Biol Psychiatry. 2014 Nov 29. pii: S0006-3223(14)00909-3. doi: 10.1016/j.biopsych.2014.11.015. [Epub ahead of print]

Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects.

Schmid Y1, Enzler F1, Gasser P2, Grouzmann E3, Preller KH4, Vollenweider FX4, Brenneisen R5, Müller F6, Borgwardt S6, Liechti ME7.

• 1Psychopharmacology Research, Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel.
• 2Practice for Psychiatry and Psychotherapy, Solothurn.
• 3Biomedicine Service, University Hospital Lausanne, Lausanne.
• 4Neuropsychopharmacology and Brain Imaging and Heffter Research Center, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Zurich.
• 5Department of Clinical Research, University of Bern, Bern.
• 6Department of Psychiatry, University of Basel, Basel, Switzerland.
• 7Psychopharmacology Research, Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel.. Electronic address: matthias.liechti@usb.ch.

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.

Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

Adverse effects; Hormones; LSD; Prepulse inhibition; Subjective effects; Sympathomimetic effects

PMID:

25575620