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How Specific Terpenes Work on Pain, Inflammation, Anxiety and More

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How Specific Terpenes Work on Pain, Inflammation, Anxiety and More
AUTHORED BY: GENESTER WILSON-KING, MD FACOG & SARAH RUSSO

How Specific Terpenes Work on Pain, Inflammation, Anxiety, and More

Scent is a strong sense which also evokes powerful abilities to help us heal. We’ve given an overview of terpenes and what they can do. Now we can delve into details on how they may work in specific situations. In general, terpenes serve three primary benefits: 

  1. Fight pain
  2. Reduce systemic inflammation
  3. Lower anxiety

Depending on the cited terpene, a plethora of other primary and secondary benefits exist, including providing antifungal and antibacterial properties. [1] Here’s a general overview of the principle ways terpenes interact in the body:

  1. Act on receptors and neurotransmitters
  2. Can act as serotonin uptake inhibitors (similar to antidepressants like Prozac)
  3. Can enhance norepinephrine activity (comparable to antidepressants like Elavil)
  4. Increase dopamine activity
  5. Augment GABA (an inhibitory neurotransmitter that counters glutamate, an excitatory neurotransmitter) [2]

Now let’s get specific. 

Terpenes for Pain Management

More than 50 million American adults suffer from chronic pain. Chronic pain is defined as pain that persists long after healing is expected, or for a period of six months and is the result of an ongoing medical condition or damage to the body. [3] Pain impacts quality of life. The influence of chronic pain on patients varies from minor restrictions to complete loss of independence.[3]

The terpenes below have been shown to assist in pain relief.  They are generally most effective in conjunction with other terpenes, cannabinoids, flavonoids, other plant essential oils and substances.

Linalool commonly appears in perfumes and is naturally found in mint, citrus, and lavender.  It has demonstrated anti-inflammatory properties, and has the potential to treat inflammatory pain. More specifically, linalool: 
    • Reduces the excitability of spinal cord cells that transmit pain signals to the brain.[4]
    • Targets acetylcholine, a brain chemical responsible for muscle movement.
    • Increases the brain’s levels of adenosine (a central nervous system depressant), thereby aiding in pain relief and sleep. [5]
    • Lavender aromatherapy may decrease the demand for opioids immediately after surgery. Linalool inhalation used in conjunction with morphine was found to decrease morphine use post operatively. [6]

    Myrcene (Beta-myrcene) is the most prevalent terpene in cannabis chemovars in the United States and Europe.  Myrcene is found in hops, lemongrass, bay leaves, eucalyptus, wild thyme and is responsible for the spicy fragrance in beer.  Its aroma is musky, earthy, and reminiscent of cloves. It has demonstrated analgesic (pain relieving) properties: [1] 

  1. Myrcene has been shown to be blocked by naloxone, suggesting an opioid-like mechanism of action. [7] 
  2. Myrcene causes TRPV1 activation. TRPV1 belongs to a group of receptor channels that are targets for treating pain. [8] 
  3. Alpha-Pinene is the most widely distributed terpene in nature. Pinene is responsible for the distinctive aromas of pine and fir. There are two structural isomers of pinene that occur naturally: α-pinene and β-pinene. Both forms are important physiologically in both plants and animals. 9,10 The pain relieving properties of pinene have been demonstrated in preclinical studies (animal or cell cultures only):

    • A Frankincense (Boswellia carterii) oil dominant in pinene was found to have higher anti-inflammatory and anti-analgesic effects than that of water extracts in a mouse model. [11]
    • Pinene has been shown to alleviate tooth pain in mice. It also decreased inflammation via GABA and μ-opioid receptors (responsible for modulating inflammatory and pain response in the body, among other things). [12] 

    Limonene is frequently found in nature, especially in citrus rinds, although not as common in cannabis as other terpenes. Cannabis predominant in this terpene is often described as having a fruity flavor and an uplifting experience. [1] Several preclinical studies showed that limonene: 

    • When inhaled, limonene reduced pain intensity, nausea, and vomiting in pregnant women. [13] 
    • Reduced sensitivity and widespread bone and muscle pain in mice. [1]

