Cannabis Flashcards
List the seven priorities of the Canadian Cannabis Act
1) Protect the health of young persons by restricting their access to cannabis
2) Minimize inducements to use cannabis
3) Increase public awareness of the health risks of using cannabis
4) Allow the legal production of cannabis to replace the illicit market
5) Deter illicit cannabis production and sale
6) Enable cannabis users to have a quality-controlled supply of cannabis
7) Reduce the burden of dealing with cannabis offences imposed on the criminal justice system
What has QC done differently to tightly regulate cannabis use?
1) Purchase age is 21
2) SQDC is the only retailer
3) Reduced the amount of cannabis that an adult could legally possess
4) Banned the growing of cannabis for personal use
5) Limit on THC content of edibles
6) Banned additives to any cannabis products that would increase attractiveness or flavour or enhance their psychoactive effects
List key trends in cannabis use prevalence in Canada.
1) Increased use
2) Greater use in men
3) Highest rates in young adults
T or F: The Cannabis Act has successfully met its objective of protecting youth.
False.
Which age group has seen a drastic increase in cannabis use in recent years? What might be some reasons to explain that?
Aging adults (>55).
→ possibly for pain management, they have more time, less stigma surrounding cannabis
List major consequences of cannabis legalization.
Cannabis legalization may support increased patterns of cannabis use due to:
1) Decreased perceived harmfulness
2) Increased cannabis availability and accessibility
T or F: Overall, the Cannabis Act is working and is reaching its targets.
False.
Cannabis use, daily cannabis use and cannabis-related problem prevalence have dramatically increased.
T or F: Cannabis legalization has had no effect on the number of injured drivers testing positive for THC.
False
Cannabis legalization has increased (x2) the prevalence of injured drivers testing positive for THC, whereas no change in alcohol was observed.
Which priority of the Cannabis Act has seen success?
Substantial reductions in criminal arrests and charges related to cannabis use — and related stigma and other personal burdens — among both adults and youth should be noted as related positive social justice and possibly indirect public health outcomes.
Read slides 3-24.
woohoo
What is cannabis?
Derived from the Cannabaceae family of plants and refers to a mixture of cut, dried, and ground flowers, leaves, and stems of the hemp plant.
What drug properties does cannabis possess?
1) Stimulant
2) Depressant
3) Hallucinogenic
T or F: Herbal cannabis contains over 400 different compounds.
True.
How many of the compounds in herbal cannabis are cannabinoids?
> 80
Which compounds are responsible for the aroma of cannabis?
Terpenes
Which compounds are responsible for the pigment and flavor of cannabis?
Flavonoids
What are the two most known cannabinoids? (Full names)
1) THC: delta-9-tetrahydrocannabinol
2) CBD: cannabidiol
T or F: CBD is responsible for psychoactive and addictive properties of cannabis.
False.
THC produces psychoactive properties and is responsible for addictive properties.
What effect does CBD have?
CBD is non-psychoactive, but still biologically active.
It does not cause a high and is not addictive.
T or F: CBD acts on dopamine reward systems.
False.
List the three cannabis species. Add any relevant CBD/THC ratios and their effects.
1) Cannabis sativa
→ high THC:CBD
→ produces more stimulating and psychotropic effects
2) Cannabis indica
→ high CBD: THC
→ produces more sedating effects
3) Ruderalis
→ low THC strain
T or F: There are only three strains of cannabis.
False.
There are >700 and they are mostly a combination of the three species.
T or F: Smoked cannabis produces greater subjective effects than vaporized cannabis.
False.
Vaporized cannabis produced significantly greater subjective drug effects (and higher blood THC concentrations) than the same doses of smoked cannabis.
List different modes of cannabis administration
1) dried flower/leaf
2) edible products
3) concentrates/extracts
4) vape pens
5) oil
6) hashish
How does cannabis interact with the brain?
Through the endocannabinoid system.
What is the endocannabinoid system?
The Endocannabinoid system is a widespread neuromodulatory system.
