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.
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.
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.
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.