Terpenes

Terpenes – An Overview

Terpenes are a family of organic compounds obtained mainly from plants and trees, such as cannabis, tea, pine, lavender, thyme and citrus fruits like lemon. Around the world, there have been around 30,000 different terpenes identified in nature.

 

Cannabis is very aromatic, with different strains having their unique scents. Some people find the smell of cannabis unpleasant while others find it very calming and enjoyable; some strains smell fruity and sweet while others smell like pine, lavender, earthy or pungent. The components responsible for the unique aromas and flavors of different cannabis strains are terpenes, aromatic molecules secreted inside the tiny resin glands of cannabis flowers. But there is more to terpenes than their scent.

 

Terpenes are also believed to have a wide range of medical effects although research remains inadequate to identify definitive clinical benefits at this time. There are at least 80-100 terpenes found in cannabis and the combination of terpenes and cannabinoids are responsible for the therapeutic effects of cannabis. For more information about terpenes, see below.

 

Links to other Pertinent Educational Pages:

 

Terpenes:

Terpenes – An Overview

 

Terpenes Therapeutic Benefits:

 

Individual Terpenes:

 

 

The medical information on this site is provided as a resource for information only, and is not to be used or relied upon for any diagnostic or treatment purposes and is not intended to create any patient-physician relationship.  Readers are advised to seek professional guidance regarding the diagnosis and treatment of their medical concerns.

 

 

Key to Links:

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  • Red text – another page on this website
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Definitions and Terms Related to Pain

 

 

Terpenes

Terpenes are the most abundant class of naturally occurring small molecules by mass on the planet, with over twenty-five thousand known terpenes. They are not only present in plants, but have  roles in most life forms on Earth including animals, fungi, marine organisms, insects, protozoa, and bacteria. For example, cholesterols are terpenes that are fundamental for cell membrane structure, carotenoids are critical in plant photosynthesis, retinal is a terpene found in the eye that plays a role in vision, while another terpene, co-enzyme Q, is for cells to provide energy.

The extraction of oils from leaves, flowers, fruit and roots of plants has been used medicinally for various ailments for thousands of years, since ancient civilizations. Attention is now upon the terpenes found in marijuana to explain the therapeutic benefits of the plant.

 

Terpenes  in Marijuana

More than 540 chemicals, including 18 different chemical classes, more than 100 different cannabinoids (including THC and CBD) and more than 400 terpenes have been identified in marijuana plants (cannabis). In addition, a group of compounds called flavonoids – about 20 of them – have also been identified in cannabis. Flavonoids, one of the largest nutrient families known, are a group of plant metabolites thought to provide health benefits through cell signalling pathways and antioxidant effects. It is believed that the therapeutic benefits attributed to cannabis are derived from all of these families of compounds. This page focuses on terpenes.

 

What are Terpenes (or Terpenoids)?

Terpenes are fragrant essential oils manufactured by many different types of plants and herbs, including cannabis. Terpenes contain only hydrocarbons while terpenoids are oxygen-containing terpenes. Terpenes (and terpenoids) are organic chemicals produced by most plants, as well as some animals such as swallowtail butterflies and termites. Terpenes are volatile aromatic molecules, meaning they evaporate easily, and are some of the primary components of plant resins and flowers, providing flavor and fragrance to fruits and spices commonly found in a normal diet. Terpenes, not cannabinoids, are responsible for the aroma of cannabis and are the source of the aromas, flavors, and other characteristics that help distinguish different cannabis strains.

The total terpene concentration in cannabisflowers ( inflorescences) was commonly in the 1% range, however, due to selective breeding over the last couple of decateds, this concentration has risen to about 3-4% in some inflorescences, reaching terpene-cannabinoid ratios of up to about 1:10.

Terpenes are built up from building blocks called isoprenes, molecules that consists of five carbon atoms attached to eight hydrogen atoms (C5H8) . Terpenes are classified according to the number of pairs of isoprenes in the individual terpene – mono, sesqui, di etc. composing either 10- carbon monoterpenes, 15-carbon sesquiterpenes or 20- carbon diterpenes, respectively. These three groups (mono-, di-, and sesqui-terpenes) are the most abundant in cannabis.

See: Types of Terpenes and Terpenoids

 

The terms terpene and terpenoid are often used interchangeably but these terms do have different meanings. The main difference between terpenes and terpenoids is that terpenes are hydrocarbons (meaning the only elements present are carbon and hydrogen); whereas, terpenoids are the oxygenated derivatives of terpenes. Terpenoids are relatively more volatile and have a higher susceptibility to degradation than terpenes by oxidation (drying and curing the flowers). The term “terpene” will be used here but recognize some “terpenes” described here may actually be terpenoids. The most commonly studied terpenes found in cannabis plants include alpha-pinene, myrcene, beta-caryophyllene, caryophyllene oxide, linalool, limonene, nerolidol and phytol.

 

Terpenes have been proposed to exert therapeutic effects, especially in combination with the cannabinoids. They are quite potent, and have been shown to affect human behavior when inhaled from ambient air at serum levels less than 10 ng/mL Terpenes that occur in plants, however, are often found in very trace amounts. Terpenes may only compose the weight of 1-2% of dried plant matter and terpenes account for less than 1% in most cannabis plants in which the monoterpenes usually predominate (limonene, myrcene and pinene).

 

Trichomes, the glands that produce resin in a cannabis plant, contain the majority of cannabinoids and terpenes found in cannabis. Terpenes comprise about 10% of trichome content by weight and are a significant component of cannabis resin. Terpene concentrations >500 ppm are of pharmacological interest, but in general, only terpene components in concentrations above 0.05% of a cannabis plant are considered potentially pharmacological active.

 

What do Terpenes do?

In general, of the 400 terpenes known in cannabis, very few have been examined at the functional level. Research evidence is convincing that the medical benefits of cannabis cannot be achieved by simple isolates of the cannabinoids THC and CBD. The different therapeutic benefits that vary between different marijuana strains cannot be explained by their THC and/or CBD content alone. Evidence shows  that non-cannabinoid marijuana plant components, including terpenes modulate the intoxicating effects of THC and the clinical effects of both THC and CBD.

 

Each terpene may have unique therapeutic effects. For example, some scents promote sleep: lavender oil, which contains the terpene linalool, improves sleep efficiency, increased total sleep time, elevated vigor the following morning, and promotes sleep in patients with insomnia. Terpenes may also contribute significantly to the synergistic (“entourage”) effects of cannabis-based products. 

 

The “entourage” effect is a proposed synergistic pharmacologic effect created by the combination of the different constituents in cannabis, especially with different cannabinoids and terpenes.  Different mechanisms of synergy have been proposed: (i) multiple effects on different targets; (ii) pharmacokinetic effects such as improved solubility or bioavailability; and (iii) modulation of adverse effects.

 

The synergy of cannabinoid-terpene interactions contribute to the medical benefits (and side effects) of cannabis with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer and infections. Terpenes are pharmacologically versatile: they are lipophilic, interact with cell membranes, neuronal and muscle ion channels, neurotransmitter receptors, G-protein coupled (odorant) receptors, second messenger systems and enzymes. 

 

Terpenes may also increase the permeability of the blood-brain barrier, allowing greater access of substances in the blood to enter the brain. It has recently been shown that most terpenes do not synergistically act directly on cannabinoid receptors (CB1 or CB2) in the body as was once proposed but may still modulate their activity.It is believed that some terpenes may increase pain benefits of THC) and reduce the anxiety side effects of THC.

 

Other receptors thought to be influenced by terpenes include transient receptor potential ankyrin 1 (TRPA1), transient receptor potential vanilloid 1 (TRPV1) and peroxisome proliferator-activated receptor (PPAR) receptors.  The majority of the anti-inflammatory effects of terpenes and terpenoids has been shown to be mediated by a decrease in the levels of pro-inflammatory mediators, such as nitrous oxide (NO), interleukins, TNF-α, and PGE2.

