Journal of Psychopharmacology
February 27, 2026
Claire T. Roberts, Mathieu Seynaeve, Anna O. Ermakova et al.
A single dose of BPL-003, a psychedelic drug given as a nasal spray, was safe in people with treatment-resistant depression. Depression scores dropped quickly and stayed lower for 12 weeks, suggesting the drug may help this hard-to-treat condition. Larger controlled trials are needed.
Biomedicines
February 25, 2026
Alice Melani, Giorgia Papini, Marco Bonaso et al.
Psychedelics are gaining renewed scientific interest as breakthrough therapies for mental disorders, with ayahuasca and its active component DMT showing particular promise. DMT acts primarily as a serotonin 5-HT2A receptor partial agonist, while 5-MeO-DMT has higher affinity for 5-HT1A receptors; both foster neuroplasticity and reorganize brain networks involved in perception, cognition, and mood. Current evidence offers an optimistic outlook for treatment-resistant depression and major depressive disorder, with four phase II studies of 5-MeO-DMT and one of DMT for TRD, plus two phase II studies of DMT fumarate for MDD. Evidence for other mental disorders remains preliminary.
ChemMedChem
February 25, 2026
Anton A. Homon, Jaxon Laramie, John J. Hayward et al.
Bufotenin and 5-MeO-DMT are potent psychedelics found in plants and toad secretions. Although used in traditional medicine, 20th-century prohibition slowed research into their therapeutic potential for psychological disorders and inflammatory and neurodegenerative diseases. Recent global trends toward legalization have increased clinical and preclinical studies, creating demand for large amounts of these compounds that are not commercially available on scale. The first bufotenin synthesis was reported in 1935, and new syntheses continue to appear in the 2020s. This review collates and compares all extant academic and patent syntheses as of fall 2024, enabling researchers to identify the most appropriate route. Outstanding challenges for reducing commercial-scale production costs are highlighted.
Current Addiction Reports
February 21, 2026
Dráulio B. Araújo, Lucas O. Maia, Tiago Arruda-Sanchez et al.
Preclinical and clinical evidence suggests that ayahuasca, a traditional Amazonian brew containing DMT and β-carbolines, may treat depression, anxiety, post-traumatic stress disorder, substance use, eating, and personality disorders. Preclinical studies indicate enhanced neuroplasticity, reduced inflammation, and oxidative stress. Human neuroimaging shows decreased default mode network activity, increased functional connectivity and brain entropy, suggesting a flexible neural state and modulation of pathways related to neuroplasticity, inflammation, and stress response. The evidence is mainly observational, with users reporting emotional breakthroughs, increased self-awareness, and mystical experiences tied to therapeutic outcomes. Ayahuasca appears to target core psychological and neurobiological processes across disorders but requires caution in psychotic or bipolar individuals and should be administered with support. Randomized trials are needed to confirm efficacy and safety.
American Journal of Therapeutics
February 20, 2026
Burton J. Tabaac, Kenneth Shinozuka, Anne Weisman et al.
5-MeO-DMT, an ultra-short-acting psychedelic, shows promise for treating depression that does not respond to other therapies, as well as other psychiatric conditions. This evidence supports the need for larger randomized controlled trials to further investigate its effectiveness.
Zenodo (CERN European Organization for Nuclear Research)
February 18, 2026
Mihai Alexandru Bucurenciu
During peak conscious states such as deep meditation and DMT or 5-MeO-DMT breakthrough, gamma-band power near 43 Hz is selectively enhanced compared to eyes-open and eyes-closed baselines. Temporal locking occurs between 43 Hz gamma surges and multifractal spectrum collapse, with consistent convergence across subjects at approximately 41 seconds. AAFT surrogate testing confirms non-random dynamics (p < 0.01 for key features). High-density 256-channel mapping examples show directed 43 Hz signal from the pineal region to the AFz electrode, with up to +34.2 dB amplification in select cases.
