Education

The Facts About DehydraTECH™

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 DehyrdaTECH-enabled 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 effective in an actual gastrointestinal system rather than just in a simplified 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 many substances that are orally consumed without technology such as ours ends up being excreted as waste by the body without meaningful absorption and bioavailability.

DehydraTECH Applications

Lexaria Bioscience Corp. has since 2015 conducted a number of in vitro studies, in vivo animal studies, and human clinical tests and has done so chiefly with hemp-derived CBD as the active pharmaceutical ingredient (“API”) under study. There are certain similarities between these fat soluble, plant-derived molecules that have led Lexaria down its investigatory pathways. Lexaria has consistently led the industry in driving for consumer improvements in bioavailability and more.

A key part of the 2015 in vitro study evaluated how APIs 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.

DehydraTECH Applicability in API Delivery

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.

There are dozens of different potential API molecules under consideration for DehydraTECH processing. Many APIs do not tolerate acidic environments. Studies have shown poor recoveries, or even 0% recoveries 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 mand APIs in their unprocessed form is very low. The molecules often 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 and processing systems. It often “wraps up” what it identifies as dangerous molecules in water-soluble chemicals that are identified for ejection through urine.

medical cannabinoid research Biotechnology Applications | Lexaria Bioscience Corp. | pH Scale

DehydraTECH Encourages Eating Instead of Smoking with Increased Bioabsorption

Bioavailability from both vaping and sublingual drops will generally be in the 14% – 40% range which is quite high but also associated with certain negative health impacts. Edible ingestion of API’s often drops to the 5%-6% range which is quite low, but with far fewer negative health impacts. Consumers don’t automatically realize that there are health consequences associated with non-ingestible forms of delivery.

Absorption of CBD through smoking or vaping is a complicated and controversial topic. Absorption into the bloodstream through the lungs is known as pulmonary absorption. Although smoking is a relatively efficient and quick acting process, it is also a well-known health hazard if through smoking. The long-term health consequences of vaping are not currently known and are thought to be far less severe than via smoking. However, there is increasing data to suggest that vaping does present many unique health consequences.

CBD degrades or is destroyed at relatively low temperatures – it has a far lower flash point than other well known cannabinoids. The idea of absorbing CBD either through combustion or through vaping – which heats an oil to produce a vaporized “mist” – is not conducive to the delivery of large proportions of CBD since those high temperatures can destroy much of the CBD prior to delivery.

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

  • In order to improve absorption levels via edible ingestion, the API has to be protected 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 allow that molecule to be put to useful work within the body.
  • Smoking is a serious health hazard, and many non-users find it objectionable.
  • The temperatures involved in vaping OR smoking are sufficient to destroy large proportions of the CBD in the original product before it ever has a chance to be absorbed into the body.

The goals of higher bioavailability of hemp products are thus threefold: improve the flavor profile that can be very bitter and pungent so that the CBD can be ingested via the healthiest method possible; increase the speed by which the API is delivered to the bloodstream; and, increase the amount of API that reaches the bloodstream

Pioneering Technologies to Shape the Future of Our Industries

Lexaria has focused on discovering new technologies that can more efficiently deliver molecular APIs to the bloodstream where they can have their desired effect. To this end, our lab and human experiments have greatly expanded our understanding of the most efficient ways to deliver APIs 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 API molecule on its journey through the gastrointestinal system and into the bloodstream.

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 hemp for higher bioavailability, the hemp molecules can be manipulated in certain ways to connect them at a molecular level with various foods. Lexaria’s DehydraTECH technology “shuttles” the hemp molecules “within” other food molecules, even unrelated to lipids. Then lipids, such the long chain fatty acids found in sunflower oil, can be added due to their well-known beneficial properties within the human GI system.

Lexaria’s Human Clinical Study Demonstrates Remarkable Improvements in Cannabidiol Absorption

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 with certain APIs that measured absorption into human intestinal cells. The results were astonishing. Utilizing a mixture of API, black tea and select lipids, processed using our patented dehydration synthesis technological method, the final result showed intestinal tissue API permeability 325% higher than API similarly processed with black tea and water but lacking our lipid incorporation. And when that same mixture of API, black tea and select lipids, processed with our DehydraTECH™ method was compared to the absorption of API 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 APIs 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 did not know what ratio of API 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 was needed to determine which might perform best. We were on the right path, but we had more work to do.

