Psychological, Physiological, Endocrine, and Pharmacokinetic Effects of LSD in a Controlled Study

The purpose of this study is to characterize the acute psychological, physiological, endocrine, and pharmacokinetic, as well as long-term psychological effects of LSD in humans.

Study Overview

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

Detailed Description

Lysergic acid diethylamide (LSD) is the prototype hallucinogen used recreationally worldwide. In the 50-70s, LSD was also used to study psychotic-like states in normals ("model psychosis") and in "psycholytic psychotherapy". Potential research and therapeutic uses of LSD are now re-recognized and may include its use in brain research, treatment of cluster headache, and aid in psychotherapy and in terminally ill patients. A better and contemporary understanding of the pharmacology of LSD is important in the light of its widespread recreational, and potential scientific and therapeutic uses. The study has no primary therapeutic intentions but aims for a solid account of the clinical pharmacological characteristics of the drug. To characterize the acute physiological, psychological, endocrine, and pharmacological response to the administration of a single dose of LSD in healthy subjects the investigators use a randomized double-blind placebo-controlled cross-over design with two experimental sessions. Subjects will participate in a placebo and a LSD session. Subjective and cardiovascular responses will be repeatedly assessed throughout the experiments and plasma samples are collected for pharmacokinetics and endocrine measurements.Additionally long-term psychological changes associated with the LSD experience are assessed.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Basel-Stadt
    • Basel, Basel-Stadt, Switzerland, 4031
      • 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 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 xanthine-containing liquids (such as coffee, black or green tea, red bull, chocolate) 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 within 48 h following LSD administration.
8. Women of childbearing potential must have a negative pregnancy test at the beginning of the study and must agree to use an effective form of birth control. Pregnancy tests are repeated before each study session.

Exclusion Criteria:

1. Chronic or acute medical condition including clinically relevant abnormality in physical exam, laboratory values, or ECG. In particular: Hypertension (>150/95 mmHg). Personal or first-grade history of seizures. Cardiac or neurological disorder.
2. Current or previous psychotic or major affective disorder
3. Psychotic or major affective disorder in first-degree relatives
4. Relevant prior illicit drug use (except tetrahydrocannabinol (THC)-containing products) more than 10 times or any time within the previous 2 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. Insufficient interpersonal relationship/rapport with study physician as judged by the study physician

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Placebo, LSD; Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but two treatment conditions in the same subject.	Drug: Placebo; Capsules containing mannitol looking identical to LSD per os; Drug: LSD; 200µg per os, single dose; Other Names: Lysergic acid diethylamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective / psychological effects of LSD	repeated assessment of subjective effects with validated questionnaires	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physiological effects of LSD	Effect on blood pressure, heart rate, body temperature, and pupillary function	24 hours
Endocrine response of LSD		24 hours
Pharmacokinetics of LSD	Time course of plasma concentration, half-life, pharmacokinetic-pharmacodynamic relationship	24 hours
Effect of LSD on prepulse inhibition	Pre-Pulse inhibition of the acoustic startle reflex	3 hours
Tolerability of LSD	Assessment of adverse effects	24 hours
Long-term psychological effects of LSD	Assessment of long-term psychological effects after 1 and 12 months	12 months
Genetic Polymorphisms	Effects of genetic polymorphisms on the response to LSD	assessed once, at time of screening visit or at time of end of study visit
Effects on social cognition and empathy	assessment of cognitive and emotional empathy, as well as of prosocial behaviour	8 h

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

• Schmid Y, Liechti ME. Long-lasting subjective effects of LSD in normal subjects. Psychopharmacology (Berl). 2018 Feb;235(2):535-545. doi: 10.1007/s00213-017-4733-3. Epub 2017 Sep 16.
• Dolder PC, Schmid Y, Steuer AE, Kraemer T, Rentsch KM, Hammann F, Liechti ME. Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects. Clin Pharmacokinet. 2017 Oct;56(10):1219-1230. doi: 10.1007/s40262-017-0513-9.
• Liechti ME, Dolder PC, Schmid Y. Alterations of consciousness and mystical-type experiences after acute LSD in humans. Psychopharmacology (Berl). 2017 May;234(9-10):1499-1510. doi: 10.1007/s00213-016-4453-0. Epub 2016 Oct 7.
• Dolder PC, Schmid Y, Muller F, Borgwardt S, Liechti ME. LSD Acutely Impairs Fear Recognition and Enhances Emotional Empathy and Sociality. Neuropsychopharmacology. 2016 Oct;41(11):2638-46. doi: 10.1038/npp.2016.82. Epub 2016 Jun 1.
• Schmid Y, Enzler F, Gasser P, Grouzmann E, Preller KH, Vollenweider FX, Brenneisen R, Muller F, Borgwardt S, Liechti ME. Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects. Biol Psychiatry. 2015 Oct 15;78(8):544-53. doi: 10.1016/j.biopsych.2014.11.015. Epub 2014 Nov 29.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: May 27, 2013
• First Submitted That Met QC Criteria: June 12, 2013
• First Posted (Estimate): June 17, 2013

Study Record Updates

• Last Update Posted (Estimate): January 21, 2016
• Last Update Submitted That Met QC Criteria: January 20, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Serotonin; Pharmacodynamics; Pharmacology; LSD; Psychedelic; Mechanism of action; Prepulse inhibition; LSD-induced neuroendocrine effects; Long-term psychological effects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Serotonin Antagonists; Hallucinogens; Lysergic Acid Diethylamide
• Other Study ID Numbers: EK 279/12