This study (2018) re-examined five cases of fatality described by media as related to “LSD toxicity,” and found that none of those cases were actually attributable to physiological LSD toxicity.

Abstract

“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 μg). 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.”

Authors: David E. Nichols & Charles S. Grob

Summary

1. Introduction

LSD is a semi-synthetic natural product derived in nature from the rye fungus, Claviceps purpurea. Clinical studies were conducted in the United States and the United Kingdom from the early 1950s through the 1960s, with very low rates of adverse effects.

Although LSD is now classified as a Schedule 1 drug, informal use by the public has continued over the past 50+ years. Experts now generally recognize that LSD is an extremely physiologically safe substance, when moderate dosages are used in controlled settings.

Although fatalities have occurred after LSD use, both cases indicate that the users had ingested massive doses of LSD.

2. Deaths associated with LSD

Gable estimated that 14 mg of LSD is the lethal oral dose in man. Later he revised his estimate to 100 mg, and cited Griggs and Ward’s estimate that 320 mg intravenously is the lethal oral dose in humans.

In two cases, a 25-year-old male died from poisoning by LSD, but the exact dose was not reported. Even heroic doses of LSD can be ingested without fatality when supportive hospital care is readily available. Eight patients who nasally insufflated pure LSD tartrate powder, believing it to be cocaine, were admitted to the emergency room with severe visual and auditory hallucinations. All eight patients fully recovered within 2 – 3 days.

A 14-year old boy who had a bad LSD trip and was restrained with hog-tying type restraint died after seven days in a coma. Tests of admitting blood samples from the hospital were positive only for LSD.

In a case described by Reay et al. , a 28-year-old healthy male was house sitting and drinking beer with his brother when they noticed someone had tampered with their van. When faced with the option of going into the house or being arrested, the victim ran. The victim was restrained in the back of a patrol car and became wedged between the front and back seats. Three min later, his breathing became gurgly and the officer called for paramedics. The victim was unresponsive when removed from the patrol car and was pronounced dead. Toxicologic tests found a blood alcohol level of 0.12 g/100 mL and several drug levels.

A 30-year-old male with a history of asthma and no significant past medical history ingested a small quantity of LSD, became frightened and claustrophobic, ran a quarter mile through a commercial area, and was physically restrained by multiple officers.

EMS arrived and placed the patient prone on a stretcher, with five sets of straps across his body, including his head. He visibly struggled against the restraints and was taken to the hospital.

A toxicology report indicated that the decedent had ingested 100 mg of LSD, but a plasma concentration of 1 ng/mL is not toxic and would not indicate a large LSD overdose. A 20-year-old female died after taking LSD at a music festival. Her blood contained LSD at low levels, consistent with one recreational dose, and no other drugs were detected.

The cause of death was listed as multi organ failure, hyperthermia, and dehydration, with coagulopathy and possible LSD intoxication. There was no report of further blood analysis to determine what drug was actually responsible for the symptoms that preceded death.

According to Cina [32], cardiac dysrhythmias may be the cause of death in persons who suddenly collapse during vigorous restraint.

Upshall and Wailling administered 160 mg of LSD tartrate to 13 human subjects and examined the plasma concentration of LSD 60 and 130 min after administration of LSD, respectively.

A recent study of LSD pharmacokinetics reported that the t1/2 was 2.6 h, the Cmax was 1.3 and 3.1 ng/mL, and the tmax was 1.4 and 1.5 h, respectively, for 100 and 200 mg of free base.

In three cases, the decedents were placed in the position of prone maximal restraint (PMR; hogtied) and died of restraint asphyxiation in “excited delirium”. In the fourth case, the cause of death is questionable.

Some recent studies have attempted to show that prone maximal restraint (PMR) is not dangerous, but it is doubtful that the results can be taken too seriously because of the short time the subjects were restrained and the fact that they were not in an agitated or excited state.

Excited Delirium Syndrome (ExDS) is a subcategory of delirium that has been primarily described retrospectively in the forensic literature. It has been recognized to occur in association with illicit drugs of abuse other than cocaine, particularly methamphetamine and PCP.

ExDS is characterized by insensitivity to pain, tachypnea, sweating, agitation, profound hyperthermia, non-compliance with police, severe agitation and combative or assaultive behavior, lack of tiring, unusual strength, inappropriately clothed, and mirror or glass attraction.

Some LSD users can experience a bad trip, which presents as acute and severe anxiety, often accompanied by fear and agitation, with varying degrees of delusional or paranoid thinking. Some individuals experiencing the ExDS may suddenly die, whereas there are no cases reported of LSD bad trips leading to fatality.

Hall et al. [40] collected data from 4828 consecutive use of force events in seven Canadian police agencies in four cities, and found that 99.8% of subjects would be expected to survive being in either the prone or not prone position following a police use of force event.

In a state of excited delirium, individuals may be more susceptible to positional asphyxia, but the effects of prone positioning remain unclear. Most importantly, no individual in their cohort had ankle and/or leg restraints connected in a hogtied fashion.

Police often come into contact with the deceased during the phase of psychotic agitation, and must use five or six officers to force the victim to the ground and apply restraints.

3. Conclusions

LSD does not have the degree of physiological toxicity alleged by recent reports, and the true causes of these reported deaths are likely to be excessive physical restraints and/or psychoactive drugs other than LSD.