Lecture 13: Cannabinoid Agonists/Antagonists Flashcards
marijuana is a mild ___ agent
sedative-hypnotic
4 ways THC resembles ethyl alcohol effects
- disrupted attn
- short term memory
- altered sensory awareness
- altered control of motor movement and posture
main psychoactive ingredient in cannabis
delta9 tetrahydro-cannabinol
THC is sold commercially as ___
Marinol
3 other significant ingredients in cannabis
- cannabinol
- cannabidiol
- terpenes
hashish (%)?
dried resinous exudate of female flowers (10-20%)
sinsemilla (%)
dried tops of unfertilized female plants (5-8%, no seeds)
bhang
dried remainder of plant; THC content 2-5%
3 methods of marijuana consumption
- smoking
2. vaping
firecracker
nutella or peanut butter on a cracker with weed sprinkled on top
2 extraction methods for edibles
- butter
2. alcohol
when was cannabis considered a narcotic that caused violent behavior?
1920s
when did weed get its public image as a killer drug?
1930s-1940s
what 2 groups don’t support weed legalization?
seniors
republicans
how many americans use marijuana?
15 million
what percentage of teenagers had smoked marijuana in the past month?
25%
heavy use at early age is associated with ___
psychopathology later in life
sativex
THC + CBD 1:1
oramucosal mouth spray
6 args in favor of legalization
- legal consistency
- regulation
- crime
- destroys lives
- racism
- cost
2 endocannabinoids
- anandamide
2. 2-AG
THC mimics the action of __
anandamide
2 cannabinoid receptors THC binds to
CB1
CB2
where are CB1 receptors?
brain and spinal cords
where are CB2?
periphery
CB receptors are ___
metabotropic; 7 membrane spanning reasons
when THC binds to CB receptors, what second messenger does it activate?
adenylate cyclase
what does adenylate cyclase ultimately do?
inhibits glu release
there are ___ more CB1 receptors than opioid receptors in the brain
10-20x
CB1 receptor function in frontal cortex (4)
- psychoactive effects
- distortions of time/sound/color/taste
- inability to concentrate
- dreamlike state
CB1 function in hippocampus (2)
- memory
2. coding of sensory input
CB1 function in bg & cerebellum
movement & postural control
CB1 function in spinal cord
on nociceptors in dorsal horn and dorsal root ganglion
what are nociceptors?
responsible for pain
are there CB1 receptors in brain stem?
no
why doesnt weed affect respiration?
no CB1 receptors in brain stem
4 areas with CB2 receptors
- lymphatic system
- heart
- tissues involved in inflammation and pain response
- some immune cells
anandamide blocks ___ responses
nerve growth factor protein-induced pain and inflammatory response
retrograde signaling
released from postsynaptic cell and act on presynaptic terminal
activation of presynaptic cannabinoid receptors temporarily ___
reduces amount of conventional NT release
endocannabinoid-mediated system permits ___
the postsynaptic cell to control its own incoming synaptic traffic
when the release of GABA is reduced, the net postsynaptic effect is ___
increase in postsynaptic excitation
typical marijuana ciagarette contains ___
75mg of THC; 25-50% available in smoke
how long does weed last?
2-3 hours
THC is metabolized by ___
CYP450
THC active metabolite
11-hydroxy-delta-9-THC
inactive THC metabolite
carboxy-THC
how long is carboxy-THC present in urine?
1-3 days in infrequent smokers
7-21 in regular smokers
30 days in chronic smokers
THC is stored in ___
body fat
THC can persist in body for ___. longer in who?
days to 2 weeks
chronic and obese smokers
reverse tolerance
delayed elimination prolongs and intensifies effects of subsequently smoked marijuana
5 ways CNS effects vary
- dose
- route
- experience
- vulnerability
- setting
mice lacking CB receptors have ___ (4)
- higher mortality rates
- weight loss
- less active
- lower pain thresholds
4 THC and opioid effects
- analgesia
- sedation
- hypothermia
- hypotension
THC activates CB1 receptors in (2), which stimulates ___
- hypothalamus
- limbic structures
appetite for sweet and fattening foods
possible MoA for memory problems
activation of CB1 receptors in hippocampus
how long can adverse cognitive effects last?
1 month
THC impaires (4)
- coordination
- perception
- reaction time
- attention
2 high dose effects of THC
- acute depressive reactions
2. acute panic reaction/mild paranoia
cannabis exposure can contribute to ___ in adolescents with ___. cannabis is likely a ___
schizophreniform psychosis
family history
component cause
cannabinoid hypothesis of schizophrenia
psychotic disorders involve disturbances in DA NT systems, with which the cannabinoid sys interacts
THC and anandamide active the ___
mesolimbic dopaminergic reward system
cannabis use during adolescence increases risk of non-affective psychosis in people who ___
experienced childhood sexual trauma
LD50
ratio of lethal to effective is ~1000
CB2 receptors in heart might protect against ___
ischemic attacks
marijuana smoking increases risk of lung cancer by ___
8% for each year of combined tobacco and marijuana use
2 effects of chronic use by males
- reduced testosterone
2. reduced sperm formation
2 effects of chronic use by females
- reduced level of follicle-stimulating hormone and luteinizing hormone
- impact on menstrual cycles and anovulatory cycles
4 effects on fetus
- impaired visuospatial function
- impulsivity/inattention
- depressive symptoms
- later substance abuse
fetal exposure is similar to effect of ___. why?
prenatal stress
impacts endocannabinoid system; exposure may interfere with stress coping ability
infants born to marijuana-smoking mothers may display (3)
- tremulousness
- abnormal responses to stimuli
- neurobehavioral performance deficits
chronic marijuana use (2)
downregulates and desensitizes CB1 receptors (behavioral tolerance)
__ in 10 people who smoke cannabis become dependent
1
8 withdrawal symptoms
- irritability
- anxiety
- craving
- disrupted sleep
- aggression
- depression
- decreased appetite
- weight loss
dronabinol
synthetic formulation of THC; most effective pharmacotherapy for withdrawal
naltrexone effectiveness
moderate, but can be overcome with high doses of cannabis
3 investigated medicines
- rimonabant (CB1 receptor reverse agonist)
- bupropion
- buspirone (serotonergic antidepressant)
6 effects of THC/things it can treat
- pain relief
- appetite stimulant
- glaucoma treatment
- sleep aid
- anti-epileptic
- muscle spasm relief
3 cannabinoids
- THC
- cannabidiol (CBD)
- cannabinol (CBN)
6 effects of CBD
- pain relief
- anti inflammatory
- anti epileptic
- strengthens bones
- anti nausea
- reduces negative effects of THC
is CBN psychoactive?
mildly
how is CBN produced?
degradation of THC
CBN MoA
weak agonist at CB1 and CB2
which receptor does CBN have higher affinity to?
CB2
what effect is CBN responsible for?
couch lock
synthetic THC
dronabinol
terpenes; how many?
100+; aromatic compounds in cannabis
5 terpenes
- A-pinene
- linalool
- beta caryophyllene
- myrcene
- limonene
ensemble effect
all compounds in weed work together to produce a greater effect
sativa may have a higher ___ ratio than indica
CBD:THC
indicas tend to be more psychoactive due to higher ___
THC:CBD ratio
indicas are used to relieve/treat (4)
- relieve stress
- aid with sleep
- muscle spasms
- nausea
drugs that stimulate cannabinoid receptor synthetically
cannabinomimetics
cannabinomimetics are ___ in blood and urine
undetectable
___ is more potent than THC
JWH-018