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.
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.
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.
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.
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.
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.