Terpenes

Caryophyllene (or β-Caryophyllene)

Terpenes are a family of aromatic organic compounds found mainly in plants such as cannabis (marijuana), tea, pine, lavender, thyme and citrus fruits like lemon. Terpenes are believed to offer a wide range of therapeutic benefits.

See: Terpenes – An Overview

 

β-Caryophyllene (or just “caryophyllene”) is one of the most common terpenes found in cannabis and is frequently the predominant terpene overall in cannabis extracts, particularly if they have been processed under heat. Caryophyllene affects cellular and metabolic systems demonstrating antioxidant, anti-inflammatory, improved wound healing, neuroprotective, anti-cancer and analgesic properties. Additionally, caryophyllene decreases neuropathic pain associated with chemotherapy, diabetes, and chronic nerve damage.

B-Caryophyllene – Found in Black Pepper

 

 

Links to other Pertinent Educational Pages:

Links to ALL Marijuana Educational Pages

Terpenes:

Terpenes – An Overview

 

Terpenes Therapeutic Benefits

Terpenes and Pain

Terpenes and Anxiety

Terpenes and Inflammation

Terpenes and Insomnia

 

Individual Terpenes:

Terpenes – β-Caryophyllene

Terpenes – Limonene

Terpenes – Linalool

Terpenes – Myrcene

 

 

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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 This page is incomplete and continues to be developed…

 

Caryophyllene (or β-Caryophyllene (BCP)

Terpenes – Brief Overview

Terpenes are organic chemicals produced by most plants, as well as some animals including swallowtail butterflies and termites. Terpenes are volatile aromatic molecules, meaning they evaporate easily, and they are some of the primary components of plant resins and flowers. They provide flavor and fragrance to fruits and spices commonly found in a normal diet. Terpenes, not cannabinoids, are mostly responsible for the aroma of cannabis. They are the source of not just the aromas and flavors of cannabis, but they are also responsible for many of the therapeutic benefits that distinguish different cannabis strains. The most commonly studied terpenes found in cannabis plants include alpha-pinene, myrcene, beta-caryophyllene, caryophyllene oxide, linalool, limonene, nerolidol and phytol.

 

Terpenes exert important therapeutic effects, especially in combination with the cannabinoids, especially THC and CBD. The synergy of cannabinoid-terpene interactions contributes to the medical benefits (and side effects) of cannabis, particularly with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer and infections. Terpenes are quite potent, and have been shown to affect human behavior when inhaled from ambient air at serum levels less than 10 ng/m.  Terpenes that occur in plants, however, are often found in very trace amounts and may only comprise 1-2% of dried plant matter. In fact, terpenes account for less than 1% in most cannabis plants. 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. 

See: Types of Terpenes and Terpenoids

 

 

β-Caryophyllene (BCP)

β-Caryophyllene (or just “caryophyllene”) is one of the most common terpenoids found in cannabis and is frequently the predominant terpenoid overall in cannabis extracts, particularly if they have been processed under heat for decarboxylation. In nature, β-caryophyllene is usually found together with small amount of its isomers α-caryophyllene (α-humulene) and γ-caryophyllene or in a mixture with its oxidation product, β-caryophyllene oxide (BCPO).

 

 

Caryophyllene in cannabis and other substances

Described as earthy and peppery, caryophyllene is found in more than two thousand plants, including black pepper (Piper nigrum), Copaiba balsam (Copaifera officinalis), clove,  cinnamon, oregano, basil, thyme, coriander, sage, hops and rosemary. Cannabis strains with prominent amounts of caryophyllene include Super Silver Haze, Sour Diesel, Skywalker, Rock Star, Fire OG, Jack Herer, and Hawaiian Haze..

 

Amount of Caryophyllene in the essential oils of other substances

Of naturally occurring sources, the essential oil of West African black pepper (Piper guineense) has the highest concentration of caryophyllene at 58%.

