MODERN CANNABISAND LUNG HEALTH

Jeff Callard PA-C DFAAPA,Diplomat SEMPALead APPSt Joseph Mercy HospitalDepartment of Emergency MedicineAnn Arbor, MIEmergency Medicine Fellowship DirectorEmergency Physicians Medical Group

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ACTIVITY DISCLOSURES

• No Commercial Support was received for this activity.

• No individuals involved in the creation of this medical educational activity had any relevant financial relationships or conflicts of interest to disclose

• But willing for the right price

DEDICATED TO:

WHO CARES???

MAINE RESTAURANT SAYS THEY HUMANELY KILL LOBSTERS BY FIRST GETTING THEM HIGH ON MARIJUANA. BY BRIAN NEWLIN

POSTED: 10:22 AM, SEPTEMBER 20, 2018 UPDATED: 10:22 AM, SEPTEMBER 20, 2018HTTPS://WWW.CLICKONDETROIT.COM/NEWS/NATIONAL/MAINE-RESTAURANT-SAYS-THEY-HUMANELY-KILLS-LOBSTERS-BY-FIRST-GETTING-THEM-HIGH-ON-MARIJUANA

MICHIGAN VOTERS TO DECIDE NOV. 6 WHETHER TO LEGALIZE RECREATIONAL MARIJUANA

GOALS/TOPICS• Changes in legislation → Changes in use patterns

• The “burning platform” for marijuana research

• Current understanding of the pulmonary effects of cannabis use

• Limitations to the current understanding

• Limitations in the efficacy and safety of our current medicinal use

• Future directions

SMOKING USE

SMOKING

• Water pipe and bongs: water filter

SMOKING

• Water pipe and bongs: water filter

• Equal amount drug

• No decrease smoking risk

SMOKING

• Water pipe and bongs: water filter

• Equal amount drug

• No decrease smoking risk

• Vaporizer

• Heat to combustion point

• Lower tar level

• Fewer adverse respiratory symptoms

SMOKING

• Vaporizer

• Heat to combustion point

• Lower tar level

• Fewer adverse respiratory symptoms

• BUT…..

• Increased ammonia

• Irritation increased

• CNS adverse effects

• Increase asthma/bronchospasms

WHAT DO WE – THINK – WE KNOW!

MARIJUANA: FACTS

• Cannabis comes from a flowering plant native to central Asia and the Indian sub continent.

• Major active compounds

• Delta 9 Tetrahydrocannabinol (THC)

• Psychoactive component

• Cannabidiol (CBD)

• Modulates the THC

• Pain

• Seizure control

MARIJUANA: FACTS

• Genus includes

• sativa-higher THC

• Indica-higher CBD

• Rudarlis-

• lowest THC

• Smells like skunk

MARIJUANA: FACTS

• Increase in allergy symptoms which is increasing in Colorado since legalization

• Increase users

• Increase exposure to non-users

• Ann Allergy Asthma Immunol 199(2017) 558-571.

MARIJUANA: FACTS

• Good?

• Internet recommends cannabis

• Pain control

• Relaxation

• Seizures

• Cures of many diseases

• May fix opiate problem

• But.. No studies • Journal of Science and Medicine in sports 20(2017) 825-829)

MARIJUANA: FACTS

• Good?

• Internet recommends cannabis

• But.. No studies

• THC

• bronchodilator

• Journal of Science and Medicine in sports 20(2017) 825-829)

MARIJUANA: FACTS

• Good?

• THC

• Bronchodilator

• There are much better bronchodilators with lower side effects

• Induces tachycardia

• Lower blood pressure

• Cannabis decreases aerobic performance

• Journal of Science and Medicine in sports 20(2017) 825-829)

MARIJUANA USE TIMELINE

2700 BC

First Medical Use

1850 AD

Added to US Pharmacopeia

1937 Marijuana

tax act

1988

Schedule 1

1991 –Present

Medical MJ legalized 23

states

2006

FDA statement

2014

Medical

Recreational

POTENCY OVER THE YEARS

REMINDER OF THE CHEMICAL

• HCN: Hydrogen cyanide: It is a colorless liquid with a piercing, acrid smell. The smell of

burnt fat is caused by glycerol in the burning fat breaking down into acrolein.

• Formaldehyde: Formaldehyde is a naturally occurring organic compound with the formula CH2O. It is the simplest of the aldehydes. The common name of this substance comes from its similarity and relation to formic acid

• Ammonia: The simplest pnictogen hydride, ammonia is a colorless gas with a

characteristic pungent smell.

