Breaking Down the Cardiovascular Risk of Cannabis - Smoked vs. Non-smoked
And then there's the new generation of cannabinoid designer drugs
You have probably heard from somewhere that cannabis is associated with an increased risk of cardiovascular events (CV) like heart attacks, strokes, and arrhythmias, etc.
So should you be concerned if you use cannabis? That depends on many different factors - like your cardiovascular (CV) history, pre-existing risk factors, the type of cannabis you use and how you use it (eg. smoked, vaporized, oral, etc.). The most important factors actually are the type of cannabis and method of administration. And the risk is not the same across the board.
Traditionally, cannabis has been plant-derived (for example, from cannabis sativa). But now a days, you can also get prescription cannabinoids like dronabinol, nabilone, and nabiximols (dronabinol is synthetic THC, nabilone is a synthetic THC analog and nabiximols is a 1:1 plant-derived THC:CBD oromucuosal spray) and other synthetic cannabinoids (basically “designer” drugs that are commonly mixtures of several potent synthetic cannabinoid receptor subtype 1 agonists) that are 10-170 times more potent than THC (i.e. these are actually illicit drugs known as K2, Spice, Black Mamba, Bombay Blue, etc.). The designer drugs are more potent than THC because THC is a partial agonist at the cannabinoid receptor subtype 1 whereas designer drugs are full agonists.
From the published scientific literature, we know that cannabis, specifically THC, is associated with an increased CV risk but most of the publications out there are actually on smoked cannabis or from case reports detailing CV events and complications caused by designer drugs. The number of clinical trials evaluating the CV risk of non-smoked cannabis is actually extremely limited or almost non-existent.
At the moment, we know that smoking cannabis does increase the risk of heart attacks, strokes, and arrhythmias. A study by Mittleman et. al found that the risk of a heart attack was 4.8-fold higher in the hour after smoking cannabis and that it declined rapidly past the first hour. For reference, smoking cocaine is associated with about a 24-fold increased risk of a heart attack one hour after use.
The exact mechanism by which smoking cannabis induces a heart attack remains unclear but is likely multi-factorial. One hypothesis is the mismatch in the heart’s oxygen supply and demand. Smoking cannabis is associated with 1) an elevation in the level of carboxyhemoglobin (a complex that forms when hemoglobin comes into contact with carbon monoxide) that ultimately reduces oxygen-carrying capacity and 2) a dose-dependent increase in the heart rate of 20-100%, increasing oxygen demand. This increase in heart rate is pretty immediate -occurring within 10 minutes of cannabis inhalation, peaking at 10-30 minutes and lasting 2-3 hours.
But the processing of smoking - whether it’s nicotine or cannabis, confers additional CV risk as it causes inflammation, endothelial dysfunction (impaired functioning of the blood vessel lining), oxidant damage, all of which promote plaque rupture, acute thrombosis and/or vasoconstriction with reduced coronary blood flow which ultimately increase the risk of stroke, acute coronary syndrome and sudden cardiac death.
Smoking cannabis may also result in elevated blood pressure or postural hypotension. In fact, published data suggest that low doses of THC activate the sympathetic nervous system and the release of norepinephrine thereby increasing heart rate and blood pressure and that high doses result in parasympathetic stimulation resulting in bradycardia and hypotension.
What about the CV risk cannabis that isn’t smoked? There isn’t a lot of published data on the CV effects of cannabis when taken orally or sublingually but from the data that is available, we know that tachycardia, hypotension and orthostatic hypotension can still occur - one study reported an increased heart rate (HR) about 1.5 hours after an oral dose of THC (vs. 0.5 hours after smoked or vaporized THC). CBD, on the other hand, may reduce HR and blood pressure and improve vasodilation. And according to one systemic review and meta-analysis of medical cannabinoids, formulations containing THC and CBD produced less tachycardia and orthostatic hypotension compared to THC-only formulations. Furthermore, none of the studies in this review reported serious CV events like stroke, heart attack or arrhythmia so the findings aren’t quite the same as smoked cannabis.
What about vaporized cannabis? In terms of cannabis onset, peak, duration and the changes in HR and blood pressure, vaporized and smoked cannabis are pretty much the same. Vaporized just means there’s significantly less inhalation of harmful bi-products like less carbon monoxide and polycyclic aromatic hydrocarbons (PAH). In terms of CV risk, it’s probably similar to smoked cannabis since they share similar pharmacokinetics profiles but with less toxic bi-products, the risk is probably a bit less. In general though, I’d recommend avoiding any form of inhaled cannabis if there are CV concerns (or asthma/COPD or any other pulmonary concerns).
Does this mean you cannot use cannabis if you have CV risk factors or a history of CV events? Not necessarily - you would want to be cautious though to be on the safe side. And you probably shouldn’t smoke it as we know the literature is full of published reports on the risk of CV events related to smoking cannabis. Nor do you want to use massive THC doses. Oral, sublingual or oromucosal formulations with a lower THC and higher CBD ratio would be more suitable options.
The good news also is that a very recent randomized controlled study (Rosa et. al) looking at the use of nabiximols (the 1:1 oromucosal spray) in post-stroke patients did not find significant changes in blood pressure or HR nor did they find any CV complications arising from nabiximols use. The average dose in this study was not exactly low either - 9 sprays, which corresponds to 24.3mg THC and 22.5mg CBD. BUT titration was done gradually and started at 1 spray a day.
As a Pharmacist and cannabis educator, I always take a cardiovascular history (technically a full medical history) when determining the appropriateness and safety of cannabis. I have had patients with hypertension or a history of CV events (eg. stroke, heart attack and stable for at least half a year) start on cannabis but with lower THC, higher CBD formulations and titrated up very slowly and gradually. Regular monitoring of HR, blood pressure and cardiac status was also done during the titration and maintenance process.
What about tolerance from repeated exposure? Many studies have demonstrated that after repeated cannabis exposure, the elevation in HR and blood pressure are attenuated and then lost, suggesting tolerance to the CV effects of cannabis. But does this mean that you’ll still be tolerant to the effects if you had taken cannabis for a while, stopped, and then resumed? Nope - tolerance is lost as soon as you stop taking cannabis, as demonstrated in a study that showed loss in CV tolerance as soon as 48 hours after oral THC intake was stopped. So generally speaking, I don’t recommend going on and off cannabis as it can cause unnecessary fluctuations in blood pressure and heart rate.
What this all means..
While there is an elevated CV risk associated with cannabis use, the data pertains to smoked cannabis, cannabinoid designer drugs or massive THC doses. This risk applies even to young and healthy individuals without any CV risk factors
If you have CV risk factors or a history of CV events, you probably shouldn’t be smoking/vaporizing cannabis, using cannabinoid designer drugs or taking massive THC doses
If you have CV risk factors or have a history of CV events and you do want to use cannabis, it would be best to use oral, sublingual or oromucosal forms of cannabis (instead of smoked) and to start with lower THC doses or a lower THC, higher CBD formulation. Blood pressure, heart rate, and cardiac status should be monitored closely during the initial titration process and regularly during maintenance.