Progress in Neuro-Psychopharmacology and Biological Psychiatry
February 18, 2026
Dimitri Henriques Daldegan-Bueno, C Donegan, Rachael L. Sumner et al.
1 citation
Taking very low doses of LSD (8 micrograms) repeatedly over a short period may temporarily improve mood in people with depression, though the effect needs confirmation in controlled experiments. The drug's behavior in the body was measured in this group, and no evidence of tolerance or increased sensitivity appeared, even when the dose was gradually increased.
bioRxiv Preprint Server
December 9, 2024
Clayton R. Coleman, Kenneth Shinozuka, Robert Tromm et al.
1 citation
preprint
Lysergic acid diethylamide (LSD) alters consciousness by affecting brain connectivity, particularly in the dorsolateral prefrontal cortex (DLPFC). Using fMRI and MEG data from healthy participants, the study found that ego dissolution—a hallmark of the psychedelic experience—was positively correlated with increased functional connectivity between the left and right DLPFC, thalamus, and fusiform face area. Emotional arousal was linked to stronger connectivity between the right DLPFC, intraparietal sulcus, and salience network. A confirmatory analysis supported these findings. MEG data showed that LSD increased directed information flow from the thalamus to the DLPFC in the theta band, suggesting disrupted thalamic gating contributes to ego dissolution. These results indicate a key role for the DLPFC in LSD-induced states of consciousness.
medRxiv : the preprint server for health sciences
October 21, 2024
Pascal Grumbach, Jan Kasper, Joerg F Hipp et al.
1 citation
preprint
Autism spectrum disorder involves altered resting-state brain function, and an imbalance between excitation and inhibition is a proposed mechanism. In two large independent cohorts, individuals with autism consistently showed reduced local brain activity in default mode network nodes and increased activity in temporal regions, cerebellum, and brainstem. These activity changes spatially overlapped with multiple neurotransmitter systems, including dopamine, glutamate, GABA, and acetylcholine. The NMDA-antagonist ketamine, but not the GABA-potentiator midazolam, induced activity changes resembling those seen in autism, suggesting that pharmacologically shifting the excitation-inhibition balance can mimic autism-related brain alterations.
UNC Libraries
April 22, 2020
Peter J. Hellyer, Luke T. Williams, Ben Sessa et al.
1 citation
Lysergic acid diethylamide (LSD) in microgram doses produces profound, sometimes life-changing experiences and is a uniquely powerful psychoactive substance. In the first modern neuroimaging study of LSD, marked changes in brain blood flow, electrical activity, and network communication patterns were observed. These changes correlated strongly with the drug's hallucinatory and consciousness-altering properties. The findings have implications for understanding the neurobiology of consciousness and for potential applications of LSD in psychological research.
bioRxiv (Cold Spring Harbor Laboratory)
March 9, 2019
Andria Pelentritou, Levin Kuhlmann, John Cormack et al.
1 citation
preprint
Equivalent stepwise subanesthetic doses of the NMDA-antagonists nitrous oxide (N2O) and xenon (Xe) produce distinct, frequency-dependent changes in cortical oscillatory source power, measured with simultaneous magnetoencephalography (MEG) and electroencephalography (EEG). At the highest Xe concentration (42%, 1.30 MAC-awake), delta and theta band power significantly increased in both MEG and EEG. N2O administration reduced frontal alpha power more strongly than equivalent Xe doses. N2O alone increased MEG (but not EEG) high-frequency gamma power, with occipital low gamma and widespread high gamma rises. These results demonstrate divergent MEG and EEG signatures of dissociative anesthesia.
bioRxiv (Cold Spring Harbor Laboratory)
October 16, 2017
Suresh Muthukumaraswamy, David T. J. Liley
1 citation
preprint
The arhythmical, scale-free brain activity (1/f β) that dominates neurophysiological recordings is dynamically linked to oscillatory alpha rhythms and is systematically modulated by excitation-inhibition balance. Using IRASA to separate arhythmical from oscillatory activity, the authors show that alpha power correlates over time with the high-frequency power-law exponent βhf, and participants with higher alpha power also have higher βhf. Pharmacological manipulations with tiagabine, perampanel, ketamine, and LSD in MEG, and propofol and ketamine in monkey ECoG, reveal consistent effects of excitation-inhibition balance on both high- and low-frequency β exponents.
Drugs Habits and Social Policy
May 27, 2026
Estelle Miller, David Menkes, Suresh Muthukumaraswamy et al.
Laws that prohibit access to illicit drugs can increase harm because manufacturers and distributors have variable control over drug supply and quality. New Zealand passed legislation in 2021 to address this by allowing licensed providers to directly analyze samples from consumers. This paper describes how researchers obtained the first such license to collect and analyze illicitly sourced psychedelic substances used by people who microdose. Obtaining the license was a lengthy process. The legislation enabled research that fills a gap in knowledge about whether drug content matches consumer expectations, and it allowed provision of harm reduction information to this population.
bioRxiv (Cold Spring Harbor Laboratory)
March 5, 2026
Venkatesh Subramani, Annalisa Pascarella, Jérémy Brunel et al.
