Drugs of abuse: TCH and marijuana Flashcards
THC through the years?
1920s portrayed as “evil drug” - laws passed banning it use
1930s looked on as a narcotic
1940s public convinced it was a “killer drug”
When was Cannabis legal in Canada? what are the three primary goals of cannabis laws?
Replaced by the cannabis act in June 2018 and legalized recreational use of cannabis on Oct 17th 2018
Goals: legalize, regulate, restrict sale of rec cannabis
What are the active compounds in marijuana?
THC (delta-9-tetrahydrocannabinol) - isolated as the active ingredient
cannabinol
cannabidiol
What are the three parts of marijuana?
Hashish: dried portions of the female flower (high potency, 10-20%)
Ganja: dried tops of female flower (medium potency, 5-8%)
Marijuana: dried remainder of the plant (low potency, 2-5%; improved growing, 30%)
What is the mechanism of THC? (receptors/location, activation causes…)
1990s - THC receptors isolated (CB1 and CB2) G protein-coupled receptor - inhibits adenylate cyclase - binds thc - binds other cannabinoids Found on presynaptic nerve terminal
Activation causes
- inhibition of calcium entry
- facilitates potassium channels
Inhibits release of other NTs (presynaptic GABA release)
What is anandamide? how does it compare to THC
Endogenous cannabinoid receptor
Weaker agonist than THC
Both are partial agonists - activates 50% of available receptors (THC activates 20%)
Where are cannabinoid receptors found - in these areas, what functions are impacted?
Found throughout the brain
- Basal ganglia and cerebellum (movement and posture)
- Frontal cortex (psychoactive effects - senses/time)
- Hippocampus (memory/memory stages)
Also, activates dopamine reward pathway (this is y it can be a drug of abuse)
How much THC is present in a joint? how much is available in smoke, and how much is absorbed into bloodstream?
75mg of THC present
25mg available in smoke
5-10mg absorbed into bloodstream
How is THC taken orally, what unique metabolite is produced?
Slower onset - first pass metabolism
only 10-29% dose reaches bloodstream
Produces active metabolite with a prolonged half-life (11 hydroxy-delta-9-THC) 4-6hrs
What are the pharmacokinetics of THC?
High is achieved quickly, effects last between 2-3 hrs
Readily passes through BBB, placental barrier
Metabolism of active metabolite produces inactive metabolite (carboxy-THC) - half life of 20-60 hrs, ideal biomarker
What are the pharmacological effects of THC? (think physical and mental effects)
Analgesic properties - helps with pain Decreases body temperature Calms aggressive behavior Temporal distortions Memory impairments Increased appetite/weight gain Acute memory impairments are paired with decreased blood flow (to hippoc) Dose-dependent loses in memory, IQ Heavy-users show parallel substance abuse
What are the two mechanisms of dependence for THC?
Down-regulation of cannabinoid R Receptor internalization (minor)
What are the symptoms of marijuana withdrawal syndrome?
Depressed mood, insomnia, lower food intake, irritability
What are the therapeutic uses of THC? What can be used to help treat marijuana addiction?
Dronabinol (marinol) used as an
- appetite simulant for AIDS patients
- Antinauseant for against (chemo)
- reduce intraocular pressure
Cannabinoid antagonist
- provides a dose dependent blockade of marijuana induced intoxication
- Assist in marijuana abstinence, enhancement of learning and memory
- Assist in controlling obesity (rimonabant - acomplia)
What are psychedelics?
Class of drug which causes hallucinations and out-of-body experiences (Greek for mind-manifesting)
Both naturally and synthetically produced - religious and recreational
Heightened sensory awareness
What are the five classifications of psychedelics?
Anticholinergic - scopolamine
Catecholamine-like - mescaline, ecstasy
Serotonin-like - LSD
Glutaminergic NMDAR antagonist - ketamine
Opioid Kappa receptor agonist - salvinorin A
What are the properties of anticholinergics (scopolamine)?
AChR antagonist
Binds to receptors, but not intrinsic activity
Found in the plant atropa belladonna (beautiful woman - ladies used to put this in their eyes to widen their pupils)
Important source of atropine - reverses cholinesterase inhibitors
- cholinesterase breaks down ACH into byproducts, this can be prevented by cholinesterase inhibitors
- atropine prevents cholinesterase inhibitors
What are the pharmacological effects of scopolamine? at low doses, at high doses?
Acts on PNS
Competitive antagonist at muscarinic R - fights for binding
Anticholinergic syndrome
- dry mouth, reduced sweating, dry skin, increased body temp, tachycardia
Low doses: drowsiness, profound amnesia, mental confusion, absence of REM
High doses: delirium, coma, respiratory depression
What are catecholamine psychedelics?
Structurally similar to NE, DA, amphetamines (have amphetamine like properties)
Includes: MDMA, mescaline, myristin (nutmeg), elemicin
Interacts with DA receptors
Psychedelic actions via 5-HT2a receptor
What are catecholamine-like psychedelics? (mescaline)
What are the pharmacological effects?
Found in peyote cactus (mescal button)
Can be chewed or soaked to make drink (used for religious purposes)
Agonist of 5-HT2a receptor Peak plasma concentration in 1-2hrs Produces an acute psychotomimetic state Targets the visual system Effects persist for up to 10hrs
What is ecstasy? and what are the symptoms during the period of activity?
Structurally similar to mescaline but more potent and toxic
Psychedelic effects are dose-dependent
Induces serotonergic neurotoxicity
Releaser and/or reuptake inhibitor or monoamines
Used recreationally or as an entheogen (induced non-natural spiritual state)
Symptoms
- hyperthermia (overheating), tachycardia, convulsions, kidney failure, cardiac arrhythmia, death, fatal syndrome
Malignant hypothermia (really cold and die)
What are serotonin-like psychedelics (lsd - stands for?)?
What brain areas does lsd activate? what are the symptoms of a bad trip?
Lysergic acid diethylamide - Found in ipomoea purpureal plant seeds
Agonistic action at the 5-ht2a receptor
LSD activates - medial prefrontal cortex - anterior cingulated cortex Symptoms of a bad trip (low-toxicity though) - alteration in perception - temporal changes - visual alteration - euphoric mood
What disorder can result from the use of lsd?
HPPD - hallucinogen persisting perception disorder
- flashback of visual experience after drug action has passed
Symptoms
- long-term
- Recurrent
- Unpleasant dysphoric affect
What are the phases of LSD-induced psychedelic experience?
Somatic phase: CNS stimulation and autonomic changes
Sensory (perceptual) phase: sensory distortions and pseudo hallucinations
Psychic phase: maximum drug effect, “bad trip”
What is glutaminergic NMDAR antagonists?
What are is the mechanisms of these drugs?
Structurally unrelated to other psychedelics (include phencyclidine, and ketamine)
Initially used in anesthesia (effects are not on 5HT, ACh, DA
Can produce schizophrenia like symptoms
Mechanism
- noncompetetive antagonist of NMDAR
- ketamine blocks by: blockade of open channel via sit within R, reduction in the frequency of opening by binding to site on th outside of R
- dissociated individuals from their environment
What are the pharmacokinetics of glutaminergic NMDAR? what state is induced?
Mechanism
- noncompetetive antagonist of NMDAR
- ketamine blocks by: blockade of open channel via sit within R, reduction in the frequency of opening by binding to site on th outside of R
- dissociated individuals from their environment
Induces a psychotic state: Rigid, unable to speak, appear very drunk, amnesia, coma/stupor (at high doses)
