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

NCT ID: NCT06899334

Last Updated: 2025-03-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2026-08-01

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

LSD

150 µg lysergic acid diethylamide followed by 20 mg ketanserin intravenously after 3 h

Group Type: EXPERIMENTAL

LSD

Intervention Type: DRUG

A moderate to high oral dose of 150 µg LSD will be administered followed by 20 mg intravenous ketanserin after 3 h

Psilocybin

30 mg Psilocybin followed by 20 mg ketanserin intravenously after 3 h

Group Type: EXPERIMENTAL

Psilocybin

Intervention Type: DRUG

A moderate to high oral dose of 30 mg psilocybin will be administered followed by 20 mg intravenous ketanserin after 3 h

DMT

Dose escalating DMT intravenous infusion up to 2 mg/min followed by 20 mg ketanserin intravenously after 3 h

Group Type: EXPERIMENTAL

DMT

Intervention Type: DRUG

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

Placebo followed by 20 mg ketanserin intravenously after 3 h

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

An oral and an intravenous placebo will be administered followed by 20 mg intravenous ketanserin after 3 h

Interventions

LSD

A moderate to high oral dose of 150 µg LSD will be administered followed by 20 mg intravenous ketanserin after 3 h

Intervention Type: DRUG

Psilocybin

A moderate to high oral dose of 30 mg psilocybin will be administered followed by 20 mg intravenous ketanserin after 3 h

Intervention Type: 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

Intervention Type: DRUG

Placebo

An oral and an intravenous placebo will be administered followed by 20 mg intravenous ketanserin after 3 h

Intervention Type: DRUG

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)

• Minimum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthias E Liechti, Prof. Dr. MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

University Hospital

Basel, , Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Matthias E Liechti, Prof. Dr. MD

Role: CONTACT

matthias.liechti@usb.ch

61 328 68 68 ext. +41

Mélusine Humbert-Droz, MSc

Role: CONTACT

melusine.humbert-droz@usb.ch

61 328 48 19 ext. +41

Facility Contacts

Matthias E Liechti, Prof. Dr. MD

Role: primary

matthias.liechti@usb.ch

61 328 68 68 ext. +41

Mélusine Humbert-Droz, MSc

Role: backup

melusine.humbert-droz@usb.ch

61 328 48 19 ext. +41

Other Identifiers

BASEC 2024-01445

Identifier Type: -

Identifier Source: org_study_id