Bioavailability of Cannabinoids via Ingestion – Developing an Advanced Delivery Model

[headline]What if you could obtain maximum benefits of CBD without inhalation or smoking?[/headline]

Many people have started eating hemp foods, or consuming either cannabis-derived or hemp oil drops, in order to take advantage of one of nature’s healthiest foods. Although there are a number of important items you should consider before making changes to your diet or consumption habits, one vital fact outweighs all the others: the vast majority of the cannabidiol (CBD) or tetrahydrocannabinol (THC) that you consume ends up in your toilet.

This article is not going to discuss the differences between cannabis and hemp; nor the many healthy attributes of hemp based foods; and, not even the human endocannabinoid system. We assume the reader is already informed regarding these topics. Instead, we explore how cannabinoids are ingested and absorbed; different delivery mechanisms; recent technological advances in bio absorption; and, how those advances offer users an alternative to smoking.

We need to understand what bioavailability is and how it differs from absorption. They are related and similar – but different: absorption is just one component of bioavailability. To truly understand bioavailability we have to speak briefly about how the human body digests food. The object of digestion is to transform large food particles into smaller molecules, which can more easily be absorbed into your water-soluble blood plasma. That is how you get nutrients and energy.

Very little digestion actually occurs in your stomach which is designed, in part, to kill pathogens and foreign substances that should not be ingested. In fact, roughly 95% of all digestion happens in your small intestine. Digestive enzymes intermingle with your food during the roughly 2 hour journey to arrive at your small intestine, breaking down the food and preparing it for absorption. Unfortunately hydrochloric acid in your stomach is also quite capable of destroying many nutritious, fragile molecules before they can ever be absorbed.

There are dozens of different cannabinoid molecules, and most of them share similar molecular characteristics. In general, cannabinoids do not tolerate acidic environments. Studies have shown poor recoveries or even 0% recoveries of cannabinoids in acidic environments¹.

The mouth and throat are a roughly neutral environment, with a pH of roughly 6.8. Stomach pH can be anywhere in the 1.0 – 3.0 range: highly acidic. In contrast, the small intestine has a highly alkaline environment conducive to molecular absorption, about 8.5. Normal water is neutral or slightly alkaline and has a pH of 6.2 – 7.0. Finally, a pH of 8.0 is ten times more alkaline than a pH of 7.0; and a pH of 3.0 is 10,000 times more acidic than a pH of 7.0.  

For these and other reasons, digestion/absorption/bioavailability of cannabinoids in their unprocessed form, is very low. The molecules typically do not survive their passage through the stomach undamaged and are not free to be absorbed in the alkaline environment of the small intestine. 

Finally, your liver has a major role to play in that it regulates what molecules are allowed to reach your general circulation after ingestion, absorption through your small intestine, and finally passage through the liver’s filtration systems. It often wraps up what it identifies as dangerous molecules in water-soluble chemicals that are identified for ejection through urine. 

The topic of cannabinoid absorption is well understood and has been repeatedly studied. Bioavailability of CBD (or of THC) varies greatly by delivery method. Smoking typically delivers cannabinoids at an average bioavailability rate of 30%². Cannabinoids that are absorbed through the mucous membranes in the mouth (buccal mucosal application) have bioavailabilities of around 13%³. By comparison, orally consumed cannabis edibles typically deliver cannabinoids at an average bioavailability rate of only 5%⁴ . 

Bioavailability from both vaping and sublingual drops, by the way, fall inside the range established at the high and low ends, by smoking and edible ingestion respectively. Absorption of cannabinoids through smoking (burning is an oxidizing process) is relatively high because the molecules are not required to pass through the hostile stomach environment, and instead are absorbed into the bloodstream through the lungs. Although smoking is a relatively efficient and quick acting process, it is also a well-known health hazard. Of the one billion people around the world who smoke, roughly six million people die each year from diseases caused directly by smoking. More on that later. 

[infobox]This is a good place to summarize what we know so far:

• In order to improve absorption levels via edible ingestion, the cannabinoid molecule has to be protected for at least two hours while it passes through the acidic stomach environment. 

• Final bioabsorption rates are comprised of several operations, including survival of a given molecule through the GI system; absorption through the walls of the small intestine; a selective filtering process by the liver; and even more processes are required to put that molecule to useful work within your body.

• Because of the above, historically, smoking has been the most effective way to absorb cannabinoids into the body. Roughly 30% of cannabinoids are absorbed via smoking, compared to only a 5% rate via edible ingestion. 

• Smoking is a serious health hazard, and many non-users find it objectionable.  [/infobox]

The goals of higher bioavailability of cannabinoids are thus threefold: to mollify objections to its smoking from non-cannabis users ; to reduce unhealthy hazards of smoking; and to more consistently deliver a higher proportion of useful molecules comprised from lower overall dosages that place less of a load on the liver. The challenges associated with efficient delivery of cannabinoids and the benefits to be experienced both by consumers and society through overcoming those challenges are now well understood.

[quote]Bioavailability matters… a lot. Improved bioavailability can lead to reduced social pressures associated with what are currently more common delivery methods such as smoking or vaping. [/quote]

New ideas are focused towards discovering new technologies that can more efficiently deliver cannabinoids to the bloodstream where they can have their desired effect. Pointedly focused research is being devoted to understanding of the human endocannabinoid system and how it can function at a higher level through the efficient and healthy ingestion of cannabinoids. To this end, recent in vitro lab experiments have greatly expanded our understanding of the most efficient ways to deliver cannabinoids through ingestion.

