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Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

Yasmin Schmid, Florian Enzler, Peter Gasser, Eric Grouzmann, Katrin H. Preller, Franz X. Vollenweider, Rudolf Brenneisen, Felix Müller, Stefan Borgwardt, Matthias E. Liechti

Biological Psychiatry November 29, 2014 DOI: 10.1016/j.biopsych.2014.11.015 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Double-blind, randomized, placebo-controlled, crossover study Peer reviewed
Sample size 16
Population Healthy subjects (8 women, 8 men)
Intervention Lysergic acid diethylamide
Dose 200 μg
Duration 12 hours for subjective effects; adverse effects subsided within 72 hours
Topics LSD Serotonin
Keywords Prepulse inhibition Hallucinogen Depersonalization Placebo Heart rate Derealization Orthostatic vital signs Mood Adverse effect Psychosis Crossover study Blood pressure Schizophrenia object-oriented programming Clinical psychology
Citations 425
Key points LSD produces pronounced hallucinogenic and empathogenic mood effects, decreases prepulse inhibition, and increases autonomic and endocrine measures in healthy subjects.

Abstract

BackgroundAfter 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.MethodsIn 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.ResultsAdministration 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.ConclusionsIn 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.

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