The Summer season typically draws us towards hot spots, locales with beaches, boardwalks, cool drinks, and fireworks, if you’re lucky. This year, the term “hot spots” likely conjures a different vision thanks to the pandemic – perhaps making us ponder our typical Summer destinations.

There are “hot spots” of an entirely different nature, however, in the areas of medicinal cannabis and therapeutic development. Solubility, stability, dose release, and bioavailability are a few major focal points of ongoing investigations. Progress in these areas is essential for establishing viable drug formulations, and the vitality of cannabis medicines moving forward.


Cannabinoid and Terpene Solubility and Stability

Cannabis production and testing have come a long way. More complete understanding of genetic, cultivation, extraction, and testing parameters have helped establish standard protocols and testing platforms. Innovations in the field, as well efforts of validation authorities, have played prominent roles in the evolution of production and testing standardization.

Despite these efforts on the raw materials front, inherent chemical and physical qualities of cannabis compounds have made bioactive formulation challenging. Products such as infused oils, tinctures, and gummy edibles benefit from the use of hydrophobic, aliphatic, or solubilizing matrices. However, these can suffer similar challenges as alternative cannabis products - edibles, topicals, infused beverages - with regard to inconsistencies in stability and shelf life.

Recent studies have looked at properties of purified cannabinoids and terpenes, and have identified differences in stability compared with full-spectrum cannabis extracts. One such recent study identified distinct qualities of purified CBD, namely thermolabile, photolytic, and oxidative properties, which were not fully realized in previous investigations centered on plant extracts. Some of these same qualities are known to challenge purified terpenes as well.

The temperature, oxidative conditions, photosensitivity, and favorable solvent conditions are all critical parameters in the development of purified CBD, THC, and other cannabinoids and terpenes as drug formulations. A growing number of investigations are examining these properties and others, to better understand the ideal conditions to support compound stability.


Dose Release and Bioavailability

Generally speaking, the bioavailability of medicinal cannabis formulations is a challenge. Traditional routes of entry through inhalation and vaporization can be very effective, although questions linger regarding the state of cannabis compounds, and potential toxins, following heating and aerosolization. Ingestion presents questions regarding the state of compounds upon exposure to the GI tract, and effective dosages surviving and available for absorption.

Much research is underway to determine the most effective mechanisms for absorption, distribution, and overall efficacy of potential cannabis therapeutics. Colloidal preparations of cannabis compounds are being pursued in order to assist solubilization and absorption via sublingual routes. Colloidal compounds have both water soluble and insoluble interfaces, forming a shield around hydrophobic cannabinoids and facilitating solubility. Nanoemulsion techniques are being investigated to assist solubilization, stability, and absorption at multiple sites including the digestive route. These colloidal materials take advantage of their submicron size to enhance solubility and assist drug delivery. Nano-encapsulation approaches, on the nanometer scale thanks to ultrasonic technologies, are driving the availability of cannabis compounds delivered by a wide variety of vehicles -- topicals, beverages, edibles, and others.

In the realm of topical absorption, skin patches have proven effective, although challenges include the rate and the duration of delivery into the body. Recent research has discovered the utility of nanoscale droplet technology loaded with cannabinoids. These “nanodepots’ support the controlled release of cannabinoids when delivered subcutaneously under the skin. A major advantage of the approach is long-lasting therapeutic delivery, with a much tighter grip on actual dosage and the rate of therapeutic activity. Another advantage is the ability to load different cannabinoids including full-spectrum preparations, for enhanced therapeutic effect.


Summary

Much work is needed to streamline cannabis drug development and evaluation. It’s been stated before -- if cannabis is to be considered medicine it will need to be tested like medicine. This includes rigorous analysis of stability, delivery, bioavailability, absorption, therapeutic effect, and of course toxicity. Despite the challenges, modern research is bringing the next phase of medicinal cannabis closer to reality.

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