PHRM845-FINAL EXAM Flashcards
Pharmacology of cannabis/cannabinoids
Cannabis sativa/indica
- More than 400 compounds
-“entourage effect”–like Taylor Swift concert (so many cannabinoids that you don’t entirely know everything, like the T Swift concert has lights, dancers, etc so is the effect really from just T Swift?)
Key components of Cannabis sativa/indica
-delta 9 Tetrahydrocannabinol (THC)
-Cannabidiol
-Cannabinol
What is marijuana?
Dried leaves and flowers
Bushy plant
Illegal
What is hashish?
Compressed stalked resin glands (trichomes) from cannabis flower blossoms
Routes that marijuana can be used
Inhalation and oral ingestion
What percentage of marijuana is THC?
15-20%
What is hemp?
-Strain of cannabis plant that is grown for agricultural products such as textiles, seeds and oils
-Federally, it is legal to grow, use, and distribute
What percentage of hemp is THC?
0.3% or less
Cannabis is a schedule ___ product under federal controlled substance act.
-In 1937,_____
-In 1996, ____
-In 2013, _____
I (One)
-Congress passed the Marijuana tax act
-California passed Prop. 215 becoming first legal medical marijuana state (NO impact on federal law; still cannot use, grow, or redistribute it; Fed law supersedes the state)
-Cole Memo creates hands-off policy for legal medical marijuana states (as long as people are following state laws; receded under Trump)
Every state has different beliefs regarding marijuana which is ____
All mixed up and ever-changing
In Connecticut, the state wants pharmacists to distribute cannabis, but the federal government says NO. What would you do?
Not grow, use, or redistribute any because do not want DEA to be taken away.
Legalization of hemp production has allowed the production and promotion of other cannabinoids.
In 2014, _____
In 2018, _____
-14: Obama signs Farm Bill allowing hemp to be cultivated for research purposes
-18: Federally legalizes hemp and hemp-derived product sales, including CBD oil, under the Farm Bill as long as THC content is below 0.3%
Delta 9 vs delta 8
-Delta 9 is the primary euphoric agent
-Delta 8 is ~25% of psychoactive activity of delta 9
-Delta 8 is legal if derived from hemp
-In 1986, a law was passed that prohibited the sale of any schedule I analog—unclear if delta 8 is considered an analog because it is grown by a plant.
-Delta 9 and delta 8 THC are in equilibrium after decarboxylation from THCA, so according to that rxn, delta 8 should be legal
“Synthetic marijuana” use is widespread, though ____.
Agents are (less/more) potent than THC
Illegal b/c analog of a schedule I substance
More
What products are the most common cannabis use for US 12th graders?
Marijuana
K2/spice (delta 9 analog)
The number of marijuana users has ___. When something was illegal and becomes legal, you are basically sending a message that it is ___.
increased
safe & not harmful
Acute cannabis intoxication:
Perceptual
-Temporal slowing (everything slows down)
-Auditory, visual, or tactile illusions
-De-personalization (feel like they are viewing their life in a movie)
Acute cannabis intoxication:
Affective
-Euphoria
-Disinhibition (say/do things they would not normally do)
-Anxiety
-Emotional lability (laugh/cry more easily)
Acute cannabis intoxication:
physical
-Tachycardia
-Postural hypotension
-Conjunctival injection (redness in sclera of eye)
-Dry mouth
-Increased appetite
Acute cannabis intoxication:
Cognitive
-Suspiciousness or paranoid ideation
-Impaired judgement
-Impaired reaction time
-Impaired attention
Endocannabinoid system
-Widely distributed in the ___
-Comprised of ___ (4 components)
CNS
1. Receptors (CB1 and CB2)
2. Ligands (Anandamide and 2-AG)
3. Transporters (EMT [bi-directional])
4. Enzymes (FAAH, MAGL, DAG)
Do humans have a THC-like compound in their brain?
NO
Endocannabinoids vs. phytocannabinoids
Endocannabinoids are natural
phytocannabinoids come from plants
Endocannabinoids & phytocannabinoids serve as ____ of neurotransmission, inhibiting the release of ___ & ___.
retrograde regulators
GABA and glutamine
THC is a ____ at CB1 receptor while synthetic cannabinoids (Spice) are ____.
-Partial agonist
-Full agonist (more potent)
Endocannabinoids are involved in ___.
Complex biosynthetic pathway and degradation pathway
Other phytocannabinoids act on ____ which is why there are multiple possible drug targets.
multiple sites
Which expression is higher in the brain (CB1 or CB2)?
CB1
Low levels of ____ in brainstem.
respiratory centers
**Low levels in brainstem so don’t suffer from respiratory depression or coma
CB2 primarily on ____
glia
CB1 involved in ______
-Memory, stress
-Movement
-Pain sensation
-Appetite
-Movement reward
-Cognition
(CB1/CB2) expression in the periphery is high than (CB1/CB2) receptor expression.
CB2; CB1
CB2 recruit ____
dendritic cells and other cytokines, such as lymphocytes (B and T cells)
(CB1/CB2) is in the liver and increases lipogenesis. It is (upregulated/downregulated) in liver fibrosis.
