chapter 12 psychedelics. psychedelic/hallucinogens called by many different names psychotogens ...
TRANSCRIPT
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CHAPTER 12
Psychedelics
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Psychedelic/Hallucinogens
Called by many different names Psychotogens Psychotomimetics Psychedelics
Primary effect is to produce perceptual changes & hallucinations
Can influence several sensory systems, perception of time, space & events
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Different Types of Psychedelics
Serotonergic LSD Psilocybin/Psilocin DMT - Ayahuaca Bufotenine Ololiuqui
Catecholamine-like Mescaline MDMA (ecstasy)
MDA MDE
DOM Myristin and Elemicin
Cholinergic Muscarine Scopolamine
Glutamatergic PCP Ketamine Dextromethorphan
Opioid Salvinorin A
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SerotonergicPsychdelics
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LYSERGIC ACID DIETHYLAMIDE (LSD)
Lysergic acid – Derived from ergot alkaloidsErgot is a poisonous fungus that infects rye &
other grains & grassesAlbert Hoffman: 1938 - synthesized #25 in
series of new molecules doing ergot alkaloid chemistry
1943 - returned to #25 making new batch & absorbed some through skin
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LSD in the USA
Came to U.S. in 1950s in two ways:• Clinical usage: Supplied to psychologists and
psychiatrists encouraged their taking drug
• Military Usage: U.S. military and CIA as incapacitating agent and truth drug
• U.S. government gave LSD to unsuspecting individuals to study effects
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LSD in the USA
1960s - popular use advocates East Coast: Timothy Leary (clinical psychologist at Harvard) West Coast: Ken Kesey (noted author)
graduate student in California got dose in psychology study shortly after this goes to work in psychiatry year later, writes One Flew Over The Cuckoo's Nest
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LSD in the USA
Spread through country with huge publicity until peak 1968 to 1972
Schedule I in 1968Stuffy politicians didn’t know what to do because
LSD was used by white, middle to upper class, college students
Early 1990s - LSD came back
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LSD & Neurotransmission
Binds to 5-HT2A receptors agonist effect
Increases amount of sensory information getting to cortex through overriding filter mechanisms
This is how the drug influences perception, especially for vision
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Pharmacology of LSD
Pharmacological Effects Effects heavily dependent
on dose taken not just intensity of effects,
but type of effectsLow doses = mild
perceptual alterations comparable to effects of
marijuana use, but greater clarity
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Effects of LSD
High Doses progression through mental and
emotional experiences 6-12 hrs duration Each trip unique, highly
dependent upon setting and personal expectations
Can alter subjects’ emotional feelings during trip by experimenter’s previous behavior warm and supportive or
suspicious and nonsupportive
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Effects of LSD
Effects of drug come on in about 30 minfirst signs are autonomic activationfollowed by overt behavioral signs - loosening of
emotional inhibitions giddiness, laughter for no reason mood euphoric and expansive, but labile mood swings
notableabnormal color sensations, luminescencecolors reported as more brilliant
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Effects of LSD
space and time disordersadded depth with loss of perspective - up/down
alteredclose in space influenced more than distantgeneral slowing of time reported
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LSD Hallucinationsgratings, latticework,
honeycomb, chessboard, tunnels, funnels, alleys, cones,
vessels, and spirals can be present with eyes open or
closed involve bright light in center
with figures moving in from periphery
forms appear to move in depth and take on color shades, red common
Sounds can take on visual forms music may take on enhanced
meaning or intensity
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LSD & Bad Trips
Psychological impact - traumatizing, imagery dark, insights appalling
Usually occur in novice users, feel out of controlGenerally negative set and setting are key
contributing factorsCan lead to suicide or prolonged psychotic
reactionCan usually be talked down from a bad trip
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LSD & Flashbacks
Spontaneous recurrence of trip after period of normalcy
can occur after long periods of abstinencemore common after multiple high dose useprolonged afterimages for days and weeks after
tripping mechanism unknown can be brought on by other drugs or setting most commonly reported in low light situationsnot intrinsically dangerous and usually go away
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Psilocybin/Psilocin
Magic Mushrooms, Liberty Caps Central America and
northwestern U.S. Last about 6-10 hours Need a lot to get same effect
as LSD 5-HT2A agonist Same basic effects as LSD Mushrooms occasionally
toxic
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DMT
Dimethyltriptamine 5-HT2A agonist Alkaloid Often smoked Main ingredient in Ayahuasca Same effects as LSD
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Bufotenine
Dimethyl-serotonin A product of
abnormal serotonin breakdown
Like LSD and others Can occur in urine of
people with psychiatric disorders Psychosis Paranoia Depression
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Ololiuqui
Substance found in morning glory seedsSimilar to LSDSignificant nausea, vomiting and cramping
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Tolerance/Dependence
Not significant producers of tolerance or dependence
No withdrawal eitherPeople and animals do not self-administerProblems related to the things people do
while under the influence Accidents Suicide Aggression/violence Toxic reactions
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Catecholamine-likePsychedelics
