Ah, the great entourage theory, or is it more of an ensemble effect? Regardless, terpenes, lightly aromatic and oftentimes smelly oils, can alter the effects of cannabis. And each strain’s ensemble of ingredients produces its own unique experience. Little discussed, however, is the fact that some terpenes are only active through olfactory neurons. This means that those terpenes might not have the same effect in an edible.

When smoked, THCa converts into active D9-THC. From there, it is absorbed into the bloodstream. As many have found out, active THC (tetrahydrocannabinol) is technically an intoxicating cannabinoid. Included in the experience of many new consumers, THC has a different effect when eaten compared to inhaled (smoked or vaped.) For the most part, enzymes in the liver convert D8 or D9-THC into another isomer known as 11-hydroxyl-THC.

Terpene metabolism

In comparison, research has slowly advanced and identified a few metabolites produced during the digestion of terpenes in humans. Hiroshima University in Japan researched the metabolic conversion of terpenes in rabbits in 1979. (1) The metabolic processes that plants utilize to produce terpenes were then characterized in depth by 1995. More recently, some of the metabolic byproducts that are created when humans digest those terpenes have been elucidated as well. Three terpenes were separately studied by Lukas Schmidt and Thomas Goen, a pair of researchers in Germany. (2)

D-3-Carene

Shmidt and Goen first studied 3-carene (CRN) which is a minor terpene found in cannabis. While data was more inconclusive for carene, they did detect one metabolite. Small amounts of a carboxylated variation of delta-3-CRN, known as chaminic acid, were found after human digestion. To add to their findings, the researchers noted other possible metabolites they did not detect.

  • Chaminic acid (CRN-10-COOH)

Alpha-pinene

Alpha-pinene is oxidized in the gut which produces myrtenol, myrtenic acid, and two isomers of verbenol. The latter, at least, can account for some biological effects according to current research.

  • Myrtenic acid
  • Myrtenol
  • Trans and cis-verbenol

R-limonene

Limonene degrades into carvone, but it further converts into a few noteworthy compounds during digestion. For example, two isomers of carveol are produced in relatively minimal quantities by human digestion of r-limonene.

Beyond carveol, more perillic acid is found in human blood (plasma) after the bitter citrus terpene is eaten compared to perillyl alcohol. The latter of which fights against tumours according to early research. LMN-8,9-diol is the most abundant metabolite of r-limonene (LMN) in humans, though, followed by relatively small quantities of a second isomer.

  • LMN-8,9-diol
  • LMN-1,2-diol
  • Perrilic acid
  • Perillyl alcohol
  • Trans and cis-carveol
Linalool applied to the skin with ice after experiencing a burn will reduce the chance of scarring or blisters. Ingested, however, linalool drastically converts to other terpenes.

Does only the nose know linalool?

The nose truly knows when it comes to strains you intend to smoke thanks to terpenes, but the effect doesn’t quite translate for edibles. Receptors in our brain and throughout our body receive cannabinoids. Whereas, different receptors found in the nasal cavity and the gut, for example, respond to at least one terpene. – linalool.

Linalool’s anti-anxiety properties might not be as prominent when taken orally compared to the smell of the terpene. A specific type of receptor is blamed. Looking at the full picture, though, a multitude of factors alter linalool’s effect based on consumption method. Firstly, the effect depends on olfactory neurons, a type receptor (GCPR) present in the nasal cavity, mouth, and gut.

In one study, linalool did not induce GABA-a, which is the same receptor that benzodiazepine drugs target, facilitating relaxation. A later study noted that linalool does induce relaxation through GABA-a but it depends on olfactory neurons. So, linalool might affect anxiety via edibles if enough of the terpene can make its way into the stomach.

Adding to that challenge is metabolism amd digestion. Linalool converts into three different terpenes as it passes through the esophagus. Beyond this, metabolism subjects linalool to several different alterations. That said, only oxygen atoms (oxygenation) can turn the floral terpene into 8-oxo-linalyl-acetate; the sole metabolite that facilitates anxiety through GABA-a. This is promising since linalool might inhibit seizures and epileptic episodes without affecting mood by simple natural processing.

