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

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-HT2 and 5-HT1c receptors, agonist at multiple 5-HT1receptors
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
<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

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-HT2A 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