Frontiers in Psychiatry
October 10, 2022
Christopher S. Stauffer, Melanie Brown, Dee Adams et al.
40 citations
Transgender and gender diverse (TGD) people face higher rates of stigma, discrimination, trauma, and PTSD, yet are underrepresented in PTSD research. Clinical trials of MDMA-assisted psychotherapy show promise for treating PTSD, but issues of equitable access, power imbalances, and vulnerable states of consciousness are magnified for TGD people. Through three virtual focus groups with 17 TGD participants who had trauma-related mental health care, the study identified barriers to adequate gender-affirming and trauma-informed care, frustration with providers lacking cultural humility, and suggested protocol amendments including routine collection of trans-inclusive gender identity data, an explicit gender-affirming treatment approach, culturally safe settings, and diverse co-therapy dyads. Inclusion of TGD voices promotes equitable access and helps tailor research to community needs.
Frontiers in Psychiatry
November 26, 2021
Ahmad Rehman, Habib Syed, Kathryn Forcer et al.
40 citations
A pilot study of NHS psychiatrists found that while 77.2% believe there should be a role for controlled or therapeutic use of psychedelics, psychiatrists at all levels do not feel prepared to deliver psychedelic-assisted psychotherapy. Trainees were better informed than non-training grade psychiatrists. Thematic analysis of focus groups revealed three main themes: need for knowledge, openness to change, and uncertainty. The study suggests that significant training needs and both professional and societal shifts are required before psychedelic-assisted therapy could become a mainstream treatment option in psychiatry.
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
February 9, 2021
Valeria Catalani, Davide Arillotta, John Corkery et al.
38 citations
During the first eight months of the COVID-19 pandemic, a web crawler called NPSfinder® identified 229 new psychoactive substances (NPSs) being discussed on drug enthusiast forums and social media. Of these, 18 NPSs were detected for the first time, including six cathinones, six opioids, two synthetic cannabinoid receptor agonists, two PCP-like molecules, and two psychedelics. Ten of these 18 substances had not been previously reported to either the UNODC or EMCDDA databases. Opioids and cathinones generated the most discussion on social media and Reddit. Automated web crawlers combined with social listening may help identify emerging NPSs, and pandemic-related restrictions may influence demand for specific NPS classes.
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
November 17, 2017
Nikola Pinterová, Rachel R. Horsley, Tomáš Páleníček
37 citations
Aminoindanes, a class of novel psychoactive substances often sold as "bath salts," gained popularity on the recreational drug market after mephedrone and other synthetic cathinones were banned in the UK in 2010. Originally developed for medical uses such as anti-Parkinsonian drugs and potential psychotherapy aids, they are now widely substituted for ecstasy. Their primary mechanism of action involves serotonin, which poses a significant risk of serotonin syndrome at high doses or when combined with other drugs. Fatally toxic effects have been observed in animal studies and in clinical cases, with reported deaths. Greater knowledge and appropriate legislation are urgently needed to reduce risks of fatal intoxication while not impeding research.
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
January 10, 2018
Klára Šíchová, Nikola Pinterová, Monika Židková et al.
28 citations
Mephedrone (MEPH) and its primary metabolite nor-mephedrone (nor-MEPH) were detected in the serum, brain, lungs, and liver of male Wistar rats, with the highest levels found in lungs. Maximum concentrations occurred at 30 minutes, and nor-MEPH levels exceeded those of the parent drug at 2 and 4 hours. Both drugs increased locomotion and altered its spatial distribution in a dose-dependent, rapid, and short-lasting manner, without disrupting prepulse inhibition. Behavioral effects disappeared within 40 minutes, but MEPH-induced rectal temperature elevations persisted for 3 hours even in singly housed rats, suggesting a dissociation between behavioral and hyperthermic effects that may contribute to prolonged somatic toxicity.
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
February 27, 2018
Joshua S. Elmore, Michael H. Baumann
26 citations
Repeated exposure to the synthetic cannabinoid JWH-018, found in psychoactive 'spice' products, produces tolerance to its own hypothermic and cataleptic effects in male rats, and transiently enhances sensitivity of 5-HT1A receptors, as shown by augmented behavioral and hypothermic responses to the 5-HT1A agonist 8-OH-DPAT one day after treatment cessation. However, it does not affect behaviors induced by the 5-HT2A/2C receptor agonist DOI.