CBD Bioavailability: Part 1 of 2


by Mark Rosenfeld -

Editor’s Note: This blog is the first of a two-part series on the bioavailability of cannabidiol (CBD). To read part two, click the following link: True Bioavailability, Hemp vs. Marijuana.

An increasing number of oral and topical offerings in the cannabis space feature claims of high bioavailability—especially as it pertains to cannabidiol (CBD)—meaning that a lot of what is taken reaches the bloodstream. Whether this is indeed the case is questionable when the proper information needed to verify is not available. Only bioavailability studies that employ proper scientific methods will prove as reliable indicators of product legitimacy and dependability. In no uncertain terms, valid data to support claims of 100 percent bioavailability are a literal impossibility given the metabolic and physical obstacles to getting cannabinoids from the mouth or skin into the bloodstream. Cannabinoids then travel from the bloodstream to their sites of action—special receptors located on certain cells. Once there, different formulations with the same active ingredient can express unequal effects on performance.


Cannabinoids, chemistry exclusive to cannabis plants (e.g., CBD, tetrahydrocannabinol (THC), cannibigerol, cannabichromene, cannabidivarin, tetrahydrocannabivarin), have progressed from illegal to legal status in more than half of the United States and in some countries. This is due more to political and social factors than scientific or medical ones, such as studies to more fully verify the therapeutic potential of cannabinoids. A bottom line is that there exists a lack of scientific work to confidently support health-related claims made about these molecules. This is due in no small way to obstacles placed by government on doing germane research. In addition, the methods of science do not come naturally to most people, and this is accompanied by a natural tendency to disregard what is difficult to understand. Ignorance and falsehood can then take precedence.

Pre-clinical studies and human clinical trials are especially striking by their absence. "Pre-clinical" refers to studies that typically occur prior to human clinical trials. It is from pre-clinical work that key parameters or attributes such as bioavailability, dosing and safety are ascertained, and therapeutic targets identified.

It is undisputable that cannabinoids for fostering human health remains far from a matured, knowledge-rich discipline. Despite the public lack of scientific information needed for making cannabinoid-containing formulations that truly and reliably work, the manufacture and sales of commercial products have gotten underway. Whether these products are worth buying can be confusing for consumers.

For example, claims of substantial bioavailability—or how efficiently a substance is able to get into the bloodstream—are being made for many commercial offerings. Greater bioavailability should be considered an essential product attribute. Difficulties in getting cannabinoids to the bloodstream are considerable, and for a product to work as desired centers in no small way on how well a particular formulation reaches the bloodstream. Greater bioavailability means more can get there.

Consumers must be diligent in differentiating between believable bioavailability claims predicated on real science and far-fetched ones based on mistaken or fraudulent premises. In that regard, the need for bona fide science cannot be understated. It provides information for being able to more confidently discern what really works.

Unfortunately, the bioavailability claims for certain products may be more due to ignorance and falsehood than facts. Background and perspective may provide information for making properly informed product choices.

What Is Absolute Bioavailability?

Absolute bioavailability refers to the fraction of a substance able to reach the bloodstream (where it can then be most readily transported to where it acts in the body) after having been introduced into the body—for example, as an injection, pills and liquids taken by mouth, or a topical treatment. Determining bioavailability is essential for ensuring product safety, effectiveness and cost.

In essence, measuring absolute bioavailability entails comparing a formulation with a target substance against intravenous (IV) administration (moving a substance into the bloodstream through a hypodermic syringe inserted into a vein). Since all of a substance reaches the bloodstream with IV, it is deemed 100 percent bioavailable by definition.

Other delivery routes are associated with absolute bioavailabilities less than 100 percent due to multiple metabolic obstacles hindering entry into the bloodstream. Oral administration, i.e., taking a pill or liquid, entails hurdles such as breakdown in the stomach, difficulties in leaving the digestive system and destruction in the liver. These can prove huge barriers for getting necessary amounts of a substance into the bloodstream.

Nevertheless, oral and topical products are overwhelmingly preferred by consumers because of convenience and ease-of-use. But those involving an active ingredient with low bioavailability, as are cannabinoids, could prove functionally worthless and/or exceedingly costly. With absolute bioavailability improperly assessed, this circumstance becomes increasingly problematic.

In no uncertain terms, bioavailability studies are the way to determine efficacy and safety, which makes them an appropriate reference point for consumers considering a purchase. In fact, a product should be considered suspect or questionable without such evidence being made available.

