This case report highlights that LSD can be dangerous, leading to seizure and brain damage, but this should be read in the context of millions of dosages (of LSD) being taken each year.
A young man with an unremarkable medical history suffered a seizure with subsequent cardiorespiratory arrest and severe neurological sequelae after ingesting a blotter. Analysis of a similar blotter and a serum sample obtained 3 hours after the event detected lysergic acid diethylamide (LSD) at the amount of 300 μg in the blotter and at a concentration of 4.0 ng/mL (12.4 nmoles/L) in serum. No other drugs were present in concentrations which may confer significant effects. In addition, no individual traits which would make the patient particularly susceptible to adverse LSD effects have subsequently been identified. This suggests that LSD may confer toxic effects in previously healthy individuals.
LSD (lysergic acid diethylamide-25) has been used experimentally and recreationally since its psychoactive properties were discovered in 1943. While earlier research has treated LSD both as a model psychotomimetic and as a potential therapeutic agent, its safety in recreational settings remains debated. Some recent reviews argue that standard recreational doses (50–200 µg) are medically safe and non-toxic, but other reports and case series have associated presumed LSD use with adverse events including seizures. Aakerøy and colleagues present a single-case report of a previously healthy young man who experienced a tonic seizure with subsequent cardiorespiratory arrest and severe, persistent neurological injury after taking a blotter believed to contain LSD. The paper aims to document the clinical course, perform comprehensive toxicological analysis of the patient’s biological samples and an analysed blotter, and consider whether LSD exposure could plausibly account for the outcome in the absence of identifiable individual vulnerabilities or other toxicological contributors.
Papers cited by this study that are also in Blossom
Dolder, P. C., Schmid, Y., Steuer, A. E. et al. · Clinical Pharmacokinetics (2017)
Leonard, J. B., Klein-Schwartz, W. · Journal of Psychopharmacology (2018)
Serum and urine samples were obtained from the patient approximately 3 hours after the onset of symptoms; two blotters reportedly identical to those ingested were also analysed. Each blotter weighed about 23 mg. One blotter was cut, dissolved and prepared for analysis by liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and by quantitative ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS-MS). Initial LC-QTOF-MS screening of the blotter detected LSD and its primary metabolite 2-oxo-3-hydroxy-LSD (2-oxo-3-OH-LSD), together with trace amounts of N,N-dimethyltryptamine (DMT), methamphetamine, amphetamine and 3,4-methylenedioxymethamphetamine (MDMA). The laboratory developed and validated quantitative UPLC-MS-MS methods for LSD, 2-oxo-3-OH-LSD and DMT in serum, urine and blotter extract; accredited routine UPLC-MS-MS methods were used for amphetamine, methamphetamine and MDMA quantification. Sample preparation involved protein precipitation with acetonitrile and injection of supernatant onto a Waters Acquity UPLC BEH C18 column with short gradient runs (total run times 2.2–3.5 minutes depending on analyte). For DMT the calibration curve was linear from 1 to 1000 ng/mL (R2 > 0.999) and the limit of quantification/limit of detection was 1 ng/mL. LC-QTOF-MS also indicated the presence of lidocaine, metoprolol, fentanyl, norfentanyl and rocuronium in serum; these compounds were interpreted as relating to medical treatment after the event and were not further quantified.
Clinically, the patient was a late-teen male with no prior medical history of seizures, cardiac arrhythmia or illicit drug use. While at a gathering he and several friends each consumed a blotter thought to contain LSD. After an initial period of typical LSD effects, he suddenly developed a tonic spastic seizure accompanied by shallow respirations, oral frothing, retching, vomiting and aspiration leading to cyanosis. Emergency services arrived about 25 minutes after symptom onset and found him in cardiorespiratory arrest; he was intubated and received cardiopulmonary resuscitation. On arrival to hospital he exhibited supraventricular tachycardia and lactic acidosis consistent with severe cerebral hypoxia. Magnetic resonance imaging and electroencephalography later confirmed severe cerebral injury. Cardiac monitoring rapidly normalised and no long QT or other persistent cardiac abnormality was detected. None of the other individuals who ingested ostensibly identical blotters reported adverse effects. At nearly one year follow-up the patient remained in rehabilitation with severe neurological sequelae. Toxicologically, analysis of an analysed blotter confirmed the presence of LSD and the metabolite 2-oxo-3-OH-LSD, together with much smaller amounts of DMT, methamphetamine, amphetamine and MDMA. Biological samples (serum and urine obtained 3 hours after onset) did not show significant amounts of these co-detected moieties, with only trace amphetamine reported in urine; LC-QTOF findings of lidocaine, metoprolol, fentanyl, norfentanyl and rocuronium in serum were ascribed to emergency medical treatment. The extracted text does not clearly report the exact measured LSD concentration in the patient’s serum sample, but the authors state that the plasma concentration measured 3 hours after loss of consciousness was compatible with an assumed dose of 300 µg and with published pharmacokinetic data for higher LSD doses.
Aakerøy and colleagues interpret the findings as most consistent with an LSD-induced seizure that led to aspiration, asphyxia and secondary hypoxic brain injury. They argue that the minor amounts of DMT, amphetamines and MDMA detected on the blotter were several orders of magnitude below recreationally active doses and were not detected in biological samples (except for trace amphetamine), so these contaminants are unlikely to have contributed materially to the event; the authors suggest such residues probably reflect contamination during illicit production rather than co-intentional ingestion. In placing the case in pharmacokinetic context, the authors cite prior controlled dosing studies in which oral LSD doses of 100 and 200 µg produced peak plasma concentrations of about 1.3 and 3.1 ng/mL, respectively, with a plasma half-life around 2.6 hours. They note that direct human plasma measurements after 300 µg are lacking, but state that the patient’s measured plasma concentration at 3 hours was not incompatible with an approximate 300 µg exposure. The discussion also situates this event within broader surveillance data: multicentre emergency-department series and a US hospital review have associated presumed LSD exposures with seizures in roughly 4% of cases, and a few prior case reports document LSD-related seizures without persistent neurological sequelae. The authors acknowledge that they have not identified any individual predisposing factors in the patient’s history or family history that would explain such an outcome. On this basis they conclude that the assumption that LSD is uniformly “non-toxic and medically safe” at typical recreational doses may be incorrect, because severe, idiosyncratic toxic effects can occur in previously healthy individuals. The extracted text does not present additional caveats or detailed mechanistic explanations beyond these points.