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Elimination

Elimination of THC is the final phase of its pharmacokinetics. THC is extensively metabolized by the body and as a result, only negligible amounts of the so-called unchanged parent compound THC are excreted as its unchanged form: of an oral dose, about 15-30% of THC is excreted in urine as metabolites with less than 0.05% as unchanged THC, and about 30-65% of the metabolites are excreted in the feces with less than 5% as unchanged drug. Of all the metabolites of THC, 11-COOH-THC is the major metabolite identified in both urine and feces in its native as well as in its glucuronidated form.1 The half-life of THC, which is defined by the time it takes to remove half of the drug from the blood (plasma) and its metabolites, can be several days. The slow elimination of THC from the plasma can be explained by redistribution from fatty tissues into the bloodstream. This means that after the THC is distributed to the fatty tissues, it is slowly released to the bloodstream from where it can distribute to other areas in the body (redistribution), or be eliminated. This makes the half-life look longer. Following single dose administration, low levels of THC metabolites have been detected for more than 5 weeks in the urine and feces.2 It should be noted that this terminal half-life is independent from the route of administration. For example, if a patient is given a dose of THC by inhalation, it will result in a blood concentration of some value, let’s say 100 units, while an oral administration results in a blood level of 80 units. With a half-life, for each unit of half-life (a period of time, we will use 1 hour), the concentration in the blood is reduced by half. So for inhalation, after 1 hour, the blood level will be 50 units, while the oral concentration will be 40 units after the same hour. And this will continue until the THC is removed from the body, 100, 50, 25, 12.5, 6.25, 3.125, etc. vs 80, 40, 20, 10, 5, 2.5, etc. for inhalation and oral, respectively. So, we see here that even after fast absorption by inhalation versus slower absorption from oral, once it is in the circulation, the THC elimination still happens at the same rate, half for each unit of time. After 5 half-lives, the THC is 97% gone from the body; this principle is important for determining how long THC, and similarly its metabolites, can be detected in drug testing, or how far apart two medicines should be dosed that can give a dangerous drug-interaction. Watch a brief summary video on cannabis inhalation vs. cannabis ingestion made in collaboration with Enlighten on YouTube or on the screens page.References:
  1. Kelly, P.; Jones, R. T. (1992). Metabolism of tetrahydrocannabinol in frequent and infrequent marijuana users. Journal of analytical toxicology, 16(4), 228--235.
  2. Lemberger, Louis; Tamarkin, N. R.; Axelrod, J.; Kopin, I. J. (1971). Delta-9-tetrahydrocannabinol: metabolism and disposition in long-term marihuana smokers. Science (New York, N.Y.), 173(3991), 72--4.