ACS pharmacology & translational science
April 9, 2021
Gabrielle Agin-Liebes, Trevor F Haas, Rafael Lancelotta et al.
121 citations
Most people who used mescaline in natural settings reported lasting improvements in depression, anxiety, PTSD, and substance use disorders, with 68–86% of those with a history of these conditions noting subjective improvement after their most memorable experience. Those who improved reported stronger acute mystical-type, psychological insight, and ego dissolution effects (Cohen's d 0.7–1.5). For 35–50% of respondents, the mescaline experience ranked among the top five most spiritually significant or meaningful events of their lives. Psychological insight during the experience was linked to higher odds of improvement in depression, anxiety, and alcohol and drug use disorders. The authors call for controlled clinical trials to confirm these preliminary findings.
Frontiers in Psychiatry
June 20, 2023
Johannes T Reckweg, Cees J van Leeuwen, Cécile Henquet et al.
86 citations
In a small clinical trial with 16 adults suffering from treatment-resistant depression, an inhaled form of the psychedelic drug 5-MeO-DMT (GH001) was well tolerated and produced rapid antidepressant effects. An individualized dosing regimen of up to three increasing doses within a single day led to 87.5% of patients achieving remission (a depression score of 10 or less on the MADRS scale) by day 7, compared to 50% and 25% for single doses of 12 mg and 18 mg, respectively. Remission occurred as early as two hours after dosing for some patients. The findings suggest that individualized dosing may be more effective than a single dose.
Journal of psychopharmacology (Oxford, England)
March 1, 2022
Malin Vedøy Uthaug, Alan K Davis, Trevor Forrest Haas et al.
64 citations
Mescaline, a naturally occurring psychoactive compound found in cacti such as Peyote and San Pedro, is used infrequently (once a year or less) by most English-speaking adults, primarily for spiritual exploration or connection with nature (74%). In a web-based survey of 452 respondents, very few reported drug craving (9%), legal problems (1%), or psychological problems (1%), and none sought medical attention. Acute mystical-type effects were rated as moderate, ego-dissolution and insight as slight, and challenging effects as very slight. About half of the sample had a psychiatric condition, and most (over 67%) reported improvements in these conditions after their most memorable mescaline experience. The findings suggest that mescaline may produce a psychedelic experience with spiritual significance and mental health benefits and has low abuse potential.
Frontiers in pharmacology
January 1, 2021
Johannes Reckweg, Natasha L Mason, Cees Van Leeuwen et al.
58 citations
Vaporized 5-MeO-DMT (GH001) produces dose-dependent increases in psychedelic experience intensity in healthy volunteers, with individualized dose escalation yielding maximal effects on peak experience, mystical experience, ego dissolution, and altered states of consciousness. Higher single doses (6, 12, 18 mg) significantly increased ratings compared to 2 mg on all measures except challenging experiences. Cognition, mood, and well-being were unaffected. Vital signs remained stable, and adverse events were mild and self-resolving. Individualized dose escalation may be preferable for clinical applications aiming to maximize the psychedelic experience for therapeutic response.
Neuroscience of consciousness
January 1, 2025
Christopher Timmermann, James W Sanders, David Reydellet et al.
19 citations
The psychedelic 5-MeO-DMT can, in its most extreme cases, produce a complete absence of self-experience and other perceptual content while preserving a quality of aroused, waking awareness. In an exploratory observational study in naturalistic ceremonial settings, micro-phenomenological interviews, questionnaires, and EEG recordings revealed a dynamic progression of effects, including variable disruptions of bodily and narrative self, reduced phenomenal distinctions, and visual imagery. EEG showed global alpha and posterior beta power reductions, suggesting inhibition of top-down brain models. The findings indicate 5-MeO-DMT's potential as a pharmacological model for deconstructed consciousness, though retrospective questionnaires have limitations.
NeuroImage
January 1, 2024
Pablo Mallaroni, Natasha L Mason, Lilian Kloft et al.
17 citations
Brain functional connectomes are unique fingerprints that persist across mental states, but their stability under altered states is unknown. After collective ayahuasca intake in 21 Santo Daime members, 7T fMRI showed reduced idiosyncrasy in static and dynamic functional connectivity, with a spatiotemporal reallocation of keypoint edges. Interindividual differences in higher-order connectivity motifs predicted perceptual drug effects, demonstrating that individualized connectivity markers can trace a subject's functional connectome across altered states of consciousness.
Translational psychiatry
July 15, 2024
Nadia R P W Hutten, Conny W E M Quaedflieg, Natasha L Mason et al.