  • Cannabis, Hemp, Marijuana (Cannabis sativa): 3.8–37.5%
  • Cloves (Syzygium aromaticum): 1.7–19.5%
  • 
Hops (Humulus lupulus): 5.1–14.5%
  • 
Basil (O. micranthum): 4.0–19.8%
  • 
Oregano (Origanum vulgare): 4.9–15.7%
  • 
Black Pepper (Piper nigrum): 7%
  • 
Lavender (Lavandula angustifolia): 4.6–7.5%
  • 
Rosemary (Rosmarinus officinalis): 0.1–8.3%
  • 
True Cinnamon (Cinnamomum zeylanicum): 6.9–11.1%
  • Ylang-ylang (Cananga odorata) [3.1–10.7%]

 

How β-Caryophyllene  Works

β-Caryophyllene’s multiple mechanisms of action are still being explored but its apparent dominant action is on the endocannabinoid system in humans, the system that THC and other cannabinoids found in marijuana interact with.

 

β-Caryophyllene as a CB2 Agonist

Cannabis contains over 65 cannabinoid-like natural products. Δ9-tetrahydrocannabinol (THC), Δ8-tetrahydrocannabinol, and cannabinol (CBN) that activate cannabinoid receptor types 1 (CB1) or 2 (CB2). CB1 and CB2 cannabinoid receptors are present on free nerve-endings as part of the endocannabinoid system (ECS). These can be activated by cannabinoid therapy to provide therapeutic benefits. The CB1 receptor is responsible for psychoactive, euphoric effects and analgesic effects, as well as other therapeutic effects.

 

The CB2 receptor is the primary peripheral receptor for cannabinoids and is mainly expressed in immune tissues where it has been shown to modulate immune cell functions. The CB2 receptor also inhibits inflammation and edema and also has analgesic effects. In the gastrointestinal tract, CB2 receptor agonists have been shown to reduce inflammation in colitis. The CB2 receptor is also a potential target for the treatment of atherosclerosis and osteoporosis.

 

Some consider β-Caryophyllene to be a cannabinoid because it strongly binds to CB2 receptors as a functional agonist although it does not bind to CB1 receptors.  The CB2 receptor mediates anti-inflammatory and analgesic responses induced by β-caryophyllene. BCP inhibits neuropathic pain through CB2 receptor activation.

  

BCPO and α-humulene, on the other hand, do not bind with CB2 receptors and exert their pharmacologic effects through different mechanisms.

.

Other Mechanisms of Action of BCP

It is proposed that BCP also offers therapeutic effects by activating the nuclear receptors, peroxisome proliferator-activated receptors (PPARs). Additionally BCP also acts on other receptors in the skin including TRPM1, TRPM6, TRPV4, TRPV6 and TRP8. BCP modulates numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. Based on these pharmacological properties and molecular mechanisms, BCP may have therapeutic potential to modulate the immune system with anti-inflammatory, organ-protective, and anti-viral properties.

Bioavailability of β-Caryophyllene

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. Both BCP and BCPO are sesquiterpenes, a class of terpenes with more complex molecular formulas compared with the monoterpenoids (pinene, carene, myrcene and limonene) which contributes to a lower solubility in water and biological fluids which in turn limits BCP and BCPO absorption into cells. This may affect the therapeutic effectiveness of BCP and BCPO when ingested orally. This poor water solubility of BCP and BCPO may be overcome with use of liposomal drug delivery systems, which provide much higher bioavailability of these compounds to ensures obtaining desired therapeutic effects. Inhaled and topical applications of BCP and BCPO have high bioavailability and should allow for their effectiveness when administered in these ways.

 

Metabolism of BCP

The metabolism of BCP and BCPO is poorly understood.

 

Oral Use of BCP

Studies in humans are lacking regarding oral use of BCP for therapeutic purposes although it is “generally recognized as safe” by the FDA as a food additive. In preclinical studies with mice the chronic oral administration of BCP has been shown to reduce neuropathic pain, including thermal hyperalgesia (excessive pain perception) and mechanical allodynia (inappropriate perception of pain in response to a stimulis that should not be painful). BCP also reduces spinal neuroinflammation, the condition that is the basis of acute pain transitioning to chronic pain. No signs of tolerance to the anti-hyperalgesic effects of BCP over 2-weeks of treatment were identified in the mouse study but, on the contrary, the BCP effect became stronger during the treatment period. Given the potentially limited bioavailability of oral BCP and BCPO, studies are needed to determine effective oral dosing.

