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Your Ultimate Guide to Terpenes

Erica Littman's avatarPosted by

What They Are & How They Work

Terpenes are aromatic oils found in cannabis that are responsible for the general smell and flavor of the plant. However, terpenes are not exclusive to cannabis, and–in fact– are found in almost every plant! Typically, they are used for reproductive purposes by luring pollinators to the plant through specific scents. But, they also have profound medicinal and pharmacological effects on mammals (including humans!) that have the potential to treat a variety of diseases and symptoms; there are over 20,000 different terpenes, and some have been studied extensively for decades, while we know relatively little about others. Cannabis strains have extremely diverse terpene profiles that can create different effects. Here are the most common terpenes found in cannabis that are known to science, and how each helps with specific symptoms!

Linalool

Linalool is a common terpene found in cannabis & lavender that gives off a citrusy & minty aroma. It is well known for its anti-inflammatory, anti-depressant, anti-anxiety, anticonvulsant, pain-relieving, and memory/cognitive protective properties. Yes, it may actually improve long-term memory!

Sedating, Pain Relief & Anti-inflammatory Effects:

Linalool interacts with the somatosensory system1, which is responsible for sending signals and information regarding pain, pressure, & temperature from the muscles, joints, and skin to your brain. By decreasing the activity of these cells, linalool relieves pain and decreases inflammation.1

Linalool has also been found to interact with adenosine receptors A1 and A2, and trigger the same effects as adenosine2: a neurotransmitter that induces pain-relieving and anti-inflammatory effects. Adenosine also promotes sleep and acts as a general central nervous system depressant. 2, 3, 4 By mimicking adenosine and activating the A1 and A2 receptors, linalool has the same sedative properties.

Cognitive & Memory Protective Properties:

Alzheimer’s disease currently has no cure, but preliminary research has found that linalool may help restore memory, and repair cognitive & emotional function through decreasing plaque buildup in the brain that is characteristic of the disease.5 Certain inflammatory markers, such as MAPK and different interleukin molecules (that will be discussed in greater detail below) that are also commonly found in higher concentrations in Alzheimer’s patients are also decreased by linalool.5

Anticonvulsant Properties:

Linalool has shown strong anticonvulsant properties. Glutamate—the most prominent excitatory neurotransmitters for adult mammals—is often found in excess in patients with epilepsy as it is released during seizures; long term, the excess glutamate can cause the death of neurons.6 Linalool has been proven to inhibit glutamate uptake in mice by up to 90%7 and significantly reduced the excess release of the neurotransmitter, therefore preventing long-term damage to neurons. One particular plant—Ocimium basilicum—that is high in linalool has been shown to reduce seizure occurrences and inhibit binding of glutamate to receptors in the cell membranes in the brain’s cortex.8,9

Myrcene

Myrcene is the most abundant terpene found in cannabis strains grown within the US and Europe. It can also be found in hops, lemongrass, and thyme, and gives off an earthy aroma. This particular terpene has been found to fight inflammation, insomnia, and pain, and even cancer!10

Pain Relieving Properties:

Myrcene has been found to have general pain-relieving effects that are blocked by naloxone10,11—a compound that inhibits the pain-relieving properties of opioids.11 The fact that naloxone also blocks the function of this particular terpene suggests that myrcene acts in a similar way to opioids to relieve pain, without the addictive and tolerance building nature of these pharmaceuticals .10,11,17

The mechanism that is employed by myrcene to relieve pain has been increasingly studied over the past few decades, and it has been found that the process involves the TRPV1 receptor: a receptor that, when activated, sends signals to the brain regarding temperature & pain. Blocking this receptor decreases these signals that would result in you feeling a painful, burning sensation, which can decrease acute pain. However, long-term activation of this receptor causes desensitization to these messages and decreases chronic pain.12,13

Currently, doctors often prescribe a topical cream for chronic pain—Capsaicin—that also works through targeting the TRPV1 receptor.13,14 However, this initially causes a burning sensation at the application site through the short-term activation of the receptor in the pursuit of long-term desensitization; similar to menthol creams or other topical mediations that cause an uncomfortable burning or cooling sensation initially.13,14 When activated, TRPV1 causes the cell to undergo pore dilation to allow an influx of small charged molecules that activates the nerve cell.

