“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, Board-Certified Neurologist
Cannabis and 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 Cannabis plant comprises of two main species – Hemp and Marijuana. The difference between the two is the profile of cannabinoids, predominantly the ratio of CBD to THC. Tetrahydrocannabinol (THC) is the compound that gives Cannabis its reputation. This is the psychoactive molecule that gets you high, none of the other cannabinoids including CBD, have this effect. Therefore taking CBD will not get you high, unless it is mixed with THC.
At the moment it is not legal to grow or sell Marijuana in the UK. It is currently legal to grow Hemp in the UK with a licence from the Home Office, however it is still not legal to harvest the buds and leaves of the Hemp plant, meaning CBD can not be extracted on British soil. However the refined product can be imported from abroad, so long as the level of THC is <0.3%.
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 things 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 of modern living. 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, bioavailability, dose and some self-experimentation.
Is CBD Safe?
Hemp has safely been used for thousands of years, and carries a fascinatingly rich cultural and spiritual history as a medicinal plant. Often referred to in folklore for its healing and agricultural properties, the seeds were used as a food source in China as early as 6000BC, and The Ebers Papyrus indicates that the ancient Egyptians had uncovered and utilised the many beneficial properties of this plant extensively.
In Sanskrit, Hemp is known as Ganja and some scholars suggest the ancient drug Soma, mentioned in the Vedas, was Cannabis. It is believed that Cannabis leaves and flowers have profound ritual and ceremonial use throughout ancient history. The act of ritual and ceremony is believed to strengthen the mind-body connection, as an adjunct to CBD’s physiological effects. Today, modern science is beginning to test and uncover some of the mysterious mechanisms of these therapeutic phytocannabinoids, and we come full circle as we begin to re-investigate some of the wonders of this plant ourselves.
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 medical prescriptions. This is in part due to the illegality of Marijuana and the damage and stigma caused by the War on Drugs.
However 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 making good choices still requires consumer education and investigation. Poor quality products will not 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 UK 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.
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?
How Do I Pick From Oils, Vapes, Smokes, Creams, Gummies etc?
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 / 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.
The below are very rough estimates, as metabolism depends on your unique composition, genetics and body fat percentage, however as a very general rule according to most studies:
Inhalation Through The Lungs (vaping and smoking – buds, liquids, resins and concentrates)
Inhaling CBD directly into the lungs is one of the most bioavailable methods of administration. According to drugscience.org.uk, if tobacco is not used (you can mix CBD buds with herbs such as spearmint instead), then the risk of lung cancer is almost the same as that of a non-smoker. Lung irritation can still occur, so use should be moderate. You can use a pen, joint, bong or vaporiser.
Onset of Action (how long it takes to work): 2-10 minutes with peak plasma levels around 3 minutes
Duration of Action (elimination half-life): 31 hours
Bioavailability (how much is actually absorbed into the blood): as high as 56% for an experienced user with proper technique (controlled and deep inhalation).
This method is personally my favourite, allowing for a rapid onset of action and longer duration of effects. 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. More CBD is inhaled with each subsequent breath, providing a continuous dose of CBD that is quickly and efficiently absorbed. This is great for people that say they want to ‘feel something‘, as daily supplementation with oils and tablets is more like a multivitamin without any immediate effects.
Intranasal Sprays (Sativex / Nabiximols)
Sprays delivered up the nose offer transmucosal delivery, they are absorbed via the thin, vascular lining of the nasal cavity.
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 at 34-46%
Oral Consumption (edibles, oils, capsules, gummies, concentrates, powders and beverages)
When CBD is taken by mouth and swallowed, popular because it is an easy method of application.
Onset of Action: 30 to 120 minutes
Duration of Action: between 1-2.5 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 4–6%
This 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 effectiveness. 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 are incredibly effective at breaking it down. Meaning that very little enters the systemic blood circulation. There are ways to get around this and its all about particle size and formulation, as explained below.
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. You can find our free healthy CBD recipe book here.
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 improving 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.
Topically – Transdermal (skin patches, salves, balms, creams, gels, serums)
Applied directly to the surface of the skin.
Onset of Action: roughly 20-90 minutes (anecdotal reports)
Duration of Action: N/A (not enough evidence / data)
Bioavailability: N/A (not enough evidence / data)
When applying CBD to the skin, it engages mainly with the Endocannabinoid receptors of the peripheral nervous system, so its best for more localised, targeted 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. You can learn how to make your own pessaries using our CBD Elixir at home here.
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.
Different Types of CBD / Cannabis Oil Profile
Isolate, Full Spectrum, Broad Spectrum
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.
1. Full Spectrum CBD Extract
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.
2. Broad Spectrum Extract
Contains all molecules from the Hemp plant, without any THC – making it legal in places such as the UK.
3. CBD Isolate
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’ 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.
How To Calculate Your CBD Dosage
Start Small And Increase
A 2011 review on CBD’s safety and side effects found that even high doses such as 1500mg a day, are generally well tolerated by humans. However there are a few more factors to consider when it comes to metabolism and efficacy.
Factors to Factor In
- The concentration of CBD you’re using
- Your weight
- Body chemistry and fat %
- Symptoms you’d like to alleviate, or use as a general health supplement
A 2017 review demonstrated that there is no “one size fits all” dosage, instead it underscored the fact that different people and animals respond to different dosages of CBD. Most of the human studies used dosages anywhere between 20 and 1500mg per day. Neuroscientist Nick Jikomes from Leafly explains that optimal CBD dosages shift throughout an individual’s lifetime. As our body’s physiology changes, so too do the receptors in our ECS.
It’s worth remembering that there’s still a lot about CBD that we don’t know, and as the cannabis industry grows, researchers will likely conduct more studies on both marijuana and hemp, along with its derivatives.
To keep it simple, here are our top 3 simple tips when it comes to dose.
- Dosage based on body weight
As with most substances, if you have a higher body mass, you are likely to require a higher dose. It is said that a good rule of thumb is to take 1-6mg CBD for every 10 pounds of body weight. You can also find online calculators such as Honest Marijuanas Simple Dosage Calculator.
- Start small and increase gradually
The best means of self-experimentation is to start low and gauge your body’s reaction to that dose, by keeping a symptom journal, before increasing over time. This will more accurately allow you to feel for the optimum dose for you. This could mean starting with 20-40mg a day, and increasing the amount by 5mg after a week. You could continue to do this until you think you have found the optimal dosage for you.
- Consult a physician
Whilst the system is a little behind the times (the ECS still isn’t even taught in medical schools), many progressive physicians are taking an interest in the promising potential of cannabis. When in doubt, it is always best to find a qualified health professional that you can consult.
This is especially important if you are on any pre-existing medication, as there may be interactions or contraindications. And any liver conditions should also be taken into consideration, as even though a 2017 study confirmed few adverse side effects, a 2019 study in mice raised some possible concerns about potential for liver damage and interactions with medications utilising specific liver enzymes.
A 2018 report from the centres for disease control and prevention noted that 52 US residents had bad reactions to certain CBD products, however it turned out that most of them used products that contained synthetic CBD and some contained little information about the manufacturer or its ingredients.
Dosing CBD Oil
Using a CBD tincture or oil is one of the easiest means of measuring dosage. A standard pipette will usually contain about 1ml of product. Therefore you can use the below formula to calculate the amount in a single dropper:
[Total CBD in Bottle] ÷ [Number of ML in Bottle]
= Mgs of CBD in a Dropper
For example say you have a 30ml solution of 300mg CBD, this will give you 10mg per 1ml dropper. If you are aiming to take say 25mg a day, you would take 2 and a half pipette-fulls. Of course this method is difficult to get 100% accuracy, especially when accounting for your body fat percentage and metabolism, but for some it is better than not measuring at all.
A single drop (not a full dropper / pipette) is about 0.05ml, this means a 10ml bottle contains around 200 drops, and if the strength is 1000mg then each drop will contain 5mg. Therefore 20mg a day will mean 4 drops a day.
Dosing CBD Buds
This preparation is popular both for effectiveness and for those who want to ‘feel something’ without getting high – many people report feeling a distinctive ‘body high’, especially through the use of herbal joints. It’s akin to a mild tingling sensation and feeling of lightness. When you buy herbal CBD as a bud, it will usually give you the weight in grams, along with the concentration of CBD.
One gram of hemp flower will contain between 100 – 200mg of CBD depending on the concentration of CBD in the strain of plant. Concentrations of cannabinoids are often advertised as percentages. I.e. a strain with a CBD concentration of 17% would contain around 170mg in a gram of flower.
You can also purchase pre-rolls where all the weighing has been done for you. The advantages of using buds are that heating plant matter is believed to ‘activate‘ the cannabinoids, which work at different optimal temperatures, and it avoids the need for additives which are found in things like Vape oils. The drawback is that it is much harder to calculate a specific dose in mg, compared to oils or capsules. However if you start low and increase, or only partially finish joints, it should be easier to progress until you reach the desired effects.
Dosing CBD Vapes
When using an e-liquid for vapes you would start by measuring the amount in a single dropper, so you can work out the amount in each tank. If you are aiming for a dose of 25mg, and using a 1000mg bottle of e-liquid, a single tank would contain approximately 33.33mg of CBD. You should note how often you need to refill the tank during the day.
Vaping is still a relatively new technology so the long term effects are not well established. It also received a lot of negative press in 2019, as some people have found that the oil droplets can be irritating to the lung lining, and contributed to a form of pleurisy.
Using a dry herb atomiser is one way around this. Instead of using oils, it heats the CBD buds to a certain temperature, allowing the cannabinoids to be inhaled as a vapour. Dosing is the same as for the CBD buds described above.
Dosing CBD Capsules
These are the easiest means of measuring set dosages as the capsules are already filled. However it should be noted that they don’t always offer the best means of absorption, as the oil cannot be placed under the tongue and CBD is not hugely bioavailable via the stomach. As described above, tinkering with the formulation or opting for a stronger concentration, can be a means of compensating for some of this.
The Bi-Phasic Effects of CBD
A Bi-phasic effect refers to the way in which a substance has a different effect on the body as its blood concentration increases. A good example is alcohol – when you start off having a drink, the effects are invigorating and stimulating, however beyond a certain point the opposite starts to happen, and you’ll become lethargic and sedated.
A similar thing happens with cannabis. When CBD is taken in different dosages, different effects seem to occur. For instance, many people use CBD to help them feel focused and energised, while others use it to help induce sleep and relieve the symptoms of insomnia.
The reason for this is due to how CBD interacts with the body and the endocannabinoid system (ECS) through different pathways and in distinct ways. CBD has the potential to activate conflicting pathways that result in what can sometimes be contradictory effects (e.g. stimulant-sedative effects).
In addition to the effects at different dosages, the biphasic effect of CBD is also important when considering the dosage. One example of such a dose-response relationship with CBD is in relation to anxiety. Several studies have shown that when combating both generalised anxiety as well as paranoia induced by THC, more does not mean better. Because of the range of complex biological responses that occur at different dosages, excessive amounts of CBD could be less effective for treating anxiety than smaller dosages.
CBD’s Bell-Curved Effectiveness
Another thing to keep in mind is that CBD has been shown to have a bell curve regarding its effectiveness. Similar to its bi-phasic effect, the bell-curved response means its efficacy will increase as dosage increases until it has reached its maximum efficiency rate. Thereafter it falls off as it reaches saturation levels, resulting in wasted product.
This means that each consumer has to monitor how they respond to different CBD dosage amounts to find their optimal dose for their particular desired effects. It is also important to keep in mind that a little CBD can often go a longer way than larger dosages.
