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Home/Research/LSD/Medicinal Chemistry & Drug Development

LSD for Medicinal Chemistry & Drug Development

37 papers and 0 clinical trials exploring lsd as a treatment for medicinal chemistry & drug development.

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 MM120 have reignited clinical development.

Full LSD profile
IndicationOver 300 million people worldwide experience depression, with many also suffering from related anxiety disorders.

Medicinal Chemistry & Drug Development

Medicinal chemistry plays a crucial role in the development of novel psychedelic compounds, focusing on their molecular structures and interactions. Researchers utilise innovative methods to enhance safety and efficacy in psychedelic substances.

Full Medicinal Chemistry & Drug Development profile

Academic Research

37 papers
Open Accessindividual

LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial

This open-label trial (n=19) found that repeated microdosed LSD (8 to 20 μg) was associated with short-term improvements in daily mood, but not same-day changes in self-reported depression, in people with major depressive disorder. It also provided pharmacokinetic data for sublingual LSD and found no evidence of tolerance or sensitisation across the 8-week dosing regimen.

Published
March 1, 2026
Journal
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Authors
Daldegan-Bueno, D., Donegan, C. J., Sumner, R., Forsyth, A., Jeong, S. H., Evans, W., Alshakhouri, M., Murphy, R. J., Reynolds, L., Hoeh, N., Allen, N., Sundram, F., Menkes, D. B., Muthukumaraswamy, S.
Open Accessindividual

Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults A Randomized Clinical Trial

In a 6‑week, multicentre, double‑blind randomised phase 2A trial of 53 adults with moderate–severe ADHD, twice‑weekly low‑dose LSD (20 μg) was physically safe and psychologically well tolerated. However, LSD did not reduce ADHD symptoms more than placebo on the AISRS.

Published
June 1, 2025
Journal
JAMA Psychiatry
Authors
Mueller, L., de Jesus, N. M. S., Schmid, Y., Müller, F., Becker, A. M., Klaiber, A., Straumann, I., Luethi, D., Haijen, E. C. H. M., Hurks, P. P. M., Kuypers, K. P. C., Liechti, M. E.
Open Accessindividual

Absolute Oral Bioavailability and Bioequivalence of LSD Base and Tartrate in a Double-Blind, Placebo-Controlled, Crossover Study

In a randomized, double‑blind, placebo‑controlled five‑period crossover study in 20 healthy volunteers, different oral LSD formulations (base and tartrate; solutions and tablet) were bioequivalent with an absolute oral bioavailability of about 80%. Intravenous LSD produced larger subjective effects and more adverse effects (anxiety, nausea, negative experiences) than oral administration.

Published
May 26, 2025
Journal
Clinical Pharmacology and Therapeutics
Authors
Arikci, D., Holze, F., Mueller, L., Vizeli, P., Rudin, D., Luethi, D., Hysek, C. M., Liechti, M. E.
Open Accessindividual

Pharmacokinetics and pharmacodynamics of sublingual microdosed lysergic acid diethylamide in healthy adult volunteers

In a double‑blind Phase 1 trial in 80 healthy male volunteers, a one‑compartment population pharmacokinetic model and LC‑MS/MS assay characterised 10 µg sublingual LSD (Cmax 0.20 µg/L, Tmax 1.51 h, t1/2 3.08 h, clearance 7.78 L/h/70 kg, Vc 32.9 L/70 kg). Microdosing produced minimal cardiovascular and subjective effects, no change in peripheral BDNF, and suggested qualitative influences of CYP genotypes (notably CYP2D6) on concentrations, indicating the need for larger genotype studies and more sensitive pharmacodynamic measures.

Published
April 18, 2025
Journal
Journal of Psychopharmacology
Authors
Morse, D. J., Jeong, S. H., Murphy, R. J., Muthukumaraswamy, S., Sumner, R. L.
Open Accessindividual

Assessing the Potential Cardiovascular Risk of Microdosing the Psychedelic LSD in Mice

Chronic administration of sub‑hallucinogenic (microdose) LSD in mice produced no ventricular thickening or other ECG-detected cardiotoxic changes, whereas serotonin (positive control) caused significant ventricular thickening. In vitro assays showed similar 5‑HT2B affinity across mouse and human receptors and that low‑dose LSD yields only transient 5‑HT2B activation compared with the cardiotoxin d‑fenfluramine, together providing no evidence of cardiovascular risk from prolonged low‑dose LSD in this mouse model.

Published
April 14, 2025
Journal
ACS Pharmacology and Translational Science
Authors
Effinger, D. P., Schalk, S. S., King, J. L., Wallingford, J. R., O'connell, C. K., Calderon, J. R., Kopecky, B. J., Mccorvy, J. D., Thompson, S. M.
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
February 28, 2025
Journal
Clinical Pharmacology and Therapeutics
Authors
Becker, A. M., Humbert-Droz, M., Mueller, L., Jelusic, A., Tolev, A., Straumann, I., Avedisian, I., Erne, L., Thomann, J., Luethi, D., Grünblatt, E., Meyer zu Schwabedissen, H. E., Liechti, M. E.

Clinical Trials

0 trials

No clinical trials have been tagged with both LSD and Medicinal Chemistry & Drug Development yet.

Trials are continuously being added as new studies are registered.

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