Frontiers in Psychiatry
April 21, 2021
James Rucker, Allan H. Young
40 citations
Psilocybin has a history of non-medical use, and some infer therapeutic utility from this. Early phase clinical trials are encouraging but only indicate a need for larger, multicentre trials, which are ongoing but will take years. Retreat centers offering paid psilocybin truffle experiences use early trial data for bold public claims, which is unwise because early trials are not designed for generalization. This risks misleading the public and conflicts with ethical principles from the Nuremberg Code and Kefauver Harris Amendments. Using psilocybin before proper testing may undermine the credibility of retreat centers and the wider field.
Frontiers in Psychiatry
March 29, 2016
M. Zhang, R. Ho
39 citations
Ketamine, an NMDA receptor antagonist, shows rapid antidepressant effects, with reductions in suicidal ideation ranging from 29% to 79% after intravenous administration. However, long-term use raises safety concerns: chronic use can cause memory impairments, dissociative symptoms, and urological problems like cystitis. A study of 11 recreational ketamine users found spatial memory disturbances linked to decreased activation in the right hippocampus and left parahippocampal gyrus. Conversely, some research suggests acute low-dose ketamine may improve visual and working memory in treatment-resistant depression, possibly through mechanisms involving BDNF and mTORC1. These conflicting findings highlight the need for further research, including comparisons with other antidepressants.
Frontiers in Psychiatry
May 14, 2024
Zijia Yu, Lisa Burback, Olga Winkler et al.
38 citations
A scoping review of 24 articles found that four psychedelic drugs—ayahuasca, psilocybin, LSD, and the entactogen MDMA—consistently alter brain functional connectivity in healthy individuals. The drugs decreased connectivity within the default mode network and increased sensory and thalamocortical connectivity. These neurophysiological changes correlated with subjective experiences such as altered consciousness, mood elevation, and mystical experiences, suggesting a brain network basis for the drugs' psychological effects. The review provides a potential neural mechanism for psychedelics' subjective effects but notes that direct clinical evidence is needed to advance therapeutic outcomes.
Frontiers in Psychiatry
November 11, 2022
Binyu Teng, Dan Wang, Conghui Su et al.
38 citations
A Chinese translation of the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2) was developed and tested in 627 participants. Exploratory factor analysis yielded a 7-factor model after removing 6 items, and confirmatory factor analysis showed good model fit. The total scale had a Cronbach's alpha of 0.822, with subscale alphas ranging from 0.656 to 0.838. Convergent validity was supported by correlations with the Five-Facet Mindfulness Questionnaire (r = −0.342 to 0.535), and discriminant validity by negative correlations with trait anxiety (r = −0.352 to −0.080). The Chinese version is a valid and reliable tool for assessing interoceptive awareness in Chinese populations.
Frontiers in Psychiatry
January 12, 2022
Shannon Dames, Pamela Kryskow, Crosbie Watler
38 citations
A multidisciplinary team developed a ketamine-assisted psychotherapy program delivered in a community-of-practice group model for healthcare providers experiencing distress. In a quality improvement evaluation of 94 patients across three cohorts, mean mental health scores improved significantly from baseline to 1–2 weeks after the 12-week program. Among those screening positive at baseline, 91% showed improvements in generalized anxiety, 79% in depression, 86% of those with PTSD no longer screened positive, and 92% had significant work/life functionality improvements. Qualitative feedback was overwhelmingly positive. Results suggest the program is effective for treating depression, PTSD, generalized anxiety, and functional impairment.
Frontiers in Psychiatry
August 11, 2021
Maria Eleni Eleftheriou, Emily M Thomas
37 citations
Mindfulness-based interventions and psychedelic-assisted therapy both show moderate to great success as alternative treatments for various psychopathologies, with long-term decreases in clinical symptoms and enhanced well-being in healthy participants. They share proposed salutogenic mechanisms, including altering present-moment awareness and anti-depressive action through corresponding neuromodulatory effects. Preliminary evidence indicates that psychedelic administration can enhance mindfulness capacities, similar to mindfulness-based interventions. Scientists have theorized and recently demonstrated synergistic effects when both are combined, yielding potentiated therapeutic benefit. These results require replication in larger samples with better controlled methodologies to delineate the effect of set and setting before extending to clinical populations.
Frontiers in Psychiatry
August 6, 2021
Juliana Mendes Rocha, Giordano Novak Rossi, Flávia de Lima Osório et al.
