title: Pharmacokinetics and Concentration-Effect Relationship of Oral LSD in Humans.
abstract: BACKGROUND
  The pharmacokinetics of oral lysergic acid diethylamide are unknown despite its common recreational use and renewed interest in its use in psychiatric research and practice.
  
  
  METHODS
  We characterized the pharmacokinetic profile, pharmacokinetic-pharmacodynamic relationship, and urine recovery of lysergic acid diethylamide and its main metabolite after administration of a single oral dose of lysergic acid diethylamide (200 μg) in 8 male and 8 female healthy subjects.
  
  
  RESULTS
  Plasma lysergic acid diethylamide concentrations were quantifiable (>0.1 ng/mL) in all the subjects up to 12 hours after administration. Maximal concentrations of lysergic acid diethylamide (mean±SD: 4.5±1.4 ng/mL) were reached (median, range) 1.5 (0.5-4) hours after administration. Concentrations then decreased following first-order kinetics with a half-life of 3.6±0.9 hours up to 12 hours and slower elimination thereafter with a terminal half-life of 8.9±5.9 hours. One percent of the orally administered lysergic acid diethylamide was eliminated in urine as lysergic acid diethylamide, and 13% was eliminated as 2-oxo-3-hydroxy-lysergic acid diethylamide within 24 hours. No sex differences were observed in the pharmacokinetic profiles of lysergic acid diethylamide. The acute subjective and sympathomimetic responses to lysergic acid diethylamide lasted up to 12 hours and were closely associated with the concentrations in plasma over time and exhibited no acute tolerance.
  
  
  CONCLUSIONS
  These first data on the pharmacokinetics and concentration-effect relationship of oral lysergic acid diethylamide are relevant for further clinical studies and serve as a reference for the assessment of intoxication with lysergic acid diethylamide.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research (Mr Dolder, and Drs Schmid, Haschke, and Liechti), and Laboratory Medicine (Mr Dolder and Dr Rentsch), University Hospital and University of Basel, Basel, Switzerland.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Dolder
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research (Mr Dolder, and Drs Schmid, Haschke, and Liechti), and Laboratory Medicine (Mr Dolder and Dr Rentsch), University Hospital and University of Basel, Basel, Switzerland.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Schmid
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research (Mr Dolder, and Drs Schmid, Haschke, and Liechti), and Laboratory Medicine (Mr Dolder and Dr Rentsch), University Hospital and University of Basel, Basel, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Haschke
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research (Mr Dolder, and Drs Schmid, Haschke, and Liechti), and Laboratory Medicine (Mr Dolder and Dr Rentsch), University Hospital and University of Basel, Basel, Switzerland.
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Rentsch
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research (Mr Dolder, and Drs Schmid, Haschke, and Liechti), and Laboratory Medicine (Mr Dolder and Dr Rentsch), University Hospital and University of Basel, Basel, Switzerland. matthias.liechti@usb.ch.
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Liechti
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006213:Hallucinogens / Q000008:administration & dosage / Q000097:blood* / Q000652:urine*; D064368:Healthy Volunteers; D006801:Humans; D016014:Linear Models; D008238:Lysergic Acid Diethylamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds; D012737:Sex Factors; D013997:Time Factors
chemical_list: D006213:Hallucinogens; D009942:Organometallic Compounds; C077684:JM 2469; D008238:Lysergic Acid Diethylamide; C118789:2-oxo-3-hydroxylysergic acid diethylamide
keywords: LSD; O-H-LSD; pharmacodynamics; pharmacokinetics; plasma; urine