Journal of Psychedelic Studies
March 25, 2020
Malin V. Uthaug, Rafael Lancelotta, Ana María Ortiz Bernal et al.
25 citations
Among 27 respondents who used the psychedelic drug 5-MeO-DMT, those who received it by intramuscular injection (IM) reported a lower rate of reactivations (21%) compared to those who vaporized it (69%). The IM group also required fewer redoses, experienced release of physical tension more consistently, and had a slower onset of acute effects (1–6 minutes) versus the vaporization group (1–50 seconds). These findings suggest that the route of administration influences the frequency of reactivations, dosing patterns, physical sensations, and the timing of the drug's effects.
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.
Network Neuroscience
November 1, 2023
Juan Carlos Farah, Pablo Mallaroni, Enrico Amico et al.
21 citations
Functional connectomes become more idiosyncratic under psilocybin, with greater dissimilarity between individuals than under placebo. While idiosyncratic features in placebo subjects appear mainly in the frontoparietal network, under psilocybin they concentrate in the default mode network (DMN). A DMN-focused pattern predicts subjective psilocybin experience, marked by reduced within-DMN and DMN-limbic connectivity and increased connectivity between the DMN and attentional systems. These findings link psilocybin's brain effects to subjective experience and demonstrate the value of brain-fingerprinting in pharmacological neuroimaging.
Frontiers in Pharmacology
March 18, 2020
Esther Papaseit, Marta Torrens, Mireia Ventura et al.
20 citations
2C-E, a psychedelic phenylethylamine similar to mescaline, acts as a partial agonist at serotonin 2A, 2B, and 2C receptors and inhibits norepinephrine and serotonin uptake. In an observational study, ten recreational psychedelic users self-administered single oral doses of 2C-E (6.5–25 mg). The drug induced alterations in perception, hallucinations, and euphoric mood, with saliva concentrations peaking 2 hours after administration. The effects resembled those of 2C-B and other serotonin-acting drugs.
Journal of Psychedelic Studies
August 26, 2021
Kim van Oorsouw, Malin V. Uthaug, Natasha L. Mason et al.
16 citations
A single ayahuasca ceremony reduced self-reported stress, anxiety, and somatization, and increased non-judging awareness four weeks later in 73 ceremony attendants. Satisfaction with life and awareness improved the day after the ceremony but returned to baseline after four weeks. No reduction in depression was found, contrary to earlier work. The intensity of ego dissolution during the ceremony predicted sub-acute mental health improvements. Effects were similar for first-time and experienced users. The authors call for placebo-controlled trials to confirm ayahuasca's therapeutic potential.
European Neuropsychopharmacology
February 25, 2021
Natasha L. Mason, Kim P. C. Kuypers, Johannes T. Reckweg et al.
16 citations
No Summary
Journal of Psychedelic Studies
December 15, 2021
Malin V. Uthaug, Natasha L. Mason, Martha N. Havenith et al.
15 citations
A naturalistic observational study of 58 Czech-speaking adults found that a single session of Holotropic Breathwork (a breathing technique intended to produce altered states of consciousness) was associated with lasting improvements in non-judgment, satisfaction with life, and reductions in stress-related symptoms. Although participants reported only low levels of psychedelic-like experience (averaging 0–34% on a 100% scale), the increase in non-judgment appeared sub-acutely and persisted for four weeks. Satisfaction with life increased and stress symptoms decreased at the four-week follow-up.
Biomedicine & Pharmacotherapy
March 24, 2022
Francisco Madrid-Gambín, Àlex Gomez‐gómez, Arnau Busquets-García et al.
14 citations
Consumption of ayahuasca increases N-acyl-ethanolamine endocannabinoids, decreases 2-acyl-glycerol endocannabinoids, and alters several large-neutral amino acids (LNAAs) in human plasma. Most LNAAs were inversely associated with nine of eleven subscales of the 5-Dimension Altered States of Consciousness Rating Scale, except tryptophan, which was positively associated. Several endocannabinoids and hexosylceramides were directly associated with ayahuasca alkaloids. Enrichment analysis confirmed dysregulation in pathways involved in serotonin and dopamine synthesis. A crosstalk between circulating LNAAs and subjective effects is suggested, independent of alkaloid concentrations, providing insights into the metabolic fingerprint and mechanism of action underlying ayahuasca experiences.
