Beyond strain specificity and relative concentrations of cannabis compounds, the bioavailability and effective routes of administration are critically important parameters in cannabis-based therapeutics.

"Bioavailibility" is defined as the rate and extent of which a therapeutic compound is taken up by the body. "Route of Administration" is the path that the therapeutic compound travels enroute to the body systems. The "vehicle" drives entry of compounds into the body and affects both of these parameters, making close examination of the therapeutic delivery process very important.

Intravenous entry of a drug is benchmarked at 100% bioavailability, a standard upon which each method of delivery is measured. The traditional method of smoking or inhalation of cannabis is quite effective with a relative bioavailability higher than other methods such as oral, sublingual, and topical. This is due to the significant surface area of the lung, conducive to absorption, as well as the proximal location of the lung to the bloodstream. Smoking cannabis is associated with risks from contaminating substances, and alternative methods including vaping and vaporization are popular alternatives. Vaporization has been shown to work very well for volatile preparations, offering both effective and consistent dosing modalities.

Oral administration is another important route and is the chief method of entry for the wide range of cannabis capsules and edibles. The bioavailability of this route can be quite variable and in some cases low depending on the vehicle of delivery. This makes accurate dosing of individuals often difficult. The main culprit for low bioavailability is first pass metabolism, or the action of enzymes in the digestive system that work to breakdown cannabis compounds before they reach their destination and achieve their therapeutic effect(s). Certain substances can boost the availability of cannabis compounds by facilitating absorption and movement into the bloodstream. An example is the enhancement of cannabidiol (CBD) by the presence of medium and long chain fatty acids.

Topical administration is another popular route for entry of certain cannabis preparations such as oils and salves. The bioavailability of cannabinoids and other cannabis components via this route is typically very low, as entry into the body is limited to the absorption by the skin and surrounding tissues. These compounds never reach the bloodstream, however, they can reach CB2 receptors in this area and thereby affect the endocannabinoid system.

In depth knowledge into the bioavailability of cannabinoids in humans has been hindered by the lack of rigorous research investigations. It is generally regarded that a healthy blend of dietary lipids can enhance the uptake of certain cannabinoids such as CBD. The route of entry strongly depends on the desired therapeutic effect as well. For instance, the systemic presence of cannabis compounds in the blood may be necessary for certain CB1, CB2, or CB1/CB2 cannabinoid receptor interactions and nervous system effects -- for the treatment of anxiety, PTSD, MS, and other disease symptoms. Whereas, the topical presence of certain compounds may be appropriate for more localized receptor interactions and immune system effects. The emerging therapeutic profiles for specific cannabinoids including THC, CBD, Cannabinol (CBN), and others are prolific and somewhat complex -- a worthy subject for subsequent articles.

The main takeaway is that the route of entry and the bioavailibity of cannabis compounds are vitally important not only in driving the desired therapeutic effects, but in testing the proper dosing methods and vehicles to ensure these effects are achieved.