In case of oral intake (or – to put it simply – eating)of cannabinoids their bioavailability (efficiency of their unmodified forms’ transport into blood plasma) depends on two things: the efficiency of transporting through the stomach to the intestine and then – on their metabolism in the liver. Here we face the first obstacle – it is known that cannabinoids can degrade in an acidic environment, as is the case in the stomach . However, this can be easily prevented with the use of a suitable carrier – other oily components of hemp plant or addition of some extra oil from seeds can effectively shield the precious active substances, as oils are generally not metabolized in the stomach, thus can effectively hinder the effect of on cannabinoids. This simple trick is effectively put into use by the producer of Marinol – in this case THC is dissolved in sesame oil which allows for the level of 90-95%  Note, that the absorbance level should not be confused with total relative bioavailability – as it was explained in a few articles published here, the latter one is measured by the active substance’s concentration in blood plasma, which might be lower than the initial level due to the fact that the large amounts of cannabinoids absorbed in the intestines are metabolized in the liver before they can occur in the blood.
By the way – the effects of cannabinoids’ metabolism in the liver are not yet known enough! The topic will be furtherly investigated here on a different occasion, yet it is already worth mentioning that metabolizing cannabinoids in the liver is not necessarily a bad thing as the metabolites produced there can still be biologically active, the obvious example being the THC-11-OH-THC. Research shows that this metabolite, in addition to its strong psychoactive effects, possesses at least similar – and sometimes much stronger – pharmacological effects as THS does . Also the second, much less researched metabolite – THC – THCCOOH – is a promising one because of its recently discovered and different than its precursor’s activity in the body, as well as because of its analgesic and effects . Even those two examples clearly suggest that the metabolism in liver results in the whole new group of biologically active substances .
As the metabolism is discussed here, it should be mentioned that endocannabinoids produced in the body are also naturally metabolised in the liver, resulting in substances with stronger, weaker or just plain different effects than the original molecule .
For all those reasons explained above, the most recent studies measure also the content of metabolites in the blood, not just of the primary forms of cannabinoids. Unfortunately, in the case of cannabinoids other than those well-researched few, their biological activity, not mentioning the one of their metabolites’ ! – is much less known. However, even the very meagre body of evidence at hand can already arise the question whether at least some of the properties attributed to cannabinoids are in fact produced by their metabolites… 
In conclusion, cannabinoids taken orally in a suitable carrier exhibit virtually full absorption in the gastrointestinal tract, yet after being swallowed, the part that passes through the liver is metabolized to the metabolites. It is very hard, though, to give figures on relative bioavailability in this form of intake – this is due to varying conditions of experiments, different doses, different (or none) carriers, various lab animals used in the tests, different forms of formulation: capsules, solutions, powders, differences in time the measurement of cannabinoid concentration was cionducted, measuring either concentration of either the basis forms only, or along with metabolites, etc. Therefore, the spread of results is enormous and the relative bioavailability of the THC observed varies between several and several dozen percent.
In case of cannabinoids administered orally, factors such as the timing of administration (during, before or after meals) and the subject’s diet may prove to be important as well. And yet, still relatively little research is devoted to these topics. Single mentions suggest that a meal can improve cannabinoid absorption . It makes sense, as such effect would be consistent with the phenomenon described earlier that a suitable carrier, such as, for example, vegetable oil, increases the absorption of active substances. Either way, to ensure reproducible effects, cannabinoid preparations should be consumed at fixed time (eg, one hour before a meal) and in the same medium.
The difficulty to accurately set the dose is often pointed to as the main disadvantage of oral administration. The titration method, easy to apply with inhalation or sublingual administration, is difficult in this case, since it takes way longer for the effects of single dose administred orally to occur. On the other hand, oral administration may be beneficial due to the longest lasting effect it produces in comparison to the other methods of administration . The dose of cannabinoids administrated orally will be absorbed on a much longer time span than when inhaled, resulting in much more stable and longer-lasting effect.
PhD, Eng. Beata Plutowska
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