Frontiers in Psychology
June 23, 2021
Alexandre Augusto de Deus Pontual, Luís Fernando Tófoli, Carlos Fernando Collares et al.
14 citations
A new questionnaire, the Setting Questionnaire for the Ayahuasca Experience (SQAE), measures the physical and social context in which ayahuasca is consumed. Developed from a literature review, interviews with 19 users, and a survey of 2,994 participants, the scale's structure was tested using exploratory graph analysis and multidimensional item response theory. Six dimensions emerged—Leadership, Decoration, Infrastructure, Comfort, Instruction, and Social—though the original theoretical model fit the data better than the exploratory model. The instrument shows evidence of validity and can support future research on how setting influences the ayahuasca experience, with potential applications for studying psychedelic use more broadly.
June 10, 2021
Drummond E-Wen Mcculloch, Gitte M. Knudsen, Frederick S. Barrett et al.
14 citations
preprint
Research into psychedelic drugs like psilocybin, LSD, and DMT is growing, with clinical trials showing promise for psychiatric conditions. Resting-state fMRI is a common method to study brain mechanisms in these contexts. A review of 42 articles from 17 datasets found high heterogeneity in methods and analyses; two datasets underlie over half the publications, and terms like "entropy" are used inconsistently. The authors suggest that the field needs greater methodological consistency and replicability to identify stable neural markers of psychedelic effects, and encourage development of new models and quantification methods.
International Journal for the Psychology of Religion
December 5, 2022
Arne Bohn, Michiel H. H. Kiggen, Malin V. Uthaug et al.
10 citations
San Pedro, a cactus containing mescaline and used for millennia, is now popular in European ceremonial retreats. In a study of 42 participants at such retreats in the Netherlands, questionnaires measured 11 dimensions of altered consciousness, ego-dissolution, mystical experiences, and challenging experiences. Results indicate San Pedro produces deviations from normal waking consciousness on all 11 subscales, moderate ego-dissolution, and a complete mystical experience in two-thirds of participants. Spiritual experiences are strongly expressed, while disembodiment, anxiety, impaired control, and transcendence of space are low; physical distress and grief can occur during challenging experiences. Network analysis revealed two separate networks of positive and negative altered states.
Frontiers in Neuroscience
October 5, 2023
Pablo Mallaroni, Lilian Kloft, Natasha L. Mason et al.
8 citations
Repeated ayahuasca use is associated with a spatially distributed pattern of brain structural changes: sensorimotor areas become more distinct from surrounding regions while transmodal areas become less distinct. These changes correlate with the expression of genes for 5-HT2A receptors and other targets of ayahuasca, as well as with genes for transcription factors and immediate early genes previously linked to psychedelic-induced neuroplasticity in animal studies. The findings suggest that molecular mechanisms of psychedelic action may scale up to large-scale brain organization in living humans, potentially helping to explain behavioral differences in experienced users.
bioRxiv (Cold Spring Harbor Laboratory)
September 18, 2023
Sepehr Mortaheb, Larry D. Fort, Natasha L. Mason et al.
7 citations
preprint
Psilocybin increases functional connectivity across the brain and induces a recurrent hyperconnected pattern with low BOLD signal amplitude, suggesting heightened cortical arousal. These brain dynamics are linked to feelings of oceanic boundlessness and visionary restructuralization, as measured by the 5-Dimensional Altered States of Consciousness Rating Scale. The brain's tendency to enter this hyperconnected-hyperarousal pattern under psilocybin may enable variant mental associations. For the first time, these findings connect brain dynamics with phenomenological alterations, offering new insights into the neurophenomenology and neurophysiology of the psychedelic state.
medRxiv
November 1, 2022
Natasha L. Mason, Attila Szabó, Kim P. C. Kuypers et al.
