Download - Nicotine and Marijuana - CHI St. Gabriel's
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Nicotine and Marijuana
March 4, 2020
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Objectives
Develop an understanding of the history of tobacco
Review the pharmokinetic and pharmacodynamics effects of nicotine and marijuana
Demonstrate negative effects nicotine and marijuana have on health
Discuss treatments of NUD and MUD
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Tobacco: still the leading cause of
preventable death in the
United States
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History
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History-Tobacco
Native American use: Medicinal and ceremonial
Christopher Columbus: brought tobacco back to Europe
Slowly spread across Europe
1612- Became a commercial crop in Virginia
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History tobacco…
Early use: pipes, chew, snuffCigars early 1800sCigarettes not popular until after civil war (although were around in the 1600s)Late 1880s 1st cigarette making machine
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History Continued…
1930s- Correlation between cancer and smoking
1944- American Cancer Society warnings
1950s- Tobacco industry research council= made it “healthier again”
1960s- Surgeon general “smoking and health” risks emphasized
1971- Broadcast advertising banned
1995- Clinton- FDA to regulate more
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Nicotine Effects
1. Psychostimulant
2. Potent parasympathomimetic
3. Arousal during fatigue
4. Relaxation during anxiety
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POLL
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Nicotine Withdrawal
Craving, irritability, frustration, anger, anxiety, depression, difficulty concentrating, restlessness, increased appetite
Maximum withdrawal intensity 24-48 hours after last use
Diminishes over a few weeks
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Pharmacokinetics
Rapid delivery to brain with smokingSmokers titrate level:
Puff volume
Number of puffs taken
Depth inhaled
Rapid delivery to brain with smoking
T 1/2 = 2 hoursRenal excretion
Metabolized to cotinine in liver/lung/brain
CYP2A6
Female faster than male
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Ethnic Differences
African Americans30% more nicotine per cigarette
Clear more slowly than Caucasians
Chinese Americans: lower nicotine intake per cigarette
Smoke fewer cigarettes per day than Caucasians
Slower metabolism: CYP2A6
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Biochemical Markers
Blood, salivary, plasma cotinine
Expired breath carbon monoxide
Blood carboxyhemoglobin
Plasma or salivary thiocyanate
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Biochemical Markers
Cotinine: Present up to 7 days
Breath carbon monoxide (CO)> 10 ppm = smoked in the last 8-12 hours
Thiocyanate- present for weeks
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Drug Interactions
Nicotine accelerates metabolism of many drugs:
CYP1A2Theophylline, propranolol, olanzapine, clozapine imipramine, haloperidol, pentazocine, estradiol
Nicotine inhibits:Reduction in BP from beta blockers,
Ulcer treatment with histamine H₂ receptor antag
Sedation from benzos
Analgesia from some opioids
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Pharmacologic Actions
Cardiac:Low doses/ acute: ↑ blood pressure/heart rate/cardiac output/cutaneous vasoconstriction
↑ ↑ ↑doses: hypotension, slowing HR
CNS effects: arousal, relaxation during stress, enhancement mood/attention/reaction time
Rapid metabolizers smoke more
Genetic markers can cause variation in effects
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Mental Illness and Nicotine
36% current smokers (vs 20% no mental illness)
Schizophrenics: 70-88% smokers
ADHD: 40% smoke
Depression: 59% lifetime prev. smokers vs 17% general population not smokers
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Neurobiological Mechanism of Action
nAChRs- nicotine acetylcholine receptors
Opened by nicotine
Innervation to [nearly] all areas in the brain
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Systemic Toxicity
≥ 50 known carcinogens
Cardiovascular risk: CO reductions in O₂ delivery to heart
Oxidant chemicals:
Imbalance in proteolytic and antiproteolytic in lung
Heightens airway responsiveness
Chronic obstructive lung diseases
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Systemic Toxicity
EyesIncreased rates of posterior subscapular cataracts
Macular degeneration
FemalesLower levels of estrogen
Earlier menopause
Increased risk of osteoporosis
MalesImpair penile erection
Decreased appetite and increased metabolic rate: weigh 6-10 lbs less
Increased LDL, Decreased HDL
Delays healing of peptic ulcers
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Pregnancy
Nearly doubles relative risk of low birth weight in infant and relative risk of spontaneous abortion
Perinatal and neonatal mortality increases of ~ 1/3
Variation in CYP1A1 and GSTT1- roles of metabolizing and excreting toxic chemicals
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Developing Fetus
Nicotine arrests neuronal replication and differentiation
* Contribute to SIDS
Activates nicotinic cholinergic receptors in fetal brain
Abnormalities of cell proliferation and differentiation=altered synaptic activity
Increased susceptibility to hypoxiaInduced brain damage
Perinatal mortality
Sudden infant death
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Second Hand Smoke
Causally associated withAcute and chronic coronary heart disease
Lung cancer
Sinus cancer
Eye and nasal irritation
If asthma: pneumonia/COPD
LBW and SIDS
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Morbidity and Mortality
Pack in US ~ $7.18 in medical care expenditures and lost productivity
440,000 premature deaths annually150,000 CV
150,000 cancer
100,000 non malignant pulmonary disease
Male: 13.2 years lost
Female: 14.5 years lost
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Tobacco and Alcohol
Increased medical complications
Oral and esophageal cancers
>1000 lives lost to household fires
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Cessation
