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The CB2 receptor and its role as a regulator of inflammation.

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“The CB2 receptor is the peripheral receptor for cannabinoids.

It is mainly expressed in immune tissues, highlighting the possibility that the endocannabinoid system has an immunomodulatory role.

In this respect, the CB2 receptor was shown to modulate immune cell functions, both in cellulo and in animal models of inflammatory diseases.

In this regard, numerous studies have reported that mice lacking the CB2 receptor have an exacerbated inflammatory phenotype.

This suggests that therapeutic strategies aiming at modulating CB2 signaling could be promising for the treatment of various inflammatory conditions.

Herein, we review the pharmacology of the CB2 receptor, its expression pattern, and the signaling pathways induced by its activation. We next examine the regulation of immune cell functions by the CB2 receptor and the evidence obtained from primary human cells, immortalized cell lines, and animal models of inflammation.

Finally, we discuss the possible therapies targeting the CB2receptor and the questions that remain to be addressed to determine whether this receptor could be a potential target to treat inflammatory disease.”

http://www.ncbi.nlm.nih.gov/pubmed/27402121

Benefits of Cannabis Terpenes: Ocimene, Terpinolene, and Guaiol

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Leafly

“Terpenes are a group of fragrant essential oils – secreted alongside cannabinoids like THC and CBD – that contribute to the complex aroma of cannabis. They are also generally responsible for many of the distinguishing characteristics of different strains, and this discovery has led to a sharp increase in interest among researchers, producers, and consumers alike.

Though cannabis contains up to 200 different terpenes, there are about 10 primary terpenes and 20 secondary terpenes that occur in significant concentrations. We’d like to introduce you to the potential health benefits of three of those terpenes: ocimene, terpinolene, and guaiol.

Ocimene is an isomeric hydrocarbon found in a wide variety of fruits and plants. It is recognized by its sweet, fragrant, herbaceous, and woodsy aromas, which feature prominently in several perfumes, and which help plants defend themselves in their natural environment. Ocimene occurs naturally in botanicals as diverse as mint, parsley, pepper, basil, mangoes, orchids, kumquats, and of course cannabis.

Ocimene’s potential medical benefits include:

  • Antiviral
  • Antifungal
  • Antiseptic
  • Decongestant
  • Antibacterial

Cannabis strains that can test high in ocimene include Golden Goat, Strawberry Cough,Chernobyl, and Space Queen. At Tilray, strains currently displaying high concentrations of ocimene include OG Kush, Elwyn, and Lemon Sour Diesel.

Terpinolene is another isomeric hydrocarbon, characterized by a fresh, piney, floral, herbal, and occasionally citrusy aroma and flavor. It is found in a variety of other pleasantly fragrant plants including nutmeg, tea tree, conifers, apples, cumin, and lilacs, and is sometimes used in soaps, perfumes, and lotions.

Terpinolene’s potential medical benefits include:

  • Anticancer
  • Antioxidant
  • Sedative
  • Antibacterial
  • Antifungal

Terpinolene is found most commonly in sativa-dominant strains; a few that frequently exhibit high concentrations of this terpene include Jack Herer and its derivatives, such as Pineapple Jack, J1, and Super Jack. At Tilray, strains currently possessing higher than average concentrations of terpinolene include Lemon Sour Diesel, Afghani, and Jean Guy.

Guaiol is not an oil but a sesquiterpenoid alcohol, and is also found in cypress pine and guaiacum. It has been used for centuries as a treatment for diverse ailments ranging from coughs to constipation to arthritis. It is also an effective insect repellent and insecticide.

Guaiol’s potential medical properties include:

  • Antimicrobial
  • Anti-inflammatory

Strains that can test high in guaiol include Chocolope, Liberty Haze, and Blue Kush. At Tilray, strains currently exhibiting relatively high concentrations of guaiol include Barbara Bud, Jean”

https://www.leafly.com/news/cannabis-101/benefits-of-cannabis-terpenes-ocimene-terpinolene-and-guaiol

Effect of myrcene on nociception in mice.

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“Myrcene, a monoterpene… The results suggest that myrcene is capable of inducing antinociception in mice, probably mediated by alpha 2-adrenoceptor stimulated release of endogenous opioids.” http://www.ncbi.nlm.nih.gov/pubmed/1983154

“Myrcene as a natural base chemical in sustainable chemistry: a critical review.”  http://www.ncbi.nlm.nih.gov/pubmed/20013989

“Single dose toxicity study of beta-myrcene, a natural analgesic substance.”  http://www.ncbi.nlm.nih.gov/pubmed/2101331

“Myrcene mimics the peripheral analgesic activity of lemongrass tea.  Terpenes such as myrcenemay constitute a lead for the development of new peripheral analgesics with a profile of action different from that of the aspirin-like drugs.”  http://www.ncbi.nlm.nih.gov/pubmed/1753786

“Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol. The top five major compounds in Bedrocan extracts were Delta(9)-THC, cannabigerol (CBG), terpinolene, myrcene, and cis-ocimene in Bedrobinol Delta(9)-THC, myrcene, CBG, cannabichromene (CBC), and camphene in Bediol cannabidiol (CBD), Delta(9)-THC, myrcene, CBC, and CBG. The major components in Bedrocan smoke were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene. The major components in Bedrocan vapor were Delta(9)-THC, terpinolene, myrcene, CBG, cis-ocimene and CBD in Bedrobinol Delta(9)-THC, myrcene and CBD in Bediol CBD, Delta(9)-THC, myrcene, CBC and terpinolene. ” http://www.ncbi.nlm.nih.gov/pubmed/20118579

Guaiol–a naturally occurring insecticidal sesquiterpene.

