LSD for Healthy Volunteers

56 papers and 27 clinical trials exploring lsd as a treatment for healthy volunteers.

Compoundclassic psychedelic

LSD

LSD is a classic psychedelic ergoline with high potency at microgram doses and an 8-12 hour duration of action, mediated primarily via 5-HT2A receptor agonism. Modern Phase IIb data in generalised anxiety disorder and FDA Breakthrough Therapy Designation for MM-120 have reignited clinical development.

Full LSD profile
IndicationApproximately 300 million people affected by depression worldwide.

Healthy Volunteers

Research involving healthy volunteers has expanded to investigate the therapeutic potentials of various psychedelics for mental health conditions. Recent findings, emphasizing compounds like psilocybin and DMT, illustrate a promising future for psychedelic-assisted therapies.

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Academic Research

56 papers
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
Journal
British Journal of Pain
Authors
Bonnelle, V., Cavarra, M., Feilding, A., Hutten, N. P. W., Kuypers, K. P. C., Liechti, M. E., Mason, N. L., Ramaekers, J. G., Schepers, J., Theunissen, E. L.
Open Accessindividual

Molecular, haemodynamic, and functional effects of LSD in the human brain

Using simultaneous PET–MRI in healthy volunteers, this first integrated molecular and functional neuroimaging study quantifies LSD occupancy at cerebral serotonin 2A receptors and establishes a dose–occupancy relationship while revealing an anticlockwise hysteresis between plasma levels and subjective effects. LSD produced distinct haemodynamic and functional changes — increasing global cerebral and internal carotid artery flow without altering artery diameter and reducing global connectivity (GCOR), with GCOR changes negatively correlated with CBF and differing from effects of psilocybin — findings relevant to clinical development.

Published
Journal
MedRvix
Authors
Andersen, T. L., Falck, N., Fisher, P. M., Geisler, M., Holze, F., Jensen, P. S., Johansen, A., Johansen, S. S., Knudsen, G. M., Larsen, K., McCulloch, D. E-W., Neufeld, V., Nielsen, M. K. K., Nykjær, C. H., Randrup, P. P., Reveles Jensen, K. H., Shulganov, V., Skov-Andersen, P., Spanggård, A., Steenstrup, E., Stenbæk, D. S., Svarer, C.
Open Accessindividual

Acute Effects and Pharmacokinetics of LSD after Paroxetine or Placebo Pre-Administration in a Randomized, Double-Blind, Cross-Over Phase I Trial

In a randomized, double‑blind, cross‑over trial in 23 healthy volunteers, daily paroxetine (a CYP2D6 inhibitor) did not change LSD's pleasant subjective effects but significantly reduced adverse effects (bad drug effect, anxiety, nausea) and increased LSD Cmax and AUC by ~1.4–1.5-fold. The findings indicate CYP2D6 contributes to LSD metabolism and suggest co‑administration with SSRIs that inhibit CYP2D6 is well tolerated and likely does not require LSD dose adjustment, although recommendations for SSRIs that do not inhibit CYP2D6 remain uncertain.

Published
Journal
Clinical Pharmacology and Therapeutics
Authors
Avedisian, I., Becker, A. M., Erne, L., Grünblatt, E., Humbert-Droz, M., Jelusic, A., Liechti, M. E., Luethi, D., Meyer zu Schwabedissen, H. E., Mueller, L., Straumann, I., Thomann, J., Tolev, A.
Paywallmeta

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
Journal
JAMA Psychiatry
Authors
Graziosi, M., Hinkle, J. T., Nayak, S., Yaden, D. B.

Clinical Trials

27 trials

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