LSD for Headache Disorders (Cluster & Migraine)

Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD A Randomized Clinical Trial

In a multicentre, double‑blind, placebo‑controlled phase 2 trial of 65 adults with chronic PTSD, once‑weekly oral TSND‑201 produced significantly greater reductions in clinician‑rated PTSD severity (CAPS‑5; LS mean difference 9.64, P = .01) and improvements in self‑reported symptoms, functioning and depression versus placebo. TSND‑201 was generally well tolerated — common adverse events included headache, decreased appetite, nausea, dizziness and transient blood‑pressure increases — supporting its potential as a rapid‑acting, durable treatment for PTSD.

Published: February 18, 2026
Journal: JAMA Psychiatry
Authors: Jones, A., Warner-Schmidt, J., Kwak, H., Stogniew, M., Mandell, B., Ching, T. H., Stein, M. B., Kelmendi, B.

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Single Treatment With MM120 (Lysergide) in Generalized Anxiety Disorder: A Randomized Clinical Trial

In a multicentre phase 2b randomised placebo‑controlled trial of 198 adults with moderate to severe GAD, a single dose of MM120 (lysergide D‑tartrate) produced a dose‑dependent reduction in HAM‑A scores at 4 weeks, with 100 µg and 200 µg showing significant improvements versus placebo (least‑squares mean differences −5.0 and −6.0 points, respectively). Adverse events were dose‑related—most commonly visual perceptual changes and nausea—supporting the efficacy and informing dose selection for phase 3 trials.

Published: October 21, 2025
Journal: JAMA
Authors: Robison, R., Barrow, R., Conant, C., Foster, E., Freedman, J. M., Jacobsen, P. L., Karas, S. M., Karlin, D. R., Solomon, T. M., Wernli, M. H., Fava, M. F., Jemisen, J.

Open Accessindividual

A randomised placebo-controlled study of the effects of lysergic acid diethylamide microdosing (15 μg) on pain perception in healthy volunteers

In a randomised placebo‑controlled trial in healthy volunteers, repeated 15 µg LSD microdoses produced no overall analgesic effects on cold‑pressor pain tolerance or subjective pain ratings, despite increasing blood pressure and subjective drug effects. Post‑hoc analyses in participants without baseline ceiling effects suggested a transient increase in pain tolerance and reduced unpleasantness after the first dose, implying the dose may be below the threshold for consistent analgesia and that larger studies with higher doses are needed.

Published: September 4, 2025
Journal: British Journal of Pain
Authors: Cavarra, M., Hutten, N. R. P. W., Schepers, J., Mason, N. L., Theunissen, E. L., Liechti, M. E., Kuypers, K. P. C., Bonnelle, V., Feilding, A., Ramaekers, J. G., Ramakers, J. G.

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The polypharmacology of psychedelics reveals multiple targets for potential therapeutics

This receptor profiling study (n=41 compounds) maps the pharmacological activity of classical psychedelics across 318 human G-protein-coupled receptors and, for LSD, over 450 human kinases. It finds that psychedelics act potently at nearly all serotonin, dopamine, and adrenergic receptors, with multiple 5-HT2A receptor signalling pathways linked to psychedelic effects in vivo.

Published: July 15, 2025
Journal: Neuron
Authors: Jain, M. K., Gumpper, R. H., Slocum, S. T., Gloriam, D. E., Nichols, D. E., Roth, B. L., Schmitz, G. P., Madsen, J. S., Tummino, T. A., Suomivuori, C. M., Huang, X. P., Shub, L., Diberto, J. F., Kim, K., Deleon, C., Krumm, B. E., Fay, J. F., Keiser, M., Hauser, A. S., Dror, R. O., Shoichet, B.

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Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis

This systematic review and meta‑analysis of 214 studies (3,504 participants with analysable adverse‑event data) found that high‑dose classic psychedelics were generally well tolerated in clinical/research settings, with serious adverse events occurring mainly in ~4% of participants who had preexisting neuropsychiatric disorders and no reports in contemporary trials of suicide, persistent psychotic disorder or hallucinogen‑persisting perception disorder. Common non‑serious adverse events (headache, anxiety, nausea, fatigue, dizziness) had similar prevalences for psilocybin and LSD, but substantial heterogeneity and limited systematic adverse‑event monitoring across studies highlight the need for improved pharmacovigilance.

Published: December 1, 2024
Journal: JAMA Psychiatry
Authors: Hinkle, J. T., Graziosi, M., Nayak, S., Yaden, D. B.

Open Accessindividual

A suite of engineered mice for interrogating psychedelic drug actions

The authors generated a suite of engineered Htr2a mouse lines—including an Htr2a‑EGFP‑CT‑IRES‑CreERT2 reporter, a humanised Htr2a line and a constitutive Htr2a‑Cre line—that enable independent visualisation of HTR2A receptors and HTR2A‑expressing cells and provide detailed anatomical and cell‑type maps. They validated the lines with psychedelic‑induced behavioural phenotypes and electrophysiology showing extracellular 5‑HT produces an HTR2A‑mediated increase in firing of genetically identified pyramidal neurons, consistent with plasma‑membrane localisation and utility for in vivo studies of psychedelic drug actions.

Published: September 26, 2023
Journal: Biorxiv
Authors: Chiu, Y. T., Deutch, A. Y., Wang, W., Schmitz, G. P., Huang, K. L., Dewran Kocak, D., Llorach, P., Bowyer, K., Liu, B., Sciaky, N., Hua, K., Chen, C., Mott, S. E., Niehaus, J., Diberto, J. F., English, J., Walsh, J. J., Scherrer, G., Herman, M. A., Wu, Z., Wetsel, W. C., Roth, B. L.

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Headache Disorders (Cluster & Migraine)

Academic Research

Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD A Randomized Clinical Trial

Single Treatment With MM120 (Lysergide) in Generalized Anxiety Disorder: A Randomized Clinical Trial

A randomised placebo-controlled study of the effects of lysergic acid diethylamide microdosing (15 μg) on pain perception in healthy volunteers

The polypharmacology of psychedelics reveals multiple targets for potential therapeutics

Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis

A suite of engineered mice for interrogating psychedelic drug actions

Clinical Trials

LSD to Improve Cluster Headache Impact Trial

Lysergic Acid Diethylamide (LSD) as Treatment for Cluster Headache

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