Cannabis Flashcards
what is cannabis?
genus of a flowering plant
what 2 bioactive compounds does cannabis contain that are most studied? (has more)
tetrahydrocannabinol (THC) and cannabidiol (CBD)
what is the primary psychoactive compound in cannabis?
THC
what are cannabinoids?
class of chemical compounds that act at cannabinoid receptors
t/f: cannabis contains few phytocannabinoids
false, contains hundreds of phytocannabinoids (∆9 THC and CBD most popular)
t/f: cannabis contains hundreds of non-cannabinoid substituents
true
what are terpenoids?
substances that give cannabis its characteristic smell
what have in vivo and in vitro studies of terpenoids found?
terpenoids have anti-inflammatory, anti-bacterial and anti-anxiety effects (no clinical trials)
what may explain difference btwn experiences of cannabis based on strains?
possible synergy btwn cannabis ingred. in diff strains (difficult for clinical use-hard to isolate effective compounds)
what is absorption/bioavailability?
fraction of an administered drug that reach effectors (plasma to CNS)
what ingred. does most pharmacokinetic info. on cannabis pertain to?
THC
what is the difference btwn bioavailability and peak plasma conc. for smoking vs ingesting THC?
smoking: 25% bioavail., peak conc in 6-10 min
ingesting: 6% bioavail., peak conc in 2-6 hours
t/f: it is easier to overdose on THC when it is smoked
false, easier to overdose when ingested as it has decr bioavail. and reaches peak plasma conc slower (may cause incr dose)
t/f: THC is highly lipophilic and is taken up in tissues w/ high blood flow
true (in heart, lungs, brain, and liver)
t/f: tissues w/ less blood flow don’t accumulate THC such as adipose tissue
false, adipose tissue can accumulate THC slowly and release it for days (chronic cannabis smokers)
which enzyme in the liver metabolizes THC?
cytochrome P450 2C9 (CYP2C9)
what is the active vs inactive metabolites for CYP2C9 degradation of THC?
active: 11-OH-THC
inactive: THC-COOH (excreted)
in 5 days, __-__% of THC is excreted, __% in feces and __% in urine
80-90% THC excreted, 65% in feces, 25% in urine
how long can THC be detected in urine after low vs chronic/daily dose?
low: 2-5 days
chronic/daily: weeks (accumulates in adipose tissue)
what kind of receptors are cannabinoid receptors?
Gi protein-coupled receptors (decr cAMP)
what are the 2 cannabinoid receptors?
CB1 and CB2
what does a decr in cAMP from cannabinoid binding to its receptor cause?
decr influx of Ca into firing neuron and decr NT release (decr synaptic transmission)
what is THC?
partial CB1 agonist
what is a theorized mechanism of action for cannabidiol (CBD)?
negative allosteric modulator at CB1 (blunt THC effects)
t/f: CB1 receptors are rarely found in the body
false, CB1 receptors are that most abundant GPCRs in the body
where are CB1 receptors found in the body? (3)
brian (sparse), peripheral organs (heart, liver, fat, stomach, testes), and peripheral nerves
where are CB2 receptors mostly?
immune cells (non-neuronal cells-can explain anti-inflammatory effects)
what does preclinical research suggest are CBD’s potential therapeutic effects? (6)
manage inflammation, anxiety, emesis, nausea, inflammatory pain, and epilepsy (lacks clinical data)
what are 6 general effects of THC?
euphoria, relaxation, disinhibition, changed perception, vasodilation, incr HR
what are 4 therapeutic effects of THC?
decr nausea, incr appetite, decr intraocular P, chronic pain relief
what are 5 unwanted effects of THC?
memory impairment, dysphoric state, hallucination, depersonalization, psychotic episodes
what are 6 acute effects of high doses of THC?
panic attacks, severe anxiety, psychosis, paranoia, convulsions, and hyperemesis
what are prenatal effects of cannabis?
can cause neuroanatomical and behavioural changes of fetus
t/f: smoking cannabis can cause lung cancer
true
what are the effects of driving w/ cannabis?
incr risk for motor accident (decr perception, psychomotor performance, cognitive functions, and rxn times)
t/f: there is documented evidence cannabis overdose can cause death
false (due to sparsity of CB1 receptors in brain)
what does data suggest about cannabis use (in adolescence) and developing psychotic disorders/schizophrenia?
lots of correlative data but don’t indicate causation (reverse causality, bias or confounding variables), can elicit acute psychosis, worsen existing schiz., or trigger development of schiz. in at-risk populations
what is psychological dependence?
compulsive drug-seeking behaviour for personal satisfaction, despite risks to health
what is physiological dependence?
symptoms produced by drug withdrawal, are usually opposite to desired effects
what is cannabis withdrawal like?
mild and short-lived (restless, irritable, agitated, insomnia, nausea, cramping) but worse in chronic users
what is addiction/substance use disorder defined as?
inability to control use of legal or illegal substances despite negative consequences
how many criterion do individuals have to meet to be diagnosed w/ addiction/substance use disorder?
