Chapter 14: Marijuana and Cannabinoids Flashcards
amotivational syndrome
Symptoms of cannabis use that relate to poor educational achievement and motivation.
anandamide
arachidonoyl ethanolamide; Common chemical name of the arachidonic acid derivative that functions as an endogenous ligand for cannabinoid receptors in the brain.
2-arachidonoylglycerol (2-AG)
An arachidonic acid derivative that functions as an endogenous ligand for brain cannabinoid receptors
cannabinoid receptor
Receptor for cannabinoids, including THC and anandamide. In the CNS, they are concentrated in the basal ganglia, cerebellum, hippocampus, and cerebral cortex.
cannabinoids
Collection of over 60 compounds found uniquely in cannabis plants.
CB1
Cannabinoid receptor of the metabotropic receptor family located in the CNS; play a role in the reward system
CB2
Cannabinoid receptor located primarily in the immune system, but also in bone, fat cells, and the GI tract. Are also expressed by microglia
Δ9-tetrahydrocannabinol (THC)
Psychoactive chemical found in cannabis plants; a cannabinoid.
endocannabinoids
Lipid-like substances that activate CB receptors. They are produced from arachidonic acid in the body.
fatty acid amide hydrolase (FAAH)
Enzyme that metabolizes endocannabinoids
hash oil
Potent oil that is derived from hashish and contains a high concentration of cannabinoids
hashish
Type of cannabis derivative that is smoked or eaten.
hyperalgesia
Condition characterized by an increased sensitivity to pain.
monoacylglycerol lipase (MAGL)
Enzyme primarily responsible for metabolism of the endocannabinoid 2-arachidonoylglycerol.
precipitated withdrawal
Method used to test dependence and withdrawal by administering an antagonist to block drug effects rapidly.
retrograde messenger
Chemical synthesized and released by a postsynaptic cell that diffuses into the nerve terminal of the presynaptic cell, often for the purpose of altering neurotransmitter release by the terminal.
rimonabant
SR 141716; Antagonist selective for the CB1 receptor. It is also called SR 141716.
sinsemilla
The potent marijuana produced by preventing pollination and seed production in the female cannabis plants.
how much THC is in a joint?
a joint is .5-1 gram of cannabis and 1 gram of cannabis contains 40mg or THC, but only 20-30% is absorbed into the lungs
smoking THC
readily absorbed through the lungs resulting in rising levels in the blood plasma
oral consumption of THC
leads to prolonged but poor absorption resulting in low and variable plasma concentrations—because of degradation in the stomach and first pass metabolism
what is THC converted into?
metabolites– 11-hydroxy-THC and 11-nor-carboxy-THC which are excreted mostly in the feces
half life of THC
20-30 hours
what family of receptors do cannabinoid receptors belong to?
metabotropic receptors
how do metabotropic receptors (and thus cannabinoids) exert their effects?
coupling with G proteins Gi and Go which inhibits cyclic adenosine monophosphate (cAMP) formation, inhibits voltage sensitive Ca2+ channels, and activation of K+ channel opening
where do CB1 receptors exist?
axon terminals
what happens when CB1 receptors are activated?
by activating these presynaptic receptors, cannabinoids can inhibit the release of many different neurotransmitters including acetylcholine, dopamine, norepinephrine, serotonin, glutamate, and GABA
is THC a full CB1 and CB2 agonist?
nope–it is a partial agonist
what are the synthetic cannabinoid agonists?
CP-55,940 and WIN 55,212-2
what does administration of THC to mice lead to?
- reduced locomotor activity
- hypothermia (decrease in core body temp)
- catalepsy (muscular rigidity)
- hypoalgesia (reduced pain sensitivity)
- -all mediated by CB1 receptors
cannabinoids and learning
they disrupt memory in several different kinds of learning tasks; it inhibits the induction of long-term potentiation (LTP) in the hippocampal CA1 area; CB1 activation in the hippocampus underlies spatial learning deficits
what effects to CB2 agonists exert?
inhibit the release of cytokines (immune cell signaling molecules such as interleukins and interferons) and can stimulate or inhibit the migration of immune cells toward the site of an inflammatory reaction
what is the principle endocannabinoid for both CB1 and CB2 receptors?
2-AG
endocannabinoid release
they are made and released when needed; the rise in intracellular Ca2+ levels trigger release
what happens after endocannabinoids are released?
they are removed from the extracellular fluid by uptake mechanisms
potential endocannabinoid uptake mechanisms
- uptake by means of a protein carrier in the cell membrane
- uptake by simple passive diffusion across the cell membrane
- uptake by means of anandamide binding to a membrane protein followed by endocytosis of the anandamide-protein complex
how are endocannabinoids metabolized?
by several enzymes
- anandamide is broken down by fatty acide amide hydrolase (FAAH)
- 2-AG is broken down by monoacyl-glycerol lipase (MAGL)
are endocannabinoids retrograde messengers?
yes–at specific synapses in the hippocampus and cerebellum
how do endocannabinoids work as retrograde messengers?
