midterm #3 Flashcards
hallucinogens:
- psychedelic
- entheogenic
- psychotomimetic
- psycholytic
psychedelic: manifesting the mind, mind-expanding
entheogenic: religious or spiritual
psychotomimetic: appearance of psychosis
psycholytic: mind-dissolving
hallucinogens operationalization
“chemical inducing perceptions of something that doesn’t exist”
problem:
- more distort reality, therefore illusionogenic
- many things can induce hallucinations at toxic levels
- hard to keep apart from delirium related to toxicity
psychedelics: reducing valve
dissociatives: numbing, depersonalisation, derealisation
deliriants: confusion
psychedelics:
- reducing valve: feeling that the brain’s filter has been removed
dissociatives:
- numbing: analgesia, amnesia, anaesthesia
- depersonalisation: dream-like or unreal perception
- derealisation: detached or removed from body
deliriants:
- confusion, inability to control behaviour
hallucinogen structural similarities:
- serotonin
- norepinephrine
- no similarity
serotonin: LSD, psilocybin, DMT
norepinephrine: ecstacy, mescaline
no similarity with anything: PCP, Ketamine, Salvia
general hallucinogen process (2 stages)
stage 1: visual images
- geometric patterns
- closed-eye, then open-eye
stage 2: meaningful images
- people/animals/places
- can change rapidly
- recognized as not being real
LSD: 4 general points
- derived from ergoline in ergot fungus
- highly volatile (water-soluble, oxidizes, photosensitive)
- highly potent (1 dose = 50-150µg)
- sympathomimetic
LSD process:
- onset
- plateau (4 effects)
- peak (3 effects)
onset
- 30-60min
- release of tension
plateau
- 30min-2h)
- closed-eye visuals
- synaesthesia
- multilevel reality perception (insula)
- distorted visual input (locus coeruleus/visual cortex)
peak
- 3-5h
- emotion/panic swings
- timelessness
- ego disintegration (PFC, glutamate)
LSD neuropharmacology
- visual cortex
- locus coeruleus
- PFC
=> agonism
visual cortex:
- 5-HT1A, 5-HT2A receptors
- decreased activity
locus coeruleus:
- metabotropic 5-HT2A receptors on glutamatergic and GABAergic neurons
- lower threshold for incoming sensory signals
- decrease in noise
PFC:
- induced glutamate release
- PFC tries to frantically interpret perceptions
LSD: tolerance
- acute tachyphylaxis
- 3-7 days to subside
- cross-tolerance to other tryptamines (psilocybin and DMT)
LSD: toxicity
- myadrasis: chronic pupil dilation
- serotonin syndrome
- hallucinogen persisting perceptopn disorder (HPPD)
serotonin syndrome
accumulation of excess serotonin in CNS
- symptoms:
1) cognitive: hypomania, confusion, hallucinations
2) autonomic: sweating, hypothermia, vasocontrition, tachycardia
3) somatic: tremor, twitchiness
psilocybin: qualitative differences in dosage
low: social, warm, down-to-earth feelings
high: resemble LSD, but more prone to bad trips
psilocybin: neuropharmacology
- PFC
- basal ganglia
=> partial agonism
PFC:
- 5-HT2A
- distort time perception, timing, feel for rhythm
- slowing down
- inability to coordinate with tempo <2-2.5s
basal ganglia:
- dopamine
- problem: no affinity for D2 receptor
- may be involved in timed performance and movement
psilocybin: tolerance
- acute tolerance
- 4-7 days to subside
- cross-tolerance to LSD and phenethylamines
- potentiation when used with MAO-inhibitors
psilocybin: therapeutic uses
reduction of 5-TH2A receptors
- alleviation of OCD symptoms for 2 months
- anxiolytic
psilocybin: Good Friday Experiment
- increase in spiritual meaning
- positive changes in attitude/behaviour
- effects for weeks/months after treatment
ibotenic acid: 4 points (origin, functionally, structurally, metabolite)
- from Muscaria mushrooms
- functionally similar to glutamate (non-selective glutamate agonist)
- structurally similar to acetylcholine
- metabolite muscimol also psychoactive
ibotenic acid:
- danger
- how to prevent
- excitotoxicity causes subjective effects and brain damage
- dextromorphan (cough syrup) can protect from excitotoxicity by blocking receptors
PCP:
- embalming fluid
- Angel Dust
- killer joints
embalming fluid: yellowish oil to dip cigarettes or joints in
Angel Dust: crystals ground and sprinkled on a mix of spices, then smoked
killer joints: mix with weed
PCP and Ketamine: neuropharmacology
- low dose
- high dose
- any dose
low dose:
- serotonin and dopamine
- reuptake inhibition
- partial agonist
high dose:
- acetylcholine
- antagonism (muscle contractions, memory deficits, arousal, analgesia)
any dose:
- glutamate NMDA antagonist
- disrupts LTP
PCP and Ketamine: dose-dependent effects
