Psychedelic/Hallucinogens - Chpt 12

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Psychedelic/Hallucinogens- Chpt 12
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Hallucinogen Class/structure

• Cholinergic
• Muscarine
• Scopolamine
• Glutamatergic
• PCP
• Ketamine
• Dextromethorphan
• Opioid
• Salvinorin A (Salvia)

• Serotonergic
• LSD-25
• Psilocybin/Psilocin
• DMT - Ayahuasca
• Bufotenine (ibogaine)
• Ololiuqui (oh-low-lee-oo-kee)
• Morning glory seeds
• Mescaline (peyote)
• MDMA (ecstasy)
• MDA
• MDE
• DOM
• Myristin and Elemicin (nutmeg and mace)

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Effects of Serotonergic Hallucinogens

• Sympathomimetic
• Visual hallucinations
• Can influence perception of time, space events
• Altered consciousness
• Intense emotional experiences
• May produce Expansive or Restrictive Effects

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LYSERGIC ACID DIETHYLAMIDE (LSD)-a brief history

• Lysergic acid Derived from ergot alkaloids
• Ergot is a poisonous fungus that infects rye
  other grains grasses (Saint Anthony's Fire)
• Albert Hoffman 1938 - synthesized 25 in series
  of new molecules related to ergot alkaloid
  chemistry
• 1943 - returned to 25 making new batch
  absorbed some through skin

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Albert Hofmann-Discovered LSD-1943
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LSD in the USA

• 1950s
• Clinical usage Psychiatric training
• 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)

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Timothy Leary and Ken Kesey
Timothy Leary LSD guru of the 1960s-Turn on,
tune in and drop out
Advocate..Author-One flew over the Cuckoos nest
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LSD in the USA

• Spread through country with huge publicity until
  peak 1968 to 1972
• Schedule I in 1968
• Early 1990s - LSD came back

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Doses of Acid
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Visual Hallucinations

• Enhanced color perception-increased
  vividness/contrast emotional significance
• Flickering of the visual field-Altered Perception
  of motion
• Synesthesia- mixing of sensory qualities, Sounds
  can take on visual forms music may take on
  enhanced meaning or intensity
• Form constants-

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FORM CONSTANTS?

• Visual hallucinations that are commonly
  experienced
• 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

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Form Constants

• Lattice Pattern
• Tunnel/Vortex
• Spiral Explosion

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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

• Effects of drug come on in about 30 min (oral or
  mucousal)
• 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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HIGH dose Effects of LSD-Tripping

• 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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Tripping can be divided into four stages

1. Onset 30 min to 1 hour visual effects begin
2. Plateau next 2 hours sense of time slows, visual effects intensify
3. Peak after about 3 hrs and lasts 2-3 hours Each trip unique, highly dependent upon setting and personal expectations In another world, synesthesia
4. Come down 2 hours May take up until next day to feel normal again
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LSD PARTY vs. PEAK EXPERIENCES?

• Many people have used hallucinogens for
  social/communion/party purposes..however,many
  claim that these substances can produce profound
  experiences
• The Peak experience-feelings of unity,
  transcendence of time and space, strong positive
  affect, sense of reality and objectivity of the
  experience, sacredness, ineffability,
  Paradoxicality, transiency, and subsequent
  positive changes in attitudes and behavior.

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Hallucinogenic drug problems

• Bad trips anxiety/panic-
• - traumatizing, dark imagery, insights appalling
• Usually occur in novice users, feel out of
  control
• Generally negative set and setting are key
  contributing factors

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Adverse reactions to Serotonergic Hallucinogens?

• Can lead to suicide or prolonged psychotic
  reaction

• Can usually be talked down from a bad trip
• Other psychological effects sometimes
  experienced- depersonalization, anxious or
  fearful state,
• disruption of logical thought.

