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Psychedex
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SynthesizedOriginNovemberAlbert 16,Hofmann synthesized it in 1938 at [[article:sandoz|Sandoz]] Laboratories in Basel, as the twenty-fifth in a series of ergot-derived compounds{{cite|name=hofmann1979|type=book|author=hofmann|year=1979|title=LSD My Problem Child|anchor=715f5c78}}{{cite|doi=10.1124/pr.115.011478|anchor=c6de8802a103bc5}}
Effects discoveredTodayAccidentally absorbed during re-synthesis five years after synthesis; deliberately dosed three days later — the first intentional psychedelic self-experiment on record{{cite|doi=10.1124/pr.115.011478|anchor=b3bc504c}}{{cite|doi=10.1016/j.cub.2016.02.010|anchor=d43481d6}}
Clinical era1950–1965: estimated 40,000 patients received LSD-assisted psychotherapy; over 1,000 clinical papers published{{cite|doi=10.1124/pr.115.011478|anchor=e952389b}}
Supply withdrawnSandoz stopped supply in 1965–1966
ProhibitedUnited States classified it [[glossary:schedule-i|Schedule I]] in 1970
Research resumedFirst controlled modern study ran in 2015{{cite|doi=10.1016/j.biopsych.2014.11.015|anchor=561e4bb7}}; multiple Phase 2 trials now active for [[effect:depression|depression]], [[effect:anxiety|anxiety]], and [[glossary:substance-use-disorder|alcohol use disorder, and cluster headache
Named afterGerman Lysergsäure-diäthylamid, abbreviated LSD-25]]
* CIA's '''Project MKUltra''' used LSD in non-consensual experiments on civilians and military personnel * April 19 is informally commemorated as Bicycle Day, marking Hofmann's bicycle ride home during his first intentional experience * Blotter art — decorative printing on perforated paper squares — has developed into a recognized folk art form, with vintage sheets collected as cultural artifacts
Tolerance onsetWithdrawalNear-completeNo [[glossary:tolerancephysical-dependence|tolerancephysical dependence]] toand psychedelic effects develops within 3–4 days of consecutive use{{cite|doi=10.1124/pr.115.011478|anchor=5cb9cbe4}}
Mechanism[[glossary:serotonin|Serotonin]]no [[glossary:downregulationwithdrawal|downregulationwithdrawal]]{{cite|doi=10.1124/pr.115.011478|anchor=0daa1fcce815}}
Full reset10–14 days{{cite|doi=10.1124/pr.115.011478|anchor=f62f6ccb}}
Cross-toleranceComplete and bidirectional with all other classical serotonin-acting psychedelics — psilocybin, [[substance:mescaline|mescaline]], [[substance:dmt|DMT]], and [[substance_class:chemical/2c-x|2C-x]] compounds{{cite|doi=10.1124/pr.115.011478|anchor=29d52a6fa}}
Physical dependenceNone{{cite|doi=10.1124/pr.115.011478|anchor=6b05ab80}}
WithdrawalNone{{cite|doi=10.1124/pr.115.011478|anchor=d21d3d7b}}
Psychological dependenceNegligible — LSD does not activate reward circuitry in patterns associated with addictive drugs{{cite|doi=10.1124/pr.115.011478|anchor=1316a08b}}
Escalating usePatterns of frequentFrequent use can develop, particularlyespecially when used to avoid confrontingavoiding difficult emotions; professional support warranted if use is escalating in frequency, interfering with responsibilities, or continuing despite negative consequences
CharacterStimulatingAlert, outward-facing electricity — mind stays alert and engagedengagement with the world rather than drawninward inward; total alteration of perception, thought, and feelingabsorption
VersusRuns longer with more physical energy than [[substance:psilocybin-mushrooms|Psilocybinpsilocybin mushrooms]] — LSD runs longer and carries more physical energy{{cite|doi=10.1038/s41386-023-01607-2|anchor=3e537edece0dd9ca}}{{cite|doi=10.1038/s41386-022-01297-2|anchor=2f404a1f}}; psilocybin tends toward introspective, emotionally saturated states while LSD maintains clarity and outward curiosity
CommonColors sharpen, thinking accelerates, familiar boundaries between inside and outside begin to blur