- low dose
- moderate dose
- high dose
low dose:
- drunk-like, numbing, anaesthetic
moderate dose:
- disconnect from surroundings
- body dissociation
high dose:
- sympathomimetic
- hallucinations
- K-hole
PCP and Ketamine:
- high-dose negative consequences
- long-term use negative effects
- lingering schizophrenic-like symptoms for up to 2 months
- supports glutamate hypothesis of schizophrenia
- chronic glutamate antagonism leads to MDD-like symptoms and deficits in memory, speech, logic
PCP and Ketamine: 2 weird effects
- superhuman strength and invulnerability feeling (due to analgesia)
- megalomania: delusional fantasies of omnipotence and god-like power
PCP and Ketamine: tolerance
- accrued tolerance (can be prevented by separating administrations by days)
PCP and Ketamine: dependence
- physical: in PCP dopaminergic centres affected, Ketamine no physical dependence
- psychological: craving related to euphoria
Ketamine Psychedelic Therapy: Morrough (2012) results
+ glucocorticoid theory explanation
treatment-resistant MDD: one dose alleviation of symptoms within hours, lasting more than a week
glucocorticoid theory: glutamate NMDA inhibition allows for glutamate to bind elsewhere and facilitate BDNF
structure-activity relationship
relationship between a chemical’s structure and its biological activity
debate: DMT endemic to human body (just look at these)
- present in other mammals’ pineal glands
- enzyme found in human body but not brain
- DMT analogue synthesis in human cancer cells in lab setting
- facilitation of immune responses on endemic receptors after taking DMT
DMT: neuropharmacology
- 3 stages
- what neurotransmitter
- where
- most important characteristics
=> agonist (SNDRA)
dopamine: o1 related to sensations
(1)
- insula
- auditory hallucinations
(2)
- amygdala
- waiting room, animated suspension
serotonin: 5-HT2A, 5-HT2C (3) - PFC - DMT Hyperspace - Machine elves
DMT: tolerance
- debate whether none or acute
- perhaps short time activating receptors makes it skip the whole tolerance thing
- cross tolerance: from LSD to DMT, but not from DMT to LSD
DMT: dependence
- no physical dependence
- psychological dependene debated
- religious connotation may protect from dependence
DMT: insight-oriented psychotherapy
- for PTSD, anxiety, phobia
- for depression, addiction
for PTSD, anxiety, phobia:
- rationalization, remove emotional component
for depression, addiction:
- therapeutic insight about fears, beliefs, desires
DMT therapeutic potential (3)
- elicits traumatic memories
- offers multiplicity of perspectives
- promotes LTP for connections underlying new perspectives
phytocannabinoids: 4 general points
- metabolites of THC are active
- metabolites exert unique effects interacting with THC
- analogues exert unique effects e.g. 11-hydroxy-THC
- highly lipid-soluble
synthetic cannabinoid alternatives
- K2, Spice
- stem from research on receptors
- aminoalkylindoles -> target serotonin system
- stimulant and hallucinogenic properties b/c contamination with other chemicals
cannabis potency: hash vs marijuana
+ 3 problems
hash more potent than marijuana
problems:
1) dosages vary and effects are dose-dependent (2-6x more THC in hash than MJ)
2) modern strains much higher concentration
3) skewed comparability of research from today and earlier
cannabis: smoke
- % absorbed
- contact high
smoking:
- 50% of THc is released into smoke
- lungs absorb about 20% of that
contact high:
- no hard evidence, only if strong hotbox
cannabis: ingestion
- % absorbed
- how long stays
- first.pass metabolism deactivates 50% of THC
- 4-5 days of use lead to ca. 7 days of long-term pharmacological action
- metabolites still psychoactive, but less than in smoking
cannabis: neuropharmacology
=> partial agonism
metabotropic receptors CB1 and CB2
- CB1: motor inhibition, ood, memory, appetite, pain
- reduces presynaptic firing rate
- CB2: immuno-facilitative (glial cells)
THC: motor activity/coordination and RT effects (low and high dose)
low dose: increase motor activity, decrease coordination
high dose: decrease motor activity, increase RT
compensate for disrupted vigilance by driving more slowly though
THC: amotivational syndrome
-> persistent lack of motivation to engage in productive activities
- no evidence for reward-based strategies (when tasks provide rewards)
- actually: cannabis makes effortful tasks seem less effortful
THC: short-term memory and attention impairment (low and high dose)
low dose: memory deficits, no attention impairment
high dose: memory, attention, reasoning impairment
