Inflammation is a very general purpose description for a rather complicated process. At its simplest it can be described as a protective response by the body in reaction to damage, infection or irritants. It is characterised by heat, pain, redness, swelling and loss of function in the inflamed area, with symptoms presenting to different degrees depending upon severity. The mechanism employed involves increased movement of blood to the affected area. By pumping more blood to the affected area, the body can clear out dying cells and tissue, initiate tissue repair and eliminate the initial cause of the injury. Typically this process is beneficial to the body, as it prevents build-up of infectious organisms that could otherwise lead to death. However, there are times when the body over expresses the inflammation response, which can cause its own problems.

The last inflammatory statement I have to make is regarding allergens and their respective immune responses, like hay fever. Also referred to as allergic rhinitis, hay fever is characterised by a runny nose, itchy eyes, sinus pressure and sneezing. These symptoms are caused by irritation of the nose, eyes, throat and sinuses by small proteins contained within pollen (NHS Inform, 2019). Normally your body ignores these proteins, but in hay fever sufferers it treats them as if they were a dangerous foreign body like a virus, and triggers an inflammatory immune response. The runny nose, watery eyes and sneezing are an attempt to flush the ‘invader’ from your system and the sinus pressure comes about from inflammation in an attempt to improve the supply of white blood cells. This all leads to the tissues of these areas becoming swollen, irritated and inflamed. So from what we’ve learned from our previous examples, it seems like CBD has potential to help alleviate at least the sinus pressure, and potentially reduce the severity of the other aspects to hay fever too.

After some trawling of the various products and methodologies involved, I’ve identified three methods of making CBD compatible with water – though whether they make the CBD “water-soluble” is a point of contention. There are likely other methods out there that do the same thing, but the three I mention here are arguably the main ones that are most common nowadays. In order that I will discuss them here they are: glycosylated, liposomal and micellar. While most people think of water-soluble in terms of micro- or nano-emulsified, these terms are confusing and vague. This is due to the distinction being based on particle size despite there being no standard cut-off for where one becomes the other.

Finally I’m going to talk about micellar CBD. Micellar may be a familiar term for those who use make-up removers, such as micellar water. A CBD micelle is effectively the same thing as

a liposome; a bubble of surfactant with CBD on the inside and water outside. The main differences are related to the size and stability. Because micelles only have a single layer rather than a bi-layer, they are much smaller than liposomes, often around 100nm or less which makes a micellar solution transparent. To put it in perspective, a human hair is 50 to 100μm (micrometers) thick, or 50,000 to 100,000nm. This single layer of surfactant also makes micelles more stable, as the CBD is attached to the fat-loving tails of the surfactant. There have been some concerns regarding nanotechnology’s safety, but most of them are related to potential increased toxicity because of the better absorption (EC, 2006). Because CBD has almost non-existent toxicity, this isn’t an issue for micellar CBD, especially when we take into account that micelles are how the body breaks down fats naturally.

Now that we understand roughly how the nervous system sends signals, we can specifically look at the ECS. The ECS is composed of two specific receptors and their relevant neurotransmitters, and is present in both the central nervous system (CNS) and peripheral nervous system (PNS). The two receptors are known as CB1 and CB2, and their relevant neurotransmitters are called anandamide (AEA) and 2-arachidonoylglycerol (2-AG) respectively. These neurotransmitters are called endocannabinoids (‘endo’ meaning ‘within’, since these chemicals are produced in the body) and are where the name of the ECS comes from.

To make matters even more confusing, there is mounting evidence as to the effects of phytocannabinoids on other signalling systems in the body. Many of the effects of CBD on aspects like anxiety, mood and sleep are thought to be a result of it affecting the 5-HT receptors in the serotonergic system (Russo et al. 2005, Yi P.L et al. 2008). Basically we can think of it as if CBD can catch a lift across the river from lots of different ferries, not just the ones for the ECS. There is constant research underway to identify what other signalling systems CBD and the other phytocannabinoids can affect.

So. Quite a complex topic. Hopefully after this we have a reasonable grasp on what a signalling system is, how the ECS works as a signalling system, and what effects the phytocannabinoids have on the ECS, as well as their impact on other systems. I could genuinely spend 3 or 4 pages going into depth on this topic but I have serious doubts anyone bar other scientists would read to the end. Cell signalling is one of the more complex topics in biology, so kudos if you’ve followed the whole thing.

Something interesting to note: approximately a quarter of all studies are backed or sponsored by GW Pharma. This itself is unsurprising, considering that they were the first company in the world to fully license a medical product containing Cannabidiol: Sativex. Sativex was licensed in 2010 for use in patients with Multiple Sclerosis to alleviate neuropathic pain, spasticity and other symptoms of MS. It consists of a 50/50 ratio of THC/CBD. Because of this mix of cannabinoids it is classed as a Class B controlled drug under the Misuse of Drugs Act 1971 and is only available on prescription by a specialist doctor with experience treating MS.

