11. Tobacco, Vaping, MJ, CBD Flashcards
What are the benefits of smoking Juul/vaping, compared to cigarettes?
- Cigarette smoke has thousands of chemicals and > 70 carcinogens; e-cigs have less chemicals (~80)
- Less damage to lungs
- Cheaper
- Tastes better
- Fingers don’t smell like smoke; stains disappear
- Whiter teetch
- Overall looks improve bc no damage to skin and hair
- Sense of smell/taste improves
- Social interactions increase bc vaping is not seen as dirty
- Dont need to go outside for a smoke break
- Helps ppl stop smoking cigs
What are reasons for vaping?
- Use by a family/friend
- Taste
- Belief that vaping is safer > tobacco products
- Curiosity
Why has vaping/Juuls become a concern?
- 19% of girls and 23% of boys in middle/HS use tobacco products: common to use both e-cigs and regular cigs; MC in older, non-hispanic white and hispanic
- Upward trend of e-cig use in 10th graders in US (68% of e-cig users use flavors):
- Students become addicted to nicotine, which can harm developing brain, which contintues to develop until ~ 25 YO.
Why are adolescents more vulnerable to doing drugs and becoming addicted?
In adolescents, the prefrontal CTX is still developing. It is responsible for executive function: causing ↑-risk taking, impulsivibity and novelty seeking behavior.
Physiologically, how does nictoine affect the brain?
- Nicotine (+) nAChR on neurons in VTA => ↑ DA release in pre-frontal CTX.
- Impairs neuroplasticity (ability of brain to change T/O persons life) => alters gene expression, cell structure, intracellular signialing, synpatic pruning, removing redundant connections), myelination
How does nicotine affect the prefrontal CTX?
- Causes long-term cognitive impairment, affecting both accuracy and impulse control.
- Adolescent smokers: ↓ prefrontal CTX activity => ↓ memory and ATN
- Behavioral disturbances later in life: substance abuse/mental health problems
Is vaping safer than smoking?
Perhaps it is safer than burned tobacco products, but vape still has harmful chemicals. Overall impact on health has not been determined: may have compounds not safe to ingest and vitamin E acetate
How does vaping damage the lungs?
Vitamin E acetate, a thickening agent used to dilutre THC oil causes acute toxic lung injury, within a few days to weeks => pneumonia patters in lungs => extensive lung damage requiring O2 and days on ventilatory and permenent damage in some.
What is DWW theory in the vaping health crisis?
Aerolizing oil lets them penetrate deep in the lungs, coating the surfaces and creating a thin layer of oil that soaks up toxins and particles from air we breathe in, based on oil-water partition coefficient => deposit of toxins that cause damage.
What are other theories of the sudden vaping crisis?
- Bad ingrediants (Vit E acetate)
- Contaminents in products
- Past cases were not detected as being due to vaping
- Home-made vape
- Chinese tarriffs made poor quality materials
- Slow regulations: FDA pushed back scheduled review until 2022
How have we moved to banning e-cigs?
- Fruit and mind flavored cartridges must be DQ, except for tank vaping systems.
- Tobacco purchase was raised from 18 => 22.
*
- Tobacco purchase was raised from 18 => 22.
What chemicals does medical marijuana have?
> 100 chemicals called cannabinoids. Main two are:
- THC (delta-9-tettrahydrocannabinol) => makes you “high”
- CBD (cannabidiol)
How is medical marijuana regulated?
- Schedule 1 drug, making research with drug difficult because of need for permits. But;
- Legal for medicinal purposes in 33 states/DC: need a written recommendation from a doctor, a qualifying condition + a medical card.
MOA of Marijuana?
What enzymes break down endocannabinoids?
- Post-synaptic neuron makes endocannabinoids by stimulai that cause ↑ in intracellular Ca2+ => (+) DAG-lipase => make anandamide (partial AGO) and 2-arachidonylglycerol (2-AG; full AGO)
- Go into synaptic space => bind to CB1-R on presynaptic neuron
- (-) AC
- Hyperpolarize presynaptic neuron due to less Ca2+ influx and K+ moves out
- Less NT release
-
To stop endocannabinoids:
- FAAH (fatty acid amide hydrolase) in post-synaptic cell hydrolyzes anandamide
- MAG-lipase, in presynaptic cells, breaks down 2-AG.
- **CB2-R are found on immune cells and cause cytokine reelase. However, endocannibinoids have higher affinity for CB1R.
What effects are mediated by the CB1-R?
- 1. Analgesia
- 2. ↑ Appetite
- 3. Relaxes muscles
- 4. Hormonal action
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5. Psychoogical effects:
- Affective: euphoria and laughter
- Sensory: increased perception of external stimuli, own body
- Somatic: feeling of floating/sinking in bed
- Cognitive: altered perceptions in time/memory lapses
What is a synthetic THC approved by the FDA?
- What receptor does it bind to?
- Use?
- Off-label use?
