic compounds, including psilocybin, LSD (lysergic acid diethylamide), DMT (N,N -dimethyltryptamine), and 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), all of which are serotonin 2A receptor agonists, are being investigated as potential treatments. This review aims to summarize the current clinical research on these 4 compounds and mescaline to guide future research. Their mechanism(s) of action, pharmacokinetics, pharmacodynamics, efficacy, and safety were reviewed. While evidence for therapeutic indications, with the exception of psilocybin for depression, is still relatively scarce, we noted no differences in psychedelic effects beyond effect duration. Therefore, it remains unclear whether different receptor profiles contribute to the therapeutic potential of these compounds. More research is needed to differentiate these compounds in order to inform which compounds might be best for different therapeutic uses.
Topics: Hallucinogens; Humans; Psilocybin; Lysergic Acid Diethylamide; Serotonin 5-HT2 Receptor Agonists
PubMed: 38301886
DOI: 10.1016/j.bpsc.2024.01.007 -
Frontiers in Pharmacology 2023Psychedelic compounds have been utilized by humans for centuries for medicinal, religious, and tribal purposes. Clinical trial data starting from the early 2000s and... (Review)
Review
Psychedelic compounds have been utilized by humans for centuries for medicinal, religious, and tribal purposes. Clinical trial data starting from the early 2000s and continuing today indicates that psychedelics are a clinically efficacious treatment for a variety of neurological and psychiatric disorders. However, all clinical trials examining these substances have excluded any individual with a past or current history of seizures, leaving a large cohort of epilepsy and non-epilepsy chronic seizure disorder patients without anywhere to turn for psychedelic-assisted therapy. These exclusions were made despite any significant evidence that clinically supervised psychedelic use causes or exacerbates seizures in this population. To date, no clinical trial or preclinical seizure model has demonstrated that psychedelics induce seizures. This review highlights several cases of individuals experiencing seizures or seizure remission following psychedelic use, with the overall trend being that psychedelics are safe for use in a controlled, supervised clinical setting. We also suggest future research directions for this field.
PubMed: 38283836
DOI: 10.3389/fphar.2023.1326815 -
BMC Psychiatry Jan 2024A significant number of individuals with alcohol use disorder remain unresponsive to currently available treatments, which calls for the development of new alternatives....
Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial.
BACKGROUND
A significant number of individuals with alcohol use disorder remain unresponsive to currently available treatments, which calls for the development of new alternatives. In parallel, psilocybin-assisted therapy for alcohol use disorder has recently yielded promising preliminary results. Building on extant findings, the proposed study is set to evaluate the feasibility and preliminary clinical efficacy of psilocybin-assisted therapy when incorporated as an auxiliary intervention during inpatient rehabilitation for severe alcohol use disorder. Moreover, it intends to pinpoint the modifications in the two core neurocognitive systems underscored by dual-process models of addiction.
METHODS
In this double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial, 62 participants aged 21-64 years will be enrolled to undergo psilocybin-assisted therapy as part of a 4-week inpatient rehabilitation for severe alcohol use disorder. The experimental group will receive a high dose of psilocybin (30 mg), whereas the control group will receive an active placebo dose of psilocybin (5 mg), both within the context of a brief standardized psychotherapeutic intervention drawing from key elements of acceptance and commitment therapy. The primary clinical outcome is the between-group difference regarding the change in percentage of heavy drinking days from baseline to four weeks posthospital discharge, while safety and feasibility metrics will also be reported as primary outcomes. Key secondary assessments include between-group differences in terms of changes in (1) drinking behavior parameters up to six months posthospital discharge, (2) symptoms of depression, anxiety, trauma, and global functioning, (3) neuroplasticity and key neurocognitive mechanisms associated with addiction, and (4) psychological processes and alcohol-related parameters.
DISCUSSION
The discussion outlines issues that might arise from our design.
TRIAL REGISTRATION
EudraCT 2022-002369-14 and NCT06160232.