11 (tolerance and withdrawal are not mandatory)
what is the severity of substance use disorder determined by?
of criterion person meets (2-mild, 4-moderate, 6-severe)
approx. what % of ppl who use cannabis develop a substance use disorder?
~9% (regardless, chronic use can incr risk for dependence/addiction)
what are synthetic cannabinoids?
manufactured compounds that imitate properties of active constituents of cannabis (THC)
what are 4 pros of synthetic cannabinoids?
incr specificity, decr off-target effects, easier dosing, more controlled studies
what 3 diseases have multiple randomized clinical trials confirmed effectiveness of cannabinoids?
nausea/vomiting, anorexia (to incr appetite), weight loss from HIV/AIDS/cancer
what is nabilone? what is it used for?
synthetic THC analog for chronic pain, multiple sclerosis, etc.
what is dronabinol? what is it used for?
trans isomer of ∆9-THC for nausea/vomiting after chemotherapy or anorexia in AIDS wasting syndrome
what are 3 similarities btwn nabilone and dronabinol?
both are partial CB1 agonists, taken orally, and less psychotropic effects than cannabis
what are nabiximols (sativex)?
sublingual botanical drugs (cannabis extract-1:1 ratio of THC and cannabinol)
why were nabiximols (sativex) created?
to relieve pain in ppl w/ multiple sclerosis and cancer (less psychotropic effects than smoked cannabinoids)
what is rimonabant?
inverse CB1 agonist (opposite effects)
why was rimonabant created but later withdrawn?
to treat obesity (inverse agonist-decr appetite) but caused depression and suicidal ideation
what are endocannabinoids?
endogenous cannabinoids (made by body) that regulate mood, feeding, and motor function
t/f: cannabinoid receptors evolved in response to cannabis
false, we have endogenous cannabinoids
what are 2 endocannabinoids?
anandamide (AEA) and 2-arachinoyl glycerol (2-AG)
how are AEA and 2-AG made in the body?
from the phospholipid bilayer of cell memb (~arachidonic acid)
what is the biochemical synthesis pathway for AEA?
N-acetyltransferase converts phosphatidylethanolamine (PE) to N-arachydonoil-PE (NAPE), phospholipase D converts NAPE to AEA
what is the biochemical synthesis pathway for 2-AG?
phospholipase C converts phospholipid to DAG, DAG lipase converts DAG to 2-AG
what does “AEA and 2-AG are retrograde NTs” mean?
act on cannabinoid receptors on presynaptic memb.
how do AEA and 2-AG sort of act in a negative feedback loop?
are synthesized on demand in postsyn. cell w/ AP, are released back into synapse where they bind to Gi CB1 receptors which inhibits future NT release
how do endocannabinoids act like THC?
decr neuronal release of other NTs (Glu)
when and where are AEA and 2-AG synthesized?
w/ incr intracellular [Ca] in depolarized postsynaptic neuron; only active regions of brain
what enzymes metabolize AEA va 2-AG in presynaptic cell?
AEA: fatty-acid amide hydrolase (FAAH)
2-AG: monoacylglycerol (MAGL)
what does suppression of FAAH and MAGL cause?
incr activity of AEA and 2-AG
why were FAAH/MAGL inhibitors created?
to incr activity of AEA and 2-AG in active areas of brain (not entire brain) to decr pain (analgesic effects) wo/ psychoactive effects, sedation, catalepsy, or hypothermia
why was a clinical trial of a FAAH inhibitor (BIA-2474) halted?
had several, severe off-target effects (death/hospitalization)
Genetic variation in which gene had been associated with incr risk of developing psychotic disorders with cannabis use?
Catechol-O-methyltransferase (COMT)
t/f: AEA and 2 -AG are stored in vesicles in postsynaptic memb
false, they’re generated on-demand after enzymatic transformation
