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Psychedelics

Psychedelics CHAPTER 12

CHAPTER 12

 

Psychedelic/Hallucinogens

Psychedelic/Hallucinogens  Called by many different names  Psychotogens  Psychotomimetics  Psychedelics  Primary effect
 
  • 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

 
Different Types of Psychedelics  Serotonergic  Cholinergic  LSD  Muscarine  Psilocybin/Psilocin  Scopolamine
  • Serotonergic

 
  • Cholinergic

   
  • LSD

  • Muscarine

  • Psilocybin/Psilocin

  • Scopolamine

  • DMT - Ayahuaca

  • Bufotenine

  • Glutamatergic

  • Ololiuqui

  • PCP

  • Catecholamine-like

  • Ketamine

  • Mescaline

  • Dextromethorphan

  • Opioid

  • MDMA (ecstasy)

    • MDA

  • MDE

  • Salvinorin A

  • DOM

 
  • Myristin and Elemicin

 
Serotonergic Psychdelics

Serotonergic

Psychdelics

 
LYSERGIC ACID DIETHYLAMIDE (LSD)  Lysergic acid – Derived from ergot alkaloids  Ergot is a
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

LSD in the USA Came to U.S. in 1950s in two ways: • Clinical usage: Supplied
 
 

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

LSD in the USA  1960s - popular use advocates  East Coast: Timothy Leary (clinical
 

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

LSD in the USA  Spread through country with huge publicity until peak 1968 to 1972
 
  • 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

LSD & Neurotransmission
  • Binds to 5-HT2 A 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
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

Effects of LSD

High Doses

 
   
  • progression through mental and

 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 LSD Effects of drug come on in about 30 min  first signs are
 

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

Effects of LSD  space and time disorders  added depth with loss of perspective -
 
  • 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 
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

LSD & Bad Trips  Psychological impact - traumatizing, imagery dark, insights appalling  Usually occur
 
  • 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

LSD & Flashbacks Spontaneous recurrence of trip after period of normalcy  can occur after long
 

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
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-HT2 A agonist
Same basic effects as LSD
Mushrooms occasionally
toxic
 

DMT

DMT  Dimethyltriptamine  5-HT2A agonist  Alkaloid  Often smoked  Main ingredient in Ayahuasca
 

Dimethyltriptamine

  • 5-HT2A agonist

  • Alkaloid

  • Often smoked

  • Main ingredient in Ayahuasca

  • Same effects as LSD

 
 

Bufotenine

Bufotenine
 

Dimethyl-serotonin

 
  • A product of abnormal

 A product of abnormal

serotonin breakdown

  • Like LSD and others

  • Can occur in urine of

people with psychiatric

disorders

  • Psychosis

  • Paranoia

  • Depression

 

Ololiuqui

Ololiuqui  Substance found in morning glory seeds  Similar to LSD  Significant nausea, vomiting
 
  • Substance found in morning glory seeds

  • Similar to LSD

  • Significant nausea, vomiting and cramping

 

Tolerance/Dependence

Tolerance/Dependence  Not significant producers of tolerance or dependence  No withdrawal either  People and
 
  • 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

Catecholamine-like

Psychedelics

 
Mescaline  Active drug in peyote  Structurally similar to NE  However, most of the
Mescaline
Active drug in peyote
Structurally similar to NE
However, most of the
effect is mediated by our
friend, the 5-HT2 A agonist
action
Legal for members of the
Native American Church
Ecstasy  MDMA (methylene-dioxy-methamphetamine)  Synthesized in 1912  Structurally related to amphetamines  Sympathomimetic 
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
Pharmacodynamics
Monoamine neurotransmission
increase synaptic DA and 5-HT
blocks 5-HT transporter
enters neuron and causes release of 5-HT
 

Ecstasy Effects

Ecstasy Effects  Stimulant effects typically noted shortly after ingestion  increased heart rate  increased
 

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
Subjective Effects
euphoria
increased
physical and
emotional
energy
heightened
sensual
awareness
subjective
feeling of
increased
closeness or
enhanced
communication
Cognitive Effects
Ecstasy Effects
memory loss

X Tox

X Tox  Malignant hyperthermia and dehydration  Idiopathic toxic response (not common but nasty) 
 
  • 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

X Tox  Potent neurotoxin  1-2 times street dose  depletes forebrain 5-HT (not DA)
 
  • 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
MDMA & MDA neurotoxicity
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 immuno- reactivity

Neocortex

Hippocampus

Caudate

MDMA

McCann et al.

(1997)

What is PMA?  Paramethoxy-amphetamine  "Death" "Mitsubishi Double Stack" "Killer" "Red Mitsubishi"  Substitute for
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

Designer Psychedelics  DOM, MDA, DMA, MDE, TMA, AMT, 5MeO-DIPT  All structurally related to mescaline
 
  • 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

Myristin and Elemicin  Found in nutmeg and mace  Structurally similar to mescaline  Significant
 
  • Found in nutmeg and mace

  • Structurally similar to mescaline

  • Significant nausea and vomiting

  • The sick usually limit use

 

Glutamatergic

Psychedelics

Psychedelics
 

DISSOCIATIVE

ANESTHETICS

 
Phencyclidine  PCP  NMDA receptor antagonist  Blocks the function of glutamate  Used as
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
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

Subjective Effects of PCP/Ketamine  Sensations of light coming through the body and/or colorful visions 
  • 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

Dextromethorphan  Active ingredient in most OTC cough medicine  NMDA receptor blockade at high doses
 
  • 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

Cholinergic

Hallucinogens

 

Muscarine/Muscimol

 
Muscarine/Muscimol  Found in mushrooms (Amanita Muscaria)  Muscimol is a GABA agonist  Trance-like, dreamy
 
  • Found in mushrooms

 

(Amanita Muscaria)

  • Muscimol is a GABA A 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
Found in – Atropa
belladonna, Datura
Stramonium, Henbane
Acetylcholine
receptor (muscarinic)
antagonists
Dissociatives that
induces delirium ,
hallucinations, and
amnesia
Classic 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.
Atropine & Scopolamine
 Comes from a plant in the mint family  Salvia Divinorum  Affinity for kappa
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
Opioid Hallucinogen - Salvinorin A
It’s still legal, but not
likely for long