JAMA Netw Open
July 1, 2024
Leor Roseman, David Erritzøe, David Nutt et al.
12 citations
Interruptions during psychedelic therapy sessions are associated with lower ratings of the intensity of the experience. This quality improvement study examined how breaks or disruptions affect the subjective depth of the psychedelic session, suggesting that maintaining a continuous, uninterrupted setting may be important for achieving a more intense experiential state.
April 12, 2023
Rebecka Bremler, Nancy Katati, Parvinder Shergill et al.
12 citations
preprint
Negative psychological responses to psychedelics, lasting at least 72 hours, are real and can include new psychiatric diagnoses or worsened symptoms, particularly anxiety. In a sample of 32 individuals who reported such experiences, 37.5% received a new psychiatric diagnosis after psychedelic use, and 87% experienced new or worsened anxiety. In-depth interviews with 15 of the most severe cases suggested that contributing factors include unsafe environments, unpleasant acute experiences, prior psychological vulnerabilities, high or unknown drug doses, and young age. The study's small, self-selected sample means these findings cannot estimate how common such harms are.
Frontiers in Psychiatry
June 4, 2024
Julia Bornemann, James B Close, Kirran Ahmad et al.
11 citations
Psilocybin-assisted therapy may help treat fibromyalgia, a chronic widespread pain condition with limited treatment options. A protocol describes a mechanistic study with 20 participants who will attend 8 visits over 8 weeks, including two dosing sessions where psilocybin is given at least once, with doses up to 25 mg. The primary focus is on brain mechanisms, measured via electroencephalography during the acute psychedelic state and magnetic resonance imaging before and after treatment. Primary outcomes are Lempel-Ziv complexity from EEG and experiential avoidance via questionnaire. Secondary measures include pain, physical and mental function, and additional neuroimaging. Results aim to clarify how psilocybin-therapy works in the brain and inform a future randomized controlled trial.
Journal of Psychedelic Studies
December 8, 2023
Brandon Weiss, Chelsea Sleep, Nicholas M. Beller et al.
11 citations
People who use psychedelics tend to be more open and extraverted and less neurotic than non-users, and non-users interested in trying psychedelics are more open and neurotic than uninterested non-users. An online survey of 218 psychedelic users, 104 interested non-users, and 104 uninterested non-users identified 52 themes of perceived personality change attributed to the most intense psychedelic experience, which clustered into eight factors: Unitive Spiritual, Gratitude Absorption, Purpose Freedom, Compassion Understanding, Emotional Stability, Openness Perspective, Connection to Self, and Neuroticism Caution. The findings suggest that personality traits influence who uses psychedelics, and that setting and drug type moderate different types of personality changes.
Research Square
May 20, 2021
Richard E. Daws, Christopher Timmerman, Bruna Giribaldi et al.
11 citations
Across two clinical trials, psilocybin therapy produced robust antidepressant effects that were linked to a decrease in brain network modularity measured by resting-state fMRI. In an open-label study of 16 adults with treatment-resistant depression, Beck Depression Inventory scores dropped sharply at one week and six months, and the reduction in network modularity one day after treatment correlated with clinical improvement at six months. In a double-blind randomized trial of 43 adults with major depressive disorder, the psilocybin arm showed superior antidepressant effects at two and six weeks compared with escitalopram, and improvements correlated with decreased modularity. These convergent findings suggest that psilocybin therapy may work by reducing the brain's network modularity.
Psychol Med
September 27, 2024
Michael Angyus, Sarah Osborn, Eline Haijen et al.
10 citations
A 9-item scale called the Imperial Psychedelic Predictor Scale (IPPS) can predict key features of the acute psychedelic experience. The scale has three factors: set (mindset), rapport (relationship with the guide or setting), and intention. In a controlled administration dataset, set and rapport together explained 40% of the variance in mystical experiences, while set alone explained 16% of the variance in challenging experiences. In another controlled dataset, rapport explained 9% of the variance in emotional breakthrough. The scale shows good internal consistency and predicts mystical, challenging, and emotional breakthrough experiences across naturalistic and controlled settings.
Drug Science Policy and Law
September 1, 2025
David Nutt, David Erritzøe, Anne Katrin Schlag et al.
9 citations
The field of psychedelic research lacks standardized terminology for clinical development, dosing, safety monitoring, and regulatory classification. A comprehensive framework is proposed that classifies psychedelics by pharmacology (serotonergic, glutamatergic, kappaergic, GABAergic, and atypical), introduces dose-dependent categories (microdose, minidose, mididose, macrodose), and standardizes terms like “short-acting” with specific pharmacokinetic parameters. Safety considerations include cardiovascular and psychological effects, with risk mitigation protocols for higher-risk compounds like ibogaine. A three-phase treatment model—preparation, dosing, and integration—is recommended as a minimum standard. The lack of comparative research on psychotherapy modalities is identified as a critical gap.
PsyArXiv
October 17, 2023
Alessia Marrocu, Hannes Kettner, Brandon Weiss et al.
9 citations
preprint
About 16% of people who used psychedelics in naturalistic settings experienced a clinically meaningful decline in psychological well-being four weeks later. Those with a prior personality disorder diagnosis were disproportionately affected, making up 31% of negative responders and facing more than a four-fold elevated risk of adverse psychological responses. The findings suggest that personality disorders may heighten vulnerability to negative outcomes from psychedelic use, highlighting the need for careful screening and robust psychological support.
PsyArXiv
April 13, 2023
Lisa Xiaolu Luan, Emma Eckernäs, Michael Ashton et al.
9 citations
preprint
A within-subjects, placebo-controlled study tested a novel method of administering N,N-Dimethyltryptamine (DMT) by combining a bolus injection with a constant-rate infusion to extend the experience to 30 minutes. The method effectively maintained stable and tolerable subjective effects over the infusion period. Anxiety ratings remained low, and heart rate habituated within 15 minutes, indicating psychological and physiological safety. Plasma DMT concentrations increased consistently starting ten minutes into administration, while psychological effects plateaued, suggesting acute psychological tolerance to DMT. These findings demonstrate the safety and effectiveness of continuous intravenous DMT administration for basic and clinical research.
The British Journal of Psychiatry
June 18, 2025
Kyle T Greenway, Nicolas Garel, Lê-Anh L Dinh-Williams et al.
8 citations
In a clinical trial of ketamine combined with psychotherapy for severe treatment-resistant depression, 32 participants received six ketamine infusions with psychological support, either with or without music. Both groups showed large and sustained reductions in depression, anxiety, and suicidality at four weeks, fully maintained at eight-week follow-up. The ketamine experiences were highly emotional and mystical, comparable to those seen with psilocybin. Converging analyses suggested that mystical-like experiences contributed to the immediate and lasting antidepressant effects. Music did not enhance outcomes or psychedelic experiences.
Journal of Psychopharmacology
September 6, 2016
Helle Ruff Laursen, Susanne Henningsson, Julian Macoveanu et al.
8 citations
Prolonged recreational use of MDMA (ecstasy) alters serotonin neurotransmission, similar to a depleted state. In this fMRI study, 14 ecstasy users and 12 non-users viewed faces expressing anger, disgust, fear, sadness, or no emotion while their amygdala activity was measured. Serotonin transporter binding, assessed via PET, correlated negatively with amygdala activity in users. Greater lifetime ecstasy intake was associated with increased amygdala activity during angry face processing, while longer time since last use showed a trend toward decreased activity during angry and sad face processing. The results indicate dose-dependent effects of long-term serotonin depletion on emotional face processing.
medRxiv
June 3, 2023
Matthew B. Wall, Lysia Demetriou, Bruna Giribaldi et al.
7 citations
preprint
Psilocybin therapy for major depressive disorder may work through a different brain mechanism than the SSRI escitalopram. In a trial comparing two groups—one receiving two 25 mg psilocybin doses plus daily placebo, the other receiving daily escitalopram plus two inactive 1 mg psilocybin doses—brain responses to emotional faces were measured with fMRI before and after six weeks of treatment. The escitalopram group showed significantly reduced brain activity in response to fear, happy, and neutral faces, including a specific reduction in amygdala response to fear faces. The psilocybin group showed no such reduction and even a slight increase in brain responsiveness, despite large improvements in depressive symptoms. Reduced emotional responsiveness may be a biomarker of SSRIs' antidepressant action not shared by psilocybin therapy.
Frontiers in Psychology
June 6, 2025
William Roseby, Hannes Kettner, Leor Roseman et al.
