How Cannabinoids Work: Part II – Paths Through the Body

Tea and packed bowl


Though medical cannabis research is expanding daily, for patients and their health-care professionals, it’s challenging to understand the interaction between many variables at play to determine dosages, the type of cannabis, and importantly, the delivery system.

Even if you know exactly how much of an active ingredient such as THC you’re getting, how you take it into your body affects its effectiveness — just as acetaminophen will be more bioavailable if it’s injected directly (96 percent) into the bloodstream rather than given by mouth (67 percent).

Cannabinoids can be smoked, vaped, taken orally, and applied topically. Each of these delivery methods results in different bioavailability, or the fraction of a drug that gets absorbed.

Where There’s Smoke, There’s Fire … and Cannabinoids

Smoking is a combustion process in which a temperature of 500 to 600 degrees Celsius, or 932 to 1,112 degrees Fahrenheit, converts all inactive ingredients to active form, and dissolves them in to a vapor that also contains carbon monoxide and tar. When dried and oil cannabis products are heated, a chemical reaction called decarboxylation begins that increases the activity of the cannabinoids and delivers it quickly to the blood through the pulmonary capillaries, or the small blood vessels in the lungs. Each puff will result in the same mixture of content.

Vaping: Setting the Temperature for Cannabinoids and Terpenes

Vaping does not involve combustion. The process happens at temperatures between 104 to 225 degrees Celsius, or 219 to 437 degrees Fahrenheit, at which point various combinations of cannabinoids, flavonoids and terpenoids are extracted. In the case of temperature-programmable vaporizers, each distinct temperature setting will vaporize a unique set of active molecules, allowing for greater control of the content that is delivered. For example, setting the temperature for 150 to 160 degrees Celsius, or 302 to 320 degrees Fahrenheit, will produce a mixture of alpha-pinene, beta-pinene and delta-9 THC, while a temperature of 161 to 170 degrees Celsius, or 322 to 338 degrees Fahrenheit, volatilizes beta-myrcene, and 171 to 180 degrees Celsius, or 340 to 356 degrees Fahrenheit, volatilizes D-limonene and CBD — allowing a consumer to inhale, for example, three different puffs with three different sets of content.

Sublingual: Delivery As Quick As a Flick of the Tongue

Sublingual absorption, as the name indicates, refers to under-the-tongue delivery. The method has an entirely different mode of action and works quickly, compared with edibles. Liquid in the form of drops or solids such as slips are well-absorbed and rapidly delivered into the circulatory system through the mucosal membrane linings under the tongue. This mode of action results in better bioavailability because it bypasses the digestive system.

In addition, a small fraction of THC can directly interact with the CB1 receptors in the salivary glands, which are part of the endocannabinoid system in our bodies. Endocannabinoid system components, such as the CB1 and CB2 receptors and the messenger molecules 2-arachidonoylglycerol and anandamide, are involved in a number of basic functions described two decades ago by biomolecular researcher Vincenzo Di Marzo as “relax, eat, sleep, forget, and protect.”


The presence of CB1 receptors in salivary glands of mammals; the presence of endocannabinoids, or the internal molecules in our body that bind CB1 and CB2 receptors, 2-arachidonoylglycerol, and anandamide in human saliva; and the decrease of saliva secretion as a side effect of cannabis consumption suggest that these delivery methods allow direct and very rapid interaction between cannabinoids and the CB1 receptor.

Edibles: Eat, Drink, and Be Merry

Edibles generally have a slower absorption rate due to the digestion process. Edibles go through the digestive system, where active ingredients such as THC are further chemically modified to 11-hydroxy-THC, a more psychoactive form, by a set of enzymes called the cytochrome P450 superfamily. This process, however, can be inhibited by the presence of flavones, such as apigonin and luteonin, which are also found in cannabis. The genetic makeup of the consumer also has a large impact on this process.

Topicals: Ay, There’s the Rub

Cannabis-infused topical ointments are absorbed through the skin. The skin receptors can receive signals from topical ointments as well as signals from the body. The effect is localized and limited to anti-inflammatory, pain relief, and itch treatment, with almost no chance of psychotropic side effects. It is effective as CBD-only, a mixture of a few cannabinoids, and as a whole-plant or -flower extract.

As new research expands scientific and medical knowledge, and as standards are developed for extraction and detection, we will see the development of more products with accurate labels and reproducible effects. This will give doctors and consumers more tools to tailor treatment to each person, taking into account their genetic makeup and medical conditions.

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