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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат LSD
  Single oral dose of 0.1 mg LSD. Participants are monitored for 13 hours for pharmacokinetics, subjective effects, autonomic responses, and safety parameters.
• Препарат Placebo
  Single oral administration of placebo. Participants are monitored for 13 hours under identical conditions to control for expectancy and procedural effects.

Первичные конечные точки

• Determine effective DDH-LSD dose [Срок оценки: During each 13-hour study session.]
• Compare duration of action and elimination half-life [Срок оценки: During each 13-hour study session.]

Вторичные конечные точки (11)

• Pharmacokinetics of DDH-LSD [Срок оценки: During each 13-hour study session]
• Subjective effects: Visual Analog Scales (VAS) [Срок оценки: During each 13-hour study session]
• Subjective effects: Adjective Mood Rating Scale (AMRS / EWL60S) [Срок оценки: Following each 13-hour study session]
• Subjective effects: 5-Dimensions of Altered States of Consciousness (5D-ASC) [Срок оценки: Following each 13-hour study session]
• Subjective effects: Spiritual Realm Questionnaire (SRQ) [Срок оценки: Following each 13-hour study session]
• Subjective effects: States of Consciousness Questionnaire (SCQ / MEQ) [Срок оценки: Following each 13-hour study session]
• Effect on heart rate (HR) [Срок оценки: During each 13-hour study session]
• Effect on blood pressure [Срок оценки: During each 13-hour study session]
• Effect on body temperature [Срок оценки: During each 13-hour study session]
• Subjective effects: Scale of Positive and Negative Experience (SPANE) [Срок оценки: Before each 13-hour study session]
• Subjective effects: Psychological Insight Questionnaire (PIQ) [Срок оценки: Following each 13-hour study session]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Другое

Центры проведения

Швейцария · 1 центр

• University Hospital Basel — Basel

Идентификаторы

NCT: NCT07309471 · 2023-01737;am23Liechti3

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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