Direct Comparison of Altered States of Consciousness Induced by LSD and Psilocybin (LSD-psilo)

Direct Comparison of Altered States of Consciousness Induced by LSD and Psilocybin in a Random-order Placebo-controlled Cross-over Study in Healthy Subjects

LSD (lysergic acid diethylamide) and psilocybin (the active substance in "magic mushrooms") are widely used for recreational purposes. Both substances are also increasingly used in psychiatric and psychological research to induce and investigate alterations in waking consciousness and associated brain functions (functional brain imaging, "model psychosis") . However, it has never been studied whether there are differences in the alterations in mind produced by these two substances. Both LSD and psilocybin are thought to induce hallucinations primarily via stimulation of the 5-HT2A receptor. However, there are differences in the receptor activation profiles between the two substances that may also induce different subjective effects. LSD potently stimulates the 5-HT2A receptor but also 5-HT2B/C, 5-HT1 and D1-3 receptors . Psilocin (the active metabolite of the prodrug psilocybin) also stimulates the 5-HT2A receptor but additionally inhibits the 5-HT transporter. In contrast to LSD, psilocybin has no affinity for D2 receptors. Both substances are used in neuroscience as pharmacological tools. However, there are no modern studies comparing these two substances directly within the same clinical study and research subjects and using validated psychometric tools. Therefore, the investigators will compare the acute effects of LSD, psilocybin and placebo.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: LSD; Drug: LSD; Drug: Psilocybin; Drug: Psilocybin

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4056
    • Clinical Pharmacology & Toxicology, University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age between 25 and 65 years.
2. Understanding of the German language.
3. Understanding the procedures and the risks that are associated with the study.
4. Participants must be willing to adhere to the protocol and sign the consent form.
5. Participants must be willing to refrain from taking illicit psychoactive substances during the study.
6. Participants must be willing to drink only alcohol-free liquids and no coffee, black or green tea, or energy drink after midnight of the evening before the study session, as well as during the study day.
7. Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
8. Women of childbearing potential must have a negative pregnancy test at the beginning of the study. Pregnancy tests are repeated before each study session.
9. Women of childbearing potential must be willing to use double-barrier birth control
10. Body mass index 18-29 kg/m2.

Exclusion Criteria:

1. Chronic or acute medical condition
2. Current or previous major psychiatric disorder
3. Psychotic disorder in first-degree relatives
4. Illicit substance use (with the exception of cannabis) more than 10 times or any time within the previous two months.
5. Pregnant or nursing women.
6. Participation in another clinical trial (currently or within the last 30 days)
7. Use of medications that may interfere with the effects of the study medications (any psychiatric medications)
8. Tobacco smoking (>10 cigarettes/day)
9. Consumption of alcoholic drinks (>10/week)
10. Bodyweight < 50 kg

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LSD-100, LSD-200, Psilocybin-15, Psilocybin-30, Placebo; Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase	Drug: LSD; LSD 0.1 mg per os, single dose; Drug: LSD; LSD 0.2 mg per os, single dose; Drug: Psilocybin; Psilocybin 15 mg per os, single dose; Drug: Psilocybin; Psilocybin 30 mg per os, single dose
Placebo Comparator: LSD-200, Psilocybin-15, Psilocybin-30, Placebo, LSD-100; Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase	Drug: LSD; LSD 0.1 mg per os, single dose; Drug: LSD; LSD 0.2 mg per os, single dose; Drug: Psilocybin; Psilocybin 15 mg per os, single dose; Drug: Psilocybin; Psilocybin 30 mg per os, single dose
Placebo Comparator: Psilocybin-15, Psilocybin-30, Placebo, LSD-100, LSD-200; Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase	Drug: LSD; LSD 0.1 mg per os, single dose; Drug: LSD; LSD 0.2 mg per os, single dose; Drug: Psilocybin; Psilocybin 15 mg per os, single dose; Drug: Psilocybin; Psilocybin 30 mg per os, single dose
Placebo Comparator: Psilocybin-30, Placebo, LSD-100, LSD-200, Psilocybin-15; Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase	Drug: LSD; LSD 0.1 mg per os, single dose; Drug: LSD; LSD 0.2 mg per os, single dose; Drug: Psilocybin; Psilocybin 15 mg per os, single dose; Drug: Psilocybin; Psilocybin 30 mg per os, single dose
Placebo Comparator: Placebo, LSD-100, LSD-200, Psilocybin-15, Psilocybin-30; Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase	Drug: LSD; LSD 0.1 mg per os, single dose; Drug: LSD; LSD 0.2 mg per os, single dose; Drug: Psilocybin; Psilocybin 15 mg per os, single dose; Drug: Psilocybin; Psilocybin 30 mg per os, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Altered states of consciousness	total 5D-ASC score (5-Dimensional Altered States of Consciousness Rating Scale)	18 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective effects assessed by VAS	VAS (Visual analog scale)	18 Months
Subjective effects assessed by AMRS scales	AMRS scales (Adjective mood Rating scale)	18 Months
Psychotomimetic effects	ESI (Eppendorf Schizophrenia Inventory)	18 Months
Mystical-type experiences assessed by SCQ	SCQ (States of consciousness questionnaire)	18 Months
Mystical-type experiences assessed by MS scales	MS scales (Mysticism scale)	18 Months
Effects on emotion processing	FERT (Face Emotion Recognition Task)	18 Months
Autonomic effects assessed by heart rate	Heart rate	18 Months
Autonomic effects assessed by blood pressure	Blood pressure (diastolic and systolic)	18 Months
Autonomic effects assessed by body temperature	Body temperature	18 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of LSD and psilocin	assessment of plasma levels of LSD and psilocin	18 Months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Matthias E Liechti, MD, MAS, University Hospital, Basel, Switzerland

Publications and helpful links

General Publications

• Holze F, Ley L, Muller F, Becker AM, Straumann I, Vizeli P, Kuehne SS, Roder MA, Duthaler U, Kolaczynska KE, Varghese N, Eckert A, Liechti ME. Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects. Neuropsychopharmacology. 2022 May;47(6):1180-1187. doi: 10.1038/s41386-022-01297-2. Epub 2022 Feb 25.

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2019
• Primary Completion (Actual): April 10, 2021
• Study Completion (Actual): April 15, 2021

Study Registration Dates

• First Submitted: July 19, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (Actual): July 27, 2018

Study Record Updates

• Last Update Posted (Actual): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin
• Other Study ID Numbers: BASEC 2018-00985

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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