Cannabidiol: What is CBD, how does it work, and what are the risks?
Cannabidiol, or CBD ,is soluble in fat, so it's often dispensed as an oil. (Unsplash: CBD Infos)
Cannabidiol, also known as CBD, appears to be having a real moment in the sun.
Last year, Australia's drug regulator approved low-dose CBD products to be sold over the counter in pharmacies.
You may have also heard celebrities, influencers and podcast presenters touting the many benefits of taking a regular dose of the medicinal cannabis concoction, from treating anxiety and insomnia to general pain relief.
Take their word for it, and you might think CBD has replaced the apple a day that keeps the doctor away.
But let's separate fact from fiction. What's the evidence that CBD oil works, what can it be used for — and when should you steer clear?
How do cannabinoids work?
CBD sits in a class of molecules called cannabinoids.
The ABCs of CBD
The cannabis plant (Cannabis satvia) produces hundreds of different compounds in its leaves and flowers
One group of cannabis compounds are cannabinoids. More than 100 different cannabinoids have been found in cannabis so far, including tetrahydrocannabinol, or THC, the chemical that gets you high
Cannabidiol, also known as CBD, is another cannabinoid. It doesn't get you high, but has anti-psychotic and anti-inflammatory effects.
Depending on the cannabinoid, they can make us hungry, sleepy, forgetful or euphoric (or any combination of these and more).
Cannabinoids do this by activating specific biological sensors on our cells called receptors, which, in turn, change how the cell behaves and the chemicals it releases.
But as to the nitty-gritty of how this system works?
"The honest answer is we don't really know how all the cannabinoids exert their activity," said Jennifer Martin, director of the Australian Centre for Cannabinoid Clinical and Research Excellence.
Part of the issue is cannabinoid receptors are on cells all through our body, and they can do different things in different places at different doses.
What's more, some cannabinoids can also act on non-cannabinoid receptors, such as opioid receptors.
"'Promiscuous' is the pharmacological term," Professor Martin said.
"Usually when we're trying to get a drug registered or design a clinical trial, we're looking at one symptom, one disease, one chemical.
"Here we have [cannabinoid] drugs that work on multiple receptors and have multiple effects.
"I think that makes them fascinating, but also makes it complicated from a clinical use perspective."
What about CBD specifically?
Claims for CBD's benefits can be broadly split into two, although they are connected: general pain relief and more specific neurological effects.
CBD may alleviate some of the distress experienced in chronic pain, although exactly how it does this isn't clear.
For acute pain, such as arthritis and nerve pain, relief from symptoms is thought to be predominantly due to CBD's anti-inflammatory actions.
It does this by engaging cannabinoid receptors on immune cells, such as macrophages.
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They also secrete chemicals called cytokines. Immune cells use these to communicate with each other, but they also cause inflammation.
"Based on animal work in the bone marrow, CBD is likely to have effects on cells of the immune system such as macrophages to reduce the release of pro-inflammatory cytokines, which cause pain," Professor Martin said. As for the highest concentration of cannabinoid receptors in the human body, that's in our brain.
CBD's purported effects there — such as calming us down and helping us nod off at night — are all controlled by evolutionarily ancient brain systems that regulate vital functions such as appetite, emotion, fear and sleep.
Indeed, cannabinoid receptors aren't only found in humans. All animals — even down to invertebrates such as insects and leeches — have them.
CBD is marketed as a sleep aid, but such advertising is currently illegal in Australia. (Unsplash: Megan te Boekhorst)
Like other cannbinoids, CBD modulates how our brain cells behave by controlling the release of chemicals called neurotransmitters, said Anand Gururajan, a neuropharmacologist at the University of Sydney's Lambert Initiative for Cannabinoid Therapeutics.
And — being a promiscuous molecule — CBD doesn't just work its magic on cannabinoid receptors. It can activate others, such as serotonin receptors.
Low levels of brain serotonin, a neurotransmitter, are involved in depression and anxiety.
In some people, and at high enough doses, CBD seems to help the brain use serotonin more effectively
What's the evidence for low-dose CBD?
There are a number of clinical trials currently running in Australia looking into the effect of CBD on conditions as varied as insomnia, Tourette's syndrome and a transplant condition called graft-versus-host disease.
But the levels of CBD administered in clinical trials are far larger than the maximum dose recently approved by the Therapeutic Goods Administration (TGA) for over-the-counter products, Professor Martin said.
Any CBD products that do go on sale in Australian pharmacies will be low dose, only around 150 milligrams per day.
"The problem is it's probably too low to be effective for most symptoms and diseases," Professor Martin said.
