What is the Terpene Humulene?

Humulene is the star of our Weight Loss formula.   In addition to being an appetite suppressant, it also has potent anti-inflammatory properties.  Humulene (also known as or α–caryophyllene) was first found in the essential oils of humulus lupulus (or common hops), a species of plant in the hemp family that gives beer its distinctive bitter “hoppy” taste. Elsewhere, its aroma is subtle: earthy and woody, with spicy, herbal notes. You’ll also find humulene in coriander, basil, clove, black pepper, sage, and the balsam fir tree. 

Humulene does it all, but works best against bacteria, inflammation, and tumors. Unlike most Cannabis strains, humulene-rich cannabis is also anorectic, meaning it suppresses hunger.

Humulene has been widely studied for its numerous therapeutic benefits. It has been traditionally been used in folk medicines for its anti-bacterial properties, but it was only in 2006 that it was formally studied and found to fight Staphyloccocus aureus infections effectively.

Humulene’s anti-inflammatory properties, in particular, are so strong that the terpene has been compared to the steroid dexamethasone, which is listed as one of the WHO’s most essential medicines.

As an additional benefit, there is also evidence that humulene has the rare ability to produce Reactive Oxygen Species (ROS), which may cause apoptosis, or cancer cell death. Research has found that humulene is able to inhibit human tumor cell growth by 50-69% on its own, and is even more effective (75-90%) with the addition of beta-caryophyllene (an example of the synergy between terpenes, known as the Entourage Effect).

What is the Terpene Caryophylene?

Caryophyllene (or β-Caryophyllene) is a common and often abundant terpene found in cannabis strains. Its distinctive flavor contributes to the spiciness of black pepper and can be found in high amounts in cloves, hops, and rosemary.

It has the distinction of being the first known “dietary cannabinoid” with GRAS (Generally Recognized as Safe) status and having approval by the FDA for food use.  

Caryophyllene-rich cannabis strains may have specific medicinal effects due to this terpene’s effect on our body’s endocannabinoid system (ECS).  The ECS helps the body regulate many functions, and contains receptors throughout the body to help it do this.  The two receptors we know about are CB1 which is in the central nervous system (brain and nerves of the spinal cord), and CB2 which is in the peripheral nervous system (nerves in your extremities), the digestive system, and specialized cells in the immune system.  Cannabinoids like CBD and THC found in cannabis plants are known to activate these cannabinoid receptors.  Over the last decade, caryophyllene has gained the attention of scientists when it was discovered to be one of the first non-cannabinoids to directly activate cannabinoid receptors. 

β-Caryophyllene was one of the first cannabis-derived compounds other than THC, CBD, and CBN shown to bind directly to endocannabinoid receptors. In fact, it was one of the first cannabis-derived compounds with a fundamentally different structure from the classical cannabinoids that interacts with the ECS. β-Caryophyllene is known to selectively bind to the ECS’s CB2 receptor; therefore, it is sometimes also classed as an atypical cannabinoid. The CB1 receptor is responsible for the psychoactive effects associated with certain cannabinoids such as THC. However, CB2, particularly in peripheral tissues in the body, is a therapeutic target for treatment of inflammation, pain, atherosclerosis, and osteoporosis

CB2 receptors are found in immune tissues throughout the body and are increased in the brain in disease or following injury. Their activation reduces inflammation, which lessens pain and reduces the damaging consequences that chronic inflammation has on brain function and risk for developing brain diseases.

The data suggest that, in many cases, caryophyllene can provide pain relief. In one study, scientists injected mice with caryophyllene and found that they experienced less pain than those treated with the control solution. Furthermore, caryophyllene enhanced the pain-reducing strength of low-dose morphine. This could be one reason why those using prescription opioids from pain are often able to decrease their dose of opioids when they begin using medical cannabis.

There are numerous inflammatory diseases that affect the digestive tract. Colitis is one such disease where inflammation of the intestines causes pain, diarrhea, abdominal cramping, and even increases risk for cancer. In mice that were experimentally given colitis, treatment with caryophyllene helped by decreasing inflammation in the colon.

The activation of CB2 receptors by caryophyllene certainly plays a role in its anti-pain effects, but it also contributes to its ability to protect the body and brain from disease. For instance, brain inflammation plays a substantial role in the onset and progression of Alzheimer’s disease. In a mouse model of Alzheimer’s disease, caryophyllene activated CB2 and PPAR-γ receptors and reduced hallmark features of Alzheimer’s such as the accumulation of brain plaques. These actions also protect against the cognitive decline that characterizes this model of disease.

Additionally, β-Caryophyllene has now been shown to be beneficial for osteoarthritis, diabetes, anxiety and depression, and liver fibrosis. In cancer studies, β-caryophyllene demonstrated synergy with the chemotherapy drug Paclitaxel on human tumor cell lines, and alone it stimulates apoptosis and suppresses tumor growth. In a Caenorhabditis elegans model, β-caryophyllene modulated stress-related genes and extended the lifespan of the organism. Importantly, it has been shown to be orally bioavailable; therefore, it would provide an important medicinal benefit to oral cannabis preparations.

