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Hallucinogens. Slides by: Bruna Brands, PhD Centre for Addiction and Mental Health Department of Pharmacology University of Toronto Live Dramatic Interpretation by: Wende Wood, B.A., B.S.P., B.C.P.P. Drug Information and Drug Use Evaluation Pharmacist

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Slides by: Bruna Brands, PhD

Centre for Addiction and Mental Health

Department of Pharmacology

University of Toronto

Live Dramatic Interpretation by:

Wende Wood, B.A., B.S.P., B.C.P.P.

Drug Information and Drug Use Evaluation Pharmacist

Centre for Addiction and Mental Health

  • group of substances that produce changes in thought, perception and/or mood
  • term hallucinogen derived from Latin alucinari - “to wander in the mind”
  • indolealkylamines (similar to 5-HT)
  • phenylethylamines (similar to nor-ep)
  • anticholinergics
  • miscellaneous category
clinical manual of chemical dependence street names of hallucinogens
Clinical Manual of Chemical DependenceStreet Names of Hallucinogens

Note LSD = lysergic acid diethylamide DMT = N,N-dimethyltryptamine DET = N,N-diethyltryptamine DOM = 2,5-dimethoxy-4-methamphetamine MDA = methylenedioxyamphetamine MDMA = methylenedioxymethamphetamine DEA = 3,4-methylendioxyethamphetamine

Edited by D.A. Ciraulo and R.I. Shader

  • LSD (d-lysergic acid diethylamide,semi-synthetic substance derived from ergot)
  • LSA (d-lysergic acid amide, from morning glory seeds)
  • psilocybin and psilocin ( isolated from hallucinogenic mushroom genus Psilocybe)
  • DMT( N,N-dimethyltryptamine), found in trees of genus Virola
history of lsd
History of LSD
  • hallucinogenic and psychotomimetic effects of LSD discovered by Hofmann who accidentally ingested a minute quantity of ergot derivatives
  • ergot alkaloids are produced by rye-plant inhabiting fungus (Claviceps purpurea)
  • outbreaks of ergotism in Middle Ages
history of lsd cont d
History of LSD cont’d
  • two types
    • gangrenous ergotism
      • gangrene of limbs, loosened before death
    • convulsive ergotism
      • erythema, diarrhea, vomiting, formication, burning sensation in limbs, convulsions, maniacal excitement, death
tryptamine related hallucinogens indolealkylamines
Tryptamine-Related Hallucinogens (Indolealkylamines)
  • naturally-occurring plant alkaloids (ex ergot alkaloids, Claviceps purpurea)
  • chemically synthesized derivatives (LSD)
tryptamine related hallucinogens lsd neuropharmacology
Tryptamine-Related Hallucinogens-LSD-Neuropharmacology
  • acts primarily through 5-HT receptor subtypes
  • antagonist or partial agonist at 5-HT2 and 5-HT1c receptors, agonist at multiple 5-HT1receptors
  • cannot attribute hallucinogenic effects to one 5-HT receptor subtype
tryptamine related hallucinogens pharmacology
Tryptamine-Related Hallucinogens-Pharmacology
  • well-absorbed from GI tract
  • LSD most potent (20-25g produces marked sympathomimetic effects)
  • 5 morning glory seeds a high of 12 hours or longer
  • LSD longer acting (8-12h) and more potent than psilocybin or psilocin (4-12h)
  • 1-2 mushrooms hallucinosis for 4-12h
  • all compounds mainly cleared by liver; excreted in feces
  • LSD no active metabolites
  • psilocybin is hydrolyzed to psilocin (active hallucinogen)
clinical symptoms of lsd intoxication
Clinical Symptoms of LSD Intoxication
  • usual doses 30-400g (20g clinically detectable symptoms)
  • tolerance occurs over time
  • symptoms within 30 min
  • maximum effects at 1-4h, symptoms subside after 8-16h
  • lower doses autonomic nervous system changes and mood changes:HR and BP and body temp, appetite, nausea, vomiting etc
  • higher doses perceptual distortions and body image changes
clinical symptoms of lsd intoxication cont d
Clinical Symptoms of LSD Intoxication (cont’d)
  • subjective experience depends on personality of user, expectations, setting
  • perception: visual distortions, blurred vision, perception of distance and depth
  • synesthesia, colours are visible
  • delusions of supernatural abilities, suicide
  • euphoria or frightening experience may occur
  • flashbacks
  • prolonged adverse reactions: psychosis, paranoid states, depression
other tryptamine related hallucinogens
Other Tryptamine related Hallucinogens
  • similar to LSD
  • intensity of effects related to dose
  • restlessness, nausea and autonomic hyperactivity
  • visual disturbances more common
  • Psilocybe mushrooms: ataxia, hyperkinesis, anticholinergic effects (symptoms within 15-30 min)
phenylethylamine hallucinogens
Phenylethylamine Hallucinogens
  • close structural resemblance to catecholamines, nor-ep and DA
  • mescaline naturally occurring substance found in peyote cactus
  • modification of mescaline molecule led to synthetic amphetamine derivatives with hallucinogenic action
  • one dried flower top (mescal button) contains 6-45mg of active compound
  • ingested fresh or as a powder
mescaline pharmacokinetics
  • <potent than LSD (5mg vs 1g)
  • readily absorbed from GI tract
  • concentrated in liver, spleen, kidney
  • clinical symptoms similar to LSD
  • nausea and vomiting 30 min to 2h after ingestion
  • mydriasis, diaphoresis, hypertension, dizziness, chills
  • hallucinogenic effects peak at 5-6h
  • vivid colours, kaleidoscopic visions, synesthesias
phenylalkylamine hallucinogens cont d
Phenylalkylamine Hallucinogens-cont’d
  • substituted phenethylamines- “designer drugs”
  • structural similarities to amphetamine and mescaline
  • MDMA
chemical structure of mdma 3 4 methylenedioxy methamphetamine
Chemical Structure of MDMA(3-4 methylenedioxy-methamphetamine)
clinical toxicology of hallucinogenic amphetamine derivatives
Clinical Toxicology of Hallucinogenic Amphetamine Derivatives
  • effective dose of MDMA 50-150mg
  • well absorbed
  • peak effect at 1-5h
  • plants: Solanum dulcamara, Atropa belladonna

