LSD Base and LSD Tartrate Bioequivalence and Bioavailability in Healthy Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Lysergic Acid Diethylamide Base oral drinking solution; Lysergic Acid Diethylamide Base solid orodispersible film; Lysergic Acid Diethylamide Tartrate oral drinking solution; Lysergic Acid Diethylamide Tartrate intravenous administration; LSD Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Other
Intervention description(s): A moderate dose of 0.1 mg LSD will be administered.; A moderate dose of 0.1 mg LSD will be administered.; A moderate dose of 0.146 mg LSD tartrate will be administered (equivalent to 0.1 mg LSD base).; A moderate dose of 0.146 mg LSD tartrate will be administered (equivalent to 0.1 mg LSD base).; Placebo for each formulation containing only the solvent or gel but no LSD.
Other intervention name(s): LSD; LSD; LSD; LSD; Placebo
Intervention MeSH terms: Lysergic Acid Diethylamide; Pharmaceutical Solutions
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Double-blind, placebo-controlled, 5-period cross-over design with five treatment conditions:
Oral drinking solution of 0.1 mg LSD base in 96% ethanol
Solid orodispersible film containing 0.1 mg LSD base
Oral drinking solution of 0.146 mg LSD tartrate in water (equivalent to 0.1 mg LSD base)
Intravenous administration of 0.146 mg LSD tartrate in water (equivalent to 0.1 mg LSD base)
Placebo
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science