37 citations
In two small randomized placebo-controlled trials, ayahuasca did not consistently change personality traits. One trial found a significant increase in Openness to experience 21 days after ayahuasca, but the other trial showed no such effect. Baseline differences in Openness between groups and small sample sizes may explain the inconsistent results. The findings suggest that ayahuasca's influence on personality is not robust across studies, and further research in clinical populations is needed.
Frontiers in Psychiatry
October 18, 2021
A. Wilkowska, M. Wiglusz, M. Gałuszko-węgielnik et al.
35 citations
Anhedonia, a core symptom of depression linked to suicidality and reduced quality of life, often resists standard treatments. In 42 patients with treatment-resistant depression, eight ketamine infusions added to ongoing therapy significantly reduced anhedonia, as measured by the Snaith-Hamilton Pleasure Scale. This reduction in anhedonia appeared to mediate ketamine's overall antidepressant effect. However, the benefit was observed only among patients not using benzodiazepines. The findings require confirmation in a larger randomized placebo-controlled trial.
Frontiers in Psychiatry
August 2, 2021
Nicolas Langlitz, Erika Dyck, Milan Scheidegger et al.
35 citations
Psychedelics may act as non-specific amplifiers that help people reconnect with their values, or they might specifically promote liberal and anti-authoritarian views, as recent studies suggest. The return of psychedelics from counterculture to mainstream science has diversified their users and uses. This article argues for a moral psychopharmacology that brings pharmacological and neuroscientific research into conversation with historical and anthropological scholarship on the full range of moral and political views linked to psychedelic use. The work highlights the cultural plasticity of drug action and has implications for designing psychedelic therapies, while also questioning whether other psychoactive drugs have similarly rich moral and political dimensions.
Frontiers in Psychiatry
September 19, 2023
Nicolas Garel, Jessica Drury, Julien Thibault Lévesque et al.
32 citations
A biopsychosocial approach to ketamine for treatment-resistant depression, called the Montreal model, pairs ketamine infusions with structured psychiatric care and psychotherapy. Developed over six years in public healthcare settings, the model conceptualizes ketamine as a brief intervention that creates windows of opportunity for enhanced care and psychological growth. It combines six ketamine infusions with psychedelic-inspired nonpharmacological adjuncts, including preparative and integrative psychological support. The model aims to bridge biomedical and psychedelic perspectives, offering a standardized yet flexible approach for severe, real-world patients. Further research is needed to assess its effectiveness and hypothesized psychological mechanisms.
Frontiers in Psychiatry
September 10, 2021
Tehseen Noorani, Jonny Martell
32 citations
A Phase II trial comparing psilocybin-assisted therapy with escitalopram for depression found no statistically significant difference on the primary outcome measure (QIDS-SR16), though secondary measures favored psilocybin. Expert commentaries noted possible issues with the choice of primary outcome, statistical power, and the limitations of depression rating scales in capturing improved mood and well-being. This opinion piece, drawing on the authors' experiences in psychedelic trials and NHS psychiatry, argues that psychedelic therapies will both open new frontiers and face a bursting bubble, exploring the stakes and opportunities involved.
Frontiers in Psychiatry
April 30, 2018
Michael Chary, David Yi, Alex F. Manini
32 citations
Over the last two decades, novel psychoactive substances (NPS) have emerged as synthetic compounds or derivatives of known drugs. Analyzing 20 years of posts from the Lycaeum forum using natural language processing and machine learning, the study found that discussions about NPS often describe combining nootropics with sedative-hypnotics, and stimulants with plant hallucinogens or psychiatric medications. Conversations mentioning synthetic hallucinogens tended to separate into those about amphetamine-derived and ergot-derived compounds, and rarely mentioned plant hallucinogens. Bath salts were commonly discussed alongside sedative-hypnotics or nootropics, while canonical stimulants appeared with plant hallucinogens and psychiatric medications. All substances were frequently compared to MDMA, DMT, cocaine, or atropine to describe their effects. This represents the largest analysis of online polysubstance use patterns to date.
Frontiers in Psychiatry
October 22, 2020
Felix Müller, Markus Mühlhauser, Friederike Holze et al.
31 citations
A woman with severe, treatment-resistant depression and a complex personality disorder received weekly, ascending doses of LSD in an open psychiatric ward. Despite adequate dosing confirmed by blood tests, she experienced no substantial acute subjective drug effects. However, she showed rapid and significant improvements in depressed mood, emotional instability, low energy, and suicidal thoughts. Questionnaire scores also decreased in global severity and various psychopathological subscales. Improvements lasted about 7 days after each dose. The case suggests that LSD can induce rapid but transient beneficial effects on several symptoms, and that these improvements can occur without acute drug experiences, resembling the time course of ketamine's antidepressant effects.
