Does getting high hurt? Characterization of cases of LSD and psilocybin-containing mushroom exposures to national poison centers between 2000 and 2016

Earlier research and recent small clinical studies have examined LSD and psilocybin for psychiatric indications, but safety and toxicity data from large, real-world populations remain limited. Controlled trials and systematic reviews of therapeutic administration report few serious medical adverse events, yet case reports and small series describe deaths and severe outcomes that typically involve trauma, restraint, or co-ingested substances. Recreational use continues to be common, doses vary widely in the illicit market, and prior literature does not adequately characterise the frequency or severity of acute toxicities outside controlled settings. Leonard and colleagues set out to describe the acute toxicity profile, management sites, and medical outcomes associated with single-substance exposures to LSD and psilocybin-containing mushrooms reported to the US National Poison Data System (NPDS) between 2000 and 2016. The study aims to fill a gap in population-level safety data that could inform clinicians, public health surveillance and policy if therapeutic or broader recreational use increases.

This was a retrospective database study of NPDS reports from 1 January 2000 to 31 December 2016. Exposures were identified by product codes (Poisindex) for LSD and for Group 6 mushrooms (psilocybin and psilocin). The investigators included only single-substance exposures with a known medical outcome and excluded cases with multiple substances or unknown outcomes, because coded data do not reliably attribute effects to a single agent. Extracted variables included age, sex, route and chronicity of exposure, coded clinical effects deemed related to the exposure, final management site (composite of management and level of care), reason for exposure (intentional abuse, unintentional, etc.), treatments given, and coded medical outcome. NPDS uses predefined outcome categories: no effect, minor, moderate, major, and death; moderate effects generally require treatment but are not life-threatening, while major effects are life-threatening or cause significant disability. Duration of exposure (acute, acute on chronic, chronic) was defined using NPDS time thresholds (acute ≤ 8 h). Descriptive statistics were reported, with medians and interquartile ranges for non-normal data. Confidence intervals for proportions were calculated using the Clopper–Pearson method. The study excluded records with unknown or estimated ages from age-group analyses and records with unknown gender from gender-based analyses. The investigators reviewed fatality abstracts for deaths. The Institutional Review Board judged the work to be not human subjects research.

The NPDS search initially identified 19,442 cases. After excluding 5,767 multiple-substance reports there were 8,649 psilocybin-containing mushroom and 5,026 LSD exposures; of these, 5,883 mushroom and 3,554 LSD single-substance cases had known outcomes and were included in the analysis. Users were predominantly adolescents and young adults: 61.5% of LSD and 53.5% of psilocybin-containing mushroom cases were aged 13–19 years, and an additional 27.4% (LSD) and 30.3% (mushrooms) were aged 20–29 years. Median age was 18 years (IQR 16–21) for LSD and 19 years (IQR 17–19) for psilocybin-containing mushrooms. Males comprised the majority of cases (74.1% LSD, 77.9% mushrooms). Intentional abuse was the commonest reason for exposure (78.5% LSD, 75.9% mushrooms); unintentional exposures accounted for smaller proportions (7.5% LSD, 12.4% mushrooms). Most exposures were acute (≤ 8 h): 89.1% for LSD and 95.3% for mushrooms. Asymptomatic presentations were uncommon (6.8% LSD, 9.5% mushrooms). The majority of symptomatic patients had two or fewer related adverse effects (60.3% LSD, 67.6% mushrooms). The most frequently recorded clinical effects were hallucinations, agitation, tachycardia, mydriasis, confusion and vomiting. Effect durations were short for most patients: < 24 h in 77.9% of LSD and 84.4% of mushroom cases. Treatments given were typically limited: benzodiazepines were administered in 34.7% of LSD cases and 17.0% of mushroom cases; other sedating agents in 8.2% (LSD) and 2.3% (mushrooms); intravenous fluids in 36.0% (LSD) and 22.4% (mushrooms). Single‑dose activated charcoal was given in 3.4% of LSD and 12.8% of mushroom cases. Disposition and severity differed by agent. Most psilocybin-containing mushroom patients were managed at home or treated and released from an emergency department, whereas a larger share of LSD patients were evaluated in emergency departments and admitted for medical care. Moderate effects were the most frequent medical outcome (61.0% mushrooms, 62.3% LSD). Hospital admission occurred in approximately 13.3% of mushroom users and 26.5% of LSD users, and critical care admission rates were higher for LSD (reported as 16.9% LSD vs 6.2% mushrooms in the text). Major effects were uncommon but more frequent in LSD cases (6.2% vs 2.1%). There were eight deaths in total: three among mushroom cases and five among LSD cases. Review of fatality abstracts suggested multiple contributing factors in all deaths. For the mushroom fatalities two were judged to have unknown contribution from psilocybin and one contributory death had objective detection of psilocin (>200 ng/mL, urine) but also involved trauma and asystolic arrest after restraint. LSD fatalities included cases with severe hyperthermia, status epilepticus, trauma with prolonged restraint, meningitis, and one with insufficient data. Objective toxicological confirmation was generally lacking for fatalities.

Leonard and colleagues interpret the NPDS data as indicating that recreational use of LSD and psilocybin-containing mushrooms reported to poison centres occurs predominantly in male adolescents and young adults and most commonly produces mild to moderate adverse effects that are short lived. The authors note that the common clinical features in this large, uncontrolled population—hallucinations, agitation, tachycardia, nausea and transient hypertension—are broadly consistent with effects reported in therapeutic trials, while also providing better estimates of incidence when these substances are used in the community. The investigators highlight differences between agents: LSD exposures were more likely than mushroom exposures to result in hospital admission, critical care admission and major effects. Serious events such as hyperthermia, seizures, rhabdomyolysis and cardiac arrest were rare but did occur, often in cases with additional complicating factors such as trauma or restraint. The authors caution that most poison centre calls represent symptomatic patients and that benign or enjoyable exposures are unlikely to be reported, which biases the dataset toward adverse outcomes. Key limitations are emphasised. The study is retrospective and depends on caller‑reported information; laboratory confirmation of the substance was usually absent; NPDS coding restricts which clinical effects and therapies are captured and some important psychiatric codes (for example anxiety, panic or psychosis) are not available and may be subsumed under "other" or "agitation". Time from exposure to call was not available, precluding assessment of delayed phenomena such as hallucinogen‑persisting perception disorder. The database does not code serotonin toxicity and dose information was unreliable or unavailable, so dose–response relationships were not assessed. Underreporting of cases, particularly those with benign courses, is also likely. Finally, the authors place the findings in a public health context: poison centre surveillance yields valuable, population‑level indicators of trends and uncommon toxicities that may not appear in small clinical trials, and the data suggest that most community exposures require only emergency management but that LSD carries a higher probability of requiring hospital care.

Leonard and colleagues conclude that when used in the community most single‑substance psilocybin‑containing mushroom and LSD exposures produce one to four related adverse effects of short duration. Common effects mirror those seen in therapeutic studies. Hospital admission occurred in about 13.3% of mushroom cases and 26.5% of LSD cases, and benzodiazepines or other sedatives were the usual treatments for symptomatic patients. Serious adverse events were uncommon but present; overall, community use as captured by poison centre reports generally did not result in life‑threatening effects.