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

NCT ID: NCT07309471

Last Updated: 2025-12-30

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2028-07-31

Brief Summary

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.

Detailed 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.

Conditions

LSD Reaction

Keywords

DDH-LSD; LSD; Psychedelics; Psychoactive substances; Pharmacokinetics; Pharmacodynamics; Healthy volunteers; 5-HT2A agonist

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

DDH-LSD

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.

Group Type: EXPERIMENTAL

DDH-LSD

Intervention Type: DRUG

Single oral dose of DDH-LSD at the dose determined in Substudy 1. Participants are monitored for 13 hours for pharmacokinetics, subjective effects, autonomic responses, and safety parameters.

LSD

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

Group Type: ACTIVE_COMPARATOR

LSD

Intervention Type: DRUG

Single oral dose of 0.1 mg LSD. Participants are monitored for 13 hours for pharmacokinetics, subjective effects, autonomic responses, and safety parameters.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Single oral administration of placebo. Participants are monitored for 13 hours under identical conditions to control for expectancy and procedural effects.

Interventions

DDH-LSD

Single oral dose of DDH-LSD at the dose determined in Substudy 1. Participants are monitored for 13 hours for pharmacokinetics, subjective effects, autonomic responses, and safety parameters.

Intervention Type: DRUG

LSD

Single oral dose of 0.1 mg LSD. Participants are monitored for 13 hours for pharmacokinetics, subjective effects, autonomic responses, and safety parameters.

Intervention Type: DRUG

Placebo

Single oral administration of placebo. Participants are monitored for 13 hours under identical conditions to control for expectancy and procedural effects.

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthias Liechti, Prof.MD

Role: STUDY_CHAIR

University Hospital of Basel

Locations

University Hospital Basel

Basel, , Switzerland

Countries

Switzerland

Central Contacts

Matthias Liechti, Prof. MD

Role: CONTACT

Phone: +41 61 328 68 68

Email: matthias.liechti@usb.ch

Mélusine Humbert-Droz

Role: CONTACT

Email: melusine.humbert-droz@usb.ch

Facility Contacts

Mélusine Humbert-Droz

Role: primary

Matthias Liechti, Prof. MD

Role: backup

Other Identifiers

2023-01737;am23Liechti3

Identifier Type: -

Identifier Source: org_study_id