The Essential Guide

The Endocannabinoid System

CBD stands for Cannabidiol – a naturally occurring compound found in the resinous flower of the cannabis plant. Hemp oil is nothing new, and as you peruse the isles of Boots it’s increasingly common to see many beauty and wellness products bearing the cannabis leaf. However it should be noted that Hemp (Seed) Oil comes from the seeds, and whilst hosting a nutritiously dense profile, it does not contain active cannabinoids like CBD. These mostly come from the leaves and flowers (buds), but misleading labelling can make it confusing to distinguish Hemp Seed Oil from Hemp Oil / Extract / Distillate.

There are many other types of phytocannabinoids (plant-derived cannabinoids) in the Cannabis plant, including CBDA, CBG, THC and more. Each is believed to have its own specific benefit. The difference between Industrial Hemp and Medical Hemp is the profile of cannabinoids, predominantly the ratio of CBD to THC. Tetrahydrocannabinol (THC) is the compound that gives Cannabis its psychoactive reputation. This is the molecule that gets you high, none of the other cannabinoids including CBD, have such a strong mind-altering effect effect. Although some users do report a relaxed ‘body high’ depending on strain, concentration and dose. 


Phytocannabinoids interact with our Endocannabinoid System (ECS). This is an extensive part of human physiology – with receptors in almost every organ of the body including the lungs, heart and brain. This signalling system is comprised of CB1 and CB2 receptors, with CB1 found mostly in the central nervous system (CNS) and CB2 primarily in the peripheral nervous system (PNS). As these receptors are linked to almost every system of the body, the ECS is involved in a huge plethora of functions – including homeostasis, sleep, mood, pain, appetite, fertility, and memory.

Whether or not you are a Cannabis user, you have an ECS that regulates your overall health and wellbeing, and your body produces its own natural cannabinoids as part of this. The body’s own supply of cannabinoids are known as endogenous cannabinoids, and those that are derived from external initiators such as the cannabis plant, are known as exogenous cannabinoids. The two are structurally similar, which means that exogenous cannabinoids interact with the body’s receptors in much the same way as endogenous ones.

The body’s supply of endocannabinoids can become disrupted via things like pollution and toxins, stress, hormonal imbalances and other common afflictions. This is why many people are turning to exogenous cannabinoids from mother nature to aid in restoring some of the balance. The market is teeming with options, however choosing the right product is not simple – it requires investigating purpose, formulation, bioavailabilitydose and some self-experimentation. There are also other lifestyle factors that affect your base level of cannabinoids, including coffee and exercise. 

There are more cannabinoid receptors in the brain than there are for ALL the neurotransmitters put together.’ The significance of cannabinoids for the body is undeniably important – and the ECS has the potential to have a powerful impact on the body. It’s a significant part of the makeup of every human being, and can have a substantial impact on our health.“ – Dr Ethan Russo

Is CBD Safe?

Quality, Quantity and Overdosing

Hemp has safely been used for thousands of years, and carries a fascinatingly rich history as a medicinal plant. Today, modern science is beginning to test and uncover some of the mysterious mechanisms of these therapeutic phytocannabinoids, and to come full circle as we begin to re-investigate some of its holistic wonders.

After much campaigning, the first CBD prescription to be approved by the FDA and made available for medical use was Epidiolex in 2018. It’s used to treat seizures caused by two forms of epilepsy: Lennox-Gastaut syndrome and Dravet syndrome. These rare but severe conditions usually appear in early childhood or infancy. Despite its long-standing history, and a wealth of contextual information about Cannabis and Cannabinoids, there are still many barriers to both research and actually receiving prescriptions. This is in part due to the legal and regulatory issues, as well as the social and political damage and stigma caused by the War on Drugs.

Various types of CBD oil can be bought relatively easily over the counter, as a health supplement. With a rapidly growing number of options available, it is of primary importance that quality and safety are made clear. The industry is becoming increasingly regulated in order to provide this, but is still nascent in its decisions and reasoning, as well as requiring pro-active consumer education. 

Extremely low dose products tend not to list the concentration in mg or as a % on their packaging, and where it is listed – you should check the website for third party lab test certificates that prove the bottle contains what it says it does. Do your research and find a trusted supplier that is sustainable, ethical, provides high-quality ingredients and is locally compliant.

The World Health Organisation (WHO) provided data, and stated a position, that pure CBD is safe for consumption. To overdose you would have to take around 20,000mg+ before it could be considered potentially harmful (for example, it can negatively affect the liver to have to process such a large amount). For comparison, an overdose of Ibuprofen is only 1000mg, which is around just 4-6 standard tablets.

