This is a blog post from Andrew Megahy, Senior Scientist at AP Organics, which first appeared on their blog in September 2019.
It is undeniable that the CBD market is flourishing. Previous posts by my colleagues have documented its growth in UK, EU and US markets, its applications in cosmetics, pain-relief and anti-inflammatory roles, and tracked its regulation by governing bodies. In this post I’d like to spend a little time going into the science behind CBD and – to a lesser extent – cannabinoids in general.
Firstly I’d like to talk about the safety profile of CBD specifically. Despite its current rise in popularity, research into CBD and its effects has been ongoing since as early as the 70s (Zuardi et al., 1982). As one would expect, early research included investigations into the toxicity of this and other cannabinoids. Toxicity is typically measured with the LD50 value, which is the Median Lethal Dose: the amount of that substance required for a fatal dose for half of the members of a tested population after a specified test duration. I was unable to source data for the LD50 in humans (something I’m actually quite relieved about) but the Toxicology Data Network states the LD50 for rhesus monkeys as 212mg of intravenous CBD per kilogram of body mass (TOXNET). They also state that in mice it was 50mg per kg body weight. If we presume a tentative correlation where tolerance increases with increasing body mass, we can do some rough science and predict a human LD50 of around 300mg/kg (more to make our next calculation easier than because of actual mathematical proof).
From there we can work out that for a 70kg human it would take 21 grams of pure CBD injected directly into their veins to cause a lethal overdose. Half of the time. Let’s put that into perspective.
Arguably the most common CBD products available today are tinctures. 10ml, 30ml or maybe 50ml bottles of Full Spectrum CBD Oil held in a carrier oil (commonly coconut oil) and delivered orally by placing a few drops under the tongue – or sublingually to use the technical term. These tinctures can range in strength from 3% to 40%, but are commonly sold between 5% and 20%. If we take a 20% tincture as our example, that means that in a 10ml bottle there are 2000mg of CBD. Disregarding all safety advice, our 70kg human would have to drink ten and a half bottles to have a 50% chance of succumbing.
Except we haven’t accounted for bioavailability. Bioavailability refers to the proportion of a drug that actually enters the bloodstream when introduced to the body. Different methods of administration have varied rates of bioavailability. As to be expected, intravenous injections have nearly 100% bioavailability because it’s literally going straight into the bloodstream. For our purposes we can assume that oral administration has a bioavailability of around 50%. It can vary depending on many factors, but 50% is usually a good estimate. So right there we’ve doubled the amount of tincture you’d need to drink to have a 50% of lethality. Now our 70kg example human is downing 21 bottles of oil, or almost a whole slim can of your favourite carbonated beverage. Let’s say our example human gets a great deal and only pays £50 per bottle. That’s still £1050 they’ve spent and, to be honest, drinking that much oil in one go is more likely to make you throw up than pass away from a CBD overdose.
To put our rough maths into perspective, I’d like to quote some LD50s for some relatively common substances you probably come into contact with. And I’m not doing this to scare anyone, but rather to point out how well diluted a lot of things you encounter are and also how relatively safe CBD is by comparison.
Mayer (2014), in a review of earlier research, estimated an LD50 of between 6.5-13mg per kg for nicotine. Peters (1967) found the LD50 for caffeine in humans to range between 150-200mg per kg, again after a review of previous literature. Aspirin, one of the most common pain and fever medications, was determined by Temple (1981) to have a potentially lethal dose at levels of 500mg per kg and above.
Obviously our stated LD50 for CBD of 300mg per kg body mass is a rough estimate, but it gives us a good idea of the general safety profile of the substance when compared to common substances that are readily available. Caffeine is purported to be consumed by 80% of the world’s population (Heckman, 2010), with coffee and tea being the most common forms. Recently there have been products such as high-caffeine energy drinks, powders and pills introduced to the market making it easier than ever to consume high amounts of this substance. Aspirin is one of the most common medicines, readily available over the counter and taken for mild to moderate pain relief. Most stores have a limit on how many packs you can purchase in a single transaction, but overall the regulation is quite loose.
I hope you’ll agree with the point I’m making about CBD being as safe (if not safer) than some very common substances that we don’t think twice about before putting them into our bodies, something that the World Health Organisation seems to agree with (WHO CBD Report, 2018). I’d have liked to discuss CBD tolerance at lower concentrations, but the reality is that it’s very well tolerated and there isn’t much more to write than that. Even when taken chronically (over a long period of time) there are very few adverse effects (Bergamaschi et al., 2011).
Action of CBD on the anxiety effects of THC (Zuardi et al., 1982)
WHO – CBD Review (WHO CBD Report, 2018)
TOXNET – CBD Toxicology (TOXNET)
How much nicotine kills a human? (Mayer, 2014)
Safety and Side Effects of CBD (Bergamaschi et al., 2011)