 

The question to be considered now is what dose is relevant to humans? Based on an effective dose in mice estimated for the human equivalent dose for a 132 lb adult, the average daily BCP intake would be in the range of 10–200 mg. This dose would be sufficient for significant CB2 cannabinoid receptor activation. It has also been estimated that BCP is commonly ingested with vegetable foods, including spinach and chard, at an estimated daily intake of 10–200 mg. This could be a dietary factor that potentially modulates inflammation. Human studies are needed.

 

Inhaled Use of BCP

Studies evaluating inhalation of BCP in mice determined that after inhalation volatile BCP is distributed into the brain via blood circulation. It is also possible that nasally inhaled BCP may also distribute directly into cerebrospinal fluid as well as blood. Inhaled BCP was also noted to distribute largely to the liver where it may increase the level of glutathione and thereby increase liver antioxidant capacity.  It was noted that upon entering the blood the half-life of BCP was 134 min.

 

Of interest it should also be noted that the olfactory nerve receptors believed to be involved in the therapeutic effects of nasally inhaled substances such as BCP are also found in the intestines, suggesting an alternative mechanism for therapeutic effect with ingested BCP and other terpenes. Additional pharmacokinetic studies need to be performed in humans but remain lacking.

 

Topical Use of BCP

 β-caryophyllene activates several different types of receptors other than olfactory receptors in the skin, including cannabinoid receptor 2 (CB2) The CB2 receptor is present in nerve cells, immune tissue, hair follicles, sebaceous glands, the dermo-muscular layer in the dermis, and vascular smooth muscle in intact skin. Additionally BCP also acts on other receptors in the skin including TRPM1, TRPM6, TRPV4, TRPV6 and TRP8.Although it is not clear which receptors are involved in BCP’s therapeutic benefits, BCP applied topically reduces pain and inflammation and can improve wounds re-epithelialization and healing.

 

 

Therapeutic Properties of β-Caryophyllene

Our understanding of the therapeutic benefits offered by Carophyllene is based almost entirely “preclinical” research, which consists of studies performed in a laboratory (in vitro) and/or animal studies. Preclinical research indicates that BCP has anti-inflammatory, analgesic and anti-cancer properties and also facilitates wound healing. Early research suggests potential benefit for substance abuse of alcohol and cocaine. Unfortunately, clinical research with humans is still very limited in all these regards.

 

The Anti-Inflammatory and Antioxidant Properties of β-Caryophyllene

Anti-inflammatory activity

β-Caryophyllene’s anti-inflammatory activity is comparable in potency to phenylbutazone, etodolac and indomethacin. BCP is often used in topical anti-inflammatory ointments and salves. In contrast to NSAIDs, however, caryophyllene protects the stomach lining  and has been claimed to be effective in treating duodenal ulcers in the United Kingdom. Tissue inflammation enhances pain sensation through the sensitization of pain receptors (nociceptors) which are peripheral nerves that respond to painful stimuli, and also through sensitization of spinal nerves which leads to enhanced transmission of pain signals to the brain. The resulting allodynia and hyperalgesia of the inflamed tissue also contributes to the recuperative process in that pain sensation typically reverts to normal levels as the inflammatory response resolves.

The anti-inflammatory properties of BCP have been extensively shown in different mouse models of disease. A recent study shows that BCP synergizes with curcumin in exerting anti-inflammatory activity in an experimental in vitro model of osteoarthritis, strongly suggesting the potential benefit of a dual combination of these two compounds for the management of osteoarthritis. This curcumin synergy has also been found with the catechins found in green tea. Similar to curcumin, carophyllene suppresses inflammation by reducing levels of IL-1β, IL-6, through activity at  prostaglandin PGE-1 and at the NLRP3 inflammasome. 