Possible Drug Interactions

Many natural herbal and plant-based compounds have the potential to interact with medication depending on how it is processed by the body. This is why you should always consult your doctor before adding a new supplement to your daily regime. 

Most notably, CBD is a an inhibitor of an enzyme called cytochrome p450 (CYP450) which is found in the liver. These enzymes are especially important for your body’s ability to metabolise drugs into inactive or more active compounds. 

If you currently take a pharmaceutical drug that is processed by cytochrome p450 (they often come with a warning not to consume grapefruit or grapefruit juice which has the same effect), CBD may interfere with your body’s ability to process these pharmaceuticals, to varying degrees.

However, this does not rule out CBD as an option altogether. In fact in some instances, CBD may help increase the effectiveness of medication, thus lowering required dose. Depending on how the drug in question is processed, CBD could elevate or decrease the concentration of the active compound in your blood stream. Therefore your doctor may suggest extra blood monitoring in order to keep these drugs at a healthy level.

How Should You Take CBD?

Oils, Vapes, Smokes, Creams Or Gummies?

Companies are getting inventive with how CBD is delivered – edibles like chocolates and coffees, topical skin creams, suppositories: cannabis can be applied pretty much everywhere and anywhere. Deciding how you want to take it will come down to considering why you want to use it (what’s it for? Pain, pleasure, general health, sleep, anxiety etc), and factoring in metabolism and bioavailability.

Metabolism and things like body fat % affect how CBD is absorbed and processed by the body (how quickly it starts working, and for how long). Meaning that even though a product has x concentration on the bottle, this isn’t necessarily the amount you will end up absorbing as an individual. Each of the different methods of administration offers a different bioavailability – some products allow CBD to be more easily absorbed than others.

Bioavailability is also affected by the formulation of the product – for example oral CBD absorbs better when combined with fats, and topical CBD may absorb better when combined with Terpenes (e.g. beta-caryophyllene and myrcene: the Cannabis plant also naturally contains Terpenes), which are believed to help draw CBD across the skin barrier.


Inhalation Through The Lungs (vaping and smoking - buds, liquids, resins or concentrates)

Inhaling CBD directly into the lungs is one of the most bioavailable methods of administration. This is thanks to the large surface area and permeability of lung tissue. As with oxygen, the lungs offer a direct route to the systemic blood circulation, so that CBD can be transported around the body. 

Cannabis can be inhaled on its own, or mixed with herbs such as spearmint and rose, instead of using tobacco and nicotine. However lung irritation can still occur from the products of combustion, so use should be moderate. You can also use extra measures and precautions such as filters, pens, water bongs or vaporisers.

Onset of Action (how long it takes to work): around 2-10 minutes with peak plasma levels after about 3 minutes.

Duration of Action (elimination half-life)31 hours.

Bioavailability (how much is actually absorbed into the blood): as high as 56% with controlled and deep inhalation.


Intranasal Sprays

Sprays delivered up the nose offer transmucosal delivery, they are absorbed via the thin, vascular lining of the nasal cavity, and have a rapid onset of action much the same as via the lungs. 

Onset of Action (how long it takes to work): 10 minutes

Duration of Action (elimination half-life): N/A not enough data

Bioavailability (how much is actually absorbed into the blood): estimated to be around 34-46%



Oral Consumption (edibles, oils, capsules, gummies, concentrates, powders and beverages)

This is popular because it is usually an easy and tasty route of administration that avoids the byproducts of combustion. It can also be easier to dose and produce long and sustained effects once metabolised. The downside is that the effects can take much longer to kick in. 

Onset of Action: 30 to 120 minutes (digestion)

Duration of Action: between 1 to 2.5 hours after a single dose, however repeated doses can mean it lasts up to 2-5 days.

Bioavailability: Around 10-20%, with some studies reporting as low as 46%

The bioavailability is due to the first pass effect: the compound has to pass through the digestive tract and is broken down in the stomach, intestines and the liver, which reduces its bioavailability. 

When CBD is absorbed by the GI tract it passes over to the liver via the hepatic portal vein, this is called hepatic first pass. Here it is metabolised by CYP450 enzymes, which further break it down. 

Different Oral Formulations:

In order to improve CBD absorption orally, many companies have tried to alter the size of the CBD molecule by making it smaller, and / or targeting its formulation by making it more water soluble. Cannabinoids are usually fat soluble, meaning they absorb as much as three times better when mixed with medium-chain triglycerides (MCTs) – healthy fats that improve uptake by the body. 

As the body consists mostly of water, lipophilic (fat-soluble) cannabinoids do not absorb well naturally (oil and water do not mix), making it difficult for them to dissolve. Improving the water solubility of CBD requires an emulsifier (breaks up fat droplets into smaller droplets) or surfactant (lowers the surface tension of a liquid), to achieve a finer dispersion of the oil into the water.

CBD particles measure around 2,000 nanometers, while human cells only absorb molecules smaller than 80 nanometers. Our liver naturally produces its own emulsifiers, however this preparation can also be useful for methods like sublingual administration which does not pass through the digestive tract. 

The 3 most common formulations for increasing oral bioavailability are currently: Liposomic, Macroemulsions, Microemulsions and Nanoemulsions: 


1. Liposomal CBD

The cannabinoids can be made to dissolve in water by giving the spherical molecules a hydrophilic (water-attracting) outer-layer, whilst the inner cavity encapsulates the fat-soluble CBD. Scientists have also understood the importance of liposomes – a body of fat that surrounds or is attached to another molecule (a vitamin, pharmaceutical, or cannabinoid for example), allowing nutrients to be delivered more effectively.

2. CBD Macroemulsions

When CBD oil is mixed with a healthy fat such as MCT, the MCT carrier oil improves absorption via the GI tract, but the molecules remain large (> 1µ) and bioavailability is roughly on par with a sublingual dose.

3. CBD Microemulsions

The same as above, except that the droplets are broken down into a smaller size (about 1/10th the size of a macroemulsion). They require more surfactant to allow them to be more stable than macro-emulsions, as there is a larger surface area for absorption.

4. Nano Particles & Nanoemulsions

In a Nano-Particle formulation, the active particles (CBD oil) and its carrier oil are disrupted and dispersed / broken down using sonic frequencies. These break the droplet size down to a tiny size in a process known as ultrasonication. Because of their small size, the droplets can then easily pass through the walls of cell membranes, resulting in a higher level of absorption and efficacy. The downside is that the effect may not last as long, as the particles are also broken down more quickly.

In a Nano-Emulsion the nano-particles are blended with a surfactant that is equally small and designed to be easily absorbed by the body. This is still considered a relatively new technology, however theoretically it should allow for improved bioavailability where CBD can reach the system quickly and effectively, by increasing stability and absorption.

CBD as a nano-emulsion allows it to be absorbed at higher rates than other methods of delivery, the size therefore makes all the difference, with a 25 nanometer emulsion being absorbed more than 50%, whereas a 500-5000 nanometer (i.e. Liposomal) emulsion will have less than 20%.

Sublingual (under the tongue: oils, tinctures and sprays)

When CBD is placed and held in the vascular region under the tongue for 1-2 minutes, before swallowing. The longer the oil is kept under the tongue, the more that shall be absorbed into the circulation.

Onset of Action: 20-40 minutes

Duration of Action: 18-32 hours

Bioavailability: Around 13-19% with some studies estimating as high as 35%

This is higher than when taken orally as it bypasses the digestive tract. Placing the oil under the tongue allows the oil to be absorbed directly by the sublingual gland, blood vessels under the tongue and the mucous membranes. 

This offers a fast and efficient means for the CBD to enter straight into the systemic circulation. The time of onset is also faster and longer lasting than oral administration. The trick here is to make sure you don’t swallow too soon, and hold the drops for at least 60 seconds. Also be sure to place the drops under the tongue, not on top.

Topical (transdermal skin patches, salves, balms, creams, gels and serums)


Onset of Action: roughly 20-90 minutes (anecdotal reports)

Duration of Action: N/A (not enough data)

Bioavailability: N/A (not enough data)

When applying CBD to the skin, it engages mainly with the Endocannabinoid receptors of the peripheral nervous system, so its best for more localisedtargeted action e.g. dry skin or sore muscles. Various studies have demonstrated the efficacy of this using topicals and transdermal patches. However there has not been enough investigation into its bioavailability to provide data on this. Nevertheless, you can find some great animations detailing how CBD interacts with receptors in the skin via Phytecs

The theory is that the application of these types of products enable the CBD to be absorbed through the surface of the skin from where it can be absorbed into the sub-dermal blood vessels while also interacting with localised cannabinoid receptors. Terpenes, which are also found in the Cannabis plant, are believed to facilitate this process, therefore topical formulations are best when combined with these molecules.