Potential Safety-Critical Change
  • interactionSeverity keyword added: "dangerous behavior;"
Common formBlotter paper
Look-alike riskLSD blotter is visually identical to [[substance_class:chemical/25x-nbome|25x-NBOMe]]-dosed paper — far more toxic than LSD with a documented fatality record
TestEhrlich's reagent — LSD produces a purplePurple/violet reaction; NBOMe compounds produce none; negative result means not LSD; positive confirms an: [[substance_class:chemical/indole|indole]]-containing compound butconfirmed; doesno reaction means not confirm purity or absence of additional substances
Set and settingUnusually sensitive to psychological state and physical environment; pre-drug [[effect:anxiety|anxiety]] and negative expectations reliably push toward distress{{cite|doi=10.1038/s41398-024-03074-9|anchor=3e62881b}}; familiar, physically safe, comfortable space with no obligations is the baseline; trusted sober companion significantly reduces riskLSD
Plan for8 to 12 hours of effects; clear 12–16 hours with no driving, work, or social obligations; avoid unfamiliar social environments and crowds
Seek help ifAttemptingSeizures to harm self or others; complete disconnection from reality with dangerous behavior; [[glossary:seizure|seizures]] — (especially if taking [[substance:lithium|lithium]]); dangerous behavior; signs of [[glossary:serotonin-syndrome|serotonin syndrome]] if other serotonergic drugs are involved
Immediate stepsMove to quiet safe space; speak calmly; do not restrain unless immediate danger to life; call emergency services if symptoms suggest a medical emergency
AfterwardsPhysical fatigue, emotional sensitivity, and residual cognitive openness typical the day after; sleep may be disrupted; plan a quiet recovery day; journaling within 24–48 hours captures insights; if distressing thoughts or perceptual disturbances persist beyond two weeks, consult a mental health professional with psychedelic integration experience
Primary targetDistinctive[[glossary:serotonin|Serotonin]] receptors on cortical [[glossary:neuron|neurons]]{{cite|doi=10.1124/pr.115.011478|anchor=6d4137ac}}
EvidenceA drug that blocks serotonin receptors completely abolished psychedelic effects in controlled trials{{cite|doi=10.1038/s41386-020-00883-6|anchor=647707c2}}
Why it lastsA proteinProtein loop folds over the binding site and traps LSD inside afterthe bindingreceptor; effects outlast blood clearance{{cite|doi=10.1016/j.cell.2016.12.033|anchor=7eb6f802}}{{cite|doi=10.1016/j.cell.2020.08.024|anchor=1189dd74}}; receptor stays activated long after LSD has cleared the bloodstream, explaining effects lasting 8–12 hours despite a blood [[glossary:half-life|half-life]] of only about 3.5 hours
BioavailabilityAbout 80% reaches the bloodstream{{cite|doi=10.1002/cpt.3726|anchor=5cbff39d}}
Half-lifeApproximately 2.7–3.6 hours (terminal){{cite|doi=10.1007/s40262-017-0513-9|anchor=6e4de71c}}{{cite|doi=10.1002/cpt.2057|anchor=532641985}}{{cite|doi=10.1038/s41386-023-01607-2|anchor=1388ac1f}}
MetabolismLiver enzyme [[glossary:cyp2d6|CYP2D6]]; slow metabolizers experience roughly 75% higher drug exposure and more intense effects{{cite|doi=10.1038/s41598-021-90343-y|anchor=912d2586b}}
Structural class'''Ergoline''' — derived from ergot fungus (Claviceps purpurea)
FormulaC₂₀H₂₅N₃O
PotencyDistinctive100 to 1,000 times more potent by weight than simpler psychedelics like psilocybin or [[substance:dmt|DMT]]{{cite|doi=10.1111/bph.17361|anchor=028d4d8ba965bf}}
=== Toxicity ===
Lethal doseNot established in humans; estimated at roughly 1,000 times the standard active dose{{flag|safety-citation-needed}}
Confirmed deaths'''None''' from LSD's direct pharmacological effects{{cite|doi=10.1124/pr.115.011478|anchor=59faa2342a66a6}}; forensic cases typically involve other drugs, misidentified substances, or accidental falls