Enhancing Absolute Bioavailability of Cannabinoids

A common rule in product development is that, if oral bioavailability is very low, less than 20 percent, a substance should probably be excluded from commercial development. This is because of the unpredictable, irregular and lacking responses associated with low bioavailability, along with the use of costly and even hazardous amounts of a substance, to circumvent this problem. Whether as a pharmaceutical, functional food or dietary supplement, this should be a major topic of concern with cannabinoids, which have bioavailabilities of only 5 to 6 percent when taken by mouth.

For orally consumed cannabinoids to become therapeutically worthwhile and economical, it consequently becomes important to employ technologies designed for safely getting more of a substance into the bloodstream. Being able to amplify cannabinoid bioavailability portends lessened dosages, which in turn make for reduced stress on the liver and other parts of the body, along with cost savings to the consumer and a more predictable therapeutic response.

How Is Bioavailability Examined?

Pre-clinical studies are the cornerstone for determining product attributes like absolute bioavailability, safety and toxicity. Such studies lead the way in providing necessary first answers about efficacy and safety for pharmaceuticals, nutraceuticals or functional foods, and dietary supplements.

Correctly executing a bioavailability study is conceptually straightforward. In essence, it consists of some test subjects receiving a formulation of interest and others getting a preparation for comparison. For cannabinoids, formulations of interest may be those treated in a manner that is supposed to improve bioavailability. The comparison will be cannabinoids not subjected to any treatment.

Statistical analysis is employed to ensure that perceived differences in a bioavailability study are meaningful and not due to chance. Essentially, there need to be enough subjects to ascertain statistical significance of a difference between the two groups.

A bioavailability study tends to be costly, and is most often done with rats or mice. It usually does not go forward without surmounting another hurdle, demonstrating that subjects will be responsibly treated. A study, prior to getting underway, must be reviewed by a special committee to decide for or against an approval to go forward. The committee weighs the benefits of the study against possible or unavoidable injury and suffering. A scientifically sound, well-designed bioavailability study will usually pass muster.

Scrutinizing Bioavailability Studies

Studies of absolute bioavailability studies must be done to make a credible claim, for which the following should be considered during consumer due diligence:

  • Is there a written data summary that justifies any bioavailability claims? If none exists, then the product in question should be deemed questionable or suspect.
  • A written report will usually include a tabulation of the data, along with a statistical analysis of the study results. The report should ideally explain what was actually done in reasonable detail, i.e., the experimental design and sample preparation, along with how or what statistics were applied.
  • It is proper to inquire if bloodstream analyses were done at an analytical laboratory experienced in examining cannabinoids in bloodstream. In the United States, there are few facilities proficient in this regard. This scarcity is due in no small way to legal prohibitions that have long plagued the cannabis industry.
  • Bloodstream samples may be either serum or plasma, as long as the same sample type is used throughout. Serum is the liquid portion left after bloodstream clots. Plasma is generated from bloodstream treated with an anticoagulant (a substance that stops the clotting of bloodstream). Gravity causes red bloodstream cells to settle to the bottom. The straw-colored liquid on top is plasma.
  • Statistical tests are the proper way to assess if differences between two different cannabinoid formulations have meaning (e.g., greater absolute bioavailability). Test results are not difficult to interpret. These are reported as probabilities or p values. As p values get lower (i.e., closer to 0 percent and farther away from 100 percent), it becomes more likely that a real difference exists. A p value of .05 is considered borderline, i.e., the cut-off for a bona fide difference. It means there is a 95 percent, or 19 in 20, chance that differences in what is being compared are real. With p values of .001, the odds are 999 in 1,000.
  • Bioavailability determinations help to ascertain how much cannabinoid should be administered to achieve a particular result. High bioavailability is associated with using lesser amounts of a target substance. The smaller the dose needed for efficiently getting a cannabinoid into the bloodstream, the more potent, predictable and cost-effective the formulation.

Editor’s Note: To read part two of the blog, visit True Bioavailability, Hemp vs. Marijuana.

Mark J. Rosenfeld, Ph.D., is CEO and chief science officer at ANANDA Scientific Inc. He has centered much of his professional attention on making cannabinoids acceptable human medicine. Rosenfeld conceived and has directed the successful development of unique nanotechnologies to resolve unmet needs that have barred cannabinoids from widespread use to benefit human health. He holds 15 patents in pharmacology and molecular disease detection. ANANDA Scientific’s science-based approach spans research, development and production. The company has a strong presence in Israel—the global center for cannabis-related research—as well as China, with product production done in the United States.