Transcript Hallucinogens

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
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
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indolealkylamines (similar to 5-HT)
phenylethylamines (similar to nor-ep)
anticholinergics
miscellaneous category
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
DMT, DET
Peyote/mescaline
Magic mushroom, mushroom
DOM
MDA
MDMA
Golden eagle, STP, psychodrine, tile
MDEA
Eve
Businessman’s lunch, snuff
Button(s), cactus, mesc, mescal, mescal buttons,
moon, peyote
Love drug
Adam, ecstasy, MDM, XTC
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
Indolealkylamines
• LSD (d-lysergic acid diethylamide,semisynthetic 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 ryeplant 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 HallucinogensLSD-Neuropharmacology
• acts primarily through 5-HT
receptor subtypes
• antagonist or partial agonist at 5HT2 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 (20-25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)
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
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
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<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
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
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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 smoothmuscle 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)
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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