Pharmacokinetics of Didehydro-LSD (DDH-LSD) Compared With LSD

University Hospital Basel

Status: Not yet enrolling

Conditions: LSD Reaction

Treatments: Drug: Placebo; Drug: LSD; Drug: DDH-LSD

Study type: Interventional

Funder types: Other

Identifiers

NCT07309471

2023-01737 am23Liechti3;

Details and patient eligibility

About

This study investigates DDH-LSD, a novel LSD-like compound expected to have a shorter duration of action than LSD. In healthy volunteers, pharmacokinetics, safety, and subjective effects, will be assessed and compare with LSD in a controlled cross-over study.

Full description

LSD is a classical serotonergic psychedelic that produces profound alterations in perception and consciousness, primarily through 5-HT2A receptor agonism. Numerous LSD analogs have emerged in recent years, some functioning as prodrugs of LSD, while others show distinct pharmacological characteristics. DDH-LSD is a newly synthesized lysergamide with LSD-like receptor activity but faster metabolism in vitro, suggesting a shorter elimination half-life and potentially briefer psychedelic effects.

This study consists of two parts.

Substudy 1 is an open-label dose-escalation trial in which healthy participants receive increasing doses of DDH-LSD to identify a dose that produces clear but tolerable psychoactive effects.

Substudy 2 is a randomized, double-blind, placebo-controlled cross-over study comparing the selected DDH-LSD dose with LSD and placebo. Each participant completes multiple supervised study days with comprehensive assessment of subjective effects, physiological responses, and pharmacokinetics.

The goal is to provide first-in-human data on DDH-LSD, characterize its effect profile, and evaluate how its duration of action compares with LSD.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Age between 25 and 65 years old
2. Sufficient understanding of the German language
3. Understanding of procedures and risks associated with the study
4. Willing to adhere to the protocol and signing of the consent form
5. Willing to refrain from the consumption of illicit psychoactive substances during the study
6. Abstaining from xanthine-based liquids from the evenings prior to the study sessions and during the sessions
7. Willing not to operate heavy machinery within 48 h of substance administration
8. Willing to use effective contraceptive measures throughout study participation
9. Body mass index between 18-32 kg/m2

Exclusion criteria

1. Chronic or acute medical condition
2. Current or previous major psychiatric disorder
3. Psychotic disorder or bipolar disorder in first-degree relatives
4. Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg)
5. Use of hallucinogenic substances (not including cannabis) more than 20 times or any time within the previous two months
6. Pregnancy or currently breastfeeding
7. Participation in another clinical trial (currently or within the last 30 days)
8. Use of medication that may interfere with the effects of the study medication
9. Tobacco smoking (>10 cigarettes/day)
10. Consumption of alcoholic beverages (>20 drinks/week)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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24 participants in 3 patient groups, including a placebo group

DDH-LSD

Experimental group

Description:

Participants receive a single dose of DDH-LSD at the dose determined in Substudy 1. The session lasts approximately 13 hours with monitoring of subjective, physiological, and pharmacokinetic effects.

Treatment:

Drug: DDH-LSD

LSD

Active Comparator group

Description:

Participants receive a single 0.1 mg dose of LSD. The session lasts approximately 13 hours with monitoring of subjective, physiological, and pharmacokinetic effects.

Treatment:

Drug: LSD

Placebo

Placebo Comparator group

Description:

Participants receive a placebo dose. The session lasts approximately 13 hours with monitoring of the same parameters to control for expectancy and procedural effects.

Treatment:

Drug: Placebo