Johannes T. Reckweg - The Consciousness Library

Brain-body integromics of the ayahuasca experience.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 1, 2026 Francisco Madrid-Gambin, Pablo Mallaroni, Noemí Haro et al.

Ayahuasca is a psychoactive brew containing N,N-dimethyltryptamine (DMT) and β-carboline alkaloids that induces marked alterations in perception, emotion and self-referential processing. However, the multiscale biological organization linking peripheral metabolism, brain network dynamics, neurochemistry, and subjective experience in humans remains poorly understood. Here, we applied an...

DOI: 10.1016/j.biopha.2026.119391 Full text Ayahuasca Dimethyltryptamine Connectome Integromics +2

Safety and cognitive pharmacodynamics following dose escalations with 3-methylmethcathinone (3-MMC): a first in human, designer drug study.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology June 1, 2025 Johannes G. Ramaekers, Johannes T. Reckweg, Natasha L. Mason et al. 8 citations

3-Methylmethcathinone (3-MMC) is a designer drug that belongs to the group of synthetic cathinones. The compound has been scheduled in many jurisdictions because of public health concerns associated with excessive use. To date, there are no clinical studies that have evaluated the risk profile of 3-MMC in the recreational range of low to moderate doses. The current, first-in-human study (N =...

DOI: 10.1038/s41386-024-02042-7 Full text

Low to moderate doses of 3-methylmethcathinone (3-MMC) produce analgesic effects in healthy volunteers: a proof of principle study with a designer drug

Psychopharmacology April 30, 2025 Johannes G. Ramaekers, Johannes T. Reckweg, Natasha L. Mason et al. 4 citations

3-Methylmethcathinone (3-MMC) is a synthetic cathinone that has been scheduled in many jurisdictions after it appeared on the consumer market as a designer drug or "legal high". At present, there are no medical applications for synthetic cathinones, but in the past cathinone and other compounds that are structurally related to amphetamine have been evaluated and recognized for their intrinsic...

DOI: 10.1007/s00213-025-06798-8 Full text Analgesic Dosing Anesthesia Placebo +5

Ayahuasca enhances the formation of hippocampal-dependent episodic memory without impacting false memory susceptibility in experienced ayahuasca users: An observational study.

Journal of psychopharmacology (Oxford, England) April 1, 2025 Manoj K. Doss, Lilian Kloft, Natasha L. Mason et al. 5 citations

Ayahuasca is an Amazonian brew with 5-HT2A-dependent psychedelic effects taken by religious groups globally. Recently, psychedelics have been shown to impair the formation of recollections (hippocampal-dependent episodic memory for specific details) and potentially distort memory while remembering. However, psychedelics spare or enhance the formation of familiarity-based memory...

DOI: 10.1177/02698811241301216 Full text Ayahuasca Episodic memory False memory Familiarity +5

Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression

American Journal of Psychiatry 2025 Johannes G. Ramaekers, Johannes T. Reckweg, Natasha L. Mason 25 citations

Unlike classical antidepressants, psychedelics such as psilocybin have been shown to induce a rapid antidepressant response. In the wake of this development, interest has emerged in ultra-fast, short-acting psychedelics such as 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and N,N-dimethyltryptamine (DMT) with the expectation that these can produce rapid antidepressant effects following an...

DOI: 10.1176/appi.ajp.20230890 5-MEO-DMT Depression Psychedelic drugs Quick-onset treatment +3

Evaluation of the peak experience scale as a rapid assessment tool for the strength of a psychoactive experience with 5-MeO-DMT.

Frontiers in Psychology 2025 Johannes T. Reckweg, Natasha L. Mason, Eef L. Theunissen et al. 2 citations

A three-item Peak Experience Scale (PES) was developed to rapidly evaluate the strength of the psychoactive experience, and to guide the dosing regimen, of the psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; mebufotenin). This paper aims to compare the PES with a range of established questionnaires designed to evaluate the psychedelic experience. Data were gathered from three separate...

DOI: 10.3389/fpsyg.2025.1543640 Full text Peak experience Psychedelic Questionnaire Intensity +15

Shared functional connectome fingerprints following ritualistic ayahuasca intake.

Neuroimage 2024 Pablo Mallaroni, Natasha L. Mason, Lilian Kloft et al. 17 citations

The knowledge that brain functional connectomes are unique and reliable has enabled behaviourally relevant inferences at a subject level. However, whether such "fingerprints" persist under altered states of consciousness is unknown. Ayahuasca is a potent serotonergic psychedelic which produces a widespread dysregulation of functional connectivity. Used communally in religious ceremonies, its...

