Translational psychiatry
May 23, 2023
Severin B Vogt, Laura Ley, Livio Erne et al.
85 citations
Intravenous DMT can produce a psychedelic state that is short-lasting and controllable. A double-blind, placebo-controlled crossover trial with 27 healthy participants tested five DMT regimens: low infusion (0.6 mg/min), high infusion (1 mg/min), low bolus plus low infusion (15 mg + 0.6 mg/min), and high bolus plus high infusion (25 mg + 1 mg/min). Bolus doses induced very intense effects within 2 minutes, with more negative feelings and anxiety than infusions. Infusions produced slowly increasing, dose-dependent effects that plateaued after 30 minutes. All effects subsided within 15 minutes of stopping the infusion. Acute tolerance developed, with stable subjective effects from 30 to 90 minutes despite rising plasma concentrations. Intravenous DMT infusion is a promising tool for tailored psychedelic therapy.
Clinical Pharmacology & Therapeutics
February 28, 2025
Lorenz Mueller, Alen Jelušić, Avram Tolev et al.
15 citations
In a double-blind, placebo-controlled crossover study with 23 healthy participants, daily paroxetine (an SSRI antidepressant) did not reduce the pleasant subjective effects of a single 100 μg dose of LSD, but it significantly lessened negative effects such as 'bad drug effect,' anxiety, and nausea. Paroxetine increased LSD's peak concentration and total exposure by 40% and 50%, respectively, by inhibiting the CYP2D6 enzyme, indicating this enzyme is involved in LSD metabolism. The interaction was strongest in normal CYP2D6 metabolizers and weakest in poor metabolizers. The findings suggest LSD can be safely added to SSRI treatment without dose adjustment when the SSRI inhibits CYP2D6, but no definitive recommendation can be made for other SSRIs.
JAMA psychiatry
June 1, 2025
Lorenz Mueller, Joyce Santos de Jesus, Yasmin Schmid et al.
14 citations
Repeated low doses of LSD (20 μg twice weekly for six weeks) did not reduce ADHD symptoms more than placebo in adults with moderate-to-severe ADHD. In a double-blind randomized trial with 53 participants, the LSD group showed an average 7.1-point improvement on the ADHD symptom scale, while the placebo group improved by 8.9 points—a difference that was not statistically significant. The treatment was physically safe and psychologically well tolerated. The findings suggest that microdosing LSD, despite popular interest, offers no advantage over placebo for ADHD symptom relief.
Clinical pharmacology and therapeutics
May 26, 2025
Denis Arikci, Friederike Holze, Lorenz Mueller et al.
6 citations
LSD base and tartrate formulations taken orally are bioequivalent, meaning they produce the same drug levels in the body. The absolute oral bioavailability of LSD is 80%, and all tested oral forms—ethanolic base solution, watery tartrate solution, and rapid-dissolving tablet—show similar pharmacokinetics. Intravenous LSD causes stronger subjective effects like ego dissolution and anxiety compared to oral forms. These findings support interchangeable oral dosing in research and clinical use.
Clinical pharmacokinetics
July 14, 2025
Lorenz Mueller, Aaron Klaiber, Laura Ley et al.
4 citations
Mescaline, a classic psychedelic, shows dose-proportional increases in blood concentration and effects after oral administration. Peak levels occur within about 2 hours, with a half-life of 3.5 hours. Effects begin around 1 hour after dosing, with intensity and duration increasing from 13% and 2.8 hours at 100 mg to 89% and 15 hours at 800 mg. About 53% of the dose is excreted unchanged in urine, and 31% as a main metabolite. Oral bioavailability is at least 53%, limited by first-pass metabolism, with renal elimination as the primary clearance route.
Translational Psychiatry
June 4, 2026
Mélusine Humbert‐droz, Anna M. Becker, Jan Valenta et al.
A booster dose of MDMA prolongs the acute subjective drug effects compared with a single dose, without increasing peak effects. In a double-blind, randomized, placebo-controlled crossover study with 23 healthy volunteers, a 120 mg dose of MDMA followed by a 60 mg booster after 2 hours extended the duration of subjective effects to an average of 5.6 hours, versus 4.6 hours with a single dose. Adverse effects were more common after both MDMA conditions than placebo. Whether the prolonged effect translates into clinical benefit for MDMA-assisted psychotherapy remains unknown.
Translational Psychiatry
March 27, 2026
Livio Erne, Lorenz Mueller, Isabelle Straumann et al.
Bolus injections of DMT produce very strong subjective effects that peak within 2 minutes and subside completely within 12–30 minutes, consistent with a short elimination half-life of about 6–7 minutes. A ceiling effect for peak subjective effects occurred at the 15 mg dose, and no tolerance developed to the acute effects. Tolerability markedly improved when doses were escalated openly rather than given double-blind, and at equivalent doses the subjective effects were rated as less intense. These results indicate that blinding and expectancy influence the subjective experience and that individual dose-escalation may improve tolerability and guide dose selection in future DMT studies.