 

 

How/Where Terpenes Work

Because terpenes are volatile (evaporate easily) and they are aromatic (detected by the sense of smell), they  act through the olfactory system (the bodily structures that serve the sense of smell). The olfactory system consists of the nose and the nasal cavities which support the olfactory mucous membrane for the perception of smell. The olfactory system that serves the perception of smell includes the olfactory nerve receptors that detect aromatic compounds.

 

While olfactory nerve receptors dominate the olfactory system, they are also found in non-olfactory tissues as well, including the skin, the gut (gastrointestinal system),  the heart and kidneys. These olfactory receptors are not involved in sensing odors but are involved in chemical reactions, such as adjusting blood pressure or stimulating secretion of hormones and enzymes. Thus, olfactory receptors can be involved when essential oils are topically applied and when they are ingested.

 

In addition, there are non-olfactory receptors in the skin and the gastrointestinal system that are also activated by odorous chemical compounds including terpenes. Thus, there are three major routes of intake or application of terpenes: the olfactory system, the skin, and the gastrointestinal system.

 

Historically, essential oils (compounds extracted from plants that capture the plant’s scent and flavor, or “essence” including terpenes) have been used therapeutically for centuries. Essential oils are obtained through distillation (via steam and/or water) or mechanical methods, such as cold pressing and contain terpenes and other volatile compounds present in the plant.

 

While terpenes can be isolated and may be available as individual products, they are generally available as components of essential oils extracted from specific plants and herbs. Therefore the therapeutic application of terpenes are most often based on use of essential oils from specific sources known to be rich in the desired terpenes. For example, the terpene linalool is most often used therapeutically through the use of extracts from cannabis or hemp, lavender or bergamot.

 

In turn, essential oils and terpenes may be used therapeutically by inhaling their vaporized forms, applying topically to the skin or ingesting orally. As one might expect, the therapeutic benefit may vary depending on the route of use. For example, for some people linalool may be more effective for anxiety when vaporized and inhaled vs oral ingestion while the reverse may be true for others. Caryophyllene may be more effective for cold desensitization when applied topically compared to when vaporized and inhaled or ingested orally.

 

Level of Evidence

Research on terpenes is mainly pre-clinical, consisting mostly of animal studies and lab (in vitro) studies. The proposed benefits of the individual terpenes described below have not, in most cases, been backed up with quality human studies. That being said, lack of evidence does not necessarily equate to lack of benefit. In the case of therapeutic benefits achieved with marijuana, it is generally accepted that terpenes play a significant role but studies are still lacking to further understand their specifics. The information presented here represents early evidence and theoretical benefits only.

 

Summary of Evidence

While much remains to be learned, in summary the four terpenes limonene, myrcene, pinene and β-caryophyllene are probably the most important clinically, possibly along with humulene.  ∝-pinene inhibits the activity of acetylcholinesterase in the brain, thus potentially minimizing the cognitive dysfunction caused by THC. Limonene elevates serotonin and dopamine levels, enhancing the anxiolytic, anti-inflammatory, and sedative effects of CBD. β-caryophyllene interacts with the CB2 cannabinoid receptors and is responsible for the. analgesic anti-inflammatory properties of cannabis as well as providing anxiolytic, antioxidant and neuro-protective effects. Humulene is proposed to have strong anti-inflammatory properties comparable to dexamethasone systemically and topically, as well as to have analgesic properties.  There are also anecdotal reports that it causes appetite suppression and weight loss.

A 2020 study found no evidence that the terpenoids tested (a-pinene, b-pinene, b-caryophyllene, linalool, limonene, myrcene or a-humulene) activate TRPA1 and TRPV1 channels or modulate their activation by THC and other cannabis-related agonists, including endocannabinoids.

 

 

Cannabis Strains

Due to a lack of research that evaluates terpenes directly for their therapeutic benefits, one means of assessing their benefits is to evaluate different Cannabis cultivars, or strains, for their peculiar therapeutic effects. Cannabis sativa strains are commonly described as energetic, uplifting, creative, euphoric, spacey and better for daytime use. Cannabis indica strains are commonly described as relaxing, calming, and sedating with full body effects and better for nightime use. These effects are not purely due to CBD:THC ratios as there are no significant differences in CBD:THC ratios between sativa and indica strains. These different subjective effects are most likely due to varying amounts and ratios of cannabinoids, terpenes and, probably, additional phytochemicals.

 

Furthermore, due to the explosive market for marijuana there has been a huge flooding of the marijuana market with different strains, all with imaginative and mysterious names that offer no information as to their specific and peculiar benefits. Complicating this is the fact that there may be no consistency of constituent amounts or ratios from one batch of a strain to another, despite their same name. In addition, different people are likely to respond differently to the same cannabis constituents at different times and, still differently than another person’s response to the same constituents.

 

Despite these obvious, and perhaps overwhelming limitations, one may still assess different cannabis strains for their purported benefits and evaluate the breakdowns of their particular chemical constituents to determine if they might allow for predicting specific therapeutic benefits based on common constituents found in different cannabis strains that are known for their specific therapeutic benefits.  A 2017 study evaluated a number of high THC cannabis strains or “chemovars,” based on their terpene content, describing 5 major group characteristics:

 

  1. Terpinolene dominant
  2. β-Caryophyllene dominant
  3. Limonene/myrcene dominant
  4. Limonene/myrcene/b-caryophyllene dominant,
  5. a-bisabolol/Myrcene dominant

 

Further study is required to determine how these groupings may correlate with therapeutic benefits. Based on the fact that the most common reasons that people turn to medical use of cannabis are for pain relief, anxiety relief and insomnia, these benefits will be reviewed first with respect to different cannabis strains.

 

Safety

Terpenes are commonly used in the manufacturing of essential oils, natural flavorings and beauty products and are extensively used in fragrances and aromatherapy. Terpenes, in the amounts found in cannabis and cannabis extracts, are believed to be safe and well tolerated with minimal or mild side effects such as sedation. All the terpenoids discussed here are Generally Recognized as Safe (GRAS) by the US Food and Drug Administration (FDA) as food additives. Additionally, they are non-sensitizing to skin when fresh, but they may cause allergic reactions. Terpenes are not associated with physical dependence (withdrawal) or tolerance nor are they associated with abuse or addiction.

 

Precautions

Storag of Cannabis Products (Flowers, buds, tinctures and extracts)

Terpenes break down easily when exposed to air, heat, humidity and light. Once the cannabis plant is harvested, if the flowers are not handled with care, terpenes can degrade so quickly. Terpenes evaporate off the plant in a way that cannabinoids like THC and CBD do not so if the flowers gets too warm, their terpenes can evaporate and simply disappear. This is largely due to the lower boiling temperatures of terpenes compared with cannabinoids and therefore these differences are greater in (in order of increasing boiling point): the monoterpenes (including myrcene, pinene, limonene, ocimene, and terpinolene), monoterpenoids  linalool, terpineol, and geraniol), sesquiterpenes (including caryophyllene and humulene), and sesquiterpenoids (including nerolidol, guaiol, and bisabolol). Some terpenes will begin to evaporate off at temperatures as low as 70°F, although most won’t begin to degrade at around 100°F.

This has real consequences not only for the taste and smell of the flower, but also its therapeutic effect since terpenes are major components in the flower that are responsible for much of the characteristic benefits offered by the flower. If these terpenes degrade or evaporate off before consumption, the terpenes won’t be useful any longer and their benefits lost.

This means that how cannabis is stored after harvest is important to maintain its quality:

    • Flower should always be kept at temperatures below 70°F (refrigerated)
    • Humidity levels may vary but should generally remain between 45% and 65%
    • Storage containers should be air-tight
    • Containers should be dark or opaque and allow no light, especially ultraviolet (UV) light, to enter

 

 

Concentrated Terpenes

One should never consume or swallow concentrated terpenes or essential oils without appropriate dilution. If you’re at all unsure about the safety of a compound, do not orally consume it without consulting a medical professional.

 

Vaping Terpenes

Vaping terpenes may offer health risks. While terpenes are typically found in cannabis flowers at levels of 2–5%, concentrations of up to 20% terpenes are marketed in some vape formulations.  Such high levels of terpenes are of particular concern as little is known about vaping terpenes or the degradation products that they might form after high heat exposure. Terpenes are highly reactive molecules that isomerize and interact with oxygen and it is a big unknown as to what happens when one heats them up, smokes them or vapes them.

