Bioavailability of CBD: what’s happening inside us?
Anastasiia Myronenko is a Medical Physicist actively practicing in one of the leading cancer centers in Kyiv, Ukraine. She received her master’s degree in Medical Physics at Karazin Kharkiv National University and completed Biological Physics internship at GSI Helmholtz Centre for Heavy Ion Research, Germany. Anastasiia Myronenko specializes in radiation therapy and is a fellow of Ukrainian Association of Medical Physicists.
Almost all of us spend most of our lives perfecting our bodies, doing yoga, passing hours in beauty salons, toying with our diets and our faces via cosmetic surgery. The body becomes the hallmark of man. What is hiding within it? Can a person find their "I" in their physical corporeality?
Regardless of the various beliefs and myths covering the human body, many philosophers state that it is only a vessel storing our souls. While serving as a shell, the body helps us to leave a life in this world and prepare for reincarnation where the new beginning is waiting for us.
Nevertheless, it’s the 21st century, and modern technology has long supplanted ancient beliefs, by providing us with real and scientifically-proven facts. May the great romantics and connoisseurs of the beautiful and unknown forgive me, but our body is just a set of numbers and processes. Numbers and processes that make us those who we are today. Numbers and processes that decide how good we will feel tomorrow and what diseases await us in five or ten years. We have 200 bones, 64 muscles, 100 billion neurons in our brains, 80 thousand genes in our DNA, and 75km of nerves throughout our bodies. These numbers are a result of dozens of years of scientific work and research; they unite people, making all of us those who we are: humans.
The response of our bodies on external irritants is crucial for our health and wellbeing. Millions of scientists all over the globe are working on increasing our immunity, improving effects from medications, and the ability of the body to resist various viruses and diseases. Upon the discovery of medicinal cannabis, modern medicine began to transform and still continues to do so to this day. Cannabinoids are the most promising cannabis compounds that are believed to cause anti-inflammatory, analgesic and soothing effects. Thanks to the numerous health benefits of these compounds, they are considered potential substitutes for a range of modern drugs.
Moreover, cannabinoids show promise for the treatment of various untreatable diseases or those that can be cured only by means of medications that pose a danger to our health, such as opioids. There has been ample anecdotal evidence of the therapeutic benefits of cannabinoids, earning them the title as “magical compounds” amongst some, given their ability to help with multiple conditions. Indeed, there have been reports of reduced anxiety, alleviated pain and the improvement of various other health ailments under the assistance of some cannabinoids.
The current number of studies and human trials worldwide remains insufficient to prescribe these compounds for patients and be completely sure of their health benefits, as well as the absence of the side effects. Knowledge of cannabinoids is fast-developing, and it is excellent. However, much of the medical world, including the FDA and other regulatory bodies, remain hesitant to officially adopt cannabinoids into mainstream medicine.
Studies are actively continuing and day after day, researchers reveal the peculiarities of the effects of the cannabinoids in our bodies and their interaction with it. Not so long ago, the term “bioavailability” began to appear, along with the characteristics of cannabinoids-based drugs. To understand the importance of bioavailability and its influence on the results cannabinoids can provide us, let’s dive into the more well-known term - pharmacokinetics.
Pharmacokinetics and drugs bioavailability. What happens when we swallow a pill?
For each of us, our bodies act like correctly assembled machines where each detail has its place and the sequence of actions and reactions in thousands of cases is ideally planned. Like each machine and mechanism, our body can break and thus needs to repair. However, not all of us think about what is happening when we take a pill and wait for its effects to kick in.
Here is where pharmacokinetics comes into play. Pharmacokinetics can be described as what our body does to a drug we take. This term includes the movement of medication into, through and out of the body; or, more scientifically, the course it undergoes from its absorption, bioavailability, distribution, metabolism, to finally, excretion. Pharmacodynamics can also be explained as what a consumed drug does to the body, how it involves itself receptor binding; causes post-receptor effects and triggers chemical interactions. Drug pharmacokinetics is “responsible” for the onset, duration, and intensity of a drug’s effect. Formulas that relate to these processes summarise the general pharmacokinetic behaviour of most drugs existing today.
Pharmacokinetics of a drug depends not only on the drug’s chemical properties but on the patient-related factors as well. Such patient-related factors include sex, age, renal function, and genetic makeup, all of which can be used to predict the pharmacokinetic parameters in populations. For example, older people react to drugs in a different way to younger people. It was discovered that the half-life of some medicines, especially those of them that require both metabolism and excretion, may be remarkably long amongst the older generation compared to the younger generation. Physiological changes occurring with age often affect many aspects of pharmacokinetics. Besides age, other factors that may influence the pharmacokinetics of drugs are related to individual physiology. The effects of individual factors may range from obesity, dehydration, renal failure or hepatic failure. Such factors are idiosyncratic and thus may cause unpredictable results. We all are different, and these differences lie not only in our character and appearance; but also in our physiological differences. The same drug taken in the same dosage by two different people may cause different effects, and this is the main challenge for physicians today. Because of our differences, drug administration must be based on the needs of each patient. Traditionally, it may be achieved by empirically adjusting dosage until the desirable therapeutic objective is met. This approach is frequently inadequate because it can delay optimal response or result in a range of unpredictable adverse effects.
Knowledge of pharmacokinetic principles helps physicians adjust necessary dosage more accurately and rapidly. Application of the pharmacokinetic tenets to individualise pharmacotherapy is also known as therapeutic drug monitoring.
Now let's look to the term “bioavailability”, which refers to the extent and rate at which the active agent (drug or metabolite) enters our blood circulation, thereby accessing the site of action. The bioavailability of a particular drug significantly depends on the properties of its dosage and its form, which, in turn, depends on its design and manufacturer. Differences in bioavailability among different formulations of a certain drug can have clinical value, thus, knowing which of the drug formulations have high or low bioavailability is essential. There are three types of equivalence characterising the effect of drugs on the body:
- Chemical equivalence. This type of equivalence indicates that drugs containing the same active compounds in the same amount and meet official standards can be considered as similar. However, in the case of chemical equivalence, inactive ingredients in drug products may be different.
- Bioequivalence. Biological equivalence of the drugs indicates that the drug products being given to the same patient and in the same dosage regimen will result in equivalent concentrations of the drug in plasma and tissues.
- Therapeutic equivalence. This type of equivalence is probably the closest to an average consumer. It indicates that drug products being given to the same patient and in the same dosage regimen will have the same therapeutic and side effects.
Two last types of drugs equivalence are very close and, in many cases, bioequivalent products are therapeutically equivalent as well. So, what about the possible differences in the number of adverse effects and the nature of such side effects? Therapeutic nonequivalence, which results in more adverse effects or less efficacy of the drug, is usually discovered during long-term treatment with patients who have been treated on one formulation and are given a nonequivalent substitute. In some cases, therapeutic equivalence is possible despite differences in the bioavailability of the drug, for example, with penicillin. The therapeutic index (or the ratio of the minimum toxic concentration to the median effective concentration) of this drug is so extensive that its efficacy and safety are usually not affected by the moderate differences in plasma concentration, due to bioavailability differences in penicillin products. At the same time, in contrast to penicillin, differences in the bioavailability of drugs that have a relatively narrow therapeutic index may cause substantial therapeutic nonequivalence.
In pharmacology, bioavailability is usually described as a subcategory of absorption and represents the amount of an administered medication that reaches our circulation. For example, the well-known drug ibuprofen has a very high bioavailability of 80%. This means that your cells actually utilise roughly 80% of the total amount of ibuprofen you take. By definition, when a drug is administered intravenously (through the veins), its bioavailability is equal to 100%. When a medication is taken via other means, its bioavailability is usually lower than that of intravenous consumption. The main reasons for such difference are the intestinal endothelium absorption and first-pass metabolism. Mathematically, the level of bioavailability equals the ratio of comparing the area under the plasma drug concentration curve versus time (AUC) for the extravascular formulation to the AUC for the intravascular formulation. AUC was chosen to assess bioavailability because it is proportional to the dose that has entered the blood circulation. Bioavailability of medication is an average value. In many cases, in order to ensure that the patient with poor absorption is dosed appropriately, the bottom value of the deviation range is used. It allows representing real bioavailability to calculate the needed medication dose for the patient to achieve systemic drug concentrations that would be similar to the intravenous formulation.
As for herbs, dietary supplements, and other nutrients in which the method of administration is almost always oral, bioavailability generally indicates simply the fraction or quantity of the ingested dose that is absorbed by the body. Also, in nutritional sciences, involving the intake of non-drug dietary ingredients and nutrients, the bioavailability concept lacks the well-defined standards that are usually associated with the pharmaceutical industry. The main explanation of why the pharmacological definition cannot apply to dietary ingredients and similar substances is that absorption and utilisation is a function of the nutritional status and physiological state of the patient. Such physiological and nutritional differences may result in significant variation of bioavailability index from one individual to another, which is also known as an inter-individual variation. Nevertheless, how does one evaluate the bioavailability for their dietary supplements correctly? Bioavailability for non-drug dietary ingredients can be defined as the proportion of the taken substance capable of being absorbed and available for use or storage.
In both nutritional sciences and pharmacology, bioavailability index can be measured by calculating the area under the AUC curve.
Factors influencing the bioavailability level. How to evaluate this parameter properly
The level of drug bioavailability, when taken via an extravascular route, is usually less than 100%. There is a range of various factors that can reduce drug availability before it enters the bloodstream. For example, whether a medication is taken with food or without it may significantly affect the absorption of an active agent. Also, drugs that are administered concurrently may influence absorption and first-pass metabolism. At the same time, intestinal motility may alter the dissolution of the drug as well, thereby affecting the degree of chemical degradation of the medication by intestinal microflora. Different diseases affecting gastrointestinal function or liver metabolism can also influence bioavailability, reducing its value. Other factors that may change the bioavailability level are:
- physical properties of the medication, such as its pKa, hydrophobicity, and solubility;
- whether the drug is taken in a fasted or fed state;
- the medication formulation;
- gastric emptying rate;
- interaction with other medications (nicotine, alcohol, antacids) or foods (cranberry juice, grapefruit juice, pomello, brassica vegetables);
- the health of the patient’s gastrointestinal tract;
- differences in circadian rhythm (sleep-wake cycle of the patient);
- individual variation in metabolic differences (age of the patient, his phenotypic differences, gender, and diet);
- disease state (for example, poor renal function or hepatic insufficiency);
- enzyme induction (increased metabolism rate) or inhibition (decreased metabolism rate) by other drugs or foods;
- gastric emptying rate.
The list you just read is a mere ballpark of all the possible factors that may influence the drug bioavailability. Indeed, each of the above-mentioned factors may vary from one patient to another (inter-individual variation) as well as in the same patient over time (intra-individual variation). In the majority of modern clinical trials, inter-individual variation is considered a critical measurement. It is used to assess the bioavailability differences from one patient to the next in order to ensure predictable dosing.
Bioavailability index is usually assessed by calculating the area under the AUC or plasma concentration-time curve. To date, AUC remains the most reliable measure of the bioavailability of medication. AUC is directly proportional to the total amount of unchanged drug that reaches the circulation. Different medicines may be considered bioequivalent in their rate and extent of absorption if their plasma concentration curves are essentially superimposable.
Let’s refer now to an example of plasma concentration-time relationship after a single oral dose of a medication.
Plasma drug concentration usually increases with the extent of absorption. The process continues until the drug elimination rate equals absorption rate, and the maximum (peak) plasma concentration is reached. The elimination of the drug begins as soon as the drug enters the bloodstream. Thus, bioavailability determinations that are based on the peak plasma concentration can be misleading. The moment when maximum plasma drug concentration occurs (peak time) is the most often used index of absorption rate - the slower the absorption, the later the peak time.
For medications that are excreted primarily unchanged in the urine, the bioavailability index can be evaluated by measuring the total amount of drug excreted after a single dose. In order to get the most accurate results, urine is collected over a period of seven to ten elimination half-lives for complete urinary recovery of the absorbed medication. After multiple doses, bioavailability level may be calculated by measuring the unchanged drug recovered from urine over a 24-hour period under steady-state conditions.
What are the causes of low bioavailability index, then? All the drugs administered orally must pass through the intestinal wall and then the portal circulation to the liver. Both of these “barriers” refer to the sites of first-pass metabolism that occurs before a medication reaches the bloodstream. Many drugs can’t pass through these barriers and are metabolised before the necessary plasma concentration levels are reached. Thus, the necessary effect doesn’t occur, and, as a result, the patient doesn’t feel any relief. Low bioavailability always goes hand in hand with oral forms of poorly water-soluble, slowly absorbed medications.
Insufficient time for drug absorption in the gastrointestinal tract is a common cause of low bioavailability level. In the instance that a drug is poorly soluble or is highly ionised and polar - which means it cannot penetrate the epithelial membrane - its time at the absorption site may be insufficient. In such a case, bioavailability tends to be low and may vary significantly. In addition to this, physiological factors of the patient, such as his age, physical activity, stress, genetic phenotype, disorders and previous gastrointestinal surgery can also influence the bioavailability of the administered drug. Chemical reactions that are aimed at reducing absorption can also decrease the bioavailability level. Such reactions formulate a complex (for example, between tetracycline and polyvalent metal ions) conjugation in the intestinal wall, hydrolysis by gastric acid or digestive enzymes, adsorption by other drugs, and metabolism by luminal microflora.
What is CBD bioavailability and why does most CBD oil go to waste in our bodies?
When purchasing CBD products, many of us have high expectations. Advertising often has us believing that cannabinoids are “cure-all” compounds, able to save us from the full range of ailments and health misfortunes. Whilst cannabinoids are potent enough to provide us with a range of health benefits and improve our mental and physical condition, they are (unfortunately) not a panacea. Maybe it is just a question of time, but for now, they are not able to cure everything.
It is always highly recommended that before making a purchase on a CBD product, you delve into the mechanisms of a medication and the way it will act in the body. This will help you understand how they provide such unique benefits. When we are honest with ourselves, however, a large proportion of us skip this key step in before purchasing CBD: research. We go on with our purchase after hearing about the greatness of cannabinoids from our friends or from ads, and decide to blindly try it without having conducted any research into its properties or the way it interacts with our system. We are all guilty of this. Usually, you are then faced with one of two realities: you either obtain the desired relief because you chose the suitable product for your case, or you don’t reap any benefits whatsoever and subsequently start to convince everyone that CBD is nothing but a myth. In the latter option, it is likely that little to no research was done prior to purchase. It is therefore vitally important to understand what medication we take, what effects we will get as well as and why we get them. Preparing in this way can mean that you get the maximum benefits out of your CBD purchase.
Why is the bioavailability of CBD products important? The answer is simple - only 6% of CBD gummies enter our bloodstream to do their job, begging the question: would you still purchase them if you knew that? It is easy to get lost in the promise and excitement surrounding CBD, such that you skip the part where you learn about the various degrees of bioavailability in cannabis products. This isn't helped by the fact that many of us don't fully understand what bioavailability is.
Now we know that bioavailability represents the degree and rate at which an active agent of the taken drug is absorbed into our bloodstream to be used where needed. Cannabis products are also subject to this biological fact, as different physiological processes and consumption methods can significantly affect cannabis absorption, changing its effects. It’s critical for us to get clued up about the bioavailability of cannabinoids in order to get the maximum medicinal potency of cannabis products, which will affect our health for the better. The general rule for cannabis consumers is quite simple - the more bioavailable your cannabis-based product, the lower the quantity of the plant you need to get its benefits. Despite the simplicity of this principle on the surface, the real picture is much more complicated and raises multiple questions. What factors influence cannabis bioavailability? Are some cannabinoids more bioavailable in comparison with others? Which are the best methods of CBD consumption? How does one increase the bioavailability of cannabis-based products? And so on and so forth. Let’s start from the very beginning and try to answer the most common questions regarding medicinal cannabis and its bioavailability.
Today, CBD or cannabidiol is available in various forms including:
- sublingual tinctures;
- various edibles;
Each of these forms has its own pros and cons and requires a different usage method. In addition to this, each of the products typically comes in multiple CBD concentrations. How does one choose from a variety of forms with different flavours, colours, aromas and prices, then? Those of us who have never used CBD might be overwhelmed by the huge range of options available. By understanding the definition of bioavailability, CBD consumers will be able to get the answers to their burning questions regarding the best method of CBD consumption and optimal dosage, amongst others. In addition to the amount and strength of the active substance, bioavailability also determines how much of the product is actually present to provide you with the necessary effects. In most cases, if a physician were to prescribe a CBD product, part of the calculation about the apt dosage would include bioavailability.
The bioavailability of CBD products varies depending on how they are taken and the concentration of CBD in the product itself. This leads us to the next crucial question: what is the best way to take CBD? Given what we have already learnt about the way to maximise bioavailability, through intravenous consumption, you might therefore assume that the best way of taking CBD is by injecting it directly into the bloodstream through the veins. Although this method delivers 100% of CBD into the body, it isn’t advised for obvious reasons. Instead, let's take a look at other popular and safe methods of using CBD and estimate how each of them affects CBD bioavailability.