6 citations
Psychedelics like psilocybin strongly increase the sense that life has meaning, based on three different studies: a clinical trial for depression, a healthy volunteer study, and naturalistic retreats. The 'presence of meaning' rose substantially after a psychedelic experience, while the 'search for meaning' dropped only slightly. These meaning enhancements were moderately linked to improvements in mental health, such as greater wellbeing and reduced depression. Mystical, ego dissolution, and emotional breakthrough experiences were associated with increased meaning, though the strength varied by context. The evidence converges to show a robust, lasting positive effect of psychedelics on meaning in life, with context influencing outcomes.
Neuroscience Applied
December 2, 2024
Kate Godfrey, Brandon Weiss, Joseph Peill et al.
5 citations
A single high dose of psilocybin (25 mg) given to healthy volunteers who had never used psychedelics reduced neuroticism one month later, consistent with prior research. The reduction was linked to how meaningful the experience felt and to the dread of ego dissolution during the drug's acute effects. Personality was measured with the Big Five Inventory and Big Five Aspect Scale; acute effects were tracked with the Altered States of Consciousness questionnaire and Psychological Insight Scale. Electroencephalography measured alpha power and Lempel-Ziv complexity. The findings suggest that acute psychedelic states can catalyze lasting personality changes in a beneficial direction, with implications for therapy and understanding personality.
Front Hum Neurosci
June 19, 2024
Giuseppe Pasculli, Pierpaolo Busan, Eric S. Jackson et al.
5 citations
Developmental stuttering involves speech-motor disruptions linked to metabolic and network anomalies in the brain, particularly in the default mode and social-cognitive networks. These networks also influence social anxiety and avoidance, which often accompany persistent stuttering. Psychedelic compounds can modify brain metabolism and connectivity in these networks and have shown clinical benefits for conditions like depression and PTSD that share features such as rumination and social anxiety. Although no controlled trials have been conducted, anecdotal reports suggest psychedelics might alleviate stuttering and its associated symptoms. The authors argue that psychedelics warrant investigation in randomized clinical trials for developmental stuttering.
Biochemistry
February 7, 2024
Vito F. Palmisano, Claudio Agnorelli, Andrea Fagiolini et al.
5 citations
Classic psychedelics, which resemble serotonin, act on 5-HT2A receptors inside neurons. This computational study used molecular dynamics simulations to examine how 12 tryptamines cross cell membranes. Dimethylation of the amine group and a methoxy group at position 5 increased permeability. Positional substitutions on the indole ring also influenced permeation, while protonation raised the energy barrier at the bilayer center, making molecules highly impermeable. These simulation-based trends can guide future drug design for psychedelics with improved activity.
Nat Med
February 16, 2026
David Erritzøe, Tommaso Barba, Tiffanie Benway et al.
4 citations
A single 21.5-mg intravenous dose of the psychedelic DMT, given with psychotherapeutic support, produced a rapid and significant reduction in depressive symptoms in adults with moderate-to-severe major depressive disorder. In a double-blind, placebo-controlled trial with 34 participants, those receiving DMT showed a greater decrease in depression scores at two weeks compared to placebo. Antidepressant effects persisted up to three months in an open-label phase. Adverse events were mostly mild to moderate, and no serious adverse events occurred.
Journal of psychopharmacology (Oxford, England)
June 10, 2025
Torsten Passie, Anja Loizaga-Velder, Alicia Danforth et al.
4 citations
A consensus-based model curriculum for education and training in substance-assisted psychotherapy (SAP) covers theoretical topics and practical components including apprenticeship observation, ongoing clinical supervision, and self-experience for trainees. The model, developed by authors with extensive SAP experience, also addresses peer and conventional supervision, respect for intercultural differences, and teachings about indigenous use of related substances. It is largely adapted to western industrialized countries with established graduate-level psychotherapy training. The curriculum may be valuable for psychedelic researchers, those training therapists for research studies, and those preparing for clinical work outside research settings.
Molecular Psychiatry
April 26, 2025
Rebecca Harding, Neomi Singer, Talma Hendler et al.
4 citations
Psilocybin therapy reduces anhedonia more than the SSRI escitalopram in major depressive disorder, yet escitalopram dampens emotional responses to musical surprises while psilocybin therapy preserves them. Escitalopram increases brain activity in memory and emotion regions during musical surprises, whereas psilocybin therapy decreases activity in the ventromedial prefrontal cortex and angular gyrus and increases sensory region activation. These contrasting neural and behavioral effects suggest fundamentally different treatment mechanisms: psilocybin may maintain subjective responses by reducing the salience of prediction errors or strengthening hedonic expectations, while escitalopram may weaken hedonic priors.
bioRxiv
July 18, 2019
Christopher Timmermann, Leor Roseman, Michael Schartner et al.