Suppositories and Pessaries (transcutaneous / mucosal)

CBD absorbs relatively well via the vascular mucosal regions of the Anus and Vagina respectively. This is due to the proximity of blood vessels to the surface in the application area. 

Onset of Action: 20-40 minutes

Duration of Action: 18-32 hours

Bioavailability: Around 13-19% with some studies estimating as high as 35%

These are also great for those looking for more localised symptom relief.


Cannabis oil profiles

Full Spectrum, Broad Spectrum or Isolate?

The predominant theory is that Full-Spectrum and Broad-Spectrum CBD oils and extracts are more bioavailable than their CBD isolate counterparts.  This is due to cannabis being inherently polypharmaceutical – the extract contains many different cannabinoids each with their own properties, and its believed that these naturally work in synergy under a concept known as ‘The Entourage Effect‘.

Although progress is being made, this has still proven difficult to provide strong evidence for scientifically as, funding and regulations aside, cannabinoids are complex molecules with many different mechanisms of action and interactions. They predominantly act on G Protein receptors which are responsible for a whole cascade of different pathways.

As well as cannabinoids, Cannabis oil naturally contains Terpenes which are responsible for the plants distinctive smell. Certain terpenes have been found to enhance the bioavailability of cannabinoids. e.g. the terpene Myrcene has the ability to affect the permeability of cell membranes, particularly the blood–brain barrier (BBB), speeding up and increasing the absorption rates of cannabinoids into the brain.

In one study, scientists investigating the anticonvulsant effects of CBD compared five types of full spectrum extracts, each of which contained the same amount of CBD but with different cannabinoid and Terpene profiles. Their results showed significant differences in the dosage requirements, efficacy and ceiling effects between each preparation, potentially indicating that certain combinations of cannabinoids and Terpenes affect bioavailability.

Full Spectrum

Contains all molecules from the Hemp or Marijuana plant, including the psychoactive molecule THC.

In the natural Cannabis plant, CBD and THC are balanced in a healthy ratio, and THC has its own therapeutic properties. However as the black market is tailored towards abuse, the illegal variety of cannabis one might buy off the street is incredibly THC heavy, and this is the component that gets you ‘stoned’. Skunk is purposefully bred to be low in CBD, as CBD reduces the ‘high’, however it is also necessary to cancel out some of the negative side effects of THC including possible paranoia and anxiety in some people.

Broad Spectrum

Contains all molecules from the Hemp plant, without any THC – making it legal in places such as the UK.


Contains only purified and concentrated CBD – can be easier to regulate by more accurately measuring the concentration, but does not provide the benefits of the ‘entourage effect’.

The Entourage Effect

The ‘entourage effect’ describes the phenomenon where the 400+ compounds in Hemp oil work in concert to have a synergistic effect. In other words, it is the holistic sum of its parts that makes this potent plant remedy so effective.

Although the entourage effect is a theoretical hypothesis, Vitamin C may be a good analogy. Many Vitamin C supplements are presented in the form of ascorbic acid. Ascorbic acid is just one of the many compounds that comprise the whole vitamin C. In order to be most effective, Vitamin C must also exist amongst Rutin, Factor K, Factor J, Factor P, Tyrosinase, and Ascorbigen. In fact, in all of his years of research, the discoverer of Vitamin C and Nobel Prize Laureate Dr Albert Szent-Georgi, was never able to cure Scurvy with isolated ascorbic acid. In contrast, eating an orange, lemon or lime, provides whole Vitamin C with all the necessary co-factors for optimum absorption.

The Cannabis plant has nearly 500 natural chemical compounds: CBN, THCA, CBG are just a few examples. As well as working together, they also have their own effects. CBN is being investigated as a natural sleep aid, THCA is thought to offer some of the benefits of THC without the high and both CBD and CBG have neuroprotective properties and are believed to help regenerate new brain cells.

While it may be cheaper and more cost-effective to extract CBD from Industrial Hemp, users may ultimately experience fewer benefits due to the absence of clinically significant levels of Terpenes and other compounds that occur in abundance in high-CBD cannabis. However you can have formulations that compensate for this by using a custom blend of compounds, for example a CBD Isolate + Terpenes, or +CBG, depending on what is required of the product. Sometimes a manufacturer will isolate CBD to ensure purity and concentration, before adding the other molecules back in. This can also make it easier to correctly measure and dose what’s in your product.

As you can see, with such a huge range of options available, self-experimentation can often feel a little overwhelming. Nevertheless it is an important part of understanding how your body makes you uniquely you, whilst investigating the differences between the various modes of application and how they make you feel.