 

Anti-oxidant activity

Studies have also shown that β-Caryophyllene and curcumin up-regulates Nrf2 activity to protect cells from oxidative damage. Nrf2 (nuclear factor erythroid 2) is a transcription factor that is involved in cellular responses to oxidative damage and inflammation.

See: Nrf2 Activators.

 

Neuroinflammation

Development of neuropathic pain is accompanied by the activation and proliferation of glia cells, immune cells in the spinal cord responsible for the development of neuroinflammation. Caryophyllene is thought to be effective against neuroinflammation by reducing activity of glial cells.

 

Inflammatory Bowel Disease

In the gastrointestinal tract, activation of CB2 receptors has been shown to prevent experi- mental colitis by reducing inflammation, suggesting the potential benefit of BCP for use in Crohn’s disease and ulcerative colitis.

 

 

Anti-Cancer Properties of β-Caryophyllene

Both sesquiterpenes BCP and BCPO have cytotoxic activities against several types of cancer cells including human cervical adenocarcinoma cells, leukemia cancer cells, lung cancer cells),  gastric cancer cells and stomach cancer cells. Aside from their direct anticancer activities, BCP and BCPO may also enhance the effectiveness of traditional anticancer drugs, such as paclitaxel and doxorubicin.

 

 

Conditions that may benefit from β-Caryophyllene:

β-Caryophyllene: Pain

Early animal research in rats/mice have identified β-caryophyllene (BCP) as a selective full agonist at the cannabinoid receptor type 2 (CB2). It has been shown to exhibit analgesic effects in neuropathic pain associated with chemotherapy, diabetes, and chronic nerve damage.  Analgesia produced by BCP is mediated by activation of CB2 receptors, which stimulates the local release from keratinocytes (superficial skin cells) of the endogenous opioid β-endorphin. When combined with morphine, a synergistic, increased analgesic benefit of low dose BCP has Q

In inflammatory hyperalgesia, indirect pain inhibition through CB2 receptors on mast and immune cells is possibly achieved by the reduc- tion of prostanoids or cytokines release, which are respon- sible for peripheral nociceptor sensitization.

 

 

β-Caryophyllene: Cold Weather and Wild Giant Pandas

The TRPM8 receptor on sensory nerves in the skin become activated upon exposure to cold, triggering the sensation of feeling cold.  This receptor may be triggered environmentally by exposure to cold or chemically by exposure to compounds such as menthol.  β-caryophyllene inhibits cold-activation of these receptors and suppresses the perception of feeling cold which helps to improve cold tolerance at low temperatures.

In fact, studies have shown that in cold weather, giant pandas roll in fresh horse manure which is rich in β-caryophyllene as a means of adapting to the cold!  As of yet I have not found studies to assess how effective topical β-caryophyllene may be in humans for tolerating cold weather, or reducing the impact of cold weather on pain. I will be looking…

β-Caryophyllene: Paclitaxel-induced Peripheral Neuropathy (PINP)

Painful peripheral neuropathy is a common side effect of paclitaxel (PTX), a chemotherapy medication used to treat a number of types of cancer. However, currently employed analgesics have several side effects and are poorly effective. β-caryophyllene (BCP), a selective CB2 agonist, has shown analgesic effect in neuropathic pain models, but its role in chemotherapy-induced neuropathic pain is not yet known. A 2017 study in mice receiving PTX indicated that BCP reduced nerve pain sensitivity to mechanical stimulation (allodynia) induced by the PTX possibly through CB2-activation in the CNS and inhibition of inflammatory cytokines. These results suggest that BCP might be useful in treating the nerve pain associated with PINP.

 

 

β-Caryophyllene: Wound Healing

β-caryophyllene may improve wound healing and reduce scarring, although it is not clear whether it does so via olfactory receptors or other receptors in the skin. Topical application of β-caryophyllene on cutaneous wounds can improve re-epithelialization, but β-caryophyllene activates several different types of receptors other than olfactory receptors, so this improved re-epithelialization may be mediated by activating other routes.  β-caryophyllene acts on the cannabinoid receptors 2 (CB2) in the skin but also on TRPM1, TRPM6, TRPV4, TRPV6 channel receptors, suggesting the possibility of the involvement of these channels in improving wound healing.