Ground-breaking 2018 Human Study

During 2018 Lexaria performed a double blinded, randomized, placebo controlled human clinical study at a medical research university in Europe. The degree and speed of CBD absorption into blood plasma and potential cardiovascular and cognitive performance enhancement in 12 healthy male volunteers were studied.

Key bioavailability data highlights from the study comparing the 90 mg dose of Lexaria’s TurboCBD™ to a 90 mg dose of a positive control formulation without Lexaria’s DehydraTECH™ technology were as follows:

 

  • 30 Minutes: CBD delivered from Lexaria’s TurboCBDTM capsules was absorbed much more effectively than from the positive control, delivering 317% more CBD to blood at the 30-minute mark of the study (i.e., 18.4 ng/mL compared to only 4.4 ng/mL on average respectively [95% CI; p=0.051]);
  • 60 Minutes: The TurboCBDTM capsules went on to deliver more CBD to the blood at the 60-minute mark (i.e., 38.8 ng/mL) than the positive control capsules were able to reach at any time during the 6-hour study, further demonstrating the exceptional rapidity of action and effectiveness of the TurboCBD™ capsules;
  • 90 Minutes: The TurboCBDTM capsules further went on to deliver significantly more CBD to the blood (86% more) than the positive control capsules at the 90-minute mark (i.e., 53.0 ng/mL compared to only 28.4 ng/mL respectively [95% CI; p=0.034]);
  • Through to Study Completion: Lexaria’s TurboCBDTM capsules continued to deliver more CBD to blood than the positive control capsules at each subsequent time point in the study through to the 6-hour mark when the study was completed.

 

These results corroborate and confirm earlier in vitro and in vivo studies that have evaluated Lexaria’s DehydraTECHTM technology and have consistently measured higher levels of drug delivery much more quickly than positive controls with matching CBD concentrations.  Although this study evaluated absorption only of CBD and its metabolites, Lexaria believes nearly identical bioavailability enhancement results would be achieved if other cannabinoids had instead been studied.

Time (Minutes) Blood levels following       90 mg

TurboCBD

(ng/mL)

Blood levels following 90 mg Positive Control

(ng/mL)

TurboCBD

Blood Level % Increase from Positive Control

0 0.0 0.0 n/a
30 18.4 4.4 317%
60 38.8 29.9 30%
90 53.0 28.4 86%
120 56.0 33.9 65%
150 41.8 37.0 13%
180 40.5 26.4 53%
240 22.0 16.1 37%
300 14.5 9.2 58%
360 10.3 7.5 38%

These study findings were of particular interest relative to a Mount Sinai study previously completed that tested orally administered CBD supplied by market leader GW Pharmaceuticals PLC at much higher doses of 400 mg and 800 mg [J. Addict. Med. 2015 May-Jun; 9(3): 204-210].  CBD delivered in the Mount Sinai study achieved peak blood levels of 181 ng/mL and 221ng/mL respectively at their 400 mg and 800 mg doses tested, respectively. These values equate to blood levels of 40.77 ng/mL and 24.87 ng/mL, respectively, when adjusted for concentration to match Lexaria’s 90 mg dosage findings described above.

 

As such, the Mount Sinai results, although potentially influenced by concomitant opioid administration within that study, were substantially lower than the 56.0 ng/mL peak blood level achieved with Lexaria’s TurboCBD™ capsules, and it is further interesting to note that the peak blood levels in the Mount Sinai study required three hours to achieve whereas the Lexaria formulation met and eclipsed these levels when adjusted for dose concentration within only the first 60 minutes of the Lexaria study as noted above. It is also particularly interesting to note the rapidity by which Lexaria’s TurboCBDTM capsules at the 90 mg dose achieved concentration-adjusted blood levels that outperformed those from the Mount Sinai study:  at the 30-minute time interval, we estimate the TurboCBDTM concentration-adjusted CBD blood level to have been over 900% higher than the levels achieved in the Mount Sinai study.

 

Lexaria was also pleased that, as expected, blood levels of THC, 11-OH-THC, and THCCOOH were non-detectable, highlighting the absence of THC and the extraordinary CBD purity within the TurboCBDTM capsules.

 

Few companies around the world have advanced to the state of achieving successful appropriately controlled (i.e., randomized, placebo-controlled and double-blinded) human clinical trial results utilizing cannabinoids. Increasing regulatory scrutiny of CBD by agencies such as the US Food and Drug Administration could result in the necessity of clinical evidence in the future to enable commerce in products containing CBD.

Reducing the Intake Needed for Active Pharmaceutical Ingredients with DehydraTECH

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.

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 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.

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 and beverages will provide 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.