The Fate of Cannabinoids Following Digestion

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The fate of cannabinoids following digestion New technology is allowing for the study of oral cannabinoid bioavailability

In Canada, cannabis may be prescribed as a physician-recommended herbal therapy. While cannabis is typically smoked, inhalation of burned dry plant matter has obvious inherent health risks. Smoke-free options include Sativex, a whole-plant cannabis extract, delivered as an oromucosal spray.

Similarly, certain licensed producers in Canada can produce and distribute cannabis oils for sublingual administration. These are also available in capsule form containing cannabis oil or fine milled cannabis powder. Hydropothecary recently released Canada’s first and only peppermint medical cannabis oil sublingual mist (

Oral administration offers several key advantages, including elimination of pulmonary health risks and more accurate dosing of active ingredients such as THC and CBD. Oral administration does, however, suffer certain shortcomings and challenges as well.

Dr. Michael Rogers, a Canadian research chair in food nanotechnology and associate professor in food science at the University of Guelph, states that “the major limitation of oral delivery of THC and CBD is the low solubility of these molecules in aqueous environments leading to poor biological availability.” He goes on to say “this is a common issue we face with many bioactives in the food and pharmaceutical industries and it is the goal of our lab to increase the bioavailability by formulating novel delivery systems to increase the biological efficacy of these compounds.”

Pulmonary absorption of the released THC causes immediate psychotropic effects beginning within seconds to minutes, reaching a peak plasma concentration in roughly 6–10 minutes and level off within 2–3 hours, with plasma THC concentrations reaching maximum levels within minutes of inhalation. Oral ingestion follows a more delayed response generally resulting in psychotropic effects starting 30-90 minutes after ingestion and reaching a peak plasma concentration at 2–6 hours; effects may last as long as 4–12 hours with oral administration, depending on dosage.

Bioavailability is defined as the proportion of a drug or other substance that enters circulation when introduced into the body and so is able to have an active effect. This is therefore an important property to assess when developing cannabis formulations for oral administration. Research has thus far shown that extensive liver metabolism reduces the oral bioavailability of THC to roughly  2–14%, while inhalation of marijuana smoke offers a systemic bioavailability generally ranging between 10–35%. Others have reported THC bioavailability after oral ingestion to be approximately 6% compared to 25% after smoking.

Assessing for bioavailability poses a challenge, as human or animal subjects are required and plasma samples must be drawn. This, in turn, significantly impedes research into novel drug delivery systems as the cost and resources required to test the effectiveness of novel formulations is staggering.

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