Psychedelics

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Psychedelics

• CHAPTER 12

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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 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

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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 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

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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
  effects
• Low 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 experimenters previous behavior
• warm and supportive or suspicious and
  nonsupportive

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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

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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

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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

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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

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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

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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 seeds
• Similar to LSD
• Significant nausea, vomiting and cramping

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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

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Catecholamine-likePsychedelics
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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

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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

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Pharmacodynamics

• 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 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 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 neurotoxicity
5-HT immunoreactive fibers in rat parietal cortex
MDA
PCA
Normal
9.9
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Squirrel monkeys 18 mo post-trtmt
Control
5-HT immuno- reactivity
Caudate
Hippocampus
Neocortex
MDMA
McCann et al. (1997)
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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)

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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 mace
• Structurally similar to mescaline
• Significant nausea and vomiting
• The sick usually limit use

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GlutamatergicPsychedelics

• Dissociative Anesthetics

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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

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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

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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 ones body
• Visions of spiritual or supernatural beings
• Emotions 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 doses
• Mostly teenage males abuse it
• Like PCP and K at 20-30 X OTC dose
• Coricidin 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) 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.

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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
• Its still legal, but not likely for long