The Lesser Known Smell of Cannabis

Mark Lewis, PhD, is a contributing author to this article (2018)

Much of the hype these days that permeates the industry is about cannabis derived molecules known as terpenes. In the parlance of the industry, your fire isn’t fire unless you have that LOUD bud. These flowers do not make noises, they are loud smelling. And are often chocked full of particular terpenes that are unusually permeating due to their combinations. Sometimes, loud buds are high in essential oil content, but not always. In fact, a low essential oil plant can still be loud if it consists of relatively ample amounts of a few potent, lesser known aroma molecules. We will get into the specifics of how a small terpene entourage can have a pungent smell. We’ll start with the basics and get technical with a few, subtle players in the aroma.

Let’s Start with Two Important Concepts

The smell of cannabis is not linked to its potency and not all terpenes are created equal. Just because a plant has an extraordinarily high THC oil content does NOT mean that its funky aroma will permeate an entire building. In fact, some high-THC plants are almost devoid of terpenes, in the pre-Cole Memo and CJS amendment era, plants were bred to less smelly to avoid detection of indoor grows. And the converse is true, there are plants that have high-terpenes and virtually no THC or CBD. Each scent molecule or terpene has a different contribution to the potency of the smell wafted up the nose. Some molecules are stronger than others on a per molecule basis, and animals, such as truffle hounds, can smell small quantities quite easily or loudly. For example, the scent of a skunk defending itself in the wild is very potent even at small concentrations. On the other hand, some molecules can be very abundant, but their aroma manifests much less potently – like myrcene. Going into the why’s and how’s of terpene potency is beyond the scope of this article, but it has to do with vapor pressures and other chemical properties of both the scent molecules themselves and the old-factory system that feeds directly into our brain’s emotional centers.

The top terpenes found in the market place tend to be limonene, terpinolene, pinene, caryophyllene, and myrcene. Based on experience or from their name alone we probably all know how limonene and pinene may smell, but lesser known is the sweet anise and mildly black licorice aromas of beta-caryophyllene and the generic sweetness of myrcene. These aromas are nice, but do not underscore the earthiness, the funks or musk. Thus, we will explore the lesser known smell of cannabis; some of the ‘complimentary’ terpenes that give the flowers you smell the full body aroma we have come to know, love, and may even play a role in our health and wellness.

 

Now, Let’s Get Started with What You Came Here to Read, Technical Information about Terpenes!  

Starting with Fenchol, here is what the scientists have to say about this bicyclic monoterpenoid, also known as fenchyl alcohol. It’s an FDA-approved flavor additive and generally recognized as safe (it’s on the GRAS list). If you’re tired of smelling it, extreme oral doses above 2 g/kg (equivalent to about 180g for an adult) were fatal in rats, demonstrating lethargy, ataxia, flaccidity, and coma, whereas a 4% cutaneous application in humans was non-sensitizing. It is a common component in basil (O. basilicum), and to California cannabis chemovars, but in low concentrations. Don’t worry your pretty little noses because the toxicity would be unlikely a factor even if inhaled from a vaporized cannabis extract. It is safe at ambient or natural levels but questionable safety issues arise at high concentrations when used as an additive or excipient.

Now, let’s get to know this molecule from a different perspective. In practical terms, fenchol has an undeniable funk, that, when combined with limonene will turn every head within a fifteen foot radius. For example, Lemon Crush is a chemovar that is cultivated by Molecular Farms in California and won best overall flower in last year’s Emerald Cup. At the competition, every single time a jar was cracked open the onlookers swooped in to see what was emitting that aroma. The flower gave the competition quite a shellacking, and was coincidentally Molecular Farms’ highest testing chemovar for fenchol content back in 2017. Those numbers have since risen and, it will be nice to see if the same pattern emerges: a direct correlation between a winning chemovar and a notable concentration of a rare and unique terpene, but this is just the tip of the terpenic iceberg.

While the breeding tendencies of fenchol-heavy varieties are lesser known, those α-Phellandrene are a bit more known. α-Phellandrene was named after Eucalyptus phellandra (renamed E. radiata) and is found widely in essential oils. In cannabis it is often inherited or coupled with terpinolene inheritance. Terpenes breed in something we have dubbed ‘cassettes,’ in this case a  tendency to be linked to OG type plants.

Technically speaking,  α-phellandrene is widespread cyclic monoterpene across the plant kingdom, but especially rich in frankincense (Boswellia sacra), comprising 42% of the essential oil. It produced cholinesterase inhibition with an IC50 of 120.2 μg/mL. Multiple assays in mice demonstrated antinociceptive effects: acetic acid-induced abdominal writhing (3.125 mg/kg/po or 0.25 mg/kg human equivalent), both phases of the formalin test (50 mg/kg/po, or 0.54 mg/kg human), capsaicin injection (3.125 mg/kg/po, or 0.25 mg/kg human equivalent), glutamate injection (12.5 mg/kg/po, or 1 mg/kg human) and carageenan injection (only at 3 h at 25 mg/kg/po, or 2 mg/kg human). Effects were blocked by multiple agents, suggesting mediation by glutamatergic, opioid, nitrergic, cholinergic, and adrenergic mechanisms.

In rats, phellandrene at 10 mg/kg/d po (1.6 mg/kg human equivalent) prevented spared nerve injury-induced mechanical and cold hyperalgesia, while also demonstrating an antidepressant effect in reducing immobility in the forced swim test 85%, but without decreasing locomotor activity in the open field. While not demonstrating antimicrobial effects per se, phellandrene mildly stimulated macrophage proliferation in mice via Mac-3 and promoted function in vivo, suggesting ability to suppress intracellular bacterial growth.

Subsequent work demonstrated a wide variety of effects on gene expression affecting DNA repair, cell cycle, and apoptosis in WEHI-3 murine leukemia cells (Lin et al., 2015, 2014). At 30 μM concentration with 24 h of exposure, 15.8% of human liver tumor J5 cells became necrotic, possibly due to depletion of ATP (Hsieh et al., 2014). Subsequently, findings were attributed to multiple pathways: regulation of mTOR, LC-3II expression, p53 signaling and NF-κB activation. In carageenan injections in rodents, phellandrene 50 mg/kg po pretreatment induced neutrophil migration inhibition, and TNF-α release (both P<0.001) (Siqueira et al., 2016) and decreased mast cell degranulation (P<0.05), suggesting applications in arthritic and allergic conditions.

In closing, all terpenes found in cannabis are GRAS by the FDA. If you doubt the therapeutic potential of smells, remember that the effects of essential oils on mood results from the ol factory neurons in the nose that feed directly into the emotional centers of the brain, and these molecules can have physiological effects in the body as well, as demonstrated by human and animal studies. These lesser known terpenes may not be identifiable immediately as individual compounds by the nose, but they can clear or entrap the senses when combined with the right entourage terpenes for an explosive bouquet, quite literally. The commercial applications of breeding for terpene cassettes represents a potential perspective or strategy for cultivators to apply to their breeding programs.  It is our hope that basic research can help guide biotechnology applications to create new and unique smells from our favorite plant.

For more information and references please see the following article:

Russo, E. B., & Marcu, J. (2017). Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads. Advances in Pharmacology (San Diego, Calif.), 80, 67–134. http://doi.org/10.1016/bs.apha.2017.03.004

Disclaimer: This article is intended for informational purposes only and does not constitute medical advice. Always consult a healthcare professional for medical diagnosis or treatment recommendations.

 

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