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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.

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Presentation on theme: "Hallucinogens Slides by: Bruna Brands, PhD Centre for Addiction and Mental Health Department of Pharmacology University of Toronto Live Dramatic Interpretation."— Presentation transcript:

1 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 Centre for Addiction and Mental Health

2 Definition group of substances that produce changes in thought, perception and/or mood term hallucinogen derived from Latin alucinari - “to wander in the mind”

3 Classes indolealkylamines (similar to 5-HT) phenylethylamines (similar to nor-ep) anticholinergics miscellaneous category

4 Clinical Manual of Chemical Dependence Street Names of Hallucinogens LSD Acid, blotter, blue devils, California sunshine, haze, microdot(s), mickeys, Mr. Natural, paper acid, purple haze, sunshine, wedges, window panes(s) Morning glory seeds Flying saucers, licorice drops, heavenly gates, pearly gates Psilocybin Magic mushroom, mushroom DMT, DET Businessman’s lunch, snuff Peyote/mescaline Button(s), cactus, mesc, mescal, mescal buttons, moon, peyote DOM Golden eagle, STP, psychodrine, tile MDA Love drug MDMA Adam, ecstasy, MDM, XTC MDEA Eve 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

5 Indolealkylamines 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

6 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

7 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

8 Tryptamine-Related Hallucinogens (Indolealkylamines) naturally-occurring plant alkaloids (ex ergot alkaloids, Claviceps purpurea) chemically synthesized derivatives (LSD)

9 Tryptamine-Related Hallucinogens- LSD-Neuropharmacology acts primarily through 5-HT receptor subtypes antagonist or partial agonist at 5- HT 2 and 5-HT 1c receptors, agonist at multiple 5-HT 1 receptors cannot attribute hallucinogenic effects to one 5-HT receptor subtype

10 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)

11 Clinical Symptoms of LSD Intoxication usual doses  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

12 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

13 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 min)

14 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

15 Mescaline-Pharmacokinetics

16 Phenylalkylamine Hallucinogens-cont’d substituted phenethylamines- “designer drugs” structural similarities to amphetamine and mescaline MDMA

17 Chemical Structure of MDMA ( 3-4 methylenedioxy-methamphetamine )

18 Clinical Toxicology of Hallucinogenic Amphetamine Derivatives effective dose of MDMA mg well absorbed peak effect at 1-5h

19 Anticholinergics –plants: Solanum dulcamara, Atropa belladonna (belladonna alkaloids: atropine and scopolamine) –Jimsonweed (Datura stramonium), seeds contain 4% anticholinergic alkaloids (scopolamine, hyoscyamine and atropine)

20 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

21 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

22 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

23 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)

24 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

25 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

26 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

27 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-HT 2A serotonin receptors (principal molecular target for classical hallucinogens) structurally distinct from DMT, psilocybin, mescaline and synthetic hallucinogens such as LSD and ketamines

28 Pharmacology not active orally, usually smoked most potent naturally occurring hallucinogen (as potent as LSD) effective dose in humans μg range when smoked intense hallucinatory experiences duration of action: several minutes to 1hr or so potent and selective κ opioid receptor agonist first non-alkaloid opioid receptor subtype selective drug

29 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)

30 Issues most of these drugs are produced in illicit laboratories purity varies, adulterants misrepresentation on the street street drugs and driving


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