Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

In a double-blind, placebo-controlled crossover study, 200 μg of lysergic acid diethylamide (LSD) given to 16 healthy subjects produced pronounced alterations in consciousness lasting 12 hours, including visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization. LSD increased subjective well-being, happiness, closeness to others, openness, and trust, and decreased prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating. It also significantly increased blood pressure, heart rate, body temperature, pupil size, and plasma levels of cortisol, prolactin, oxytocin, and epinephrine. All adverse effects subsided within 72 hours, with no severe acute adverse effects observed. LSD produces empathogenic mood effects similar to methylenedioxymethamphetamine and alters sensorimotor gating in a human model of psychosis, supporting its potential use in psychotherapy and translational psychiatric research.

Study at a glance

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.