Harm potential of magic mushroom use: A review

The review used the EMCDDA thematic report "Hallucinogenic mushrooms: an emerging trend case study" as a primary basis and incorporated two additional Dutch-language reviews. The authors updated the material by conducting Medline searches covering 2000–2010 using terms such as "magic mushrooms", "hallucinogenic mushrooms", "LSD", "psilocybin", "psilocin", "suicide", and "alcohol". The review is restricted to fungi that contain psilocybin and/or psilocin except where explicitly stated otherwise. The extracted text does not clearly report formal inclusion or exclusion criteria, whether study selection followed a systematic protocol, or whether a formal risk-of-bias or quality assessment of included studies was performed. The report therefore appears to be a narrative review synthesising published literature, surveillance data and case reports together with grey literature and public-health records rather than a systematic review with pre-specified methodological safeguards.

Products and potency: The review describes commonly sold species (notably Psilocybe cubensis varieties and Psilocybe semilanceata, the so-called liberty caps) and emphasises large variability in psilocybin and psilocin content by species, origin, growing conditions and age. Typical psilocybin content cited is about 10 mg per gram of dried mushroom (1% w/w) for P. cubensis and P. semilanceata. The dose of psilocybin reported to induce hallucinogenic effects averages 4–10 mg (about 50–300 µg/kg body weight), implying roughly 1 g of dried mushrooms or 10 g fresh as a minimum recreational dose; reported recreational dosing ranges up to 3.5–5 g dried. Other compounds present (for example phenylethylamines, baeocystin) may contribute to cardiovascular and other effects and concentrations vary markedly. Availability and prevalence: While legal in the Netherlands until December 2008, magic mushrooms were sold primarily via smart shops, souvenir shops and increasingly online, with 120–150 smart shops reported in 2006. After legislative changes in 2008, possession and use became illegal and reported prevalence declined. European school surveys (ESPAD) suggested 4–8% of 15–16 year olds in some countries could obtain mushrooms easily, though access estimates vary widely by country. Lifetime use among young people in EU member states varied from <1% to 8%; in the Netherlands lifetime use among 15/16 year olds was around 5% in earlier surveys, decreasing over time to lower figures and a last-month prevalence of 0.1% in 2009 after prohibition. Subjective and psychological adverse effects: Trips typically last 2–6 hours, with mild after-effects up to about 12 hours. Reported subjective experiences range from relaxation and euphoria to sensory enhancement and, in some cases, unintended delusions, altered perception and hallucinations. Surveys reported substantial rates of anxiety (about 32%) and paranoia (about 35%) in one UK sample. "Bad trips" produce severe anxiety, agitation, disorientation and occasionally acute psychotic-like episodes that can lead to accidents, self-injury or suicide attempts; persistence of unpleasant symptoms for days to months was described. The review notes that combining mushrooms with other substances, including alcohol, may increase the risk of bad trips. Set and setting: The investigators emphasise that both individual factors ("set") and the social-environmental context ("setting") strongly influence outcomes. Clinical research from the 1950s–1960s often neglected these factors; later, better preparation and interpersonal support correlated with fewer adverse reactions. Even in controlled settings, substantial proportions of volunteers experienced significant anxiety or transient paranoia at higher doses: one cited study reported 22% experienced notable anxiety and, at a dose up to 30 mg/70 kg, 31% experienced significant fear and 17% transient paranoia. A meta-analysis of 110 healthy subjects given 45–315 µg/kg under controlled conditions reported no serious psychological adverse effects. Acute physical effects: Typical physiological effects described are dizziness, nausea, muscle weakness, mydriasis and gastrointestinal symptoms. Cardiovascular changes are generally mild; at 0.2 mg/kg psilocybin p.o. heart rate increased by ~10 bpm and systolic/diastolic blood pressure by about +25/+10 mm Hg. Body temperature usually remains normal. Severe physical complaints reported in some cases (severe abdominal pain, persistent vomiting) are attributed to consuming mushrooms rather than to psilocybin per se. Elevated blood pressure could pose risk for users with existing cardiovascular disease. Fatal and severe incidents: Fatalities directly attributable to magic mushroom overdose are rare. The paper states only two fatalities in the literature