HeartModerate, temporary increases in blood pressure (~10–20 mmHg) and heart rate (~10–20 bpm) at clinical doses; no significant rhythm abnormalities documented{{cite|doi=10.1007/s00213-021-05978-6|anchor=a8a8100b}}{{cite|doi=10.1002/cpt.3618|anchor=70a4372a}}
Heart valvesPsychologicalMechanistically plausible — LSD is related to ergot drugs known to cause valve damage; no clinical cases reported; one echocardiographic study at 8 weeks of microdosing found no abnormalities{{cite|doi=10.1177/02698811231225609|anchor=b8789744}}
Controlled studiesNo serious adverse events across multiple controlled studies; side effects mild to moderate: [[effectglossary:nauseahppd|nauseaHPPD]], [[effect:headache|headache]], and [[effect:anxiety|anxiety]]{{cite|doi=10.1007/s00213-021-05978-6|anchor=90ba1e06}}{{cite|doi=10.1007/s00213-021-05978-6|anchor=f3453e35}}
=== Psychological risks ===
HPPDType I — brief, intermittent [[effect:flashbacks|flashbacks]], generally harmless and self-limiting; Type II —: chronic distressing perceptual changesdisturbances; thatcan persistoccur long-termafter a single exposure{{cite|doi=10.1007/7854_2016_457|anchor=fd742c91}}; LSD most commonly linked in clinical reports; can occur after single exposure{{cite|doi=10.3390/brainsci8030047|anchor=8c29949b}}{{cite|doi=10.1007/7854_2016_457|anchor=b07ec7e71d58}}; treatments with reported benefit include [[substance_class:chemical/benzodiazepine|benzodiazepines]], levetiracetam, and [[substance:clonidine|clonidine]]{{cite|doi=10.1097/hrp.0000000000000439|anchor=6bb9916e}}; '''Risperidone contraindicated — documented to worsen HPPD symptoms'''{{cite|doi=10.1097/hrp.0000000000000439|anchor=39957dbf}}
PsychosisSignificant risk for people with pre-existing psychotic disorders{{cite|doi=10.1038/s41380-024-02800-5|anchor=90c9a3eb}}; personal or family history of schizophrenia or bipolar disorder type I is an exclusion criterion across all modern clinical trials{{cite|doi=10.1016/j.biopsych.2014.11.015|anchor=2e93317f}}
=== Interactions ===
DangerousLithium — [[glossary:seizure|seizures]] reported within 30 minutes of ingestion; about half of documented combined cases resulted in seizures; absolutely contraindicated{{cite|pubmed=38986146|anchor=61443fef}}{{cite|url=https://pure.johnshopkins.edu/en/publications/classic-psychedelic-coadministration-with-lithium-but-not-lamotri/|title=Classic psychedelic coadministration with lithium, but not lamotrigine, is associated with seizures: an analysis of online psychedelic experience reports|anchor=d344467a}}
DangerousMAOIs — slows serotonin breakdown while LSD directly stimulates serotonin receptors; risks dangerous serotonin overload; adequate washout period from irreversible MAOIs recommended{{flag|citation-needed}}
DangerousMDMA, MDA — theoretical [[glossary:serotonin-syndrome|serotonin syndrome]] risk from combined receptor stimulation and serotonin release, plus additive cardiovascular strain; no controlled data exist{{flag|citation-needed}}
DangerousSSRIs — paroxetine increased LSD blood levels by 40–50%; chronic SSRI use reduces serotonin receptor sensitivity; appears well-tolerated based on current data{{cite|doi=10.1002/cpt.3618|anchor=d37a37ce}}{{cite|doi=10.1002/cpt.3618|anchor=164a69eb}}
=== Contraindications ===
AbsolutePersonal or family history of schizophrenia or psychotic disorder{{cite|doi=10.1038/s41380-024-02800-5|anchor=7273b927}}{{cite|doi=10.1016/j.biopsych.2014.11.015|anchor=f67ad83a}}; bipolar disorder type I{{cite|doi=10.1038/s41380-024-02800-5|anchor=94fc0a03}}; current lithium therapy{{cite|pubmed=38986146|anchor=c29c27ec}}{{cite|url=https://pure.johnshopkins.edu/en/publications/classic-psychedelic-coadministration-with-lithium-but-not-lamotri/|title=Classic psychedelic coadministration with lithium, but not lamotrigine, is associated with seizures: an analysis of online psychedelic experience reports|anchor=704da3ef}}; seizure disorder{{flag|safety-citation-needed}}; pregnancy and breastfeeding{{flag|safety-citation-needed}}