Because myrcene activates this receptor as well, it is thought to work to relieve pain in the same way as Capsaicin. However, the effect of Myrcene is distinct from the Capsaicin12 and does not cause the same initial pain response. When Myrcene activates TRPV1, it does not cause the same degree of pore-dilation. Therefore, the neuron is not activated to send a signal to your brain of a painful burning sensation. Myrcene does, however, cause desensitization of the receptor over time, treating chronic pain without initial pain as a side effect!12,15

Sedating & Anticonvulsant Properties:

If you’ve ever experienced “couch-lock” after using cannabis–the feeling of being glued to the sofa, just wanting to watch movies–you’ve probably smoked (or vaped, or ate) a product with high concentrations of Myrcene10. This is because Myrcene creates a sedative effect through muscle relaxation, and it has also been found to prolong the sleeping time of barbiturate medications—making this particular terpene an excellent treatment for insomnia and other sleeping disorders.16

Along with muscle relaxation comes anticonvulsant properties. While high doses of medications like Diazepam (Valium) can be given for seizure disorders, essential oils high in Myrcene have been shown to decrease the frequency of convulsions and increase the chances of survival in laboratory animals.18 Also, when given in conjunction with Diazepam, it was found that the effects of the pharmaceuticals were actually enhanced by the presence of Myrcene, which suggests that the terpene works in a similar mechanism and could be used to lower the dosage of other anticonvulsant medications that may cause dependency.16,18

Cancer-Fighting Properties (Anti-Carcinogenic):

Surprisingly, Myrcene has been found to block cancer-causing (carcinogenic) effects of a particular mold that has been found to cause cancer and extensive liver damage: aflatoxin.10,19 A toxin released by this mold is known to cause genetic mutations that have been linked to cancer, and this particular terpene has been shown to inhibit these effects, thereby preventing tumor formation.19

Anti-Inflammatory Properties:

Myrcene is a proven anti-inflammatory agent that works by targeting a particular molecule in the bloodstream that causes an inflammatory response within your body. Prostaglandin E2 (PGE-2) promotes inflammation and has been found to worsen the symptoms of certain inflammatory diseases.21,22 Myrcene, like many over-the-counter non-steroidal anti-inflammatories (NSAIDs) medications such as ibuprofen, work to reduce inflammation by preventing the production of PGE-2 and other similar pro-inflammatory substances.20,21

Nitric oxide, which is another inflammatory compound produced in the body, has been found to contribute to osteoarthritis.10,23 Osteoarthritis is the most common form of arthritis that causes a patient’s bones and cartilage to wear down and degenerate over time. Myrcene can slow down the progress of the disease and stop the destruction of cartilage by preventing the formation of nitrous oxide.23

Alpha-Pinene

Anti-Inflammatory & Pain Relieving Properties:

A particular oil—Boswellia carterii— that has high levels of pinene was found to have anti-inflammatory and pain-relieving effects.25,26 One way in which this terpene works to decrease inflammation is through the inhibition of proinflammatory molecules such as COX-2.26,28 COX-2 is found in abnormally high levels in patients with Rheumatoid Arthritis and promotes the production of Prostaglandins (PG).27,28 By preventing the production of this COX-2– and, therefore, PG– pinene decreases chronic inflammation.

α-pinene has also been found to have specific anti-inflammatory properties through suppressing the production of mitogen-activated protein kinases (MAPKS) in macrophages.29 A macrophage is a specialized cell in the immune system that detects and destroys harmful substances like toxins, bacteria, or viruses.30 MAPKs are activated and released in the bloodstream by macrophages32 and are responsible for regulating pro-inflammatory molecules such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF- α).26,31,32 α-pinene has been proven to suppress the activation of MAPKs, thereby decreasing the presence of these pro-inflammatory molecules that tend to cause joint pain and deterioration.29,31

Similar to Myrcene, Pinene was found to topically reduce pain associated with the initial application of Capsaicin.33 Additionally, where Capsaicin was found to initially increase concentrations of COX-2—thereby temporarily increasing inflammation—a decrease in COX-2 was observed when the pain was treated with α-pinene. 33

Cognitive Protective Properties:

