Cannabinoids suppress acute and anticipatory nausea in pre-clinical rat models of conditioned gaping.

Posted on February 19, 2015 by David

“The sensation of nausea is one of the most debilitating human experiences. Current anti-emetic therapies are effective in reducing vomiting, but are less effective in reducing acute and delayed nausea and are completely ineffective in reducing anticipatory nausea.

Recent pre-clinical evidence using a selective rat model of nausea (conditioned gaping reactions) has revealed that cannabinoids have great promise as treatments for nausea and that their anti-nausea effects may be mediated by the interoceptive insular cortex.”

http://www.ncbi.nlm.nih.gov/pubmed/25691302

http://www.thctotalhealthcare.com/category/nauseavomiting/

Evaluation of Phytocannabinoids from High Potency Cannabis sativa using In Vitro Bioassays to Determine Structure-Activity Relationships for Cannabinoid Receptor 1 and Cannabinoid Receptor 2.

Posted on February 13, 2015 by David

“Cannabis has been around for thousands of years and has been used recreationally, medicinally, and for fiber.

Over 500 compounds have been isolated from Cannabis sativa with approximately 105 being cannabinoids. Of those 105 compounds, Δ9-tetrahydrocannabinol has been determined as the primary constituent, which is also responsible for the psychoactivity associated with Cannabis.

Cannabinoid receptors belong to the large superfamily of G protein-coupled receptors.

Targeting the cannabinoid receptors has the potential to treat a variety of conditions such as pain, neurodegeneration, appetite, immune function, anxiety, cancer, and others.

Developing in vitro bioassays to determine binding and functional activity of compounds has the ability to lead researchers to develop a safe and effective drug that may target the cannabinoid receptors…”

http://www.ncbi.nlm.nih.gov/pubmed/25419092

Activation of Cannabinoid Type Two Receptors (CB2) Diminish Inflammatory Responses in Macrophages and Brain Endothelium.

Posted on February 11, 2015 by David

“Chronic neuroinflammatory disorders (such as HIV associated neurodegeneration) require treatment that decreases production of inflammatory factors by activated microglia and macrophages and protection of blood brain barrier (BBB) injury secondary to activation of brain endothelium.

Cannabioid type 2 receptor (CB2) is highly expressed on macrophages and brain microvasular enndothelial cells (BMVEC) and is upregulated in inflammation and HIV infection. It has been shown that CB2 activation dampened inflammatory responses in macrophages and BMVEC.

In this study, we assessed by PCR array the expression of a wide range of genes increased in macrophages and BMVEC in inflammation. TNFα treatment upregulated 33 genes in primary human BMVEC, and two highly selective CB2 agonists diminished expression of 31 and 32 genes.

These results were confirmed by functional assays (BBB protection after inflammatory insult and decreased migration of monocytes across BMVEC monolayers after CB2stimulation). Similarly, CB2 stimulation in primary human macrophages led to the suppression of 35 genes out of the 50 genes upregulated by LPS. Such changes in gene expression paralleled diminished secretion of proinflammatory factors.

These results indicate the potential utility of CB2agonists for the treatment of neuroinflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/25666933

THE EFFECT OF PHYTOCANNABINOIDS ON AIRWAY HYPERRESPONSIVENESS, AIRWAY INFLAMMATION AND COUGH.

Posted on February 7, 2015 by David

“Cannabis has been demonstrated to have bronchodilator, anti-inflammatory and anti-tussive activity in the airways, but, information on the active cannabinoids, their receptors and the mechanisms for their effects is limited.

We compared the effects of Δ9-tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, cannabidiolic acid and tetrahydrocannabivarin…

The other cannabinoids did not influence cholinergic transmission and only Δ9-THC demonstrated effects on airway hyperresponsiveness, anti-inflammatory activity and antitussive activity in the airways.”

http://www.ncbi.nlm.nih.gov/pubmed/25655949

http://jpet.aspetjournals.org/content/early/2015/02/05/jpet.114.221283.long

Cannabinoid CB2 receptor stimulation attenuates brain edema and neurological deficits in a germinal matrix hemorrhage rat model.