REMINDER OF THE CHEMICAL

• PAHs: Polycyclic aromatic hydrocarbons are hydrocarbons—organic compounds

containing only carbon and hydrogen—that are composed of multiple aromatic rings. The simplest such chemicals are naphthalene, having two aromatic rings, and the three-ring compounds anthracene and phenanthrene.

• NO2: Nitrogen dioxide is the chemical compound with the formula. It is one of several nitrogen oxides. is an intermediate in the industrial synthesis of nitric acid, millions of tons of which are produced each year which uses is primary in production of fertilizers

• Acrolein: It is a colorless liquid with a piercing, acrid smell. The smell of burnt fat is

caused by glycerol in the burning fat breaking down into acrolein.

SIMILARITIES TO TOBACCO

Cannabinoids Nicotine

Tar

Acrolein

Formaldehyde

Ammonia

PAHs

HCN

NO2

ADVERSE EFFECTS OF TOBACCO SMOKING

• Cause of 1 in 5 deaths in the United States• Cause of 1 in 5 deaths in the United States

ADVERSE EFFECTS OF TOBACCO SMOKING

• Cause of 1 in 5 deaths in the United States

• Coronary Artery Disease

ADVERSE EFFECTS OF TOBACCO SMOKING

• Cause of 1 in 5 deaths in the United States

• Coronary Artery Disease

• Cerebrovascular Accidents

ADVERSE EFFECTS OF TOBACCO SMOKING

• Cause of 1 in 5 deaths in the United States

• Coronary Artery Disease

• Cerebrovascular Accidents

• Lung Cancer (Bladder, blood/AML, Cervix, Colon/Rectal, Esophagus, Kidney, Ureter, Larynx, Liver, Oropharynx, Pancreas, Stomach, Trachea, Bronchus)

ADVERSE EFFECTS OF TOBACCO SMOKING

• Cause of 1 in 5 deaths in the United States

• Coronary Artery Disease

• Cerebrovascular Accidents

• Lung Cancer (Bladder, blood/AML, Cervix, Colon/Rectal, Esophagus, Kidney, Ureter, Larynx, Liver, Oropharynx, Pancreas, Stomach, Trachea, Bronchus)

• COPD

ADVERSE EFFECTS OF TOBACCO SMOKING

• Cause of 1 in 5 deaths in the United States

• Coronary Artery Disease

• Cerebrovascular Accidents

• Lung Cancer (Bladder, blood/AML, Cervix, Colon/Rectal, Esophagus, Kidney, Ureter, Larynx, Liver, Oropharynx, Pancreas, Stomach, Trachea, Bronchus)

• COPD

• Adverse effects on pregnancy

“UNDERSTANDING” TO DATE

Habitual

Smoked

Cannabis Use

Airways Disease(1) Chronic Bronchitis(2) Abnormal

histopathology

Immunomodulation(1) Activation of cannabinoid

system(2) Upper and Lower airways

infections

HABITUAL INHALED CANNABIS RESULTS IN AIRWAY PATHOLOGY

Roth, Am J Respi Crit Care Medicine 1998

CHRONIC USE AND RESULTS

• Marijuana smoke contains particular matter that induces

• oxidative stress

• inflammation

• Annals of Internal Medicine 2018; 169:106-115

CHRONIC USE AND RESULTS

• Marijuana smoke contains particular matter that induces

• oxidative stress

• inflammation

• Endobronchial biopsy data users v non-users

• Chronic airway inflammation

• Epithelial injury

• Basal cell hyperplasia

• Goblet sell hyperplasia

• Subepithelial inflammation

• Annals of Internal Medicine 2018; 169:106-115

ALTERED IMMUNE RESPONSES

Croxford, Journal of Neuroimmunology 2005

CANNABINOID EXPOSURE INCREASES OXIDATIVE STRESS INDICES IN VITRO

Murine lung epithelial cells

2013

Human endothelial cells

1999

INHALED CANNABIS EXPOSURE IS ASSOCIATED WITH IMPAIRED ALVEOLAR MACROPHAGE FUNCTION

AJRCCM 1997 1 μg/mL E coli LPS

CANNABINOID EXPOSURE DECREASES MACROPHAGE VIABILITY

Mouse

peritoneal

macrophages

1998

Murine peritoneal macrophages

2013

DO ALTERATIONS IN IMMUNE RESPONSES AND OXIDATIVE STRESS AFFECT CLINICAL OUTCOMES?