The variability of vape-oil compositions makes it particularly challenging when studying the health effects of vaping terpenes. Vaping oils require a thinning agent, such as propylene glycol, poly(ethylene glycol), or vegetable glycerin—the same chemicals used in e-cigarette liquids. Some companies use medium-chain triglycerides from refined coconut oil. When these thinning agents are heated, they emit formaldehyde, not something you want to inhale.

 

Vaping Temperatures

Vaporizers should provide the option of setting a vape temperature. The reason for this is that different cannabinoids and terpenes vaporize at different temperatures. If the flower is not heated to a temperature sufficient to vaporize the particular constituents in the flower, these constituents won’t be able to be inhaled and their benefits will be lost. In exxploring the vaporizing temperature (boiling point), the literature is not always consistent.

The boiling point of a terpene is the temperature at which it completely dissipates. This is much higher than the point at which terpenes begin to evaporate, yet still slightly lower than at which many phytocannabinoids burn off.

 

 

Lower Temperatures

In general, cannabinoids vaporize at temperatures from 315• – 430• F (157• – 220• C)  while terpenes vaporize at temperatures from 150• – 390• F (66• – 198• C). While it may be best to set the temperature as low as possible to avoid irritation of the airways, the temperature should be set 10• – 15• F) above the vaporizing point (VP), or boiling point, of the desired constituent with the highest VP. With each flower listed below, the minimum VP is identified based on the terpene profile (when known).

One can also modify the effects of vaping flower by adjusting the temperature directed at modulating the THC which vaporizes at 315• F. By vaping at, or just above this temperature, less THC will be released allowing for a more subtle effect compared with higher settings which will create a greater burst of vaporized THC. And, depending on the terpene profile of the strain, one can also modify the experience by modulating the terpene vaporization.

For example, the terpene pinene (which promotes alertness) is vaporized at 311• F, so keeping the temperature around 315• – 320• allows for a more subtle THC experience with the addition of the uplifting pinene effects, while at the same time by keeping the temperature below 330• F it will avoid the sedating effects of any myrcene present since it needs 330• F to vaporize. 

One should be aware that β-caryophyllene, arguably the most important terpene for pain benefits, vaporizes at a significantly lower temperature (266• F) and would therefore be available at the temperatures discussed above. 

 

Higher Temperatures

Some cannabinoids have higher vaporization temperatures, including cannabichromene (CBC – 428• F), cannabinol (CBN – 365• F) and THCV (428• F). Of note, CBD doesn’t have a clear set VP, it is more of a vaporization range from 320-356• F (160-180°C), slightly higher than THC.

Therefore, to be certain to get the benefit of the full complement of cannabinoids and a more rapid vaporization of THC and CBD for the strongest impact, higher vaporizing temperatures should be used (430-450• F).

While vaporization points are meaningful, they are not absolute.  The fact is, to a small degree both may sublimate off at a lower temperature. An additional factor is the vape chamber of the device may not heat the chamber contents perfectly evenly, creating hot and cold spots in the flower that will affect over-all vaporization.

 

The minimum vaporizing temperatures listed with each cannabis product on this site is the temperature at which all significant constituent cannabinoids and terpenes will vaporize.

 

Bioavailability

Bioavailability refers to the proportion of a drug or other substance which enters the blood circulation when introduced into the body via inhalation, through the skin or through ingestion. For example, the bioavailability of a substance introduced directly into the vein by injection is, by definition, 100%. The bioavailability of the terpenes in cannabis is not well studied yet but most are generally considered to have high bioavailability with inhalation and oral ingestion.

Once entering the blood, terpenes are highly distributed in the body’s tissues but metabolized and cleared from the blood quickly, within a few hours, and accumulation is unlikely. The majority of terpenes are metabolised in the liver and exhaled as CO2 or, mostly, eliminated as phase-II conjugates by the kidneys.

 

Dermal absorption

Because terpenes are usually lipophilic (fat soluble), they are generally absorbed well from the gut and they will pass into the brain through the blood brain barrier. Due to their lipophilic character monoterpenoids,  including alpha- and beta-pinene, camphor, 3-carene, myrcene and limonene,  have high bioavailability through the skin.

 

Application of monoterpenoids in an ointment results in a rapid increase of blood levels of these compounds, reaching maximum blood levels within 10 minutes of application. The extent of absorption depends on the size of  skin area being treated, skin properties, concentrations of the administered compounds and on the time of exposure. These results still need confirmation by additional studies.

 

Absorption after oral administration

Few studies have assessed the absorption of terpenes after oral ingestion. In a human pharmacokinetic study, enteric-coated capsules containing a  mixture of limonene, 1,8-cineole and a-pinene,were evaluated but only 1,8-cineole was detected in sufficient quantities in the blood of all patients. This study suggests that the upper part of the gastrointestinal tract has no significant role with respect to the absorption of 1,8-cineole.

It’s also important to remember when cooking cannabis that terpenes can be destroyed by high temperatures, so always cook it “low and slow.” The goal is to ensure that the terpenes remain intact through the cooking or baking process to maintain the unique, special benefits they offer.

 

Pulmonary absorption

Monoterpenes are particularly suitable for inhalation. Following inhalation, these compounds are absorbed by the lung, and are available systemically. For a-pinene, camphor and menthol, 54-76% of the dose are absorbed However, in one study only 4-6% of the amount absorbed was actually found in the blood, suggesting rapid distribution to other tissues. The extent of pulmonary absorption depends on the compound and the breathing mechanics of the subject.

 

Excretion

The major portion of these compounds aand their metabolites are eliminated by the kidneys and the lung, with a small portion eliminated in the feces with an elimination half-life of about one hour.

 

 

Conditions Potentially Responsive to Terpenes

Certain strains, or chemovars, of Cannabis sativa  as a whole plant product may worsen symptoms of mental health disorders in some people, particularly high THC, low CBD strains. Additionally, some strains can also increase the likelihood of developing mood or psychiatric illnesses . On the other hand,  a large body of pre-clinical and clinical evidence suggests that other strains offer a range of therapeutic benefits in psychiatric and neurological illnesses, including anxiolytic, anti-depressant, antipsychotic, neuroprotective, anti-inflammatory, anti-oxidant, and pro-cognitive effects.

 

The  following is a list of conditions that, while still highly speculative, might respond to terpenes or to a cannabinoid-terpene synergy:

  1. Pain
  2. Anxiety
  3. Depression
  4. Insomnia
  5. Dementia
  6. Addiction
  7. Oxidative Stress
  8. Inflammatory diseases – Respiratory inflammation, Atopic Dermatitis, Arthritis, and Neuroinflammation

 

Pain

Terpenes have a great deal of popular support for their pain benefits although most of the research that explores this is preclinical: animal or lab-based (in-vitro). The following terpenes are most commonly recognized for their benefits for pain:

 

 Cannabis strains noted for their benefits for pain

While there are no rules, users tend to report more effective pain-relief with indica strains. In one survey, participants reported that indicas helped more than sativas when it came to headaches, joint pain, neuropathy, and spasticity. Users also reported indicas to be more helpful when it comes to sleep and sedation. While sativa-dominant strains don’t seem as popular for pain management, they  tend to have less sedative effects compared to indica strains. However, over the several decades of widespread cannabis breeding, the ability to distinguish indica strains from sativa strains has become vague and unreliable.

For more information regarding which cannabis strains are best for pain,

See: Terpenes and Pain

 

Arthritis (Osteoarthritis)

Osteoarthritis (OA) is a degenerative joint disease characterized by inflammation and progressive loss of the joint (articular) cartilage that is associated with changes in the subchondral bone and other joint tissues. Although the mechanisms of joint tissue destruction in OA is not yet completely understood, pro-inflammatory cytokines, such as interleukin-1β (IL-1β), play a major role by inducing activity of cartilage-degrading enzymes in cartilage cells (chondrocytes). This enzymatic process, coupled with impaired repair responses, results in progressive cartilage loss, the hallmark of OA.