What functions is the endocannabinoid system involved in?
1) CNS development
2) Regulation of physical and cognitive processes
How does the endocannabinoid system work to maintain homeostasis?
1) Controls the level and activity of other neurotransmitters
2) Influences and is influenced by other signaling pathways
T or F: The endocannabinoid system is active even in the absence of cannabis.
True.
T or F: The endocannabinoid system is implicated in a number of pathological conditions (e.g.,
schizophrenia)
True.
List some elements that the endocannabinoid system can have an effect on.
Slide 33 mama
List the three forms of cannabinoids. Where do they come from?
1) Endocannabinoids
→ endogenous
2) Phytocannabinoids
→ flora
3) Synthetic cannabinoids
→ artificial
T or F: Endocannabinoids serve as neurotransmitters.
False.
Endocannabinoids serve as neuroregulatory modulators. They are lipid molecules synthesized on demand.
How do endocannabinoids act on the nervous system?
Endocannabinoids are retrograde messengers; they are released from postsynaptic cells and travel backwards across the synapse to then bind to cannabinoid receptors located on the presynaptic cell.
How many cannabinoid receptors exist?
2.
→ CB1R & CB2R
Where is each CBR predominantly located in the body?
1) CB1R: CNS
2) CB2R: periphery and immune cells
List the two best characterized endocannabinoids and the enzymes linked to their degradation. (Full names)
1) Anandamide
→ enzyme: fatty acid amino hydrolase (FAAH)
2) 2-Arachidonylglycerol (2-AG)
→ enzyme: monoacylglycerol lipase (MAGL)
T or F: Our bodies produce endocannabinoids which bind to CB1R and CB2R.
True.
T or F: Anandamide is a partial agonist at CB1R and CB2R.
True.
T or F: 2-AG is an inverse agonist at CB1R and CB2R.
False.
2-AG is a full agonist at CB1R and CB2R.
List the brain regions where CB1R can be found. Which ones are highly concentrated regions?
1) Basal ganglia*
2) NAcc*
3) Hippocampus*
4) Cerebellum*
5) Neocortex
6) Hypothalamus
7) Amygdala
8) Brain stem
T or F: THC is a partial agonist at CB1R and CB2R.
True.
How is THC metabolized?
Metabolized into the inactive metabolite Carboxy-THC (THC-COOH) by Cytochrome P450 enzymes.
T or F: THC has a relatively short half-life.
False.
THC has a long half-life (20-30 hours). It deposits in adipose tissue and later re-released into blood.
How long do THC metabolites remain detectable?
Approx. 28 days after last use.
Describe the distribution PK of THC when smoking.
1) THC is rapidly absorbed through lungs after inhalation quickly reaching high concentration in blood: peak 6-10 minutes; post-inhalation and brain: peak within 15 to 30 minutes
2) THC is highly lipid soluble. It is rapidly taken up by fat tissue where it accumulates reaching peak concentration 4-5 days later.
3) From these fat deposits, THC is slowly released back into the bloodstream
T or F: The distribution and elimination pattern of THC is similar when smoking vs when taking an edible.
False.
Smoking is characterized by increase of metabolites in fat tissue over time.
Edibles are characterized by a highly delayed peak of onset.
T or F: THC cannot be tested in urine.
True.
Only its metabolites.`
T or F: THC dose-dependently increases dopamine in the shell of the NAcc.
True.
T or F: THC directly increase DA release through CB1R.
False.
THC does not increase dopamine directly.
CB1R are not localized to dopamine terminals.
How does THC have an effect on DA release?
1) THC increases dopamine neural firing by decreasing GABAergic inhibition of dopamine neural activity
2) THC allosterically modulates opioid receptors, which may provide additional indirect routes for altering dopamine transmission
How does THC have an effect of Glutamatergic neurons? What effect might this have?
THC inhibits VTA Glutamatergic transmission, which decreases dopamine release.
This may underlie aversive effects associated with THC.
T or F: Human studies have failed to demonstrate the addictive properties of THC.
