title: Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects.
abstract: BACKGROUND
  After no research in humans for >40 years, there is renewed interest in using lysergic acid diethylamide (LSD) in clinical psychiatric research and practice. There are no modern studies on the subjective and autonomic effects of LSD, and its endocrine effects are unknown. In animals, LSD disrupts prepulse inhibition (PPI) of the acoustic startle response, and patients with schizophrenia exhibit similar impairments in PPI. However, no data are available on the effects of LSD on PPI in humans.
  
  
  METHODS
  In a double-blind, randomized, placebo-controlled, crossover study, LSD (200 μg) and placebo were administered to 16 healthy subjects (8 women, 8 men). Outcome measures included psychometric scales; investigator ratings; PPI of the acoustic startle response; and autonomic, endocrine, and adverse effects.
  
  
  RESULTS
  Administration of LSD to healthy subjects produced pronounced alterations in waking consciousness that lasted 12 hours. The predominant effects induced by LSD included visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization phenomena. Subjective well-being, happiness, closeness to others, openness, and trust were increased by LSD. Compared with placebo, LSD decreased PPI. LSD significantly increased blood pressure, heart rate, body temperature, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine. Adverse effects produced by LSD completely subsided within 72 hours. No severe acute adverse effects were observed.
  
  
  CONCLUSIONS
  In addition to marked hallucinogenic effects, LSD exerts methylenedioxymethamphetamine-like empathogenic mood effects that may be useful in psychotherapy. LSD altered sensorimotor gating in a human model of psychosis, supporting the use of LSD in translational psychiatric research. In a controlled clinical setting, LSD can be used safely, but it produces significant sympathomimetic stimulation.
authors.affiliation: Psychopharmacology Research, Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Schmid
authors.affiliation: Psychopharmacology Research, Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel.
authors.forename: Florian
authors.initials: F
authors.lastname: Enzler
authors.affiliation: Practice for Psychiatry and Psychotherapy, Solothurn.
authors.forename: Peter
authors.initials: P
authors.lastname: Gasser
authors.affiliation: Biomedicine Service, University Hospital Lausanne, Lausanne.
authors.forename: Eric
authors.initials: E
authors.lastname: Grouzmann
authors.affiliation: Neuropsychopharmacology and Brain Imaging and Heffter Research Center, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Zurich.
authors.forename: Katrin H
authors.initials: KH
authors.lastname: Preller
authors.affiliation: Neuropsychopharmacology and Brain Imaging and Heffter Research Center, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Zurich.
authors.forename: Franz X
authors.initials: FX
authors.lastname: Vollenweider
authors.affiliation: Department of Clinical Research, University of Bern, Bern.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Brenneisen
authors.affiliation: Department of Psychiatry, University of Basel, Basel, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Müller
authors.affiliation: Department of Psychiatry, University of Basel, Basel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Borgwardt
authors.affiliation: Psychopharmacology Research, Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel.. Electronic address: matthias.liechti@usb.ch.
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Liechti
mesh_terms: D000328:Adult; D000818:Animals; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage* / Q000009:adverse effects; D064368:Healthy Volunteers / Q000523:psychology*; D006801:Humans; D008238:Lysergic Acid Diethylamide / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011613:Psychotherapy; D013216:Reflex, Startle / Q000187:drug effects*; D055139:Sensory Gating / Q000187:drug effects*; D013566:Sympathomimetics
chemical_list: D006213:Hallucinogens; D013566:Sympathomimetics; D008238:Lysergic Acid Diethylamide
keywords: Adverse effects; Hormones; LSD; Prepulse inhibition; Subjective effects; Sympathomimetic effects