Clinical trial NCT06899334: Direct Comparison of Altered States of Consciousness Induced by LSD, Psilocybin, and DMT in Healthy Participants
Official title: Direct Comparison of Altered States of Consciousness Induced by LSD, Psilocybin, and DMT in a Randomized, Placebo-controlled, Cross-over Trial in Healthy Participants (LPD-Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy
Keywords: Psychedelics
LSD
Psilocybin
DMT
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2025-03-27
Enrollment: 24
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 4-period, random order, placebo-controlled, double-blind cross-over study
Primary purpose: BASIC_SCIENCE

Brief summary: The primary objective of this study is to determine whether equivalent moderately high doses of LSD, psilocybin, and DMT produce qualitatively similar peak effects when the effect duration is standardized with ketanserin. A DMT infusion mimicking oral LSD and psilocybin administrations will be tested, as well as intravenously administered ketanserin.

Detailed description: Lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT) are serotonergic hallucinogens (psychedelics) and currently investigated as therapeutic tools for the treatment of various psychiatric disorders. They are usually administered in a dose range which induces an alteration of consciousness via the stimulation of the serotonin (5-HT)2A receptor. However, there are differences in the receptor activation profiles between the three substances that may induce different subjective effects. Moreover, they exhibit different pharmacokinetic qualities. In comparative studies of LSD and psilocybin blinding was impaired by the different duration of subjective effects. This study aims to ensure blinding by ending all experiences at the same time with the 5HT2A antagonist ketanserin. Moreover, no study has yet directly compared DMT to LSD and psilocybin. The DMT infusion will be modeled in accordance with the course of an oral LSD and psilocybin administration. Therefore, the LPD-study compares the acute and subacute effects of LSD, psilocybin, and DMT while standardizing the time course and the duration of action for all substances.

Eligibility criteria: Inclusion Criteria:

1. Good understanding of the German language
2. Understanding of procedures and risks associated with the study
3. Willing to adhere to the protocol and signing of the consent form
4. Willing to refrain from the consumption of illicit psychoactive substances during the study
5. Willing not to operate heavy machinery within 48 h after administration of a study substance
6. Willing to use effective birth control throughout study participation
7. Body mass index 17 - 34.9 kg/m2

Exclusion Criteria:

1. Relevant chronic or acute medical condition
2. Current or previous major psychiatric disorder (e.g. psychotic disorder)
3. Psychotic disorder or bipolar disorder in first-degree relatives
4. Hypertension (SBP\>140/90 mmHg) or hypotension (SBP\<85 mmHg)
5. Bradycardia (\< 45 bpm)
6. Prolonged QTc interval (males: \>450 ms, females: \>470 ms)
7. AV block II° (Mobitz type and Webckebach type) and III°
8. Hallucinogenic substance use (not including cannabis) more than 20 times or any time within the previous two months
9. Pregnancy or current breastfeeding
10. Participation in another clinical trial (currently or within the last 30 days)
11. Use of medication that may interfere with the effects of the study medication
12. Tobacco smoking (\>10 cigarettes/day)
13. Excessive consumption of alcoholic beverages (\>15 drinks/week)

Primary outcomes:
measure: 1. Altered state of consciousness profile (5D-ASC)
timeFrame: 18 months
Secondary outcomes:
measure: Subjective effects (VASs)
timeFrame: 18 months
measure: Mystical-type experiences (PES)
timeFrame: 18 months
measure: Mystical-type experiences (PAE-PS-ext)
timeFrame: 18 months
measure: 3. Emotional breakthrough inventory (EBI+)
timeFrame: 18 months
measure: Plasma levels of LSD
timeFrame: 18 months
measure: Plasma levels of psilocybin
timeFrame: 18 months
measure: Plasma levels of DMT
timeFrame: 18 months
measure: Plasma levels of ketanserin
timeFrame: 18 months
measure: Plasma levels of oxytocin
timeFrame: 18 months
measure: Plasma levels of prolactin
timeFrame: 18 months
measure: Plasma levels of cortisol
timeFrame: 18 months
measure: Autonomic effects I
timeFrame: 18 months
measure: Autonomic effects II
timeFrame: 18 months
measure: Autonomic effects III
timeFrame: 18 months
measure: Adverse effects (B-LR)
timeFrame: 18 months
measure: Adverse effects (SPSI)
timeFrame: 18 months
measure: Adverse Events (AE)
timeFrame: 18 months
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias E Liechti, Prof. Dr. MD
role: PRINCIPAL_INVESTIGATOR
References: