Tag Archives: Cannabinoids

The Use of Medicinal Marijuana for Posttraumatic Stress Disorder: A Review of the Current Literature.

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“This study seeks to understand the current literature regarding the use of medicinal marijuana in the treatment of posttraumatic stress disorder (PTSD).

Analysis revealed that most reports are correlational and observational in basis with a notable lack of randomized, controlled studies.

Many of the published studies suggest a decrease in PTSD symptoms with marijuana use… there is a growing amount of neurobiological evidence and animal studies suggesting potential neurologically based reasons for the reported efficacy.

CONCLUSIONS:

Posttraumatic stress disorder is 1 of the approved conditions for medicinal marijuana in some states. While the literature to date is suggestive of a potential decrease in PTSD symptomatology with the use of medicinal marijuana, there is a notable lack of large-scale trials, making any final conclusions difficult to confirm at this time.”

http://www.ncbi.nlm.nih.gov/pubmed/26644963

http://www.thctotalhealthcare.com/category/post-traumatic-stress-disorder-ptsd/

Endocannabinoid Regulation of Neuroendocrine Systems.

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“The hypothalamus is a part of the brain that is critical for sustaining life through its homeostatic control and integrative regulation of the autonomic nervous system and neuroendocrine systems. Neuroendocrine function in mammals is mediated mainly through the control of pituitary hormone secretion by diverse neuroendocrine cell groups in the hypothalamus.

Cannabinoid receptors are expressed throughout the hypothalamus, and endocannabinoids have been found to exert pronounced regulatory effects on neuroendocrine function via modulation of the outputs of several neuroendocrine systems.

Here, we review the physiological regulation of neuroendocrine function by endocannabinoids, focusing on the role of endocannabinoids in the neuroendocrine regulation of the stress response, food intake, fluid homeostasis, and reproductive function.

Cannabis sativa (marijuana) has a long history of recreational and/or medicinal use dating back to ancient times. It was used as an analgesic, anesthetic, and antianxiety herb as early as 2600 B.C.

The hedonic, anxiolytic, and mood-elevating properties of cannabis have also been cited in ancient records from different cultures. However, it was not until 1964 that the psychoactive constituent of cannabis, Δ(9)-tetrahydrocannabinol, was isolated and its chemical structure determined (Gaoni & Mechoulam, 1964).”

Endocannabinoid Mechanisms Influencing Nausea.

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“One of the first recognized medical uses of Δ(9)-tetrahydrocannabinol was treatment of chemotherapy-induced nausea and vomiting.

Although vomiting is well controlled with the currently available non-cannabinoid antiemetics, nausea continues to be a distressing side effect of chemotherapy and other disorders.

Indeed, when nausea becomes conditionally elicited by the cues associated with chemotherapy treatment, known as anticipatory nausea (AN), currently available antiemetics are largely ineffective.

Considerable evidence demonstrates that the endocannabinoid system regulates nausea in humans and other animals.

In this review, we describe recent evidence suggesting that cannabinoids and manipulations that enhance the functioning of the natural endocannabinoid system are promising treatments for both acute nausea and AN.”

The Endocannabinoid System and Its Role in Regulating the Intrinsic Neural Circuitry of the Gastrointestinal Tract.

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“Endocannabinoids are important neuromodulators in the central nervous system.

They regulate central transmission through pre- and postsynaptic actions on neurons and indirectly through effects on glial cells.

Cannabinoids (CBs) also regulate neurotransmission in the enteric nervous system (ENS) of the gastrointestinal (GI) tract.

The ENS consists of intrinsic primary afferent neurons, interneurons, and motor neurons arranged in two ganglionated plexuses which control all the functions of the gut.

Increasing evidence suggests that endocannabinoids are potent neuromodulators in the ENS.

In this review, we will highlight key observations on the localization of CB receptors and molecules involved in the synthesis and degradation of endocannabinoids in the ENS.

We will discuss endocannabinoid signaling mechanisms, endocannabinoid tone and concepts of CB receptor metaplasticity in the ENS. We will also touch on some examples of enteric neural signaling in relation neuromuscular, secretomotor, and enteroendocrine transmission in the ENS. Finally, we will briefly discuss some key future directions.”

Inhibitors of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase: New Targets for Future Antidepressants.

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“Cannabis and analogs of Δ9-tetrahydrocannabinol have been used for therapeutic purposes…

Endogenous cannabinoids have been discovered, and dysregulation of endocannabinoid signaling is implicated in the pathophysiology of major depressive disorder (MDD).

Recently, endocannabinoid hydrolytic enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have become new therapeutic targets in the treatment of MDD.

Several FAAH or MAGL inhibitors are reported to have no cannabimimetic side effects and, therefore, are new potential therapeutic options for patients with MDD who are resistant to first-line antidepressants (selective serotonin and serotonin-norepinephrine reuptake inhibitors).

In this review, we focus on the possible relationships between MDD and the endocannabinoid system as well as the inhibitors’ therapeutic potential.

MAGL inhibitors may reduce inflammatory responses through activation of cannabinoid receptor type 2.

In the hypothalamic-pituitary-adrenal axis, repeated FAAH inhibitor administration may be beneficial for reducing circulating glucocorticoid levels. Both FAAH and MAGL inhibitors may contribute to dopaminergic system regulation. Recently, several new inhibitors have been developed with strong potency and selectivity. FAAH inhibitor, MAGL inhibitor, or dual blocker use would be promising new treatments for MDD. Further pre-clinical studies and clinical trials using these inhibitors are warranted.”

http://www.ncbi.nlm.nih.gov/pubmed/26630956

CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord

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Figure 1

“Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents.

In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas.

Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region.

We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1HIGH cell subpopulation described in rodents.

Our results support the existence of ependymal CB1HIGH cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions.”

http://www.nature.com/articles/srep17745

Computational Prediction and Biochemical Analyses of New Inverse Agonists for the CB1 Receptor.

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“Human cannabinoid type 1 (CB1) G-protein coupled receptor is a potential therapeutic target for obesity.

The previously predicted and experimentally validated ensemble of ligand-free conformations of CB1 are used here to predict the binding sites for known CB1-selective inverse agonists including rimonabant and its seven known derivatives.

This binding pocket, which differs significantly from previously published models, is used to identify 16 novel compounds expected to be CB1 inverse agonists by exploiting potential new interactions.

We show experimentally that two of these compounds exhibit inverse agonist properties including inhibition of basal and agonist-induced G-protein coupling activity, as well as an enhanced level of CB1 cell surface localization.

This demonstrates the utility of using the predicted binding sites for an ensemble of CB1 receptor structures for designing new CB1 inverse agonists.”

Anandamide-induced Ca2+ elevation leading to p38 MAPK phosphorylation and subsequent cell death via apoptosis in human osteosarcoma cells.

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“The effect of anandamide on human osteoblasts is unclear. This study examined the effect of anandamide on viability, apoptosis, mitogen-activated protein kinases (MAPKs) and Ca2+ levels in MG63 osteosarcoma cells. Anandamide at 50-200 microM decreased cell viability via apoptosis as demonstrated by propidium iodide staining and activation of caspase-3. Immunoblotting suggested that anandamide induced expression of ERK, JNK and p38 MAPK. Anandamide-induced cell death and apoptosis were reversed by SB203580, but not by PD98059 and SP600125, suggesting that anandamide’s action was via p38 MAPK, but not via ERK and JNK. Anandamide at 1-100 microM induced [Ca2+]i increases. Removal of extracellular Ca2+ decreased the anandamide response, indicating that anandamide induced Ca2+ influx and Ca2+ release. Chelation of intracellular Ca2+ with BAPTA reversed anandamide-induced cell death and p38 MAPK phosphorylation. Collectively, in MG63 cells, anandamide induced [Ca2+]i increases which evoked p38 MAPK phosphorylation. This p38 MAPK phosphorylation subsequently activated caspase-3 leading to apoptosis.”

http://www.ncbi.nlm.nih.gov/pubmed/17222495

Involvement of PAR-4 in cannabinoid-dependent sensitization of osteosarcoma cells to TRAIL-induced apoptosis.

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“Osteosarcoma is the most common malignant bone tumor in childhood and adolescence.

Cannabinoids (CBs), the active constituents of Cannabis sativa, are known to exert a wide range of central and peripheral effects.

Recently, numerous studies evidenced the role of cannabinoids in the regulation of cell death and survival, focusing the anti-proliferative effects of these compounds in various tumours… cannabinoids can also activate autophagic process…

The aim of the present study was to investigate the effects induced by cannabinoids in osteosarcoma cells and the molecular pathway…

The synthetic cannabinoid WIN 55,212-2 is a potent cannabinoid receptor agonist with anticancer potential.

Moreover, we indicate that a key role in WIN action is played by the tumor suppressor protein PAR-4.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007360/

 

Potentiation of the antitumor activity of adriamycin against osteosarcoma by cannabinoid WIN-55,212-2

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“Osteosarcoma is the most frequent primary malignant bone tumor that occurs in children and adolescents. Osteosarcoma is a bone malignancy that predominantly affects children and adolescents, and exhibits high invasion and metastasis rates.

Although adriamycin (ADM) is an effective benchmark agent for the management of osteosarcoma, it also results in harmful side-effects including toxicity and chemoresistance that substantially affect the quality of life of patients. Therefore, novel therapeutic approaches and drugs must be sought for the treatment of osteosarcoma.

Natural products which have potential antitumor activities have become a focus of attention for study in previous years. Cannabinoids, the active components naturally derived from the marijuana plant Cannabis sativa L., have been reported as potential antitumor drugs based on their ability to limit inflammation, cell proliferation and cell survival.

To date, several cannabinoids have been identified and characterized, including Δ(9)-tetrahydrocannabinol (THC), cannabidiol, cannabinol (CBN) and anandamide, as well as synthetic cannabinoids, including WIN-55,212-2, JWH-133 and (R)-methanandamide.

In the early 1970s, THC and CBN were shown to inhibit tumor growth in Lewis lung carcinoma. Subsequently, cannabinoids were found to induce apoptosis and inhibit the proliferation of various cancer cells, including those of glioma and lymphoma, and prostate, breast, skin and pancreatic cancer…

In conclusion, the present study indicated that cannabinoid WIN-55,212-2 is antiproliferative, antimetastatic and antiangiogenic against MG-63 cells in vitro, and presented evidence that cannabinoid WIN-55,212-2 may result in synergistic antitumor action in combination with ADM against osteosarcoma.

These findings may offer a novel strategy for the treatment of osteosarcoma.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580018/