There is limited information available regarding the pharmacokinetics and pharmacodynamics for either tetrahydrocannabinol (THC) and cannabidiol (CBD) in humans. Only a few studies have been published so far, and most of them were conducted in healthy adult volunteers with very small sample sizes. Additionally, frequent cannabis smokers were included in some of the studies, not all included both males and females, and none of the studies addressed the subjects’ fat content as a factor to account for the cannabinoid’s highly lipophilic nature. Overall, there is considerable variability between studies and further research is warranted. Below is a summary of the available information.
Inhalation of cannabinoids exhibit similar pharmacokinetics to those administered intravenously. Peak concentrations are attained within 10 minutes and are higher in comparison to ingestion. Bioavailability after inhalation ranges from 10-35% with the variability attributed to the number, duration, and interval of puffs, breath hold time, inhalation volume, inhalational device, size of inhaled particles, and site of deposition within the lungs. The absorption of vaporized and smoked cannabinoids are comparable.
Cannabinoids have poor oral bioavailability (estimated to be as low as 6%) due to their high lipophilicity and extensive first-pass hepatic metabolism (i.e. liver metabolizes most of it). Peak concentrations are delayed by 2-4 hours and are much lower in comparison to inhalation. Increased peak concentrations and total absorption, but not time to peak concentration, are seen when cannabinoids are administered with food or in a fed state.
The psychoactive effects from ingestion and inhalation of THC are comparable. However, since the legalization of marijuana, edible products are responsible for the majority of emergency department visits due to cannabinoid intoxication. This is likely due to the failure of users to appreciate the delayed effects of ingestion compared to inhalation. Typically, a tenth of a product (cookie, packet of gummy bears, etc.) is recommended for intoxication. Because many find it difficult to eat a tenth of a cookie, unintentional overdose is common. These patients usually present with severe anxiety, panic attacks, intractable vomiting, or other nonspecific symptoms precipitated by marijuana use.
CBD is without euphoriant properties, and exerts antipsychotic, anxiolytic, antiepileptic, and anti-inflammatory effects. Unfortunately, we could not find any studies comparing the effects of orally administered CBD to inhalation. The effects are likely to be comparable to other cannabinoids in the respect that inhalation will produce a more rapid onset with a shorter duration while ingestion would produce a more consistent plasma-time profile suitable for symptomatic relief over a longer period.
This question prepared by: Justin Loden, PharmD, CSPI, DABAT
References
- Cherniakov I, Izgelov D, Barasch D, et al. Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration. J Control Release. 2017 Nov; 266:1-7.
- Liu Z, Martin JH. Gaps in predicting clinical doses for cannabinoids therapy: overview of issues for pharmacokinetics and pharmacodynamics modelling. Br J Clin Pharmacol. 2018 Nov; 84(11):2483-7.
- Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and pharmacodynamics of cannabinoids. Br J Clin Pharmacol. 2018 Nov; 84(11):2477-82.
- Millar SA, Stone NL, Yates AS, et al. A systematic review on the pharmacokinetics of cannabidiol in humans. Front Pharmacol. 2018 Nov 26; 9:1365.
- Monte AA, Zane RD, Heard KJ. The implications of marijuana legalization in Colorado. JAMA. 2015 Jan 20; 313(3):241-2.
- Newmeyer MN, Swortwood MJ, Barnes AJ, et al. Free and glucuronide whole blood cannabinoids’ pharmacokinetics after controlled smoked, vaporized, and oral cannabis administration in frequent and occasional cannabis users: identification of recent cannabis intake. Clin Chem. 2016 Dec; 62(12):1579-92.
Thanks to the reader (in South Dakota!!-hope you have dug out of the snow by now) for this great question.
I am interested in any questions you would like answered in the Question of the Week. Please email me with any suggestion at donna.seger@vanderbilt.edu
Donna Seger, MD
Executive Director
Tennessee Poison Center
Poison Help Hotline: 1-800-222-1222