  • 8-oxo-linalyl-acetate
  • 8-hydroxylinalool
  • 8-carboxylinalool
  • Several other hydroxylated, carboxylated, and oxygenated metabolites
  • Geraniol
  • Nerol
  • a-terpineol
Terpenes are often clear liquids oils; a little goes a long way.

Myrcene and the monoterpene family

Monoterpenes are one family of molecules and become transient under certain conditions. In fact, beta-myrcene is an important precursor molecule for other terpenes like linalool or citronella. During digestion, oxidation turns myrcene into four different molecules, two diols and two hydroxyl acids. One diol is known as 10-hydroxylinalool, whereas one of the acids is 10-carboxylinalool.

  • 10-hydroxylinalool
  • 7-methyl-3-methylene-oct-6-ene-1,2-diol
  • 10-carboxylinalool
  • 2-hydroxy-7-methyl-3-methylene-oct-6-enoic acid

Caryophyllene, edible oil, and cannabinoid receptors

Linalool and the other three aforementioned terpenes are in a group of unique molecules comprised of ten carbon atoms, known as monoterpenes. Whereas, sesquiterpenes consist of 15 carbons atoms; heavier terpenes that are more common in edibles. This is because lighter monoterpenes boil away during processing (decarboxylation).

β-caryophyllene is not only the primary sesquiterpene found in cannabis, it also directly activates an acutely therapeutic cannabinoid receptor. In regards to edibles, the evidence does suggest beta-caryophyllene taken orally will indeed agonize the therapeutic cannabinoid receptor.

Do industries know how terpenes effect edibles?

Terpenes heavily impact an industry worth billions, driving cannabis. Odour and scent drive cannabis, craft beer, and fragrance markets. For this reason, how terpenes affect different biological human receptors holds widespread implications for industries and marketplaces. Producers, processors and the retail department must all execute decisions based on terpene profiles. Of course, a product’s fragrance is still pivotal from restaurants to grocery stores and breweries alike even though terpenes are less effective when eaten.

Let us know in the comments if you have experience a noticeable effects with any terpenes in edibles. And which terpenes do you want to know more about?

  1. Ishida, T., Asakawa, Y., Takemoto, T., & Aratani, T. (1981). Terpenoids biotransformation in mammals III: Biotransformation of alpha-pinene, beta-pinene, pinane, 3-carene, carane, myrcene, and p-cymene in rabbits. Journal of pharmaceutical sciences70(4), 406–415.
  2. a.) Schmidt, L., Belov, V. N., & Göen, T. (2015). Human metabolism of Δ3-carene and renal elimination of Δ3-caren-10-carboxylic acid (chaminic acid) after oral administration. Archives of toxicology89(3), 381–392. b.) Schmidt, L., & Göen, T. (2017). Human metabolism of α-pinene and metabolite kinetics after oral administration. Archives of toxicology91(2), 677–687. C.) Schmidt, L., & Göen, T. (2017). R-Limonene metabolism in humans and metabolite kinetics after oral administration. Archives of toxicology91(3), 1175–1185. D.) G Schmidt, L., Lahrz, T., Kraft, M., Göen, T., & Fromme, H. (2015). Monocyclic and bicyclic monoterpenes in air of German daycare centers and human biomonitoring in visiting children, the LUPE 3 study. Environment international83, 86–93.
  3. Milanos, S., Elsharif, S. A., Janzen, D., Buettner, A., & Villmann, C. (2017). Metabolic Products of Linalool and Modulation of GABAA Receptors. Frontiers in chemistry5, 46.
  4. Madyastha, K. M., & Srivatsan, V. (1987). Metabolism of beta-myrcene in vivo and in vitro: its effects on rat-liver microsomal enzymes. Xenobiotica; the fate of foreign compounds in biological systems17(5), 539–549. https://doi.org/10.3109/00498258709043961

Footnote(s)

https://doi.org/10.1007/s00204-014-1251
https://doi.org/10.1007/s00204-015-1656-9
https://doi.org/10.1007/s00204-016-1751-6-5
https://doi.org/10.1016/j.envint.2015.06.004
https://doi.org/10.3389/fchem.2017.00046