DOI: 10.1016/j.neuroimage.2023.120480 Full text DMT Entheogens Brain connectivity connectome Neuroimaging FMRI +8

Cortical structural differences following repeated ayahuasca use hold molecular signatures

Frontiers in Neuroscience October 5, 2023 Pablo Mallaroni, Lilian Kloft, Natasha L. Mason et al. 8 citations

Introduction Serotonergic psychedelics such as ayahuasca are reported to promote both structural and functional neural plasticity via partial 5-HT 2A agonism. However, little is known about how these molecular mechanisms may extend to repeated psychedelic administration in humans, let alone neuroanatomy. While early evidence suggests localised changes to cortical thickness in long-term...

DOI: 10.3389/fnins.2023.1217079 Ayahuasca Neuroplasticity Serotonergic Immediate early gene +1

Psilocybin induces acute and persisting alterations in immune status in healthy volunteers: An experimental, placebo-controlled study

Brain Behavior and Immunity September 7, 2023 Natasha L. Mason, Attila Szabo, Kim P. C. Kuypers et al. 83 citations

Patients characterized by stress-related disorders such as depression display elevated circulating concentrations of pro-inflammatory cytokines and a hyperactive HPA axis. Psychedelics are demonstrating promising results in treatment of such disorders, however the mechanisms of their therapeutic effects are still unknown. To date the evidence of acute and persisting effects of psychedelics on...

DOI: 10.1016/j.bbi.2023.09.004 Psilocybin Placebo Immune system Cytokine +4

A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression

Frontiers in Psychiatry June 20, 2023 Johannes T. Reckweg, Cees van Leeuwen, Cécile Henquet et al. 86 citations

Background Treatment-resistant depression (TRD) is a substantial public health burden, but current treatments have limited effectiveness. The aim was to investigate the safety and potential antidepressant effects of the serotonergic psychedelic drug 5-MeO-DMT in a vaporized formulation (GH001) in adult patients with TRD. Methods The Phase 1 part ( n = 8) of the trial investigated two single...

DOI: 10.3389/fpsyt.2023.1133414 5-MEO-DMT Treatment-resistant depression Clinical trial Individualized dosing +9

Assessment of the Acute Effects of 2C‐B vs. Psilocybin on Subjective Experience, Mood, and Cognition

Clinical Pharmacology & Therapeutics May 30, 2023 Pablo Mallaroni, Riccardo Paci, Sabrina Ritscher et al. 34 citations

2,5‐dimethoxy‐4‐bromophenethylamine (2C‐B) is a hallucinogenic phenethylamine derived from mescaline. Observational and preclinical data have suggested it to be capable of producing both subjective and emotional effects on par with other classical psychedelics and entactogens. Whereas it is the most prevalently used novel serotonergic hallucinogen to date, it's acute effects and distinctions...

DOI: 10.1002/cpt.2958 Full text Psilocybin Mescaline Serotonergic Hallucinogen +7

Altered State of Consciousness and Mental Imagery as a Function of N, N-dimethyltryptamine Concentration in Ritualistic Ayahuasca Users

Journal of Cognitive Neuroscience 2023 Johannes G. Ramaekers, Pablo Mallaroni, Lilian Kloft et al. 15 citations

Abstract Consumption of the psychedelic brew ayahuasca is a central ritualistic aspect of the Santo Daime religion. The current observational, baseline controlled study was designed to assess whether members (n = 24) of the Santo Daime church would show enhanced capacity for mental imagery during an ayahuasca experience. In addition, this study assessed whether the effects of ayahuasca on...

DOI: 10.1162/jocn_a_02003 Ayahuasca DMT Psychedelics Consciousness research +1

Psilocybin induces acute and persisting alterations in immune status and the stress response in healthy volunteers

medRxiv November 1, 2022 Natasha L. Mason, Attila Szabo, Kim P. C. Kuypers et al. 6 citations preprint

Abstract Patients characterized by stress-related disorders such as depression display elevated circulating concentrations of pro-inflammatory cytokines and a hyperactive HPA axis. Psychedelics are demonstrating promising results in treatment of such disorders, however the mechanisms of their therapeutic effects are still unknown. To date the evidence of acute and persisting effects of...

DOI: 10.1101/2022.10.31.22281688 Full text Psilocybin Placebo Immune system Hallucinogen +6

Ritualistic use of ayahuasca enhances a shared functional connectome identity with others

bioRxiv (Cold Spring Harbor Laboratory) October 11, 2022 Pablo Mallaroni, Natasha L. Mason, Lilian Kloft et al. 4 citations preprint

Abstract The knowledge that brain functional connectomes are both unique and reliable has enabled behaviourally relevant inferences at a subject level. However, it is unknown whether such “fingerprints” persist under altered states of consciousness. Ayahuasca is a potent serotonergic psychedelic which elicits a widespread dysregulation of functional connectivity. Used communally in religious...

