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

Chemical Structure of MDMA

(3-4 methylenedioxy-methamphetamine)

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)

Issues

• most of these drugs are produced in illicit laboratories

• purity varies, adulterants• misrepresentation on the

street• street drugs and driving