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Chapter 15: Hallucinogens - Coggle Diagram
Chapter 15: Hallucinogens
5 Criteria
main effect is on thought, perception, and mood
minimal intellectual or memory impairment
stupor or psychostimulation is NOT an integral part of drug action
Autonomic side effects are NOT disabling
little-no dependence liability
Tripping: produces unusual perceptual and cognitive distortions
novel, stimulating, spiritually uplifting
Mescaline
found in cactus
used by natives for religious and healing rituals
Psilocybin: "Magic mushrooms"
produce alkaloids with hallucinogenic properties
dried mushrooms eaten raw or cooked or made into tea (shrooming)
main compound is psilocybin --> converted to psilocin (psychoactive agent)
Aztec and Mayans: religious rituals are psilocybin mushrooms
TImothy Leary (Harvard)
concord prison experiment: psychedelics reduced recidivism from 60%. to 20%
LSD: fungal alkaloids from ergot
Hoffman: wanted to generate a new circulatory and respiratory stimulant (analeptic)
psychedelic properties not recognized until 1943
originally perceived as a psychomimetic
World's first acid trip: Hoffman accidentally got LSD droppings on his hands
restlessness, slight dizziness, hallucinations, dreamlike, kaleidoscopic play of colors, dilated pupils
Bicycle Day (4/19): Hoffman took too much LSD the 2nd time
Sandoz first market LSD for neurosis: uncovering repressed feelings (truth serum)
Therapeutic potential in psychotherapy
Nonmedical use: hippie culture in 1960s
very potent and orally active
single dose in crystalline form is barely visible
larger amounts are dissolved in water --> droplets containing single-dose units are applied to a sheet of paper ("blotter") and dried
paper is divided into individual square "tabs"
Ayahuasca (and DMT)
rapidly diffusing from aboriginal and mestizo society into mainstream culture
orally active tryptamine-based hallucinogen
prepared by boiling the bark or crushed stems of leaves
leaves contain substantial concentrations of DMT (structural analogue of 5HT and other tryptamine psychedelics)
Banisteriopsis contains high concentrations of beta-carbonile alkaloids
potent MAO inhibitors
protect DMT from degradation in liver and gut
Pharmacology of Hallucinogens
hallucinogens vary widely in potency: LSD - most potent, mescaline - least
psychedelic effects begin: 30-90 minutes after ingestion
LSD trip: 6-12hours
DMT (smoked): felt within seconds, peak over a few minutes, gone within an hour
only sympathetic effect: dilated pupil
Most hallucinogens have either a 5HT-like or catecholamine-like structure
5HT-like: LSD, psilocybin, psilocin, DMT, synthetic trymptamine
Phenetyhylamine hallucinogens: mescaline (structurally similar to NE and AMPH)
RECEPTORS
LSD binds with high affinity to at least 8 different 5HT receptor subtypes
phenylethylamines: also bind to some 5HT receptors
common subtypes: 5HT2A and 5HT2C (central role in producing hallucinations)
In humans, 5HT2A activation --> hallucinations
hallucinations are blocked by 5HT2A antagonists
Why does LSD produce long drug effects? LSD has extremely slow on and off rate at 5HT2B and 5HT2A receptors
CANNOT use animal models to study hallucinations
can't assess if an animal is experiencing a change of consciousness
can be trained in drug discrimination tasks to recognize the subjective effects of hallucinogens vs. saline
selective antagonists of 5HT2A receptors blocks drug discrimination
DON'T have high abuse potential. (Animals don't self admin for further effect): no withdrawal symptoms and NOT an effective reinforcer
In humans, dependence DOES occur in very small number of people
Most hallucinogens produce rapid tolerance with repeated use --> down-regulation of 5HT2A receptors in rats
Negative effects
"bad trip": acute anxiety or panic (can be severe)
flashbacks: reexperiencing the hallucinations after drug use has stopped
psychotic reactions if individual already has psychiatric disorder
Clinical Studies of Hallucinogenics
LSD
low dose LSD: decreases pain perception (analgesic)
LSD acutely impairs fear recognition and enhances emotional empathy and sociality: overcome anxiety/depression
LSD to treat Alzheimers and neurodegenerative diseases: antiinflammatory properties: treat neuroinflammation
Psilocybin
produces decreases in depression and anxiety with cancer patients (decrease in death anxiety)
treats tobacco addiction
Mushrooms are the safest drug you can take
Psychedelics promote structural and functional neural plasticity
Dissociative Anesthetics: PCP and Ketamine
PCP
doesn't cause respiratory depression
atypical response: catanoic-like state, motor rigidity, blurry vision and dizzy, hallucinations, severe agitation
angel dust, hog: powdered or pill (taken PO intranasally, injected, in cigarettes)
Ketamine: safer alternative to PCP (less potent, shorter acting)
Anesthetic for certain procedures
ADULTS lose all contact with environment, but eyes are open and muscle tone remains, confusion, agitation, hallucinations after medication wears off
CHILDREN DO NOT
used by veterinarians as sedative
street supply comes from medical or veterinary sources
K, special K, cat valium
injectable liquid that is converted to a powder --> smoked or snorted
half life: 2.5hrs
Pharmacology of PCP and Ketamine
Noncompetitive antagonists of NMDA receptors
binding site inside receptor's ion channel
blockade in cortex and hippocampus contributes to cognitive deficits in users
PCP effects: like schizophrenia (psychomimetic)
Subjective effects: feeling detached from body, floating sensation, numbness, dreamlike
Affective reactions: drowsiness and apathy, loneliness, negativism or hostility VS. euphoria and inebriation
cognitive disorganization: difficulty concentrating, distrumption in abstract thinking, halting speech
Ketamine subjective effects
doses in anesthetic range --> dissociated state with subjective effects (K hole)
can be spiritually uplifitng or terrifying
PCP and Ketamine: highly reinforcing and high abuse potential
both activate midbrain DA cell firing and stimulate DA release (esp. in PFC)
Repeated admin of high dose ketamine --> apoptotic cell death in developing brains of RATS and MONKEYS (super high dose, not in humans)
ketamine is a recommended anesthetic for pediatric procedures
Clinical and Basic Studies of Ketamine
rapid and potent antidepressant effects of ketamine in treatment-resistant depression
rapid (within hours) reduction in depression
subanesthetic doses
effects last weeks
plasma half-life: 2.5hrs
antidepressant effects emerge about 4hrs after IV admin
patients maintained on regimens of 1x every 2wks-2months
Neurobiology of ketamine
chronic stress causes excess extracellular glutamate --> dendritic retraction, reduced dendritic arborization, spine density
24hrs posttreatment --> subanesthetic dose of ketamine REVERSES chronic stress-induced structural deficits
rapid induction of BDNF
increased synaptogenesis and spine density
similar effects to traditional antidepressants
neuroadaptive state occurs much faster with ketamine
modeling schizophrenia
therapeutic dose produces transient cognitive dysfunction similar to schizo
too high of a dose (into anesthetic range) LOSES its antidepressant effects
Ketamine alleviates depression but IS NOT EUPHORIC
patients with comorbid anxiety are poor responders to SSRI but respond well to anxiety
Dextromethorphan
DM in Robitussin DM
antitussive agent: low doses supress cough reflex
high dose: noncompetitive antagonist of NMDA receptor
high dose: subjective effects similar to those of hallucinogens --> can be extracted from cough syrup and repackaged in pills