Hallucinogens

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 DependenceStreet
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 Businessmans 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-metha
mphetamine 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 contd

• 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-Neuropharmaco
logy

• 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 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

12
Clinical Symptoms of LSD Intoxication (contd)

• 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 15-30
  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

• ltpotent 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-contd

• 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 50-150mg
• 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 contd

• 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

• ketamineanesthetic
• 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 (Contd)

• 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 200-1000 µg range when
  smoked
• intense hallucinatory experiences
• duration of action several minutes to 1hr or so
• potent and selective ? opioid receptor agonist
• first non-alkaloid opioid receptor subtype
  selective drug

29
Potential Therapeutic Use

• psychomimetic selective for ? opioid receptors,
  therefore ? 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