    Beta-caryophyllene is the most common terpenoid in cannabis extracts. Beta-Caryophyllene has the distinctive flavor that gives black pepper its kick. You can also find it in hops, cloves, and rosemary. It was the first non-cannabinoid compound found to activate cannabinoid receptors. It works as a powerhouse to reduce inflammation and pain. [14] 

    • Beta caryophyllene binds to CB2 receptors but not CB1 receptors. (See What is the Endocannabinoid System? for more information). Substances targeting CB2 receptors have been proposed as therapies for the treatment or management of acute, chronic inflammatory, and neuropathic pain. The selective activation of CB2 may be considered part of BCPs analgesic properties. In addition, the activation of CB2 receptors does not produce psychotropic effects. [1,15,16]
    • Beta-caryophyllene oxide, a plant compound resulting from the oxidation of beta-caryophyllene, does not bind to CB1 or CB2 receptors. When one says beta caryophyllene, one is referring to the family of compounds including trans-caryophyllene, iso-caryophyllene, alpha-caryophyllene (alpha humulene) and beta caryophyllene oxide. [17]
    • Beta caryophyllene oxide is what the drug sniffing dogs are trained to find when searching for cannabis. [1]

    Alpha Humulene is also known as alpha caryophyllene. It is found in hops and is what gives the plant its bitter taste. Humulene’s aroma is subtle, with earthy, woody tones with a little bit of spiciness. It can be found in hops, black pepper, cloves, cannabis, rosemary, basil, cinnamon.17 Alpha Humulene has been found to reduce inflammatory pain when applied topically. [18] 

    Terpenes for Sleep

    A lack of sleep influences everyday living. Most people do not function well on less than seven hours per night. Sixty-eight percent (68%) struggle with sleep at least once per week. Forty-eight percent (48%) of people using over-the- counter sleep aids take them several times per week. Insufficient sleep interferes with concentration and increases the risk of chronic illness such as cardiovascular disease, hypertension, and diabetes. It also boosts the likelihood of obesity and depression. [19]

    The terpenes below have been shown to assist with sleep. Terpenes in isolation are not as effective as when used in conjunction with other whole plant compounds. In fact, most of the studies use terpenes along with other components and hardly ever use them in isolation. 

    Myrcene is believed to be responsible for the sedative effects in many of the common preparations in cannabis commerce. Myrcene creates the “couch-lock” effect commonly attributed to today’s cannabis chemovars.[1] 

    • A study in 2002 supported “the sedative effect of myrcene and its effectiveness for those suffering with anxiety, insomnia, and other sleep disorders”. 
    • Myrcene has been shown to increase the sleeping time of barbiturate medications. 
    • The duration of its analgesic effect exceeds that of morphine (four hours) and was weakened by Narcan administration. This supports an opioid-related mechanism of action.[20]

    Linalool has been used for centuries as a sleep aid. 

    • Linalool lessens the anxious emotions provoked by pure THC, thus making it potentially helpful in the treatment of both psychosis and anxiety. 
    • This terpene was found to have a sedating effect upon inhalation in a mouse study. [1,21]
    • Linalool elevates the brain levels of adenosine, a central nervous system depressant that is notably blocked by caffeine. When adenosine levels are elevated, it causes drowsiness. [22]

    Beta-caryophyllene may be beneficial for insomnia because of its relaxing properties. A pharmacology study demonstrated that a multichannel essential oil containing caryophyllene was found to be a potential treatment for insomnia. [23]

    Terpinolene is found in lilacs, nutmeg, cumin, and apples. It is one of cannabis’ least common terpenes. Scientific investigation has established that it has sedating effects, especially when inhaled. Terpinolene was found to be a potent suppressor of the central nervous system. [24]

    Terpenes for Focus and Memory

    Focus, memory and concentration: you can’t have one without the others! Your focus is the length of time you can pay attention before you become bored or overloaded. It varies from person to person and the type of activity. Concentration is the ability to focus the attention on a single thought, subject, or object while ignoring distractions. Memory consists of short-term and long-term memory. Memory loss can be temporary or permanent depending on the cause. Disease, pharmaceuticals or other substances, or aging can all have effects on memory. [25] 

    The following terpenes have been shown to assist with focus, memory, and concentration.  As in other situations, terpenes work best in conjunction with other compounds in the cannabis plant.

