THC is widely distributed, especially in fatty tissues, but less than 1% of the administered dose reaches the brain, while the spleen and body fat are long-term storage sites. The elimination of THC and its numerous metabolites (by all routes) occurs through feces and urine. As already mentioned, THC is lipophilic, so it is easily absorbed by the intestines as it passes through the body. THC formulations that are administered orally have variable absorption and are extensively metabolized in the liver 28, which results in a lower maximum plasma concentration of THC than in the case of inhalation 29 and a longer delay (~120 minutes) to reach the maximum concentration 20, 30.
The high lipophilicity of THC causes greater reabsorption and low renal excretion of the unmodified drug. After oral administration of CBD, a plasma concentration-time profile similar to that of oral THC has been observed 20. THC is mainly metabolized to 11-hydroxy-THC (11‐OH‐THC) and 11‐carboxy‐THC (11‐COOH‐THC), which undergoes glucuronidation 42 and is subsequently excreted in feces and urine 26, 28. After inhalation, peak plasma concentrations of THC and CBD are reached rapidly (within 3 to 10 minutes) 20, 21 and peak concentrations are higher relative to oral ingestion 16, 22. This is because THC travels through the digestive tract to the liver, where it is metabolized and converted to a different form of THC, called 11-hydroxyTHC. Reportedly, the bioavailability of THC after inhalation ranges from 10% to 35% 20, which is attributed to the variability (both within the subject and between subjects) of the inhalation characteristics (number, duration, and interval of inhalations, breath retention time, inhalation volume), the inhalation device 17, 23, the size of the inhaled particles, and the place of deposition in the respiratory system 17. THC and CBD are highly lipophilic and have poor oral bioavailability (estimated at only 6% 26), 27. Importantly, lipophilic THC can cross the placenta 30 and is excreted in human breast milk.
44 — raising concern about toxicity to the developing brain. After a single inhaled dose of THC, the alteration was greater during the first hour after the dose and decreased in the following 2 to 4 hours. The metabolism of THC is predominantly hepatic, through the isoenzymes CYP2C9, CYP2C19 and CYP3A4. In the body, THC molecules conjugated to glucuronic acid are eliminated in the urine (renal excretion). With prolonged drug exposure for long-term users, THC is concentrated in adipose tissues, where it is stored until elimination.
The rapid absorption of the drug into the lungs is why smoking THC is an effective form of administration to maximize the amount of drug in the bloodstream.
