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.

terpene	target	CyP	Solvent	odor	MP/BP
α Bisabolol	ROS		EtOH
D-Borneol	GABAA, α2		EtOH	camphor	210.0 °C
Camphene	PPAR-γ,		EtOH /oils	camphor	159.5 °C
Camphor	TrpV3		EtOH/oils	camphor	205.7 °C
3 Carene	GABAA		EtOH slight		<25°C/170 °C
β Caryophyllene	PPAR-γ, CB2	CyPA3A	olive oil	black pepper	/263oC
Caryophyllene Oxide	GABAA??		EtOH, fat		62.5 °C/
carvacrol	TrpA1/3 & GABAA, TRPV4&TRPM2		EtOH, alkali	smoke/thymol	~0/237.7 °C
α Cedrene	OR10J5 ?	CYP2B6 β ?↓
Cedrol	OR10J5 ?	CYP2B6, CYP3A4 ↓	EtOH,~H2O		86°C/286 °C
Citronellol	PPARγ
p Cymene	mitochondria		EtOH		-68 °C/47 °C cc
Eucalyptol	TRPM8 L-type VGCC		EtOH		1.5 °C /176 °C
Fenchol	TrpA1, ffar2	Cyp2A6	EtOH, oils	basil	35-40/202oC
Fenchone	TrpA1 ffar2	Cyp2A6, 2B6	EtOH	herbal	5°C/193oC
Geraniol	PPARγ		EtOH	rose	<-15°C /228°C
Geranyl Acetate			70% EtOH	lavender	/242 °C
Guaiol	GABAA
α Humulene	GABAA
Isoborneol	GABAA,		EtOH	camphor	209 °C/212 °C
Isopulegol	GABAA		EtOH	minty herby	78 °C/
Limonene	adenosine A2A		EtOH	lemon	/176.0 °C
Linalool	PPARα, VGCC	CYP2C19 CYP2D6	EtOH,	lavender	<25°C/198 °C
Menthol	GABAA and TrpM8		EtOH	mint	39°C/
Myrcene	TrpV1		EtOH	balsamic	< -10  /167 °C
Nerol*	OR2w3		EtOH	rose	<-15  /225 °C
Nerolidol	HMG CoA reductase ? and membranes	CYP1A2, CYP2B and CYP3A	EtOH	rose apple	/122 °C
E-β-Ocimene			EtOH/oils	herb
α Phellandrene	CB2 ?		EtOH	peppery	/172°C
α Pinene	GABAA		EtOH/oils	pine	-63°C/
β Pinene				piney	/166°C
trans-Phytol	membranes		EtOH	floral	<25°C/
R-(+)-Pulegone			EtOH	herb/mint	<25/224 °C
Sabinene	PPARα ???				/164 °C
Sabinene Hydrate
α Terpinene	AdA2A ??
γ Terpinene	CB1/2 ??
Terpineol	CB1/2 ??		70% EtOH	lilac	37/220 °C
Terpin-4-ol	GABAA		oils	peppery	/209oC
Trans β Farnesene					/95-107oC
Valencene	Cox2 NS H1		oils	citrus	/123 °C

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.

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 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