Cannabis trichomes: How cannabinoids, terpenes, and flavonoids are made

Trichomes are the hairs found on the surface of plants and are responsible for producing the protective, therapeutic, psychoactive, and intoxicating properties of a cannabis plant. Certain trichomes contain resin glands that create the terpenes, flavonoids, THCA, CBDA, and other phytocannabinoids for which cannabis is known.

The crystal-like sheen and sticky feeling of cannabis buds are caused by high accumulations of trichomes. While they’re most visible to the naked eye on cannabis flower, trichomes can also be found on the leaves and stems of the plant, though not all of the trichomes will be glandular. Non-glandular trichomes do not produce the same psychoactive compounds as glandular trichomes, but do aid in maintaining the plant’s surface balance and are thought to add a layer of protection against pests and adverse environmental conditions.

The glandular type of trichome produces cannabinoids, terpenes, and flavonoids. Within the glandular trichomes, there are three main types: bulbous, capitatesessile and capitate-stalked. Non-glandular trichomes are called cystoliths.

cannabis trichomes
The glandular type of trichome produces cannabinoids, terpenes, and flavonoids.

Bulbous trichomes are tiny bulbs that dot the surface of the plant. They cannot be seen without a microscope. While their production of cannabinoids is still in question, they add a crystal-like sheen to the cannabis plant and add to the stickiness of the flower. Bulbous trichomes aren’t restricted to particular areas of cannabis; they are evenly distributed throughout the surface of the plant.

Capitate sessile trichomes are more abundant than bulbous trichomes, but still typically only visible with the aid of a microscope. Like bulbous trichomes, capitate sessile trichomes have large bulbs, but with more of a classic mushroom-shaped structure. This type of trichome is primarily found on the underside of the sugar leaves and fan leaves.

Capitate-stalked trichomes are shaped like mushrooms and contain a large bulb at the head of the stalk. These are the largest and most abundant trichomes in cannabis, and they are most familiar with consumers because they can be easily seen with the naked eye. The capitate-stalked trichomes are primarily found on the surface of cannabis flowers and are rarely seen on sugar leaves, fan leaves, or stems.

Capitate-stalked trichomes
Capitate-stalked trichomes are shaped like mushrooms and contain a large bulb at the head of the stalk.

How compounds are created in the trichome

Cannabinoids, terpenes, and flavonoids are produced within the trichome cells through biosynthesis, in which enzymes catalyze a series of chemical reactions to produce complex molecules from simple (smaller) molecules. A quick review: Cannabinoids produced by the cannabis plant, or phytocannabinoids, interact with our body’s receptors to produce numerous psychotropic and therapeutic effects. Terpenes are compounds responsible for the aroma and flavors of cannabis, and support cannabinoids in producing desired effects. Flavonoids are similar to terpenes in that they contribute to a plant’s aroma and flavor profile, but may offer their own unique therapeutic effects.  

The three basic steps for cannabinoid biosynthesis are binding, prenylation, and cyclization. On a molecular level, the activity is as follows: Nanoscale macromolecules called enzymes bind to one or two small molecules (substrates), attach the substrates to each other (prenylation, catalytic chemical conversion of the substrates), then pass the small molecule (transformed substrate) down to another enzyme that processes it, making sequential changes to the small molecule (cyclization). Think of enzymes as biological nanomachines that use chemical energy rather than mechanical energy to build structures. Enzymes have inspired numerous studies in nanotechnology, biology, and other fields.

The following figures depict some of the molecular structures involved in cannabinoid biosynthesis. In these figures, each line is a bond between atoms. When two lines meet at a point and no letter is written, the atom is carbon by default. Oxygen and phosphorus atoms are explicitly indicated. Hydrogen atoms are only drawn in when bonded to oxygen or on the aromatic ring; they are not drawn on the alkyl chains. The curved arrows that point from one atom to another indicate that a new bond is formed between those atoms during the reaction, they also indicate the motion or exchange of electrons which make up a bond. Not all steps are shown, so there are some bonds that break and by-products that are formed which are not displayed.

