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


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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POLL


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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POLL


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


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.


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 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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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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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


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


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?!


CASE

ContinuedSmoking daily marijuana

Weekend binging of ETOH

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QUESTIONS?!


CASE

Smoking to “calm down” and sleep

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Next steps?!


CASE

Follow up at 3 weeks

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Nicotine and Marijuana - CHI St. Gabriel's

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