The terpenes myrcene, pinene and limonene have been found in preclinical research to have anti-inflammatory and anti-catabolic (breakdown) properties in human chondrocytes, although myrcene may show the greatest potential. Caryophyllene has also been identified as an agonist of the CB2 receptor which suggests it may also have anti-inflammatory benefits. Clinical studies are needed to identify how these benefits may be applied.

See: Terpenes – Inflammation and Arthritis

 

Headaches

See: Terpenes and Headaches

 

Anxiety

Abundant evidence supports the key role of the endocannabidiol system in moderating both depression as well as anxiety, whether induced by aversive stimuli, such as post-traumatic stress disorder or pain. CBD’s anxiolytic effects are reasonably supported in the literature, especially regarding the belief that CBD reduces the side effect of anxiety that is associated with the use of THC (See: Cannabidiol).

 

Terpenes are frequently promoted as having sedative and anxiety benefits. The following is a list of terpenes commonly believed to have sedative or anxiolytic effects:

  1. β-Caryophyllene
  2. Limonene
  3. Linalool
  4. Myrcene
  5. α-Pinene
  6. Phytol
  7. α-Terpineol
  8. Terpinolene

 

Anxiety – Cannabis strains and their terpenes, noted relative to their benefits for anxiety

A 2018 publication evaluated (by surveys) the opinions of 442 patients using cannabis for medical purposes. Of these, 266 (60%) patients reported that they used cannabis to treat their anxiety whereas only 15% of these patients reported being diagnosed with a specific anxiety disorder.

 

Most Effective

The top four cannabis strains reported to be most effective for reducing anxiety were Bubba Kush,  Skywalker OG Kush, Blueberry Lambsbread and Kosher Kush. Three of these four are “Kush” varieties, which all share a similar chemotype with high levels of the terpenes: trans-nerolidol, myrcene, β-Caryophyllene, D-limonene and linalool. Kush strains contain genetics originating from the pure Indica strains found in the Kush mountain range in Central Asia, Afghanistan, Northern Pakistan and North-Western India.  “Hindu Kush” strains of Cannabis were brought to the United States in the mid-to-late 1970s.

Click here for a graph of weighted average terpene concentrations for the top four most effective cannabis strains for anxiety (taken from “Cannabis and the Anxiety of Fragmentation—A Systems Approach for Finding an Anxiolytic Cannabis Chemotype”).

Of note, while CBD has been identified as being effective for anxiety, in the strains identified in this study as being most effective for anxiety the cannabinoids cannabigerol (CBG) and cannabichromene (CBC) were measured at higher levels than CBD (0.68%, 0.13% and 0.075% respectively). It has been proposed that CBG may also have anxiolytic benefits.

 

Bubba Kush terpene profile (from industrialhempfarms.com):

Humulene (1.76%), Linalool (1.46%), Caryophyllene oxide (0.62%), Caryophyllene (0.4%), alpha-Pinene (<0.01%), Terpinolene (<0.01%), Myrcene (<0.01%),  beta-Pinene (<0.01%), Limonene (<0.01%).

Total terpenes 4.24%

 

Skywalker OG Kush terpene profile (from industrialhempfarms.com):

Humulene (1.77%), alpha-Pinene (0.88%), Myrcene (0.69%), Caryophyllene oxide (0.42%), Caryophyllene (0.37%),  Terpinolene (<0.01%), Linalool (<0.01%), beta-Pinene (<0.01%), Limonene (<0.01%).

Total terpenes 4.13%

 

Least Effective

Of the four cannabis strains considered least effective (but not necessarily ineffective), myrcene dominant strains and the terpinolene dominant strains were found to be less effective. These results could be due to different symptom etiology requiring different pharmacological interventions or may also arise from differences in personal biochemistry between patients with similar etiology.

For a complete analysis of weighted averages of all terpenes and cannabinoids for the top four most effective and least effective (for anxiety) cannabis strains in this study, click here (taken from “Cannabis and the Anxiety of Fragmentation—A Systems Approach for Finding an Anxiolytic Cannabis Chemotype”

 

Terpene Blends for Calming

Seeking to relax and feel calm is a significant driving motivation for cannnabis users and this can be distinguished from anxiety although an overlap is present. The terpenes linalool, limonene and caryophylene are prominent in those strains thought to induce a calming and mood-elevating effect.

TrueTerpenes.com promotes a terpene blend product, Calm, purported “to enhance a person’s ability to unwind from a busy world.”

 

 

 

Depression

While the possible benefits of THC on depression remain controversial, CBD- or CBG-predominant preparations have greater support. Research supporting benefit for depression treated solely with a citrus scent strongly suggests the possibility of synergistic benefit of a phytocannabinoid-terpenoid preparation with limonene.

 

Dementia

A recent study supports the concept that CBD, when present in significant proportion to THC, is capable of reducing or eliminating induced cognitive and memory deficits in normal subjects smoking cannabis.  Furthermore, CBD may also reduce b-amyloid in Alzheimer’s disease. The psycho-pharmacological effects of limonene, pinene and linalool could possibly offer benefits in mood in such patients.

 

Insomnia

The effects of cannabis on sleep remain inconclusive, but there may be benefits that can accrue in this regard, particularly with respect to symptom reduction permitting better sleep, as opposed to a mere hypnotic effect. Certainly, terpenoids with pain-relieving, anti-anxiety or sedative effects may supplement such benefits, particularly caryophyllene, linalool and myrcene.

See: Terpenes and Insomnia

 

Addiction

CBD has been proposed as a treatment for heroin, cocaine, and alcohol craving and addiction relapse although research remains inconclusive. It is theorized that terpenoids might provide adjunctive support including myrcene via sedation, pinene via increased alertness, and especially caryophyllene via CB2 agonism due to a newly discovered possible mechanism of action in addiction treatment. CB2 is expressed in dopaminergic neurons in the ventral tegmental area and nucleus accumbens, areas mediating addictive phenomena. Activation of CB2 in rats has been shown to inhibit dopamine release and cocaine self-administration. Caryophyllene, as a high-potency selective CB2 agonist would likely produce similar effects.

See: CBD – Treatment of Addiction

 

Oxidative Stress

Oxidative stress is a condition that results from an imbalance between the production of reactive oxidative species (ROS), such as free radicals, and their elimination by protective mechanisms. ROS are highly reactive chemicals that damage tissues, epecially proteins, lipids, and DNA/RNA. They are produced naturally by cells, especially when producing energy in the mitochondria. The excessive production of ROS causes tissue injury that leads to inflammation as well as irreversible damage to cells, possibly resulting in mutations, cancer and cell death. Terpenes may be protective by reducing the activity of enzymes involved in the production of ROS, or by protecting against oxidative damage by a wide range of ROS through several mechanisms of antioxidant activity including binding with, and neutralizing the ROS.

 

Due to their antioxidant behavior, terpenes have been shown to protect against different diseases, including neurodegenerative and cardiovascular diseases, cancer, diabetes, and aging processes. Many studies have demonstrated antioxidant properties of terpenes and terpenoids. D-Limonene has powerful antioxidative properties as does myrcene, pinene, d-limonene, terpinolene, humulene, linalool, β-caryophyllene and many others.

See: Antioxidants and Oxidative Stress, Oxidative Stress, Pain and Disease

 

Inflammation

Inflammation is a complex biological response to tissue damage as a consequence of wounds or infections or due to exposure to pathogens or other foreign substances. Initially inflammation is a normal part of the healing process. In some disease states, however, the immune system produces an inflammatory response in the absence of injury, foreign substances or infection. This response is characterized by an overproduction of inflammatory substances called cytokines. The general effect of the terpenes in most studies is reducing the pro-inflammatory cytokines. Certain terpenes have been found to reduce inflammation by decreasing the release of pro-inflammatory cytokines, including limonene, terpinolene and linalool. Other terpenes including α-pinene, limonene, and myrcene decrease the expression of these cytokines in inflammatory cells called macrophages.

