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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DDH-LSD | Experimental | 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. |
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| LSD | Active Comparator | Participants receive a single 0.1 mg dose of LSD. The session lasts approximately 13 hours with monitoring of subjective, physiological, and pharmacokinetic effects. |
|
| Placebo | Placebo Comparator | Participants receive a placebo dose. The session lasts approximately 13 hours with monitoring of the same parameters to control for expectancy and procedural effects. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DDH-LSD | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Determine effective DDH-LSD dose | 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 | Compare DDH-LSD with LSD and placebo regarding elimination half-life and duration of subjective effects. | During each 13-hour study session. |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of DDH-LSD | Measure plasma concentration over time | During each 13-hour study session |
| Subjective effects: Visual Analog Scales (VAS) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Matthias Liechti, Prof. MD | Contact | +41 61 328 68 68 | matthias.liechti@usb.ch | |
| Mélusine Humbert-Droz | Contact | melusine.humbert-droz@usb.ch |
| Name | Affiliation | Role |
|---|---|---|
| Matthias Liechti, Prof.MD | University Hospital of Basel | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel | Recruiting | Basel | 4031 | Switzerland |
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| ID | Term |
|---|---|
| D008238 | Lysergic Acid Diethylamide |
| ID | Term |
|---|---|
| D008237 | Lysergic Acid |
| D004873 | Ergolines |
| D004876 | Ergot Alkaloids |
| D000470 | Alkaloids |
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Part 1: Open lable, within-subject, dose-escalation study of DDH-LSD to identify a dose producing measurable psychoactive effects.
Part 2: randomized, double-blind, placebo-controlled, balanced cross-over study comparing DDH-LSD with LSD and placebo, allowing direct assessment of pharmacokinetics, duration of action, and subjective effects. Each participant completes multiple supervised study sessions separated by washout periods.
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| LSD | Drug | Single oral dose of 0.1 mg LSD. Participants are monitored for 13 hours for pharmacokinetics, subjective effects, autonomic responses, and safety parameters. |
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| Placebo | Drug | Single oral administration of placebo. Participants are monitored for 13 hours under identical conditions to control for expectancy and procedural effects. |
|
| During each 13-hour study session |
| Subjective effects: Adjective Mood Rating Scale (AMRS / EWL60S) | 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) | 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) | 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) | 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) | During each 13-hour study session |
| Effect on blood pressure | During each 13-hour study session |
| Effect on body temperature | During each 13-hour study session |
| Subjective effects: Scale of Positive and Negative Experience (SPANE) | 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) | 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 |
| D006571 |
| Heterocyclic Compounds |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |