January 7, 2021

Therapeutic Value of Cannabis Terpenes

Introduction

The therapeutic value of cannabis is becoming more understood by healthcare professionals as research is continually published. However, one area of cannabis that is lacking strong studies is terpenes.

Terpenes are molecules found in plants and cannabis that help create unique aroma and flavours. There is some research, largely in animal and test tube studies, showing that terpenes may have beneficial medicinal effects. It is theorized that terpenes, along with cannabinoids, work together in cannabis to produce a more robust medicinal effect; this phenomenon is called the entourage effect. Each cannabis strain has a unique profile of terpenes, which mean different strains may have different medicinal effects.

Below are brief summaries of different terpenes found in cannabis and their potential therapeutic benefits. This list is not comprehensive since there are over hundreds of terpenes found in cannabis. The information regarding terpene research came from an excellent review published by author Tarmo Nuutinen titled “Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus”

Disclaimer: Most of the current research on terpenes has been limited to test tube or animal studies. Currently, there are few studies specifically testing terpenes in humans. The limitation of animal studies is that often the conclusions from these studies do not translate to humans. This means most of the clinical recommendations regarding terpenes should be viewed as possibilities and not facts. In the terpene summaries below, information about anti-cancer or antibiotic effects of terpenes have been excluded. For information about those topics please refer to the original article “Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus”

Source: WeedMaps

Myrcene

Found in lemon grass, bay leaves, ylang-ylang , wild thyme, parsley, cardamom and basil. Myrcene is used as fragrance in soaps, detergents and a flavour agent in the food industry.
Possible uses: Insomnia, osteoarthritis, antioxidant, liver protectant, stomach ulcer prevention, physical and neuropathic pain, UVB skin protection.
May be useful in insomnia, however this was only found in high doses in mice.
May slow the progression of osteoarthritis through processes that slow the breakdown of joint tissues and via anti-inflammatory processes.
Found to increase antioxidant enzymes such as glutathione peroxidase, catalase and superoxide dismutase in mice. May be useful as an antioxidant. It was also found in rats to protect against liver damage
Myrcene was shown to protect against stomach ulcers via increased levels of glutathione reductase and glutathione in gastric tissues. It also decreased the production of inflammatory prostaglandins that may contribute to ulcer formation.
In mice it was shown to help reduce physical and neuropathic pain.
Myrcene has some evidence to show it can protect against UVB sun damage to human skin which may make it useful in skin care/sunscreen products.

β-caryophyllene

β-caryophyllene is found in clove, rosemary, black pepper and lavender
Possible uses: Inflammation, immune boosting, neuropathic pain, multiple sclerosis, neuroprotective, pain, depression, anxiety, atherosclerosis (plaque formation of arteries/veins), addiction.
One of the few, possibly only, terpenes that activates CB2 receptors. These receptors are known to be modulated by THC and CBD. CB2 receptors have effects on inflammation, pain and modulating the immune system.
β-caryophyllene may also be effective in neuropathic pain as it interacts and antagonizes several receptors involved in the pain pathway.
It was found to suppress neuroinflammation in a multiple sclerosis model test.
In animal models β-caryophyllene was found to have anti-inflammatory effects comparable to dexamethasone (a corticosteroid)
Found to decrease damage to brain in tests that simulate brain injury by reducing inflammation in the central nervous system.
β-caryophyllene has anti-anxiety and antidepressant properties mediated through the CB2 and serotonin receptor signalling.
In rats β-caryophyllene was shown to protect the heart by reducing plaque formation in the arteries/veins via antioxidant activity.
CB2 activity may have a role in addiction behavior. Studies have shown β-caryophyllene decreasing alcohol consumption in mice.

Caryophyllene oxide

Caryophyllene oxide is the oxidized form of β-caryophyllene. It can be found in guava, oregano, cinnamon, clove, black pepper, lemon balm and eucalyptus
It is used as a preservative in foods, medications, cosmetics and insecticides.
Possible uses: Diabetes type 1 and 2, cardiovascular disease, hypertension, kidney disease, Alzheimers and Parkinsons.
Inhibits the CYP3A, CYP2C19 AND CYP2C9 enzymes in the liver which in turn can affect the metabolism of other medications.
Caryophyllene inhibits an enzyme, 15-lipoxygenase, that is involved in inflammatory processes in the body. 15-lipoxygenase reacts with fatty acids in a pathway that is involved in several diseases such as diabetes, cardiovascular disease, hypertension, kidney diseases, Alzheimers and Parkinsons.

Humulene

Humulene is found in sage, ginseng and the myrtaceae family of plants.
Possible uses: inflammation, edema, asthma.
In mice and rats it was shown to reduce inflammation via modulating several inflammatory signalling molecules. The study provided evidence that humulene may be effective treatment for edema and had similar anti-inflammatory effects as the prescription medication dexamethasone.
Humulene may also be useful in asthma as it reduces the recruitment of allergy signalling molecules in lung fluid.
Interestingly, humulene can increase the production of a cancer-causing inflammatory molecule IL-8 in the intestines. This may actually increase the risk of cancer.

α-Pinene

α-Pinene is the most abundant terpene in the environment since its found in large quantities in conifer trees. It is also found in sage plants, black plum and lesser galangal.
Possible uses: antioxidant, inflammation, topical pain reliever, insomnia, anxiety, asthma.
α-Pinene has antioxidant actions by boosting the amount of antioxidant enzymes of CAT, SOD, GPx, GSR and HO-1.
In mice, the topical application of the α-Pinene reduced inflammation and pain.
It also has systemic anti-inflammatory actions by reducing the production of pro-inflammatory signalling molecules.
α-Pinene has anti-anxiety and sedation effects by binding to GABAa receptors in the brain. The terpenes also may also increase duration of sleep.
Another mice study showed that α-Pinene reduced anxiety several days after administration, meaning that it may accumulate in the body and maintain its effects after stopping use.
At low concentrations α-Pinene can help open up the lung airways

β-Pinene

β-Pinene, like α-Pinene, is found in conifer trees. It’s also in cumin and Clausena anisate.
β-Pinene is readily oxidized in air and converted to other terpenes such as pinocarveol and myrtenol
Possible uses: depression, insomnia, pain.
In mice models, β-Pinene has shown antidepressant and sedative effects
β-Pinene may have partial activity at opioid receptors, which can provide pain management. However, if a patient is already taking prescription opioids like morphine, β-Pinene may actually worsen pain by blocking the action of morphine.

Linalool

Linalool can be found in lavender
Possible uses: depression, anxiety, aggression, inflammation, edema, neuropathic and physical pain, seizures, high blood pressure, anti-oxidant, Alzheimers.
In mice studies linalool showed that it may have anti-anxiety effects. It’s also theorized that linalool exerts its antidepressant effect by acting on noradrenergic and serotonin receptors in the brain.
In mice studies linalool also reduced aggressive behavior and improved social interactions.
A study in men showed that inhaled linalool caused sedation and reduced anxiety.
The terpene also reduced inflammation, edema and neuropathic pain in mice.
There’s some evidence that linalool has anti-seizure properties by inhibiting the Nmethyl-D-asparate receptor in the brain.
Inhalation of linalool was shown to reduce blood pressure and pulse in patients with carpal tunnel syndrome.
Linalool was shown to have antioxidant properties similar to vitamin E in a guinea pig brain study. This was also seen in a test tube test, indicating that linalool has significant antioxidant action.
In an animal study, linalool treated Alzheimer symptoms and reduced the oxidative stress in mice brain.
Linalool showed to have liver protective properties against lipopolysaccharides.

Limonene

Limonene can be found in lemon rind, citrus fruits, ajwain, Bupleurum gibraltarium, celery, ebolo, Canadian horseweed and Bolivan coriander.
It’s also used in cleaning products, food manufacturing, perfumes, hygiene products and insecticides.
Possible uses: anxiety, scar prevention, stress, physical and neuropathic pain, gut health, osteoarthritis, IBS, insomnia, muscle tightness, depression.
Limonene has anti-anxiety properties in mice by activating serotonin receptors in the brain. It also showed anti-stress properties in another rat study.
In rats and mice limonene also showed to improve wound healing. It may have clinical use in scar prevention treatment.
Limonene reduced mechanical and neuropathic pain in rats. It’s theorized that the pain management was likely due to activation of opioid receptors in the brain.
Elderly patients who took orange peel extract (which contains limonene) had lower inflammatory markers in the gut. This suggests that limonene may improve gut health.
In test tube studies simulating osteoarthritis, limonene decreased inflammatory molecules and genes associated with destruction of joint tissue.
Limonene also showed that it was protective against kidney damage due to its ability to boost antioxidant enzyme activity.
Several other animal studies indicate that limonene has muscle relaxant properties, can increase duration of sleep, improve mood, and reduce intestinal contraction.