α-pinene has also been shown to improve focus, memory, and improve symptoms of dementia in Alzheimer’s patients. In Alzheimer’s disease, a specific neurotransmitter–Acetylcholine (ACh)– is usually found in lower than normal concentrations in the brain cortex and hippocampus (which is responsible for memory retention).26,34,36 A common treatment for Alzheimer’s disease is an Acetylcholinesterase (AChE) inhibitor– which blocks the function of the enzyme AChE, which breaks down ACh, causing the characteristic low levels of the neurotransmitter. 26,34,35

Scopolamine (SCO), a drug that is often used to test against Alzheimer’s disease treatments, actually increases the level of AchE in the cortex & hippocampus– so it can mimic Alzheimer’s disease in test subjects (in this case, mice).34,35 When tested in the presence of SCO, pinene was found to increase the expression of another particular enzyme (ChAT) that is responsible for speeding up the production of ACh, thereby increasing the concentration of the neurotransmitter in the cortex.26,34,36 Pinene was also found to improve memory by preventing low levels of ACh by inhibiting the expression of AChE, even when in the presence of SCO, which is known to cause low levels of ACh.

Pinene has also been shown to have neuroprotective properties through antioxidative properties. Oxygen reactive species (ROS) are molecules that contain oxygen and are highly reactive with other molecules within a cell.40 An imbalance in ROS can cause damage to DNA, RNA, and proteins and has been linked to neurodegenerative diseases like Alzheimer’s and Parkinson’s through something known as oxidative stress.40,41 Specific enzymatic and non-enzymatic antioxidants are known to mediate this imbalance and prevent cell damage and death. When hydrogen peroxide-based oxidative stress was induced in cells that had been treated previously with α- pinene, cell damage & death were prevented, and the expression of enzymatic antioxidants increased dramatically.41,42

Anti-Anxiety, Sedating & Anticonvulsant Properties:

α-pinene was also found to improve sleep quality by increasing the duration of non-rapid eye movement sleep (non-REM sleep) without decreasing the length of REM sleep and reduces the amount of time it takes to fall asleep.26 GABA is a neurotransmitter that is known to increase sleep and decrease wakefulness.37 Current medications that are used for sleep, such as benzodiazepines (Valium, Xanax), function by binding to certain GABA receptors to mimic the effect of the neurotransmitter.38 Pinene has been proven to bind to these same receptors and cause the same sedating effects.38 α-pinene has in fact been proven to be more effective at increasing the quality of sleep when compared to traditional medications like zolpidem.38

Pinene was also found to have anti-anxiety properties by increasing the concentration of a particular enzyme (tyrosine hydroxylase) that speeds up the production of dopamine.26,39 60 minutes after inhalation of α-pinene, the expression of tyrosine hydroxylase in the midbrain was dramatically increased—which would lead to an increase in the synthesis of dopamine, and, in turn, anxiety-relieving properties.39  

Additionally, pinene was shown to have anticonvulsant properties—decreasing the initiation time and duration of myoclonic and tonic-clonic seizures.26,42 It is believed that both pinene’s antioxidant properties and the fact that this terpene binds to GABA receptors that are known to have anti-epileptic properties give this terpene its anticonvulsant properties.38,42  

Anti-Bacterial & Anti-Parasitic Properties:

α-pinene was found to be as effective at fighting drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), when compared to the current treatments, such as vancomycin.26,43 This terpene was also found to have antimicrobial abilities against C. albicans, C. neoformans, and R. oryzae. When combined with traditional antibiotics, pinene was able to decrease the antibiotic dosage necessary to prevent cell damage and biofilm formation (this is also known as the minimum inhibitory concentration or MIC).43  

α-pinene was also found to modify antibiotic resistance in Campylobacter jejuni by decreasing the MIC of ciprofloxacin, erythromycin, and triclosan.26,44 This specific terpene also decreases the expression of an antibiotic efflux pump, which is one of the mechanisms that bacteria will use to pump antibiotics and antimicrobials out of the cells, thereby causing resistance. By decreasing the expression of this pump, pinene decreases the bacteria’s ability to pump out (efflux) antibiotics. Additionally, pinene was found to increase membrane permeability, allowing for a greater influx of antibiotics.44 (This is a research project I participated in that investigated the role of a specific efflux pump in antibiotic resistance if you would like to learn more about efflux pumps!)