- Oral consumption. Basically, this term means to consume something through your mouth - easy. In the world of CBD products, common products that demand oral consumption include CBD capsules, CBD beverages and CBD edibles. This method offers a range of advantages, one of which is its simplicity. You can take a CBD capsule or eat a couple of CBD gummies anywhere, without worrying that it may disturb other people or that it may be confiscated. In terms of bioavailability, the oral consumption method is definitely not the best choice for consumers aimed at obtaining the maximal possible bioavailability index. Any substance you consume orally will have to pass through your metabolic and digestive systems, both of which will filter out a large portion of the CBD product, thereby significantly reducing its bioavailability. According to a study held in 1986, the bioavailability of CBD products consumed orally was equal to only 6%. However, in another study performed in 2009, it was reported that the bioavailability index in the case of oral consumption of CBD products varies between 4% and 20%. The results of these studies differ significantly, although both sets of results speak to the low bioavailability of oral CBD consumption, even taking into account the possibility of 20% bioavailability. Simply put, if you eat a CBD edible that contains 100mg of cannabidiol, only 20mg from the total amount will actually reach your bloodstream. Of course, part of an active agent will always be lost in the digestive tract, but over 75%, as in this example, is a lot. In conclusion, those who want to get the maximum effects from CBD should consider electing a different mode of CBD consumption.
- Sublingual consumption. Whilst oral consumption doesn’t impress much with its bioavailability index; sublingual consumption of cannabidiol-infused products does. The secret of this method lies in a particular vein under the tongue, called the sublingual gland. When an active substance is administered to this gland, it is absorbed directly into the bloodstream of the consumer. The most common sublingual administration methods include CBD sprays, CBD tinctures, and CBD lozenges. In comparison with oral consumption, the sublingual way of taking CBD products is more direct: it has a quicker impact on the body and has a higher level of bioavailability, only being degraded by enzymes in the saliva found in the mouth. There are different factors that may influence the CBD bioavailability of sublingual consumption, with most of them involving CBD product quality. While taking into account all of these factors, the ranges of CBD bioavailability in the case of sublingual consumption varies from 12% to 35% - significantly higher than in the method of oral consumption, then.
- Vaporised consumption. Vaporised consumption of CBD involves inhaling cannabidiol directly into the lungs by using a vaporiser device or a vape pen. While entering the lungs directly without any “obstacles” in its way, CBD can quickly and directly enter the bloodstream of the consumer, thereby providing us with decreased breakdown rates and a higher index of bioavailability. According to the results of numerous studies investigating this method of CBD consumption, bioavailability rates in the case of the sublingual method of use vary between 34% and 46%, while some of the sources even report up to 56%. To date, vaporising CBD is considered as one of the most effective methods of CBD consumption and is recommended by many cannabis experts.
The knowledge about how cannabidiol bioavailability works can not only help you to increase the effectiveness of CBD products you are taking but also save you from overspending on other methods with a low level of bioavailability. Let’s consider one simple example and calculate the cost of two different CBD options. For example, you may have a choice to purchase a 500mg CBD edible and spend £50 on it, or buy a 500mg CBD e-liquid and pay the same price. Let’s check what your body will gain from both these options.
- CBD edibles. If taking into account the highest rate of bioavailability, CBD edibles are equal to 10%, so 50mg of CBD would enter your bloodstream. To continue the earlier example of paying £50 for a 500mg pack, this means you would be paying £1 per 1mg of CBD.
- CBD e-liquids. CBD e-liquids for vaporisers have a bioavailability rate of 35%, which means 175mg of your CBD would enter the bloodstream. While spending £50 on 500mg of CBD, you would be paying 28p per 1mg of CBD which is 72% cheaper in comparison with CBD edibles.
That is just one of the numerous examples of calculations that could be made to estimate regular spending on CBD. If we take this calculation to a larger scale, imagine that an average consumer uses 1000mg of CBD every month. Over the course of the year, this would be equal to 12,000 mg of CBD and thus £12,000. Impressive, right?
When purchasing CBD products, we should try to see beyond potentially misleading advertisements that promise instant results and exciting new CBD edibles. First and foremost, we should think about our health and wellness, not forgetting the main reason why we decided to purchase these products in the first place. Health benefits and effectiveness of cannabidiol-infused products should remain the primary reason for consuming them and, in this case, the bioavailability of your choice plays a vital role.
Although it is wildly popular and novel, CBD can still be a minefield for many first-time users. In order not to get lost in CBD wilds and learn how to filter information from various sources, you should understand the main CBD concepts. By highlighting the most critical cannabidiol characteristics, you will be able to get the most out of your CBD products and spare yourself the potential disappointment of ineffectiveness. The first thing that should be taken into account when deciding to use CBD is the bioavailability of its different forms.
Don’t rush and take time to determine the bioavailability rate of a chosen product. Compare several options, calculate spending, and decide which of the CBD products and methods suit your requirements the most. Remember, ads are useful and often serve as the engine of progress. However, look upon them with caution and do your own groundwork; read reviews, learn the features of CBD and how it acts, sharpen up on your knowledge about CBD and cannabinoids in general, and make your final choice!