(belladonna alkaloids: atropine and scopolamine)

  • Jimsonweed (Datura stramonium), seeds contain4% anticholinergicalkaloids (scopolamine, hyoscyamine and atropine)
anticholinergics cont d
Anticholinergics cont’d
  • low doses of scopolamine- mild euphoria, sedation, drowsiness
  • much higher doses intense cns and pns effects:
    • clinical findings: muscarinic effects: dry mouth, decreased GI motility, urinary retention, tachycardia, dry mouth, hyperpyrexia with dry, flushed skin
    • CNS effects: visual, auditory and tactile hallucinations; disorientation and confusion, memory loss, dilation of pupils, seizures
  • entire episode may last for 24 to 48 hours
belladonna alkaloids
Belladonna Alkaloids
  • atropa belladonna (deadly nightshade)
  • berries used as poison (Atropa, after Atropos, one of Greek Fates who cut the thread of life and was responsible for death)
  • belladonna means beautiful woman – refers to putting a drop of the juice of the plant to dilate pupils
  • also used by witches in Middle Ages
datura stramonium
Datura stramonium
  • Jimson weed (“locoweed”, thorn apple)
  • Solanaceae family
  • all parts of plant are poisonous
  • seeds contain 4% anticholinergic alkaloids (scopolamine, hyposcyamine and atropine)
  • leaves can be eaten raw, prepared as tea or smoked
  • as little as 4-5g of crude leaf may be lethal for children
  • adolescents smoke the dried leaves or consume dried seeds to induce toxic delirium
  • effects dose dependents
miscellaneous category
Miscellaneous Category
  • PCP and Ketamine
  • dissociative anesthetics
  • both drugs produce hallucinogenic effects at low levels
  • PCP can produce stimulant, depressant, analgesic, anesthetic, and hallucinogenic effects (dose-dependent)
medical uses
Medical Uses
  • ketamine:anesthetic
  • atropinic alkaloid: to control smooth-muscle spasms, hyperirritability of the GI tract, excessive salivation and bronchial secretions etc
  • scopolamine for motion sickness
  • no medical uses for LSD, MDMA etc
undesirable effects
Undesirable Effects
  • acute; usually mild and transient feelings of physical discomfort, anxiety, depression
  • sometimes intense anxiety, panic, paranoia; rarely toxic psychosis
  • “bad trips” not always related to dose
  • PCP and LSD are hallucinogens most frequently associated with serious and lethal accidents
  • atropine, scopolamine, hyoscyamine dangerous at high doses
  • PMA highly lethal
undesirable effects cont d
Undesirable Effects (Cont’d)
  • deaths associated with MDA, MDMA, PCP
  • flashbacks
  • brain damage
  • tolerance develops to psychoactive effects of many hallucinogens (ex LSD)
  • psychological dependence may develop to some
  • development of physical dependence not supported by literature
salvia divinorum
Salvia divinorum
  • mint family
  • main active ingredient is Salvinorin A
  • used in spiritual practices for its psychoactive properties by Mazatecs of Oazaca, Mexico
  • no actions on 5-HT2A serotonin receptors (principal molecular target for classical hallucinogens)
  • structurally distinct from DMT, psilocybin, mescaline and synthetic hallucinogens such as LSD and ketamines
  • not active orally, usually smoked
  • most potent naturally occurring hallucinogen (as potent as LSD)
  • effective dose in humans 200-1000 μg range when smoked
  • intense hallucinatory experiences
  • duration of action: several minutes to 1hr or so
  • potent and selective κopioid receptor agonist
  • first non-alkaloid opioid receptor subtype selective drug
potential therapeutic use
Potential Therapeutic Use
  • psychomimetic selective for κ opioid receptors, therefore κ opioid selective antagonists may be helpful to treat diseases which involve perceptive disorders (e.g., schizophrenia, dementia, and bipolar disorders)
  • most of these drugs are produced in illicit laboratories
  • purity varies, adulterants
  • misrepresentation on the street
  • street drugs and driving