Cannabis has been consumed in many different forms over many years for its various effects due to the several different chemical compounds that comprise it including cannabinoids, terpenoids, and flavonoids (1). The two most well-known components include Delta-9- Tetrahydrocannabinol (THC) responsible for the psychoactive effects felt, and cannabidiol (CBD) which has relaxing and calming effects. Cannabis is consumed through various methods, the more popular ones including inhalation, ingestion, and transdermal formats. For the populations using cannabis for its calming, anti-anxiety and chronic pain treatment effects from the CBD component, edibles and oils are more common formats for intake. However, there are
several issues with the current market of edibles including the delay of onset time and dosage variances. Currently, the average onset times for edibles and oils found in market are 30-60 minutes with effects lasting for 6-8 hours in some cases. This is due to the low bioavailability of cannabis in humans, especially in edible formats with peak bioavailability hitting 6% (2). Other formats such as smoking have lower onset times and higher bioavailability but also can contribute to respiratory issues as well as simply having ‘bad taste and smells’ (3). New technology is being researched and produced to reduce the onset times by several different methods of delivering the cannabinoid particles.
When an edible is consumed, most nutrients are absorbed in the small intestine after passing the stomach and then cross the intestinal walls and enter the liver through the hepatic veins to get processed into metabolites. This process is known as the first pass metabolism and directly contributes to the low oral bioavailability of cannabis (4). Other factors do include dosage, delivery vehicle and physiological factors such as metabolism (4). To create a more static, stable experience of taking CBD orally, several new technologies exist to decrease onset time, increase bioavailability, and provide a relatively similar, stable dosage with each intake. Although these technologies vary greatly, they can be grouped into nano-vectors and lipid-based formulations (including liposomes).
Cannabidiol’s lipophilicity is one of the contributing factors to the low oral bioavailability considering the human body is primarily water based. Nanotechnology has a huge role in helping create a faster onset for CBD products. For example, nano-emulsions can help increase the bioavailability of highly lipophilic compounds as it is small enough to bypass first pass metabolism and go into the blood stream for a faster onset. Additionally, nano-emulsions are kinetically stable where they can last for longer periods of time (5). Other nano-carriers exist, with companies researching and commercializing nano-encapsulation methods, individual molecule encapsulations and so forth. Azuca’s Thermodynamic individual molecular encapsulation (TiME) technology is just one example in the market where onset times for their products have been shown to be as low as 5 to 15 minutes. Other companies that use nanotechnology include Emerald health therapeutics, Evolve Formulas, Organigram, Kiva Confections, Cannafex and so forth. Most companies have technology involving similar mechanisms boasting nano-encapsulation and emulsions (or molecular encapsulations/emulsions) which are more bioavailable with a more rapid onset ranging from 5- 20 minutes. However, drawbacks with this technology are still present as accumulation may occur in specific tissues as well as unspecific entry of these molecules cellularly (6).
Lipid carriers are common as vehicles for CBD due to its lipophilicity. These formulations use long chain fatty acids that can enhance the bioavailability of lipophilic compounds and drugs as these are preferentially absorbed through the lymphatic transport system and therefore decreases the first pass metabolism effect of the liver (7). Liposomes are spherical structures with 50-500nm diameters formed by phospholipid bilayers and aqueous phase inside and in-between bilayers which entrap water-soluble active components inside water compartment and water insoluble active ingredients in bilayer (8). These lipid formulations are advantageous as it improves solubility and permeability as well as varying the methods of CBD consumption as it is a good vehicle for topical formulations involving CBD. Companies that are using this format of delivery system include Dehydratech where lipid membranes capture the ingredients and are delivered to the blood stream for a more rapid and sustained release. Other companies include 1906 (Drops product), as well as Evolve Formulas which combine nanotechnology and lipid carrier methods to produce CBD products with rapid onsets. There is the disadvantage of low encapsulation efficiency, but this can be tested and measured for.
Although these are primarily the two main vehicles used for reducing CBD onset times and increasing the bioavailability of the compound, other vehicle forms exist for transporting cannabis particles in an accessible format. Self emulsifying drug delivery technology (SEDDS) can improve oral forms of CBD as they cover the particle with oil surfactants and hydrophilic solvents which can easily be transported to blood vessels and avoid liver metabolism (8). Additionally, cannabinoid distillates are another form of technology being produced by companies such as Caliper Foods, where the final product is just one specific cannabinoids. However, this form strips terpenoids and other compounds which may play a role in having a combined medicinal effect that is removed from the distillate form. Despite there being many different technologies researched for a more rapid CBD onset, there is still much more research to be done considering clinical research involving the efficacies and safeties of these technologies are still lacking.
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