Lecture 4: cocaine Flashcards
1
Q
what are the priorities of the Cannabis act?
A
- Protect the health of young persons by restricting their access to cannabis
- Minimize inducements to use cannabis
- Allow the legal production of cannabis to replace the illicit market
- Deter illicit cannabis production and sale
- Reduce the burden of dealing with cannabis offences imposed on the
criminal justice system - Enable cannabis users to have a quality-controlled supply of cannabis
- Increase public awareness of the health risks of using cannabis
2
Q
did the cannabis act work?
A
not really since the rate of cannabis use increased, and many are using daily, which is associated with physical and mental health problems
although it has decreased slightly in youth, it has not significantly decreased
3
Q
which population represent the fastest growing population
of cannabis users in Canada?
A
the aging adults (55 and older)
4
Q
what are the consequences of cannabis legalization?
A
- Decreased perceived harmfulness (People perceive cannabis to be beneficial rather than harmful, most people think it has no effect)
- Increased cannabis availability and accessibility (sales are rising exponentially)
- Outcomes related to health have increased or remained steady since legalization
- But….. Substantial reductions in criminal arrests and charges related to cannabis use and related stigma
5
Q
what is cannabis?
A
a substance derived from Cannabaceae family of plants that has stimulant, depressant, and hallucinogenic properties
6
Q
what are some compounds found in cannabis?
A
> 80 cannabinoids
* Terpenes
* Flavonoids
7
Q
what do Terpenes do?
A
responsible for the aroma of cannabis
8
Q
what do flavonoids do?
A
pigment and flavor
9
Q
what are the most common cannabinoids?
A
THC and CBD
10
Q
is THC and CBD psychoactive and addictive?
A
THC: psychoactive and addictive
CBD: psychoactive and not addictive
11
Q
what are the 3 families of cannabis?
A
- Cannabis sativa: contains a higher ratio of THC to CBD, producing more stimulating, psychotropic effects
- Cannabis indica: contains a higher ratio of CBD:THC and is typically more sedating
- Ruderalis: contains low THC
12
Q
what does the mode of administration affect?
A
different onset of effects, duration of action and distinct health effects
13
Q
what are the most common modes of adminstrations?
A
dried flower/leaf, edible products, vapes, oils
14
Q
The Endocannabinoid system is a widespread __________ system
A
neuromodulatory
15
Q
the endocannabinoid system is import for what processes?
A
- CNS development
- Regulates many physiological and cognitive processes
- works to maintain homeostasis (Controls the level and activity of other neurotransmitters and influences many signaling pathways)
- implicated in pathological conditions
16
Q
what makes up the endogenous cannabinoid system?
A
endocannabinoids, cannabinoid receptors, endocannabinoid enzymes
17
Q
what are the different forms of cannabinoids?
A
- Phytocannabinoids - derived naturally from flora
- Endocannabinoids - produced endogenously
- Synthetic Cannabinoids – created artificially
18
Q
how does the endogenous cannabinoid system work?
A
- Lipid molecules synthesized on demand
- “Retrograde” messengers: released from postsynaptic cells and travel backwards across the synapse
- Bind to cannabinoid receptors located on the presynaptic cell
19
Q
what are the best characterized endocannabinoids?
A
anandamide and 2-arachidonylglycerol (2-AG)
20
Q
what are the 2 enzymes part of the endocannabinoid system?
A
Fatty acid amino hydrolase (FAAH) and monoacylglycerol lipase (MAGL)
21
Q
role of FAAH
A
degrade anandamide
22
Q
role of MAGL
A
degrade 2-AG
23
Q
what are the 2 types of cannabinoid receptors? where are they predominantly found?
A
- CB1R – predominantly found in the central nervous system
- CB2R – predominantly found in the periphery and immune cells
24
Q
which receptor does anandamide and 2-AG bind to?
A
Anandamide is a partial agonist at CB1R and CB2R
2-AG is a full agonist at CB1R and CB2R
25
where are there high concentrations of CB1R in the brain? what are the implications here?
basal ganglia (movement control), nucleus accumbens (reward and motivation), cerebellum (movement coordination)
26
how is THC metabolized?
Metabolized into active Hydroxy THC (11-OH-THC) and inactive Carboxy-THC (THC-COOH) by Cytochrome P450 enzymes
27
how is THC stored and excreted?
Deposits in adipose tissue and later re-released into blood
- Long half-life (20-30 hours)
- Metabolites remain detectable for ~ 28 days after last use
28
what are the pharmacokinetics of smoking THC?
THC is rapidly absorbed through lungs after inhalation quickly reaching peak
concentration in blood 6-10 min post-inhalation and brain within 15 to 30 min
THC is highly lipid soluble. It
is rapidly taken up by fat
tissue where it accumulates
reaching peak concentration
4-5 days later. From these
fat deposits, THC is slowly
released back into the
bloodstream
29
why is cannabis addictive?