False.
Human studies also confirm that THC induces dopamine release in the human striatum.
→ Acute THC administration (8 mg of vaporized THC) increased dopamine release in the striatum in humans (N=7)
→ Acute cannabis smoking (33 or 50 mg of THC per cigarette) increased dopamine in the striatum in humans (N=14)
T or F: Cannabis capture rate has remained steady over the past 20 years.
False.
Capture rate has doubled (10% vs 22%).
What might be a reason behind the increase in capture rate?
Higher potency of THC!
List some acute effects of THC.
1) red eyes
2) dry mouth
3) muscle relaxation
4) increased heart rate
5) skin sensations
6) memory loss
7) paranoia
8) impaired motor coordination
9) increased appetite
10) pleasure/bliss
11) delayed response
12) altered perception
List some acute high-dose effects of THC.
1) chest pain
2) rapid heartbeat
3) nausea/vomiting
4) psychotic episode (hallucinations/delusions)
5) respiratory depression
List some long-term/chronic effects of THC.
1) Physical health problems (respiratory and cardiovascular)
2) Psychiatric symptoms and disorders (CUD)
3) Psychosocial problems (poor academics)
4) Cognitive disfunction
What is a long-term high-dose effect of THC? Describe its characteristics.
Cannabinoid Hyperemesis Syndrome.
→ Recurrent episodes of nausea, vomiting, and dehydration with frequent visits to the emergency department
→ Patients are typically young adults with a long history of cannabis use
→ The most effective treatment is the use of hot showers
→ Resolves when cannabinoids are discontinued
→ Pathophysiology is unknown but may involve chronic overstimulation of cannabinoid receptors
What are two important neurobiological changes that occur with CUD?
1) CB1R downregulation
2) Decrease in grey matter volume in hippocampus and amygdala
List some proposed therapeutic properties of CBD.
1) Anxiolytic
2) Antidepressant
3) Antipsychotic
4) Analgesic
5) Anti-inflammatory
6) Add-on therapy for social anxiety disorders, schizophrenia, non-motor symptoms in Parkinson’s disease, and substance use disorders
T or F: Therapeutic properties of CBD have been backed by many clinical trials.
False.
There is a lack of evidence supporting these claims.
T or F: CBD has a strong affinity for CBRs.
False.
It has little binding affinity for CB1 or CB2 receptors.
T or F: CBD is a full agonist of the CB1R.
False.
CBD is a non-competitive allosteric modulator of CB1R.
What effect for CBD binding to CB1R produce?
1) Reduces the affinity/efficacy of THC and anandamide
2) Improves tolerability and safety of THC by antagonizing adverse effects of THC (psychosis, anxiety, sedation, tachycardia)
T or F: CBD inhibits MAGL.
False.
CBD inhibits FAAH, thus increasing anandamide.
T or F: CBD only binds to CBRs.
False.
CBD has several non-cannabinoid targets - over 65 molecular targets have been identified.
How does CBD modulate the following receptor types:
1) Serotonin
2) Opioid
3) TRPV1
1) Agonist at the serotonin 5-HT1A receptor
2) Allosteric modulation of opioid receptors
3) Agonist at transient potential vanilloid-1 receptors (TRPV1) – multisensory receptor
How is CBD metabolized?
Metabolized by cytochromes P450 (CYPs) 2C9, 2C19, and 3A4
→ Active metabolite: 7-hydroxy-CBD (7-OH-CBD)
→ Inactive metabolite: 7-carboxy-CBD (CBD-COOH)
T or F: Unlike THC, CBD elimination occurs quickly.
False.
Since CBD is lipid soluble, prolonged elimination is observed.
CBD has a half-life between 1 hour to 30 hours.
List the risks and harms associated with CBD.