DOI: 10.1101/2022.10.07.511268 Full text Ayahuasca Serotonergic Connectome Resting State FMRI +3

A Phase 1, Dose-Ranging Study to Assess Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N,N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers

European Psychiatry June 1, 2022 Johannes T. Reckweg, Natasha L. Mason, Cees van Leeuwen et al. 3 citations

Introduction 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a tryptamine with ultra-rapid onset and short duration of psychedelic effects. Prospective studies for other tryptamines have suggested beneficial effects on mental health outcomes. Objectives In preparation for a study in patients with depression, the present study GH001-HV-101 aimed to assess the impact of four different dose levels...

DOI: 10.1192/j.eurpsy.2022.1846 Full text Psilocybin Tolerability Mood Adverse effect +2

Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience

Biomedicine & Pharmacotherapy March 24, 2022 Francisco Madrid-Gambin, Alex Gomez-Gomez, Arnau Busquets-García et al. 14 citations

There has been a renewed interest in the potential use of psychedelics for the treatment of psychiatric conditions. Nevertheless, little is known about the mechanism of action and molecular pathways influenced by ayahuasca use in humans. Therefore, for the first time, our study aims to investigate the human metabolomics signature after consumption of a psychedelic, ayahuasca, and its connection...

DOI: 10.1016/j.biopha.2022.112845 Ayahuasca Metabolomics Pharmacology

The clinical pharmacology and potential therapeutic applications of 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeO‐DMT)

Journal of Neurochemistry February 12, 2022 Johannes T. Reckweg, Malin V. Uthaug, Attila Szabo et al. 108 citations

Abstract 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeO‐DMT) is a naturally occurring tryptamine that primarily acts as an agonist at the 5‐HT1A and 5‐HT2A receptors, whereby affinity for the 5‐HT1A subtype is highest. Subjective effects following 5‐MeO‐DMT administration include distortions in auditory and time perception, amplification of emotional states, and feelings of ego dissolution that...

DOI: 10.1111/jnc.15587 Anxiety Agonist Depression economics Pharmacology +1

Spontaneous and deliberate creative cognition during and after psilocybin exposure

Translational Psychiatry April 8, 2021 Natasha L. Mason, Kim P. C. Kuypers, Johannes T. Reckweg et al. 132 citations

Abstract Creativity is an essential cognitive ability linked to all areas of our everyday functioning. Thus, finding a way to enhance it is of broad interest. A large number of anecdotal reports suggest that the consumption of psychedelic drugs can enhance creative thinking; however, scientific evidence is lacking. Following a double-blind, placebo-controlled, parallel-group design, we...

DOI: 10.1038/s41398-021-01335-5 Full text Psilocybin Default mode network Creativity Cognition +6

A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats

Psychopharmacology March 10, 2021 Malin V. Uthaug, Natasha L. Mason, Stefan W. Toennes et al. 116 citations

Abstract Ayahuasca is a plant concoction containing N,N -dimethyltryptamine (DMT) and certain β-carboline alkaloids from South America. Previous research in naturalistic settings has suggested that ingestion of ayahuasca can improve mental health and well-being; however, these studies were not placebo controlled and did not control for the possibility of expectation bias. This naturalistic...

DOI: 10.1007/s00213-021-05817-8 Full text Ayahuasca Anxiety Mental health Placebo +6

Psychotomimetic symptoms after a moderate dose of a synthetic cannabinoid (JWH-018): implications for psychosis

Psychopharmacology January 26, 2021 Eef L. Theunissen, Johannes T. Reckweg, Nadia R. P. W. Hutten et al. 20 citations

BACKGROUND: Synthetic cannabinoids (SCs) are the largest class of novel psychoactive substances (NPS) and are associated with an increased risk of overdosing and adverse events such as psychosis. JWH-018 is one of the earliest SCs and still widely available in large parts of the world. Controlled studies to assess the safety and behavioural profiles of SCs are extremely scarce. AIM: The current...

DOI: 10.1007/s00213-021-05768-0 Full text Cannabis Psychotomimetic Psychosis Synthetic cannabinoids +5

A Phase 1, Dose-Ranging Study to Assess Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N, N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers.

Frontiers in Pharmacology 2021 Johannes T. Reckweg, Natasha L. Mason, Cees van Leeuwen et al. 58 citations

5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a tryptamine with ultra-rapid onset and short duration of psychedelic effects. Prospective studies for other tryptamines have suggested beneficial effects on mental health outcomes. In preparation for a study in patients with depression, the present study GH001-HV-101 aimed to assess the impact of four different dose levels of a novel vaporized...

DOI: 10.3389/fphar.2021.760671 Full text 5-MEO-DMT Cognition Dose finding Psychedelic agents +1

Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology November 1, 2020 Natasha L. Mason, K P C Kuypers, F Müller et al. 261 citations

There is growing interest in the therapeutic utility of psychedelic substances, like psilocybin, for disorders characterized by distortions of the self-experience, like depression. Accumulating preclinical evidence emphasizes the role of the glutamate system in the acute action of the drug on brain and behavior; however this has never been tested in humans. Following a double-blind,...

DOI: 10.1038/s41386-020-0718-8 Full text

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