The cannabis plant produces more than 700 chemical compounds, of which the best known is THC, or tetrahydrocannabinol. Yet THC is just a single component of a remarkable chemical ecology produced within cannabis, which comprises dozens of medicinally active substances. Cannabis is not just THC, and different varieties of cannabis produce differing ratios of active ingredients. The complex interactions and ratios of these chemicals produce varying medicinal effects. This variation in potency and constituency, plus the complex chemical interactions, further combined with the way in which the body metabolizes these cannabis constituents, make consistent medicinal cannabis dosage very challenging. Understanding how and where the constituents of cannabis medicines are absorbed, metabolized, excreted, and stored within the body is important for establishing a basic understanding of how cannabis works as a medicine. But such an understanding is, from a scientific standpoint, a moving target. There is only so much that is currently known about how the body acts upon cannabis medicines (called the pharmacokinetics of cannabis) and how the cannabis medicines act upon the body (called pharmacodynamics). When smoked, the THC in cannabis medicines reaches its peak blood plasma concentrations within six to seven minutes of ingestion. THC from smoking is actually detectable a few seconds after inhalation. The ability of a patient to absorb THC through smoking or vaporization appears to be a learned behavior, with experienced users more than twice as efficient in their rate of absorption as occasional users. The efficiency of inhaled cannabis is dependent on the size and duration of the inhalation, plus how long the breath is held. Holding one’s breath only slightly increases absorption.24 Sublingual (under the tongue) or oromucosal (on the tissues of the mouth) administration of cannabis medicines is not as efficient as administration by inhalation, although absorption and onset of cannabis medicines placed beneath the tongue has been known to occur as quickly as five to 15 minutes after application. Peak blood concentrations for sublingual THC are reached within four hours, with other cannabinoids such as CBD taking slightly longer to peak.25 Oral absorption of THC (sublingual or oromucosal) in cannabis medicines is both slow and inconsistent. This inconsistency has often been cited as the reason why many oral cannabis preparations that were popular in the nineteenth century subsequently fell out of favor with both doctors and patients. Maximum blood plasma levels are often reached within two hours, but in some studies human subjects have needed up to seven hours to reach these levels. Furthermore, some THC is destroyed by stomach acid. Then, the liver grabs much of the THC before it can become bioavailable. This liver absorption of THC is called a first-pass effect. Topical absorption of THC is difficult and not particularly efficient but can be accomplished by blending the THC into a fatty acid and propylene glycol. This approach has been used to treat skin conditions including psoriasis and inflammatory ailments including osteoarthritis. Once absorbed, 90 percent of THC will be bound to proteins in the blood plasma. Because it’s being moved by the blood, THC ends up being distributed to tissues that have lots of blood vessels, including the heart, liver, fat cells, etc. Only about 1 percent of the administered THC will find its way to the brain. Certain organs in the body can break THC down into other molecules called metabolites. This metabolism takes place primarily within the liver, but also within the tissues of the heart and lungs. When the liver breaks down THC, the primary metabolite is 11-hydroxy-THC, twice as psychoactive and lasting twice as long as THC. Eventually, 11-hydroxy-THC undergoes further metabolic changes into an inert metabolite, before being excreted from the body. Cannabidiol is metabolized by the liver into 7-hydroxy-CBD. Very little is known about the pharmacology of this CBD metabolite.
HOW CANNABIS WORKS WITHIN THE BODY
Absorption of Cannabis Medicines
Metabolism of Cannabis Medicines
Absorption, Metabolism, Excretion
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