resulted from overdosing without concurrent drugs. Most reported fatal incidents involved concomitant substances, notably alcohol, or were inferred from press reports and lacked confirmatory toxicology in some cases. The authors list multiple case examples from the grey literature and coroner reports where death followed falls, hypothermia or other traumatic causes, often with alcohol and/or other drugs detected. The review cautions that official statistics may undercount mushroom-related deaths when mushroom use is contributory rather than the primary cause. Drug interactions: Psilocin and psilocybin are metabolised by monoamine oxidase (MAO); MAO inhibitors therefore can potentiate effects. The authors discuss how ethanol metabolism may produce endogenous MAO inhibitors and thus potentially enhance psilocybin effects. Tobacco smoking is associated with lower MAO activity and could modulate effects; chocolate contains MAO inhibitors but at clinically negligible levels. Flashbacks and HPPD: Flashbacks, defined as spontaneous recurrences of perceptual alterations after drug use, are reported but uncommon. Hallucinogen Persisting Perception Disorder (HPPD) is acknowledged as an existing but infrequent condition, more often reported after LSD than after psilocybin. One web-based survey noted 38 of 174 respondents reporting HPPD symptoms, with 22% attributing them primarily to psilocybin and 55% to LSD, although many reports involved poly-drug users or psychiatric patients. Psychosis and psychiatric vulnerability: Acute psilocybin effects can mimic certain aspects of schizophrenia, and the review notes concerns that hallucinogens may precipitate or exacerbate enduring psychosis in vulnerable individuals. The authors recommend that people with psychiatric illness or a family history of psychiatric disease abstain from use; in schizophrenic patients psilocybin may provoke acute psychotic states requiring hospital care. Dependence potential: No evidence was found that magic mushrooms produce physical or psychological dependence. Rapid short-term tolerance to psychedelic effects is common, but withdrawal syndromes and sustained psychological dependency appear to be very rare compared with other illegal drugs. Information, emergencies and public-health burden: Retailers often supplied English-language warnings targeted at tourists and at-risk groups (under-18s, pregnant women, those on medication or with mental illness), advising against combination with alcohol and recommending small initial doses. The quality and completeness of consumer information varied, and many sources emphasised positive effects. Calls to poison centres and emergency services for psilocybin intoxication are generally low across countries cited: Swedish data recorded 25 cases over 1980–1995 with more recent increases to ~30–40 calls annually; the Dutch National Poisoning Information Center reported about 60 information requests per year and the Amsterdam Municipal Health Service recorded 2,837 ambulance calls related to recreational drugs in 2005 of which 70 (2.5%) were mushroom-related, 92% involving tourists. Intensive care was required in about 1.5% of mushroom-related ambulance cases compared with 11–20% for cocaine, heroin or ecstasy. Following the December 2008 prohibition in the Netherlands, reports and information requests declined. Public order and criminality: Forensic and police data indicated limited public-order impact and negligible organised crime involvement. Annual police "lock-ins" related to mushroom intoxication in Amsterdam were reported as 30–36, mostly for public nuisance or traffic violations, substantially fewer than for alcohol. Customs and police occasionally confiscated shipments, but large-scale criminal networks were not identified.

The authors conclude that magic mushrooms rarely produce physical or psychological dependence, that acute and chronic adverse effects are relatively infrequent and generally mild, and that public-health, public-order and criminal impacts are limited. Nonetheless, they flag infrequent but potentially severe outcomes, notably flashbacks and accidents resulting from panic reactions or severe intoxication, particularly when mushrooms are taken in combination with alcohol or other drugs or in unsupervised settings. The review stresses that many adverse incidents involve tourists and that prevention is possible through appropriate user surveillance and information; one proposed harm-reduction option is restricting psilocybin use to supervised premises. Based largely on the CAM expert report, magic mushrooms were rated among the least harmful illicit drugs, yet the Dutch Minister of Health moved to prohibit possession, use, production and trafficking in December 2008 and reclassified magic mushrooms to List II despite the CAM panel's advice.