Category Archives: Uncategorized

Cannabinoids protect cells from oxidative cell death: a receptor-independent mechanism.

Posted on by
Reply

Journal of Pharmacology and Experimental Therapeutics

“Serum is required for the survival and growth of most animal cells. In serum-free medium, B lymphoblastoid cells and fibroblasts die after 2 days.

We report that submicromolar concentrations of Delta(9)-tetrahydrocannabinol (THC), Delta(8)-THC, cannabinol, or cannabidiol, but not WIN 55,212-2, prevented serum-deprived cell death. Delta(9)-THC also synergized with platelet-derived growth factor in activating resting NIH 3T3 fibroblasts.

The cannabinoids‘ growth supportive effect did not correlate with their ability to bind to known cannabinoid receptors and showed no stereoselectivity, suggesting a nonreceptor-mediated pathway.

Direct measurement of oxidative stress revealed that cannabinoids prevented serum-deprived cell death by antioxidation.

The antioxidative property of cannabinoids was confirmed by their ability to antagonize oxidative stress and consequent cell death induced by the retinoid anhydroretinol.

Therefore, cannabinoids act as antioxidants to modulate cell survival and growth of B lymphocytes and fibroblasts.”

http://www.ncbi.nlm.nih.gov/pubmed/10869379/

“Marijuana has been known for centuries to be a psychoactive medicinal plant. Cannabinoids, especially the nonpsychoactive cannabinoids, may become clinically useful antioxidants in preventing and treating the oxidative stress-related diseases.” http://jpet.aspetjournals.org/content/293/3/807.long

US states that allow medical marijuana see drop in prescriptions for other drugs, study finds

Posted on by
Reply

“American states that allow patients access to medical marijuana are seeing fewer prescriptions per doctor for pharmaceutical drugs in several disease categories where marijuana is a potential treatment, a study in Health Affairs has found.

Proportionally, the greatest reduction was in medicines for spasticity. The average physician in a state without medical marijuana prescribed 2068 doses, but in states with access to medical marijuana this fell by 20% to 1645 doses.”

http://www.bmj.com/content/354/bmj.i3942

The Effect of Medical Marijuana on Sickness Absence.

Posted on by
Reply

“Utilizing the Current Population Survey, the study identifies that absences due to sickness decline following the legalization of medical marijuana. The effect is stronger in states with ‘lax’ medical marijuana regulations, for full-time workers, and for middle-aged males, which is the group most likely to hold medical marijuana cards.”

http://www.ncbi.nlm.nih.gov/pubmed/27416978

Potential therapeutic targets and the role of technology in developing novel cannabinoid drugs from cyanobacteria.

Posted on by
Reply

“Cyanobacteria find several applications in pharmacology as potential candidates for drug design. The need for new compounds that can be used as drugs has always been on the rise in therapeutics. Cyanobacteria have been identified as promising targets of research in the quest for new pharmaceutical compounds as they can produce secondary metabolites with novel chemical structures. Cyanobacteria is now recognized as a vital source of bioactive molecules like Curacin A, Largazole and Apratoxin which have succeeded in reaching Phase II and Phase III into clinical trials.

The discovery of several new clinical cannabinoid drugs in the past decade from diverse marine life should translate into a number of new drugs for cannabinoid in the years to come. Conventional cannabinoid drugs have high toxicity and as a result, they affect the efficacy of chemotherapy and patients’ life very much. The present review focuses on how potential, safe and affordable drugs used for cannabinoid treatment could be developed from cyanobacteria.”

http://www.ncbi.nlm.nih.gov/pubmed/27416557

Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells.

Posted on by
Reply

Logo of plosone

“Characterization of intrinsic and extrinsic factors regulating the self-renewal/division and differentiation of stem cells is crucial in determining embryonic stem (ES) cell fate.

ES cells differentiate into multiple hematopoietic lineages during embryoid body (EB) formation in vitro, which provides an experimental platform to define the molecular mechanisms controlling germ layer fate determination and tissue formation.

This work has not been addressed previously and yields new information on the function of cannabinoid receptors, CB1 and CB2, as components of a novel pathway regulating murine ES cell differentiation.

This study provides insights into cannabinoid system involvement in ES cell survival and hematopoietic differentiation.

