Editing Tetrahydrocannabinol (section)

====Absorption====
With oral administration of a single dose, THC is almost completely [[absorption (pharmacokinetics)|absorbed]] by the [[gastrointestinal tract]].<ref name="MarinolLabel2023">{{Cite web | url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/018651s033lbl.pdf | title=Highlights of prescribing information | website=www.accessdata.fda.gov}}</ref> However, due to [[first-pass metabolism]] in the [[liver]] and the high [[lipid solubility]] of THC, only about 5 to 20% reaches circulation.<ref name="pmid12648025" /><ref name="MarinolLabel2023" /> Following oral administration, concentrations of THC and its major [[active metabolite]] [[11-hydroxy-THC]] (11-OH-THC) [[Tmax (pharmacology)|peak]] after 0.5 to 4{{nbsp}}hours, with median time to peak of 1.0 to 2.5{{nbsp}}hours at different doses.<ref name="MarinolLabel2023" /><ref name="pmid12648025" /> In some cases, peak levels may not occur for as long as 6{{nbsp}}hours.<ref name="pmid12648025" /> Concentrations of THC and 11-hydroxy-THC in the circulation are approximately equal with oral administration.<ref name="MarinolLabel2023" /> There is a slight increase in [[dose proportionality]] in terms of [[Cmax (pharmacology)|peak]] and [[area-under-the-curve (pharmacokinetics)|area-under-the-curve]] levels of THC with increasing oral doses over a range of 2.5 to 10{{nbsp}}mg.<ref name="MarinolLabel2023" /> A high-fat meal delays time to peak concentrations of oral THC by 4{{nbsp}}hours on average and increases area-under-the-curve exposure by 2.9-fold, but peak concentrations are not significantly altered.<ref name="MarinolLabel2023" /> A high-fat meal additionally increases absorption of THC via the [[lymphatic system]] and allows it to bypass first-pass metabolism.<ref name="pmid35523678">{{cite journal | vauthors = Tagen M, Klumpers LE | title = Review of delta-8-tetrahydrocannabinol (Δ8 -THC): Comparative pharmacology with Δ9 -THC | journal = Br J Pharmacol | volume = 179 | issue = 15 | pages = 3915–3933 | date = August 2022 | pmid = 35523678 | doi = 10.1111/bph.15865 | url = | doi-access = free }}</ref> Consequently, a high-fat meal increases levels of 11-hydroxy-THC by only 25% and most of the increase in [[bioavailability]] is due to increased levels of THC.<ref name="pmid35523678" />

The bioavailability of THC when [[smoking]] or [[inhalational administration|inhaling]] is approximately 25%, with a range of 2% to 56% (although most commonly between 10 and 35%).<ref name="pmid30001569">{{cite journal | vauthors = Lucas CJ, Galettis P, Schneider J | title = The pharmacokinetics and the pharmacodynamics of cannabinoids | journal = Br J Clin Pharmacol | volume = 84 | issue = 11 | pages = 2477–2482 | date = November 2018 | pmid = 30001569 | pmc = 6177698 | doi = 10.1111/bcp.13710 | url = }}</ref><ref name="pmid31152723">{{cite journal | vauthors = Foster BC, Abramovici H, Harris CS | title = Cannabis and Cannabinoids: Kinetics and Interactions | journal = Am J Med | volume = 132 | issue = 11 | pages = 1266–1270 | date = November 2019 | pmid = 31152723 | doi = 10.1016/j.amjmed.2019.05.017 | s2cid = 173188471 | url = }}</ref><ref name="pmid12648025" /> The large range and marked [[interindividual variability|variability between individuals]] is due to variation in factors including product matrix, ignition temperature, and inhalational dynamics (e.g., number, duration, and intervals of inhalations, breath hold time, depth and volume of inhalations, size of inhaled particles, deposition site in the lungs).<ref name="pmid30001569" /><ref name="pmid31152723" /> THC is detectable within seconds with inhalation and peak levels of THC occur after 3 to 10{{nbsp}}minutes.<ref name="pmid12648025" /><ref name="pmid31152723" /> Smoking or inhaling THC results in greater blood levels of THC and its metabolites and a much faster [[onset of action]] than oral administration of THC.<ref name="pmid30001569" /><ref name="pmid31152723" /> Inhalation of THC bypasses the first-pass metabolism that occurs with oral administration.<ref name="pmid30001569" /> The bioavailability of THC with inhalation is increased in heavy users.<ref name="pmid12648025" />

[[Transdermal administration]] of THC is limited by its extreme [[hydrophobicity|water insolubility]].<ref name="pmid30001569" /> Efficient skin transport can only be obtained with permeation enhancement.<ref name="pmid30001569" /> Transdermal administration of THC, as with inhalation, avoids the first-pass metabolism that occurs with oral administration.<ref name="pmid30001569" />