-
Dronabinol: orally-administered synthetic THC, that binds to has equal affinity for CB1R = CB2R, but high efficacy at CB1-R
-
Use: anorexia in AIDS patients, chemotherapy-induced N/V
- Off label: moderate - severe obstructive sleep apnea
-
Use: anorexia in AIDS patients, chemotherapy-induced N/V
What drug is approved ONLY for chemotherapy induced N/V?
Nabilone, a capsule.
Why is cannabis better than synethesized cannabinoids, like Dronabinol or Nabilone?
- Less expensive
- Overall effect is different: “entourage effect”
AE of Medical MJ
- Most AE are minor
- Affects judgement and coordination
- Sedation, bloodshot eyes, depression, dizzy, tachycardia, hypOtension, hallucinations and dry mouth
- Affects intelligence and mental fx in younger people, whose brains are still developing.
- Addictive and “gateway drug”/
What conditions is cannibis effective for?
- Chronic pain: esp neuropathic pain, RA, fibromyalgia, cancer pain
- N/V (Ondansetron = more effective)
- ↑ appetite in cancer or HIV/anorexic patients (Megestrol = more effective)
- Multiple sclerosis (spastiticty and pain and bladder fx)
- Anxiety and PTSD
- Sleep quality
Cannabinis is effective for N/V and increasing appetitie in cancer/AIDS pts. However, what drugs work better?
N/V = Ondansetron
Increasing appetitite = Megastrol
Does cannabinis work for Tourettes, Parkinsons or Alzheimers?
- Tourettes = limited benefit
- Parkinsons and Alzheimers = unclear
Can cannabis be taken with opioids?
Yes, allowing us to give lower doses of opioids.
What conditions does cannabis LACK efficacy?
- Acute pain
- Tremors in MS
- Huntingtons/ schizo/ depression
- Glaucoma
- Slowing growth of cancer cells
CI of Cannabis
- Hx of psychosis
- Current/past substance abuse disorder
- CV/ respiratory disease
Caution of using Cannabis (start LOW and go SLOW)
- < 25 YO
- Active mood disorder
- RF for CV disease
- Pt using high doses of alcohol /benzos
What are the qualifying conditions for a Missouri Medical MJ card?
- Cancer
- Epilepsy
- Glaucoma
- Intractable migraines
- Chronic conditions that cause pain/muscle spasms: MS, Parkinsons, Tourettes
- Psych disorders: PTSD
- HIV/AIDS
Getting a medical MJ card allows you to home-grow how much weed and under what conditions?
- < flower plants; < in a vegetative state; < seedlings
Why has FAAH (fatty acid amide hydrolase) of interest to pharmacetical manufactors?
- FAAH inhibitors/inactivators have been developed because of their ability to ↑ the concentration of endocannabinoids.
- Scottish W with a FAAH mutation: experiences little anxiety/fear, does not feel pain and heals quickly.
- Many inhibitors made, no successful clinical trials: BIA 10-2474 caused severe AE in 5th pt and death of 6th.
Legally, where does CBD (cannabidoil) stand?
- Illegal to sell a s food, dietary supplement or animal feed
-
Hemp CBD was delisted as a scheduled substance and can be sold as a cosmetic ingredient.
- FDA regulations still apply.
What enantiomer of CBD is used?
(-) CBD enantiomer
How is CBD administered?
Metabolism?
- Generally, orally as a capsule or dissolved in sesame/olive oil: it has poor aqueous ability, making absorption in GI tract erractic. Because a significant 1st-pass metabolism => 6% oral bioavailability.
- If inhaled, sublingual, intranasal: higher BA and peak concentration in blood in 5-10 min.
How is CBD similar to THC?
- Rapidly distrubutes
- High volume of distribution
- Accumulates in fat tissue due to high lipophilicity.
How is CBD different from THC?
The effects of CBD are very different from THC, often opposing.
- Inverse AGO and negative allosteric modulator of CB1/2 -R
- TRPV1, PPARy and 5HT-1A AGO
CBD is metabolized in the _____ by ______ and _______
Liver by 7 CYPS, mainly CYP3A4 and 2C19.
AE of CBD
-
Well-tolerated:
- no psychoactive effects
- no potential for abuse: no reports of tolerance/withdrawal,
CBD effects on
- embryonic development
- immune system
- drug interaction?
- No effect on: embryonic development, wide range of physiological/biochemical parameters (unless at high doses),
- Unclear effects on immune system (high concentration = immune suppression but low doses = stimulate immune system)
- Potential for drug interactions, when CYP450 is inhibited
What is the FDA-approved CBD and what recommendations are made?
-
Epidiolex, oral CBD that is a Schedule 5 drug approved for tx of r_are childhood epilepsy_ in ppl > 2YO
-
Use:
- Lennox-Gastuat syndrome (tonic seizure that occur in non-REM sleep)
- Dravet syndrome (myoclonic szrs triggered by warm baths)
- Rec: look for liver toxicity and suidical ideation
-
Use:
Other therapeutic uses of CBD
- Alzheimers (anti-inflamm actions)
- N/V
- Fragile X syndrome
- Skin diseases (NL unwanted skin growth, reduce excesive oils, reduce inflamm and infection)
- CBD tampons for menstrual pain