Topics: Humans; Psilocybin; Alcoholism; Acceptance and Commitment Therapy; Double-Blind Method; Alcohol Drinking; Treatment Outcome; Randomized Controlled Trials as Topic; Clinical Trials, Phase II as Topic
PubMed: 38279085
DOI: 10.1186/s12888-024-05502-y -
Neuropsychiatric Disease and Treatment 2024Post-traumatic stress disorder (PTSD) is associated with significant patient burden. While pharmacotherapies and evidence-based psychotherapy interventions (EBPI) are... (Review)
Review
Trauma-Informed Care in Psychedelic Therapy Research: A Qualitative Literature Review of Evidence-Based Psychotherapy Interventions in PTSD and Psychedelic Therapy Across Conditions.
INTRODUCTION
Post-traumatic stress disorder (PTSD) is associated with significant patient burden. While pharmacotherapies and evidence-based psychotherapy interventions (EBPI) are effective, studies consistently highlight inadequate outcomes and high treatment dropout. Psychedelic therapy (PT) has shown preliminary promise across difficult-to-treat conditions, including MDMA-assisted therapy for PTSD, however trials of classical psychedelics in PTSD are lacking. Understanding patients' experiences of EBPI could help promote safety in PT.
AIM
To systematically review qualitative research on patients' subjective experience of EBPI for PTSD, and of PT, and examine areas of overlap and divergence between them.
METHODS
Systematic literature searches for studies published between 2010 and 2023 were conducted on OVID, PubMed, Web of Science, and PsycInfo. Included were original studies in English that presented qualitative data of patient experiences of EBPI in PTSD, or PT for any indication. Extracted data from included studies were analysed using thematic synthesis. Syntheses were completed separately for EBPI and PT, before similarities and differences between the therapies were identified.
RESULTS
40 research articles were included for review: 26 studies on EBPI for PTSD, and 14 studies on PT. EBPI studied were CBT, EMDR, CPT and PE. Psychedelic compounds studied were psilocybin, ibogaine, LSD, MDMA and ketamine, for treatment of substance use disorders, anxiety relating to physical illness, depression, and PTSD. Core themes from patient experiences of EBPI: 1) patient burden in PTSD treatment; 2) readiness; 3) key mechanisms of change; 4) psychological safety and trust. Themes identified in the review of PT: 1) indirect trauma processing; 2) reorganisation of self-narratives via processes of relatedness and identification; 3) key treatment characteristics.
CONCLUSION
This study suggests overlap between patients' experience of EBPI and PT in terms of key mechanisms of change, the importance of psychological safety and readiness to engage in treatment. Trauma-informed care paradigms and practices may improve safety and acceptability of PT research.
PubMed: 38268571
DOI: 10.2147/NDT.S432537 -
Frontiers in Psychiatry 2023The use of the psychedelic compound psilocybin in conjunction with psychotherapy has shown promising results in the treatment of psychiatric disorders, though the...
INTRODUCTION
The use of the psychedelic compound psilocybin in conjunction with psychotherapy has shown promising results in the treatment of psychiatric disorders, though the underlying mechanisms supporting these effects remain unclear. Psilocybin is a Schedule I substance that is dephosphorylated to form an active metabolite, psilocin. Psilacetin, also known as O-acetylpsilocin or 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), is an unscheduled compound that has long been suggested as an alternative psilocin prodrug, though direct support for this hypothesis has thus far been lacking.
METHODS
This study employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess the time-course and plasma concentrations of psilocin following the intraperitoneal (IP) administration of psilacetin fumarate or psilocybin to male and female C57Bl6/J mice.
RESULTS
Direct comparisons of the time courses for psilocin exposure arising from psilocybin and psilacetin found that psilocybin led to 10-25% higher psilocin concentrations than psilacetin at 15-min post-injection. The half-life of psilocin remained approximately 30 min, irrespective of whether it came from psilocybin or psilacetin. Overall, the relative amount of psilocin exposure from psilacetin fumarate was found to be approximately 70% of that from psilocybin.
DISCUSSION
These findings provide the first direct support for the long-standing assumption in the field that psilacetin functions as a prodrug for psilocin . In addition, these results indicate that psilacetin fumarate results in lower peripheral psilocin exposure than psilocybin when dosed on an equimolar basis. Thoughtful substitution of psilocybin with psilacetin fumarate appears to be a viable approach for conducting mechanistic psychedelic research in C57Bl6/J mice.
PubMed: 38264637
DOI: 10.3389/fpsyt.2023.1303365