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)

Overview

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.

Interventions

• Drug LSD
  A moderate to high oral dose of 150 µg LSD will be administered followed by 20 mg intravenous ketanserin 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
• 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
• Drug Placebo
  An oral and an intravenous placebo will be administered followed by 20 mg intravenous ketanserin after 3 h

Primary outcome measures

• 1. Altered state of consciousness profile (5D-ASC) [Time frame: 18 months]

Secondary outcome measures (12)

• Subjective effects (VASs) [Time frame: 18 months]
• Mystical-type experiences (PES) [Time frame: 18 months]
• Mystical-type experiences (PAE-PS-ext) [Time frame: 18 months]
• 3. Emotional breakthrough inventory (EBI+) [Time frame: 18 months]
• Plasma levels of LSD [Time frame: 18 months]
• Plasma levels of psilocybin [Time frame: 18 months]
• Plasma levels of DMT [Time frame: 18 months]
• Plasma levels of ketanserin [Time frame: 18 months]
• Plasma levels of oxytocin [Time frame: 18 months]
• Plasma levels of prolactin [Time frame: 18 months]
• Plasma levels of cortisol [Time frame: 18 months]
• Autonomic effects I [Time frame: 18 months]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Basic science

Study locations

Switzerland · 1 center

• University Hospital — Basel

Identifiers

NCT: NCT06899334 · BASEC 2024-01445

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