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Mescaline
Active drug in peyoteStructurally similar to
NEHowever, most of the
effect is mediated by our friend, the 5-HT2A
agonist actionLegal for members of
the Native American Church
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Ecstasy
MDMA (methylene-dioxy-methamphetamine)
Synthesized in 1912Structurally related to amphetamines
Sympathomimetic Weak in altering perceptual functions But strong effects on emotions - empathogen Used in combo with psychotherapy
MDMA
CH2 NHCH CH3
CH3O
O
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PharmacodynamicsPharmacodynamics
Monoamine neurotransmission increase synaptic DA and 5-HT blocks 5-HT transporter enters neuron and causes release of 5-HT
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Ecstasy Effects
Stimulant effects typically noted shortly after ingestion increased heart rate increased blood pressure dry mouth decreased appetite increased alertness elevated mood jaw clenching
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Ecstasy Effects
Subjective Effects
euphoria increased
physical and emotional energy
heightened sensual awareness
subjective feeling of increased closeness or enhanced communication
Cognitive Effects
memory loss
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X Tox
Malignant hyperthermia and dehydrationIdiopathic toxic response (not common but
nasty) Renal failure Rhabdomyolysis – disintegration of muscle tissue
Street X is even more of a problem because it’s not always X or may have other drugs
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X Tox
Potent neurotoxin 1-2 times street dose depletes forebrain 5-HT (not DA) Kills the transporter receptor (SSRI) Degeneration of 5-HT terminals
Fine axons from dorsal raphe Can get 30% loss with single injection Up to 80% with repeated injections
Can induce psychiatric disturbance in vulnerable individuals. Treatment refractory depression
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MDMA & MDA neurotoxicityMDMA & MDA neurotoxicity
9.9
Normal MDAPCA
5-HT immunoreactive fibers in rat parietal cortex
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McCann et al.(1997)
Control
MDMA
Squirrelmonkeys 18 mo post-trtmt
Neocortex Hippocampus Caudate5-HT immuno-reactivity
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What is PMA?
Paramethoxy-amphetamine"Death" "Mitsubishi Double Stack"
"Killer" "Red Mitsubishi"Substitute for MDMACheaper to makeSlower, longer effectsMore hallucinogenicIncidence of toxic side effects much higher
than MDMA (narrow safety margin)
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Designer Psychedelics
DOM, MDA, DMA, MDE, TMA, AMT, 5MeO-DIPT
All structurally related to mescaline and methamphetamine; therefore MDMA.
MDA is a metabolite of MDMA. May be responsible for much of the MDMA effect.
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Myristin and Elemicin
Found in nutmeg and maceStructurally similar to mescalineSignificant nausea and vomitingThe sick usually limit use
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DISSOCIATIVE ANESTHETICS
GlutamatergicPsychedelics
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PhencyclidinePCPPCPNMDA receptor antagonistNMDA receptor antagonist
Blocks the function of glutamateBlocks the function of glutamate
Used as an analgesic and anestheticUsed as an analgesic and anestheticCan be administered by any routeCan be administered by any routeOddly enough, animals self-administer Oddly enough, animals self-administer
(euphoria) (euphoria)Induces amnesia and true psychosisInduces amnesia and true psychosis
Hallucinations, paranoia, agitation, dissociation Hallucinations, paranoia, agitation, dissociation
Higher doses lead to stupor, coma Higher doses lead to stupor, coma seizures, death seizures, death
A perfect example of a Schedule I drugA perfect example of a Schedule I drug
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Ketamine
Special KVery similar to PCP,
not as powerfulLiquid, but can be
powdered for snorting or smoking
But just as dumb, stupid, useless and unsafe
Another perfect example of a Schedule I drug
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Subjective Effects of PCP/Ketamine
Sensations of light coming through the body and/or colorful visions
Complete loss of time senseBizarre distortions of body shape or sizeAltered perception of body consistencySensations of floating or hovering in spaceFeelings of leaving one’s bodyVisions of spiritual or supernatural beingsEmotions ranging from euphoria to hositlity
Dalgarno & Shewan (1996)
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Dextromethorphan
Active ingredient in most OTC cough medicine
NMDA receptor blockade at high dosesMostly teenage males abuse itLike PCP and K at 20-30 X OTC doseCoricidin –Bad news
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CholinergicHallucinogens
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Muscarine/Muscimol
Found in mushrooms (Amanita Muscaria)
Muscimol is a GABAA agonist Trance-like, dreamy state
with dreamlike illusions Like Ambien
Muscarine is an Acetylcholine agonist (muscarinic receptors) Not psychotropic Peripheral effects: sweating,
limb twitching, seizure activity
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Atropine & Scopolamine
Found in – Atropa belladonna, Datura Stramonium, Henbane
Acetylcholine receptor (muscarinic) antagonistsDissociatives that induces delirium , hallucinations, and amnesiaClassic anti-cholinergic symptoms
Hot as hell Dry as a bone Mad as a hatter Blind as a bat Red as a beet
Used in the treatment of motion sickness & to dilate pupils during eye-exams.
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Opioid Hallucinogen - Salvinorin A
Comes from a plant in the mint family Salvia Divinorum
Affinity for kappa opioid receptors Agonist action
Like LSD and psilocybin
Fresh leaves are chewed and left in mouth
Dried leaves smoked Not effective if taken
orally
Most potent, but not most powerful, of all naturally occurring hallucinogens
It’s still legal, but not likely for long