Direct Comparison of Altered States of Consciousness Induced by LSD, Psilocybin, and DMT in Healthy Participants

Phase 1

Recruiting

• Conditions: Healthy
• Interventions: Drug: LSD; Drug: Psilocybin; Drug: DMT; Drug: Placebo

• Registration Number: NCT06899334
• Lead Sponsor: University Hospital, Basel, Switzerland

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.

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-14
• Study First Submitted QC: 2025-03-20
• Last Update Submitted: 2025-03-20
• Study First Posted: 2025-03-27
• Last Update Posted: 2025-03-27
• Study Start: 2025-04-01
• Primary Completion: 2026-08-01
• Study Completion: 2026-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
LSD	LSD	150 µg lysergic acid diethylamide followed by 20 mg ketanserin intravenously after 3 h
Psilocybin	Psilocybin	30 mg Psilocybin followed by 20 mg ketanserin intravenously after 3 h
DMT	DMT	Dose escalating DMT intravenous infusion up to 2 mg/min followed by 20 mg ketanserin intravenously after 3 h
Placebo	Placebo	Placebo followed by 20 mg ketanserin intravenously after 3 h

Primary Outcome Measures

Name	Time	Method
1. Altered state of consciousness profile (5D-ASC)	18 months	5 Dimensions of Altered States of Consciousness (5D-ASC) consisting of 94 items to be rated on a visual analog scale (0-100 mm), with higher values indicating stronger effects.

Secondary Outcome Measures

Name	Time	Method
Subjective effects (VASs)	18 months	Visual Analog Scales assessing the intensity and duration of subjective effects on a scale from 0 - 100 percent with higher scores representing more intense effects.
Mystical-type experiences (PES)	18 months	This 100-item Psychedelic Experience Questionnaire/Scale (PES100) is rated on a six-point scale (0 indicating "not at all" and 5 indicatin "extremely"). It comprises distractor items as well as subscales which measure mystical-type effects.
Mystical-type experiences (PAE-PS-ext)	18 months	This Phenomenological-Autobiographical-Existential Psychedelic Scale extended (PAE-PS-ext) questionnaire rates psychedelic experiences with a focus on phenomenological, autobiographical, and existential psychedelic experiences (scale from 0 - 100 percent with higher scores representing more intense effects).
3. Emotional breakthrough inventory (EBI+)	18 months	This 18-item questionnaire is a visual analog scale (from 0 - 100 percent with higher scores representing more intense effects) assessing emotional breakthrough throughout the study sessions.
Plasma levels of LSD	18 months	Assessed 20 times on each study day via blood samples
Plasma levels of psilocybin	18 months	Assessed 20 times on each study day via blood samples
Plasma levels of DMT	18 months	Assessed 20 times on each study day via blood samples
Plasma levels of ketanserin	18 months	Assessed 20 times on each study day via blood samples
Plasma levels of oxytocin	18 months	Assessed 2 times on each study day via blood samples
Plasma levels of prolactin	18 months	Assessed 2 times on each study day via blood samples
Plasma levels of cortisol	18 months	Assessed 2 times on each study day via blood samples
Autonomic effects I	18 months	Assessed 16 times on each study day via systolic and diastolic blood pressure
Autonomic effects II	18 months	Assessed 16 times on each study day via heart rate
Autonomic effects III	18 months	Assessed one time at screening visit and twice on each study day via ECG (QT-time)
Adverse effects (B-LR)	18 months	The 2011 revised Beschwerden-Liste (B-LR) consists of a 40-item list covering a wide variety of symptoms and complaints that are answered with a four-point intensity-scoring ranging from 0 indicating "not at all" to 3 indicating "strong."
Adverse effects (SPSI)	18 months	The Swiss Psychedelic Side Effects Inventory evaluates side effects associated with psychedelics using a binary "yes or no" approach. Severity is recorded using a three-point intensity scale ranging from 1 indicating "light" to 3 indicating "strong." The impact is recorded using a five-point scale ranging from -2 "very disadvantageous" to +2 "very advantageous." The relation to the drug is recorded using a five-point scale ranging from 0 indicating "unknown" to 4 indicating "certain."
Adverse Events (AE)	18 months	Any report of adverse events will be recorded on a AE-Form.

Trial Locations

Locations (1)

University Hospital; 🇨🇭 Basel, Switzerland