The therapeutic effect of cannabinoids depends on the absorption, systemic distribution, breakdown, and excretion patterns.

When cannabinoids are taken as medicine, they need to be absorbed by the body before they can be distributed, metabolised, and excreted out of the body. These processes are collectively referred to as ‘pharmacokinetics’. The therapeutic effect of cannabinoids is obtained after absorption, when they are distributed via systemic blood circulation to the cannabinoid receptors (CB1 and CB2), to which they bind and enable activation. The effect of the cannabinoids declines as their concentration in the blood decreases as a result of metabolism and excretion into faeces and urine.

Pharmacokinetics of cannabinoids
Advantages and disadvantages with different administration routes of medical cannabis

Advantages and disadvantages with different administration routes of medical cannabis.


The rate and degree of absorption of medical cannabis has much to do with how it is taken. The most common ways are oral (absorption in the digestive tract after swallowing), oromucosal (through the mucous membranes in the mouth) or through inhalation (through the alveoli in the lungs). The fastest absorption into the systemic blood circulation and onset of action occurs by inhalation (5-10 minutes), which enables rapid relief and real-time adjustment of the required dosage. The oromucosal and oral routes have a slower onset of action (15-45 minutes and 60-180 minutes, respectively) and are suitable for treating chronic symptoms because the observed effects last longer. The duration of effect through inhalation is 2-4 hours, and 6-8 hours for oral and oromucosal administration1. These time intervals are rough estimates, and exact effects vary from patient to patient. Other factors can affect the absorption, such as drug design, food intake, inhalation pattern and more.

Pharmacokinetics of cannabinoids. The profiles pictured are rough estimates, and exact effects vary from patient to patient.

Pharmacokinetics of cannabinoids. The profiles pictured are rough estimates, and exact effects vary from patient to patient.


After absorption, compounds from the cannabis plant first reach organs with a high blood supply (lung, heart, brain, liver). They are distributed more slowly into body fat, where they can be stored and released gradually back into the systemic blood circulation over time. Distribution is affected by factors such as body size and composition as well as diseases2.

Distribution of cannabinoids in the body after absorption

Distribution of cannabinoids in the body after absorption8.


Cannabinoids are mainly broken down in the liver by CYP450 enzymes (CYP2C9, CYP2C19, CYP3A4), generating both active and inactive metabolites. THC is primarily metabolised to the active and euphoric metabolite 11-OH-THC, which can be further metabolised into the inactive THC-COOH3. The most abundant metabolites of CBD are inactive 7-COOH and active 7-OH metabolites4-6. Bioavailability (the amount of ingested drug that reaches the systemic blood circulation) can be as low as 6% for medical cannabis taken orally. This is due to ‘first-pass metabolism’: Drugs ingested orally are transported from the intestines via the hepatic portal vein to the liver, where a fraction is metabolised before it has a chance to reach the systemic blood circulation for distribution throughout the body. Bioavailability is an estimated 10-35% for inhalation and somewhere in between for the oromucosal route – most likely due to only partial absorption of the lipophilic cannabinoids across the mucous membranes in the mouth and due in part to swallowing and hence oral ingestion2,7.

Metabolism of THC and CBD

Metabolism of THC and CBD.


Cannabinoids excretion varies, depending on the patient’s body composition, age, health status and more. The half-life (i.e. the time for the concentration in the blood to decrease by half) is very short in the beginning and can be as little as 6 minutes for THC shortly after intake. Due to the accumulation of cannabinoids in body fat and their slow release into the bloodstream, the half-life increases later on following intake and can reach 22 hours or more for THC. With repeated daily administration, the half-life of cannabinoids can even reach several days; cannabinoids are thus potentially detectable in blood samples several days after administration. The components of cannabis are excreted with faeces and urine2,3.

Excretion of cannabinoids

Excretion of cannabinoids.


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2. Lucas, C. J., Galettis, P. & Schneider, J. The pharmacokinetics and the pharmacodynamics of cannabinoids. British Journal of Clinical Pharmacology vol. 84 2477–2482 (2018).

3. Heuberger, J. A. A. C. et al. Population Pharmacokinetic Model of THC Integrates Oral, Intravenous, and Pulmonary Dosing and Characterizes Short- and Long-term Pharmacokinetics. Clinical Pharmacokinetics 54, 209–219 (2015).

4. Landmark, C. J. & Brandl, U. Pharmacology and drug interactions of cannabinoids. Epileptic Disorders 22, S16–S22 (2020).

5. Taylor, L., Gidal, B., Blakey, G., Tayo, B. & Morrison, G. A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Dose, and Food Effect Trial of the Safety, Tolerability and Pharmacokinetics of Highly Purified Cannabidiol in Healthy Subjects. CNS Drugs 32, 1053–1067 (2018).

6. Ujváry, I. & Hanuš, L. Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy. Cannabis and Cannabinoid Research vol. 1 90–101 (2016).

7. Grotenhermen, F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics vol. 42 327–360 (2003).

8. Ashton, C. H. Pharmacology and effects of cannabis: A brief review. The British Journal of Psychiatry 178, 101–106 (2001).