 

β-Caryophyllene: Depression and Stress

β-caryophyllene shows promise for treating depression and stress related mental illnesses due to its direct binding to CB2 receptors.

 

β-Caryophyllene: Diabetes and Associated Complications

Preclinical studies show underlying mechanisms of BCP in skeletal muscles, adipose tissues, liver, and pancreatic β-cells that suggest BCP has the capability to increase insulin secretion, insulin sensitivity, glucose uptake and reduce glucose absorption. Additionally it may reduce levels of triglycerides and cholesterol.

 

Based on the health benefits, low toxicity, relatively safety in humans use with plausible pharmacological activity and molecular mechanisms, BCP appears to be a promising candidate for use in insulin resistance, T2DM, obesity, hyperlipidemia, and diabetic complications. BCP has potential for use as an adjuvant to reduce the doses of the currently used medications and  synergistically enhance therapeutic effects. However, further studies are required to explore these preclinical studies towards offering therapeutic benefits in humans.

 

 

β-Caryophyllene: Multiple Sclerosis

Multiple sclerosis (MS) is a severe inflammatory demyelinating disease of the central nervous system (CNS). It affects over two million people worldwide although the cause of MS is  not completely understood. However, studies with MS patients suggest that the demyelination associated with MS in the CNS results from a T cell-mediated autoimmune response. Due to growing research indicating that some of the constituents found in cannabis possess anti-inflammatory properties and may suppress certain functions withing the immune response, research is focusing on cannabis use to treat MS.

In an investigation published in 2017 to evaluate the therapeutic potential of BCP in an experimental animal model of multiple sclerosis (MS),  it was found that BCP significantly reduces both the clinical and pathological features of the animal model. The mechanisms underlying BCPs immunomodulatory effect appears to be linked to its ability to inhibit microglial cells, CD4+ and CD8+ T lymphocytes and pro-inflammatory cytokines. Furthermore, it reduce axonal demyelination  through the activation of CB2 receptor. The study has important implications for clinical research and strongly supports the effectiveness of BCP as a possible molecule to target in the development of effective treatment for MS.

 

β-Caryophyllene: Alcohol and Cocaine Abuse

Research also suggest that CB2 receptors play a major role in alcohol reward and the CB2 receptor system may be involved in alcohol and cocaine dependence via modulation of dopamine reward pathways. In mice, β-caryophyllene has been shown to reduce voluntary alcohol intake as well as decrease cocaine self-administration. It may therefore represent a potential pharmacological target for the treatment of alcohol and cocaine abuse.

 

β-Caryophyllene: Other Potential Therapeutic Benefits

BCP is believed to be a neuroprotective,, antioxidant, and anticonvulsive agent with antiviral and antibacterial activities as well as being able to improve lipid profiles, alleviate endometriosis, and show promise for interstitial cystitis and protection against nonalcoholic fatty liver disease.

Caryophyllene: Products

Despite its promising biological activities, β-caryophyllene is characterized by high lipid solubility but poor solubility in water-based media such as biological fluids, which limits its bioavailability and absorption into cells. The poor solubility of this terpene in water-based fluids can hinder its uptake into cells, resulting in inconsistent therapeutic effects, thus limiting its application. β-caryophyllene’s absorption is good when it is delivered in an oil-based medium but new products are being developed in which the β-caryophyllene is enveloped in a fatty layer (liposomal) to enhance its bioavailabity when delivered in aqueous media.

 

Over-the-Counter (OTC) Products

Topical BCP Products

Because β-caryophyllene is generally considered safe, it is available in over-the-counter (OTC) products. A particularly useful formulation for β-caryophyllene is in topical creams because there are many CB2 receptors as well as TRPM8 receptors in the skin allowing for potentially effective treatment of nerve pain and cold sensitiviy respectively.

 

Entourage Bio-Therapeutics

There are growing numbers of commercial topical products now available, including Entourage Bio-Therapeutics, which also contain CBD but are described as THC-free. 