cannabis: developmental persistence
- for every 5 years of marijuana use, 1-word decrease in verbal memory of a 15-word list
- no other impairment in cognitive functions
=> weed associated with worse verbal memory
cannabis: decelerated time - associations (4)
- associated with stoned phase
- decreased blood flow to cerebellum
- temporal disintegration: no continuous temporal processing
- flight of ideas: spontaneous random thoughts, decreased cognitive threshold
THC: executive function impairment
- updating WM / shift / inhibiiton
- chronic users: impairment while abstinent
cannabis: gateway drug
- support for process, but not outcome
- problems:
- not all users progress to next drug (only 10-20%)
- users still use early drugs
cannabis: gateway drug vs correlated vulnerabilities
- drug use progression is due to user’s characteristics, not due to drug properties
- individual propensity for drug use defines process
cannabis: long-term verbal fluency and divided attention
- compared to non-users, differences in
- verbal fluency
- divided attention (persevering on previous rules)
cannabis: intellectual impairment
- intellectual impairment of heavy users reversed with abstinence
cannabis onset <17
- severe verbal and IQ deficits
- 40% higher chance for schizophrenia, GAD, depression
cannabis tolerance and withdrawal
- downregulation with prolonged use
- withdrawals (irritability, insomnia, hostility) dissipate after 6 weeks
Cannanbis Hyperemesis Syndrome
+ supportive features
nausea, vomiting, colicky abdominal pain as result of weekly cannabis use following a history of cannabis use for years
(-> physiological, outcome, no allergy)
supportive features:
- taking compulsive hot showers
- colicky abdominal pain (possibly due to toxic buildup)
THC: toxicity
- in plant, low toxicity, no ODs reported
- dronabinol, toxic effects (e.g. postural hypotension, slurred speech); pure THC
THC: drug discrimination (vs placebo, vs other drugs)
THC vs placebo:
- 100% accuracy
THC vs other drugs:
- low dose: 100% accuracy
- high dose: 85% accuracy
=> THC has unique subjective effects
cannabis: different cannabinoids have different effects
- THC users: higher incidence of hallucinations/delusions
- no difference non-users and THC+CBD users
- CBD users: anxiety reducing
heroin, morphine: intake and effects (3)
oral: mood alleviation, cough suppression
inhalation: euphoria
intravenous: euphoria, pain relief
heroin morphine injection: 3 stages
stage 1:
- 0-2min
- rush
- tingling lower abdominal feeling, orgasm
stage 2:
- 2-3h
- on the nod: tranquil drowsiness
stage 3:
- 4+h
- withdrawal
fentanyl (4)
- designed
- 100x more potent than morphine
- intake: oral, transdermal, insufflation, but: fast absorption has high potential for respiratory depression
- less nausea and itching than morphine
desomorphine
- synthesized from codeine
- 8x more potent than morphine
- increased respiratory depression and cardiac arrest
- high toxicity from impurity and contamination
opioids: neuropharmacology
=> agonism
1) cleavage enzyme: cuts free-floating inactive peptides into active metabolites
2) G-protein metabotropic action: returns neurons to resting potential sooner
opioids: agonism pure, partial, mixed
pure: pain relief
partial: pain relief w/o respiratory effects
mixed (agonist-antagonist): treating opioid addiction - binds to receptors without activating them, but blocks other chemicals from binding
opioids:
- agonistic mechanism
- inhibitory mechanism
agonistic mechanism:
- GABA receptor antagonist
- VTA: stops inhibition of dopamine release
- NA: activates µ-opioid receptors that inhibit GABA neurons
- > dopamine release in VTA
inhibitory mechanism:
- nociception
- interferes with pain signalling from periphery to spinal cord and spinal cord to thalamus
- > blunting of pain
opioids: tolerance
- dose-dependent
- accrued and relational
- tolerance selective to analgesia, euphoria, respiratory depression
opioids: withdrawal
- 5-10 days
- 90% relapse after withdrawal related with environment
- craving instensifies at 1-3 days
- flu-like symptoms
opioids: detoxification
rapid (10 days):
- naloxone
- inverse agonist, binds and induces opposite response
- increased withdrawal symptoms, decreased duration
short- (30 days) or long-term (180 days):
- methadone
- prevents withdrawal, weak/no euphoria
- long-lasting effects
DMT: The Hoasca Project results
- ayahuasca-sect adolescents 7x lower incidence of anxiety, body dysmorphism, attention problems
- > religious context has protective effect