1) Decreased alertness (sedation/drowsiness)
2) Changes in mood (irritability/agitation)
3) Decreased appetite, GI symptoms
4) Drug interaction effects with over-the-counter and prescription medications
→ Acts as an inhibitor or inducer of several cytochrome P450 isoforms (e.g., 3A4, 2C19, 2C8, 2C9, 2D6, 1A2 and 2B6)
5) Entirely unregulated market for CBD products, leaving consumers without reliable information about product purity and safety
The FDA has approved only one CBD product. Which disorders might it be used for as therapy?
Used to treat seizures associated with:
1) Lennox Gastaut syndrome (LGS)
2) Dravet syndrome (DS)
3) Tuberous sclerosis complex (TSC)
List some symptoms of cannabis withdrawal.
1) Cravings
2) Irritability
3) Anxiety
4) Depression
5) Decreased appetite
6) Sleep disturbances
7) Weird dreams
8) Restlessness
9) Headaches
10) Sweating
11) Nausea/vomiting
12) Abdominal pain
T or F: Severity of symptoms is proportional to severity of cannabis use.
True.
Read slides 61 & 62
almost thereeee
Describe the trajectory of cannabis withdrawal.
Cannabis withdrawal follows a distinct and protracted trajectory:
1) symptoms begin 24 hours after cessation
2) peak within 7 days
3) symptoms dissipate following 28 days of abstinence
Why do symptoms dissipate after 28 days?
28 days coincides with the complete urinary elimination of cannabis
T or F: Cannabis users tend to only stick to cannabis.
False.
Tobacco co-use is common in people who use cannabis (~80%).
What effect might tobacco use have on cannabis withdrawl?
Tobacco co-use increases the severity and duration of cannabis withdrawal symptoms, thus increasing the risk of cannabis use relapse.
List some cannabis treatments.
1) Behavioural
2) Harm reduction
No approved pharmacological treatments
List some behavioural therapies for CUD.
1) CBT
2) MI
3) Contingency management
Which behavioural therapy has the most success?
Trick question! Combining all three has the greatest efficacy.
List some pharmacotherapies for CUD. Which is the most promising?
1) Sedatives (Zolpidem)
2) Antidepressants (Buproprion)
3) Synthetic cannabinoids (nabilone)
4) CB1R antagonist (Rimonabant)
5) FAAH inhibitor***
List some novel avenues for CUD treatment. Explain how they work.
1) Neuromodulation: Repetitive Transcranial Magnetic Stimulation (rTMS)
A non-invasive brain stimulation treatment in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction.
→ applied to DLPFC, PCC/precuneus
2) Neuromodulation: Transcranial direct current stimulation (tDCS)
A non-invasive, brain stimulation treatment that uses direct electrical currents to stimulate specific parts of the brain
→ applied to DLPFC
Define self-medication
Self-medication is the use of a substance to alleviate, cope with, or reduce psychological or physical symptoms.
T or F: Cannabis as medication for anxiety has shown success.
True/False.
Cannabis, in low doses, can produce anxiolytic effects for some people.
T or F: Cannabis as medication for affective disorders has shown success.
False.
There is little evidence that cannabis use improves affective symptoms. If anything, chronic cannabis use and CUD are associated with negative mental health outcomes.
List common disorders that might be a consequence of cannabis use.
1) CUD
2) Depression
3) Anxiety
4) Suicidality
5) Cognitive deficits
6) Psychosis
Define Cannabis Use Disorder (CUD).
According to the DSM-V, CUD is a problematic pattern of cannabis consumption that leads to clinically significant levels of impairment or distress to the user. 2 out of 11 symptoms must be manifested within a 12 month span.
Which factors might make someone vulnerable to CUD?
1) daily/almost daily use
2) adolescent and young adult use (<25)
3) family history of addiction
4) other psychiatric co-morbidities
Define: Residual effects.
Effects that persists following drug use and getting the “high”
How might acute cannabis intoxication affect cognition?
Acute intoxication has been shown to lead to cognitive impairments in domains like memory, learning, attention, perceptual motor skill, executive functions, and processing speed
List the residual cognitive effects of acute cannabis intoxication.