THC dose-dependently increases dopamine in the shell of nucleus accumbens
THC increases dopamine indirectly via decreasing GABAergic inhibition of dopamine neural activity
30
what is the capture rate of cannabis?
9.1%
31
how does THC potency change with time?
increases with time (today may be up to 20%)
32
what are some short-term effects of THC?
- red eyes
- dry mouth
- skin sensation
- memory loss
- paranoia
- impaired motor coordination
- increased appetite
- pleasure/bliss
- delayed response
- altered perception
- muscle relaxation
- increased heart rate
33
what are acute responses for very high doses of THC?
- Chest pain
- Rapid heartbeat
- Nausea/vomiting
- Psychotic episode - hallucinations/delusions
- Respiratory depression
34
what are long-term effects of THC?
- Physical Health Risks: respiratory and cardiovascular problems
- Psychiatric Symptoms and Disorders: cannabis addiction, depression, anxiety, psychosis
- Psychosocial Problems: poor academic and employment performance, socially withdrawn
- Cognitive Dysfunction: memory impairment
35
what are neurobiological changes seen with chronic cannabis use?
CB1Rs are downregulated in CUD participants
Amygdala volume negatively correlated with severity of CUD; hippocampus volume negatively correlated with weekly cannabis use
36
what are the therapeutic properties of CBD?
Anxiolytic, antidepressant, antipsychotic, analgesic, anti-inflammatory
Has been studied as an add-on therapy for social anxiety disorders, schizophrenia, non-motor symptoms in Parkinson’s disease, and substance use disorders
There is a lack of evidence to support many of these claims
37
effect of CBD
Non-competitive negative allosteric modulator of CB1R
- Reduces the affinity/efficacy of THC and anandamide
- Improves tolerability and safety of THC by antagonizing adverse effects of THC
Inhibits FAAH
38
what are some non-cannabinoid targets of CBD?
- Agonist at the serotonin 5-HT1A receptor
- Allosteric modulation of opioid receptors
- Agonist at transient potential vanilloid-1 receptors (TRPV1) – multisensory receptor
39
what are the CBD pharmacokinetics?
Metabolized by cytochromes P450 (CYPs) 2C9, 2C19, and 3A4
* Active metabolite: 7-hydroxy-CBD (7-OH-CBD)
* Inactive metabolite: 7-carboxy-CBD (CBD-COOH)
Lipid soluble
* Prolonged elimination
* Half life 1 hours – 30 hours (variation between studies)
40
side effects of CBD
- Decreased alertness (e.g., drowsiness and sedation)
- Changes in mood (e.g., irritability and agitation)
- Decreased appetite, gastrointestinal symptoms/distress (e.g., diarrhea)
- Drug interaction effects with over-the-counter and prescription medications
41
what are the targets of synthetic cannabinoids?
Full agonist at cannabinoid receptors (Elicit maximal activation of the receptor, beyond what is achievable with THC)
Does not contain CBD
42
The documented toxic effects of synthetic cannabinoids are _________ than those associated with cannabis
more severe and far more extensive
43
what makes cannabis difficult to quit?
withdrawal with similar severity to tobacco
44
what withdrawal symptoms are seen with cannabis withdrawal?
- Cravings
- Irritability
- Anxiety
- Depression
- Decreased appetite
- Sleep disturbances
- Weird dreams
- Restlessness
- Somatic symptoms:
headaches, sweating,
nausea, vomiting,
abdominal pain
**proportional to severity of cannabis use**
45
what is the cannabis withdrawal trajectory?
Follows a distinct and protracted trajectory: symptoms begin 24 hours after cessation, peak within 7 days, and dissipate following 28 days of abstinence
46
what are some types of cannabis withdrawal treatments? which work better?
behavioural treatments, which work the best
some pharmacotherapies that target withdrawal and the harm reduction approach
47
what is the harm reduction approach for cannabis use?
1. avoid adding tobacco
2. use safer routes (edible > vaporize > smoking)
3. use a regulated supply when able (medical or recreational)
48
what are the behavioural therapies to stop cannabis?
- Cognitive-behavioral therapy
- Motivational enhancement therapy
- Contingency management
49
what pharmacotherapies are used to treat cocaine withdrawal?
- Sedatives (e.g., Zolpidem)
- Antidepressants (e.g., bupropion)
- Synthetic Cannabinoid (oral THC, nabilone)
- CB1R antagonist (e.g., Rimonabant)
- FAAH Inhibitor (PF-04457845)
50
how well do FAAH inhibitors work to stop cannabis use?