    Alpha pinene has been shown to improve cognitive function and to increase focus and alertness. [26] Specific studies have demonstrated:

    • This terpene may increase cognitive function due to its inhibition of the neurotransmitter acetylcholinesterase. This action has been shown to improve learning and memory impairment in preclinical studies. [27]
    • A mouse study in 2017 showed alpha pinene having promising effects for those suffering from memory loss and other neurodegenerative diseases. Certainly, more research is needed. [28]

    Limonene – Poor blood flow to the brain over time is a leading cause of cognitive decline and memory loss. Preclinical studies have shown that limonene can slow this process. Preclinical studies do not always translate to human subjects. 

    • D-limonene substantially slowed cognitive decline and improved behavioral function in an animal model. [29] 

    Linalool - Alzheimer's is a difficult to treat condition which currently has no cure. A preclinical study points to linalool as a potential treatment, since it can reduce the brain plaque responsible for causing cognitive decline. [30]

    Anti-Inflammatory Terpenes

    Inflammation is the body's attempt at self-protection. It is part of the body's immune response and removes harmful stimuli to begin the healing process. There are two kinds of inflammation. 

    Acute inflammation starts rapidly and quickly becomes severe. This reaction is beneficial and helps to heal the injured area. However, acute inflammation is supposed to cease at some point.  When it doesn’t, it becomes chronic inflammation.

    Chronic inflammation is long-term inflammation, which can last for several months and even years. Chronic inflammation can eventually lead to several ongoing conditions such as rheumatoid arthritis, osteoarthritis, organ dysfunction, and various autoimmune diseases. The reason acute inflammation leads to chronic inflammation is currently unknown. 

    Inflammatory pain is due to tissue damage and inflammation (e.g., postoperative pain, trauma, arthritis). [31] With inflammation being the root cause of many ailments, further investigation on anti-inflammatory agents is of scientific interest. The following terpenes have been shown to have anti-inflammatory properties in various studies. In general, they are mainly effective in conjunction with other terpenes, cannabinoids, flavonoids, and other plant compounds.  

    Limonene 

    • Preclinical studies show limonene reduced inflammation scores and levels of tumor necrosis factor (a proinflammatory marker) in rat colitis. 
    • In a human clinical study, it decreased a specific inflammatory marker in elderly participants receiving a supplement that was 95% limonene for 56 days. [32] 

    Myrcene inhibits the production of certain inflammatory markers. Here are the studies with supporting evidence: 

    • Myrcene is anti-inflammatory via prostaglandin E2 (PGE-2), a proinflammatory substance. [33] 
    • It inhibits nitrous oxide production by inflammatory cells. Nitrous oxide is another pro-inflammatory substance. 
    • The terpene was found to lower a specific inflammatory marker in the blood for osteoarthritis by 78%. [34]

    Linalool

    • One study indicated that linalool and linalool acetate may play a major role in anti-inflammatory activity when they are dominant in essential oils. This suggests that these terpenes are potential anti-inflammatory agents. [35] 

    Beta-Caryophyllene (BCP)

    • BCP may act in synergy with CBD to impart anti-inflammatory benefits. 
    • BCP has been found to synergize with THC to relieve itching and protect stomach cells from damage. 
    • BCP was shown to modulate numerous molecular targets by altering their gene expression, signaling pathways, or via direct interaction. It has demonstrated therapeutic promise as a neuroprotective agent for neuropathic pain and metabolic diseases. [36]

    Beta-ocimene is a pheromone important for the social regulation of honeybee colonies. The cannabis industry has taken advantage of this attraction by creating “cannabis honey”. This feature was proposed by law enforcement to train honey bees to smell ocimene in cannabis, with the intention of potentially replacing drug sniffer dogs. Of course that never occurred. This terpene has been associated with anticonvulsant, antifungal, and antitumor activity in essential oil combinations. [1] 