Thus, these observations together with our results strongly suggest that both CB1 and CB2 activation are involved in the maintenance of mES cells and that the endocannabinoid system is essential in stem cell survival and stem cell hematopoietic differentiation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1919431/

 

Regulation of hematopoietic stem cell trafficking and mobilization by the endocannabinoid system.

Posted on by
Reply

“The cannabinoid receptors CB(1) and CB(2) are seven-transmembrane Gαi protein-coupled receptors and are expressed in certain mature hematopoietic cells.

We recently showed that these receptors are expressed in murine and human hematopoietic stem cells (HSCs) and that CB(2) agonists induced chemotaxis, enhanced colony formation of marrow cells, as well as caused in vivo mobilization of murine HSCs with short- and long-term repopulating abilities. Based on these observations, we have further explored the role of CB(2) and its agonist AM1241 on hematopoietic recovery following sublethal irradiation in mice.

Cannabinoid receptor 2 knockout mice (Cnr2(-/-) deficient mice) exhibited impaired recovery following sublethal irradiation as compared with irradiated wild-type (WT) mice, as determined by low colony-forming units and low peripheral blood counts. WT mice treated with CB(2) agonist AM1241 following sublethal irradiation demonstrated accelerated marrow recovery and increased total marrow cells (approximately twofold) and total lineage- c-kit(+) cells (approximately sevenfold) as well as enhanced HSC survival as compared with vehicle control-treated mice.

When the CB(2) agonist AM1241 was administered to WT mice 12 days before their sublethal irradiation, analysis of hematopoiesis in these mice showed decreased apoptosis of HSCs, enhanced survival of HSCs, as well as increase in total marrow cells and c-kit+ cells in the marrow.

Thus, CB(2) agonist AM1241 promoted recovery after sublethal irradiation by inhibiting apoptosis of HSCs and promoting survival, as well as enhancing the number of HSCs entering the cell cycle.”

http://www.ncbi.nlm.nih.gov/pubmed/22074629

Cannabinoid Receptor-2 Regulates Embryonic Hematopoietic Stem Cell Development via Prostaglandin E2 and P-Selectin Activity

Posted on by
Reply

Cannabinoids (CB) modulate adult hematopoietic stem and progenitor cell (HSPCs) function, however, impact on the production, expansion, or migration of embryonic HSCs is currently uncharacterized.

Here, using chemical and genetic approaches targeting CB-signaling in zebrafish, we show that CB receptor (CNR) 2, but not CNR1, regulates embryonic HSC development.

Together, these data suggest CNR2-signaling optimizes the production, expansion, and migration of embryonic HSCs by modulating multiple downstream signaling pathways.

Our work indicates that CB/CNR2 activity acts as a modifier of embryonic HSC formation by fine-tuning signaling pathways essential for HSC emergence and colonization of secondary niches.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781665/

Mechanical and material properties of cortical and trabecular bone from cannabinoid receptor-1-null (Cnr1-/-) mice.

Posted on by
Reply

“The endocannabinoid system is known for its regulatory effects on bone metabolism through the cannabinoid receptors, Cnr1 and Cnr2. In this study we analysed the mechanical and material properties of long bones from Cnr1-/- mice on a C57BL/6 background. Tibiae and femora from 5- and 12-week-old mice were subjected to three-point bending to measure bending stiffness and yield strength. Elastic modulus, density and mineral content were measured in the diaphysis. Second moment of area (MOA2), inner and outer perimeters of the cortical shaft and trabecular fractional bone volume (BV/TV) were measured using micro-CT. In Cnr1-/- males and females at both ages the bending stiffness was reduced due to a smaller MOA2. Bone from Cnr1-/- females had a greater modulus than wild-type controls, although no differences were observed in males. BV/TV of 12-week-old Cnr1-/- females was greater than controls, although no difference was seen at 5-weeks. On the contrary, Cnr1-/- males had the same BV/TV as controls at 12-weeks while they had significantly lower values at 5-weeks. This study shows that deleting Cnr1 decreases the amount of cortical bone in both males and females at 12-weeks, but increases the amount of trabecular bone only in females.”

http://www.ncbi.nlm.nih.gov/pubmed/27401043

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

Posted on by
Reply

Image result for Cell Mol Life Sci

“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

Posted on by
Reply

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