Immediately Decreased risk CV death
Decreased blood coagability, improved tissue oxygenation
Decreased predisposition to cardiac arrhythmia
Reduced risk of death continues for 10-15 years
After 10-15 years abstinence, risk of all-cause mortality nearly that of non-smokers
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Nicotine Treatment
BehavioralBrief interventions
Individual counseling
Group counseling
Apps, web resources, telephone counseling
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Nicotine Treatment
Pharmacologic (FDA approved)First line:
Nicotine replacement therapy (NRT): patches, gum, lozenge, spray
Bupropion
Varenicline (Chantix)
Second line:Nortriptyline
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Nicotine Treatment
Eagles Study (Lancet 2016)No increase in neuropsychiatric adverse events due to Varenicline, Buproprion, or patch
Varenicline > Buproprion = nicotine patch
Buproprion + nicotine patch > placebo
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Nicotine Treatment- Special Populations
Pregnancy:Counseling
NRT or Buproprion
Adolescents:Counseling
NRT
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Nicotine Treatment
End of treatment continuous smoking abstinence rates- clinical trials: (relative abstinence)
Varenicline: 44%
Buproprion SR: 30%
Placebo: 18%
Short acting NRT + patch -> 2.3 X more likely to be abstinent at 6 months
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Marijuana
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NIDA
“…there is evidence that cannabis or cannabinoids can treat certain medical conditions, which include nausea and vomiting from chemotherapy, spasticity from multiple sclerosis, and pain.”
“I have concerns that the report summary and press coverage may give the impression that the findings apply equally to the cannabis plant (“medical marijuana”) and to the cannabinoid formulations that have undergone rigorous clinical trials.”
Dr. Nora Volkow – Director (National Institute on Drug Abuse, NIH)
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Is Botanical Marijuana a Medicine?
Impure plant: with 750+ chemicals, 100+ cannabinoids; actions, interactions unknown
Doses: THC, CBD, inconsistent, unregulated
Smoking: most common route, health hazard to lungs
Evidence for Safety: no long term studies or adverse events
Evidence for effectiveness: Poor quality or non-existent
Edibles, vapors, resins: evidence zero or very limited
Short, long term adverse effects: Cognitive- and motor-impairment; amotivation, psychosis, etc.
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Marijuana + Anxiety
Relaxation common reason marijuana is used
HOWEVER
• Anxiety and panic most commonly noted negative effect
• Factors associated with anxiety:• Genetic vulnerability
• Personality traits
• Female
• Infrequent use
• High dose
• High THC/low CBD
• History anxiety
• Basal anxiety
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Marijuana + Anxiety
THCDecrease anxiety at lower doses
Increase anxiety at higher doses
CBDAnxiolytic
Reduces anxiety in patients with social anxiety disorders acutely, no studies for chronic
• Regular marijuana use would result in tolerance to medicinal anxiolytic effects, thus increasing risk of rebound anxiety- fostering cannabis dependence
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National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) 2016
Cannabis associated with increased prevalence and incidence of anxiety and mood disorders including (panic, social anxiety disorder, phobia, generalized anxiety)
After adjusting for: family history SUD, family environment, childhood parental loss, low self-esteem, early onset anxiety, social deviance, education years, trauma, axis I, axis II, divorce, history of AUD, history of SUD, nicotine dependency, gender, non-white)- only increased prevalence of alcohol and drug use disorders not specific anxiety disorders
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Marijuana + Anxiety
Social anxiety disorder as a risk factor for subsequent cannabis dependence
Self- medicate
Vs panic disorder avoids cannabis to avoid precipitated panic
Marijuana use may alleviate some social anxiety disorder-related impairments in the short-term but also present increased risk of harm in the long term
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Stoner SA. Effects of Marijuana on Mental Health: Anxiety Disorders. Alcohol & Drug Abuse Institute, University of Washington, June 2017.
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Marijuana
Major psychoactive ingredient- THC
Two cannabinoid receptors: CB1 and CB2CB1- primarily CNS sites
CB2- peripheral and central sites
Receptors when activated decrease neurotransmitter release
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Marijuana
IntoxicationEuphoria, hunger relaxationOccasional panic and anxietyMore rare-paranoia/panic
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Marijuana
Toxicity/adverse effectsDecrease in cognition/concentration
Decreased reaction time, slowed time, decreased motor performance
Increased risk of schizophrenia
Amotivational syndrome
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Marijuana
Effects on other organsLungs: COPD
Heart: increased HR and decreased BP
Liver: linked to numerous issues
Reproductive systems: Disrupts both male and female
May cause galactorrhea
Concentrates in fat and breast milk
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FDA Approved Cannabinoids
Marinol Capsules (1985): THC to treat nausea and vomiting associated with cancer chemotherapy only if safer conventional antiemetics are ineffective
Marinol Capsules (1992): THC to treat anorexia associated with weight loss in patients with AIDS only if safer conventional antiemetics are ineffective
Syndros (dronabinol oral solution): same indications
Cesamet Capsules (1985): Nabilone to treat nausea and vomiting associated with chemotherapy only if safer conventional antiemetics are ineffective
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Marijuana and Adolescence
Use by age 15=3.6 times less likely to graduate from high school2.3 times less likely to enroll in college3.7 times less likely to get college degree.
