LSD Base and LSD Tartrate Bioequivalence and Bioavailability in Healthy Subjects

NCT ID: NCT04865653

Last Updated: 2024-02-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-17
• Study Completion Date: 2023-10-11

Brief Summary

Lysergic acid diethylamide (LSD) is used as recreational substance and as a research substance to study the mind. Recreationally, LSD is typically used in the form of "blotters" containing LSD tartrate. In research, both LSD base (LSD alone) or LSD salt in the form of LSD tartrate are used. The oral bioavailability of LSD is not known and LSD alone and LSD as salt have never been directly compared regarding their equivalence of plasma concentrations and effects. Because different forms of LSD are used in research it is important to know their difference or equivalence for correct dosing of LSD. The present study will compare equivalent doses of LSD base in ethanol orally, LSD tartrate in water administered orally, LSD base in an orodispersible film administered orally and LSD tartrate in water administered intravenously, as well as a placebo using a double-blind, randomized, counterballanced cross-over design in healthy participants.

Detailed Description

LSD is widely used for recreational and spiritual purposes. Additionally LSD is currently reused in experimental studies with healthy subjects and in studies investigating its effects on patients suffering from anxiety, depression, addiction personality disorders, cluster headache, migraine, and other pathological conditions.

When LSD is used recreationally, it is administered mostly in the form of LSD tartrate on filter paper (blotter) or as a liquid. In experimental research over the past years, LSD has mostly been used in the form of LSD base, which is lipophilic and therefore has typically been administered as a solution in ethanol. However, some researchers have also use LSD tartrate orally or LSD base intravenously. Currently, it is not clear how these different forms of LSD compare regarding their bioequivalence and effects.

The present study therefore compares four different formulations of LSD and placebo: (1) An oral drinking solution of LSD base currently used in many research studies (100 μg LSD in 96% ethanol), (2) A solid orodispersible film containing LSD base (100 μg LSD), (3) LSD tartrate used in research and recreationally (100 μg LSD equivalent of LSD tartrate in water), (4) an intravenous administration of LSD tartrate (100 μg LSD equivalent of LSD tartrate in water), and (5) placebo for all formulations (quadruple-dummy). The primary goals are to document the bioequivalence of LSD base (1) and tartrate (3) and to define the oral bioavailability of LSD using an additional intravenous LSD administration.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Intravenous administration of LSD tartrate

Intravenous administration of 0.146 mg LSD tartrate in water

Group Type: EXPERIMENTAL

Lysergic Acid Diethylamide Tartrate intravenous administration

Intervention Type: DRUG

A moderate dose of 0.146 mg LSD tartrate will be administered (equivalent to 0.1 mg LSD base).

Placebo

Placebo for all formulations

Group Type: PLACEBO_COMPARATOR

LSD Placebo

Intervention Type: OTHER

Placebo for each formulation containing only the solvent or gel but no LSD.

Oral drinking solution of LSD base

Oral drinking solution of 0.1 mg LSD base in 96% ethanol

Group Type: EXPERIMENTAL

Lysergic Acid Diethylamide Base oral drinking solution

Intervention Type: DRUG

A moderate dose of 0.1 mg LSD will be administered.

Solid orodispersible film containing LSD base

Solid orodispersible film containing 0.1 mg LSD base

Group Type: EXPERIMENTAL

Lysergic Acid Diethylamide Base solid orodispersible film

Intervention Type: DRUG

A moderate dose of 0.1 mg LSD will be administered.

Oral drinking solution of LSD tartrate

Oral drinking solution of 0.146 mg LSD tartrate in water

Group Type: EXPERIMENTAL

Lysergic Acid Diethylamide Tartrate oral drinking solution

Intervention Type: DRUG

A moderate dose of 0.146 mg LSD tartrate will be administered (equivalent to 0.1 mg LSD base).

Interventions

Lysergic Acid Diethylamide Base oral drinking solution

A moderate dose of 0.1 mg LSD will be administered.

Intervention Type: DRUG

Lysergic Acid Diethylamide Base solid orodispersible film

A moderate dose of 0.1 mg LSD will be administered.

Intervention Type: DRUG

Lysergic Acid Diethylamide Tartrate oral drinking solution

A moderate dose of 0.146 mg LSD tartrate will be administered (equivalent to 0.1 mg LSD base).

Intervention Type: DRUG

Lysergic Acid Diethylamide Tartrate intravenous administration

A moderate dose of 0.146 mg LSD tartrate will be administered (equivalent to 0.1 mg LSD base).

Intervention Type: DRUG

LSD Placebo

Placebo for each formulation containing only the solvent or gel but no LSD.

Intervention Type: OTHER

Other Intervention Names

LSD; LSD; LSD; LSD; Placebo

Eligibility Criteria

Inclusion Criteria

1. Age between 25 and 65 years old

2. Sufficient understanding of the German language

3. Understanding of procedures and risks associated with the study

4. Willing to adhere to the protocol and signing of the consent form

5. Willing to refrain from the consumption of illicit psychoactive substances during the study

6. Abstaining from xanthine-based liquids from the evenings prior to the study sessions to the end of the study days

7. Willing not to operate heavy machinery within 48 hours after substance administration

8. Willing to use double-barrier birth control throughout study participation

9. Body mass index between 18-29 kg/m2

Exclusion Criteria

1. Chronic or acute medical condition

2. Current or previous major psychiatric disorder

3. Psychotic disorder or bipolar disorder in first-degree relatives

4. Hypertension (>140/90 mmHg) or hypotension (SBP<85 mmHg)

5. Hallucinogenic substance use (not including cannabis) more than 20 times or any time within the previous two months

6. Pregnancy or current breastfeeding

7. Participation in another clinical trial (currently or within the last 30 days)

8. Use of medication that may interfere with the effects of the study medication

9. Tobacco smoking (>10 cigarettes/day)

10. Consumption of alcoholic beverages (>20 drinks/week)

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthias E Liechti, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

Clinical Pharmacology & Toxicology, University Hospital Basel

Basel, , Switzerland

Countries

Switzerland

Other Identifiers

BASEC 2020-02331

Identifier Type: -

Identifier Source: org_study_id