16 citations
Repeated low doses of LSD (15 mcg) affect arousal, attention, and memory depending on a person's baseline cognitive state. In a randomized placebo-controlled trial with 53 healthy participants, LSD reduced resting-state EEG delta, theta, and alpha power (indicating stimulation) and enhanced pre-attentive processing during acute dosing sessions. LSD also blunted visual long-term potentiation (a marker of perceptual learning and memory) by the fourth dosing session. Stimulatory effects were strongest in individuals with low baseline arousal and attention, while inhibitory effects on memory were strongest in those with high baseline memory performance. Some EEG changes persisted at a one-week follow-up, suggesting possible neuroadaptations from repeated low-dose LSD.
Biological psychiatry. Cognitive neuroscience and neuroimaging
July 1, 2024
Sepehr Mortaheb, Larry D Fort, Natasha L Mason et al.
15 citations
Psilocybin produces profound alterations in both brain connectivity and subjective experience. In a randomized study, healthy volunteers received psilocybin or placebo and underwent ultrahigh field 7T fMRI scanning during the peak drug effect. Psilocybin caused widespread increases in averaged brain functional connectivity and a recurrent hyperconnected brain pattern with low blood oxygen level-dependent signal amplitude, suggesting heightened cortical arousal. This hyperconnected pattern was linked to feelings of oceanic boundlessness and visionary restructuralization. The brain's tendency to enter this hyperconnected-hyperarousal state may underlie the variant mental associations characteristic of the psychedelic experience.
Journal of Cognitive Neuroscience
January 1, 2023
Johannes G Ramaekers, Pablo Mallaroni, Lilian Kloft et al.
15 citations
In members of the Santo Daime church who regularly consume ayahuasca in a ritual setting, the brew's main psychoactive compound DMT drives feelings of oceanic boundlessness, visual restructuring, and ego dissolution, with these effects correlating with peak DMT concentration in the blood. However, measures of mental imagery—including visual perspective shifting, vividness of imagery, and associative thinking—did not noticeably differ between sober and ayahuasca conditions, though subjective cognitive flexibility was lower under ayahuasca. Two mental imagery measures (perspective shifts and cognitive flexibility) correlated with peak DMT levels. Long-term ayahuasca use may produce compensatory or neuroadaptive effects that dampen the acute impact on mental imagery.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
December 31, 2023
Francisco Madrid-Gambin, David Fabregat-Safont, Alex Gomez-Gomez et al.
12 citations
Psychedelics like LSD, mescaline, DMT, ayahuasca, 5-methoxy-DMT, and psilocybin induce altered states of consciousness and are being studied for treating mental health disorders. This review examines metabolic and metabolomics studies in humans after administration of these drugs. The main metabolites for classical psychedelics have been robustly established, but the metabolic alterations they induce need further exploration. Integrating metabolomics with pharmacokinetics may help understand the therapeutic role of psychedelics by revealing molecular interactions with multiple targets.
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
In a first-in-human trial, low to moderate doses of the synthetic cathinone 3-MMC were well tolerated and safe, with potential health risks only at high or excessive doses. 3-MMC caused dose-dependent increases in heart rate and blood pressure that were not clinically significant, along with feelings of subjective high. It also enhanced performance on several neurocognitive tasks, including processing speed, cognitive flexibility, psychomotor function, attention, and memory, while impulse control was unaffected. Participants reported mild dissociative and psychedelic effects, decreased appetite, and transient liking and wanting for the drug. The cardiovascular, psychostimulant, and psychotomimetic profile resembles that of amphetamine-related compounds.
Biological psychiatry. Cognitive neuroscience and neuroimaging
October 1, 2024
Manoj K Doss, Pablo Mallaroni, Natasha L Mason et al.
7 citations
Two psychedelics, psilocybin and 2C-B, impair the encoding of detailed recollections and distort feelings of familiarity for emotional memories. In a double-blind, placebo-controlled study with 20 participants, both drugs reduced estimates of recollection and familiarity the next day, but increased false alarms based on familiarity, especially for negative and positive images. The drugs also tended to impair metamemory for negative and neutral memories while enhancing it for positive ones, though these effects were less reliable. The similar pattern across both substances suggests a shared neurocognitive mechanism among psychedelics that may underlie other phenomena.
Journal of psychopharmacology (Oxford, England)
April 1, 2025
Manoj K Doss, Lilian Kloft, Natasha L Mason et al.
5 citations
In experienced users, ayahuasca acutely enhances recollection-based memory—the ability to recall specific details—without increasing false memories or affecting familiarity-based memory, a feeling of knowing. In an observational study of 24 Santo Daime members who had consumed ayahuasca over 500 times on average, participants completed a false memory task before and after taking a self-selected church dose. After ayahuasca, hit rates, memory accuracy, and recollection improved, while familiarity and false memory remained unchanged. The authors suggest that β-carboline activity in the brew may account for this recollection enhancement, which contrasts with past psychedelic research showing impaired recollection. Practice effects could not be ruled out, but multiple measures of false memory and metamemory did not improve across sessions.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
August 1, 2024
Zeus Tipado, Kim P C Kuypers, Bettina Sorger et al.