In order to succeed in delivering a higher percentage of ingested cannabinoids into the human bloodstream, we first need to figure out how to protect the cannabinoid molecule on its journey through the gastrointestinal system.

It is well known that ingesting fats ( the terms “fats” and “lipids” can often, though not always, be used synonymously) while simultaneously ingesting other focused-upon substances can often lead to higher absorption levels of those key substances.“The US FDA recommended high fat meals for food-effect studies because such fatty meals (800–1000 cal, 50%–65% fat, 25%–30% carbohydrates and 15%–20% proteins) affect GI physiology and maximize drug transfer into the systemic circulation.⁵”

The reasons for this increased absorption have, in part, been previously discussed within this article. Fats are emulsified by gallbladder secretions, breaking it down into more easily absorbed particles in the small intestine. And some types of fats take a different path into the human bloodstream than most other nutrients: they bypass the portal vein that otherwise goes straight from the intestine to the liver for filtering before nutrients are generally allowed to reach the majority of the body. Instead, the body re-assembles certain fats and shuttles them to the lymphatic and circulatory systems where they enter the general bloodstream without passage through the liver. Many fats bypass the portal vein “freeway” to the liver, whereas smaller fatty acids that are more water soluble do indeed go to the liver first.

As well, in order to prepare cannabinoids for higher bioavailability, the cannabinoid molecules can be manipulated in certain ways to connect them at a molecular level with various foods. Technologies exist that “shuttle” the cannabinoid molecules “within” other food molecules, even unrelated to lipids. Foods to be selected should offer certain characteristics that work synergistically with cannabinoids, such as black tea. Then lipids such as sunflower oil and milk powder and others can be added due to their well known properties within the human GI system.

In the summer of 2015, a US laboratory performed some of the first tests ever known to be conducted, on cannabidiol absorption into human intestinal cells. The results were astonishing. Utilizing a mixture of hemp oil, black tea and select lipids, and processed with a patent-pending technological method, resulted in intestinal tissue CBD permeability 325% higher than CBD mixed with black tea and water. And when that same mixture of hemp oil, black tea and select lipids, and processed with the patent-pending technological method is compared to the absorption of CBD and water alone, the absorption levels into the human intestinal cells rose to a 499% improvement.

This sort of vital scientific research adds to our cumulative understanding that cannabinoids can indeed be ingested with bioabsorption levels that approach or perhaps even surpass those achieved from smoking. However much remains to be learned. For example we do not know what ratio of cannabinoids might be delivered to the liver for filtration via the portal vein as compared to delivery straight to the lymphatic and circulatory systems for higher bioavailability. And, additional laboratory testing with different individual lipids will have to be undertaken to determine which might perform best.

Live animal tests, or even human testing, may be required to learn more about how the newest forms of technology are able to manipulate cannabinoid molecules along with certain food molecules to deliver such dramatic changes in absorption. Once the processes are more thoroughly researched we will begin to have a more complete understanding of the most efficient ways to deliver cannabinoids to humans.

Since all cannabinoid molecules are so closely related, it is reasonable to believe that the processes that work for  
higher bioavailability rates in CBD will also work for THC and other cannabinoid molecules. One potential outcome is that in pursuing more efficient delivery methods for any of these molecules, it may be possible to lower overall dosages for all of them.

The benefits are obvious: a person requiring 10 mg of a substance in order to achieve a desired outcome would have to consume 200 mg of that substance, if the bioavailability is only 5%. But raise the bioavailability rate to say, 30%, and consumption drops to just 33 mg. This is a massive reduction in intake with a lower risk of overdosage, and leads to a potentially lighter workload on the liver accompanied by certain reductions in waste and consumer cost.

Until recently, smoking was the most effective way to ingest cannabinoids, provided one was willing to overlook the unhealthy side effects and the social stigma. This creates a deadly paradox: “some cannabinoids are good for me, but smoking is not”.

Smoking is an increasingly unacceptable activity in large segments of society. The death and misery toll from disease caused by smoking is unarguable. There is a large segment of society which reasonably argues that the act of smoking marijuana impacts non-smokers. The moment a smoker impacts a non-smoker, either through odor or second hand smoke, smoking is no longer a personal decision, even though it may deliver beneficial molecules such as cannabidiol.

Now, because our understanding of bioavailability has increased, and the new and exciting advances in technology, it is possible to deliver comparable bioavailability as smoking, but without the negative side effects. It is actually possible that one day, using disruptive, absorption enhancing technologies, foods will be reasonably able to replace smoking as the most effective delivery mechanism for cannabinoids.

Bioavailability matters… a lot. Improved bioavailability can lead to reduced social pressures associated with what are currently more common delivery methods such as smoking or vaping. Reducing smoking can lead to fewer societal objections for both cigarette and cannabis smoking. Positive community health outcomes are likely to be associated with lowered rates of smoking. And, higher bioavailability could be associated with lower overall dosages of certain molecules which can itself be associated with reduced stress on the liver and other organs, as well as financial cost savings for consumers.

 References:

1Detection And Quantification Of 17 Synthetic Cannabinoids And One Metabolite (JWH-018- COOH) In Blood And Urine, J Sobhani Sefy.
²Huestis (2007) Chem. Biodivers. 4:1770–1804; McGilveray (2005) Pain Res. Manag. 10 Suppl. A:15A – 22A
³Karschner et al. (2011)  Clin. Chem. 57:66–75
⁴Karschner et al. (2011)  Clin. Chem. 57:66–75
⁵Food and Drug Administration, Guidance for industry: food-effect bioavailability and fed bioequivalence studies, food and drug administration. www.fda.gov/cder/guidance/5194fnl.html