Perillyl alcohol

Found in lavender, sage, peppermint, mints, cherries, citrus fruits and lemon grass.
It’s an ingredient used in cometic products and cleaning agents.
Perillyl alcohol is a metabolite of limonene.
Possible uses: liver protection, inflammation, asthma, scar prevention, pain, stress, Alzheimers.
Perillyl alcohol in a rat model decreased liver damage associated with ethanol (alcohol) ingestion.
Perillic acid, which is the metabolite of perillyl alcohol, has anti-inflammatory actions that suppress the pro-inflammatory molecule IL-2 in the body.
It may also be effective in reducing the allergic response associated with respiratory airways. This means perillyl alcohol may be useful in asthma treatment.
Perillyl alcohol showed to improve tissue regeneration which may indicate its use in scar prevention.
It’s also an effective painkiller in mice, with results comparable to morphine.
Perillyl alcohol administered to rats significantly reduced their stress.
There is potential for perillyl alcohol to treat Alzheimers since it can decrease damage to brain tissues associated with the disease.

Terpinolene

Terpinolene can also be referred to as -Terpinene.
Found in sage, apple, cumin, lilac, tea tree, lemon, pine and fir trees.
Possible uses: insomnia, heart health, pain.
Terpinolene when administered nasally caused sedation in mice.
In blood plasma preparations, terpinolene was found to prevent oxidation of cholesterol. This may be useful in preventing heard disease.
Terpinolene showed it worked well with a traditional anti-inflammatory drug (diclofenac) in mice models to reduce inflammation. However, it’s theorized to use serotonin receptors to modulate pain and therefore does not increase the risk of stomach lining damage like traditional anti-inflammatory agents such as Advil or diclofenac.

γ-Terpinene

γ-Terpinene has been found in thyme and in Satureja
Possible uses: pain, inflammation, insomnia, anti-oxidant, cardiovascular disease.
In rats γ-Terpinene showed pain relief properties. It’s theorized that it uses opioid and cholinergic systems to achieve pain relief.
γ-Terpinene can also act as an anti-inflammatory in mice by modulating pro-inflammatory molecules and reducing neutrophil movement to the inflamed site in the body.
γ-Terpinene stops cholesterol particles from becoming oxidized in the blood, which can have a beneficial impact on cardiovascular disease.
Studies have also shown anti-oxidant activity and sedative properties too.

α-Terpinene

α-Terpinene can be found in allspice, tea tree and Litsea ceylanica
Possible uses: antioxidant.
α-Terpinene has good antioxidant activity; however, it can form allergens by auto-oxidation. This means it may induce an allergic response in some people.
In a rat study α-Terpinene caused memory deficits due to DNA damage. The study indicated that it can cause damage to brain tissue.

Terpineols

Terpineols consist of a group of terpene derivatives: α- terpineol and γ-terpineol and terpinen- 4-ol.
They can be found in tea tree oil, cajuput oil, pine oil, petitgrain oils, lilacs, pine trees, lime blossoms and eucalyptus. These terpenes can be created from limonene and pinene terpenes.
Terpinen- 4-ol possible uses: Seizure, insomnia, pain, high blood pressure.
Terpinen- 4-ol showed anti-seizure activity and sedative properties via the GABA receptor system in the body. Interestingly it’s thought that terpinen- 4-ol uses different GABA receptors compared to traditional benzodiazepines.
Terpinen- 4-ol has shown anti-pain effects theorized to be exerted via opioid and serotonin receptors.
In a study using rats, Terpinen- 4-ol showed a reduction in blood pressure after it was injected into the test subjects.
α- terpineol possible uses: IBS, brain health, stomach ulcers, inflammation.
α- terpineol showed muscle relaxant properties on the intestines, possibly making it useful in IBS.
In a rat study simulating brain damage, α- terpineol improved memory and the ability of the brain to adapt to the damage.
α- terpineol also showed gastric lining protection against ulcers. The terpene supresses inflammatory molecule production in the body which help protect the stomach.

