Clinical trial NCT01878942: Psychological, Physiological, Endocrine, and Pharmacokinetic Effects of LSD in a Controlled Study
Official title: Psychological, Physiological, Endocrine, and Pharmacokinetic Effects of LSD in a Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Healthy
Keywords: LSD
Pharmacology
Pharmacokinetics
Pharmacodynamics
Mechanism of action
Psychedelic
Serotonin
Prepulse inhibition
LSD-induced neuroendocrine effects
Long-term psychological effects
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2013-06-17
Enrollment: 16
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Subjective / psychological effects of LSD
timeFrame: 24 hours
Secondary outcomes:
measure: Physiological effects of LSD
timeFrame: 24 hours
measure: Endocrine response of LSD
timeFrame: 24 hours
measure: Pharmacokinetics of LSD
timeFrame: 24 hours
measure: Effect of LSD on prepulse inhibition
timeFrame: 3 hours
measure: Tolerability of LSD
timeFrame: 24 hours
measure: Long-term psychological effects of LSD
timeFrame: 12 months
measure: Genetic Polymorphisms
timeFrame: assessed once, at time of screening visit or at time of end of study visit
measure: Effects on social cognition and empathy
timeFrame: 8 h
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
state: Basel-Stadt
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias E Liechti, MD, MAS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.