HallucinogensSlides by: Bruna Brands, PhD
Centre for Addiction and Mental HealthDepartment 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
Definition
• group of substances that produce changes in thought, perception and/or mood
• term hallucinogen derived from Latin alucinari - “to wander in the mind”
Classes
• indolealkylamines (similar to 5-HT)• phenylethylamines (similar to nor-
ep)• anticholinergics• miscellaneous category
Clinical Manual of Chemical Dependence
Street Names of HallucinogensLSD 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 EveNote 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
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
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
• 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)
• naturally-occurring plant alkaloids (ex ergot alkaloids, Claviceps purpurea)
• chemically synthesized derivatives (LSD)
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
• well-absorbed from GI tract• LSD most potent (20-25g 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
• usual doses 30-400g (20g 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)
• 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
• 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
• 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 1g)• 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
• substituted phenethylamines- “designer drugs”
• structural similarities to amphetamine and mescaline
• MDMA
Clinical Toxicology of Hallucinogenic
Amphetamine Derivatives
• effective dose of MDMA 50-150mg
• well absorbed• peak effect at 1-5h
Anticholinergics
– plants: Solanum dulcamara, Atropa belladonna
(belladonna alkaloids: atropine and scopolamine)
– Jimsonweed (Datura stramonium), seeds contain 4% anticholinergic alkaloids (scopolamine, hyoscyamine and atropine)
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
• 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
• 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
• 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
• 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
• 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)
• 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
• 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
Pharmacology
• 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 κ opioid receptor
agonist• first non-alkaloid opioid receptor subtype
selective drug
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)
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