Geraniol

Geraniol is found in palmarosa oil, rose oil, citronella oil ang Geranium. In industry it’s used as a preservative, insect replant and attractant.
Geraniol is converted via biosynthesis to several other terpenes.
Possible uses: eczema, diabetes, heart health, high cholesterol, colitis, IBS, liver health, asthma, brain health, depression.
The terpene showed to suppress inflammation of the skin by reducing the production of several inflammatory molecules in the body. It may be useful for skin conditions such eczema.
In diabetic rats geraniol showed beneficial effects on the cardiovascular tissues and on management of high blood sugars.
Another rat study showed heart benefits via the antioxidant properties of geraniol.
Geraniol also may reduce cholesterol production in the body by inhibiting the HMGCR enzyme.
In a rat study, geraniol reduced inflammation in the colon suggesting it may be useful in colitis and IBS.
It may also help stimulate liver tissue regeneration. In a study it was seen to have similar effects of Silymarin which is a natural product used in the treatment of liver cirrhosis.
In a mice study, geraniol treated asthma by reducing the inflammatory allergic response.
Geraniol has been shown to have antioxidant effects in the brain.
In chronically stressed mice geraniol provided antidepressant effects over a 3-week administration timeframe.

Nerolidol

Nerolidol can be found in hemp, paper bark tea tree oil, Siparuna, Myrceugenia, Piper claussenianum, New England peppermint tree, salvia and neroli.
It’s also used in food flavouring, cosmetics and cleansers.
Possible uses: anxiety, depression, memory, brain health, insomnia, antioxidant.
Nerolidol was shown to have anti-anxiety effect in mice similar to diazepam.
It also acted as an antidepressant and improved memory. It did this by increasing neurotransmitters in the brain and acting as an anti-oxidant in the test subjects.
Another study suggested nerolidol has pain relieving and anti-inflammatory actions. The mechanism of action may be via the GABA receptor system and a reduction of inflammatory molecules in the body.
In a mouse brain, nerolidol acted as an antioxidant and had similar effectiveness as vitamin c. It also acts as an antioxidant in mice liver, heart and blood.
In animal study nerolidol was just as effective as diazepam in causing sedation.

Borneol

Bonreal can be found in plants such as Mugworts , Blumea, Kaempferia, Dryobalanops and valerian.
Possible uses: Blood thinning, topical pain, physical pain, neuropathic pain, asthma, colitis, IBS, inflammation, diabetes, liver health, Crohn’s disease, Scar prevention.
It has anticoagulant (blood thinning) effects by suppressing certain signalling molecules in the body TNF-α, iNOS, IL-1β and COX-2. This may be useful in heart disease or may negatively interact with prescription blood thinners.
Borneal has a similar mechanism of camphor as a topical painkiller and shown to be effective in a small patient study.
In mice borneal was effective at treating physical and neuropathic pain. It had similar effectiveness as indomethacin (anti-inflammatory medication) and morphine in pain tests on mice.
Borneal may be useful in the health and function of the brain. In tests it helped improve the structure of neurons and reduced cell destruction in the brain.
In a mouse model, borneal reduced lung inflammation. It also reduced inflammatory molecules in the intestinal tract associated with colitis.
Borneal has anti-inflammatory properties and found to have similar effectiveness as aspirin in one study.
In diabetic rats, the consumption of borneal significantly improved the diabetic sugar control and cardiovascular risk factors.
In an animal model borneal improved liver health via optimizing proteins, lipids and glycogen in the liver.
In a cell model, researchers found that borneal has anti-fibrosis activity by effecting fibroblast mitosis, collagen and TIMP-1 production. This is suggestive that borneal may be an option to manage Crohn’s disease.
Borneal show improved wound healing in rats by reducing myeloperoxidase activity and increasing collagen synthesis.