Frontiers in Psychiatry
October 12, 2022
Robert J Sottile, Thomas Vida
30 citations
Post-traumatic stress disorder (PTSD) affects millions worldwide, with 40–70% of patients experiencing refractory disease despite available treatments. MDMA, like classic psychedelics such as psilocybin, has been used to enhance psychotherapy since its discovery, but research into its mechanisms has been limited due to its Schedule 1 classification. The pro-social effects of MDMA are thought to improve therapeutic alliance and facilitate trauma processing, but this may not fully explain its efficacy. A more nuanced explanation combines MDMA's pro-social effects with molecular mechanisms, such as increased brain-derived neurotrophic factor (BDNF) availability in fear memory learning pathways, potentially accounting for its therapeutic actions in PTSD.
Frontiers in Psychiatry
February 6, 2023
Candace R. Lewis, Joseph Tafur, Sophie Spencer et al.
29 citations
Epigenetic changes in hypothalamic-pituitary-adrenal (HPA) axis genes may predict successful psychotherapy for post-traumatic stress disorder (PTSD). In a pilot sub-study of a Phase 3 clinical trial, 23 participants (16 receiving MDMA-assisted therapy, 7 receiving placebo with therapy) provided saliva samples. Methylation at 259 CpG sites across three HPA genes (CRHR1, FKBP5, NR3C1) was measured before and after treatment. Methylation changes across both groups significantly predicted symptom reduction on 37 of the sites, with two surviving false discovery rate correction. The MDMA group showed greater methylation change on one NR3C1 site compared to placebo. Therapy-related PTSD symptom improvements may be linked to DNA methylation changes in HPA genes, and such changes may be larger with MDMA-assisted therapy.
Frontiers in Psychiatry
February 1, 2024
Alessandro Rodolico, Pierfelice Cutrufelli, A. di Francesco et al.
28 citations
Ketamine and its enantiomer esketamine show promise for quickly relieving suicidal thoughts in unipolar and bipolar depression, but the evidence is weak. An overview of 26 systematic reviews and 44 randomized controlled trials involving 3,316 subjects found the intervention effective and well-tolerated, but the quality of the included reviews and original studies is poor, resulting in low certainty of evidence. Insufficient data prevent differentiation between effects in unipolar versus bipolar depression. Enhanced methodological rigor in future research is needed to inform treatment guidelines.
Frontiers in Psychiatry
April 25, 2023
Rachael Grazioplene, Calvin Bohner, Giuliana DePalmer et al.
27 citations
A randomized, double-blind, placebo-controlled trial tests whether a single dose of psilocybin (0.25 mg/kg) is safe, tolerable, and effective for obsessive-compulsive disorder (OCD) symptoms. Thirty adults who have not responded to at least one standard treatment will receive either psilocybin or an active placebo (niacin). OCD symptoms are assessed by blinded raters at 48 hours post-dosing, with 12 weeks of follow-up. Resting-state neuroimaging explores neural mechanisms. The study aims to provide preliminary evidence for psilocybin's effects on OCD and pave the way for future research on neurobiological mechanisms.
Frontiers in Psychiatry
December 7, 2021
Henry J. Whitfield
27 citations
A newly optimised psychological flexibility model adapts Contextual Behavioural Science and Acceptance and Commitment Therapy to the unique challenges of psychedelic-assisted therapy for depression and PTSD, including ego inflation, traumatic memories, and the perceived presence of entities. The model integrates practices and data from psychedelic research into a CBS framework, questioning and adapting psychological flexibility processes to psychedelic contexts. It introduces a Spectrum of Selves model for psychedelic-assisted therapy and examines how to select and retain new self-perspectives and behaviours using evolutionary science principles. A case example and a psychedelic integration checklist guide practical implementation, aiming to increase theoretical-practical coherence, broaden treatment benefits, and reduce relapse.
Frontiers in Psychiatry
November 29, 2022
Ana María Ortiz Bernal, Charles L. Raison, Rafael Lancelotta et al.