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“The dichloromethane fraction of Ferula ferulaeoides was analyzed by GC and GC-MS, and thirty-four compounds were identified. The main component in the fraction, guaiol (37.0%) was separated by chromatographic methods and identified from spectroscopic data, including 1H and 13C NMR, and X-ray crystallographic diffraction. Guaiol showed significant inhibition of aphids at a concentration of 70 mg/L. It also showed good contact activities against the 4th instar larvae of Mythimna separate and 3rd instar larvae of Plutella xylostella, with LD50 values of 0.07 and 8.9 mg/larva, as well as fumigation activity against the 4th instar larvae ofM. separata and adult Musca domestica, with LC50 values of 3.5 microL/L and 16.9 microL/L, respectively.” http://www.ncbi.nlm.nih.gov/pubmed/24354171

Anticancer and antioxidant properties of terpinolene in rat brain cells.

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“Terpinolene (TPO) is a natural monoterpene present in essential oils of many aromatic plant species.

Our findings clearly demonstrate that TPO is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.” http://www.ncbi.nlm.nih.gov/pubmed/24084350

“Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol. The major components in Bedrocan smoke were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene.”  http://www.ncbi.nlm.nih.gov/pubmed/20118579

“The sedative effect of inhaled terpinolene in mice and its structure-activity relationships.” http://www.ncbi.nlm.nih.gov/pubmed/23339024

 “Anticancer and antioxidant properties of terpinolene in rat brain cells.”  http://www.ncbi.nlm.nih.gov/pubmed/24084350

Cannabinoid receptor 1 binding activity and quantitative analysis of Cannabis sativa L. smoke and vapor.

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cpb

“Cannabis sativa L. (cannabis) extracts, vapor produced by the Volcano vaporizer and smoke made from burning cannabis joints were analyzed by GC-flame ionization detecter (FID), GC-MS and HPLC. Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol.

Cannabinoids plus other components such as terpenoids and pyrolytic by-products were identified and quantified in all samples. Cannabis vapor and smoke was tested for cannabinoid receptor 1 (CB1) binding activity and compared to pure Delta(9)-tetrahydrocannabinol (Delta(9)-THC).

The top five major compounds in Bedrocan extracts were Delta(9)-THC, cannabigerol (CBG), terpinolene, myrcene, and cis-ocimene in Bedrobinol Delta(9)-THC, myrcene, CBG, cannabichromene (CBC), and camphene in Bediol cannabidiol (CBD), Delta(9)-THC, myrcene, CBC, and CBG.

The major components in Bedrocan vapor (>1.0 mg/g) were Delta(9)-THC, terpinolene, myrcene, CBG, cis-ocimene and CBD in Bedrobinol Delta(9)-THC, myrcene and CBD in Bediol CBD, Delta(9)-THC, myrcene, CBC and terpinolene.

The major components in Bedrocan smoke (>1.0 mg/g) were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene.

There was no statistically significant difference between CB1 binding of pure Delta(9)-THC compared to cannabis smoke and vapor at an equivalent concentration of Delta(9)-THC.”

http://www.ncbi.nlm.nih.gov/pubmed/20118579

Inhibition of the cataleptic effect of tetrahydrocannabinol by other constituents of Cannabis sativa L.

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“Tetrahydrocannabinol (THC) induced catalepsy in mice, whereas a cannabis oil (6.68% w/w THC), four cannabinoids and a synthetic mixture did not. Cannabinol (CBN) and olivetol inhibited THC-induced catalepsy in the mornings and the evenings, but cannabidiol (CBD) exhibited this effect only in the evenings. A combination of CBN and CBD inhibited THC-induced catalepsy equal to that of CBN alone in the mornings, but this inhibition was greater than that produced by CBN alone in the evenings.”  http://www.ncbi.nlm.nih.gov/pubmed/2897447

Isolation from Cannabis sativa L. of cannflavin–a novel inhibitor of prostaglandin production.

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“The isolation from Cannabis sativa L. of an inhibitor of prostaglandin (PG) E2 production by cultured rheumatoid synovial cells is described. This agent, for which the name Cannflavin has been coined, is distinct from cannabinoids on the basis of isolation procedure, preliminary structural analysis and biological properties. The activity of Cannflavin has been compared with several established anti-inflammatory drugs and the major cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/3859295

Cannflavins from hemp sprouts, a novel cannabinoid-free hemp food product, target microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase

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“Hemp seeds are of great nutritional value, containing all essential amino acids and fatty acids in sufficient amount and ratio to meet the dietary human demand.

Hemp seeds do not contain cannabinoids, and because of their high contents of ω-3 fatty acids, are enjoying a growing popularity as a super-food to beneficially affect chronic inflammation.

Seeds also lack the typical phenolics of hemp leaves and inflorescences, but we found that sprouting, while not triggering the production of cannabinoids, could nevertheless induce the production of the anti-inflammatory prenylflavonoids cannflavins A and B.

This effect was especially marked in Ermo, a cannabinoid-free variety of Cannabis sativa L. Microsomal prostaglandin E2 synthase (mPGES-1) and 5-lipoxygenase (5-LO) were identified as the molecular targets of cannflavins A and B, solving an almost three-decade old uncertainty on the mechanism of their the anti-inflammatory activity.

No change on the fatty acid profile was observed during sprouting, and the presence of lipophilic flavonoids combines with the high concentration of ω-3 essential acids to qualify sprouts from Ermo as a novel anti-inflammatory hemp food product worth considering for mass production and commercial development.”

http://www.sciencedirect.com/science/article/pii/S2213434414000176