CB1
Upregulated
Marinol (Dronabinol)
-FDA approved cannabinoid drug
-Synthetic delta 9 THC in sesame oil (appetite suppression in cancer patients)
-Schedule III
-Counter loss of appetite
-Tachycardia, red eyes
Nabilone (Cesamet)
-FDA approved cannabinoid drug
-THC mimetic
-Schedule II
-Anti-emetic (not as effective and not well-studied)
-Chronic pain (off label)
~Fibromyalgia
~Multiple sclerosis
Challenges with medical marijuana use
-Lack of product quality control (hard to tell what product people used in the study; only thing measured was delta 9 THC content)
-Absence of adequately designed studies for assessing efficacy and ADR
-Highly politicized environment precludes a rational approach
-Growing influence of big tobacco and alcohol industries in cannabis industry (Industries driven to increase consumption and don’t care about pt safety)
Cannabidiol (CBD) pharmacology and use
-____ affinity for CB receptors
-May antagonize delta 9 THC @ ____
-Promiscuous effects on ___
-Lacks euphoric effects
Low
CB1
ECS
Cannabidiol interacts with many receptors including ____
-CB1 and CB2
-GPR55 and PPAR gamma
-Allosteric modulation (alpha1gamma glycine; mu and delta opioid receptor)
-5HT1A
-TRPV1, TRPV2, TRPA1, TRPM8
CBD oil legality in Indiana
<0.3% THC
**Most common reported use is for pain (data does not support that it is useful for pain)
**FDA approved drug for seizure disorder
What forms is CBD oil in?
-Oral
-Topical
-Cosmetic
-Edibles
-Vaporizers
CBD products are (regulated/unregulated) and of unknown and variable quality
Unregulated
**Falls under dietary/health supplements so FDA has no regulation over it
Range of concentration of cannabidiol
0.10-655.27 (huge range b/c unregulated)
Delta 9 THC range
0-6.43 (some has higher than permissible delta 9 THC content)
CBD approved for rare seizure disorders. Which seizure disorders are they?
-Dravet syndrome
-Lennox-Gastaut syndrome
**Arises from chromosomal abnormalities and have very poor prognosis
**Some pts respond to these agents (went through all the steps for quality control)
THC content has (increased/decreased/stayed the same) markedly
Increased
***4-5 times more potent than in 1995
CBD content has (increased/decreased/stayed the same).
Stayed the same over the years
What classifies as cannabis use disorder?
At least 2 of the criteria are met
**More then 6 for severe cannabis use disorder classification
Criteria for cannabis use disorder
- Cannabis is often taken in larger amounts or over a longer period than was intended.
- There is a persistent desire or unsuccessful efforts to cut down or control cannabis use.
- A great deal of time is spent on activities necessary to obtain cannabis, use cannabis, or recover from its effects.
- Craving, or strong desire or urge to use cannabis.
- Recurrent cannabis use results in failure to fulfill role obligations at work, school, or home.
- Continued cannabis use, despite having persistent or recurrent social or interpersonal problems causes or exacerbated by the effects of cannabis.
- Important social, occupational, or recreational activities are given up or reduced because of cannabis use.
- Recurrent cannabis use in situations in which it is physically hazardous.
- Cannabis use continues despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by cannabis.
- Tolerance
- Withdrawal
Can we predict if someone will develop cannabis use disorder?
NO! So many factors are involved
**It is estimated that 10% of cannabis users will develop cannabis use disorder
Is cannabis use associated with mental health disorders?
-Extremely difficult to prove and is controversial
-Growing evidence for association (NOT causation) with several disorders; cause and effect not established
Using cannabis at a younger age is associated with having a greater risk of developing ____
Schizophrenia-like psychosis
Heavy cannabis use risk factors and pathway to psychosis
-Age of use onset and potency appear to be the key determinants
3 stages of cannabinoid hyperemesis syndrome
- Prodromal
-Normal eating habits
-Continued cannabis use - Hyperemetic (up to 48 hours)
-N/V (cyclical)
-Compulsive hot showers/baths
-Abdominal pain - Recovery
-Restored eating habits
-Relative wellness
Diagnostic criteria for cannabinoid hyperemesis syndrome
-Cyclic vomiting and abdominal pain
-Presentation after prolonged, excessive use (days-weeks of heavy cannabis use)
-Relief by sustained cessation
-May be associated with pathological bathing
Tx of cannabinoid hyperemesis syndrome
- Cannabis cessation
-Benzodiazepines (if pt gets very anxious)
-Haloperidol
-Capsaicin cream (abdomen)
MOA of capsaicin cream for cannabinoid hyperemesis syndrome
- Substance P activates neurokinin-1 receptors in the medullary vomiting center of the CNS causing N/V
- Activation of transient receptor potential vanilloid-1 (TRPV-1) receptor by heat, capsaicin, or acidic conditions causes depletion of substance P.
- Chronic cannabis use causes desensitization and downregulation of TRPV-1 receptors which increases N/V.
- Topical capsaicin activates TRPV-1, directly depletes substance P, and is a local analgesic to decrease N/V.
