The safety and effectiveness of Lexaria’s DehydraTECH™ technology has been studied in a series of controlled and well designed in vitro and in vivo human focus studies, examining factors such as total bioabsorption directly and indirectly through surrogate biomarkers, time to onset of effectiveness, flavor appeal and quality of effectiveness. Studies to-date have focused on cannabinoid applications where Lexaria is most advanced commercially, although research is underway for the other bioactive compounds named in Lexaria’s patent portfolio and described under Commercial Applications.
Pre-Clinical Research into Lexaria’s DehydraTECH™
An in vitro absorption study was performed to assess unidirectional CBD permeability using a human epi-intestinal tissue model with various formulations in the presence of simulated intestinal fluid. The study was designed to, as closely as possible, mimic intestinal absorption as it would occur in a live subject. Samples of Lexaria’s commercially available CBD-fortified ViPova™ black tea were administered in the model compared with concentration-matched CBD control preparations that lacked Lexaria’s patented formulation and process enhancements. The study showed as much as a 499% improvement, on average, in intestinal tissue permeability with the ViPova™ black tea formulation relative to a concentration-matched CBD control preparation without any Lexaria technology enhancements. The study also showed a 325% improvement, on average, in intestinal tissue permeability comparing the ViPova™ black tea preparation to a concentration-matched CBD control preparation that utilized Lexaria`s dehydration synthesis processing methodology but lacked its fatty acid ingredient incorporation, demonstrating the power of the Lexaria technology as a whole (see Figure 1).
Following this study, a series of independent, well designed, well controlled human focus studies were undertaken corroborating Lexaria’s in vitro performance findings. A study in healthy volunteers (n=6) suggested as much as a 5-10X increase in CBD absorption, which was assessed indirectly through measurement of the increase in salivary nitric oxide as a directly proportional surrogate biomarker, with onset of action in as little as 15-30 minutes. In all cases, the maximum increased level of salivary nitric oxide remained evident at the 60-minute end period of this particular test. Further testing is required to determine the full duration of elevated nitric oxide levels.
Thereafter, a blinded human focus study was conducted to evaluate the performance of THC-infused chocolates formulated using Lexaria’s DehydraTECH™ technology. This study compared the performance of the THC-infused chocolates powered by Lexaria’s technology to concentration matched THC-infused chocolates formulated using a commercial dextrin absorption enhancer. The subjects (n=12) that participated in this study indicated a clear preference on taste and overall effectiveness with the chocolates formulated using Lexaria’s technology, and onset of effectiveness was again observed very quickly, in as little as 15-20 minutes.
Lexaria is pleased to be working with Canada’s National Research Council to further investigate characteristics of the DehydraTECH™ technology in what is one of the few active research collaborations in the world with government organizations in the field of cannabinoid related research. Several studies are planned or underway designed to investigate and optimize the ability of Lexaria’s patented technology to enable delivery of lipophilic active agents including cannabinoids, vitamins, NSAIDs, and nicotine. Advanced analytical techniques, including mass spectrometry and nuclear magnetic resonance testing, are being employed to evaluate the chemical nature of the molecular association that Lexaria`s DehydraTECH™ technology is believed to form between lipophilic active agents and the flavor and delivery enabling fatty acid agents that are integral to Lexaria’s formulation methodologies. Practical applications of this work could include further broadening or strengthening of Lexaria’s intellectual property portfolio and may also provide the foundation for new commercial arrangements.
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.
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:
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
|Blood levels following 90 mg Positive Control
Blood Level % Increase from Positive Control
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 THC blood level to have been over 900% higher than the levels achieved in the Mount Sinai study.
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.
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.