NCT03604744

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
28

participants targeted

Target at P25-P50 for early_phase_1 healthy

Timeline
Completed

Started Mar 2019

Longer than P75 for early_phase_1 healthy

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 19, 2018

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 27, 2018

Completed
8 months until next milestone

Study Start

First participant enrolled

March 27, 2019

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 10, 2021

Completed
5 days until next milestone

Study Completion

Last participant's last visit for all outcomes

April 15, 2021

Completed
Last Updated

April 27, 2021

Status Verified

April 1, 2021

Enrollment Period

2 years

First QC Date

July 19, 2018

Last Update Submit

April 26, 2021

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

  • Altered states of consciousness

    total 5D-ASC score (5-Dimensional Altered States of Consciousness Rating Scale)

    18 Months

Secondary Outcomes (9)

  • Subjective effects assessed by VAS

    18 Months

  • Subjective effects assessed by AMRS scales

    18 Months

  • Psychotomimetic effects

    18 Months

  • Mystical-type experiences assessed by SCQ

    18 Months

  • Mystical-type experiences assessed by MS scales

    18 Months

  • +4 more secondary outcomes

Other Outcomes (1)

  • Plasma levels of LSD and psilocin

    18 Months

Study Arms (5)

LSD-100, LSD-200, Psilocybin-15, Psilocybin-30, Placebo

EXPERIMENTAL

Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase

Drug: LSDDrug: Psilocybin

LSD-200, Psilocybin-15, Psilocybin-30, Placebo, LSD-100

PLACEBO COMPARATOR

Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase

Drug: LSDDrug: Psilocybin

Psilocybin-15, Psilocybin-30, Placebo, LSD-100, LSD-200

PLACEBO COMPARATOR

Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase

Drug: LSDDrug: Psilocybin

Psilocybin-30, Placebo, LSD-100, LSD-200, Psilocybin-15

PLACEBO COMPARATOR

Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase

Drug: LSDDrug: Psilocybin

Placebo, LSD-100, LSD-200, Psilocybin-15, Psilocybin-30

PLACEBO COMPARATOR

Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase

Drug: LSDDrug: Psilocybin

Interventions

LSDDRUG

LSD 0.1 mg per os, single dose

LSD-100, LSD-200, Psilocybin-15, Psilocybin-30, PlaceboLSD-200, Psilocybin-15, Psilocybin-30, Placebo, LSD-100Placebo, LSD-100, LSD-200, Psilocybin-15, Psilocybin-30Psilocybin-15, Psilocybin-30, Placebo, LSD-100, LSD-200Psilocybin-30, Placebo, LSD-100, LSD-200, Psilocybin-15
PsilocybinDRUG

Psilocybin 15 mg per os, single dose

LSD-100, LSD-200, Psilocybin-15, Psilocybin-30, PlaceboLSD-200, Psilocybin-15, Psilocybin-30, Placebo, LSD-100Placebo, LSD-100, LSD-200, Psilocybin-15, Psilocybin-30Psilocybin-15, Psilocybin-30, Placebo, LSD-100, LSD-200Psilocybin-30, Placebo, LSD-100, LSD-200, Psilocybin-15

Eligibility Criteria

Age25 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age between 25 and 65 years.
  • Understanding of the German language.
  • Understanding the procedures and the risks that are associated with the study.
  • Participants must be willing to adhere to the protocol and sign the consent form.
  • Participants must be willing to refrain from taking illicit psychoactive substances during the study.
  • 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.
  • Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
  • Women of childbearing potential must have a negative pregnancy test at the beginning of the study. Pregnancy tests are repeated before each study session.
  • Women of childbearing potential must be willing to use double-barrier birth control
  • Body mass index 18-29 kg/m2.

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Clinical Pharmacology & Toxicology, University Hospital Basel

Basel, 4056, Switzerland

Location

Related Publications (2)

  • Holze F, Becker AM, Kolaczynska KE, Duthaler U, Liechti ME. Pharmacokinetics and Pharmacodynamics of Oral Psilocybin Administration in Healthy Participants. Clin Pharmacol Ther. 2023 Apr;113(4):822-831. doi: 10.1002/cpt.2821. Epub 2022 Dec 31.

    PMID: 36507738DERIVED

  • 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.

    PMID: 35217796DERIVED

MeSH Terms

Interventions

Lysergic Acid DiethylamidePsilocybin

Intervention Hierarchy (Ancestors)

Lysergic AcidErgolinesErgot AlkaloidsAlkaloidsHeterocyclic CompoundsHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingIndole AlkaloidsIndolesHeterocyclic Compounds, 2-RingTryptaminesIndolizidinesIndolizines

Study Officials

  • Matthias E Liechti, MD, MAS

    University Hospital, Basel, Switzerland

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 19, 2018

First Posted

July 27, 2018

Study Start

March 27, 2019

Primary Completion

April 10, 2021

Study Completion

April 15, 2021

Last Updated

April 27, 2021

Record last verified: 2021-04

Data Sharing

IPD Sharing
Will not share

Locations

CH(1)