they are synthesized and released in response to depolarization of the postsynaptic cell due to the influx of Ca2+ through voltage-gated Ca2+ channels. they then cross the synaptic cleft, activate CB1 receptors on the nerve terminal and inhibit ca2+ mediate neurotransmitter release from the terminal
endocannabinoids as second messengers in the hippocampus
they are generated by pyramidal neurons and diffuse to nearby terminals of GABAergic interneurons that normally suppress the firing of the pyramidal cells. The resulting inhibition of GABA release temporarily permits the pyramidal cells to fire more rapidly
endocannabinoids and pain
they act on both CB1 and CB2 to modulate pain perception
endocannabinoids and hunger
CB1 receptor antagonists reliably reduce food consumption; they enhance incentive motivational properties of food and food mediate reward; possible treatment for obesity
endocannabinoids and fear
play a great role in the extinction of learned (fear) responses; CB1 knockout mice do not show normal extinction; endocannabinoids released during extinction and acting on CB1 receptors in the basolateral amygdala alter synaptic plasticity in a manner that enables the animals to learn that the tone is no longer dangerous; involved in the alleviation of fear; increased anandamide levels due to reduced FAAH activity enhance the ability to turn off neural and behavioral responses to threatening stimuli
stages of marijuana use
- buzz- brief period of initial responding during which the user may feel lightheaded or even dizzy; tingling sensations
- high- feelings of euphoria and exhilaration; sense of disinhibition
- stoned- user usually feels calm, relaxed, perhaps even in a dreamlike state; floating sensations, enhanced visual and auditory perception, visual illusions, and a tremendous slowing of time passage
- come down- gradual cessation of effects
physiological responses
increased blood flow to the skin, warmth and flushing, increases hunger, stimulated heart rate
what determines high?
it is dose dependent and partially mediated by CB1 receptors
negative side effects
psychotic symptoms, depersonalization, derealization, agitation, paranoia
when does the maximum level of intoxication occur?
when plasma THC concentrations are already declining
cognitive deficits
illogical or disordered thinking, fragmented speech, difficulty in remaining focused on a given topic of conversation; heavy usage may eliminate cognitive effects
memory
cannabinoids appear to interfere with all aspects of memory processing–encoding, consolidation, and retrieval; can be reversed in 2-3 weeks after stopping
what can heavy use impair?
executive functioning
psychomotor functioning
can impair it especially under demanding task conditions (driving)
reward/reinforcement
one factor in cannabinoid reinforcement may be activation of the mesolimbic dopamine (DA) system as cannabinoids stimulate firing of DA neurons in the VTA, and to enhance DA release in the nucleus accumbens; close interactions between cannabinoid and opioid systems (opioid agonists enhance cannabinoid self-administration)
factors that influence early marijuana use
lax parental monitoring and early behavioral problems, early conduct problems
risk factors for heavy early marijuana
emotional problems in family, heavy drug use in household or by peers, dislike of school, poor school performance, early age of first use of marijuana
early positive experiences with marijuana
lead to greater risk of later dependence
tolerance
repeated exposure to THC and other CB1 agonists developed profound tolerance to the behavioral and physiological effects; mostly parmacodynamic involving both desensitization and down regulation of CB1 receptors
dependence
10% of users will become dependent; difficulty in stopping one’s use, craving, unpleasant withdrawal
withdrawal symptoms
irritability, increased anxiety, depressed mood, sleep disturbances, heightened aggressiveness, and decreased appetite; symptoms are greatest during first 1-2 weeks
abstinence syndrome
decreased DA cell firing in the VTA and reduced DA release in the nucleus accumbens, increased corticotropin-releasing factor (CRF) release in the central nucleus of the amygdala, increase secretion of stress hormones, and changes in the endocannabinoid system
educational performance
greater use is associated with poorer grades, more negative attitudes about school, and increased absenteeism
IQ
the amount of cannabis use and the appearance of symptoms of cannabis dependence were significantly associated with neuropsychological impairment, including lower IQ at age 38 even after controlling for educational attainment
psychiatric features
significant relationship between early heavy marijuana smoking and increased risk for the later development of psychotic disorders such as schizophrenia
carcinogens
tar from cannabis smoke actually contains higher concentration of certain carcinogens known as benzanthracenes and benzpyrens; the amount of car and carbon monoxide taken in per cigarette are much greater for marijuana joints than for tobacco
respiratory symptoms
chronic cough, increased phlegm, wheezing, bronchitis
immune function
CB1 and CB2 receptors are expressed by various immune cells and activation of these receptors generally suppresses immune function; THC has been found to impair an organism’s resistence to bacterial and viral infections
reproductive system
THC suppresses the release of luteinizing hormone (LH), an important reproductive hormone secreted by the pituitary gland in males and females.
animals and pregnancy
pregnancy failure, retarded embryonic development, fetal death
male reproduction
reduce testosterone levels, sperm counts, and sperm motility
association model
individuals who are already vulnerable to developing psychosis have an increased likelihood of using cannabis when they’re young
causal model
cannabis use predisposes individuals to develop psychosis later in life
indicator-variable model
one or more other factors lead jointly to cannabis use and psychosis proneness
prenatal marijuana exposure
cognitive deficits, poor school achievement, increased risk for tobacco/ marijuana use later in life have all been associated with prenatal marijuana exposure