 

Direct Effects™ Topical β-Caryophyllene (? available)

As part of a patent process regarding topical therapy with β-Caryophyllene, it was reported that 30 mg of β-caryophyllene applied to the back of neck, spinal regions or at peripheral areas of neurological dysfunction provided relief and benefit for the following conditions within 10 to 15 minutes of topical application:

      • Muscle Tension & Spasm
      • Peripheral Neuropathic Pain
      • Post-Herpetic Neuralgia/Zoster

      • Tinnitus/Ringing in Ears

      • Trigeminal Neuralgia

      • Blepharospasm

It was reported that the duration of therapeutic effect ranged from a few hours to an entire day, depending on condition treated; and its severity and duration. The only side effects reported were occasional tingling and slight transient burning sensation following topical cream application. There was a rare headache. Rash or irritation at the site of application was experienced in less than 5% of patients treated. Because of its non-systemic nature, no systemic side effects or drug-drug interactions were observed.

 

Oral BCP Products

Nootropics Depot  250 mg capsules with 6% BCP  (equal to 15 mg BCP)

Nootropics Depot powder with 6% BCP

 

Products combining CBD and β-Caryophyllene:

There is evidence that combining  CBD and β-Caryophyllene may have a synergistic benefit, called the “Entourage Effect” in which the two together will work better than either by themselves. One highly recommended CBD product for sublingual or oral use that is rich in β-Caryophyllene is Energy and Focus, available from Carolina Cannabinoids.

 

 

Prescription BCP Products (Cannabis-based)

Topical

In addition to OTC products, prescription cannabis-based products that also contain THC are available in LA, including “Soothe” by Ilera.

 

Caryophyllene: In Food

β-caryophyllene is commonly ingested with vegetables, and an estimated daily intake of 10–200 mg of this terpene could be a dietary factor to benefit inflammation and other pathophysiological processes.

 

β-caryophyllene can be obtained in the diet by including fresh, aromatic herbs such as clove, black pepper, rosemary, cinnamon, and basil. Other source foods include carraway, hops, lavender, and sage. Chai, a spicy tea which usually blends tea with cinnamon, black peppercorns, clove, and ginger, is a good source of BCP.

 

β-Caryophyllene Oxide (BCPO)

This terpenoid is an oxidation metabolic byproduct of beta-caryophyllene and is found in dried hemp. Like BCP, β-caryophyllene oxide (BCPO) is also found in eucalyptus, lemon balm, cloves, basil, oregano, black pepper, rosemary, and hops. It has a characteristic herbal flavor and a woody aroma and it is said that this terpene is one that allows sniffing dogs to recognize cannabis because of its strong scent.

 

BCPO’s therapeutic benefits have not been well studied but it is purported to have anti-inflammatory and pain-relieving properties as well as anticancer activity by suppressing growth and proliferation of numerous cancer cells. β-caryophyllene oxide does not bind to CB1 or CB2 receptors.

While BCP binds to peripheral cannabinoid receptor type 2 (CB2) leading to β-endorphin release from keratinocytes and activation of opioid receptors, the analgesic benefits of BCPO may be obtained by inhibition of central pain receptors.

 

 

 

 

Resources:

National Academy of Sciences

  1. 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:

β-Caryophyllene (BCP)

BCP – Overviews

  1. The Effects of Essential Oils and Terpenes in Relation to Their Routes of Intake and Application – 2020

 

BCP – Aging/Geroprotection

  1. Terpenoids as Potential Geroprotectors – 2020

 

BCP – Anxiety

  1. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice – 2014
  2. β-Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats – PubMed – 2018
  3. 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

 

BCP – Antioxiant/Oxidative Stress

  1. Improvement of Oxidative Stress and Mitochondrial Dysfunction by β-Caryophyllene – A Focus on the Nervous System – 2021
  2. β-Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats – PubMed – 2018

 

BCP – Arthritis

  1. Cannabinoid CB2 Receptors Regulate Central Sensitization and Pain Responses Associated with Osteoarthritis of the Knee Joint
  2. β-Caryophyllene Ameliorates MSU-Induced Gouty Arthritis and Inflammation Through Inhibiting NLRP3 and NF-κB Signal Pathway – In Silico and In Vivo – 2021
  3. β-Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats – PubMed – 2018
  4. Exploiting Curcumin Synergy With Natural Products Using Quantitative Analysis of Dose–Effect Relationships in an Experimental In Vitro Model of Osteoarthritis – 2019

 

BCP – Bioavailability & Pharmacokinetics

  1. Distribution of inhaled volatile β‐caryophyllene and dynamic changes of liver metabolites in mice – 2021
  2. β-caryophyllene Delivery Systems Enhancing the Oral Pharmacokinetic and Stability – PubMed – 2018
  3. SPC Liposomes as Possible Delivery Systems for Improving Bioavailability of the Natural Sesquiterpene β-Caryophyllene – 2018

 

BCP – Central Sensitization

  1. Cannabinoid CB2 Receptors Regulate Central Sensitization and Pain Responses Associated with Osteoarthritis of the Knee Joint
  2. A systematic review on the neuroprotective perspectives of beta-caryophyllene – PubMed – 2018

 

BCP – Colitis

  1. β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway – 2011

 

 BCP – Cold Weather / TPRM8 Receptor

  1. Why wild giant pandas frequently roll in horse manure – 2020
  2. Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain. – 2006
  3. The menthol receptor TRPM8 is the principal detector of environmental cold – PubMed – 2007
  4. Molecular basis of peripheral innocuous cold sensitivity – 2018
  5. Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing – 2021

 

BCP – Dental

  1. β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors – 2020

 

BCP – Diabetes

  1. Therapeutic Potential of β-Caryophyllene – A Dietary Cannabinoid in Diabetes and Associated Complications – 2021

 

BCP – Diet

  1. A focused review on CB2 receptor-selective pharmacological properties and therapeutic potential of β-caryophyllene, a dietary cannabinoid – 2021
  2. Beta-caryophyllene is a dietary cannabinoid – 2008 
  3. β-caryophyllene Delivery Systems Enhancing the Oral Pharmacokinetic and Stability – PubMed – 2018
  4. Cannabimimetic phytochemicals in the diet – an evolutionary link to food selection and metabolic stress adaptation? – 2016
  5. Therapeutic Potential of β-Caryophyllene – A Dietary Cannabinoid in Diabetes and Associated Complications – 2021
  6. β-Caryophyllene, A Natural Dietary CB2 Receptor Selective Cannabinoid can be a Candidate to Target the Trinity of Infection, Immunity, and Inflammation in COVID-19 – 2021

 

 

BCP – Infection/COVID-19

  1. β-Caryophyllene, A Natural Dietary CB2 Receptor Selective Cannabinoid can be a Candidate to Target the Trinity of Infection, Immunity, and Inflammation in COVID-19 – 2021

 

BCP – Inflammation/Neuroinflammation

  1. (−)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis – 2017
  2. β-Caryophyllene Ameliorates MSU-Induced Gouty Arthritis and Inflammation Through Inhibiting NLRP3 and NF-κB Signal Pathway – In Silico and In Vivo – 2021
  3. β-Caryophyllene, A Natural Dietary CB2 Receptor Selective Cannabinoid can be a Candidate to Target the Trinity of Infection, Immunity, and Inflammation in COVID-19 – 2021
  4. Role of β-Caryophyllene in the Antinociceptive and Anti-Inflammatory Effects of Tagetes lucida Cav. Essential Oil – 2020
  5. β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors – 2020
  6. A systematic review on the neuroprotective perspectives of beta-caryophyllene – PubMed – 2018
  7. Protective Effects of (E)-β-Caryophyllene (BCP) in Chronic Inflammation – 2020

 

BCP – Misc

  1. Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion – 2018

 

BCP – Multiple Sclerosis

  1. (−)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis – 2017

 