1) Memory
2) Verbal learning
3) Executive function
NO residual effects for attention, processing speed and language
Which factors might make someone vulnerable to increased residual cognitive effects of cannabis use.
1) Adolescents
2) Level of use
What effect does cannabis use have on education? Give examples from different studies.
Cannabis can have negative effects on the functioning of students at school.
→ less likely to complete their homework, attend class, and achieve high marks
→ CUD severity was a better predictor of educational impairment than MDD and PTSD
→ craving predicted both cannabis use and reduced academic motivation
Define psychosis.
A mental state/behaviour characterized by a loss of contact with reality
Define hallucinations.
Disorder in the experience of sensory events.
Define delusions.
Disorder in the representation of reality.
List and define the symptoms of schizophrenia.
1) Positive: hallucinations, delusions
2) Negative: avolition, anhedonia, blunted affect
3) Disorganized: disorganized speech, inappropriate affect
T or F: Cannabis has a dose-dependent relationship for schizophrenia symptoms.
True.
→ Low [THC]: anxiolytic, feeling calm, less anxious, relaxed, slowed down
→ High [THC]: can produce feelings of anxiety, hallucinations, delusions (e.g. paranoia), derealization
Read slides 20-21 for D’Souza findings.
slayyyyyy
T or F: Cannabis use is a risk factor to the development of schizophrenia.
True.
Elevated odds ratio.
List the factors that might affect SCZ development with cannabis use. Provide an explanation.
1) Dose
→ dose-response relationship
2) Sex
→ higher prevalence in men
3) Timing of use
→ strengthened relationship when used during adolescence
4) Genetics
→ polymorphisms in COMT, AKT1, DAT1, BDNF
Describe how mutations in COMT might be linked to SCZ development.
COMT is responsible for the breakdown of DA in the brain and a polymorphism at codon 158 can cause a substitution of Val to Met.
→ adolescent cannabis users with Val/Val mutation had a heightened prevalence of SCZ development.
T or F: Cannabis abstinence does not reduce cognitive residual effects in people with SCZ.
False.
A study found clinically significant improvements in verbal memory and learning in people with SCZ after 28 days of cannabis abstinence.
What’s the difference between a causal relationship vs a reverse-causal relationship in the context of substance use?
Causal: substance use → mental health problem
Reverse-causal: mental health problem → substance use
T or F: Cannabis use during adolescence causes depression and suicidal idealation.
False.
Cannabis use during adolescence significantly increased the risk of developing depression and suicidality, however a causal relationship cannot be established; other substances must be controlled for.
T or F: From a 30-year longitudinal study, adolescent cannabis use was correlated with the development of MDD and GAD.
False.
Adolescent cannabis use was associated with adult MDD and suicidality, but not with GAD. Factors like young age of use and increased frequency increased risk.
What link does adolescent cannabis use have on GAD?
Greater cannabis use at baseline predicted slower improvements in anxiety (ie. maintenance of symptoms over time)
T or F: Anxiety in adolescents causes them to consume more cannabis.
False.
Reverse-causal hypothesis was not supported: anxiety at baseline did not predict change in cannabis use.
Define flourishing vs languishing
Flourishing refers to positive feelings of psychosocial wellbeing and functioning.
Languishing refers to the absence of positive mental wellbeing and a life that feels hollow and empty.
What effect does cannabis have on flourishing?
Even after controlling for depression and anxiety symptoms, flourishing was a better predictor of cannabis use levels: Flourishing was associated with lower cannabis use.
Higher scores on Flourishing-Languishing Scale (worse mental health) predicted higher odds of cannabis use, regardless of anxiety and depression.
List two pieces of evidence for dysregulation of endocannabinoid system after chronic cannabis use.
1) CB1R downregulation
2) Dysregulation in plasma and CSF endocannabinoid levels
T or F: Studies have shown that downregulation of CB1R reverses after 28 days of cannabis abstinence.
True.
T or F: Affective symptoms do not improve after 28 days of cannabis abstinence.
False.
Most studies show that affective symptoms do improve.
Read slide 50 :)
DONE!