There is no one-size fits all approach to health. Where a compound such as CBD is generally considered safe, with a large therapeutic window, it’s important to get to know your body, to experiment via some trial and error, and to be the informed scientist in your life.
How To Choose The Product Concentration
Mg and Percentages
Most commonly you’ll see products labelled using either milligrams or percentages. If a product does not list its concentration on the packaging in this form (as with many beauty products and creams on the market), then it will contain next to no CBD and have very little effect.
Milligrams – The absolute amount of cannabinoids
The number of mg typically refers to the total absolute amount of cannabinoids in the product.
The other variable that needs to be taken into account is the volume. If you have a 1000mg product in a 10ml and a 20ml container then the products will be different strengths. The 20ml product will be half the strength of the 10ml product drop for drop. This is where percentages come in.
Percentages – The concentration per drop
The percentage given represents the concentration, i.e. the true measure of the drop-for-drop strength of the product.
1 milliliter = 1 gram = 1000 milligrams of CBD oil
So for a 30 ml bottle of CBD with a concentration of 15% CBD
→ 15% of 3,000 mg = 1.5 x 3,000 = 4,500 mg of CBD per bottle
→ 4,500 ÷ 30 = 150 mg of CBD per 1 ml
A 1000mg of CBD in a 10ml bottle is a concentration of 10%. Therefore 1000mg in a 20ml bottle is 5% concentration, as it is diluted by twice the volume, drop for drop. As a beginner you may want to start with around 2-3%, if you have a product of a larger volume that offers less than this, you just need to take it slightly more often, or use slightly more of it. Depending on how and why you are using the product, this will be down to personal choice. You can use this calculator or the table below.
|
CBD Oil Strength Conversion Table |
||||||
| Volume | 10ml | 20ml | 30ml | 50ml | 60ml | 100ml |
| mg on label | ||||||
| 250 | 2.5% | 1.25% | 0.83% | 0.5% | 0.42% | 0.25% |
| 400 | 4% | 2% | 1.33% | 0.8% | 0.67% | 0.4% |
| 500 | 5% | 2.5% | 1.67% | 1% | 0.83% | 0.5% |
| 750 | 7.5% | 3.75% | 2.5% | 1.5% | 1.25% | 0.75% |
| 1000 | 10% | 5% | 3.33% | 2% | 1.67% | 1% |
| 1500 | 15% | 7.5% | 5% | 3% | 2.5% | 1.5% |
| 2000 | 20% | 10% | 6.67% | 4% | 3.33% | 2% |
| 2500 | 25% | 12.5% | 8.33% | 5% | 4.17% | 2.5% |
| 3000 | 30% | 15% | 10% | 6% | 5% | 3% |
| 6000 | 60%* | 30% | 20% | 12% | 10% | 6% |
(*You’re unlikely to find any oil that is 60% strength, it’s very hard to dissolve that amount of CBD in the given volume.)
So in summary, if you already measure your doses by calculating the exact milligrams of CBD that you’re taking then you don’t have to worry about percentages because you’ll already be adjusting your dose with stronger or weaker CBD products by taking a lesser or greater volume of the product respectively.
Therefore instead of measuring your doses in drops, droppers or mls, start by considering how much absolute CBD you would like to be taking per day, e.g. 20-30mg a day, and then depending on what product you use, adjust accordingly.
Concentration using Isolate, Broad and Full Spectrum Products
This is a complex issue, because as we discussed, the strength is not just determined by the concentration of CBD itself, but may also be strengthened by the Entourage Effect when all cannabinoids are present, so even though a product has a higher concentration of CBD, it may in fact be less potent as an isolate, than a Broadspectrum oil of a lower concentration.
Further to this, some labels simply list ‘Hemp Extract’, which does not tell you the absolute amount of just CBD in the product. A 1000mg (10%) Broad Spectrum CBD oil might in fact contain 600mg CBD, and 400mg of another cannabinoid like CBDa. In spite of the possible entourage effect, some would argue that this is important to know because cannabinoids like CBDa may have far fewer proven benefits than CBD itself, as not as many studies have been conducted yet.
