Clinical trial NCT04865653: LSD Base and LSD Tartrate Bioequivalence and Bioavailability in Healthy Subjects
Official title: LSD Base and LSD Tartrate Bioequivalence and Bioavailability in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2021-04-29
Enrollment: 20
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind, placebo-controlled, 5-period cross-over design with five treatment conditions:

1. Oral drinking solution of 0.1 mg LSD base in 96% ethanol
2. Solid orodispersible film containing 0.1 mg LSD base
3. Oral drinking solution of 0.146 mg LSD tartrate in water (equivalent to 0.1 mg LSD base)
4. Intravenous administration of 0.146 mg LSD tartrate in water (equivalent to 0.1 mg LSD base)
5. Placebo
Primary purpose: BASIC_SCIENCE

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.

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)

Primary outcomes:
measure: LSD plasma AUC
timeFrame: 18 months
measure: LSD Cmax
timeFrame: 18 months
measure: Bioavailability of LSD base
timeFrame: 18 months
measure: Bioavailability of LSD tartrate
timeFrame: 18 months
Secondary outcomes:
measure: Acute subjective effects I
timeFrame: 18 months
measure: Acute subjective effects II
timeFrame: 18 months
measure: Acute subjective effects III
timeFrame: 18 months
measure: Acute subjective effects IV
timeFrame: 18 months
measure: Autonomic effects I
timeFrame: 18 months
measure: Autonomic effects II
timeFrame: 18 months
measure: Autonomic effects III
timeFrame: 18 months
measure: Bioavailability of orodispersible film
timeFrame: 18 months
measure: NEO-Five-Factor-Inventory (NEO-FFI)
timeFrame: Baseline
measure: Freiburger Personality Inventory (FPI-R)
timeFrame: Baseline
measure: Saarbrücker Personality Questionnaire (SPF)
timeFrame: Baseline
measure: HEXACO personality inventory
timeFrame: Baseline
measure: Defense Style Questionnaire (DSQ-40)
timeFrame: Baseline
measure: Absence of tolerance
timeFrame: 18 months
measure: Appreciation Scale (AS)
timeFrame: Baseline
measure: Subjective well-being I
timeFrame: 18 months
measure: Subjective well-being II
timeFrame: 18 months
measure: Subjective well-being III
timeFrame: 18 months
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Clinical Pharmacology & Toxicology, University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias E Liechti, MD
role: PRINCIPAL_INVESTIGATOR
References: