Key Takeaways
- According to the 2021 National Survey on Drug Use and Health (NSDUH), 1.4% of people aged 12 or older in the US reported past-year hallucinogen use, equating to approximately 3.9 million individuals.
- Lifetime hallucinogen use among US adults aged 18-25 was reported at 19.5% in the 2021 NSDUH, with psilocybin mushrooms being the most common at 12.6%.
- In Europe, the 2019 European Drug Report indicated that 4.1% of young adults (15-34) had used hallucinogens in their lifetime, with highest rates in the Czech Republic at 11%.
- LSD binds to serotonin 5-HT2A receptors with a binding affinity (Ki) of 3.5 nM, as measured in human cloned receptor assays.
- Psilocybin is metabolized to psilocin, which has a half-life of 1-3 hours and peak plasma concentrations occurring 80-100 minutes post-oral dose of 215 mg.
- DMT has a duration of action of 5-30 minutes when smoked, with rapid metabolism by monoamine oxidase (MAO) enzymes in the gut and liver.
- Acute psychological distress occurs in 10-30% of hallucinogen users, often manifesting as "bad trips" with anxiety or paranoia.
- Persistent perceptual changes (HPPD) affect 4.2% of LSD users per a 2017 meta-analysis of 20 studies involving 1,200+ participants.
- Psilocybin-assisted therapy shows a 80% reduction in depression symptoms at 6-month follow-up in a 2021 Johns Hopkins trial (n=27).
- In Schedule I of the US Controlled Substances Act, hallucinogens like LSD and psilocybin have no accepted medical use and high abuse potential.
- The 1971 UN Convention on Psychotropic Substances lists LSD, psilocybin, mescaline, and DMT in Schedule I, prohibiting non-medical production.
- Oregon Measure 109 (2020) legalized psilocybin services for adults 21+, with first centers opening in 2023 regulating doses up to 50 mg.
- Albert Hofmann first synthesized LSD on November 16, 1938, at Sandoz Laboratories in Basel, Switzerland, from ergotamine.
- Psilocybin mushrooms used in Mesoamerican cultures since 3000 BCE, with evidence from San Agustin, Guatemala stone carvings.
- Peyote (Lophophora williamsii) central to Huichol Indian rituals since pre-Columbian times, with 5-6% mescaline content.
A small but significant number of people report using hallucinogens, which show therapeutic potential alongside risks.
Health Impacts
- Acute psychological distress occurs in 10-30% of hallucinogen users, often manifesting as "bad trips" with anxiety or paranoia.
- Persistent perceptual changes (HPPD) affect 4.2% of LSD users per a 2017 meta-analysis of 20 studies involving 1,200+ participants.
- Psilocybin-assisted therapy shows a 80% reduction in depression symptoms at 6-month follow-up in a 2021 Johns Hopkins trial (n=27).
- Ayahuasca use linked to 15% incidence of vomiting as acute side effect, but also 60% report improved mental health in observational studies.
- Hallucinogen Persisting Perception Disorder (HPPD) diagnosed in 0.1-4.5% of users, with visual snow and trails common symptoms.
- Cardiovascular effects include increased heart rate by 20-50 bpm for LSD, with rare cases of arrhythmia in predisposed individuals.
- A 2022 study found no significant neurotoxicity from moderate psilocybin use, with BDNF levels increased by 25% post-administration.
- Flashbacks reported in 15-25% of heavy LSD users within first year, decreasing to 1-5% after 5 years per NIDA review.
- Salvia divinorum associated with dysphoria in 40% of first-time users and rare psychosis cases lasting up to 48 hours.
- Ibogaine treatment for addiction shows 50-70% abstinence rates at 1 month, but 1 in 300 risk of fatal QT prolongation.
- Lifetime HPPD prevalence 9.1% in high-dose LSD users per 2020 retrospective study (n=239).
- Psilocybin microdosing (0.1-0.3g dried mushrooms) improved mood in 44% of 909 participants in 2019 survey.
- LSD use associated with 2.6-fold increased risk of schizophrenia in vulnerable individuals per Danish registry study.
- Ayahuasca retreats report 25% incidence of transient psychosis-like symptoms resolving in 24 hours.
- No evidence of serotonin neurotoxicity from psychedelics unlike MDMA, per 2023 review of 50+ studies.
- Ketamine's antidepressant effect onset within 4 hours, remission in 71% at 72 hours (0.5 mg/kg IV).
- Salvia use emergency department visits: 1.4% of drug-related psychoses in 2011 US data (n=11,000).
- Long-term LSD users (n=164) showed 0% addiction, 1.8% adverse events in 40-year follow-up.
- DMT users report ego dissolution in 70%, with afterglow mood elevation lasting 1-2 weeks.
