Cannabis Flashcards
emergent view
only one lineage
produces cannabis phytocannabinoid chemotypes
e.g. TCH and CBD + others
experience is chemical-dependent
cultivars
‘strains’
sativa
indica
ruderalis
synthesis
phytocannabinoids, terpenes, etc. are synthesized in heads = produced in trichomes
cannabis extraction
solvent or solvent-less
super-critical
goal: high purity or a single isolated compound
forms of cannabis
flower
pre-rolls
extracts
oil
soft gels
topicals
vapes
beverages
edibles
calculation of THC%
% is mg per g (1/1000)
15% = 150mg / 1g = 150/1000mg = 0.15
THC vs total THC (THC + THCA) per unit
chemical composition
psychoactive, non-psychoactive, synthetic
most are in acid forms in plant
THC acid; CBD acid
THC acid
psychoactive
CBD acid
anti oxidant
anti convulsant
anti inflammatory
anti anxiety
anti psychotic
neuro protective
CBG + THCV
CBG: precursor to other cannabinoids; individual effects in vitro
THCV: ‘metabolic reset’ - Ozempic
cultivar selection
personalize
tailor therapeutic effect to the disease + individual
medical cannabinoid
only CBD
administration
to optimize absorption: THCA → THC by heat or pressure (decarboxylation)
inhalation, ingestion, oral - sublingual, topical
smoke
solid/liquid particulates and gases created during combustion
similar levels of tar, CO, acetaldehyde, etc. as seen in cigarettes
poorer filtration of cannabis = more irritation
risks of inhalation
increased risk of chronic cough, bronchitis
no link to lung cancer or COPD
combustion/pyrolysis generates carcinogens (O2 + high temp)
ingestion
slower onset of effect
less predictability of action
more user control
distribution
THC is fat-soluble (lipophilic) → easily crosses BBB
brain, liver
peak effects 15-60 min
TI > 1000
metabolism
CYP450 system - liver
long half-lives
duration: 2-12 hrs
metabolites can stay in body for days or weeks
first pass metabolite - 11-hydroxy-9-THC
absorption - inhalation
10-15 sec onset
22% bioavailability
absorption - ingestion
45-60 min onset
10% bioavailability
absorption - oral
20-45 min onset
excretion
kidney
endogenous CBR ligands
arachidonoyl ethanolamide (AEA)
2-arachidonoylglycerol (2-AG)
CB1 receptors
expressed in CNS, eye, pancreas, liver, skin, uterus, testes
= widely
Gi/o linked
CB2 receptors
expressed in immune cells, spleen, tonsils
Gi/o linked
acute effects in brain
affect appetite, sex, and sleep
inhibited memory encoding + retrieval
impaired coordination
analgesia
behavioural + psychological acute effects
euphoria
relaxation
lethargy
physiological mechanisms
pleasure, reward, enhanced perceptions
high CB1 expression in hippocampus, cerebellum, basal ganglia, hypothalamus, cortex
stimulant = sympathomimetic effects
eye vessel dilation = red, bloodshot eyes
analgesia
CB1- mediated blockage of pain neurotransmission
CB1 in hypothalamus
energy metabolism, increased appetite + thirst
sex drive, sperm production, fertilization, implantation, fetal development + suckling in newborns
modulates DA + 5HT release
cellular mechanisms of action
retrograde signaling
cannabinoids modulate the release of other NTs
targets
CB1/2
transient receptor potential cation channels (TRPV1/2)
5HT 2 subtype
TRPV1/2
Na+/Ca2+ channels = depolarizing
pleiotropic signaling → multiple downstream target effects
tolerance
regular use → metabolic, cellular, + behavioural
faster metabolism
reduced CB1 receptor expression
reduced high, hypothermic, cardiovascular, analgesic, locomotor, and immune effects
withdrawal
mild burn out (lethargy + apathy)
not severe
chronic users will retain higher levels of residual metabolites → ease withdrawal
dependence
limited, slight psychological
less addictive
acute adverse effects
green out
higher THC impairs learning, memory, concentration via hippocampal effects; inhibits LTP
psychosis
anxiety, paranoia
heart rhythm complications
pesticide contamination
green out
vomiting, nausea, complicated 5HT signaling
anti-5HT effects can account for anti-emetic activity vs chemo
overdose
nope
very low risk compared to alcohol or tobacco
4g of orally administered THC is lethal (2.67g smoked)
[a lot]
driving under the influence
decreased attention, reaction time, hand-eye coordination, and concentration
affects automated tasks relative to attention tasks
doubles risk of accident
synergistic effect when combined with alcohol
stoned drivers may be defensive drivers
long term health risks
increased risk of chronic cough, bronchitis
reproductive risks
reversible effects
gateway drug hypothesis
younger teens are when they first use substances, the more often they use and the more likely they are to use other drugs
~untrue~
vaping
delivers de-carbed chemicals without burning
THC vaporizes at 157 C
select the chemical composition of vape smoke by controlling temp
volcano administration
similar THC delivery smoking but reduced CO delivery
(vaping)
entourage effect
chemical interactions with receptors enhance each other’s effects
potential additive effect
mechanism of reinforcement
increases DA levels in rats 2x
CB1-mediated inhibition of GABA release in VTA [disinhibition of DAergic VTA → NAc neurons]
striatal dopamine release → link to schizophrenia
8 mg of THC inhaled
raises DA levels 136% 45-85 min post administration
(humans)
10mg oral → no measurable DA increase (kinetics)
bloodshot eyes
NE causes narrowing of blood vessels
AEA relaxes blood vessels
AEA is dependent on CB1 receptor + NO
CBD induces relaxation of arteries
munchies
result from hunger signaling
increased smell, olfaction sensitivity
increased pleasure when eating → induces DA release
anterior olfactory nucleus + piriform cortex = centrifugal glutamatergic input to main olfactory bulb
cortical feedback projections to olfactory bulb regulate food intake via CB1 signaling
hunger signling
olfactory afferent information from bipolar mitral neurons in olfactory bulb
inhibitory GABA ergic interneurons project to mitral neuron soma
glutamatergic neuron expressing CB1 presynaptic receptors triggers inhibitory GABAergic interneurons in main olfactory bulb
enhanced olfactory sensitivity
glutamatergic inputs trigger GABAergic firing
sets baseline mitral afferent firing to the brain
endocannabinoids naturally reduce GABAergic internuron firing leading to increased transmission through mitral cells
dishinhibition of mitral neurons and increased afferent inputs to the brain hypersensitizes smell
gene/protein knockouts
study a physiological (in vivo) process
pro-appetite effects
increased olfactory sensitivity triggers feeding
greater pleasure from food
appetite-related hormones are modulated by cannabinoids
nausea + vomiting
primary signal is 5HT3R-mediated in medulla by afferent input from gut
anti-emetic activity
THC inhibits 5HT release in medulla via presynaptic CB1
THC binds and decreases activity of 5HT3 receptors
CBD is an agonist at 5HT1A autoreceptors → prevents 5HT release + antagonizes 5HT3R
spice, K2 synthetic cannabis
contamination with toxins (rat poison) causes severe bleeding
cannabinoid detection/testing
colourimetric - ELISA or dipsticks
immunoassays, lateral flow
gas chromatography mass spectrometry
cancer
cannabinoids may protect cells from oxidative stress