The main thing is that it’s important to know what you’re taking, so that you can accurately reflect on the effects of different compounds and their strengths on you, at any given time.
Low Strength CBD Oils
These typically range from less than 100 mg to around 400 mg. Good for novice users, those with a sensitive endocannabinoid systems, as a daily dietary / supplementary use, or mild symptoms.
Mid Strength CBD Oils
Contains around 400 mg to 800 mg of CBD per bottle. Good for those wishing to progress from lower strengths after having built up some tolerance, or who are finding they need to take many doses a day to achieve the desired effects, more severe symptoms and digestive issues.
High Strength CBD Oils
Containing between 800 mg to 1,200 mg of total CBD. Good for experienced users, chronic symptoms, shows increasing research promise as providing relief from addiction and withdrawal.
Very High Strength CBD Oils
Contain upward of 1,200 mg of total CBD per bottle with some going as high as 4,000 mg. Good for more experienced users, as an adjunct for people with more extreme symptoms or conditions, chronic pain and inflammation.
Dosage and Concentration for Specific Symptoms
As mentioned, guidance on CBD dosage recommendations are unclear and hampered by a lack of dose-determination studies and desired plasma concentrations for minimum effective doses. Additionally, the role of different formulations and routes of administration on absorption rates and bioavailability in humans is also limited. There are also countless biological and physiological variables including body composition, metabolism, genetics and overall health variables that make a universally applicable CBD dosage impossible.
This is why, as a general rule its stated that you should start small (20-40mg once or twice CBD a day) and increase until the desired effects are achieved. Conversely, if going higher and symptoms worsen, decrease CBD dosage by around 25 mg in graduated amounts.
Although effective CBD dosages in different disease states remains unclear, we can draw some conclusions by reviewing what does exist of the limited experimental and clinical settings, as well as by collating, testing and evaluating the large sums of anecdotal reports. According to MHRA guidelines, we are not at liberty to state that CBD supplementation offers medical value, however we can independently share findings from the latest research papers, some of which can be found via the links below.
Pain & Inflammation
CBD dosing for pain and inflammation can vary greatly depending on the underlying cause. For instance, relief from chronic pain can be as little as 0.4 mg/kg per day when used as and adjunct therapy to pain medication. However, the usual dose recommendation is between 2.5 and 20 mg/day either taken with or without THC.
Sleep
In an early study on the effects of CBD on sleep, researchers found that people who do not suffer from sleeping disorders needed very high doses of around the 600 mg mark, while insomniacs only needed doses of 150 mg to 160 mg of CBD to induce sleep. Therefore, it is suggested to start off with a dose of 40 mg, gradually working up to anywhere between 150 mg to 600 mg until relief is found.
Anxiety & Depression
When seeking relief from conditions such as anxiety and depression, CBD dosages as low as 0.6 mg/kg per day, up to 6.7 mg/kg and 10 mg/kg per day produce positive results in the reduction of symptoms, improving quality of life, increase sleep quality and duration, as well as decrease anxiety secondary to PTSD.
Schizophrenia
Several studies have investigated the efficacy of CBD for treating symptoms of schizophrenia. A review of these indicated that positive reductions in psychotic and/or psychiatric symptoms are achieved with an average dose of 15 mg/kg per day over a four to eight week period. However, one study describe a higher average dose of 25 mg/kg of CBD per day over 4 weeks as effective.
Epilepsy
To date, Epidiolex is the only CBD-based medicine approved by the Federal Drug Administration (FDA), National Institute of Health and Care Excellence (NICE), and the European Medicines Agency (EMA). As such, CBD dosage with Epidiolex for seizure conditions such as Dravet syndrome and Lennox-Gastaut syndrome (LGS) is known which are a starting dosage of 2.5 milligrams per kilogram of body weight (mg/kg) twice daily, with a total dosage of 5 mg/kg per day. After 1 week, dosage may be increased to 5 mg/kg twice daily, or a total of 10 mg/kg per day.