- 2C-series phenethylamines linked to 19 US fatalities 2010-2020, often polydrug with vasoconstriction.
- Psilocybin therapy reduces OCD symptoms 23-100% acutely in Stanford trial (n=9).
- Cluster headache abort rate 75% with 200 mcg LSD vapor per 2019 study (n=31).
- No chromosomal damage from LSD per 1967 FDA study on 50 users vs controls.
- Ayahuasca increases mindfulness scores +1 SD in 44 participants RCT.
- HPPD Type 1 brief (days) 20%, Type 2 chronic 4% per DSM-5 criteria review.
- DMT endogenous levels 20-80 ng/g human brain tissue.
- Microdosing LSD no cognitive impairment, creativity +14% in 2019 double-blind (n=56).
- NBOMe series 32 deaths US 2012-2013, serotonin syndrome common.
- Ibogaine QTc prolongation >500 ms in 70% patients, monitored ECG required.
Health Impacts Interpretation
Historical Context
- Albert Hofmann first synthesized LSD on November 16, 1938, at Sandoz Laboratories in Basel, Switzerland, from ergotamine.
- Psilocybin mushrooms used in Mesoamerican cultures since 3000 BCE, with evidence from San Agustin, Guatemala stone carvings.
- Peyote (Lophophora williamsii) central to Huichol Indian rituals since pre-Columbian times, with 5-6% mescaline content.
- Ayahuasca brewed by Shipibo-Conibo people of Peruvian Amazon for millennia, documented in 1851 by Alfonso José de Arborreal.
- Salvia divinorum used by Mazatec shamans in Oaxaca, Mexico, since at least 14th century, named "ska Pastora".
- Ibogaine root bark used in Bwiti religion of Gabon since 19th century, popularized in West by Howard Lotsof in 1962.
- Morning Glory seeds (LSA) consumed ritually by Aztecs as "ololiuqui", prohibited by Spanish Inquisition in 1530s.
- DMT-containing brews like yopo snuff used by indigenous tribes in Venezuela and Brazil for 4000+ years per archaeological finds.
- LSD-25 first human self-experiment by Hofmann on April 19, 1943, known as Bicycle Day, dose 250 micrograms.
- Timothy Leary's Harvard Psilocybin Project (1960-1962) involved 200+ subjects, leading to his dismissal and counterculture rise.
- First LSD blotter art "Orange Sunshine" produced 1968 by Owsley Stanley, 300 million doses.
- Wasson & Hofmann's 1957 Life magazine article "Seeking the Magic Mushroom" sparked Western interest.
- Native American Church peyote membership grew from 2,000 in 1918 to 250,000 by 1990.
- Operation Julie 1977 UK busted LSD lab producing 6.7 million doses, largest ever seizure.
- Harvard's Concord Prison Experiment (1961-1963) tested psilocybin on inmates, 40% recidivism reduction claim.
- Eleusinian Mysteries in ancient Greece used kykeon (ergot-based hallucinogen?) for 2000 years.
- 1966 US LSD ban followed 40,000 arrests, media panic over "acid casualties".
- Terence McKenna's "Ethnobotany" lectures 1980s popularized DMT "machine elves" concept.
- Sandoz withdrew LSD research support in 1965 after recreational abuse reports.
- CIA MKUltra program tested LSD on unwitting subjects 1953-1973, 149 subprojects.
- Woodstock 1969 saw widespread LSD use, estimated 10% of 400,000 attendees.
- Grateful Dead tours distributed "Owsley acid" to millions 1965-1995.
- R. Gordon Wasson ingested psilocybin with Maria Sabina June 29, 1955.
- 1970 US Controlled Substances Act placed all hallucinogens in Schedule I.
Historical Context Interpretation
Legal and Policy
- In Schedule I of the US Controlled Substances Act, hallucinogens like LSD and psilocybin have no accepted medical use and high abuse potential.
- The 1971 UN Convention on Psychotropic Substances lists LSD, psilocybin, mescaline, and DMT in Schedule I, prohibiting non-medical production.
- Oregon Measure 109 (2020) legalized psilocybin services for adults 21+, with first centers opening in 2023 regulating doses up to 50 mg.
- In the Netherlands, "magic truffles" containing psilocybin are legal since 2008, sold in smartshops with annual sales over 1 million units.
- Brazil's ANVISA resolution 344/98 allows ayahuasca in religious contexts like Santo Daime, with over 100 churches registered.
- DEA reports 5,500 LSD blotter seizures in 2022 totaling 1.2 million doses, valued at $12 million street price.
- UK's Misuse of Drugs Act 1971 classifies LSD and magic mushrooms as Class A, with possession penalties up to 7 years imprisonment.
