LSD Base and LSD Tartrate Bioequivalence and Bioavailability in Healthy Subjects

Healthy Clinical Trial

— LSD-Bio  

Official title:

LSD Base and LSD Tartrate Bioequivalence and Bioavailability in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04865653
• Other study ID #: BASEC 2020-02331
• Status: Completed
• Phase: Phase 1
• Start date: March 17, 2022
• Est. completion date: October 11, 2023

Study information

• Verified date: February 2024
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 11, 2023
• Est. primary completion date: October 11, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Lysergic Acid Diethylamide Base oral drinking solution
A moderate dose of 0.1 mg LSD will be administered.
• Lysergic Acid Diethylamide Base solid orodispersible film
A moderate dose of 0.1 mg LSD will be administered.
• 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).
• 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).

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

Locations

Country	Name	City	State
Switzerland	Clinical Pharmacology & Toxicology, University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	LSD plasma AUC	Assessed 22 times on each study day via blood samples	18 months
Primary	LSD Cmax	Assessed 22 times on each study day via blood samples	18 months
Primary	Bioavailability of LSD base	Assessed 22 times on each study day via blood samples	18 months
Primary	Bioavailability of LSD tartrate	Assessed 22 times on each study day via blood samples	18 months
Secondary	Acute subjective effects I	Visual Analog Scales (VAS) assessing the intensity and duration of subjective effects on a scale from 0% - 100% with higher scores representing more intense effects	18 months
Secondary	Acute subjective effects II	5 Dimensions of Altered States of Consciousness (5D-ASC) consisting of 94 items to be rated on a visual analog scale (0-100 mm), with higher values indicating stronger effects	18 months
Secondary	Acute subjective effects III	Spiritual Realm Questionnaire assesses the spiritual phenomenons elicited by psychedelic substances through 11 main questions to be answered on a total of 65 sub-ordered 100mm visual analog scales	18 months
Secondary	Acute subjective effects IV	States of Consciousness Questionnaire assesses the emergence and intensity of phenomenons occurring in altered states of consciousness on a 6-point Likert scale ranging from 0 ("not at all") to 5 ("extremely")	18 months
Secondary	Autonomic effects I	Assessed 23 times on each study day via systolic and diastolic blood pressure	18 months
Secondary	Autonomic effects II	Assessed 23 times on each study day via heart rate	18 months
Secondary	Autonomic effects III	Assessed 23 times on each study day via tympanic body temperature	18 months
Secondary	Bioavailability of orodispersible film	Assessed 22 times on each study day via blood samples	18 months
Secondary	NEO-Five-Factor-Inventory (NEO-FFI)	The NEO-FFI is a self-description questionnaire with 60 items for the measurement of the "big five": neuroticism, extraversion, openness, agreeableness, and consciousness. It uses a 5-point Likert scale ranging from "completely disagree" to "fully agree".	Baseline
Secondary	Freiburger Personality Inventory (FPI-R)	The FPI-R version comprises 138 items and covers 12 dimensions of personality: life satisfaction, social orientation, performance orientation, inhibition, excitability, aggressiveness, stress, physical complaints, health concerns, openness, as well as the secondary factors according to Eysenck's Extraversion and Emotionality (Neuroticism). It uses a 2-point scale ("true" and "not true").	Baseline
Secondary	Saarbrücker Personality Questionnaire (SPF)	The SPF defines empathy as the "reactions of one individual to the observed experiences of another." It assesses 28-items on a 5-point Likert scale ranging from "Does not describe me well" to "Describes me very well". The measure has 4 subscales (Perspective Taking, Fantasy, Empathic Concern, Personal Distress) each made up of 7 different items.	Baseline
Secondary	HEXACO personality inventory	The HEXACO personality inventory is a six-dimensional model of human personality with 100 items.The six factors are: Honesty-Humility, Emotionality, Extraversion, Agreeableness, Conscientiousness and Openness to Experience. The HEXACO uses a 5-point Likert scale ranging from "completely disagree" to "fully agree".	Baseline
Secondary	Defense Style Questionnaire (DSQ-40)	The DSQ-40 can provide scores for 20 individual defenses, and scores for the three factors "mature", "neurotic", and "immature". Each item is evaluated on a scale from 1 to 9, where "1" indicates "completely disagree" and "9" indicates "fully agree".	Baseline
Secondary	Absence of tolerance	Absence of tolerance (no significant order effect) with repeated dosing of LSD with a between dosing interval of at least 10 days assessed with Visual Analog Scales (any drug response over time)	18 months
Secondary	Appreciation Scale (AS)	The Appreciation Scale comprises 57 items used to measure eight aspects of appreciation. The eight subscales are respectively focus on what one has ("Have" Focus), Awe, Ritual, Present Moment, Self/Social Comparison, Gratitude, Loss/Adversity, and Interpersonal. Each item is evaluated on a scale from 1 to 7 in terms of either attitude intensity ("strongly disagree" to "strongly agree") or frequency ("never" to "more than once a day").	Baseline
Secondary	Subjective well-being I	The Scale of Positive and Negative Experience (SPANE) is a 12-item questionnaire to capture the affective component of subjective well-being. It includes six items to assess positive feelings and six items to assess negative feelings. The feelings are reported on a 5-point scale ranging from "very rarely" to "very often or always".	18 months
Secondary	Subjective well-being II	The Positive Attitude towards life is an 8-item subscale of the 39-item Bern Subjective Well-Being Questionnaire and assesses different dimensions of subjective well-being. Evaluations are made using a six-point rating scale ranging from 1 ("strongly disagree") to 6 ("strongly agree").	18 months
Secondary	Subjective well-being III	Global Life Satisfaction (GLS) is assessed on a single item life satisfaction measure. The question is answered on a 11-point scale with 0 as "not at all satisfied with your life" and 10 " completely satisfied.	18 months