What is the Terpene Trans-Nerolidol?

Trans-nerolidol, one of the powerhouses in our CALM formula, is one of the 200+ volatile aromatic compounds called terpenes that create the unique flavors and aromas of plants and different cannabis strains. Each terpene also has unique therapeutic properties. Trans-nerolidol has a woody, fruity, citrus aroma reminiscent of citrus, apples and roses.  Many botanicals contain high levels of trans-nerolidol, including lemongrass, jasmine, tea tree, ginger and neroli (an essential oil distilled from bitter orange flowers).  

Trans-nerolidol produces potent cognitive effects and has been traditionally used for its relaxing, slightly sedative effects. Additionally, researchers suspect this terpene may ease anxiety without altering motor skills.  A 2016 study published in the Indian Journal of Pharmacology examined the effects of trans-nerolidol on oxidative stress in neuronal cells. The mice exposed to this terpene displayed high levels of sedation and showed lower levels of stress. 

In addition to its anti-anxiety properties, nerolidol calms with slight sedative effects.  Widespread anecdotal evidence supports this, along with a 2013 study published in the journal Neurochemical Research revealed that nerolidol appeared to have both a sedative and antioxidant effect on rodent test subjects.

Not only does this powerful terpene assist with stress and anxiety, nerolidol has also been shown to be an antioxidant, antibacterial, antimicrobial, and antibiotic, it has even arrested the growth of cancer cells in some studies

What is the Terpene Linalool?

Linalool is not specific to cannabis. Its characteristic lavender scent with a hint of spiciness is common to over 200 types of plants, including mint, cinnamon and coriander. So many plants produce linalool most likely for its protective anti-microbial properties.  These also represent a potential therapeutic use in people. Whether it was used as an early antibiotic is unknown, but linalool has been used in traditional medicine practices for its sedative and anti-epileptic properties since ancient times.

Modern day studies show this amazing terpene may have sedative properties, lower anxiety and depression symptoms, help to guard the immune system against damage from stress, and have pain relieving properties . Particularly important for sleep: Linalool has been shown to  increase adenosine, a sedating hormone that helps us fall asleep. Adnosine is an inhibitory brain chemical that is notably blocked by caffeine.  

Studies indicate that linalool’s behavioral effects may largely be mediated by its effects in the brain. One way is through blocking the receptors for the primary excitatory brain chemical, glutamate, which could account for linalool’s potentially anti-epileptic properties in some forms of epilepsy. This terpene also has the ability to enhance the effect of other sedatives, such as pentobarbital.

Linalool may also be muscle-relaxing and have pain-relieving effects through additional distinctive mechanisms. For instance, linalool reduces the signaling strength of acetylcholine, a brain chemical that’s required for muscle contraction and movement. Linalool can have anesthetic-like effects by reducing the excitability of cells in the spinal cord that transmit pain signals to the brain.

Additionally, a recent study looked at how inhalation aromatherapy helped elderly volunteers with insomnia. The researchers discovered that the act of sniffing lavender oil before bed increased sleep quality. It also increased energy levels in the morning after. Of course, lavender contains a lot of linalool.

In more  scientific studies, Mice exposed to linalool vapors show reduced levels of anxiety and lower depression-like behaviors. In these tests, mice exposed to linalool vapors spend more time in fear-inducing environments, and they’ll continue to work to escape a seemingly hopeless situation. It’s not exactly like testing anxiety and depression in the clinic, but in these well-validated measures, linalool appears to help.  Reduction in anxiety levels is crucial to sleep.  

Linalool also makes the immune system more resilient to the destructive effects of stress. Stress causes a shift in the distribution of white blood cells in the body (i.e., the cells of the immune system); the percent of lymphocytes decrease, and neutrophils increase. In rats, linalool prevented this shift, and in doing so, prevented the stress-induced changes in how the rats’ DNA was expressed. Interestingly, the authors reasoned that this protection was mediated by linalool’s ability to activate the body’s parasympathetic response, which is activated when the body is resting and digesting food, thereby fitting with linalool’s anti-anxiety effects.

Some of linalool’s pain-relieving abilities can be ascribed to its elevation of adenosine, the sleep hormone. Together, this multitude of nervous system targets contribute to its sedative, anxiety-reducing, and pain-relieving benefits.  These effects provide foundational support for linalool’s benefits in pain therapy. In one study, obese patients who underwent gastric banding surgery were either exposed to linalool-rich oil vapor or an unscented control. Only 46% of the patients who inhaled the oil required post-operative opioid medication, compared to 82% of the control group. Further, the morphine needs of those in the linalool-rich oil group were nearly half that of the control group, together suggesting that linalool can reduce the need for post-surgery opioid-based pain treatment.