6 citations
preprint
Psilocybin immediately reduced concentrations of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), while other inflammatory markers (interleukin-1α, IL-1β, IL-6, and C-reactive protein) remained unchanged. Seven days later, TNF-α returned to baseline, but IL-6 and CRP were persistently reduced in the psilocybin group. Changes in immune profile were linked to acute neurometabolic activity: reductions in TNF-α were associated with lower hippocampal glutamate concentrations. Greater reductions in IL-6 and CRP at seven days correlated with persisting positive mood and social effects. Psilocybin also blunted the cortisol response to a psychosocial stressor compared to placebo.
Current Opinion in Psychology
August 6, 2025
Iva Totomanova, Eline Haijen, Petra P M Hurks et al.
5 citations
Regular use of low doses of LSD or psilocybin, known as microdosing, has been studied in 57 human studies. Reported benefits include improved mood, enhanced cognition, social functioning, and mental health, but findings are inconsistent and largely based on self-reports. Adverse effects such as anxiety, physical discomfort, and cognitive disruption are also common. Outcomes vary greatly by individual and are shaped by expectations, context, and baseline state. Experimental studies of single doses often yield null findings, while observational studies of repeated use report more benefits. The evidence remains inconclusive and warrants caution.
bioRxiv (Cold Spring Harbor Laboratory)
October 11, 2022
Pablo Mallaroni, Natasha L. Mason, Lilian Kloft et al.
4 citations
preprint
Brain functional connectomes are unique and reliable identifiers of individuals, but it was unknown whether these 'fingerprints' persist during altered states of consciousness. Ayahuasca, a serotonergic psychedelic, disrupts functional connectivity. In a within-subject study using 7T fMRI, 21 members of the Santo Daime church were scanned after collective ayahuasca intake. Connectome fingerprinting revealed a shared functional space and a spatiotemporal reallocation of key edges. Differences in higher-order functional connectivity motifs predicted perceptual drug effects, showing that individualized connectivity markers can trace a subject's functional connectome across altered states.
Drugs Education Prevention and Policy
September 10, 2020
Jan Van Amsterdam, Johannes G. Ramaekers, Ton Nabben et al.
4 citations
Ecstasy (MDMA) is a popular recreational drug with low abuse and dependence liability compared to several other illicit drugs and alcohol, and there is little evidence of long-term harm. A potential health risk is acute hyperthermia, which occurs at an unknown incidence rate and is more prevalent when ecstasy is consumed with heavy exercise at high ambient temperatures or with other substances including alcohol. However, illegal production and trade in the Netherlands have developed into a serious public order and ecological problem, with organized crime related to production and trafficking growing. This review provides a science-based summary to assist debate on future Dutch ecstasy policy to reduce organized crime while maintaining harm reduction.
JAMA Psychiatry
March 25, 2026
Wiesław Jerzy Cubała, Malek Bajbouj, Michael Bauer et al.
3 citations
A single day of treatment with an inhaled synthetic formulation of mebufotenin (GH001) significantly reduced depression symptoms in adults with treatment-resistant depression compared to placebo. In a randomized, double-blind trial of 81 patients, those receiving up to three escalating doses of GH001 showed an average 15.5-point greater improvement on the Montgomery-Åsberg Depression Rating Scale by day 8 than those on placebo. Remission rates were 57.5% for GH001 and 0% for placebo. No severe or serious adverse events occurred. The findings suggest GH001 may be a rapid-acting, well-tolerated treatment option for treatment-resistant depression.
bioRxiv (Cold Spring Harbor Laboratory)
August 19, 2024
Naji Alnagger, Paolo Cardone, Charlotte Martial et al.
3 citations
preprint
Disorders of consciousness, such as unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have few treatments. Using whole-brain computational models built from individual patients' fMRI and diffusion-weighted imaging data, this virtual clinical trial simulated the effects of LSD and psilocybin. The psychedelics shifted the brains of patients with disorders of consciousness closer to a critical dynamical state, with a larger effect in MCS patients. In UWS patients, the treatment response depended on structural connectivity, whereas in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for considering psychedelics in treating disorders of consciousness and highlight the role of computational modeling in drug discovery and personalized medicine.
