Lecture 14: Cannabis & Cannabinoids Flashcards
What is the definition of cannabis?
genus of flowering plant
contains many bioactive compounds, but most studied are tetrahydrocannabinol (THC) and cannabidiol (CBD)
THC is the primary psychoactive compound in cannabis
What is the definition of cannabinoids?
class of chemical compounds that act at the cannabinoid receptors
What are terpenoid non-cannabinoid constituents in cannabis?
cannabis also contains hundreds of non-cannabinoid constituents, including terpenoids which give plant characteristic smell
in vitro and in vivo studies found some terpenoids to have anti-inflammatory, anti-bacterial and anti anxiety effects, but no clinical trials to support this
possibility of synergy between compounds may explain differences in experience based on strains, makes harnessing clinical utility very difficult
What is the absorption of THC?
absorption, aka bioavailability = fraction of an administered drug that reaches effectors (plasma, central nervous system)
most pharmacokinetic information relates to THC, only
smoking provides rapid and efficient delivery from lungs to the brain; bioavailability of smoked THC is 25%, reaching peak plasma concentration in 6-10 minutes
when ingested, bioavailability around 6%, time to peak plasma concentration is 2-6 hours
What is the distribution of THC?
THC is highly lipophilic so rapidly taken up by tissues with high blood flow, including heart, lungs, brain, and liver
tissues with less blood flow accumulate THC more slowly and release it over a longer period of time (i.e. adipose tissue)
THC stored in fat in chronic; frequent cannabis smokers can be released into the blood for days
What is the metabolism and elimination of THC?
THC metabolism occurs mostly in the liver by cytochrome P450 2C9 enzyme producing the metabolites 11-OH-THC and THC-COOH
within 5 days, 80-90% of a THC dose is excreted, primarily as metabolites, 65% in feces and 25% in urine
can detect THC in urine 2-5 days for low dose THC, but can extend to weeks in chronic daily cannabis smokers (because THC is lipophilic can accumulate in adipose tissue)
What are the characteristics of cannabinoid receptors?
cannabinoid receptors are inhibitory G-protein coupled receptors (Gi coupled)
cannabinoid receptors come in two flavors: CB1 and CB2
CB receptors leads to decrease in cyclic adenosine monophosphate (cAMP) accumulation which inhibits the influx of calcium in the firing neuron and inhibits neurotransmitter release
decrease synaptic transmission, inhibit neurotransmitter release
What are the pharmacodynamics of THC?
THC is a partial agonist at CB1
cannabidiol (CBD) mechanism of action is poorly understood; binds a lot different targets poorly (low affinity)
some evidence it can act as negative allosteric modulator at CB1 (binds outside the binding pocket to block receptor activation)
CBD can blunt psychotropic effects of THC (maybe?)
What are CB1 receptors?
CB1 receptors are among the most abundant GPCRs
CB1 receptors found in brain, peripheral organs (heart, liver, fat, stomach, testes) and peripheral nerves
What are CB2 receptors?
receptor distribution mostly on immune cells
What are the general effects of THC?
euphoria
relaxation
disinhibition
changes in perception
vasodilation
increase pulse rate
What are the potential therapeutic effects of THC?
attenuation of nausea
increased appetite
decreased intraocular pressure
chronic pain relief
What are unwanted effects of THC?
memory impairment
dysphoric state
visual hallucinations
depersonalization
psychotic episodes
What are CBD effects?
some preclinical research suggests CBD has therapeutic potential for management of inflammation, anxiety, emesis, nausea, inflammatory pain and epilepsy (but usually doses many fold higher than what is biologically possible in vivo, off target effects?)
strong clinical data lacking for these claims
pediatric epilepsy is the only condition in which high quality clinical data (randomized, placebo controlled, control clinical trials)
What was the effect of CBD on Dravet Syndrome?
patients (2-18 years old) with confirmed diagnosis of Dravet Syndrome (genetic disorder associated with severe seizures from birth)
oral CBD significantly reduced frequency of seizures more than placebo
What are the adverse acute effects of THC?
panic attacks, severe anxiety, psychosis, paranoia, convulsion, hyperemesis
these are rare and usually associated with high doses of THC
What are the adverse prenatal effects of THC?
cannabis use may lead to neuroanatomical and behavioral changes in offspring
fetal growth affected (particularly neurodevelopment), but dose-response relationship not identified
How is lung cancer an effect of THC?
particularly through smoked cannabis
What are the effects of THC on driving?
driving while intoxicated seems to increase the risk of being in a motor vehicle accident
THC impairs perception, psychomotor performance, cognitive functions and affective functions
decreased reaction time
Does THC overdose cause death?
no documented evidence of a death that can be exclusively attributed to overdosing with cannabis, probably because sparsity of CB1 receptors in the brain stem region that controls respiratory and cardiovascular systems
Does cannabis use (particularly in adolescence) increase the risk of later developing psychotic disorders, such as schizophrenia?
a lot of correlative data suggesting schizophrenics are more likely to use cannabis, and early cannabis use dose-dependently predicts the development of schizophrenia later on
however, these studies do not indicate causation; does not take into account reverse causality bias, and confounding variables
majority of people who use cannabis do not develop schizophrenia; however, cannabis can elicit acute psychosis, can worsen course of pre-existing schizophrenia, and may be a trigger in the development of schizophrenia in at-risk populations (i.e. those with genetic predisposition)
What is psychological dependence on cannabis?
compulsive drug-seeking behavior in which the individual uses the drug receptively for personal satisfaction, often in the face of known risks to health
What is physiological dependence on cannabis?
revealed when withdrawal of the drug produces symptoms and signs that are frequently opposite of those sought by the user
What are the symptoms of cannabis withdrawal?
relatively mild and short-lived
symptoms of restlessness, irritability, mild agitation, insomnia, nausea, and cramping
may be worse in chronic, long-term users, and may contribute to continued drug use
