Keep off the grass: Cannabis and Cardiovascular Disease ......Adverse CV Outcomes: Cardiomyopathy...
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Keep off the grass: Cannabis and Cardiovascular Disease ACC Rockies 2020 Sheri L. Koshman BScPharm, PharmD, ACPR, FCSHP Associate Professor, Division of Cardiology, Faculty of Medicine and Dentistry [email protected] @iheart_Rx
Transcript of Keep off the grass: Cannabis and Cardiovascular Disease ......Adverse CV Outcomes: Cardiomyopathy...
Keep off the grass: Cannabis and
Cardiovascular DiseaseACC Rockies 2020
Sheri L. Koshman BScPharm, PharmD, ACPR, FCSHP
Associate Professor, Division of Cardiology, Faculty of Medicine and Dentistry
@iheart_Rx
Conflict of Interest
None to declare
Objectives
Overview of “cannabasics”
Pathophysiological effect of the endocannabinoid system
Review cardiovascular safety of cannabinoid use
Cannabis in Canada: 2019
https://www150.statcan.gc.ca/n1/pub/11-627-m/11-627-m2019057-eng.htm
Cannabis in Canada: 2019
https://www150.statcan.gc.ca/n1/pub/11-627-m/11-627-m2019057-eng.htm
Statistics Canada. National Cannabis Survey, 4th Quarter 2018.
Statistics Canada 2019
Cannabis Users and CVD
DeFilippis et al. J Am Coll Cardiol 2020; 75:320-32
Cannabis in Canada: Sales
Stats Canada 2019
Products include:• Flower• Extracts• Tinctures• Edibles• Drinks• Topicals• Pre-rolls / wraps• Seeds• Bath Bombs• Vape• Pet
Potguide.com
Cannabis in Canada: Availability in AB 2020
378 Dispensaries
Cannabasics
- > 700 chemical compounds- 104 unique cannabinoids
https://www.cpha.ca/cannabasics
DronabinolNabiloneNabiximolsCannabidiol
Synthetic cannabinoids(K2, Spice)
CB2 CB1 / CB2
Cannabasics
Basic delivery methods
Inhalation
Smoked/vapourized
Oral – Mucosal
Ingestion (a.k.a. edibles)
Topical
https://www.cpha.ca/cannabasics
Cannabasics: Pharmacokinetics
Absorption
Highly lipophilic (THC >>> CBD)
High dependent on formulation
Inhaled Oral
Peak concentration 3-10 min 120 min
Bioavailabilty 10-35% 6%
Onset of action 5-10 min 30-60 min
Duration of action 2-4 hrs 4-8hrs
Lucas C, et al. Br J Clin Pharmcol 2018;84:2477-82
Cannabasics: Pharmacokinetics
Distribution
Vd = 32 L/kg
Rapid distribution into well vascularized organs
Accumulates in adipose tissue with chronic use
Affected by body size, composition, disease states
Metabolism
Hepatic:
THC: CYP 2C9/2C19/3A4
CBD: CYP 2C19/3A4/1A1/1A2/2C9/2D6
Elimination
Feces, urine
Terminal half-life
THC = 22h
CBD = 30 h – 5 day (chronic administration)
Lucas C, et al. Br J Clin Pharmcol 2018;84:2477-82
CV Drug interactions:
DeFilippis et al. J Am Coll Cardiol 2020: 75: 320-32
Cannabasics
Dose (medicinal):
THC
“Average” joint = 0.5gm of 10% THC dried cannabis
50% lost to combustion = 25mg THC
1 puff = 1-10mg THC
1-2 puffs qhs
CBD
2-3 mg po qhs
Cost:
$8-20/g
Potency of Cannabis
Volkow N, et al. N Engl J Med 2014;370:2219-27
https://www.rxfiles.ca/rxfiles/uploads/documents/CANNABINOIDS-Newsletter-CHT-QandA-RxFiles.pdf
Therapeutic Uses of Cannabis
https://www.rxfiles.ca/rxfiles/uploads/documents/CANNABINOIDS-Newsletter-CHT-QandA-RxFiles.pdf
Adverse Effects of Cannabis
Endocannabinoid System / Cannabinoid Receptor:
**- Pain- Memory- Mood- Metabolism- Reproduction- Immune function- Sleep - Stress- Appetite
Pathophysiological effects of endocannabinoid system