    • Essentials oil rich in ocimene may have the potential to suppress the production of several different inflammatory substances produced by the immune system (when used in combination with other essential oils). [37]

    Alpha-Humulene 

    • Alpha-Humulene has exhibited pronounced anti-inflammatory properties in animal models. In one study using an essential oil extracted from Cordia verbenacea, alpha-humulene decreased inflammation both orally and topically. [38]
    • Another study found that alpha-humulene exhibited marked anti-inflammatory properties in a mouse model of allergic inflammation in the lungs, providing an antihistamine response. [39] This suggests that alpha-humulene may have therapeutic potential for allergies and asthma. Further research is needed. 

    Pinene– Essential oils from various plants (such as frankincense) rich in alpha- and beta-pinene were found to decrease inflammation in various animal models. It appears to do this via the inhibition of COX enzymes, which are responsible for the production of pro-inflammatory compounds within the body (prostaglandins). [11]

    Anticonvulsant Terpenes

    An anticonvulsant is a substance used to prevent or reduce the severity of epileptic seizures or other convulsions. The following terpenes have been investigated as anticonvulsants in various studies. As previously mentioned, terpenes are generally most effective when used in combination with other botanical components. 

    Linalool 

    • Linalool demonstrated anticonvulsant activity by blocking receptors for glutamate, a chemical in the brain. Glutamate is elevated in seizure disorders. Significant elevations in glutamate initiate the death of neurons. [40]
    • In a preclinical study, an essential oil of Basil (O. basilicum) including linalool blocked the glutamate receptors and reduced seizures. [41,42]
    • Recent reports support the possibility that small concentrations of linalool found in certain cannabis chemovars may exert anticonvulsant benefits in human patients. [43]  

    Beta-ocimene in essential oils is associated with anticonvulsant activity. The effects of cannabinoid and ocimene co-administration remain unclear but warrant further attention. [1] 

    Terpenes for Anxiety and Stress

    Stress affects virtually everyone. Forty-four percent (44%) of people in the United States feel more stressed than they did five years ago. One in five people in the country experience extreme stress with symptoms of shaking, heart palpitations, and depression. In addition, stress is the basic cause of 60% of illnesses and disease. Three out of four physician office visits are for stress related ailments, costing the United States $300 billion every year. [44]

    The following terpenes have been shown to be helpful with anxiety and stress relief in various studies. They are generally most effective in conjunction with other terpenes, cannabinoids, flavonoids, additional plant essential substances.

    Linalool – A dab of lavender oil on the wrist can reduce anxiety because it is rich in linalool. 

  4. Linalool and alpha pinene were combined in an essential oil from Litsea glaucescens (Mexican Bay Leaf) and showed antidepressant-like activity at high doses.[45]
  5. Limonene is known to produce a feeling of well-being.

    • Experiments in mice confirm limonene is strongly anxiolytic (anti anxiety) and boosts serotonin levels— similar to what some antidepressants do.[1] 
    • Limonene has been found to increase the permeability of cell membranes, or how easily substances pass into and out of the cell wall. This process may contribute to its anxiolytic effect. [46]
    • One of limonene's significant properties is reducing anxiety that some people experience when they’ve taken too much THC. [47]

    Alpha Pinene 

    • Inhalation of α-pinene in mice produced an anxiolytic effect.[48] 
    • Anti-anxiety effects were maintained in mice that underwent chronic inhalation (90 minutes per day) of alpha pinene for over five days. [49]

    Myrcene is a recognized sedative as part of hops preparations used to aid sleep in Germany. [34] 

    Beta-caryophyllene 

    • The anxiolytic effects of this terpene may or may not be mediated through 5HT1A (serotonin) receptors similar to some antidepressant and antianxiety medications. An increase in serotonin levels has a stress relieving effect.[50]

    Since anxiety and stress generally coexist with depression, terpenes that act as antidepressants are also worth noting.