α-Bisabolol

Bisabolol (also known as levomenol) is found in candeia tree, salvia, Plinia Eremanthus, chamomile oil and cat’s claw.
Bisabolol is commonly used in cosmetics.
Possible uses: antioxidant, inflammation, stomach ulcers, kidney health, Alzheimers, eczema, skin inflammation, pain, anxiety, insomnia.
Bisabolol can increased the permeability of other medications through the skin. This may be useful in topical creams and lotions to facilitate better absorption.
In Alzheimers it can reduce damage and cell death similar to the prescription drug donepezil.
One study showed that Bisabolol acted as an antioxidant and reduced inflammation associated with stomach lining damage from alcohol.
Bisabolol showed that it’s protective against stomach ulcers caused by traditional anti-inflammatory medication like Advil.
In a mouse study bisabolol showed kidney protective mechanisms after a kidney sustained damage.
Bisabolol in animal and test tube studies showed that it may be effective in reducing skin inflammation and treating eczema.
It also showed pain killing effects in animal tests after a single dose was administered. It was most effective in pain associated with inflammation.
Bisabolol has anti-anxiety and sedative actions by interacting with the GABA receptor system in the body.

Bisabolenes

α-, β- and γ-bisabolene are found in cubeb, lemon and oregano.
Possible uses: seizures.
In zebra fish, bisabolene had anti seizure activity. However, its unclear how it does this.

β-elemene

β-elemene is used as a pheromone by some insects
Possible uses: heart health, liver health, inflammation.
In animal and test tube studies β-elemene has shown protective mechanisms against plaque buildup in arteries. It may be useful in cardiovascular health.
β-elemene helped treat and reduce liver damage in rats.
β-elemene provides anti-inflammatory actions in the body to counter the actions of lipopolysaccharides in the body.

Fenchone

Fenchone can be found in fennel, olive leaves and French lavender
Its used in the food ang perfume industries
Possible uses: inflammation, anti-oxidant, skin health.
There’s some evidence from studies showing anti-inflammatory, anti-oxidant and increased collagen synthesis properties.

Pulegone

Pulegone is commonly found in mint plants, rosemary and Agastache formosanum
This terpene is used in perfume and as a flavouring agent in the food industry.
Possible uses: insomnia, physical pain, anxiety.
One animal study found that it can increase duration of sleep with co-administration of phenobarbital.
Pulegone can also treat mechanical pain. It’s thought that it does not use opioid receptors as part of its mechanism of action.
A mouse study found that pulegone and anti-anxiety activity. The researchers deduced that the mechanism of action was different than traditional benzodiazepines as it does not use the GABA receptor system.
Pulegone has shown to have negative effects mammals heart functions reducing the force at which the heart can beat.
At high doses Pulegone has shown to cause toxic effects on heart, renal and liver functions.

α-Phellandrene

α-Phellandrene is found in Eucalyptus phellandra, water fennel, rose pepper and Canada basalm oil.
α-Phellandrene is used in the perfume and food industry.
Possible uses: immune booster, inflammation, physical pain, neuropathic pain.
In mice α-Phellandrene modulated the immune system and improved its function.
α-Phellandrene also has anti-inflammatory actions by decreasing the production of certain pro-inflammatory molecules.
In rats it showed pain killing effects against physical pain, cold temperatures and nerve injury. Its theorized that α-Phellandrene may use several receptor systems in the body to treat pain.

β-eudesmol

β-eudesmol can be found in gingers and Atractylodes lancea
Possible uses: inflammation, muscle relaxant, pain, appetite, anorexia, IBS.
β-eudesmol produced anti-inflammatory results by blocking certain enzymes from making pro-inflammatory molecules.
In a lab test looking at brain slices, β-eudesmol was found to have muscle relaxant and anesthesia properties.
In animal studies β-eudesmol stimulated appetite and caused weight gain.
β-eudesmol has some evidence linking it to improved intestinal motility and stimulating the passage of food through the gastrointestinal system.

Conclusion

There are hundreds of terpenes and each one of them may impart some medicinal value in cannabis. It will be exciting to see new research regarding terpenes and how it shapes clinical recommendations. More cannabis research will help healthcare professionals provide more meaningful care to their patients.

For healthcare professionals or patients interested in a personalized cannabis consult, check out Apothecare Chemists