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LSD Base and LSD Tartrate Bioequivalence and Bioavailability in Healthy Subjects (LSD-Bio)

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ClinicalTrials.gov Identifier: NCT04865653
Recruitment Status : Recruiting
First Posted : April 29, 2021
Last Update Posted : March 31, 2022
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Tracking Information
First Submitted Date  ICMJE April 26, 2021
First Posted Date  ICMJE April 29, 2021
Last Update Posted Date March 31, 2022
Actual Study Start Date  ICMJE March 17, 2022
Estimated Primary Completion Date March 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2021)
  • LSD plasma AUC [ Time Frame: 18 months ]
    Assessed 22 times on each study day via blood samples
  • LSD Cmax [ Time Frame: 18 months ]
    Assessed 22 times on each study day via blood samples
  • Bioavailability of LSD base [ Time Frame: 18 months ]
    Assessed 22 times on each study day via blood samples
  • Bioavailability of LSD tartrate [ Time Frame: 18 months ]
    Assessed 22 times on each study day via blood samples
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2021)
  • Acute subjective effects I [ Time Frame: 18 months ]
    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
  • Acute subjective effects II [ Time Frame: 18 months ]
    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
  • Acute subjective effects III [ Time Frame: 18 months ]
    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
  • Acute subjective effects IV [ Time Frame: 18 months ]
    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")
  • Autonomic effects I [ Time Frame: 18 months ]
    Assessed 23 times on each study day via systolic and diastolic blood pressure
  • Autonomic effects II [ Time Frame: 18 months ]
    Assessed 23 times on each study day via heart rate
  • Autonomic effects III [ Time Frame: 18 months ]
    Assessed 23 times on each study day via tympanic body temperature
  • Bioavailability of orodispersible film [ Time Frame: 18 months ]
    Assessed 22 times on each study day via blood samples
  • NEO-Five-Factor-Inventory (NEO-FFI) [ Time Frame: Baseline ]
    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".
  • Freiburger Personality Inventory (FPI-R) [ Time Frame: Baseline ]
    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").
  • Saarbrücker Personality Questionnaire (SPF) [ Time Frame: Baseline ]
    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.
  • HEXACO personality inventory [ Time Frame: Baseline ]
    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".
  • Defense Style Questionnaire (DSQ-40) [ Time Frame: Baseline ]
    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".
  • Absence of tolerance [ Time Frame: 18 months ]
    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)
  • Appreciation Scale (AS) [ Time Frame: Baseline ]
    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").
  • Subjective well-being I [ Time Frame: 18 months ]
    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".
  • Subjective well-being II [ Time Frame: 18 months ]
    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").
  • Subjective well-being III [ Time Frame: 18 months ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE LSD Base and LSD Tartrate Bioequivalence and Bioavailability in Healthy Subjects
Official Title  ICMJE LSD Base and LSD Tartrate Bioequivalence and Bioavailability in Healthy Subjects
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
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
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: Lysergic Acid Diethylamide Base oral drinking solution
    A moderate dose of 0.1 mg LSD will be administered.
    Other Name: LSD
  • Drug: Lysergic Acid Diethylamide Base solid orodispersible film
    A moderate dose of 0.1 mg LSD will be administered.
    Other Name: LSD
  • 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).
    Other Name: LSD
  • 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).
    Other Name: LSD
  • Other: LSD Placebo
    Placebo for each formulation containing only the solvent or gel but no LSD.
    Other Name: Placebo
Study Arms  ICMJE
  • Experimental: Oral drinking solution of LSD base
    Oral drinking solution of 0.1 mg LSD base in 96% ethanol
    Intervention: Drug: Lysergic Acid Diethylamide Base oral drinking solution
  • Experimental: Solid orodispersible film containing LSD base
    Solid orodispersible film containing 0.1 mg LSD base
    Intervention: Drug: Lysergic Acid Diethylamide Base solid orodispersible film
  • Experimental: Oral drinking solution of LSD tartrate
    Oral drinking solution of 0.146 mg LSD tartrate in water
    Intervention: Drug: Lysergic Acid Diethylamide Tartrate oral drinking solution
  • Experimental: Intravenous administration of LSD tartrate
    Intravenous administration of 0.146 mg LSD tartrate in water
    Intervention: Drug: Lysergic Acid Diethylamide Tartrate intravenous administration
  • Placebo Comparator: Placebo
    Placebo for all formulations
    Intervention: Other: LSD Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 26, 2021)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2023
Estimated Primary Completion Date March 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Matthias E Liechti, MD 061 328 68 68 ext +41 matthias.liechti@usb.ch
Contact: Friederike Holze, MSc 061 556 54 37 ext +41 friederike.holze@usb.ch
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04865653
Other Study ID Numbers  ICMJE BASEC 2020-02331
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University Hospital, Basel, Switzerland
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University Hospital, Basel, Switzerland
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Matthias E Liechti, MD University Hospital, Basel, Switzerland
PRS Account University Hospital, Basel, Switzerland
Verification Date March 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP