Mechanisms of Action and Pharmacokinetics of Cannabis

Summary & key facts

This review explains how the main cannabis chemicals, especially THC and CBD, act in the body and how the body absorbs and breaks them down. THC and CBD bind to cannabinoid receptors (CB1 and CB2) in the brain and other organs. Inhaling THC delivers it to blood and brain fast (peak in about 6–10 minutes) and gives higher bioavailability (about 10%–35%) than eating it (oral bioavailability about 4%–12%). THC is fat‑soluble and can build up in fat, which helps explain why its plasma half‑life is about 1–3 days in occasional users and about 5–13 days in chronic users. CBD has low oral bioavailability (around 6%), higher inhaled bioavailability (about 11%–45%), and a reported plasma half‑life of

Key facts:

• THC and CBD bind to cannabinoid receptors called CB1 and CB2, which are present in the brain and many organs.
• When inhaled, THC reaches peak levels in blood and brain within about 6 to 10 minutes.
• Bioavailability of inhaled THC is reported as about 10% to 35%.
• Bioavailability of orally ingested THC is reported as about 4% to 12%.
• THC is highly lipid soluble and is rapidly taken up by fat tissue, where it can accumulate and be slowly released.
• Plasma half‑life of THC is approximately 1 to 3 days in occasional users and about 5 to 13 days in chronic users.
• CBD inhalation bioavailability is reported as about 11% to 45%, while oral CBD bioavailability is about 6%.
• Plasma half‑life of CBD is reported as about 18 to 32 hours.
• In the liver, THC is metabolized to 11‑OH‑THC (which is also psychoactive) and then to 11‑COOH‑THC (which is not psychoactive).
• Most cannabis is excreted in feces (over 65%) and about 20% is excreted in urine; roughly 80%–90% of metabolites are excreted within 5 days.

Abstract

At least 100 cannabis species are compounds known as cannabinoids, a molecule with a 21-carbon terpenophenolic skeleton. Cannabinoids produce more than 100 naturally occurring chemicals, the most abundant of which are Δ-9-tetrahydrocannabinol (THC), cannabidiol (CBD), terpenes, and flavonoids. THC and CBD bind with cannabinoid receptors (CB1 and CB2), which are present in the brain and many organs. Metabolism of cannabis is determined by the route of consumption. When inhaled, THC and its metabolites enter the bloodstream rapidly via the lungs; they achieve peak levels within 6 to 10 minutes and reach the brain and various organs. The bioavailability of inhaled THC is 10% to 35%. After THC is absorbed, it travels to the liver where most of it is eliminated or metabolized to 11-OH-THC or 11-COOH-THC. The remaining THC and its metabolites enter the circulation. The bioavailability of ingested THC is only 4% to 12%. THC is highly lipid soluble and is therefore rapidly taken up by fat tissue. The plasma half-life of THC is 1 to 3 days in occasional users and 5 to 13 days in chronic users. The bioavailability of CBD via inhalation is 11% to 45%, whereas that of oral CBD is 6%. CBD has high lipophilicity and therefore is rapidly distributed in the brain, adipose tissue, and other organs. CBD is hydroxylated to 7-OH-CBD and 7-COOH-CBD by cytochrome P450 enzymes CYP3A4 and CYP2C9 in the liver and is excreted mainly in feces and less in urine. The plasma half-life of CBD is 18 to 32 hours.

Topics

Cannabis and Cannabinoid Research Forensic Toxicology and Drug Analysis Psychedelics and Drug Studies

Categories

Health Sciences Medicine Pharmacology

Tags

Adipose tissue Anticonvulsant Bioavailability Cannabidiol Cannabinoid Cannabinoid receptor Cannabinol Cannabis Chemistry CYP2B6 CYP2C9 CYP3A4 Cytochrome P450 Dronabinol Drug Drug metabolism Effects of cannabis Endocannabinoid system Inhalation Lipid metabolism Lipophilicity Mechanism of action Medicine Metabolism Metabolite Oral administration Pharmacokinetics Pharmacology Receptor Tetrahydrocannabinol Toxicokinetics Δ9-tetrahydrocannabinol