Thurstone, Christian, Dr. Marijuana Use & Pregnancy. May 14, 2014. Available at http://drthurstone.com/?s=pregnancy&x=0&y=0.
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Marijuana Lowers your IQ
A recent study found that those who used marijuana heavily in their teens and continued through adulthood showed a permanent drop in IQ of 8 points.
A loss of 8 IQ points could drop a person of average intelligence into the lowest third of the intelligence range.
1M.H. Meier, Avshalom Caspi, et al. 2012. “Persistent cannabis users show neuropsychological decline from childhood to midlife.” Proceedings of the National Academy of Sciences
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For Parents
Marijuana use will hurt YOUR child’s IQ, grades, and ability to graduate from high school!
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For Teachers/Schools
Increased marijuana use will result in reduced academic achievement for which teachers/school system will be blamed
College students with high levels (17 days/month) of marijuana use were twice as likely as those with minimal use (less than 1 day/month) to have an enrollment gap while in college.
In 2015, 38 percent of college students indicated that they had used marijuana in the prior 12 months, up from 30 percent in 2006http://www.monitoringthefuture.org//pressreleases/16collegedrug.pdf
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Mental Health
Regular marijuana use by adolescents and young adults is strongly associated with developing psychotic symptoms and disorders such as schizophrenia in adulthood for those people with an underlying genetic vulnerability to developing this disease
This risk is higher among those who start using marijuana at a younger age
This risk is higher with more frequent marijuana use
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Lung Cancer
One study found that in 16% of those who smoked 50 or more times, their risk for getting lung cancer doubled.
Callaghan RC, Allebeck P, Sidorchuk A. Marijuana use and risk of lung cancer: a 40-year cohort study. Cancer Causes Control. 2013 Oct;24(10):1811-20. doi: 10.1007/s10552-013-0259-0. Epub 2013 Jul 12. PubMed PMID: 23846283.Also see: http://www.wmur.com/health/study-shows-high-rate-of-marijuana-use-among-nh-youth/23987818.
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Work Performance
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Employability
1 in 17 12th graders smoke daily 2016 Monitoring the Future (MTF) Study
These students are virtually unemployable
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Companies Conducting Drug Testing
Target
Walmart
McDonalds
Police/Fire departments
Military
Transportation
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Marijuana and Driving
A new NIDA study found:
Marijuana's active chemical THC affects weaving within a road lane in a similar way to a blood alcohol level of .08, the legal limit in many states.
Marilyn Huestis of NIDA:
“One of the things we know happens with cannabis is that it reduces your field of vision and you get tunnel vision, so you're unable to react as quickly.”
http://www.dailymail.co.uk/news/article-3137943/Marijuana-DOES-impair-driving-kind-comprehensive-government-study-reveals-cannabis-use-affect-motor-skills-three-drinks.html
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Marijuana and Driving
Marijuana is the most prevalent illegal drug detected in impaired drivers, fatally injured drivers, and motor vehicle crash victims.
National Highway Traffic Safety Administration. Drug Involvement of Fatally Injured Drivers. U.S. Department of Transportation Report No. DOT HS 811 415. Washington, DC: National Highway Traffic Safety Administration, 2010.
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Marijuana and Driving
Driving under the influence of marijuana is associated with a 92% increased risk of vehicular crashes. Such driving is associated with a 110% increase in fatal crashes.
Asbridge, M., Hayden, JA, Cartwirght, JL. Acute cannabis consumption and motor vehicle collision risk: systematic review of observational studies and meta-analysis. British Medical Journal, 2012; 344 (ePub): e536. PMID: 22323502.
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Marijuana and Driving
Researchers at the University of Massachusetts, Amherst, found 44 % of college men said they drove after smoking marijuana in the previous month, compared with 12% who said they drove after drinking.
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Denver
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210 Licensed Medical Marijuana Centers
108 Pharmacies
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Traffic Fatalities
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65SOURCE: Colorado State Patrol
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66SOURCE: Colorado DOT 2018
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SOURCE: City and County of Denver, March 2017
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SOURCE: Colorado Department of Revenue, Colorado Liquor Excise Tax
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State of Minnesota Data
http://www.health.state.mn.us/topics/cannabis/about/update0418.pdf
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The New Miracle Elixir?
Miracle Elixir- 1945
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CASE
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CASE
20 yo white male
Presents with:Anxiety concerns
Poor school performance
Missing class
No history of mental health issues
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QUESTIONS?!
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CASE
ContinuedSmoking daily marijuana
Weekend binging of ETOH
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QUESTIONS?!
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CASE
Smoking to “calm down” and sleep
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Next steps?!
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CASE
Follow up at 3 weeks
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