4 citations
preprint
Intravenous DMT, a fast-acting psychedelic, markedly alters human brain activity. Compared with a placebo, DMT reduced oscillatory power in alpha and beta brainwaves and increased spontaneous signal diversity. Time-referenced analyses linked changes in subjective experience to changes in brain activity. Emergence of delta and theta frequency oscillations correlated with the peak of the experience, particularly its eyes-closed visual component. These findings advance understanding of the neurobiological underpinnings of immersive states of consciousness.
Meghan Good, Tiffanie Benway, Zelah Joel et al.
4 citations
DMT (N,N-dimethyltryptamine) is being developed as a treatment for major depressive disorder. In a phase I trial, 24 healthy adults received escalating intravenous doses of DMT fumarate (SPL026) that were safe and well-tolerated. DMT exposure increased proportionally with dose over the 9–21.5 mg range. Peak plasma concentration occurred at about 10 minutes, and the mean elimination half-life was 9–12 minutes. In vitro experiments showed that DMT is cleared by monoamine oxidase A (MAO-A) and modified by the enzymes CYP2D6 and CYP2C19. The unbound fraction of DMT in plasma was approximately 70%. These findings support the development of DMT infusion regimens for treating major depressive disorder.
Frontiers in Psychiatry
August 6, 2025
Grace Blest‐hopley, Giuseppe Pasculli, Simon Ruffell et al.
3 citations
Veterans with traumatic brain injuries who participated in psilocybin retreats showed improvements in PTSD, depression, and anxiety symptoms four weeks afterward. PTSD scores decreased by 50%, depression scores by 65%, and anxiety scores by 28%. Electroencephalography measurements revealed decreased delta and theta brainwave power in frontal and temporal regions, along with enhanced coherence in alpha and beta bands, suggesting improved cognitive control, emotional processing, and neural communication. The preliminary findings provide a rationale for larger controlled studies.
Annals of the New York Academy of Sciences
July 21, 2025
Marcel Socoró-garrigosa, Yonatan Sanz Perl, Morten L Kringelbach et al.
3 citations
The scale at which the brain represents information remains a key question in neuroscience. Evidence shows that information is encoded not just in localized areas but across distributed, hierarchical networks. The hierarchy of causal influences shaping brain activity patterns is a signature of different brain states, relevant to neuropsychiatric disorders. Using whole-brain models guided by the thermodynamics of mind framework, researchers estimated brain hierarchy and studied in-silico transitions in static functional connectivity. Applying this to major depressive disorder, they built resting-state whole-brain models of depressed patients before and after treatment with psilocybin or escitalopram.
Journal of Clinical Medicine
February 20, 2025
Shakila Meshkat, Taha Malik, Jennifer Swainson et al.
3 citations
A systematic review examined whether psychedelic therapies can rapidly reduce suicide risk. Four randomized controlled trials reported significant reductions in suicidal ideation with psilocybin (three studies) and MDMA-assisted therapy (one study), with effect sizes (Cohen's d) ranging from 0.52 to 1.25 and no safety issues. Five additional randomized trials also showed reductions. Among 24 non-randomized and cross-sectional studies, results were mixed: psilocybin reduced suicidal ideation (odds ratios 0.40–0.75), MDMA-assisted therapy for PTSD showed a pooled effect of d = 0.61, while LSD was associated with increased odds of suicidality (odds ratios 1.15–2.08). DMT studies showed no significant effects. The evidence remains inconclusive, underscoring the need for further trials.
Research Square
October 15, 2024
Alexandra R. Gordon, Brennan M. Carrithers, Broc A. Pagni et al.
3 citations
Among individuals who reported a personality disorder diagnosis, psychedelic use was associated with improvements in mental health outcomes. In two observational studies, participants showed reductions in anxiety and depression symptoms lasting up to 2-3 months, with moderate to large effect sizes. Suicidal ideation decreased, and no participants moved to high risk of suicidal behavior after use. A small proportion experienced clinically significant worsening of anxiety (up to 8.2%) or depression (up to 7.1%). Transient increases in cognitive flexibility and sustained increases in cognitive reappraisal were observed, with the latter linked to reduced anxiety and depression. The findings are limited by small sample sizes and self-reported data.