Advanced Science
November 20, 2025
Paolo Cardone, Charlotte Martial, Yonatan Sanz Perl et al.
2 citations
Simulated administration of LSD and psilocybin in computational models of patients with disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), shifted brain activity closer to criticality—the phase transition between order and chaos. The effect was greater in MCS patients. In UWS patients, the treatment response correlated with structural connectivity, while in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for using psychedelics in DoC treatment and highlight the potential role of computational modeling in drug discovery and personalized medicine.
bioRxiv (Cold Spring Harbor Laboratory)
October 22, 2024
Pablo Mallaroni, S. Parker Singleton, Natasha L. Mason et al.
2 citations
preprint
A double-blind, placebo-controlled crossover study with 22 healthy volunteers compared the acute brain effects of the psychedelic phenethylamine 2C-B (20 mg) and the tryptamine psilocybin (15 mg) using 7T resting-state functional MRI. Both compounds reduced connectivity within brain networks and broadly increased connections between networks and between subcortical and cortical regions. Compared to psilocybin, 2C-B caused less reduction in between-network connectivity but increased connectivity in transmodal regions. Both drugs similarly increased brain complexity. The neural effects aligned with differences in monoaminergic and serotonergic receptor binding beyond 5-HT2A, suggesting 2C-B's distinct pharmacology shapes its functional brain dynamics.
bioRxiv (Cold Spring Harbor Laboratory)
February 16, 2023
Pablo Mallaroni, Natasha L. Mason, Johannes T. Reckweg et al.
2 citations
preprint
2C-B, a hallucinogenic phenethylamine derived from mescaline, produces subjective psychedelic effects that are shorter in duration and milder than those of psilocybin. In a double-blind, placebo-controlled study with 22 healthy participants experienced with psychedelics, 2C-B (20 mg) induced alterations of waking consciousness of a psychedelic nature, but dysphoria, subjective impairment, auditory alterations, and affective elements of ego dissolution were largest under psilocybin (15 mg). Both compounds caused equivalent psychomotor slowing and spatial memory impairments compared to placebo, and neither produced empathogenic effects on the Multifaceted Empathy Test. 2C-B also induced transient pressor effects similar to psilocybin, with self-reported effects largely resolving within 6 hours. These findings support categorizing 2C-B as a subjectively 'lighter' psychedelic.
Molecular Psychiatry
April 8, 2026
Johannes G. Ramaekers, Kim P. C. Kuypers, Franz X. Vollenweider
1 citation
MDMA, originally developed for military purposes and later used recreationally, is now being tested in clinical trials for PTSD. A narrative review of placebo-controlled single-dose studies in healthy volunteers found that 75-125 mg of MDMA acutely enhances mood, empathy, trust, and arousal while transiently impairing memory encoding through increased serotonin signaling. Motor coordination and cognitive flexibility decline modestly, but inhibitory control and executive function remain largely intact. Post-acutely, fatigue and low mood may occur. These effects may support trauma processing by facilitating fear extinction and disrupting negative memory reconsolidation, though they also complicate trial design by compromising blinding and inflating expectancy.
Journal of Psychedelic Studies
September 8, 2025
Malin Vedøy Uthaug, Giancarlo Allocca, Martha Havenith et al.
1 citation
The paper introduces the concept of 'bodyset'—the state of the body, including both body and brain—as a vital element in preparing for psychedelic experiences, expanding the traditional 'set and setting' framework. Through a literature review, it argues that the body likely matters for wellbeing, peak performance, and peak experiences. Comprehensive multidisciplinary research, especially on biomarkers, is needed to clarify the role of bodyset in psychedelic experiences and therapy outcomes. The authors suggest that considering physical state alongside psychological and environmental factors may enhance understanding of psychedelic effects and inform other treatments like breathwork.
Neuropsychopharmacology
April 22, 2025
Johannes G. Ramaekers
1 citation
No Summary