Healthy VolunteersSchizophreniaPersonality & Trait FactorsLSD

Acute effects of lysergic acid diethylamide in healthy subjects

This double-blind, placebo-controlled study (n=16) described the effects of LSD (200 μg) in healthy subjects. It inhibited prepulse inhibition (startle reflex), increased blood pressure, elicited a positive mood, and had no adverse effect after 72 hours.

Authors

  • Yasmin Schmid
  • Stefan Borgwardt
  • Matthias Liechti

Published

Biological Psychiatry
individual Study

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.

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Research Summary of 'Acute effects of lysergic acid diethylamide in healthy subjects'

Introduction

Classic serotonergic hallucinogens such as lysergic acid diethylamide (LSD) produce profound alterations of perception and cognition and were widely studied in mid-20th century psychiatry, but modern controlled pharmacological data on LSD in humans are lacking. In particular, contemporary studies have not systematically characterised LSD's subjective, autonomic, and endocrine effects, and the drug's influence on prepulse inhibition (PPI) of the acoustic startle response—a translational measure of sensorimotor gating relevant to schizophrenia—had not been examined in humans. Schmid and colleagues therefore set out to re-examine the acute effects of LSD in healthy volunteers. The study aimed to characterise subjective experiences with validated psychometric instruments, test the hypothesis that LSD impairs PPI, and document cardiovascular, autonomic, endocrine, and adverse effects using a modern, double-blind, placebo-controlled, crossover design.

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Study Details

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Acute effects of lysergic acid diethylamide in... — Research Summary & Context | Blossom