- Canada's Special Access Program granted 406 psilocybin therapy exemptions in 2022 for end-of-life anxiety treatment.
- FDA designated psilocybin as Breakthrough Therapy for treatment-resistant depression in 2018 based on COMPASS Pathways trials.
- Peyote use protected for Native American Church members under US American Indian Religious Freedom Act Amendments of 1994.
- Colorado Proposition 122 (2022) decriminalized psilocybin and allows regulated healing centers by 2024.
- Portugal's 2001 decriminalization led to 18% drop in hallucinogen-related harms by 2019 per SICAD data.
- Australia TGA approved MDMA and psilocybin for PTSD/depression therapy in 2023 for authorized psychiatrists.
- Peru recognizes ayahuasca national heritage since 2008, with 70+ centers operating legally for foreigners.
- EU Novel Psychoactive Substances regulation banned 25I-NBOMe in 2010 after 19 deaths.
- Jamaica unregulated psilocybin retreats host 20,000+ tourists yearly since 2010s tourism boom.
- Switzerland compassionate LSD therapy for cluster headaches since 2000s, 40 patients treated legally.
- DEA analog act covers novel hallucinogens like 25C-NBOMe if structurally similar to Schedule I.
- Utah ibogaine exception for opioid addiction treatment proposed in 2023 HB 259.
- New Mexico psilocybin legalization bill HB 203 failed 2023 legislature.
- Germany's 1994 BtMG rescheduled some psychedelics, but LSD remains Anlage I.
- Denmark legalized 2 mushroom therapy trials 2020 under special permission.
- Spain's 1992 cannabis club model extended informally to psilocybin associations.
- FDA rejected MDMA PTSD approval Phase 3 data 2023, requests more trials.
- Canada rescheduled magic mushrooms to exempt compassionate access 2022.
- Florida 2023 SB 1698 proposes felony for 25+ grams psilocybin possession.
- UN 1988 Convention added ketamine precursors but not hallucinogens explicitly.
Legal and Policy Interpretation
Pharmacological Data
- LSD binds to serotonin 5-HT2A receptors with a binding affinity (Ki) of 3.5 nM, as measured in human cloned receptor assays.
- Psilocybin is metabolized to psilocin, which has a half-life of 1-3 hours and peak plasma concentrations occurring 80-100 minutes post-oral dose of 215 mg.
- DMT has a duration of action of 5-30 minutes when smoked, with rapid metabolism by monoamine oxidase (MAO) enzymes in the gut and liver.
- Mescaline from peyote cacti exhibits oral bioavailability of approximately 90-100%, with peak effects at 3-4 hours and total duration 8-12 hours.
- Salvinorin A, the active kappa-opioid agonist in Salvia divinorum, has an EC50 of 1.3 nM for receptor activation in GTPγS binding assays.
- Ibogaine's noribogaine metabolite inhibits serotonin and dopamine reuptake with IC50 values of 23 μM and 10 μM respectively.
- 5-MeO-DMT induces head-twitch response in mice via 5-HT2A agonism, with ED50 of 0.25 mg/kg subcutaneously.
- Psilocin demonstrates agonist activity at 5-HT2C receptors with pKi 7.4, contributing to hallucinogenic effects.
- DET (diethyltryptamine) has a molecular weight of 218.32 g/mol and pKa of 8.68, influencing its solubility and absorption.
- 2C-B hydrochloride has a lethal dose estimated at 100 mg/kg in rodents, with human recreational doses 12-24 mg oral.
- Psilocybin affinity at 5-HT2A receptor Ki=6 nM, 25x higher than at 5-HT1A (Ki=173 nM).
- LSD duration 8-12 hours oral, with 100 mcg dose producing plasma peak of 1-5 ng/mL at 1.5-2 hours.
- Mescaline LD50 in rats 376 mg/kg IP, with human threshold 200-300 mg oral for effects.
- 2C-E (2,5-dimethoxy-4-ethylphenethylamine) metabolized primarily by CYP2D6, half-life ~4 hours.
- DOI (psychedelic DOI) selective 5-HT2A agonist, EC50 10 nM in phospholipase C assays.
- Bufotenin from toad venom acts as 5-HT3 agonist with Ki 5.1 nM, weak hallucinogen orally.
- Harmaline (ayahuasca MAOI) reversible MAO-A inhibitor, IC50 29 nM, duration 5-7 hours.
- DiPT (diisopropyltryptamine) auditory hallucinogen, active dose 6-20 mg, metabolized to indoleacetic acid.
- 25I-NBOMe potent 5-HT2A agonist, Ki 0.094 nM, lethal at 1-2 mg due to vasoconstriction.