Receptors are located:- Myocardium- Vascular
endothelium- Smooth muscle
cells- Circulating blood
cells- Peripheral
nervous system, including the vagal nerve
Pacher et al. Nature Rev Cardiol 2018;15:151-166
ANTI-ATHEROGENIC
PRO-ATHEROGENIC
Cardiol Ther 2018;7:45-59
arrhythmias
Nature Rev Cardiol 2018;15:151-166
CV Risk Associated with Marijuana
Largely based on:
Case reports
Case series
Observational studies
Lower risk cohorts
Confounded by:
Adverse heath behaviours (e.g. concurrent tobacco use)
Recall bias
“dose”
THC:CBD
Acute vs chronic use
Timing relative to acute event
Variable results
Smoking Marijuana
Similar combustion byproducts to smoking tobacco↑ carboxyhemoglobin = ↓oxygenLarger puff volumes + longer breath hold = ↑ delivery of inhaled elementsSimilar second hand effects as tobacco
Angina
Decrease in time to exercise induced angina
ACS
2-4 fold increase risk of MI
Trigger for MI
3rd most common
2.5-4 fold increased risk of mortality
Temporal relationship to ACS
RR 4.8 risk of MI 1 hr post ingestion
RR 1.7 risk of MI 2 hr post ingestion
Younger patients
No significant lesions on angiography
Aronow WS, et al. N Eng J Med 1974; 291:65-7Nawrot TS, et al. Lancet 2011; 377:732-40
Mittleman MA et al. Circ 2001:103:2805-9Mukamal KJ et al. Am J Heart 2008;155;465-470
Adverse CV Outcomes: SIHD / ACS
Adverse CV Outcomes: Stroke
Mechanisms
Direct vasculotoxic effects
Alterations in hemodynamics
Incident AF
Reports of:
Ischemic stroke
Intracranial hemorrhage
3.3x higher incidence in stroke in user
Younger age associated with users
Case-reports of recurrent stroke in re-exposure
Hemachandra D, et al. Aust N Z J Public Heath 2016;40:226-30Singh NN, et al. J Stroke Cerebrovasc Dis 2012:21:555-60
Wolff V, et al. J Am Coll Cardiolol 2015; 66:2052-3
Adverse CV Outcomes: Arrhythmias
Limited to case-reports and retrospective studies
Atrial and ventricular arrhythmias
Acute – tachycardia
Chronic / overdose - bradycardia
NIS database:
2.5 million patients
2.7% experience arrhythmias, AF most common
2010 – 2014
2x increase in incidence
↑all cause mortality - 3.7% to 4.4%
Desai R, et al. In J Cardiol 2018;264:91-2
Pacher et al. Nature Rev Cardiol 2018;15:151-166
Adverse CV Outcomes: Cardiomyopathy
Case reports of
Stress cardiomyopathy
Myocarditis
Independent predictor of HF in 18-50 yo
Synthetic cannabinoid overdose
Cardiac shock and arrest
Kalla A, et al. J Cardiovasc Med 2018;19:480-84Grigoriadia CE, et al. J Emerg Med 2019;56:319-22
Kariyanna PT, et al. Am J Med Case Rep 2018;6:169-72Leontiadis E, et al. Ann Thorac Surg 2008;86:1982-5
No reference to any risk
with CVD
https://www.canada.ca/en/services/health/campaigns/cannabis/health-effects.html
Key Points
Evidence is limited, however there seems to be an association with cannabis use and adverse cardiovascular outcomes
Higher concentrations of THC
Changing demographics of users
Given the legalization and widespread availability of cannabis, more research is need to further elicit risk
Clinician need to routinely ask about cannabis use (dose, route frequency)
Smoking cannabis = smoking tobacco
Avoidance is the best strategy, especially in high risk groups
Questions
Sheri L. Koshman BScPharm, PharmD, ACPR, FCSHP
Associate Professor, Division of Cardiology, Faculty of Medicine and Dentistry
@iheart_Rx
