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

• ClinicalTrials.gov Identifier: NCT03604744
• Recruitment Status: Completed
• First Posted: July 27, 2018
• Last Update Posted: April 27, 2021
• Sponsor: University Hospital, Basel, Switzerland
• Information provided by (Responsible Party): University Hospital, Basel, Switzerland

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: LSD; Drug: Psilocybin	Early Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Direct Comparison of Altered States of Consciousness Induced by LSD and Psilocybin in a Random-order Placebo-controlled Cross-over Study in Healthy Subjects
• Actual Study Start Date: March 27, 2019
• Actual Primary Completion Date: April 10, 2021
• Actual Study Completion Date: April 15, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Altered states of consciousness [ Time Frame: 18 Months ]
   total 5D-ASC score (5-Dimensional Altered States of Consciousness Rating Scale)

Secondary Outcome Measures :

1. Subjective effects assessed by VAS [ Time Frame: 18 Months ]
   VAS (Visual analog scale)
2. Subjective effects assessed by AMRS scales [ Time Frame: 18 Months ]
   AMRS scales (Adjective mood Rating scale)
3. Psychotomimetic effects [ Time Frame: 18 Months ]
   ESI (Eppendorf Schizophrenia Inventory)
4. Mystical-type experiences assessed by SCQ [ Time Frame: 18 Months ]
   SCQ (States of consciousness questionnaire)
5. Mystical-type experiences assessed by MS scales [ Time Frame: 18 Months ]
   MS scales (Mysticism scale)
6. Effects on emotion processing [ Time Frame: 18 Months ]
   FERT (Face Emotion Recognition Task)
7. Autonomic effects assessed by heart rate [ Time Frame: 18 Months ]
   Heart rate
8. Autonomic effects assessed by blood pressure [ Time Frame: 18 Months ]
   Blood pressure (diastolic and systolic)
9. Autonomic effects assessed by body temperature [ Time Frame: 18 Months ]
   Body temperature

Other Outcome Measures:

1. Plasma levels of LSD and psilocin [ Time Frame: 18 Months ]
   assessment of plasma levels of LSD and psilocin

Eligibility Criteria

• Ages Eligible for Study: 25 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Switzerland

Clinical Pharmacology & Toxicology, University Hospital Basel

Basel, Switzerland, 4056

Sponsors and Collaborators

University Hospital, Basel, Switzerland

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT03604744
• Other Study ID Numbers: BASEC 2018-00985
• First Posted: July 27, 2018
• Last Update Posted: April 27, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Psilocybin; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs