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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: LSD; Drug: Psilocybin; Drug: DMT; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Matthias E Liechti, Prof. Dr. MD; Phone Number: +41 61 328 68 68; Email: matthias.liechti@usb.ch
• Study Contact Backup: Name: Mélusine Humbert-Droz, MSc; Phone Number: +41 61 328 48 19; Email: melusine.humbert-droz@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4056
    • Recruiting
    • University Hospital
    • Contact: Matthias E Liechti, Prof. Dr. MD; Phone Number: +41 61 328 68 68; Email: matthias.liechti@usb.ch
    • Contact: Mélusine Humbert-Droz, MSc; Phone Number: +41 61 328 48 19; Email: melusine.humbert-droz@usb.ch
    • Principal Investigator: Matthias E Liechti, Prof. Dr. MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LSD; 150 µg lysergic acid diethylamide followed by 20 mg ketanserin intravenously after 3 h	Drug: LSD; A moderate to high oral dose of 150 µg LSD will be administered followed by 20 mg intravenous ketanserin after 3 h
Experimental: Psilocybin; 30 mg Psilocybin followed by 20 mg ketanserin intravenously after 3 h	Drug: Psilocybin; A moderate to high oral dose of 30 mg psilocybin will be administered followed by 20 mg intravenous ketanserin after 3 h
Experimental: DMT; Dose escalating DMT intravenous infusion up to 2 mg/min followed by 20 mg ketanserin intravenously after 3 h	Drug: DMT; A moderate to high, dose-escalating, intravenous infusion up to 2 mg/min DMT will be administered followed by 20 mg intravenous ketanserin after 3 h
Placebo Comparator: Placebo; Placebo followed by 20 mg ketanserin intravenously after 3 h	Drug: Placebo; An oral and an intravenous placebo will be administered followed by 20 mg intravenous ketanserin after 3 h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. Altered state of consciousness profile (5D-ASC)	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.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective effects (VASs)	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.	18 months
Mystical-type experiences (PES)	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.	18 months
Mystical-type experiences (PAE-PS-ext)	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).	18 months
3. Emotional breakthrough inventory (EBI+)	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.	18 months
Plasma levels of LSD	Assessed 20 times on each study day via blood samples	18 months
Plasma levels of psilocybin	Assessed 20 times on each study day via blood samples	18 months
Plasma levels of DMT	Assessed 20 times on each study day via blood samples	18 months
Plasma levels of ketanserin	Assessed 20 times on each study day via blood samples	18 months
Plasma levels of oxytocin	Assessed 2 times on each study day via blood samples	18 months
Plasma levels of prolactin	Assessed 2 times on each study day via blood samples	18 months
Plasma levels of cortisol	Assessed 2 times on each study day via blood samples	18 months
Autonomic effects I	Assessed 16 times on each study day via systolic and diastolic blood pressure	18 months
Autonomic effects II	Assessed 16 times on each study day via heart rate	18 months
Autonomic effects III	Assessed one time at screening visit and twice on each study day via ECG (QT-time)	18 months
Adverse effects (B-LR)	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."	18 months
Adverse effects (SPSI)	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."	18 months
Adverse Events (AE)	Any report of adverse events will be recorded on a AE-Form.	18 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Matthias E Liechti, Prof. Dr. MD, University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: March 14, 2025
• First Submitted That Met QC Criteria: March 20, 2025
• First Posted (Actual): March 27, 2025

Study Record Updates

• Last Update Posted (Actual): March 27, 2025
• Last Update Submitted That Met QC Criteria: March 20, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Psilocybin; Psychedelics; DMT; LSD
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin
• Other Study ID Numbers: BASEC 2024-01445

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No