See: Terpenes – Inflammation & Arthritis

 

Neuroinflammation
 Neuroinflammation,  inflammation involving the nervous system, is the foundation of central sensitization, the process in which acute pain becomes chronic. Certain terpenes have been shown to suppress microglia-mediated inflammation involved in acute or chronic neurodegenerative diseases. Studies strongly suggest that linalool has neuroprotective activity and limonene is also involved in neuroinflammation regulation process by reducing the inflammatory response and decreasing the levels of inflammatory cytokines.

See: Terpenes –  Neuroinflammation

Respiratory Inflammation

Respiratory conditions associated with inflammation include asthma, allergic rhinitis, bronchitis, pneumonia and, recently, COVID-19. Several animal studies have shown the beneficial effects of some  terpenes including limonene and α-Pinene. However, adverse effects of inhaled terpene on airways has also be found. Oxidation products of α-pinene and d-limonene have been shown to cause irritation both in the upper airways and lungs in mice.

See: Terpenes – Inflammation & Arthritis

 

Creativity

For many people who use marijuama, stimulating creativity is a significant driving motivation. When cannabis users evaluate marijuana strains for therapeutic benefits, “stimulating creativity” is not infrequently noted. While THC is commonly thought to enhance creativity, a search of the marijuana and aromatherapy essential oils literature, the terpenes and terpenoids most often associated with creativity include limonene, citronellol, alpha phellandrene, alpha-pinene and linalool.

TrueTerpenes.com promotes a terpene blend product, Creativity, purported to stimulate the creative spirit.

Individual Terpenes

While the over 200 different terpenes found in the cannabis plant have been much less researched compared to THC and CBD, they do show promise for their ability to provide therapeutic benefits. Below are some of the most frequent terpenes:

Myrcene

Myrcene is the most abundant terpene in cannabis, making up as much as 65% of total terpene profile in some strains. Strains that contain 0.5% or more of myrcene are usually indicas with sedative and anxiolytic effects. Myrcene has also been reported to be useful in reducing inflammation, chronic pain and muscle spasm and is a prominent sedative and potentiates sleep at high doses.  If the level of myrcene is >0.5% it may result in a “couch lock,” or heavy sedative effect, while low levels of myrcene (<0.5% myrcene) can produce a higher energy.

See: Terpenes – Myrcene

Limonene

Limonene is the second most abundant terpene in cannabis, but it is not necessarily found in all strains. Strains that have “lemon” or “sour” in their name are usually rich in limonene. Limonene is non-toxic, highly bioavailable with 70% pulmonary uptake and rapidly metabolized. It boosts up the level of serotonin and dopamine, thereby inducing anxiolytic, anti-stress, and sedative effects. Additionally, limonene has therapeutic potential for diseases associated with inflammatory and oxidative-stress processes.

Although limonene has been widely studied and reported to have strong anxiolytic and anti-inflammatory properties, very limited information is available about its analgesic effects based on preclinical, animal research. It appears that limonene does not reduce thermal measures of pain such as hot-plate and cold allodynia, but shows effectiveness against inflammatory and neuropathic mechanical allodynia pain. Of note, there is no definitive clinical evidence available supporting these purported pain benefits in humans, either inhaled or with oral use.

See:Terpenes- Limonene

 

Linalool

See: Terpenes: Linalool

 

 

β-Caryophyllene (BCP)

See: Caryophyllene

 

Humulene (obsolete name: α-caryophyllene)

Humulene (previously termed α-caryophyllene) is an isomer of β-caryophyllene and plays a significant role in many of the distinguishing characteristics between different cannabis strains like White Widow, Headband, Girl Scout Cookies, Sour Diesel, Pink Kush and Skywalker OG. It is also found in herbs and spices such as hops, clove, basil, sage, ginger, spearmint, and ginseng as well as some fruits and vegetables. It has strong anti-inflammatory properties comparable to dexamethasone systemically and topically, as well as analgesic properties.  There are anecdotal reports that it causes weight loss and appetite suppression and it is often promoted for weight-loss as an appetite suppressant. Humulene is also said to have anti-bacterial properties.

 

Pinene

Pinene is one of the most most commonly occurring terpene in nature. In nature, two structural isomers of this terpene exist, α-pinene and β-pinene. Extensively investigated for its medicinal properties, alpha-pinene has been found to have sedative and anxiolytic properties along with significant antioxidant, anti-inflammatory, sleep and analgesic benefits. Terpene strains that are high in α-pinene and terpinolene may provide an uplifting effect. Claims have been made that it improves a person’s ability to focus their attention as well as to reduce perception of stress.

 

β-Pinene

Related to α-pinene, β-Pinene is another important monoterpene present in different strains of Cannabis. β-pinene has antimicrobial, antiseptic and antioxidant activity. It also may have anti-depressant-like and sedative-like properties is thought to aid memory and minimize cognitive dysfunction induced by THC intoxication.

See: Terpenes – Pinene

 

Carene (Delta 3-Carene)

Delta 3-carene (Carene) is a terpene found in basil, bell peppers, rosemary, and cannabis that promotes the drying up of excess liquid and has anti-inflammatory effects. Side effects often associated with this terpene are dry mouth and red eyes. Carene has a pungent but pleasant earthy aroma that is piney in resemblance. This terpene is thought to stimulates memory and help memory retention.

 

Eucalyptol (Cineole)

Also known as cineole, eucalyptol is the primary terpene of the eucalyptus tree. It is also found in tea tree, rosemary, sweet basil, wormwood, tea trees, mugwort, bay leaves and common sage. Most cannabis strains do not contain large amounts of eucalyptol, usually only making up around 0.06% of a strains complete terpene profile. Eucalyptol can be found in the cannabis strains Super Silver Haze and Headband.

 

It has been proposed to improve memory and cognitive learning and because of its cholinesterase inhibitory activity, it has potential for use in Alzheimer’s disease and protection against amyloid beta-induced inflammation. Eucalyptol has antioxidative, anti-inflammatory and analgesic properties and has been suggested as a potential long-term therapy in the prevention of COPD exacerbations and asthma and inflammatory bowel disease. It helps treat nasal and sinus inflammation and secretions and is used as a nasal decongestant and cough suppressant.

 

Terpinene

Terpinene is considered an anti-inflammatory, antimicrobial, analgesic, and anticancer agent.

 

Terpinolene

Terinolene can be found in apples, cumin and lilac. It is purported to be sedating and calming, often found in cannabis indica. Terpene strains that are high in terpinolene and α-pinene may provide an uplifting effect.

 

Terpineol

Terpineol is found in pine trees, lilacs, eucalyptus, and lime blossoms, and has a pleasant scent, similar to lilac, and is a common ingredient in perfumes, cosmetics, and flavors. Terpineol can be found  in Girl Scout Cookies, Jack Herer, and OG Kush strains. Animal and preclinical studies sugges it has anti-inflammatory, analgesic and antioxidant properties and it may have anxiolytic and sedative effects. There is no evidence that terpineol interacts with CB receptors.

 

Nonetheless, terpineol shows different pharmacological properties that include analgesic, antifungal, anti-inflammatory, and antidiarrheal. Terpineol has been investigated in different animal models of pain and research suggests that terpineol may have analgesic benefit by activation of descending inhibitory pain system. Its analgesic effect is reversed by naloxone (opioid antagonist), and ondansetron (5-HT3 serotonin antagonist) suggesting multiple modes of action. Terpineol has been demonstrated to be a safe and effective drug for control of sarcoma-induced cancer pain in mice.

 

Regarding it anti-inflammatory properties, terpineol has also been investigated for the treatment of allergic inflammation and asthma. Terpineol decreases leucocyte migration and TNF levels and suppresses the production of inflammatory mediators (e.g., NF-κB, p38, ERK, and MAPK signaling pathways) in human macrophages.

 

Terpineol properties go beyond the above. It has been shown to have bactericidal and antifungal properties and strong anti-proliferative activity on cancer. Terpineol is a versatile compound with a wide variety of beneficial effects which could lead to the development of new antibiotics, antifungal, and anticancer agents.

