terpenes

What is a terpene? Terpene, any of a class of hydrocarbons occurring widely in plants and animals and empirically regarded as built up from isoprene, a hydrocarbon consisting of five carbon atoms attached to eight hydrogen atoms (C 5 H 8). The term is often extended to the terpenoids, which are oxygenated derivatives of these hydrocarbons. Terpenes are the aromatic compounds that give cannabis strains their unique scent. In other words, terpenes are the reason Tangie smells like sweet oranges, Permafrost like a pine forest, and Sour…Terpenes are organic chemicals constituents of essential oils produced by most plants, and even some animals such as swallowtail butterflies and termites.

Well, if we start with a list of fragrant cannabis small molecules of interest to consumers, terpenes are products of geranyl pyrophosphate molecular Origami. Many of these “terpenes” interact with protein targets in our bodies and may or may not interact with drug metabolizing Cytochrome P450s (CyP) in our livers, etc. Whether to “do” plant, Big Pharma, or a combination of these drugs is a conversation a reader must have with their health care provider. Keep checking as this table is filled out.

terpenetargetCyPSolventodorMP/BP
α BisabololROS  EtOH 
D-Borneol GABAA, α2  EtOHcamphor 210.0 °C
Camphene  PPAR-γ,   EtOH /oilscamphor 159.5 °C
Camphor ADRα, µ Opioid, 5-HT.[1]  EtOH/oilscamphor 205.7 °C
3 Carene GABAA  EtOH slight <25°C/170 °C
β Caryophyllene PPAR-γ, CB2 CyPA3A olive oilblack pepper /263oC
Caryophyllene Oxide GABAA??  EtOH, fat 62.5 °C/
    
α Cedrene    
Cedrol   EtOH,~H2O 86°C/286 °C
 Citronellol PPARγ
   
p Cymene CaV1 CaV2.1-3 [1]  EtOH -68 °C/47 °C cc
Eucalyptol   EtOH1.5 °C /176 °C
Fenchol   EtOH, oils 
Fenchone   EtOH 5°C/
Geraniol   PPARγ   EtOHrose<-15°C /228°C
Geranyl Acetate   70% EtOHlavender /242 °C
GuaiolGABAA   
α Humulene GABAA   
Isoborneol   EtOHcamphor209 °C/212 °C 
Isopulegol   EtOHminty herby 78 °C/
     
Limonene adenosine A2AEtOHlemon/176.0 °C
Linalool PPARα  EtOH, lavender <25°C/198 °C
Menthol   EtOHmint 39°C/
Myrcene TrpV1  EtOHbalsamic< -10  /167 °C
Nerol*   EtOHrose<-15  /225 °C
NerolidolHMG CoA reductase ? and membranesCYP1A, CYP2B and CYP3A  EtOHrose apple/122 °C
E-β-Ocimene   EtOH/oilsherb 
α Phellandrene   EtOHpeppery /172°C
α Pinene  GABAA  EtOH/oilspine -63°C/
β Pinene  piney /166°C
     
trans-Phytol   EtOHfloral <25°C/
R-(+)-Pulegone   EtOHherb/mint <25/224 °C
Sabinene   /164 °C 
Sabinene Hydrate    
α Terpinene    
γ Terpinene    
Terpineol NOS [1]  70% EtOHlilac37/220 °C 
Terpinolene    
Trans β Farnesene   /95-107o
Valencene   oilscitrus /123 °C
CaV voltage gated Ca2+ channels; NOS nitric oxide synthase, TrpV1

Linear Terpenes?

No fancy folding in these terpenes. The plant just makes minor modifications to geranyl pyrophosphate percursor.

Menthol and Limonene

Menthol and limonene are some of the common terpenes derived from geranyl pyrophosphate.

Upper left hand corner: feranyl pyrophosphate, the precursor of the simplest monoterpenes.

The Camphors

These terpenes are also derived from geranyl pyrophosphate. This image was from Wikipedia with inspiration from other internet images. geranyl pyrophosphate forms an L-limonene intermediate. The limonene molecule essentially folds in half creating our first intermediate towards the formation of iso-borneol. The + charge is a site for negatively charged pyrophosphate. Exit of pyrophosphate leaves a hydroxyl group, The solid arrow▼ tells us that the H is coming out at us from the lane of the screen. The striped Ξ in going into the plane of the screen. You will note that the (-)/(+) α-and β- pinenes are mirror images of each other much like the left and right shoes are mirror images of each other. This handedness / “chirality” imposes restrictions on the targets of these terpenes.

Quite often, it seems that the targets of these terpenes are reactive oxygen species rather than proteins.

Uncategorized terpenes

Some terpenes found in cannabis that do not fit into the other categories. Note that alpha-caryophyllene is the same compound as Humulene, only humulene is all trans double bonds.

Some of these “uncategorized” cannabis terpenes make finding protein targets seem doubtful. The β-caryophyllene comes in a right she (+) and left shoe(+) isomer. To make matters more perplexing α-caryophyllene comes with cis/trans isomerization movable parts much like the “fortune teller” Origami children’s toy. For now we will speculate that the targets of some of these terpenes are reactive oxygen species.

This website started out with a certain level of naivety. My journey has presented at least three classes of terpenes. Do these three main classes have similar targets? I’m not sure they all have protein targets. Maybe some of them just like to react with stuff. We can speculate that sabinene likes to react with reactive oxygen species to give us sabinene hydrate, Keep checking back as my journey continues

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References

  1. Assis, D. B., Aragão Neto, H. C., da Fonsêca, D. V., de Andrade, H., Braga, R. M., Badr, N., Maia, M., Castro, R. D., Scotti, L., Scotti, M. T., & de Almeida, R. N. (2020). Antinociceptive Activity of Chemical Components of Essential Oils That Involves Docking Studies: A Review. Frontiers in pharmacology, 11, 777. PMC free article
  2. Wang, Z. J., & Heinbockel, T. (2018). Essential Oils and Their Constituents Targeting the GABAergic System and Sodium Channels as Treatment of Neurological Diseases. Molecules (Basel, Switzerland), 23(5), 1061. PMC free article
  3. Ghosh, M., Schepetkin, I. A., Özek, G., Özek, T., Khlebnikov, A. I., Damron, D. S., & Quinn, M. T. (2020). Essential Oils from Monarda fistulosa: Chemical Composition and Activation of Transient Receptor Potential A1 (TRPA1) Channels. Molecules (Basel, Switzerland), 25(21), 4873. PMC free article
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