All other CBD oils and products fall outside regulations, meaning that there are no official guidelines for their dosage. However, epilepsy is one of the most frequently studied medical conditions, with several studies describing the beneficial effects of CBD at various dosages. From that it can be concluded that an average dose of 15 mg/kg per day may successfully reduce the severity and / or frequency of seizures.
Parkinsons Disease
Research into CBD for Parkinson’s disease indicate that, in line with the bi-phasic effect of CBD, different dosages will yield relief for different symptoms. So, for instance, a 5 mg/kg per day dose of CBD could improve wellbeing and general quality of life scores, while psychotic symptoms are decreased with a CBD dosage of 7 mg/kg/d. In addition, improved rapid eye movement (REM) sleep was achieved at 1 mg/kg/d and dyskinesia was decreased with 2 to 3 mg/kg/d doses. Overall, the recommended CBD dosage for relief of exaggerated Parkinson’s disease symptoms seems to be best achieved at 5 and 7 mg/kg/d.
Multiple Sclerosis
The recommended CBD dosages for the active management of many of the symptoms of multiple sclerosis range from between 5 mg/kg to 10 mg/kg per day of CBD for the reduction of neural inflammation, spasticity, pain, fatigue and depression. When using whole-plant CBD:THC cannabis extracts like Sativex for MS, it is recommended to take 2.5 to 120 milligrams daily for two to 15 weeks.
The Molecular Science
Emerging Research
The current research is a new and emerging field and currently supports the use of CBD as a supplementary compound rather than curative, with fewer side effects than some of the synthetic alternatives in the market. Whilst we are not able to make any medical claims about specific products in accordance with the MHRA, we will present some of the most recent findings and theories in scientific research below. From a neurological perspective, the human body is wired to interact with nature in its processing of Cannabis, given that the molecules interact perfectly with our receptors.
The complex and exact mechanisms of CBD is still a bit of a mystery, as such substances have been previously difficult to research due to prohibition, the science is not where it should be. However our knowledge is rapidly scaling and expanding, with some exciting results. We do know that CBD interacts with the body in a variety of different ways. For one, they affect levels of Endogenous Cannabinoids, which are involved in neuromodulation, feedback and homeostasis.
Theoretical Mechanisms Of Action
There are some excellent animations provided by Dr Ethan Russo’s innovative company: Phytecs. There are also a great many videos on Youtube for those that prefer more visual explanations.
Mimicry
Within the brain, CBD may mimic serotonin by binding and activating your body’s 5-HT1A serotonin receptors. This neurotransmitter has a large impact on mood and emotions in the brain. 95% of serotonin is believed to be housed in the gut, with effects on digestion, immunity, bone synthesis and cardiovascular function.
Cannabidiol is believed to have more than 65 targets throughout the body, which makes it difficult to pinpoint the exact sources and mechanisms of its many different therapeutic properties. Most people associate Serotonin with happiness. However like everything in life, the role of this neurotransmitter is actually a lot more complex, and its effects depend on where it is and what it binds to.
Contrary to popular belief, more serotonin is not necessarily better, and dysfunction can stem from low or high levels, as well as malfunctions at the receptors. Serotonin has at least 14 different receptors, but 5-HT1A is thought to have the strongest role in anxiety disorders. The anti-anxiety drug Buspirone also binds to this particular receptor.
Allosteric modulation
Studies show that CBD may bind to CB1 at a different spot from where other cannabinoids normally bind to the receptor. This process is called allosteric modulation. It leaves the normal binding site free, but changes the shape of the receptor so that it has a weaker affinity – rendering it less responsive.
Although decreasing your body’s endocannabinoid response might seem counterintuitive, it’s believed that many disruptions to the endocannabinoid system might actually stem from an overactive system. If your body struggles with the burden of constant anxiety or excess weight, then certain receptors may be over-stimulated. Scientists also believe that this dampening effect is one of the main reasons why CBD can buffer some of the negative side effects of THC.
