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

University Hospital Basel

Status and phase: Enrolling; Phase 1

Conditions: Healthy

Treatments: Drug: Placebo; Drug: Psilocybin; Drug: LSD; Drug: DMT

Study type: Interventional

Funder types: Other

Identifiers

NCT06899334

BASEC 2024-01445

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: 25+ years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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24 participants in 4 patient groups, including a placebo group

LSD

Experimental group

Description:

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

Treatment:

Drug: LSD

Psilocybin

Experimental group

Description:

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

Treatment:

Drug: Psilocybin

DMT

Experimental group

Description:

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

Treatment:

Drug: DMT

Placebo

Placebo Comparator group

Description:

Placebo followed by 20 mg ketanserin intravenously after 3 h

Treatment:

Drug: Placebo