5 citations
Psychedelics like LSD and psilocybin alter perception by activating serotonin receptors in cortical and subcortical brain regions, often causing visual disturbances or hallucinations. While current theories focus on disrupted communication between these brain areas, rare conditions like Charles Bonnet syndrome suggest the retinofugal pathway may also play a key role. Interneurons in the retina called amacrine cells could be the first site of psychedelic modulation, disrupting how visual information is hierarchically processed. This paper presents a new theory of psychedelic modulation in the retinofugal pathway, drawing parallels with clinical conditions to explain visual perceptual changes.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 1, 2025
Francisco Madrid-Gambin, Noemí Haro, Natasha L Mason et al.
4 citations
The metabolome—the collection of small molecules in blood—differs between occasional and chronic cannabis users both when sober and after acute THC intoxication. Fourteen metabolites, mainly involved in endocannabinoid and amino acid metabolism, distinguished the two groups with 80% accuracy. During intoxication, occasional users showed attentional impairment and elevated subjective high, accompanied by increases in organic acids, β-hydroxybutyrate, and ceramides; chronic users did not show these changes. The findings demonstrate that metabolomic profiling can identify metabolic alterations specific to the neurocognitive state of cannabis intoxication and to cannabis use frequency.
Frontiers in psychology
January 1, 2025
Johannes T Reckweg, Natasha L Mason, Eef L Theunissen et al.
2 citations
A three-item Peak Experience Scale (PES) was developed to quickly gauge the intensity of the psychoactive experience with the psychedelic 5-MeO-DMT and to guide dosing. Data came from three studies involving 84 healthy volunteers and patients with treatment-resistant depression who inhaled a 5-MeO-DMT formulation at doses of 0 (placebo), 2, 6, 12, or 18 mg, or an incremental individualized dosing regimen. PES ratings increased significantly with dose, peaking after the individualized regimen. The scale showed strong internal consistency and high correlation with other psychedelic assessment tools like the Mystical Experience Questionnaire and Ego Dissolution Inventory, but not with the Challenging Experience Questionnaire. The PES is an effective, simple tool for rapidly assessing psychedelic experience strength and may help guide dosing of rapid-acting psychedelics.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
June 1, 2026
Francisco Madrid-Gambin, Pablo Mallaroni, Noemí Haro et al.
The psychedelic state induced by ayahuasca arises from coordinated, system-level interactions between peripheral metabolism and brain network dynamics, rather than isolated neurochemical events. In 20 experienced ceremonial users, the subjective dimensions of oceanic boundlessness, visionary restructuralization, and auditory alterations covaried with circulating DMT and β-carbolines, shifts in lipid, amino acid, and energy metabolism, and reconfiguration of dorsal attention and default mode network connectivity. Shared features across these experiences were most strongly linked to endocannabinoid-related N-acylethanolamines, acylglycerols, and ceramides, extending beyond canonical serotonergic models to downstream lipid-signaling and metabolic processes. The findings offer translational insight into metabolic pathways that may modulate brain function and subjective response.
Psychopharmacology
April 29, 2026
Anne-Fiona Griesfeller, Lotte Kooman, Lilian Kloft-Heller et al.
A scoping review of 53 sources found no coherent explanation for how psychedelics might recover repressed memories, nor consistent evidence that they do so reliably. Most publications focused on LSD, but few defined what they meant by repressed memory. Proposed mechanisms—psychoanalytical reductions of defensive memory blockades and neurobiological alterations of executive control—lacked empirical support. The review concludes that future work should provide clear definitions, test effects across multiple psychedelic substances, use placebo-controlled designs, and account for the potential occurrence of false memories.
International review of neurobiology
January 1, 2025
Iva Totomanova, Eline C H M Haijen, Petra P M Hurks et al.
Small doses of LSD and psilocybin produce subtle acute effects on neural connectivity, brain electrophysiology, blood pressure, sleep duration, pain perception, temporal processing, and mood, and reduce symptoms of depression and obsessive-compulsive behavior in patient samples. Extra-pharmacological factors such as baseline subjective state, expectations, and individual differences in drug metabolism influence treatment outcomes. Controlled microdosing studies suggest potential therapeutic applications, but large-scale clinical trials are still needed.
Neuroscience and biobehavioral reviews
July 1, 2022
Drummond E-Wen Mcculloch, Gitte Moos Knudsen, Frederick Streeter Barrett et al.
A large group of psychedelic imaging researchers reviewed 42 articles from 17 unique studies that used resting-state functional magnetic resonance imaging (rs-fMRI) to examine psychedelic effects. They found that nearly all studies varied in data processing and analysis methods, two datasets underpin over half of the published literature, and key outcome terms are used ambiguously. The authors recommend guidelines to improve consistency and replicability in future research, arguing that the field must balance novel methods with standardized approaches to reliably understand the neural mechanisms of psychedelics.