CBD is also a positive allosteric modulator of the mu and deltoid opioid receptors. This means it enhances the ability of these receptors to receive endogenous Enkephalins. Endorphins and Enkephalins are the body’s natural pain killers. The former works principally at the brain stem, whereas the latter is believed to block signals in the spinal cord. Both are morphine-like substances.
Enzymatic Inhibition
As well as interacting with our receptors, CBD has been shown to interact directly with a variety of enzymes and other proteins in the body. For example, CBD is a competitive inhibitor of the enzyme that normally degrades the ‘Bliss Molecule’, aka Anandamide. This is a neurotransmitter involved in learning, memory and mood via its interactions with the CB1 receptor.
When the enzyme that recycles this neurotransmitter is inhibited (the FAAH enzyme), there is more Anandamide in our synapses, allowing it to work its magic for longer. This is called re-uptake inhibition. The term might ring a bell for those familiar with SSRIs (selective serotonin re-uptake inhibitors), the synthetic pharmaceutical drugs commonly prescribed for depression and anxiety.
Anandamide is being investigated for its anti-anxiety effects, ability to slow the proliferation of breast carcinoma, and increase neurogenesis. Anandamide plays a role in memory and forgetting, creating a potential natural value for PTSD, which also needs to be studied further.
Other enzymes believed to be targeted by CBD are involved in Cholesterol metabolism, Mitochondrial function, and Melatonin synthesis – to name a few.
Neuroprotection
Although chronic stress can negatively affect neurones and even shrink areas of the brain, the nervous system is still capable of regeneration. Throughout our lives we continue to form new neurones, make new connections and grow our grey matter – and CBD holds the potential to boost this process.
This is one of the ways in which CBD counterbalances some of the effects of chronic stress. A few studies have demonstrated that CBD encourages neural regeneration, particularly in the hippocampus.
Anti-inflammatory
CBD has demonstrated a number of anti-inflammatory properties. An example of this is its effect on acne. Acne is a common skin condition thought to be caused by numerous factors such as genetics, diet, bacteria, inflammation and sebum production. A recent study conducted in vitro (via a test tube), found that CBD oil prevented sebaceous gland cells from producing too much pore-clogging sebum, and prevented the action of ‘pro-acne’ agents such as inflammatory Cytokines.
CBD also interacts with TRPV1 receptors (short for transient receptor potential cation channel subfamily V member 1). These are located throughout your body where they detect temperature and deliver the sensation of heat and pain. It’s TRPV1 that’s essential for helping you to quickly respond to situations that could damage your body – like if you accidentally place your hand on a burning hot pan.
Unfortunately, when faced with inflammation or injury, chemicals released by your body can increase the sensitivity of these pain receptors. Fortunately, some molecules such as the active compound in chilli peppers: Capsaicin, can activate and then desensitise TRPV1 receptors. Similarly, CBD also de-sensitises these pain receptors, and this effect on TRPV1 is considered pivotal to CBD’s usefulness in other conditions.
There are many reasons to choose sun-grown CBD from sustainable farms, over Industrial Hemp. Lower quality CBD may be the same strength, but if it comes from a source with lower purity standards it could contain synthetic pesticides, fertilisers, and even heavy metals. Monocultures are not good for the environment, and farm-fresh vegetables often smell and taste better than their supermarket counterparts because they’re brimming with healthy Terpenes and Phenolics.
At Portland State University, researchers are toying with the idea that the soil can lend unique characteristics to Cannabis, like terroir for wine. They distributed genetically identical plants to farmers that shared a climate, yet grew on different soils. Over the coming years they will then track if the identical plants provide flower with varying levels of cannabinoids and terpenes, with the current hypothesis ruling in favour of this.
This list is by no means exhaustive, the exciting area of CBD research is a rapidly growing and changing landscape, to stay up to date with the latest information subscribe to research groups such as drugscience.org.uk