 

Nerolidol (trans-Nerolidol)

Nerolidol (trans-nerolidol) is a secondary terpene found in many herbs and spices including lavender, lemon grass, ginger, jasmine, tea tree, oranges, and it is present at low levels in the peels of citrus fruit. Cannabis strains like Island Jack Herer, Sweet Skunk, and Skywalker OG are rich in nerolidol. Nerolidol has sedative properties and is useful in insomnia. The mechanism of action for proposed analgesic activity of trans-nerolidol involves the GABAergic system, but not the opioidergic system.

 

Alpha-bisabolol (α-bisabolol, bisabolol, levomenol)

Alpha-bisabolol (also known as levomenol and bisabolol) has a pleasant floral aroma and can also be found in chamomile flowers. This terpene is used primarily in the cosmetics industry, but the pharmacological attributes of α-bisabolol include wound healing, gastroprotection, antitumor, antioxidant, analgesic and anti-inflammatory properties. While animal and preclinical studies support the folk use of herbs and plants containing bisabolol for pain and inflammation, human studies are lacking. Alpha-bisabolol can be found in cannabis strains like Harle-Tsu, Pink Kush, Headband, OG Shark, and ACDC.

 

Ocimene

Ocimene may also be found in basil, mango, and parsley. Its benefits are thought to include easing congestion and protect against viruses and bacteria.

Alpha Phellandrene

Alpha Phellandrene has an aroma that is described as herbaceous, citrus, peppery, minty, and slightly green/woody. Strains containing large amounts of Alpha Phellandrene can often be identified by their exceptionally minty taste. Alpha Phellandrene can be naturally sourced from corn parsley (Ridolfia segetum) and the elemi tree (Canarium luzonicum).

Type of Terpene: Monoterpene

 

Commercial Products

 

Terpene Products

Commercial terpene products are availabe for use as supplements to be used independently or in combination with cannabis-based products, including THC and CBD.  Some companies promote their products by claiming the constituents in their terpene products are formulated to simulate the same terpene blends of specific cannabis strains.  Upon investigation, it was not possible to find on their website evidence to confirm their claims regarding their blends, probably to protect their proprietary interests. Links to some of these products are available here for educational purposes but are not meant to recommend or endorse the products. It should also be emphasized that these terpene products do not contain THC, CBD or other cannabinoids.

 

CBD Products

In addition to commercial terpene products, there are many CBD products that contain terpenes. CBD products with terpenes are labeled as “broad spectrum” when the constituents have no THC and “full spectrum” when they contain THC at levels up to a 0.3%. Unfortunately, CBD products frequently do not identify their specific terpenes and their concentrations, again, probably to protect their proprietary interests.

See: CBD

 

Resources:

National Academy of Sciences

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research

 

www.Healer.com

This website appears to be good resource for exploring medical marijuana.

 

References:

   

Terpenes – Overviews

  1. Therapeutic and Medicinal Uses of Terpenes – 2019
  2. Terpenes:Terpenoids in Cannabis – Are They Important? – 2020
  3. Advances in Pharmacological Activities of Terpenoids – 2020
  4. Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant – 2020
  5. The Cannabis Terpenes – 2020
  6. The “Entourage Effect” – Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders – 2020
  7. Cannabis Essential Oil – A Preliminary Study for the Evaluation of the Brain Effects – 2018
  8. A Systematic Review of Essential Oils and the Endocannabinoid System – A Connection Worthy of Further Exploration – 2020
  9. Efficacy of Essential Oils in Pain – A Systematic Review and Meta-Analysis of Preclinical Evidence – 2021
  10. A Review of the Potential Use of Pinene and Linalool as Terpene-Based Medicines for Brain Health- 2021
  11. An Optimized Terpene Profile for a New Medical Cannabis Oil – 2022
  12. Terpenoids Commonly Found in Cannabis sativa Do Not Modulate the Actions of Phytocannabinoids or Endocannabinoids on TRPA1 and TRPV1 Channels – 2020
  13. The terpenes camphene and alpha-bisabolol inhibit inflammatory and neuropathic pain via Cav3.2 T-type calcium channels – 2021
  14. Analgesic Potential of Terpenes Derived from Cannabis sativa – 2021
  15. Spices, Condiments, Extra Virgin Olive Oil and Aromas as Not Only Flavorings, but Precious Allies for Our Wellbeing – 2021

 

Terpenes – Aromatherapy

  1. Aromatherapy and Aromatic Plants for the Treatment of Behavioural and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease Clinical Evidence and Possible Mechanisms – 2017
  2. Corrigendum – A question of scent – lavender aroma promotes interpersonal trust -2015
  3. Odors enhance slow-wave activity in non-rapid eye movement sleepOdors enhance slow-wave activity in non-rapid eye movement sleep
  4. Essential Oils and Animals – Which Essential Oils Are Toxic to Pets?
  5. Essential Oils and Pets
  6. Herbs and Their Uses for Animals – Patchouli and Pets
  7. Reactivating memories during sleep by odors – odor specificity and associated changes in sleep oscillations – 2014
  8. Increasing Explicit Sequence Knowledge by Odor Cueing during Sleep in Men but not Women – 2016
  9. Effects of odorant administration on objective and subjective measures of sleep quality, post-sleep mood and alertness, and cognitive performance – 2003
  10. An Olfactory Stimulus Modifies Nighttime Sleep in Young Men and Women – 2005
  11. Massage with or without aromatherapy for symptom relief in people with cancer. – PubMed – NCBI
  12. Aromatherapy hand massage for older adults with chronic pain living in long-term care. – PubMed – NCBI
  13. A Systematic Review of Essential Oils and the Endocannabinoid System – A Connection Worthy of Further Exploration – 2020
  14. Human olfactory receptors – novel cellular functions outside of the nose,” – 2017
  15. The diversified function and potential therapy of ectopic olfactory receptors in non-olfactory tissues – PubMed – 2017
  16. How does your kidney smell? Emerging roles for olfactory receptors in renal function,” – 2017
  17. The Effects of Essential Oils and Terpenes in Relation to Their Routes of Intake and Application – 2020
  18. Pharmacology of Natural Volatiles and Essential Oils in Food, Therapy, and Disease Prophylaxis – 2021

 

Terpenes – CB2 Receptor

  1. Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain – an updated review – 2021
  2. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice – 2014
  3. The CB2 receptor and its role as a regulator of inflammation – 2016

 

Terpenes – Synergy with Cannabinoids:

  1. Taming THC – potential cannabis synergy and phytocannabinoid-terpenoid entourage effects – 2011
  2. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI
  3. Entourage Effect 2.0
  4. Cannabis and the Anxiety of Fragmentation—A Systems Approach for Finding an Anxiolytic Cannabis Chemotype – 2018
  5. Terpenoids and Phytocannabinoids Co-Produced in Cannabis Sativa Strains Show Specific Interaction for Cell Cytotoxic Activity – 2019
  6. Absence of Entourage – Terpenoids Commonly Found in Cannabis sativa Do Not Modulate the Functional Activity of Δ9-THC at Human CB1 and CB2 Receptors – 2019
  7. Terpenoids From Cannabis Do Not Mediate an Entourage Effect by Acting at Cannabinoid Receptors – 2020
  8. The “Entourage Effect” – Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders – 2020

 

Terpenes – Marijuana Strains

  1. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018
  2. Terpenoid Chemoprofiles Distinguish Drug-type Cannabis sativa L. Cultivars in Nevada – 2018
  3. Terpenoids and Phytocannabinoids Co-Produced in Cannabis Sativa Strains Show Specific Interaction for Cell Cytotoxic Activity – 2019
  4. Identification of Terpenoid Chemotypes Among High (−)-trans-Δ9- Tetrahydrocannabinol-Producing Cannabis sativa L. Cultivars 0 2017
  5. The Cannabinoid Content of Legal Cannabis in Washington State Varies Systematically Across Testing Facilities and Popular Consumer Products – 2018

 

Terpenes – Routes of Use:

