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Psychedelics
CHAPTER 12
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
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

Serotonergic
Psychdelics
LYSERGIC ACID DIETHYLAMIDE (LSD)
 Lysergic acid – Derived from ergot alkaloids
 Ergot is a poisonous fungus that infects rye &
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
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
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

LSD in the USA
 Spread through country with huge publicity until
peak 1968 to 1972
 Schedule I in 1968
 Stuffy politicians didn’t know what to do because
LSD was used by white, middle to upper class,
college students
 Early 1990s - LSD came back
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
Pharmacology of LSD
Pharmacological Effects
 Effects heavily dependent
on dose taken

not just intensity of effects,
but type of effects
 Low doses = mild
perceptual alterations

comparable to effects of
marijuana use, but greater
clarity
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
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

 abnormal color sensations, luminescence
 colors reported as more brilliant
Effects of LSD
 space and time disorders
 added depth with loss of perspective - up/down
altered
 close in space influenced more than distant
 general slowing of time reported
LSD Hallucinations
 gratings, 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
LSD & Bad Trips
 Psychological impact - traumatizing, imagery
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
LSD & Flashbacks
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

tripping mechanism unknown
 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
MDMA
NH
CH 3
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
Cognitive Effects

memory loss
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 it’s not
always X or may have other drugs
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
MDMA & MDA neurotoxicity
5-HT immunoreactive fibers in rat parietal cortex
PCA
Normal
MDA
9.9
Squirrel
monkeys 18
mo post-trtmt
Control
5-HT immunoreactivity
MDMA
McCann et al.
(1997)
Neocortex
Hippocampus
Caudate
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.
Myristin and Elemicin
 Found in nutmeg and mace
 Structurally similar to mescaline
 Significant nausea and vomiting
 The sick usually limit use
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
(euphoria)
 Induces amnesia and true psychosis

Hallucinations, paranoia, agitation, dissociation
 Higher doses lead to stupor, coma
seizures, death
 A perfect example of a Schedule I drug
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
Subjective Effects of PCP/Ketamine
 Sensations of light coming through the body
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 one’s 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
 Like PCP and K at 20-30 X OTC dose
 Coricidin –Bad news
Cholinergic
Hallucinogens
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
Found in – Atropa
belladonna, Datura
Stramonium, Henbane
Acetylcholine
receptor (muscarinic)
antagonists


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
Used in the treatment
of motion sickness & to
dilate pupils during
eye-exams.
Atropine & Scopolamine

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
Opioid Hallucinogen - Salvinorin A