    Limonene 

    • Human clinical work supports the use of limonene for depression. A study in Japan demonstrated that depressed patients exposed to citrus scent experienced normalization of Hamilton Depression Scores (HADS). This resulted in a discontinuation of antidepressants in nine out of 12 hospitalized patients. [51]

    Alpha-pinene 

    • Studies have shown that beta-pinene acts as a mood stabilizer. [11] 

    Linalool 

    • Possesses antidepressant and antianxiety properties and is also said to make antidepressant medications (SSRIs) more effective. This is primarily anecdotal information. [52]

    Antimicrobial Terpenes 

    An antimicrobial is a compound that targets antibacterial, antifungal and antiviral pathogens. The antimicrobial activity of various terpenes have been reported in hundreds of studies. However, most of the studies do not analyze them independently. Essential oils, and the terpenes they are composed of, consist of a complex mixture of compounds (usually from 20 to 60) at different concentrations.[53] The following terpenes have been shown to have antimicrobial activity in various studies. They are generally most effective when used in conjunction with other plant compounds. 

    Alpha-Pinene (α-Pinene)

    • An alpha-pinene dominant essential oil acted as an antibiotic that was equally effective as vancomycin against MRSA and other drug resistant bacteria. [54] This is particularly significant as vancomycin is the drug of choice for treating most MRSA infections. 
    • Efficacy was noted for α-pinene for bacterial and fungal diseases such as Cryptococcus neoformans and Candida albicans biofilms. [55] 
    • α-Pinene dramatically increased antibiotic efficacy of three prescription antibiotic medications against Campylobacter, a gastrointestinal pathogen.[56]  
    • The terpene was discovered to be beneficial against a specific form of leishmaniasis, a parasitic disease that is found in the tropics, subtropics, and southern Europe. [57] 
    • α-Pinene demonstrated larvicidal activity against one of the strains of mosquitoes that causes malaria. [58]

    Beta-Pinene is commonly encountered in conjunction with alpha-pinene.  

    • The terpene has demonstrated equal antibiotic efficacy as α-pinene above against S. aureus (MRSA), and C. neoformans and C. albicans bio- films. [55] C. neoformans and C. albicans are the most common causes of yeast infections. 

    Ocimene - A study published in 2008 analyzed the antiviral traits of essential oils, where ocimene was the primary ingredient.  Other commonly found cannabis terpenes such as pinene and myrcene were also present, which showed promise in the treatment of the SARS virus.[59]

    Limonene demonstrated a potent antifungal effect against T. rubrum in a 2009 study. T. rubrum is a fungus that generally causes athlete’s foot, ringworm, “jock itch”, and nail fungus. [60,61]

    Caryophyllene Oxide acted as an antifungal in onychomycosis (nail fungus) comparable to ciclopiroxolamine and sulconazole (both known antifungal agents).  An 8% solution of terpene led to an onchomycosis cure in 15 days.[1]

    Terpenes that Demonstrate Anticancer Activity

    Scientific investigation has examined the anticancer cell activity of cannabis terpenes. In general, most of them are mainly effective in combination with other plant components. These are preclinical studies and shouldn’t be used in lieu of standardized cancer treatments and protocols.

    Limonene has demonstrated chemotherapeutic properties by inducing cancer cell death in breast cancer as well as others. There are ongoing trials on limonene for breast cancer.

    • High doses of limonene were used in a Phase II randomized clinical trial.[62] Limonene had a strong safety profile but demonstrated less marked efficacy than anticipated. 
    • A 2013 human study in women with preoperative breast cancer found that oral ingestion of two grams of D-limonene a day led to cell-cycle arrest and lowered cancer proliferation. [63] 

    Alpha pinene 

    • Ongoing exposure to pinene led to decreased melanoma growth in mice.[64]
    • There was an observed synergistic benefit with α-pinene in combination with paclitaxel on lung carcinoma cells with evidence of cancer cell death (apoptosis).[65] Paclitaxel is a commonly used chemotherapeutic agent. 
    • α-Pinene inhibited human hepatoma (liver) cell growth by 79.3%. [66]

    Myrcene blocks carcinogenic effects of aflatoxin (a toxic compound produced by a mold that can cause liver damage and cancer).[67]

    Linalool significantly weakens cigarette smoke-induced infiltration of inflammatory cells. [68]

    Humulene has been found to hinder tumor growth by encouraging the production of reactive oxygen species, which are chemicals that can help combat cancer cells. [69,70]

    Miscellaneous Terpene Properties

    There are a few other interesting properties of terpenes. 