INHALED CANNABIS USE IS ASSOCIATED WITH UPPER AND LOWER AIRWAY INFECTIONS

EFFECTS ON SPIROMETRYAIRWAY FUNCTION

• Similar to inhaled isoproterenol in asthmatics

• Mediated via CB1 receptor agonism

• Decrement in FEV1 in ‘chronic smokers’ which is reversible with cessation

• Increased risk for decrement of FEV1/FVC

• Driven by an increase in FVC

• No increased risk of COPD

• Asthma?

CANNABIS SMOKING ON LUNG FUNCTION AND INFECTION CONTINUED• Experimental

• Bronchodilator effect (THC)

• Analgesic effect

• npj Primary care Respiratory Medicine (2016)26 www.nature.com/npjcrm

CANNABIS SMOKING ON LUNG FUNCTION AND INFECTION CONTINUED• Reality

• Increased FVC with chronic use

• Similar reactions of tobacco

• Additive affect if use both

• Cannabinoids

• Varies with THC concentration

• Partial agonist

• Even be antagonist

• npj Primary care Respiratory Medicine (2016)26 www.nature.com/npjcrm

LIMITATIONS TO OUR KNOWLEDGE

• Lack of homogeneity of exposure (type of marijuana/THC/CBD and route of smoking such as vaping)

LIMITATIONS TO OUR KNOWLEDGE

• Lack of homogeneity of exposure (type of marijuana/THC/CBD and route of smoking such as vaping)

• Confounding variables (tobacco or smoked WITH cannabis)

LIMITATIONS TO OUR KNOWLEDGE

• Lack of homogeneity of exposure (type of marijuana/THC/CBD and route of smoking such as vaping)

• Confounding variables (tobacco or smoked WITH cannabis)• Limited longitudinal data

LIMITATIONS TO OUR KNOWLEDGE

• Lack of homogeneity of exposure (type of marijuana/THC/CBD and route of smoking such as vaping)

• Confounding variables (tobacco or smoked WITH cannabis)• Limited longitudinal data• No funding due to status as schedule 1

LIMITATIONS TO OUR KNOWLEDGE

• Cannabis exposure is different• In vitro data → exposure to only one cannabinoid (>60 in cannabis)• Human data → THC content has significantly increased

• Honesty/Reliability of cannabis quantification• Quantification of cannabis exposure – “joint year?”

QUITTING MARIJUANA AND ASTHMA

• Asthma associated with use of Cocaine, Heroin and Marijuana

• Bad

Journal of Asthma 54:7 714-722

QUITTING MARIJUANA AND ASTHMA

• Asthma associated with use of Cocaine, Heroin and Marijuana

• Chronic Marijuana smokers

• Greater than 52 times over year

• Quit smoking

Journal of Asthma 54:7 714-722

QUITTING MARIJUANA AND ASTHMA

• Asthma associated with use of Cocaine, Heroin and Marijuana

• Chronic Marijuana smokers

• Greater than 52 times over year

• Quit smoking

• Returned to normal clinically

• Morning cough

• Sputum production

• Wheezing

Journal of Asthma 54:7 714-722

INCREASING THC CONTENT

Volkow et al NEJM 2014

SCHEDULE 1

THE TIDE MAY BE TURNING

THE TIDE MAY BE TURNING

MICHIGAN MEDICAL MARIJUANA PROGRAM

HTTPS://WWW.THORACIC.ORG/PATIENTS/PATIENT-RESOURCES/RESOURCES/MARIJUANA

FUTURE DIRECTIONS

• Advocate for change in the schedule 1 status

• Improve understanding of medicinal uses

• Opioid crisis

• Epilepsy

• Asthma?

FUTURE DIRECTIONS

• Advocate for change in the schedule 1 status

• Improve understanding of medicinal uses

• Opioid crisis

• Epilepsy

• Asthma?

• Improve our knowledge about – pulmonary – long term side effects

• Educate our patients and the public

CONCLUSIONS

• Use is INCREASING and will continue

• It is predominantly smoked and Vaped

CONCLUSIONS

• Use is INCREASING and will continue

• It is predominantly smoked and Vaped

• The medicinal benefit and long-term effects are poorly understood

• Current “understanding” is outdated and inaccurate

CONCLUSIONS

• Use is INCREASING and will continue

• It is predominantly smoked and Vaped

• The medicinal benefit and long-term effects are poorly understood

• Current “understanding” is outdated and inaccurate

• Limitations to studying it based on schedule 1 designation

• Lack of knowledge is a public health concern

• A unique opportunity for activist? For many of the reasons above →Pulmonologists?

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Questions?

jcallard@epmg.com

734-712-5401