- Lower self-reported cannabis use at 4 weeks with PF-04457845 relative to placebo
- Reduced symptoms of cannabis withdrawal
- Lower urinary THC-COOH concentrations
- Well tolerated
51
what is self-medication?
using a substance to alleviate, cope with, or reduce psychological or physical symptoms
52
is there evidence that medicating with cannabis works?
although there are some studies that show that low dose cannabis can produce anxiolytic effects for some people, more studies show that it should not be recommended for treatment
53
what are consequences of cannabis use?
cognitive impairments, psychosis, depression, suicidality, anxiety
54
what is cannabis use disorder, according to the DSM-5?
Problematic pattern of cannabis consumption that leads to clinically significant levels of impairment or distress to the user, manifested by at least two of the following 11 symptoms within a period of 12-months
55
what are some things that makes people vulnerable to cannabis use disorder?
- Daily or almost daily users
- Adolescents and young adults, especially under the age of 25
- Family history of addiction
- Those with psychiatric history
56
Acute intoxication has been shown to lead to _____________
cognitive impairments in domains like memory, learning, attention, perceptual motor skill, executive functions, and processing speed
57
what are residual effects, and which symptoms are shown to have this?
cognitive impairments that remain after acute intoxication: memory, verbal learning, executive functioning, attention, processing speed, and language
58
Cannabis can have negative effects on the ________ of
_______________ (group of people)
functioning of
students at school
59
how does vulnerabilities to residual deficits change with age?
Potential age-dependent deficits in different brain structures
60
what is psychosis?
Mental state/behaviours characterized by a “loss of contact with reality” with or without presence of hallucinations and delusions
61
what are hallucinations and delusions?
hallucinations: disorder in the experience of sensory events (e.g. see or hear aren’t there)
delusions: disorder in the representation of reality (e.g. delusions of persecution, grandiosity, paranoia)
62
what are the symptoms of schizophrenia?
- Positive symptoms: hallucinations and/or delusions
- Negative symptoms: flat affect, avolition, anhedonia, alogia
- Disorganized symptoms: disorganized speech, inappropriate affect
63
what is the dose-dependent relationship seen with cannabis on psychosis symtoms?
- Low [THC]: anxiolytic ~ feeling calm, less anxious, relaxed, slowed down
- High [THC]: can produce feelings of anxiety, hallucinations, delusions (e.g. paranoia), derealization
64
upon THC administration to people without CUD, but that have already used cannabis, what symptoms can be seen?
- Positive symptoms (similar to patient with SCZ)
- Negative symptoms
- Perceptual alterations (e.g. spaced out, detached)
- Anxious
- Tired
65
Cannabis use is a risk factor to the development of ___________
schizophrenia
66
what are factors that affect the prevalence of SCZ development with cannabis use?
1. Dose-response relationship
2. Sex Effects
(The link between CUD and SCZ is more prevalent in males)
3. Timing of use
(Using in adolescence increases the strength in the relationship between cannabis use and SCZ)
4. Genetics
(Polymorphisms: COMT, AKT1, DAT1, BDNF)
67
what is the role of COMT?
enzyme responsible for the breakdown of dopamine in the brain, on the surface of the receptor
68
what are the two explanations that can be seen for the trend where students that report consuming cannabis frequently are also meeting the criteria for anxiety and depression?
causal relationship (Substance-induced pathway) and reverse-causal relationship (symptom-driven pathway)
69
Adolescent cannabis use was associated with adult ____ and
_______, but not with _____.
MDD and
suicidality, but not with GAD.
70
with depression, Factors like _______ and __________ increased risk
young age of use and
increased frequency
71
Greater cannabis use at baseline predicted ____________ in anxiety --> _______________
slower improvements; maintenance of symptoms over time
72
was the reverse-causal hypothesis supported for anxiety and cannabis use?
no, anxiety at baseline did not predict change in cannabis use
73
what is flourishing?
the presence of positive mental health inclusive of emotional, psychological and social prosperity and is a good indicator of overall wellbeing
74
how is flourishing associated with cannabis use?
Even after controlling for depression and anxiety symptoms, flourishing was a better predictor of cannabis use levels: Flourishing was associated with lower cannabis use
75
what is the evidence for dysregulation of endocannabinoid system after chronic
cannabis use?
1. Downregulation of CB1r
2. Dysregulation in plasma and CSF endocannabinoid levels
76
what is the abstinence paradigm and what did it show?
- Participants with a CUD quit cannabis for 28 days to measure changes in different outcomes.
- Cannabis withdrawal symptoms have an onset of 24-48hours (then decrease over time)
77
why choose 28 days for the abstinence paradigm?
- Coincides with the complete urinary elimination of cannabis
- Most withdrawal symptoms dissipate after 28 days of cannabis abstinence
- Evidence that downregulation of CB1r reverses after 28 days of cannabis abstinence
78
With abstinence, withdrawal symptoms peak on day __ and dissipate over __ days
7 ; 28
79
when looking at cannabis abstinence and depression, how are they linked?
Depressive symptoms returned to baseline, which provides evidence that cannabis does not remedy depressive symptoms
