Review Article Is LSD toxic? David E. Nichols a, *, Charles S. Grob b a Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA b Department of Psychiatry, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA 90509, USA A R T I C L E I N F O Article history: Received 27 November 2017 Received in revised form 3 January 2018 Accepted 6 January 2018 Available online xxx Keywords: LSD Toxicity Death Positional asphyxiation Maximal restraint Hog-tying A B S T R A C T LSD (lysergic acid diethylamide) was discovered almost 75 years ago, and has been the object of episodic controversy since then. While initially explored as an adjunctive psychiatric treatment, its recreational use by the general public has persisted and on occasion has been associated with adverse outcomes, particularly when the drug is taken under suboptimal conditions. LSD’s potential to cause psychological disturbance (bad trips) has been long understood, and has rarely been associated with accidental deaths and suicide. From a physiological perspective, however, LSD is known to be non-toxic and medically safe when taken at standard dosages (50–200 mg). The scientific literature, along with recent media reports, have unfortunately implicated “LSD toxicity” in five cases of sudden death. On close examination, however, two of these fatalities were associated with ingestion of massive overdoses, two were evidently in individuals with psychological agitation after taking standard doses of LSD who were then placed in maximal physical restraint positions (hogtied) by police, following which they suffered fatal cardiovascular collapse, and one case of extreme hyperthermia leading to death that was likely caused by a drug substituted for LSD with strong effects on central nervous system temperature regulation (e.g. 25i-NBOMe). Given the renewed interest in the therapeutic potential of LSD and other psychedelic drugs, it is important that an accurate understanding be established of the true causes of such fatalities that had been erroneously attributed to LSD toxicity, including massive overdoses, excessive physical restraints, and psychoactive drugs other than LSD. © 2018 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 2. Deaths associated with LSD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 3. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 Author statements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 1. Introduction Lysergic acid diethylamide (LSD) is a semi-synthetic natural product derived in nature from the rye fungus, Claviceps purpurea. It was first synthesized in 1938 by Swiss chemist Albert Hofmann, who was at that time exploring the putative medicinal effects of a series of ergot derivatives. Hofmann, five years later in 1943, accidentally discovered the unique psychological effects of the compound he identified as LSD-25, which he found was profoundly psychoactive at remarkably low microgram level doses. From the early 1950s, through the 1960s considerable clinical research activity with LSD raised hopes and enthusiasm that a valuable new treatment tool would be available to psychiatrists and other mental health professionals, particularly for use in cases that were refractory, or treatment resistant, to the standard mainstream approaches of that time. In all, about 1000 clinical case reports were published from the early 1950s through the 1960s, discussing * Corresponding author. E-mail addresses: drdave@purdue.edu, denichol@email.unc.edu (D.E. Nichols), cgrob@labiomed.org (C.S. Grob). https://doi.org/10.1016/j.forsciint.2018.01.006 0379-0738/© 2018 Elsevier B.V. All rights reserved. Forensic Science International 284 (2018) 141–145 Contents lists available at ScienceDirect Forensic Science International journal homepage: www.elsevier.com/locat e/f orsciint