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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
• mechanism unknown
• can be brought on by other drugs or setting
• most commonly reported in low light situations
• not intrinsically dangerous and usually goes away

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Experimental receptor study

• Vollenweider (1998)
• Administration of antagonists
• Risperidone, Ketanserin (5-HT2A D2 DA)
• Decreased drug-induced visual illusions/hallucinat
  ions
• Haloperidol (Only D2 DA Not 5-HT2A)
• Completely failed to prevent hallucinogenic
  effects
• 5-HT2A is key mediator of hallucinogenic action
• Tolerance acquired via down-regulation of
  receptors
• Very rapid tolerance nearly complete in 4 days

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LSD Neurotransmission

• Binds to 5-HT2A receptors
• agonist effect
• Increases amount of sensory information getting
  to cortex through excitation of the Locus
  Coereleus

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TOLERANCE AND DEPENDENCE?

• Very rapid tolerance (Tachyphylaxis) nearly
  complete in 4 days
• Tolerance acquired via down-regulation of
  receptors
• No withdrawal syndrome
• No indication from any study of either
  psychological or physical dependence
• animals do not self-administer

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Adverse Effects Myth Reality

• Birth defects/chromosome damage
• Myth!
• Acute Psychotic Reactions (Bad Trips)
• Fairly Common
• Use 7 times and legally insane
• Myth!
• Residual Psychosis
• Rare not certainly related to LSD

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Adverse Effects Myth Reality

• Flashbacks
• Fairly common among heavy users
• For some people, flashbacks are constant
• Rare, but true hallucinogen persisting
  perception disorder
• Stored in spine?
• MythCauses of flashbacks unclear
• The largest Problem relates to
  decisions/behaviors while intoxicated
• Accidents, Suicide, Aggression/violence

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Psilocybe Mushrooms
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Psilocybe Mushrooms
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Psilocybin/Psilocin

• Psilocybin
• magic mushrooms or shrooms
• Fungi that manufactured alkaloids with
  hallucinogenic properties
• Oral consumption
• Eaten raw, boiled in water to make tea, or cooked
  with other foods to cover its bitter flavor
• Major ingredients
• Psilocybin metabolized to psilocin.

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Psilocybin/Psilocin

• Last about 6-10 hours
• Less potent than LSD-25
• 5-HT2A agonist
• Same basic effects as LSD
• Mushrooms occasionally toxic

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Yage/AyahuascaDMT

• employed for divinatory and healing purposes by
  peoples of the Amazonian regions of S.A., is
  known by a number of different names.
• Supreme Court has ruled in favor of religious use
  of hoasca (Ayahuasca) tea (DMT) as of 2009)

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DMT, 5-MeOA-DMT

• DMT (dimethyltryptamine)
• Derived from plants (Virola Shrub)in South
  America
• Devoid of psychoactivity when taken orally
• Except with ayahauasca, vine of the soul
• In solid powder form and smoked.
• Onset of Effects is Rapid (45 sec.) but are short
  lasting (5-15 min.)
• 5-MeO-DMT (5-methoxy-dimethyltryptamine)
• Foxy Methoxy
• Oral active synthetic DMT analog is considerably
  more potent

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Ololiuqui

• Substance found in morning glory seeds
• Similar to LSD
• Significant nausea, vomiting and cramping

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Mescaline

• From the Peyote cactus
• Mescal (peyote) button
• Native to SW United States and N Mexico
• Administration
• Chewed raw or cooked and eaten
• Pure powder form

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Mescaline

• 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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Peyote cactus-mescaline
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Religious Use of Hallucinogens

• Right to peyote ritual is protected for Native
  Americans

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Peyote cactus-mescaline
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Pharmacology of selected Hallucinogenic Drugs

• Pyschedelic effects
• begin within 30-90
• min (oral)
• LSD or mescaline trip lasts for 6-12 hrs
  Psilocybin dissipates sooner
• DMT effects user within seconds and dissipates in
  an hour or less

• Depicts the typical dose range taken by
  recreational users (psilocybin is most potent and
  mescaline is the least)

Drug Route of Admin Typical Dose Range
LSD Oral .05-.10 mg
Psilocybin Oral 10-20 mg
Mescaline Oral 200-500 mg
DMT Smoking 20-50 mg