From June 2015 to August 2015, Lexaria commissioned an independent, third-party laboratory to test our DehydraTECH™ technology under carefully monitored in vitro conditions. Specifically, we wanted to gain scientific evidence of two hypothesis. As it turned out, we learned that and more.
First, does our technological process yield an improvement in intestinal absorption? The answer was YES. Second, does our lipid formulation yield an improvement in intestinal absorption? The answer was also YES. In addition, we also learned that our processed, lipid-infused tea was absorbed at higher levels in the presence of “gastric juices” than in a more sterile environment without any “gastric juices”, suggesting though certainly not proving that our DehydraTECH™ technology may be more effective in an actual gastrointestinal system than in an in vitro simulation.
Below, we explore why bioavailability is such an important consideration, and how it affects more than one might at first imagine. There are a number of important considerations to contemplate before making changes to one’s diet or consumption habits, but one vital fact outweighs all the others: the vast majority of the cannabidiol (CBD) or tetrahydrocannabinol (THC) that is consumed without technology such as ours – via ANY method – ends up being excreted as waste by the body without meaningful absorption and bioavailability.
A key part of the 2015 in vitro study evaluated how cannabinoids are ingested and absorbed, assessing different delivery mechanisms, recent technological advances in bioabsorption, and how those advances offer users an alternative to smoking. In undertaking this study, it was important 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 one’s water-soluble blood plasma. That is how humans get nutrients and energy.
Very little digestion actually occurs in the stomach, which is designed, in part, to kill pathogens and foreign substances that should not be ingested. In fact, roughly 95% of all digestion and absorption happens in the small intestine. Digestive enzymes intermingle with food during the roughly 2-hour journey to arrive at the small intestine, breaking down the food and preparing it for absorption. Unfortunately, hydrochloric acid in the 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 environments (Source: Detection and Quantification Of 17 Synthetic Cannabinoids And One Metabolite (JWH-018- COOH) In Blood And Urine, J Sobhani Sefy).
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, which is highly acidic. In contrast, the small intestine has a highly alkaline environment conducive to molecular absorption, with a pH of about 8.5. Normal water is neutral or slightly alkaline and has a pH of 6.2 – 7.0. For scale, 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, and 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, the liver has a major role to play in that it regulates what molecules are allowed to reach the general circulation after ingestion, absorption through the 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% (Huestis  Chem. Biodivers. 4:1770–1804; McGilveray  Pain Res. Manag. 10 Suppl. A:15A – 22A). Cannabinoids that are absorbed through the mucous membranes in the mouth (buccomucosal application) have bioavailabilities of around 13% (Karschner et al.  Clin. Chem. 57:66–75). By comparison, orally consumed cannabinoid infused edibles typically deliver cannabinoids at an average bioavailability rate of only 5% (Karschner et al.  Clin. Chem. 57:66–75).
Bioavailability from both vaping and sublingual drops fall inside the range established at the high and low ends of 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 below.
This is a good place to summarize what we know so far:
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 efficiently and effectively 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.
Lexaria has focused on discovering new technologies that can more efficiently deliver cannabinoids and other lipophilic (i.e., fat soluble) beneficial molecules to the bloodstream where they can have their desired effect. Our pointedly focused research is devoted to understanding the human endocannabinoid system and how it can function at a higher level through the efficient and healthy ingestion of cannabinoids. To this end, our 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 needed 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.” (Food and Drug Administration, Guidance for industry: food-effect bioavailability and fed bioequivalence studies, food and drug administration. https://www.fda.gov/OHRMS/DOCKETS/98fr/5194fnl.pdf).
The reasons for this increased absorption have, in part, been previously discussed. Fats are emulsified by gallbladder secretions, breaking them 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 hepatic 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 circulatory systems where they enter the general bloodstream without passage through the liver. Many so called long chain fatty acid compounds, therefore,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. Lexaria’s DehydraTECH™ technology “shuttles” the cannabinoid molecules “within” other food molecules, even unrelated to lipids. Foods that we select have certain characteristics that work synergistically with cannabinoids, such as black tea. Then lipids, such the long chain fatty acids found in sunflower oil, can be added due to their well-known properties within the human GI system.
In the summer of 2015, the US laboratory we commissioned performed some of the first tests ever known to be conducted on long chain fatty acid processed cannabidiol absorption into human intestinal cells. The results were astonishing. Utilizing a mixture of hemp oil, black tea and select lipids, processed using our patented dehydration synthesis technological method, the final result showed intestinal tissue CBD permeability 325% higher than CBD similarly processed with black tea and water but lacking our lipid incorporation. And when that same mixture of hemp oil, black tea and select lipids, processed with our DehydraTECH™ method was compared to the absorption of CBD suspended in water alone without any benefits of lipid incorporation and our processing techniques, the absorption levels into the human intestinal cells rose to a 499% improvement via our methodology.
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, and 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 cannabinoid molecules are so closely related, it is reasonable to believe that the processes that work for higher bioavailability rates in CBD also apply for THC and other cannabinoid molecules. Lexaria is committed to pursuing more efficient delivery methods for both of these molecule classes, as well as a variety of other lipophilic beneficial molecules outside of the cannabinoid space, and believes that it may be possible to create more efficient and effectively delivered product formats with lower overall dosages for all of the beneficial molecules we are investigating.
The benefits are obvious: a person requiring 10mg of a substance in order to achieve a desired outcome would have to consume 200mg of that substance if the bioavailability is only 5%. But raise the bioavailability rate to 30%, and the necessary consumption level drops to just 33mg. This is a massive reduction in intake with a lower risk of over-dosage, 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 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 with the new and exciting advances in technology, it is possible to deliver comparable bioavailability to that of smoking, but without the negative side effects. It is actually possible that one day, using disruptive, absorption enhancing technologies like DehydraTECH™, foods will be reasonably able to replace smoking as the most effective delivery mechanism for cannabinoids and nicotine, while also providing a powerful new way to deliver a host of other beneficial molecules more efficiently and effectively like pain relievers, vitamins, supplements and more.
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.