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

March 9, 2026 updated by: University Hospital, Basel, Switzerland
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Switzerland
      • Basel, Switzerland, 4031
        • Recruiting
        • University Hospital Basel
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Mélusine Humbert-Droz

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.
Active Comparator: 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.
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.
Placebo Comparator: 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.
Drug: Placebo
Single oral administration of placebo. Participants are monitored for 13 hours under identical conditions to control for expectancy and procedural effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine effective DDH-LSD dose
Time Frame: During each 13-hour study session.
Identify the dose of DDH-LSD that produces clear psychoactive effects.
During each 13-hour study session.
Compare duration of action and elimination half-life
Time Frame: During each 13-hour study session.
Compare DDH-LSD with LSD and placebo regarding elimination half-life and duration of subjective effects.
During each 13-hour study session.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics of DDH-LSD
Time Frame: During each 13-hour study session
Measure plasma concentration over time
During each 13-hour study session
Subjective effects: Visual Analog Scales (VAS)
Time Frame: During each 13-hour study session
Assess subjective alterations in consciousness using 100 mm horizontal lines (0 = "not at all", 100 = "extremely"). Multiple items (e.g., "any drug effect", "good drug effect", "high", "anxiety") are administered repeatedly during sessions to capture intensity and time course of drug effects.
During each 13-hour study session
Subjective effects: Adjective Mood Rating Scale (AMRS / EWL60S)
Time Frame: Following each 13-hour study session
A 60-item Likert scale assessing six dimensions of mood (activation, positive mood, extraversion, introversion, inactivation, emotional excitability). Scores range from 0-100 per subscale, with higher values indicating greater intensity of the dimension.
Following each 13-hour study session
Subjective effects: 5-Dimensions of Altered States of Consciousness (5D-ASC)
Time Frame: Following each 13-hour study session
A 94-item questionnaire assessing altered consciousness, perception, mood, and derealization/depersonalization. Scores 0-100 per subscale, with higher values indicating stronger alteration of consciousness.
Following each 13-hour study session
Subjective effects: Spiritual Realm Questionnaire (SRQ)
Time Frame: Following each 13-hour study session
A 65-item visual rating scale assessing spiritual and psychedelic experiences across four dimensions (spirituality, human condition, personal problem solving, worldview/beliefs). Scores 0-100 per subscale, higher values indicate stronger experience.
Following each 13-hour study session
Subjective effects: States of Consciousness Questionnaire (SCQ / MEQ)
Time Frame: Following each 13-hour study session
A 100-item questionnaire with a 43-item Mystical Experience Questionnaire (MEQ) embedded. Scores 0-100% per domain, with higher percentages reflecting stronger mystical-type experiences.
Following each 13-hour study session
Effect on heart rate (HR)
Time Frame: During each 13-hour study session
During each 13-hour study session
Effect on blood pressure
Time Frame: During each 13-hour study session
During each 13-hour study session
Effect on body temperature
Time Frame: During each 13-hour study session
During each 13-hour study session
Subjective effects: Scale of Positive and Negative Experience (SPANE)
Time Frame: Before each 13-hour study session
A 12-item questionnaire measuring positive and negative affect. Subscales range 0-24, with higher scores indicating greater positive or negative affect; the overall balance score reflects general well-being.
Before each 13-hour study session
Subjective effects: Psychological Insight Questionnaire (PIQ)
Time Frame: Following each 13-hour study session
A 14-item questionnaire assessing insight into emotions, behavior, beliefs, or relationships. Items rated 0-5 (0 = "not at all", 5 = "extremely"), higher scores indicate greater perceived psychological insight.
Following each 13-hour study session

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Basel, Switzerland

Investigators

  • Study Chair: Matthias Liechti, Prof.MD, University Hospital of Basel

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 6, 2026

Primary Completion (Estimated)

July 1, 2028

Study Completion (Estimated)

July 1, 2028

Study Registration Dates

First Submitted

December 15, 2025

First Submitted That Met QC Criteria

December 15, 2025

First Posted (Actual)

December 30, 2025

Study Record Updates

Last Update Posted (Actual)

March 10, 2026

Last Update Submitted That Met QC Criteria

March 9, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-01737;am23Liechti3

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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