The precursors to all natural cannabinoids, geranyl pyrophosphate and olivetolic acid, are produced themselves by a complex series of biosynthetic reactions. Geranyl pyrophosphate and olivetolic acid bond to each other with the assistance of an enzyme in the prenyltransferase category known as GOT, thus creating the first cannabinoid, CBGA (see Figure 1). CBGA, or cannabigerolic acid, contains a carboxylic acid group (with the molecular formula COOH), and due to the presence of that acidic group, an “A” is placed at the end of CBGA. This is true for the rest of the cannabinoids whose acronyms end with the letter A (THCA, CBDA, etc.). The carboxylic acid groups spontaneously break off the cannabinoid structures as carbon dioxide (CO2) gas when heated. This process is called decarboxylation, after which the “A” designation is lost. For example, decarboxylated CBGA becomes CBG. This is considered a degradation process because it does not require enzymes and occurs after the plant is harvested. The CBG type of cannabinoids have one ring in the molecular structure; it’s the aromatic ring that came from the olivetolic acid (see Figure 1).

Biosynthesis of CBGA and decarboxylation to CBG
Figure 1: Biosynthesis of CBGA and decarboxylation to CBG. Note: All reaction steps are not shown and reactions are not balanced.

So, CBGA is the first cannabinoid formed from a biosynthetic reaction that joined two smaller pieces together — it is also the precursor to all other natural phytocannabinoids. Next, CBGA is cyclized into THCA, CBDA, or CBCA via the enzymes known as THCA synthase, CBDA synthase, and CBCA synthase. The presence and relative quantities of the specific enzymes determine which cannabinoid is the major product from each particular strain and each particular cell. Remember, the CBG type cannabinoids have only one ring in their structure. After the cyclization reactions, the THCA, CBDA, and CBCA cannabinoids have more rings in their structures (see Figure 2).

For THCA, two new rings are formed by the creation of two new covalent bonds, a carbon-oxygen (C-O) bond and a carbon-carbon (C-C) bond. The CBDA synthase enzyme catalyzes a reaction that creates one new C-C bond at the same position that the C-C bond formed in THCA, but without the new C-O bond, thus forming CBDA. The formation of CBCA occurs by the formation of one (C-O) bond at a different position of the molecule than the (C-O) bond formed in THCA. Compounds with two rings fused to one another, such as in CBCA and CBC, are said to be bicyclic. That’s how THCA, CBDA, and CBCA are made through biosynthesis.

Cyclization of CBGA into the three cannabinoids THCA, CBDA, and CBCA, followed by decarboxylation to produce THC, CBD, and CBC.
Figure 2: Cyclization of CBGA into the three cannabinoids THCA, CBDA, and CBCA, followed by decarboxylation to produce THC, CBD, and CBC.

When cannabis flower is dried and cured properly, the most prominent cannabinoids will be the acidic forms of the cannabinoids (THCA, CBDA, CBCA, or CBGA). When smoked or baked into edibles, these molecules decarboxylate. While decarboxylated forms of cannabinoids might be produced to a small extent biosynthetically during drying, acidic forms are the major product. The decarboxylation products are delta-9-THC, cannabidiol (CBD), and cannabichromene (CBC) (see Figure 2).

As you can see, cannabis’ effects are the result of complex developments of cannabinoids, flavonoids, and terpenes that take place in the plant’s glandular trichomes.


Burke, Anthony. “Cannabinoid Biosynthesis Part 1 – CBG, THC, CBD and CBC.”, 23 June 2014.

Fellermeier, Monica, et al. “Biosynthesis of cannabinoids: Incorporation experiments with 13C-Labeled glucoses.” European Journal of Biochemistry, no. 268, 2001, pp. 1596–1604.

ElSohly, Mahmoud A., editor. Marijuana and the Cannabinoids. Humana Press, 2007.

Reviewed by Dr. Itzhak Kurek, Ph.D on 2/4/21

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