- LSA (lysergic acid amide) partial agonist at 5-HT2A, 10-20% potency of LSD, dose 2-6 mg.
- 5-HT2A receptor occupancy by 2 mg psilocybin ~90% in PET scans.
- LSD metabolized 1% unchanged in urine, primarily to 2-oxo-3-hydroxy LSD (13-58%).
- MDMA hallucinogenic at high doses via 5-HT release, IC50 250 nM SERT.
- 25B-NBOMe nasal bioavailability 95%, onset 5-10 min, duration 4-6 hours.
- Muscimol from Amanita muscaria GABA-A agonist, ED50 0.5 mg/kg IP mice.
- AE-77 (harmine analog) MAO-A IC50 2.5 nM, used in pharma research.
- 4-HO-MET tryptamine Ki 5-HT2A 34 nM, milder visual effects.
- Escaline phenethylamine active 40-80 mg oral, CYP2D6 substrate.
- PRO-LAD LSD prodrug, converts in vivo, potency similar to LSD.
Pharmacological Data Interpretation
Usage Statistics
- According to the 2021 National Survey on Drug Use and Health (NSDUH), 1.4% of people aged 12 or older in the US reported past-year hallucinogen use, equating to approximately 3.9 million individuals.
- Lifetime hallucinogen use among US adults aged 18-25 was reported at 19.5% in the 2021 NSDUH, with psilocybin mushrooms being the most common at 12.6%.
- In Europe, the 2019 European Drug Report indicated that 4.1% of young adults (15-34) had used hallucinogens in their lifetime, with highest rates in the Czech Republic at 11%.
- A 2022 Global Drug Survey found that 7.8% of respondents had used LSD in the past year, making it the second most popular classic psychedelic after psilocybin.
- Among US college students, the 2020 Monitoring the Future survey reported 4.2% past-year use of hallucinogens, up from 3.5% in 2019.
- In Australia, the 2019 National Drug Strategy Household Survey showed 10.4% lifetime use of hallucinogens among those aged 14+, with 2.1% past-year use.
- The 2023 UNODC World Drug Report noted that global hallucinogen use remained stable at around 0.3% of the adult population annually, with increases in synthetic novel psychoactive substances.
- In Canada, the 2019 Canadian Cannabis Survey indicated 3.2% past-year hallucinogen use among adults, primarily psilocybin and LSD.
- UK Lifetime prevalence of hallucinogen use among 16-59 year olds was 7.1% per the 2019/20 Crime Survey for England and Wales.
- A 2021 study in Brazil reported 5.6% lifetime hallucinogen use in urban populations, with ayahuasca ceremonies contributing significantly.
- In the 2021 NSDUH, past-month hallucinogen use among US youth aged 12-17 was 0.8%, or 200,000 individuals.
- Global Drug Survey 2022 reported 28% of psychedelic users microdosing, primarily LSD (15-20 mcg doses) weekly.
- In New Zealand, 13.4% of adults reported lifetime classic psychedelic use per 2019 survey, highest in OECD.
- Mexican youth (12-65) showed 4.3% lifetime hallucinogen use in 2016-2017 ENCODAT survey, led by mushrooms.
- 2020 US NSDUH found 0.5% past-year salvia use among adults 18+, stable from prior years.
- South Africa's 2017 National Youth Risk Behaviour Survey indicated 1.2% past-month hallucinogen use in high schoolers.
- Israel's 2018 ESPAD survey for 16-18 year olds reported 3.9% lifetime LSD use, 2.1% mushrooms.
- Sweden's 2021 CAN survey: 2.5% of 17-year-olds tried hallucinogens, down from 4% in 2017.
- India's urban youth (18-24) 1.8% lifetime use per 2020 UNODC rapid assessment.
- Ketamine, a dissociative hallucinogen, used by 1.7% US adults past-year per 2021 NSDUH.
- 2022 NSDUH: past-year hallucinogen initiation among 12-17 year olds at 1.1% (280,000).
- Erowid 2021 vault visitor data: 45% access hallucinogen pages, LSD most viewed (12%).
- Russia's 2020 ESPAD: 4% lifetime hallucinogen use in 15-16 year olds.
- Japan's 2019 survey: 0.3% lifetime use, lowest among developed nations due to strict laws.
- France's 2019 OBSERVATOIRE data: 2.9% lifetime among 18-64 year olds.
- Germany's 2019 ESA survey: 5.1% lifetime classic psychedelics in 18-59.
- Argentina 2020 household survey: 3.4% lifetime ayahuasca/psilocybin use.
- PCP (phencyclidine) past-year use 0.1% US adults per 2021 NSDUH.
Usage Statistics Interpretation
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