  1. The Effects of Essential Oils and Terpenes in Relation to Their Routes of Intake and Application – 2020
  2. Antiviral effect of phytochemicals from medicinal plants – Applications and drug delivery strategies – 2020
  3. Cannabinoid Delivery Systems for Pain and Inflammation Treatment – 2018
  4. Optimal Treatment with Cannabis Extracts Formulations Is Gained via Knowledge of Their Terpene Content and via Enrichment with Specifically Selected Monoterpenes and Monoterpenoids – 2022

 

Terpenes – Bioavailability

  1. Bioavailability and Pharmacokinetics of Natural Volatile Terpenes in Animals and Humans – 2000
  2. Bioavailability of Bioactive Compounds
  3. SPC Liposomes as Possible Delivery Systems for Improving Bioavailability of the Natural Sesquiterpene β-Caryophyllene – 2018

 

Terpenes – Arthritis

  1. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. – 2015

 

Terpenes – Anxiety

  1. Cannabis and the Anxiety of Fragmentation—A Systems Approach for Finding an Anxiolytic Cannabis Chemotype – 2018
  2. The “Entourage Effect”: Terpenes Coupled With Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders – PubMed – 2019
  3. Medicinal cannabis for psychiatric disorders – a clinically-focused systematic review – 2020
  4. A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models – 2015
  5. A Systematic Review on the Anxiolytic Effect of Aromatherapy during the First Stage of Labor – 2019
  6. A Systematic Review on the Anxiolytic Effectsof Aromatherapy in People with Anxiety Symptoms – 2011
  7. Anxiolytic Terpenoids and Aromatherapy for Anxiety and Depression – PubMed – 2020
  8. Effect of Aromatherapy on Dental Anxiety Among Orthodontic Patients – A Randomized Controlled Trial – 2019
  9. Essential Oils and Their Constituents – An Alternative Source for Novel Antidepressants – 2017
  10. Essential Oils and Their Constituents Targeting the GABAergic System and Sodium Channels as Treatment of Neurological Diseases – 2018
  11. Possible Use of Phytochemicals for Recovery from COVID-19-Induced Anosmia and Ageusia – 2021
  12. The calming effect of roasted coffee aroma in patients undergoing dental procedures – 2021
  13. The Effect of Lavender Aroma on Anxiety of Patients Having Bone Marrow Biopsy- 2020
  14. The-Effects-of-Essential-Oils-and-Terpenes-in-Relation-to-Their-Routes-of-Intake-and-Application-2020
  15. Therapeutic Effect and Mechanisms of Essential Oils in Mood Disorders – Interaction between the Nervous and Respiratory Systems – 2021
  16. Anxiolytic-Like Effects of Bergamot Essential Oil Are Insensitive to Flumazenil in Rats – 2019

 

Terpenes – Infectious Diseases

  1. Phytochemical Analysis and in vitro Antiviral Activities of the Essential Oils of Seven Lebanon Species – 2008
  2. Antiviral effect of phytochemicals from medicinal plants – Applications and drug delivery strategies – 2020
  3. Essential Oils and Coronaviruses – 2020

 

Terpenes – Pain:

  1. Analgesic-like Activity of Essential Oils Constituents – 2011
  2. Analgesic-Like Activity of Essential Oil Constituents – An Update – 2017
  3. Medicinal Plants of the Family Lamiaceae in Pain Therapy – A Review – 2018
  4. Analgesic Potential of Essential Oils – 2016
  5. Analgesic Potential of Terpenes Derived from Cannabis sativa – 2021
  6. Medicinal Plants of the Family Lamiaceae in Pain Therapy – A Review – 2018
  7. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018
  8. Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant – 2020
  9.  The Molecular Mechanisms That Underpin the Biological Benefits of Full-Spectrum Cannabis Extract in the Treatment of Neuropathic Pain and Inflammation – PubMed – 2020
  10. Cannabis-based medicines and the perioperative physician – 2019
  11. Cannabis‐based medicines for chronic neuropathic pain in adults – 2018
  12. Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain – An Update on Current Evidence and Cannabis Science – 2018
  13. Role of Cannabinoids and Terpenes in Cannabis-Mediated Analgesia in Rats – PubMed – 2019
  14. Antinociceptive effect of inhalation of the essential oil of bergamot in mice – 2018
  15. Analgesic Potential of Essential Oils – 2016
  16. Analgesic-Like Activity of Essential Oil Constituents – An Update – 2017
  17. Terpenoids Commonly Found in Cannabis sativa Do Not Modulate the Actions of Phytocannabinoids or Endocannabinoids on TRPA1 and TRPV1 Channels – 2020
  18. The terpenes camphene and alpha-bisabolol inhibit inflammatory and neuropathic pain via Cav3.2 T-type calcium channels – 2021
  19. Myrcene and terpene regulation of TRPV1 – 2019

 

 

Terpenes – Headaches:

  1.  Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain – An Update on Current Evidence and Cannabis Science – 2018
  2. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018

 

Terpenes – Inflammation:

  1. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. – 2015 
  2. Cannabis sativa L. and Nonpsychoactive Cannabinoids – Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer – 2018
  3. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018
  4. Therapeutic Potential of Volatile Terpenes and Terpenoids from Forests for Inflammatory Diseases – 2020
  5.  The Molecular Mechanisms That Underpin the Biological Benefits of Full-Spectrum Cannabis Extract in the Treatment of Neuropathic Pain and Inflammation – PubMed – 2020
  6. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. – 2015
  7. Cannabis, Cannabinoids, and the Endocannabinoid System—Is there Therapeutic Potential for Inflammatory Bowel Disease? – 2019
  8. Therapeutic Applications of Terpenes on Inflammatory Diseases – 2021

 

Esssential Oils

 

Essential Oils – Overviews

  1. Essential Oils, Part I Introduction – PubMed – 2016
  2. Essential Oils, Part II General Aspects – PubMed – 2016
  3. Essential Oils, Part III Chemical Composition – PubMed – 2016
  4. Essential Oils, Part IV Contact Allergy – PubMed- 2016
  5. Essential Oils, Part V Peppermint Oil, Lavender Oil, and Lemongrass Oil – PubMed 2016

 

 

Essential Oils – Bearded Irises

  1. Identification of Floral Scent Profiles in Bearded Irises – 2019

 

 

Essential Oils – Bergamot

  1. The Anxiolytic Effect of Aromatherapy on Patients Awaiting Ambulatory Surgery – A Randomized Controlled Trial – 2013
  2. Antinociceptive effect of inhalation of the essential oil of bergamot in mice – 2018
  3. Anxiolytic-Like Effects of Bergamot Essential Oil Are Insensitive to Flumazenil in Rats – 2019
  4. Bergamot – Natural Medicines – Professional.pdf
  5. Citrus bergamia essential oil – from basic research to clinical application – 2015
  6. Role of 5-HT1A Receptor in the Anxiolytic-Relaxant Effects of Bergamot Essential Oil in Rodent – 2020 Neuropharmacological Properties of the Essential Oil of Bergamot for the Clinical Management of Pain-Related BPSDs – PubMed – 2019
  7. Possible involvement of the peripheral Mu-opioid system in antinociception induced by bergamot essential oil to allodynia after peripheral nerve injury – PubMed – 2018
  8. Peripherally injected linalool and bergamot essential oil attenuate mechanical allodynia via inhibiting spinal ERK phosphorylation – PubMed – 2013
  9. Neuropharmacology of the essential oil of bergamot – PubMed – 2010
  10. Effect of Harvesting Time on Volatile Compounds Composition of Bergamot (Citrus × Bergamia) Essential Oil – 2019
  11. Chemical Composition and Biological Activities of Essential Oils from Peels of Three Citrus Species – 2020
  12. Chemical_Composition_of_Bergamot_Citrus_Bergamia_Risso_Essential_Oil_Obtained_by_Hydrodistillation – 2010
  13. Cannabinoid Signaling in the Skin – Therapeutic Potential of the “C(ut)annabinoid” System – 2019
  14. Rational Basis for the Use of Bergamot Essential Oil in Complementary Medicine to Treat Chronic Pain – PubMed – 2016

 

Essential Oils – Plumeria

  1. Constituents of essential oils from the leaf and flower of Plumeria alba grown in Nigeria – PubMed – 2014

 