RelativeBipolar disorder II with careful assessment; significant heart condition{{cite|doi=10.1007/s00213-021-05978-6|anchor=87580606}}; current MAOI therapy{{flag|citation-needed}}
* LSD disrupts the [[glossary:default-mode-network|default-Default mode network]] —disruption is the brainneural system that maintains the sensebasis of self — producing [[effect:ego-dissolution|ego dissolution]] as the network loses coherence{{cite|doi=10.1073/pnas.1518377113|anchor=a4972782}} * The visual [[glossary:cortex|cortex]] simultaneously forms new connections with regions not normally involved in vision, producing vivid [[glossary:hallucination|hallucinations]]{{cite|doi=10.1073/pnas.1518377113|anchor=dbe28e73686b9b}} * One influential model proposes LSD pushes brain activity into a higher-entropy, less constrained state, weakening habitual thought patterns{{cite|doi=10.3389/fnhum.2014.00020|anchor=62ea470a}} * LSD promotes growth of new synaptic connections in the [[glossary:prefrontal-cortex|prefrontal cortex]] through a pathway linked to [[substance_class:psychoactive/antidepressant|antidepressant]] effects that operates independently of the hallucinogenic mechanism{{cite|doi=10.1038/s41593-023-01316-5|anchor=abd013fb}}{{cite|doi=10.1016/j.celrep.2018.05.022|anchor=48542fca}} * Open: LSD-assisted therapy produces mood improvements lasting months after a single session{{cite|doi=10.1192/bjp.2024.99|anchor=5725186d}}, but whether this durability comes from synaptic remodeling, [[effect:cognitive-flexibility|cognitive flexibility]], or psychological processing is not yet known * Open: Pre-drug personality, [[effect:anxiety|anxiety]] levels, and prior experience predict response direction{{cite|doi=10.1038/s41398-024-03074-9|anchor=75b4af57}}, but no validated model exists to predict individual outcomes in clinical settings
InternationalSchedule I, of the United NationsUN Convention on Psychotropic Substances (1971); no jurisdiction has rescheduled for medical use as of April 2026
UnitedTypical Statesnational statusSchedule I (Controlled Substancesin Act,virtually 1970);all federallynamed controlled since October 24, 1968; research requires DEA Schedule I researcher license and FDA IND exemption{{cite|url=https://www.dea.gov/factsheets/lsd|title=LSD Factsheet – Drug Enforcement Administration|anchor=f6351f0f}}
United KingdomClass A (Misuse of Drugs Act 1971), Schedule 1; maximum penalties: possession 7 years, supply/production life imprisonment; research requires Home Office Schedule 1 license{{cite|url=https://www.legislation.gov.uk/ukpga/1971/38|title=Misuse of Drugs Act 1971|anchor=152c962d}}
CanadaSchedule III (CDSA, 1996); possession up to 3 years indictable; trafficking up to 10 years; Section 56 ministerial exemptions for research{{cite|url=https://laws-lois.justice.gc.ca/eng/acts/c-38.8/|title=Controlled Drugs and Substances Act – Schedule III|anchor=3a1efbfb}}
AustraliaSchedule 9 — Prohibited Substance (SUSMP); no therapeutic use permitted; research requires TGA permit; same schedule as [[substance:heroin|heroin]]{{cite|url=https://www.tga.gov.au/resources/legislation/poisons-standard|title=Poisons Standard (Standard for Uniform Scheduling of Medicines and Poisons) – Schedule 9|anchor=fddf4fac}}
GermanyBetäubungsmittelgesetz (BtMG) — illegal; not marketable for therapeutic usejurisdictions; research exemptions available
NetherlandsOpium Act, List I — illegal; personal possession not prosecuted in practice
FranceSchedule I equivalent — illegal; no therapeutic use provisions
SwitzerlandControlled narcotic; compassionate use authorization granted since approximately 2014; active Phase 2/3 clinical trials at University Hospital Baselsome
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