Linalool has even shown promise as an anti-inflammatory agent.  Inflammation is often characterized by pain, swelling, a sensation of heat, and redness. It is one of our body’s crucial defense systems and it is often a beneficial response. However, sometimes, it could result in chronic inflammatory conditions if left untreated. There are a few studies that suggest linalool’s anti-inflammatory effects are real. Huo et al. had a study published in The Journal of Surgical Research in March 2013. It looked at the anti-inflammatory effects of linalool. The research analyzed rats and found that linalool inhibits inflammation in vitro and in vivo. The paper also suggested that it was a possible therapeutic candidate for inflammatory disease treatment.

Perhaps the most exciting therapeutic use for linalool is its emerging potential as a novel Alzheimer’s disease treatment. Alzheimer’s disease is a progressive and currently irreversible disease caused by the buildup of brain plaques and cellular tangles that lead to brain degeneration. This degeneration causes severe memory and cognitive impairment. There are currently no cures for Alzheimer’s disease and current treatment strategies are largely ineffective at recovering function. This has set scientists on a quest to identify techniques that reduce plaques and tangles in an effort to reverse the disease’s course and recover normal brain function.

A promising study published in 2016 points to linalool as a potential Alzheimer’s treatment. In a genetic mouse model of Alzheimer’s disease, linalool reversed many of the behavioral and cognitive impairments associated with the disease. Further, it reduced the number of brain plaques and cellular tangles that define the disease and contribute to brain degeneration.

Linalool still has many hurdles before it makes its way into the clinic. But these Alzheimer’s studies together with previous studies demonstrating benefits in pain, anxiety, and depression point to the importance of continued investigation into the therapeutic benefits of linalool and other terpenes in cannabis.

All these studies show promising results on Linalool’s multitude of nervous system targets contributing to its potential ability to help with not only insomnia, but also anxiety, stress, immunity, pain and even Alzheimers.

What are Terpenes?

More than 20,000 terpenes appear throughout nature, in every plant, every flower, and even some insects.  They are highly aromatic and may protect the plants that produce them.  In some plants, terpenes attract pollinators, while in other plants, they cause a strong reaction to repel predators, such as insects or foraging animals. Some terpenes play a protective role in the plant, helping it to recover from damage; others act as a part of the plant’s immune system to keep away infectious germs.

Terpenes determine the unique smells of plants and herbs, such as rosemary, eucalyptus  and lavender.  Terpenes and terpenoids (the oxidized, or dried and cured byproduct of terpenes) are the primary constituents of the essential oils of many types of plants and flowers.[6] Essential oils are used widely as fragrances in perfumery and traditional medicine, such as aromatherapy.  Once thought responsible only for the aroma of plants, terpenes are now known to possess serious medicinal value. Additionally, our sense of smell is linked to the brain’s memory and emotion centers. This means terpenes can hold a significant influence over our greater psyche.

As a result, there is a probable link between the scent of a terpene and its effect. 

Although relatively few of these aromatic hydrocarbons – about 200 – are found in cannabis, terpenes are highly associated with Cannabis and its many different strains.  Studies on the therapeutic effects of different terpenes are increasing in the medical community as more and more states legalize cannabis.  With a wide variety of therapeutic effects, terpenes can help the body destroy bacteria, detoxify, fungus, combat inflammation, relax and more.

Terpenes have been shown to act on receptors and neurotransmitters; they can act as serotonin uptake inhibitors (similar to antidepressants like Prozac); they can enhance norepinephrine activity (similar to tricyclic antidepressants like Elavil); they can increase dopamine activity; and they can augment GABA (the “downer” neurotransmitter that counters glutamate, the “upper”). However, more specific research is needed for improved accuracy in describing and predicting how terpenes in cannabis can be used medicinally to help treat specific ailments and health conditions.

What are the Health Benefits of CBD?

Many people are seeking alternatives to pharmaceuticals with harsh side effects – medicine more in sync with natural processes. By tapping into how we function biologically on a deep level, there is evidence that CBD can provide relief for chronic pain, anxiety, inflammation, depression and many other conditions.  However,  until recently there have been very few well-conducted trials to back up these claims.

The main reason there are few trials to back up the perceived health benefits of CBD is that previous laws lumped marijuana and hemp together in the same basket. However, in December 2015, the FDA eased the regulatory requirements for CBD, which allowed for more scientific research to begin.  New research and mounting anecdotal accounts from patients and physicians highlight CBD’s potential as a treatment for a wide range of maladies, including (but not limited to):

CBD has proven neuroprotective effects and its anti-cancer properties are being investigated at several academic research centers in the United States and elsewhere. A 2010 brain cancer study by California scientists found that CBD “enhances the inhibitory effects of THC on human glioblastoma cell proliferation and survival.” This means that CBD makes THC even more potent as an anticancer substance. Also in 2010, German researchers reported that CBD stimulates neurogenesis, the growth of new brain cells, in adult mammals.

There is no evidence CBD has any abuse or dependence potential and to date there is no evidence that it is associated with any serious side effects, according to the World Health Organization.