Tag Archives: analgesic

Endocannabinoids: new targets for drug development.

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“The possible therapeutic use of marijuana s active principles, the cannabinoids, is currently being debated.

It is now known that these substances exert several of their pharmacological actions by activating specific cell membrane receptors, the CB1 and CB2 cannabinoid receptor subtypes.

This knowledge led to the design of synthetic cannabinoid agonists and antagonists with high therapeutic potential.

The recent discovery of the endocannabinoids, i.e. endogenous metabolites capable of activating the cannabinoid receptors, and the understanding of the molecular mechanisms leading to their biosynthesis and inactivation, opened a new era in research on the pharmaceutical applications of cannabinoids.

Ongoing studies on the pathological and physiological conditions regulating the tissue levels of endocannabinoids, and on the pharmacological activity of these compounds and their derivatives, may provide a lead for the development of new drugs for the treatment of nervous and immune disorders, cardiovascular diseases, pain, inflammation and cancer.

These studies are reviewed in this article with special emphasis on the chemical features that determine the interaction of endocannabinoids with the proteins mediating their activity and degradation.”

http://www.ncbi.nlm.nih.gov/pubmed/10903398

Preparation and characterization of Δ(9)-tetrahydrocannabinol-loaded biodegradable polymeric microparticles and their antitumoral efficacy on cancer cell lines.

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“Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer, AIDS and multiple sclerosis), analgesics, and in the treatment of multiple sclerosis and cancer, among other conditions.

However, despite their high clinical potential, only few dosage forms are available to date.

In this paper, the development of Δ(9)-tetrahydrocannabinol (THC) biodegradable microspheres as an alternative delivery system for cannabinoid parenteral administration is proposed.

As THC has shown therapeutic potential as anticancer drug, the efficacy of the microspheres was tested on different cancer cell lines.

Interestingly, the microspheres were able to inhibit cancer cell proliferation during the nine-day study period.

All the above results suggest that the use of biodegradable microspheres would be a suitable alternative delivery system for THC administration.”

http://www.ncbi.nlm.nih.gov/pubmed/23773072

Arthritis and cannabinoids: HU-210 and Win-55,212-2 prevent IL-1alpha-induced matrix degradation in bovine articular chondrocytes in-vitro.

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“Cannabinoids have analgesic, immunomodulatory and anti-inflammatory properties and attenuate joint damage in animal models of arthritis.

Chondrocytes appeared to constitutively express cannabinoid receptors CB1 and CB2.

It is concluded that biologically stable synthetic cannabinoids protect cartilage matrix from degradation induced by cytokines and this effect is possibly CB-receptor mediated and involves effects on prostaglandin and nitric oxide metabolism.”

http://www.ncbi.nlm.nih.gov/pubmed/16536902

Cannabinoids in pain and inflammation.

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“Cannabinoids exhibit medicinal properties including analgesic, anti-inflammatory and immunosuppressive properties. This paper reviews some of the recent findings in the study of cannabinoids in pain and inflammation. Some of the effects of cannabinoids are receptor mediated and others are receptor independent. Endocannabinoids naturally reduce pain and are cerebroprotective. Natural and synthetic cannabinoids have the potential to reduce nociception, reverse the development of allodynia and hyperalgesia, reduce inflammation and inflammatory pain and protect from secondary tissue damage in traumatic head injury.”

http://www.ncbi.nlm.nih.gov/pubmed/15265314

The future of cannabinoids as analgesic agents: a pharmacologic, pharmacokinetic, and pharmacodynamic overview.

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“For thousands of years, physicians and their patients employed cannabis as a therapeutic agent.

Despite this extensive historical usage, in the Western world, cannabis fell into disfavor among medical professionals because the technology available in the 1800s and early 1900s did not permit reliable, standardized preparations to be developed.

However, since the discovery and cloning of cannabinoid receptors (CB1 and CB2) in the 1990s, scientific interest in the area has burgeoned, and the complexities of this fascinating receptor system, and its endogenous ligands, have been actively explored.

Recent studies reveal that cannabinoids have a rich pharmacology and may interact with a number of other receptor systems-as well as with other cannabinoids-to produce potential synergies.

Cannabinoids-endocannabinoids, phytocannabinoids, and synthetic cannabinoids-affect numerous bodily functions and have indicated efficacy of varying degrees in a number of serious medical conditions.

Cannabinoid receptor agonists and/or molecules that affect the modulation of endocannabinoid synthesis, metabolism, and transport may, in the future, offer extremely valuable tools for the treatment of a number of currently intractable disorders.”

 http://www.ncbi.nlm.nih.gov/pubmed/17890938

The cannabinoids: therapeutic potentials.

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“A review of the therapeutic potentials of the cannabinoids is presented. With respect to the antifertility aspects of cannabinoids, 2 mg delta 9-THC suppressed luteinizing hormone secretion in rats and 2 and 3 mg/kg resulted in a deterioation of male sexual performance. A new chapter in marijuana research was opened in 1964 with the identification of delta 9-tetrahydrocannabinol as the active ingredient. Antiedema, analgesic, antipyretic, antiinflammatory, antifertility, antiepileptic, anticonvulsant, antihypertensive, cardiotonic, pulmonary, and antidepressant effects along with potentiation of barbiturates and analgesics are reviewed leading one to the conclusion that marijuana is “a drug for all reasons”. During the past decade many investigators have pursued the possibility of modification of the delta 9 structure to delineate activities. 1 compound, Abbott 40656, SP106, a water-soluble benzopyran derivative is presently under Phase 1 clinical evaluation as a sedative-hypnotic.”

http://www.ncbi.nlm.nih.gov/pubmed/12307093/

New Study Finds Marijuana To Be Effective Against Depression, Migraine and Anxiety

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“Research has suggested that cannabis may be a promising treatment option for a number of different physical and mental health conditions, from post-traumatic stress disorder to chronic pain. A study released this week suggests that depression , anxiety and migraine can be added to that list.

