Journal of psychopharmacology (Oxford, England)
June 25, 2026
Pavan S Brar, Rebecca B Price, Stephen Ross et al.
Psychedelic compounds like psilocybin and LSD are being studied again as potential treatments, but research usually excludes people at risk for psychosis. This narrative review examines the historical and theoretical links between psychedelics and schizophrenia spectrum disorders (SSDs), including the psychotomimetic hypothesis. The authors compare the phenomenological experiences induced by psychedelics with those of SSDs, finding both overlap and important qualitative differences that challenge a simple equivalence. They review neural mechanisms involving serotonin, dopamine, and glutamate. Clinical evidence shows psychedelics can worsen existing psychotic illness and may trigger psychosis in vulnerable individuals, though the risk magnitude is not well quantified. The authors suggest potential therapeutic applications for carefully selected symptoms in stable patients using low-dose, controlled approaches and provide recommendations for managing psychosis-related risk.
Zenodo (CERN European Organization for Nuclear Research)
June 24, 2026
Ramiro Solis
The brain's ability to rewire itself declines with age, but why remains unclear. This paper examines whether the compound N,N-dimethyltryptamine (DMT) helps maintain neuroplasticity, and whether its decline contributes to age-related loss of cognitive flexibility. DMT promotes synaptic growth and neurogenesis in animals, and levels are reportedly highest during development. However, evidence is mixed: one study finds DMT concentrations comparable to serotonin, while another finds it undetectable in rat brain. DMT's affinity for the sigma-1 receptor is three orders of magnitude higher than physiological concentrations, and a key finding about intracellular 5-HT2A receptor binding has not been replicated. The paper does not claim the hypothesis is established, but proposes a research program to test whether DMT depletion causes lost plasticity or is incidental.
Future Pharmacology
June 23, 2026
Gabriella de Souza Gomes Ribeiro, Pieter Annaert, Frederico Severino Martins et al.
CYP2D6 genetic variants substantially alter the body's exposure to the psychedelic brew ayahuasca's active compounds, N,N-dimethyltryptamine (DMT) and harmine (HRM). Using physiologically based pharmacokinetic modeling, poor metabolizers showed 53.3% higher area under the curve (AUC) and 40.5% higher peak concentration (Cmax) for DMT, with similar but smaller increases for HRM; ultra-rapid metabolizers showed reduced exposure to both. These results indicate that CYP2D6 polymorphisms contribute to interindividual variability in ayahuasca pharmacokinetics, with potential clinical implications.
Figshare
June 23, 2026
Elena Bray, Grant C. Glatfelter, Alexander D. Maitland et al.
A new chemical synthesis of 4-bromo-N,N-dimethyltryptamine (4-Br-DMT) was developed, enabling the creation of novel tryptamine molecules with modifications at the C4 position via palladium cross-coupling reactions. This approach facilitates rapid development of a library of compounds for studying structure-activity relationships with serotonergic targets. Compared to psilocin and DMT, 4-Br-DMT exhibits a serotonergic profile but lacks psychedelic-like effects in mice, though it has a reduced safety profile.
Zenodo (CERN European Organization for Nuclear Research)
June 22, 2026
Ramiro Solis
The human body has enzymes that both make and rapidly break down DMT, a molecule structurally nearly identical to serotonin that binds to the same serotonin receptors. This raises the question of whether DMT serves an endogenous physiological function or is merely a metabolic byproduct. Evidence is mixed: one report finds DMT concentrations in the nanomolar range comparable to serotonin and dopamine, while another finds DMT undetectable in rat brain. DMT's affinity for the sigma-1 receptor is far weaker than its likely physiological concentrations, and a key finding about intracellular 5-HT2A receptor binding has not been replicated.
Metabolic Engineering
June 14, 2026
Zachary N. Abrahms, Mohammad Majdi, Siena M. Madsen et al.
A new genome engineering strategy called ePathIntegrate uses CRISPR-associated transposases to stably insert complex metabolic pathways into the chromosome of E. coli. When plasmid-optimized pathways for the psychedelic compounds psilocybin and DMT were moved directly to the genome, productivity dropped because promoters behaved differently in the new context. A library of mutant T7 promoters was developed to restore proper transcriptional control. With ePathIntegrate, the re-optimized pathways yielded 1.88 g/L psilocybin and 1.62 g/L DMT in fed-batch bioreactors. Whole-genome sequencing showed precise on-target integration but also some off-target integrations and small mutations, indicating both the promise and current limitations of this approach.
Neurology
June 9, 2026
Emmanuelle Schindler, Kevin Lenaburg, Robert Wold
A survey of adults with cluster headache found that many use N,N-dimethyltryptamine (DMT) to treat their condition, with some reporting benefits. The text does not provide specific numbers or effect sizes.
Psychopharmacology bulletin
June 5, 2026
Michael E Thase, Brian Brennan, Rachael Macisaac et al.
In patients with treatment-resistant depression, a single-day individualized dosing regimen of inhaled GH001 (synthetic mebufotenin) produced rapid and large improvements in depressive symptoms compared with placebo in a Phase 2b trial, with 57.5% achieving remission at Day 8 versus 0% on placebo. A post hoc analysis of 40 patients who received GH001 found no meaningful correlation between the number of prior lifetime antidepressant treatment failures and improvement on the Montgomery-Åsberg Depression Rating Scale at Day 8 or among 6-month open-label extension completers. Remission rates at Day 8 were similar across subgroups with 2, 3, 4, or 5 or more prior failures (range 53.9%-63.6%) and were maintained at Month 6 (range 61.5%-85.7%). The efficacy of GH001 appears largely independent of how many prior antidepressant treatments a patient has tried.
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.
Universität Zürich, ZORA
June 1, 2026
Klemens Egger, Robert Bozsak, Helena D Aicher et al.
A psychedelic dose of DMT combined with the MAO-A inhibitor harmine, mimicking ayahuasca, globally increased cerebral glucose metabolism by 12.5% compared to placebo in 14 healthy males. Scans acquired during peak drug effects using FDG-PET showed widespread cortical increases, particularly in higher-order brain networks. Higher harmine plasma levels correlated with greater global glucose metabolism, while DMT levels and subjective intensity did not. This metabolic signature recapitulates a classic finding for psilocybin, suggesting a potential hallmark of the psychedelic state.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
June 1, 2026
Klemens Egger, Robert Bozsak, Helena D Aicher et al.
A psychedelic dose of DMT combined with harmine (mimicking ayahuasca) globally increased cerebral glucose metabolism by 12.5% in 14 healthy males, as measured by FDG-PET scans during peak drug effects. Widespread cortical increases appeared in higher-order brain networks. Global glucose metabolism correlated positively with harmine plasma levels but not with DMT levels or subjective intensity. This recapitulates a classic finding for psilocybin, suggesting a potential metabolic signature of the psychedelic state.