Journal of Psychopharmacology
February 16, 2026
Marten Kase, Karl Kristjan Kaup, Jaan Aru
1 citation
A systematic review of 32 placebo-controlled studies from 1990 to 2025 examined the acute and post-acute effects of LSD, DMT, and psilocybin on cognitive and psychological functions. Psychedelics tended to enhance emotional empathy but had no effect on cognitive empathy. Effects on memory varied by task and timing, with some impairments, enhancements, or no change. Dose-dependent impairments occurred in reaction time, attention, and inhibition tasks, though some studies found no effects. Recognition of negative stimuli was impaired under acute effects. Findings on cognitive flexibility were mixed. Many studies had small samples, and finding a reliable placebo is challenging due to psychedelics' unique subjective effects.
Metabolites
February 14, 2026
Prajwal Punnamraju, Sascha K Manier, Selina Hemmer et al.
A liquid chromatography–high-resolution mass spectrometry workflow was used to investigate the metabolism of two N1-sulfonated N,N-dimethyltryptamine derivatives, which have potential for both therapeutic use and recreational abuse. Zebrafish larvae and pooled human liver S9 fractions revealed key phase I and phase II biotransformations. Untargeted metabolomics showed significant downregulation of L-threonine associated with compound exposure. These findings advance the understanding of tryptamine metabolism and highlight the value of toxicometabolomics for evaluating novel psychoactive substances.
Zenodo (CERN European Organization for Nuclear Research)
February 12, 2026
Mihai Alexandru
The brain produces its own DMT, a psychedelic compound, but its function has been unclear. The Axis Mundi hypothesis proposes that endogenous DMT serves two distinct evolutionary roles. At the cellular level, it acts as a sigma-1 receptor agonist that protects neurons during stress like low oxygen. At the network level, it modulates the boundary between conscious and subconscious awareness by acting on 5-HT2A receptors in the default mode network, regulating how much subconscious content reaches consciousness. This dual-function model integrates evidence from endogenous DMT biochemistry, brain imaging, memory suppression mechanisms, shared visual phenomenology, and receptor evolution. Seven testable predictions are offered to evaluate the framework.
Open Access CRIS of the University of Bern
February 9, 2026
Mikael Palner, Elisabeth Kolesnik, Christina Baun et al.
The mammalian brain may contain an endogenous pool of the psychedelic N,N-dimethyltryptamine (DMT), possibly acting as a co-transmitter with serotonin. In rats, inhibiting monoamine oxidase with pargyline did not make endogenous DMT detectable, while probenecid slightly elevated the acidic metabolite 3-indoleacetic acid (3-IAA), suggesting formation from tryptamine, especially in the striatum. After administering DMT plus harmine, peak brain DMT occurred at 45 minutes and peak 3-IAA at 60 minutes, with nearly complete washout by 210 minutes. Escitalopram did not alter exogenous DMT or 3-IAA disposition, and dihydrotetrabenazine slightly increased 3-IAA in some regions. The results do not support an endogenous DMT pool or retention of exogenous DMT in serotonin terminals.
Neuropharmacology
February 9, 2026
Mikael Palner, Elisabeth Kolesnik, Christina Baun et al.
The study tested whether the psychedelic compound N,N-dimethyltryptamine (DMT) exists naturally in the mammalian brain and acts as a co-transmitter with serotonin. In rats, blocking monoamine oxidase with pargyline did not allow detection of endogenous DMT, while blocking acidic metabolite transport with probenecid slightly elevated the DMT metabolite 3-indoleacetic acid, likely from tryptamine. Exogenous DMT was rapidly taken up and cleared from the brain, with peak concentrations at 45 minutes and near-complete washout by 210 minutes. Blocking serotonin reuptake or vesicular monoamine transporters did not alter DMT levels. The results do not support the hypothesis that DMT is an endogenous co-transmitter with serotonin.
Preprints.org
February 9, 2026
Philippe Henry
preprint
A novel treatment approach for treatment-resistant depression and chronic anxiety combines the rapid neuroplastic effects of the psychedelic 5-MeO-DMT with the anxiolytic properties of the cannabinoid THCV, delivered via a precision vaporization device. The THCV acts as a 'cushion' to prevent the panic and acute activity increase often triggered by high-potency psychedelics, while allowing the tryptamine to promote synaptic growth and reset the Default Mode Network. This synergistic combination aims to provide more effective and tolerable relief than existing antidepressants, which require weeks to work and do not address synaptic atrophy.