Neuroscientists from the University of Buffalo’s Research Institute on Addictions found that endocannabinoids — chemical compounds in the brain that activate the same receptors as THC, an active compound in marijuana — may be helpful in treating depression, anxiety and migraine that results from chronic stress.

In studies on rats, the researchers found that chronic stress reduced the production of endocannabinoids, which affect our cognition, emotion and behavior, and have been linked to reduced feelings of pain and anxiety, increases in appetite and overall feelings of well-being. The body naturally produces these compounds, which are similar to the chemicals in cannabis. Reduction of endocannabinoid production may be one reason that chronic stress is a major risk factor in the development of depression.

Then, the research team administered marijuana cannabinoids to the rats, finding it to be an effective way to restore endocannabinoid levels in their brains — possibly, thereby, alleviating some symptoms of depression.

“Using compounds derived from cannabis — marijuana — to restore normal endocannabinoid function could potentially help stabilize moods and ease depression,” lead researcher Dr. Samir Haj-Dahmane said in a university press release.

Recent research around marijuana’s effect on symptoms of post-traumatic stress disorder further bolsters the Buffalo neuroscientists’ findings, since both disorders involve the way the brain responds to stress. A study published last year in the journal Neuropsychopharmacology, for instance, found synthetic cannabinoids triggered changes in brain centers associated with traumatic memories in rats, preventing some of the behavioral and physiological symptoms of PTSD. Another study published last year found that patients who smoked cannabis experienced a 75 percent reduction in PTSD symptoms.

However, it’s important to note that the relationship between marijuana and depression  is complex. Some research has suggested that regular and heavy marijuana smokers are at a higher risk for depression, although a causal link between cannabis use and depression has not been established. More studies are needed in order to determine whether, and how, marijuana might be used in a clinical context for patients with depression.”  http://painphysicianjournal.co/2016/06/30/new-study-finds-marijuana-to-be-effective-against-depression-migraine-and-anxiety/

http://painphysicianjournal.co/2016/06/30/new-study-finds-marijuana-to-be-effective-against-depression-migraine-and-anxiety/

Cannabinoid Modulation of Cutaneous Aδ Nociceptors During Inflammation

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“Previous studies have demonstrated that locally administered cannabinoids attenuate allodynia and hyperalgesia through activation of peripheral cannabinoid receptors (CB1 and CB2).

These results suggest that attenuation of mechanically evoked responses of Aδ nociceptors contributes to the behavioral antinociception produced by activation of peripheral CB1 receptors during inflammation.

Several studies have demonstrated that locally administered cannabinoids produce antinociception in animal models of both acute and persistent pain through peripheral mechanisms.

Taken together, our data suggest that peripherally acting cannabinoids could be a potential therapeutic treatment for chronic inflammatory pain.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585399/

 

Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption.

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“Cannabinoids, components of the Cannabis sativa (marijuana) plant, are known to exert potent anti-inflammatory, immunomodulatory and analgesic effects through activation of cannabinoid-1 and -2 (CB1 and CB2) receptors located in the central nervous system and immune cells.

The limitation of the therapeutic utility of the major cannabinoid, Δ9-tetrahydrocannabinol, is the development of psychoactive effects through central nervous system CB1 receptor. In contrast, cannabidiol (CBD), one of the most abundant cannabinoids of Cannabis sativa with reported antioxidant, anti-inflammatory, and immunomodulatory effects is well tolerated without side effects when chronically administered to humans and is devoid of psychoactive properties due to a low affinity for the CB1 and CB2 receptors.

A nonpsychoactive cannabinoid cannabidiol (CBD) has been shown to exert potent anti-inflammatory and antioxidant effects and has recently been reported to lower the incidence of diabetes in nonobese diabetic mice and to preserve the blood-retinal barrier in experimental diabetes.

In this study we have investigated the effects of CBD on high glucose (HG)-induced, mitochondrial superoxide generation, NF-κB activation, nitrotyrosine formation, inducible nitric oxide synthase (iNOS) and adhesion molecules ICAM-1 and VCAM-1 expression, monocyte-endothelial adhesion, transendothelial migration of monocytes, and disruption of endothelial barrier function in human coronary artery endothelial cells (HCAECs).

HG markedly increased mitochondrial superoxide generation (measured by flow cytometry using MitoSOX), NF-κB activation, nitrotyrosine formation, upregulation of iNOS and adhesion molecules ICAM-1 and VCAM-1, transendothelial migration of monocytes, and monocyte-endothelial adhesion in HCAECs. HG also decreased endothelial barrier function measured by increased permeability and diminished expression of vascular endothelial cadherin in HCAECs.

Remarkably, all the above mentioned effects of HG were attenuated by CBD pretreatment.

Since a disruption of the endothelial function and integrity by HG is a crucial early event underlying the development of various diabetic complications, our results suggest that CBD, which has recently been approved for the treatment of inflammation, pain, and spasticity associated with multiple sclerosis in humans, may have significant therapeutic benefits against diabetic complications and atherosclerosis.

Collectively, our results suggest that the nonpsychoactive cannabinoid CBD have significant therapeutic benefits against diabetic complications and atherosclerosis by attenuating HG-induced mitochondrial superoxide generation, increased NF-κB activation, upregulation of iNOS and adhesion molecules, 3-NT formation, monocyte-endothelial adhesion, TEM of monocytes, and disruption of the endothelial barrier function.

This is particularly encouraging in light of the excellent safety and tolerability profile of CBD in humans.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228254/

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