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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Placebo
* Drug: LSD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 25 and 65 years Understanding of the German language Understanding the procedures and the risks 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 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. Participants must be willing not to drive a traffic vehicle within 48 h following LSD administration. 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: 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. Current or previous psychotic or major affective disorder Psychotic or major affective disorder in first-degree relatives Relevant prior illicit drug use (except tetrahydrocannabinol (THC)-containing products) more than 10 times or any time within the previous 2 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) Insufficient interpersonal relationship/rapport with study physician as judged by the study physician

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Placebo, LSD<br>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<br>* Capsules containing mannitol looking identical to LSD per os<br>Drug: LSD<br>* 200µg per os, single dose<br>* Other names: Lysergic acid diethylamide;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LSD, Pharmacology, Pharmacokinetics, Pharmacodynamics, Mechanism of action, Psychedelic, Serotonin, Prepulse inhibition, LSD-induced neuroendocrine effects, Long-term psychological effects