    • Alpha Pinene acts as a bronchodilator (meaning opening air passages) and may help support healthy lung function.[1]
    • Beta-caryophyllene, through a CB2 receptor dependent pathway, may be an excellent therapeutic agent to prevent nephrotoxicity (poisonous effect on the kidneys) from the chemotherapeutic drug cisplatin.1,71 BCP was also found to be gastric cytoprotective in a preclinical study.[72]
    • Humulene is very common in North Amercian chemovars.  It has been found to inhibit fruitfly mating.  It also protected astrocytes (cells of the central nervous system) from hydrogen peroxide induced cell death by 50%.[1]

    All in All

    Terpenes are unique substances that add to the therapeutic benefits of plants. They are responsible for their scent but also benefit their evolution. And luckily for us, they also provide a diversity of medicinal attributes along the way.  

    It is clear that the synergy of the terpene alliance makes them more effective together than apart. They seem to work best with other substances in the plant such as cannabinoids, flavonoids, and Omega 3 fatty acids, etc. Terpenes can exhibit different properties or effects depending on how they are combined. 

    The best way to get the full benefit of plant medicine is to evoke all your senses, especially smell. Your nose can guide much of your experience. Despite ongoing scientific advancements, the aromatic signatures of nature still have us mystified. Research still has a long way to go to elucidate the “magic” of terpenes. 

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    Dr. Genester Wilson King Headshot

    Genester Wilson-King, MD FACOG is a Board-Certified Obstetrician and gynecologist with over 25 years of clinical experience providing compassionate and research-driven care to patients. After years of working as a full-service OB/GYN, she founded Victory Rejuvenation Center (VRC), a private holistic and preventive medicine practice that provides life-transforming management modalities and customized medicines to patients. She is the Medical Advisor to Treadwell Farms.

    As the Medical Director of VRC, Dr. Wilson-King provides services that help her patients age gracefully and achieve holistic well-being. She focuses on plant-based medicine, integrated health, nutrition, supplements, cannabis education, and hormone balance. 

    Dr. Wilson-King is Co-Vice President of the Society of Cannabis Clinicians (SCC). The SCC is an educational and scientific society of physicians and other professionals dedicated to the promotion, protection and support of cannabis for medical use.  Dr. Wilson-King co-authored the Best Practices Guidelines for Cannabis Use in Pregnancy and Breastfeeding, and Cannabis Use in Women – Special Considerations (in progress).  She is also on the Board of the Doctors For Cannabis Regulation (DFCR), the first and only national physicians’ association dedicated to the legalization and regulation of cannabis for adults. Advancing the DFCR’s commitment to addressing the disproportionate criminalization of cannabis use among communities of color and the nation’s poor, she regularly provides expert opinions for legal cases involving cannabis.

    Dr. Wilson-King is a nationally recognized advocate, clinician, and educator for cannabis and hormone and wellness therapies.  She presents on cannabis use in obstetrics and gynecology, hormone therapy for PMS, various stages of menopause, and for applications in nutrition.
     

    Sarah Russo Headshot

    Sarah Russo is a longtime plant enthusiast and globetrotter. She got her degree in environmental studies and social justice, with a focus on plant medicine from the Evergreen State College. She is a freelance writer, consultant, and project manager with over 13 years of experience in the cannabis and herbal medicine space. Her main objectives are fighting for the right to use plants, implementing social justice approaches in the cannabis industry, as well as encouraging sustainable agricultural practices. She is currently based on an island in the Mediterranean. Sarah is a content creator for Treadwell Farms. 

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