Individual Terpenes

Terpenes: β-Caryophyllene:

  1. (−)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis – 2017
  2. Antiallodynic effect of β-caryophyllene on paclitaxel-induced peripheral neuropathy in mice. – PubMed – NCBI
  3. Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion – 2018
  4. Antiallodynic effect of β-caryophyllene on paclitaxel-induced peripheral neuropathy in mice. – PubMed – NCBI
  5. Cannabimimetic phytochemicals in the diet – an evolutionary link to food selection and metabolic stress adaptation? – 2016
  6. The anxiolytic-like effect of an essential oil derived from Spiranthera odoratissima A. St. Hil. leaves and its major component, β-caryophyllene, in male mice – 2012
  7. β‐caryophyllene and β‐caryophyllene oxide—natural compounds of anticancer and analgesic properties – 2016
  8. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice – 2014
  9. Toxicological Evaluation of β-Caryophyllene Oil: Subchronic Toxicity in Rats. – PubMed – NCBI 2016
  10. The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic… – PubMed – NCBI – 2014
  11. The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain – 2013
  12. SPC Liposomes as Possible Delivery Systems for Improving Bioavailability of the Natural Sesquiterpene β-Caryophyllene – 2018
  13. β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway – 2011
  14. Why wild giant pandas frequently roll in horse manure – 2020
  15. Beta-caryophyllene is a dietary cannabinoid – 2008
  16. Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain. – 2006
  17. The menthol receptor TRPM8 is the principal detector of environmental cold – PubMed – 2007
  18. Molecular basis of peripheral innocuous cold sensitivity – 2018
  19. Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception – PubMed – 2013
  20. NON-CANNABIS THERAPY – Cannabinoid Therapy Without Using Cannabis: Direct Effects™ Topical β-Caryophyllene
  21. Beta-caryophyllene enhances wound healing through multiple routes – 2019
  22. Preparation and Characterization of Liposomal β‐Caryophyllene (Rephyll) – 2020

 

Terpenes – Bisabolol

  1. The terpenes camphene and alpha-bisabolol inhibit inflammatory and neuropathic pain via Cav3.2 T-type calcium channels – 2021

 

Terpenes: Linalool:

  1. GS12-linalool
  2. Linalool – 1997
  3. The “Entourage Effect”: Terpenes Coupled With Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders – PubMed – 2020
  4. An olfactory stimulus modifies nighttime sleep in young men and women. – PubMed – NCBI
  5. Lavender and sleep – A systematic review of the evidence – 2012
  6. Lavender and the Nervous System – 2013
  7. Effects of odorant administration on objective and subjective measures of sleep quality, post-sleep mood and alertness, and cognitive performance – 2003
  8. In-vitro inhibition of human erythrocyte acetylcholinesterase by salvia lavandulaefolia essential oil and constituent terpenes. – PubMed – NCBI – 2000
  9. Odors enhance slow-wave activity in non-rapid eye movement sleep – 2016
  10. A question of scent – lavender aroma promotes interpersonal trust – 2015
  11. Is Lavender an Anxiolytic Drug? A Systematic Review of Randomised Clinical Trials – 2012
  12. Efficacy of Silexan in subthreshold anxiety – meta-analysis of randomised, placebo-controlled trials – 2019
  13. Essential oil of lavender in anxiety disorders – Ready for prime time? – 2017
  14. Linalool is a PPAR ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome – 2014
  15. A Review of the Potential Use of Pinene and Linalool as Terpene-Based Medicines for Brain Health – Discovering Novel Therapeutics in the Flavours and Fragrances of Cannabis – 2021
  16. The Efficacy of Lavender Aromatherapy in Reducing Preoperative Anxiety in Ambulatory Surgery Patients Undergoing Procedures in General Otolaryngology – 2017
  17. Efficacy, Safety and Tolerability of Aroma Massage with Lavender Essential Oil – an Overview – 2020
  18. Antinociceptive and anticonvulsant effects of the monoterpene linalool oxide – 2017
  19. Exploring Pharmacological Mechanisms of Lavender (Lavandula angustifolia) Essential Oil on Central Nervous System Targets – 2017
  20. Linalool Ameliorates Memory Loss and Behavioral Impairment Induced by REM-Sleep Deprivation through the Serotonergic Pathway – 2018
  21. Effects of lavender on anxiety, depression and physiologic parameters – Systematic Review and Meta-Analysis – 2021
  22. Lavender and sleep – A systematic review of the evidence – 2012
  23. Lavender and the Nervous System – 2013
  24. A question of scent – lavender aroma promotes interpersonal trust – 2015

 

 

Terpenes, Linalool: – Silexan

  1. A Multi-Center, Double-Blind, Randomised Study of the Lavender Oil Preparation Silexan in Comparison to Lorazepam for Generalized Anxiety Disorder – 2010
  2. Is Lavender an Anxiolytic Drug? A Systematic Review of Randomised Clinical Trials – 2012
  3.  An Orally Administered Lavandula Oil Preparation (Silexan) for Anxiety Disorder and Related Conditions- An Evidence Based Review – 2013
  4. Lavender oil preparation Silexan is effective in generalized anxiety disorder – a randomized, double-blind comparison to placebo and paroxetine – 2014
  5. Silexan in anxiety disorders – Clinical data and pharmacological background – 2017
  6. Effectiveness of Silexan Oral Lavender Essential Oil Compared to Inhaled Lavender Essential Oil Aromatherapy for Sleep in Adults- A Systematic Review – 2018
  7. Silexan in anxiety disorders Clinical data and pharmacological background – PubMed – 2018
  8. Efficacy and safety of lavender essential oil (Silexan) capsules among patients suffering from anxiety disorders – A network meta-analysis – 2019
  9. Efficacy of Silexan in subthreshold anxiety – meta-analysis of randomised, placebo-controlled trials – 2019
  10. Therapeutic effects of Silexan on somatic symptoms and physical health in patients with anxiety disorders – A meta- analysis – 2020
  11. Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of ‘subsyndromal’ anxiety disorder a randomized, double-blind, placebo controlled trial – PubMed – 2010
  12. A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder – PubMed – 2009
  13. No Abuse Potential of Silexan in Healthy Recreational Drug Users – A Randomized Controlled Trial – 2021

 

Terpenes – Limonene

  1. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. – 2015
  2. Neuroprotective Potential of Limonene and Limonene Containing Natural Products – 2021

 

Terpenes: Myrcene

  1. β-MYRCENE – IARC MONOGRAPHS
  2. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. – 2015
  3. Myrcene—What Are the Potential Health Benefits of This Flavouring and Aroma Agent? – 2021
  4. Terpenoids Commonly Found in Cannabis sativa Do Not Modulate the Actions of Phytocannabinoids or Endocannabinoids on TRPA1 and TRPV1 Channels – 2020
  5. Myrcene and terpene regulation of TRPV1 – 2019
  6. Anti-Inflammatory and Analgesic Properties of the Cannabis Terpene Myrcene in Rat Adjuvant Monoarthritis – 2022

 

Terpenes: Pinene

  1. A Review of the Potential Use of Pinene and Linalool as Terpene-Based Medicines for Brain Health – Discovering Novel Therapeutics in the Flavours and Fragrances of Cannabis – 2021
  2. Therapeutic Potential of α- and β-Pinene- A Miracle Gift of Nature – 2019
  3. The effects of alpha-pinene on inflammatory responses and oxidative stress in the formalin test – PubMed. – 2023

 

 

Medical Marijuana – Product Evaluation

  1. The Cannabinoid Content of Legal Cannabis in Washington State Varies Systematically Across Testing Facilities and Popular Consumer Products – 2018
  2. Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016
  3. Cannabinoid, Terpene, and Heavy Metal Analysis of 29 Over-the-Counter Commercial Veterinary Hemp Supplements – 2020

 

Emphasis on Education

 

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

 

For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.

 

Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.

 

For more information, please contact Accurate Clinic.

 

Supplements recommended by Dr. Ehlenberger may be purchased commercially online or at Accurate Clinic.

Please read about our statement regarding the sale of products recommended by Dr. Ehlenberger.

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