Lysergic acid diethylamide (LSD) loosens the brain's usual alignment between anatomical structure and neural activity in a frequency-dependent way. Low-frequency brain waves (theta, alpha, beta) become less constrained by the structural connectome, indicating a global relaxation of large-scale dynamics. High-frequency gamma activity shows selective reorganization rather than uniform disruption. Greater gamma-band decoupling within core default-mode network regions predicts the intensity of ego dissolution across individuals. LSD does not cause indiscriminate disintegration but drives system-specific rebalancing: visual and attentional systems decouple while auditory networks strengthen coupling. These findings suggest psychedelic states emerge from frequency-dependent relaxation of structural constraints, with default-mode reorganization as a neural correlate of ego dissolution.
Ther Adv Psychopharmacol
December 4, 2025
Carina Joy Donegan, Dimitri Daldegan-Bueno, Rachael L. Sumner et al.
People with depression who microdosed LSD described their experiences in interviews from an open-label trial. The analysis identified themes such as improved mood, increased energy, and greater emotional openness, though some participants also reported anxiety or discomfort. The findings suggest that microdosing may offer benefits for some individuals, but the open-label design means results should be interpreted cautiously.
Journal of chromatographic science
November 15, 2025
Mahima Bansal, Estelle Miller, Rachael Sumner et al.
A new high-performance liquid chromatography method accurately measures LSD and separates it from its degradation product iso-LSD. Validated according to international guidelines, the method works even when LSD is exposed to stress conditions that cause breakdown. Applied to illicit microdosing samples from a New Zealand drug checking service, the analysis found a significant discrepancy between users' estimated doses and actual LSD levels. This highlights risks for people using non-pharmaceutical microdosing preparations and underscores the need for reliable quality control to ensure safety.
Journal of Humanistic Psychology
November 10, 2025
Robin J. Murphy, Mia Wardlaw, Thomas A. Smith et al.
After a six-week double-blind placebo-controlled trial of 10 µg of lysergic acid diethylamide taken every third day, healthy male participants reported changes in emotions, mood, social life, mindfulness, cognition, work, creativity, and physiological effects. Openness to experience and bidirectionality of effects were overarching themes. Some reported changes have potential clinical relevance for mood disorders, and reports of changes in anxiety suggest careful patient and dose selection. Participants' experiences with set and setting, uncertainty from placebo control, and perceived bidirectionality of effects inform psychedelic clinical trial design.
medRxiv
August 7, 2025
Ben Deverett, Duan Li, Theresa R. Lii et al.
preprint
Ketamine produces dissociative, analgesic, and antidepressant effects, but it is unclear whether its underlying neurophysiological signatures can be separated. In this observational cohort study, 52 participants (healthy volunteers, elective surgery patients, and patients with depression) received a subanesthetic infusion of ketamine or placebo, with or without general anesthesia. When ketamine was given under general anesthesia, its characteristic low-frequency brain wave augmentation was absent, while high-frequency power modulation was preserved. This selective modulation suggests a method for investigating the distinct roles of high- and low-frequency neural activity in ketamine's behavioral effects.
The International Journal of Neuropsychopharmacology
August 1, 2025
C Donegan, D Daldagen-Bueno, Robin J. Murphy et al.
In an open label trial, 17 people with major depressive disorder took 15 doses of LSD at home and one in a clinic over 8 weeks. Afterward, participants reported increased connectedness to self, others, and nature; greater motivation for activities; improved mood; and better coping with negative situations. Some experienced side effects or no change in symptoms. The findings suggest that microdosing LSD may create a positive feedback loop where improved mood, behavioral activation, and connectedness reinforce each other, and that adding a titration protocol and encouraging psychologically beneficial activities could enhance benefits and reduce side effects.
July 25, 2025
Rachael L. Sumner, Yuxin Ni, Suresh Muthukumaraswamy
preprint
People with premenstrual dysphoric disorder (PMDD) microdose psilocybin to manage their symptoms, and all 14 interview participants reported benefit, though their regimens and treatment goals varied widely. PMDD is a severe mood disorder with limited treatment options. Participants described how PMDD harmed their quality of life and why they turned to microdosing. The findings suggest clinical trials into microdosing psychedelics for PMDD are warranted, as current information to support people engaging in this practice is lacking.
February 27, 2025
Anna-Leigh Hodge, Anna Forsyth, Tehseen Noorani et al.
preprint
A Māori-led research project, Tū Wairua, will integrate traditional Māori healing practices (rongoā Māori) with psilocybin-assisted therapy to address problematic methamphetamine use in Māori communities. Based at Rangiwaho Marae in Te Tairāwhiti, the project is driven by kaupapa Māori methodology and biomedical psychedelic science. It aims to develop a culturally-appropriate treatment, build a skilled Māori workforce, and challenge legislation restricting Indigenous psychedelics. The work represents a shift toward health interventions that respect Indigenous wisdom and address the unique needs of Māori communities.
June 13, 2023
Suresh Muthukumaraswamy
preprint
Effect sizes in randomized controlled trials of psychedelic-assisted therapies are likely inflated because participants and study personnel can often tell who received the active drug, breaking the blind. Causal mediation analysis using objectively measured biomarkers could identify genuine causal pathways between treatment and outcome even when blinding fails. Psychedelic therapies should not be approved as regular medicines until such causal pathways are clearly established. Premature approval risks expanding indications based on low-quality evidence, setting a precedent for other therapies, and allowing efficacy to become unstable after approval.