"To get a therapeutic benefit, particularly for seizures or acute pain, it appears you probably need to take around 10 to 20 milligrams per kilogram, so roughly a gram of cannabidiol per day."
But, she added, your risk of side effects runs much higher at those doses.
Who should be cautious about using CBD?
In short, anyone taking any medication should be careful.
That's because it slows the liver's processes that break down some drugs in your bloodstream, meaning they can stay floating around in your blood at higher levels for longer.
"Maybe by taking a low dose [of CBD], people are also getting higher levels of their other pain or depression medicines," Professor Martin said.
It's legal to buy gummy lollies containing low levels of CBD in some countries, but not Australia. (Unsplash: Jan Zwarthoed)
To get therapeutic benefit from a drug, levels need to fall in a Goldilocks zone of sorts — not too low that it doesn't do anything, and not so high that you start to see side effects.
If a medication is allowed to hang around at high levels in your body for longer, that increases your risk of side effects, Dr Gururajan said.
"That's why you have to be really, really careful, especially if you're taking other medications.
"CBD tends to push everything higher. So that can be a bad thing."
Plus there are plenty of gaps in the research, he added.
"We don't know what long-term effects are for cannabidiol.
"And if you have someone who's pregnant and needs to be on cannabidiol, does that have an effect on the baby? We don't know." So is CBD available in Australia now? It is, but it's not freely accessible.
There are two cannabis-based prescription-only medicines currently on the Australian Register of Therapeutic Goods (ARTG).
In September last year, the TGA approved a cannabidiol-based medicine that can be prescribed to treat rare, but incredibly severe, drug-resistant forms of epilepsy that start in childhood.
The other has been around for a while — it was given the green light by the TGA in 2012 — and it contains CBD and another cannabinoid, THC. It's prescribed as a muscle relaxant for people with multiple sclerosis.
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Prescription-only cannabis-derived medicines are classified as Schedule 8, or "controlled drugs". Drugs in this group include opioids such as morphine, methadone and oxycodone.
As well as the two cannabinoid medicines on the Australian Register of Therapeutic Goods, there are also at least 100 different unregistered cannabis products.
These products can be capsules or oils containing THC or CBD, or dried flowers, which authorised doctors can prescribe.
In 2015, cannabidiol was included as Schedule 4, prescription-only medicine if it contained at least 98 per cent cannabidiol.
This means no more than 2 per cent of the medicine can be another cannabinoid, such as THC, or other ingredients.
In December, the TGA revised that to Schedule 3, or available over the counter.
People tend to take CBD for its therapeutic effects or as a general "wellness" supplement, Rhys Cohen, a consultant and journalist who sits on the Lambert Initiative's external advisory board, said.
"It's like a sexier fish oil."
But regardless of your reasons for taking CBD, the TGA's decision doesn't mean you can pop out to your local pharmacy and pick up some up right this minute.
That's because any CBD products sold at a pharmacy must first be put on the Australian Register of Therapeutic Goods as a Schedule 3 drug — and none so far have passed muster.
"The TGA has said anyone who proves their CBD product is effective for an appropriate indication, up to this specific dose [of 150 milligrams per day], may be allowed to sell it over the counter," Mr Cohen said.
And it's jumping through the efficacy hoop that will be the tricky part.
With little current evidence that low-dose CBD has much medical benefit, he added, it may be years before the first CBD products appear on your pharmacist's shelves.
What about the stuff online? CBD has been available without a prescription in the UK and some US states for a few years now.
But buying CBD online from overseas isn't just illegal, it's also risky.
The problem, Dr Gururajan says, is quality control — or lack thereof.
While any CBD products sold in chemists in Australia will be subject to TGA regulations, oils and capsules bought online could contain anything.
"A lot of cannabidiol that's available for public consumption right now is cannabidiol mixed with a bunch of other stuff from cannabis. It's not pharmaceutical-grade cannabidiol," Dr Gururajan said.
"So you don't know exactly what you're getting, and you don't know the actual compound that's giving you relief."
Given these unknowns, as well as cannabidiol's ability to slow your liver's ability to metabolise other drugs, anyone considering taking CBD should speak to a medical professional first, no matter the claims you see pushed by influencers.
"I certainly wouldn't recommend people refer to or look at social media for guidance," Dr Gururajan said.
"It's best to have these conversations with people like your GP or your specialist." Originally published here: https://www.abc.net.au/news/science/2021-10-17/cannabidiol-cbd-oil-cannabis-cannabioids-medicine-therapeutic/100536158?