26 citations
Reactivations—similar to flashbacks—are common after using the psychedelic 5-MeO-DMT and are often neutral or positive rather than distressing. Analysis of survey data from 513 people who used 5-MeO-DMT outside clinical settings found that women, older age at first dose, higher education, and dosing in a structured group setting were linked to higher odds of reporting a reactivation. Higher mystical experience scores, greater personal wellbeing, and having had a non-substance-induced non-dual awareness experience were associated with neutral or positive emotional valence of the reactivation. The findings suggest reactivations are typically a benign byproduct of the experience, but more research is needed to identify those at risk for negative reactivations.
Frontiers in Psychiatry
June 27, 2023
Irene Li, Rodney Fong, Molly M. Hagen et al.
25 citations
Medical students in Nevada hold generally positive attitudes toward psychedelics and psychedelic-assisted therapies but lack knowledge about them. In a survey of 132 students (22.7% response rate), 78.6% agreed that psychedelics have therapeutic potential, and 95.2% agreed they deserve further research. Students expressed uncertainty about neurocognitive risks. Demographic factors such as age, sex, and level of training did not significantly affect attitudes. The authors suggest that as psychedelic therapies may soon gain federal approval for psychiatric conditions, medical training should include early education on these agents to prepare future clinicians.
Frontiers in Psychiatry
September 28, 2022
K. Hassan, W. Struthers, Aditya Sankarabhotla et al.
25 citations
Sublingual rapid-dissolve ketamine tablets, self-administered at home, safely reduce symptoms of depression and anxiety in people with treatment-resistant depression. After three doses, nearly half of patients showed meaningful improvement on standard depression and anxiety questionnaires. Improvement rates were higher among those who completed a full course of six doses. This delivery method offers a practical alternative to intravenous ketamine.
Frontiers in Psychiatry
May 22, 2018
Laura Orsolini, Michela Ciccarese, Duccio Papanti et al.
25 citations
A new 'psychedelic trend' has emerged, driven by psychonauts who consume a variety of novel psychoactive substances (NPS) from animals. This review identifies several species—including ants, amphibians, and fish—that possess psychoactive properties and are abused recreationally. Routes of administration vary by animal, substance, metabolism, toxicity, and cultural context. Online access to these animals is facilitated through tourism-related search terms such as 'frog trip' and 'religious trip.' The review combines online psychonaut reports with literature searches from PubMed/Medline and Google Scholar to provide an overview of commonly abused 'psychedelic animals.'
Frontiers in Psychiatry
November 3, 2022
Lauren Okano, Bri Deyo, Alida Brandenburg et al.
24 citations
Research on psychedelic-assisted therapies is growing, but few studies examine extra-pharmacological factors that may influence treatment efficacy. One critical factor is the therapeutic setting—the physical and socio-cultural environment where the drug session occurs. Despite consensus that setting matters, recommendations for reporting key setting variables remain sparse. This paper reviews what is known about setting's influence, focusing on MDMA-assisted therapy, and proposes reporting guidelines for clinical trials based on MDMA-for-PTSD research. The authors suggest expanding these to include the subject's mood, expectations, and psychological condition once that area matures. The guidelines aim to increase data for future empirical study while preserving practitioner and patient autonomy.
Frontiers in Psychiatry
July 7, 2022
Maggie Kiraga, Kim P. C. Kuypers, Malin V. Uthaug et al.
24 citations
A single dose of psilocybin-containing truffles, taken in a supportive group setting, produced rapid and lasting reductions in both state and trait anxiety among self-reported healthy volunteers. Medium reductions in anxiety were observed the morning after the ceremony and persisted for at least one week. At one week, participants also showed increased non-judging mindfulness and decreased neuroticism. The acute experience of ego dissolution and changes in neuroticism were the strongest predictors of anxiety reduction. Average psilocin consumption was 27.1 mg. Results suggest potential anxiolytic effects for sub-clinical anxiety and support further research in clinical populations.
Frontiers in Psychiatry
November 5, 2021
Enzo Tagliazucchi, Federico Zamberlán, Federico Cavanna et al.
23 citations
Inhaled DMT, a classic psychedelic, produces short but profound shifts in consciousness. In 35 healthy volunteers, electroencephalography recorded before and during the drug's acute effects in a natural setting showed marked reductions in alpha and beta brain oscillations and increases in delta, theta, and gamma power, particularly in posterior regions. The power of fronto-temporal theta oscillations inversely correlated with feelings of unity and transcendence—core features of mystical-type experiences. These findings suggest that baseline brain activity prior to psychedelic use may help predict the likelihood of such experiences, which are linked to lasting well-being and improved therapeutic outcomes.