With this in mind, why then are there so few clinical trials compared to the number of scientific studies on the matter of CBD? A quick search on Google Scholar for these studies involving the term “cannabidiol” turns up nearly 40,000 results – even removing patents and citations. While some of these will be repeats or passing mentions, that’s still considerably more papers than clinical trials. One reason is the stringency with which clinical trials are regulated. Another is the cost and length of time clinical trials require. A large scale Phase III trial (the phase looking into the efficacy of a potential medicine on its targeted demographic) can be anything from several hundred thousand pounds to potentially tens of millions. When considered in conjunction with the fact that they often take up to a year to complete, it makes sense that it requires the resources of a considerable-sized pharmaceutical company to carry out.

While this all sounds rather daunting, since we’re primarily interested in self-dosing a food supplement we can afford to be pretty vague. CBD is incredibly safe, even by the World Health Organisation’s standards (WHO). Their official quote is:

“Cannabidiol is found in cannabis and cannabis resin, but does not have psychoactive properties and has no potential for abuse and no potential to produce dependence. It does not have significant ill-effects”.

Let’s start with oral dosage. Typically oral drugs come in the form of capsules or tablets, though for CBD you can also get gummies. Unfortunately for us, the stomach is incredibly efficient at processing what comes into it. As a result oral bioavailability can be as low as 9-19% (Cherniakov et al. 2017, Scuderi et al. 2009). This is often accounted for in medications by including absorption enhancers in the formula or by increasing the total percentage of active substance. For CBD though, this means you’ll typically need a higher dosage to attain the same effect of a higher bioavailability route.

Capsules usually state the mass of CBD per capsule on the packaging which makes things easy, but tinctures often only state the CBD content per bottle. For a standard tincture we can reasonably assume that a single drop is 0.05ml. Thus, a 10ml bottle of 1000mg (10%) CBD will contain 200 drops – each drop containing 5mg of CBD (so a 5% drop will contain 2.5mg and a 20% drop will contain 10mg). From there you can determine how many drops to take for your desired dose.

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.

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.

Scientific studies are showing Cannabidiol (CBD) to be the cure all plant. Making it the most talked about wellness and beauty ingredient anticipated to expand at a CAGR of over 33% through 2027. A market report published by Future Market Insights titled ‘CBD Skin Care Market: Global Industry Analysis and Opportunity Assessment 2019-2027,’ the revenue generated from sales of CBD skin care products is estimated to be valued at over US$ 645 million (~€570 million) in 2019. (1)

Is a £45+ Marijuana Manicure worth it?

CBD manicures are popping up all over America but CBD treatments are making their way onto Spa and Salon menus throughout the UK such as the Cowshed and The Natural Health Spa. The manager of The Natural Health Spa says “Our decision to add CBD to our Spa Menu is beyond being ‘on trend, it’s based on the vast therapeutic potential of cannabinoids. We are excited to incorporate CBD into our Spa as part of our continuous efforts to source the best in beauty and wellness solutions for our guests and clients (7).” Studies have shown that CBD is a potent antioxidant, it can kill off free radicals and prevent the development of fine lines and wrinkles which is perfect for the hands as that is where ageing first starts to show.

However, it wasn’t until 1940 that scientists took a closer look at the benefits of isolating the CBD compound. At the time they did not know exactly what they had discovered. It is only in recent years we have successfully found the remarkable benefits of CBD when used in skincare, beauty products, soaps and hair care.

Despite cannabis being a taboo for decades, it is today flourishing into a multi-billion-pound industry. The American CBD industry alone was predicted to reach 20 billion by 2020 (2). Future Market reported in its Global Industry Analysis and Opportunity Assessment (2019 – 2027) that the CBD skincare market is estimated to be valued at over $645 million in 2019. (4) The United Kingdom is also seeing a drastic shift in the consumers approach towards CBD products. The Cannabis Trades Association states that the number of CBD oil users doubled in 2017 and currently sits at 250,000 regular customers. Making it the fastest growing industry in the UK. (3)

Regulations & Law – UK

The Cosmetics Regulation is directly applicable in the UK and therefore, CBD may be used in cosmetics placed on the UK market provided they are obtained from cannabis, cannabis resin, cannabis extracts and cannabis tinctures originating from the seeds and leaves that are not accompanied with the fruiting tops of the cannabis plant.

Cosmetics operators may contact one of the safety assessors available from the UK industry body Cosmetic, Toiletry and Perfumery Association (CTPA) to comply with the safety assessment requirements imposed under Annex I of the Cosmetics Regulations. The Regulation also requires manufacturers to notify the European Commission directly of every cosmetic product placed on the market, using the Cosmetic Product Notification Portal (CPNP).

It’s not going away anytime in our lifetimes – in fact it going to become even more of a prominent theme. To put it in perspective the pharmaceutical industry in the United Kingdom is projected to hit £33 billion by 2020 1. and the CBD sector will be £1.6 billion. 2

That is 4.8% of the entire industry poured into a product that has been in the public eye for barely 2 years!

Another study that looked at opioid abuse found a 44% decrease in consumption after subjects were given access to medical cannabis and CBD. 6

So far this doesn’t seem very threatening. In fact, if approached well this could be a revolution for the industry as more and more of the public look for an alternative to the ‘pill for any problem’ culture in modern medicine.

Cannabis, hemp and CBD in particular seem to operate in the perfect middle ground between holistic and conventional medicine. Perhaps offering an opportunity for conventional medicine to regain the confidence of millions who have started to look elsewhere for their health care.