This particular terpene has proven to be a promising treatment against certain parasitic diseases like Leishmaniasis and malaria.26, 45 Pinene was discovered to have anti-parasitic properties through modifying immune system activity; α-pinene actually increases the activation rate of macrophages, which are responsible for ridding the body of harmful toxins and organisms.26,45

Anti-Cancer Properties:

α-pinene has been proven to inhibit cancer cell growth in liver cancer up to 79.3%.26,46 Pinene causes an increase in the expression of particular genes or signals that are known to regulate and inhibit the cell cycle (p53, Chk2) and suppressing the expression of those that promote the cell cycle (cyclinB, CDK), as uncontrolled cell growth leads to tumors and metastasis.46,48 This terpene, overall, inhibits the transition from the growth phase of the cell cycle (G) to the division phase (mitotic or M).46,48

Pinene was also able to induce cell death by disrupting the mitochondrial membrane, production of ROS, increase caspase-3 and other apoptotic molecules, and causing DNA fragmentation.47 In mice with metastatic melanoma, treatment with α-pinene was shown to decrease the growth of lung tumors, indicating antimetastatic activity.47

Beta-Caryophyllene (BCP)

Beta-Caryophyllene (BCP) is the most common terpene found in cannabis extracts, but can also be found in hops, cloves, & rosemary; it is known for its black pepper profile.10 This particular terpene has strong anti-inflammatory properties and is a safe, non-toxic treatment for pain. It is also the main terpene that drug-sniffing dogs are trained to detect! 10

Pain Relieving, Anti-Nausea, & Anti-Inflammatory Properties:

BCP interacts with and activates a non-psychoactive cannabinoid receptor known as CB2 to decrease pain and inflammation.49,51 It is known that when CB2 is activated, the concentration of inflammatory molecules known to activate macrophages and other immune cells are reduced in the bloodstream.50,51,52 BCP has been proven to decrease neuropathic pain and pain related to chemotherapy through its interaction with CB2, and without building a tolerance to the treatment.52 This terpene is also shown to reduce and prevent liver damage resulting from chronic and binge alcohol use by decreasing the expression of E-Selecting and P-Selectin: two pro-inflammatory molecules that cause liver damage and, over time, liver disease.53 Decreasing this expression may help prevent long-term liver failure.

Anti-Anxiety & Anti-Depressant Properties:

BCP works to alleviate anxiety and depression through a different system than the benzodiazepine system. Without altering motor control and coordination, BCP may interact with the 5 HT receptor—a specific serotonin receptor—to induce anti-anxiety and anti-depressant effects54,56.

Additionally, the CB2 receptor that BCP is known to interact with can induce anti-anxiety and anti-depressant properties.55 The CB2 pathway is known to stabilize emotions and moods. In mice that were treated with BCP, symptoms of anxiety and depression subsided after this pathway was activated55,56.

Anti-Fungal & Cancer Fighting (Anti-Carcinogenic) Properties:

BCP is also shown to help alleviate symptoms of gastrointestinal diseases, such as irritable bowel disease.59 When rats were treated with BCP, the terpene inhibited damage to the mucosal membrane in the stomach and gastrointestinal system. Whereas typical non-steroidal anti-inflammatory medications may cause gastric mucosal damage, BCP acts as an anti-inflammatory agent to reduce disease activity without causing this damage.57,10

Currently, the bacteria that causes stomach ulcers—Heliobacter pylori—is beginning to evolve resistance to antibiotics, and new treatments are being investigated.58 In addition to inhibiting the gastric inflammation that is typical of ulcers, BCP actually displayed antibiotic properties through killing H. pylori, making it a promising prospect.58

Inflammatory bowel diseases (IBD) such as Chron’s and ulcerative colitis cause chronic inflammation in the gastrointestinal tract. Cannabinoid receptors CB1 and CB2, which are expressed in the human colon, can trigger anti-inflammatory responses.10,59 BCP has been previously proven to have a strong interaction with CB2, and, in colitis patients, treatment with the terpene was shown to decrease disease activity, colon damage, expression of pro-inflammatory molecules characteristic of IBD, and expression of factors known to contribute to colon cancer.59

Overall

Terpenes seem to have magnificent potential to be used as a treatment for a variety of diseases that can occur in a diverse array of bodily systems. While there is still much to be discovered in this field, the interactions on a cellular level that terpenes are known to carry out are promising!

References

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