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CHAPTER 12
Psychedelic/Hallucinogens
& hallucinations Can influence several sensory systems, perception of time, space & events
Cholinergic
Catecholamine-like
MDA MDE
DOM
Myristin and Elemicin
Serotonergic Psychdelics
other grains & grasses Albert Hoffman: 1938 - synthesized #25 in series of new molecules doing ergot alkaloid chemistry 1943 - returned to #25 making new batch & absorbed some through skin
Military Usage: U.S. military and CIA as incapacitating agent and truth drug U.S. government gave LSD to unsuspecting individuals to study effects
peak 1968 to 1972 Schedule I in 1968 Stuffy politicians didnt know what to do because LSD was used by white, middle to upper class, college students Early 1990s - LSD came back
Pharmacology of LSD
Pharmacological Effects Effects heavily dependent on dose taken
perceptual alterations
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 experimenters previous behavior warm and supportive or suspicious and nonsupportive
Effects of LSD
Effects of drug come on in about 30 min first signs are autonomic activation followed by overt behavioral signs - loosening of emotional inhibitions
giddiness, laughter for no reason mood euphoric and expansive, but labile mood swings notable
Effects of LSD
altered close in space influenced more than distant general slowing of time reported
LSD Hallucinations
gratings, latticework,
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
dark, insights appalling Usually occur in novice users, feel out of control Generally negative set and setting are key contributing factors Can lead to suicide or prolonged psychotic reaction Can usually be talked down from a bad trip
Spontaneous recurrence of trip after period of normalcy can occur after long periods of abstinence more common after multiple high dose use prolonged afterimages for days and weeks after
can be brought on by other drugs or setting most commonly reported in low light situations not intrinsically dangerous and usually go away
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
DMT
Dimethyltriptamine 5-HT2A agonist Alkaloid Often smoked Main ingredient in Ayahuasca Same effects as LSD
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
Ololiuqui
Substance found in morning glory seeds Similar to LSD Significant nausea, vomiting and cramping
Tolerance/Dependence
Not significant producers of tolerance or
dependence No withdrawal either People and animals do not self-administer Problems related to the things people do while under the influence
Accidents Suicide Aggression/violence Toxic reactions
Catecholamine-like Psychedelics
Mescaline
Active drug in peyote Structurally similar to NE However, most of the
effect is mediated by our friend, the 5-HT2A agonist action Legal for members of the Native American Church
Ecstasy
MDMA (methylene-dioxy-methamphetamine)
Synthesized in 1912 Structurally related to amphetamines Sympathomimetic Weak in altering perceptual functions But strong effects on emotions - empathogen Used in combo with psychotherapy
O CH 3 O CH 2 CH NH CH 3
MDMA
Pharmacodynamics
Monoamine neurotransmission
increase synaptic DA and 5-HT blocks 5-HT transporter enters neuron and causes release of 5-HT
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
Subjective Effects
euphoria increased physical and emotional energy heightened sensual awareness subjective feeling of increased closeness or enhanced communication memory loss
Cognitive Effects
Ecstasy Effects
X Tox
Malignant hyperthermia and dehydration Idiopathic toxic response (not common but nasty) Renal failure Rhabdomyolysis disintegration of muscle tissue Street X is even more of a problem because its not
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
9.9
Control
5-HT immunoreactivity
Neocortex
Hippocampus
Caudate
MDMA
McCann et al. (1997)
What is PMA?
Paramethoxy-amphetamine "Death" "Mitsubishi Double Stack"
"Killer" "Red Mitsubishi" Substitute for MDMA Cheaper to make Slower, longer effects More hallucinogenic Incidence of toxic side effects much higher than MDMA (narrow safety margin)
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.
Glutamatergic Psychedelics
DISSOCIATIVE ANESTHETICS
Phencyclidine
PCP NMDA receptor antagonist Blocks the function of glutamate Used as an analgesic and anesthetic Can be administered by any route Oddly enough, animals self-administer
Ketamine
Special K Very similar to PCP, not
as powerful Liquid, but can be powdered for snorting or smoking But just as dumb, stupid, useless and unsafe Another perfect example of a Schedule I drug
and/or colorful visions Complete loss of time sense Bizarre distortions of body shape or size Altered perception of body consistency Sensations of floating or hovering in space Feelings of leaving ones body Visions of spiritual or supernatural beings Emotions ranging from euphoria to hositlity
Dalgarno & Shewan (1996)
Dextromethorphan
Active ingredient in most OTC cough medicine NMDA receptor blockade at high doses Mostly teenage males abuse it
Cholinergic Hallucinogens
Muscarine/Muscimol
Found in mushrooms
Muscarine is an
Found in Atropa
Dissociatives that induces delirium , hallucinations, and amnesia Classic anticholinergic symptoms
Hot as hell Dry as a bone Mad as a hatter Blind as a bat Red as a beet
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 Its still legal, but not likely for long