Transcript Hallucinogens - People Server at UNCW

Psychedelic/Hallucinogens
- Chpt 12
Hallucinogen Class/structure
• 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)
• Cholinergic
– Muscarine
– Scopolamine
• Glutamatergic
– PCP
– Ketamine
– Dextromethorphan
• Opioid
– Salvinorin A (Salvia)
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”
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
Albert Hofmann-Discovered LSD1943
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
LSD in the USA
• 1960s - popular use advocates
– East Coast: Timothy Leary (clinical
psychologist at Harvard)
– West Coast: Ken Kesey (noted author)
Timothy Leary and Ken Kesey
Timothy Leary LSD guru of the
1960’s-“Turn on, tune in and drop
out”
Advocate..Author-”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
• Early 1990s - LSD came back
Doses of Acid
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-
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
Form Constants
• Lattice Pattern
• Tunnel/Vortex
• Spiral Explosion
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 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
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
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
experimenter’s previous behavior
– warm and supportive or
suspicious and nonsupportive
“Tripping”
can be divided into four stages:
1. Onset – 30 min to visual effects begin
1 hour
2. Plateau – next 2
hours
sense of time slows, visual effects
intensify
3. Peak – after about Each trip unique, highly dependent
3 hrs and lasts 2-3
upon setting and personal
hours
expectations
“In another world”, synesthesia
4. Come down – 2
hours
May take up until next day to feel
normal again
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.
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
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 experienceddepersonalization, anxious or fearful state,
•disruption of logical thought.
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
Experimental receptor study
• Vollenweider (1998)
– Administration of antagonists
• Risperidone, Ketanserin (5-HT2A + D2 DA)
– Decreased drug-induced visual illusions/hallucinations
• 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
LSD & Neurotransmission
• Binds to 5-HT2A
receptors
– agonist effect
• Increases amount of
sensory information
getting to cortex through
excitation of the Locus
Coereleus
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
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
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?
– Myth—Causes of flashbacks unclear
The largest Problem relates to
decisions/behaviors while intoxicated
– Accidents, Suicide, Aggression/violence
Psilocybe Mushrooms
Psilocybe Mushrooms
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.
Psilocybin/Psilocin
•
•
•
•
•
Last about 6-10 hours
Less potent than LSD-25
5-HT2A agonist
Same basic effects as LSD
Mushrooms occasionally toxic
Yage’/Ayahuasca…DMT
• 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)
DMT, & 5MeOA-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
Ololiuqui
• Substance found in morning glory seeds
• Similar to LSD
• Significant nausea, vomiting and cramping
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
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
Peyote cactus-mescaline
Religious Use of Hallucinogens
• Right to peyote ritual is protected for Native
Americans
Peyote cactus-mescaline
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
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
 Depicts the typical dose range
taken by recreational users
(psilocybin is most potent and
mescaline is the least)