Transcript Psy 5260 – Summer I 2009 Week Six Lecture Notes

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Animism
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All objects derive their special
characteristics from a spirit contained
within objects
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If a plant contains a spirit, eating the
plant transfers that spirit to the person
who eats it
Shaman – medicine man/woman
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Specialist in harvesting and utilizing
plants for medicinal properties
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Phantastica
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Drugs that create a world of fantasy
in our minds
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Other names used over the years
 Psychedelic (mind manifester)
 Psychotomimetics(mimics psychosis)
 Entheogen (creating spirit or divine within)
 Entactogen (touching within)
 Empathogen (empathy creator)
 Hallucinogen (creating hallucinations)
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Classifying Hallucinogens
Chemical Structures (e.g., Indole, Catechol, Other)
Pharmacological Effects (e.g., 5-HT agonists, NMDA
glutamate antagonists, anticholinergics)
 Effects on Conscious Awareness (e.g., visual perception,
body awareness)
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Classical Phantastica
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Capable of altering perceptions while allowing one to
remain conscious of surroundings
 Individual is simultaneously aware of both
fantasy and reality
 Later memory for experience is relatively clear.
They produce little acute physiological toxicity
In contrast, dissociative anesthetics and
anticholinergics produce physiological
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toxicity and impair memory.
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Two chemical classes of classical phantastica
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Indole hallucinogens (Serotonin-Like)
Catechol hallucinogens (Dopamine-Like)
Images obtained from
http://www.nida.nih.gov/ResearchReports/Hallucinogens/Structure.jpg
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d-lysergic acid diethylamide (LSD)
Psilocybin
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Ololiuqui
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Morning Glory seeds (lysergic acid amide)
Argyreia nervosa
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Mushrooms
Hawaiian baby woodrose seeds
Dimethyltryptamine (DMT)
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Several plant substances
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LSD is not found in nature
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First synthesized from grain fungus
 Ergotism (St. Anthony’s fire)—Condition experienced
from eating bread made from fungus infected grain
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LSD discovery and early research
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Synthesized in 1938 by Albert Hoffman, Sandoz
 First experience from accidental absorption, 1943
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Extensive medical use in U.S., 1953 to 1966
Turned over to government in 1966
Secret Army/CIA research with LSD
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Physical properties of LSD
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In pure form - colorless, odorless, tasteless
Absorption from GI system rapid
Metabolism and Elimination
Half-life approx. 3 hours
 > 90% is excreted within 24 hours
 Subjective effects can last 2-12 hours
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Cellular Tolerance develops rapidly
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Repeated daily doses become ineffective within a
few days
No evidence for Physical Dependence with
LSD
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Acute Physiological Effects
 Sympathomimetic effects
 Pupil dilation, increased body temp., heart
rate, and blood pressure
 Parasympathetic effects
 salivation and nausea
Mechanism of Action
 Serotonin Agonist (5-HT2A receptor agonist)
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Altered senses/perceptions
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Adverse Reactions
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Synesthesia
Body distortions
Panic
Flashbacks
Some beliefs about LSD
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Creativity
Therapy
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Varieties of psychoactive
mushrooms
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Effects
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Psilocybe mexicana
Psilocybe cubensis
Hallucinogenic effects similar to LSD
Similar autonomic effects to LSD
Cross tolerance occurs among
psilocybin, LSD, and mescaline
Clinical Benefits of Entheogens
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Recent studies by Griffiths et al. at
Johns Hopkins.
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Dimethyltryptamine (DMT)
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A short-acting hallucinogen (duration less than an
hour)
Found in seeds of certain leguminous trees and
prepared synthetically
No effects when taken orally, taken as snuff or
smoked
Ayahuasca (vine of the soul)
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Religious sacrament in South American tribes
Contains:
 Banisteriopsis caapi vine (contains harmaline, an MAO
inhibitor)
 Psychotria viridis leaves (contains DMT)
 Neither plant has psychoactive effects when ingested
alone
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Mescaline (Peyote)
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Structurally similar to amphetamine, but effects are
more like those of LSD.
Mescaline is the most active drug in peyote; it
induces intensified perception of colors and
euphoria.
Effects include dilation of the pupils, increase in body
temperature, anxiety, visual hallucinations, and
alteration of body image, vomiting, muscular
relaxation, and in very high doses may cause death.
Street samples are rarely authentic.
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Chemically related to amphetamines
Varying degrees of hallucinogenic and CNS
stimulant effects
Phenylethylamines that predominantly:
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Release serotonin are dominated by their
hallucinogenic effects
Release dopamine are dominated by their stimulant
effects
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2,5-Dimethoxy-4-methylamphetamine (DOM
or STP)
3,4-Methylenedioxyamphetamine (MDA)
3,4-Methylenedioxymethamphetamine
(MDMA, Ecstasy)
“Designer” amphetamines
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2-CB, 2-C-T7, TMA
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Phencyclidine (PCP)
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Developed as an intravenous anesthetic, but found to
have serious adverse side effects.
NMDA Glutamate Antagonist
Effects differ from those of other traditional
hallucinogens
 It is a general anesthetic in high doses
 It causes incredible strength and extreme violent
behavior
 Management of the severe psychological reactions
requires drug therapy
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Physiological effects
Hallucinogenic effects, stimulation,
depression, anesthesia, analgesia
 Large doses can cause coma, convulsions,
and death
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Psychological effects
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Feelings of strength, power,
invulnerability, perceptual distortions,
paranoia, violence, psychoses
Other PCP-like drugs
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Ketamine
 Veterinary anesthetic
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Dextromethorphan at high doses
 Synthetic derivative of codeine, OTC cough
suppressant
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Nitrous Oxide
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Belladonna
Mandrake
Henbane
Datura
These products contain the
anticholinergic agents, atropine
and scopolamine.
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Amanita Muscaria
 Red and white speckled mushroom found in forests
in many parts of the world
 Active ingredient once thought to be muscarine, a
cholinergic agonist
 1960s, ibotenic acid and muscimol found in significant
amounts
 Muscimol is a GABA agonist: produces confusion,
disorientation, sensory disturbances, muscle twitches,
fatigue, sleep
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Salvia Divinorum
“Magic Mint”, “Diviners sage”
 Religious sacrament among Mazatec people of Oaxaca,
Mexico
 Only recently used in U.S. and Europe, considered legal
hallucinogen, not currently listed as a controlled substance
 Kappa opioid agonist
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Drug Discrimination
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All hallucinogens are capable of establishing
discriminative stimulus control and the
discrimination appears to be specific to a particular
drug’s mechanism of action.
 Animals trained to discriminate LSD will generalize to
other indole hallucinogens as well as mescaline, but not
to catechol hallucinogens (MDMA) , the dissociative
anesthetics (PCP, ketamine), or the anticholinergics
(atropine, scopolamine).
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Self Administration in Nonhumans
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Hallucinogens that ARE self administered
 MDMA, PCP, ketamine
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Hallucinogens that are NOT self-administered
 LSD, psilocybin, mescaline
 However, a recent study showed that monkeys with a
history of MDMA self-administration may self
administer psilocybin and mescaline (Fantegrossi et al.,
2004).