BCP – Pain

  1. β‐caryophyllene and β‐caryophyllene oxide—natural compounds of anticancer and analgesic properties – 2016
  2. Antiallodynic effect of β-caryophyllene on paclitaxel-induced peripheral neuropathy in mice. – PubMed – NCBI
  3. The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic… – PubMed – NCBI – 2014
  4. The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain – 2013
  5. Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception – PubMed – 2013
  6. Cannabinoid CB2 Receptors Regulate Central Sensitization and Pain Responses Associated with Osteoarthritis of the Knee Joint
  7. Role of β-Caryophyllene in the Antinociceptive and Anti-Inflammatory Effects of Tagetes lucida Cav. Essential Oil – 2020
  8. A systematic review on the neuroprotective perspectives of beta-caryophyllene – PubMed – 2018
  9. Efficacy of Essential Oils in Pain – A Systematic Review and Meta-Analysis of Preclinical Evidence – 2021

 

BCP – Products

BCP – Product Formulations

  1. Preparation and Characterization of Liposomal β‐Caryophyllene (Rephyll) – 2020
  2. SPC Liposomes as Possible Delivery Systems for Improving Bioavailability of the Natural Sesquiterpene β-Caryophyllene – 2018

 

BCP – Sources

  1. Development of a Gas Chromatography Method for the Analysis of Copaiba Oil – 2017
  2. Fast-Acting_and_Receptor-Mediated_Regulation_of_Neuronal Signaling Pathways by Copaiba Essential Oil
  3. β-Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats – PubMed – 2018
  4. Role of β-Caryophyllene in the Antinociceptive and Anti-Inflammatory Effects of Tagetes lucida Cav. Essential Oil – 2020
  5. 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

 

BCP – Synergy: Curcumin & Echinacea

  1. Exploiting Curcumin Synergy With Natural Products Using Quantitative Analysis of Dose–Effect Relationships in an Experimental In Vitro Model of Osteoarthritis – 2019

 

BCP – Topical

  1. NON-CANNABIS THERAPY – Cannabinoid Therapy Without Using Cannabis: Direct Effects™ Topical β-Caryophyllene
  2. Beta-caryophyllene enhances wound healing through multiple routes – 2019
  3. The fragrance chemical beta-caryophyllene-air oxidation and skin sensitization – PubMed – 2005

 

BCP – Toxicity

  1. The fragrance chemical beta-caryophyllene-air oxidation and skin sensitization – PubMed – 2005
  2. Toxicological Evaluation of β-Caryophyllene Oil: Subchronic Toxicity in Rats. – PubMed – NCBI 2016

 

BCP – Wound Healing

  1. Beta-caryophyllene enhances wound healing through multiple routes – 2019

 

Terpenes

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. The Effects of Essential Oils and Terpenes in Relation to Their Routes of Intake and Application – 2020

 

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

 

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
  4. Cannabinoid CB2 Receptors Regulate Central Sensitization and Pain Responses Associated with Osteoarthritis of the Knee Joint

 

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 – 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 – 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. Medicinal Plants of the Family Lamiaceae in Pain Therapy – A Review – 2018
  6. 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
  7. Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant – 2020
  8.  The Molecular Mechanisms That Underpin the Biological Benefits of Full-Spectrum Cannabis Extract in the Treatment of Neuropathic Pain and Inflammation – PubMed – 2020
  9. Cannabis-based medicines and the perioperative physician – 2019
  10. Cannabis‐based medicines for chronic neuropathic pain in adults – 2018
  11. 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
  12. Role of Cannabinoids and Terpenes in Cannabis-Mediated Analgesia in Rats – PubMed – 2019
  13. Antinociceptive effect of inhalation of the essential oil of bergamot in mice – 2018
  14. Analgesic Potential of Essential Oils – 2016
  15. Analgesic-Like Activity of Essential Oil Constituents – An Update – 2017

 

 

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
  9. Protective Effects of (E)-β-Caryophyllene (BCP) in Chronic Inflammation – 2020

 

Terpenes – Wound Healing

  1. Beta-caryophyllene enhances wound healing through multiple routes – 2019

 

 

 Individual Sources of Terpenes

Terpenes – 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

 

 

 

 

 

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.

 

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