Posted on January 31, 2015 by David

“Germinal matrix hemorrhage (GMH) is one of the most common and devastating cerebrovascular events that affect premature infants, resulting in a significant socioeconomic burden. However, GMH has been largely unpreventable, and clinical treatments are mostly inadequate.

In the present study, we tested the hypothesis that a selective CB2 receptor agonist, could attenuate brain injury and neurological deficits…

This current study suggests a potential clinical utility for CB2R agonists as a potential therapy to reduce neurological injury and improve patient outcomes after GMH.”

http://www.ncbi.nlm.nih.gov/pubmed/25625355

Protective effects of cannabidiol on lesion-induced intervertebral disc degeneration.

Posted on January 23, 2015 by David

“Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content…

Cannabidiol (CBD) is the major nonpsychotropic phytocannabinoid of Cannabis sativa (up to 40% of Cannabis extracts). Contrary to most cannabinoids, CBD does not produce psychotomimetic or cognitive effects. Interesting, in the last years it has been suggest that CBD produces a plethora of others pharmacological effects, including antioxidant, neuroprotective, anti-proliferative, anti-anxiety, hypnotic and antiepileptic, anti-nausea, anti-ischemic, anti-hyperalgesic, and anti-inflammatory…

The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI) and histological analyses…

Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration.

In summary our study revealed anti-degenerative effects of intradiscal microinjection of CBD 120 nmol. CBD represents one of the most promising candidates present in the Cannabis sativa plant for clinical use due to its remarkable lack of cognitive or psychotomimetic actions.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269422/

http://www.thctotalhealthcare.com/category/spinal-cord-injury/

Selective CB2 receptor agonists.

Posted on January 18, 2015 by David

“Selective CB2 receptor agonists. Part 1: The identification of novel ligands through computer-aided drug design (CADD) approaches. Computer-aided drug design scaffold hopping strategies were utilized to identify new classes of CB2 agonists when compounds of an established series with low nanomolar potency were challenging to optimize for good drug-like properties. Use of ligand-based design strategies through BI Builder (a tool for de novo design) and PharmShape (a virtual screening software package) approaches led to the discovery of new chemotypes. Specifically, compounds containing azetidine-, proline-, and piperidine-based cores were found to have low nanomolar and picomolar CB2 agonist activities with drug-like properties considered appropriate for early profiling.” http://www.ncbi.nlm.nih.gov/pubmed/25556098

“Selective CB2 receptor agonists. Part 2: Structure-activity relationship studies and optimization of proline-based compounds. Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure-activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. In a streptozotocin induced diabetic neuropathy model, 22 demonstrated a dose-dependent reversal of mechanical hyperalgesia.” http://www.ncbi.nlm.nih.gov/pubmed/25556092

“Selective CB2 receptor agonists. Part 3: The optimization of a piperidine-based series that demonstrated efficacy in an in vivo neuropathic pain model. A novel class of potent cannabinoid receptor 2 (CB2) agonists based on a (S)-piperidine scaffold was identified using ligand-based pharmacophore models. Optimization of solubility and metabolic stability led to the identification of several potent CB2 agonists (e.g., 30) that displayed selectivity over cannabinoid receptor 1 (CB1) and acceptable drug like properties. In rats, compound 30 demonstrated a favorable pharmacokinetic profile and efficacy in a Streptozotocin-induced diabetic neuropathy model, with full reversal of mechanical hyperalgesia.” http://www.ncbi.nlm.nih.gov/pubmed/25575658

Association Between Marijuana Exposure and Pulmonary Function over 20 Years

Posted on January 17, 2015 by David

TU Dublin Kevin St Library: New: American Medical Association journals (JAMA) collection now available via IReL “Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function.

Marijuana may have beneficial effects on pain control, appetite, mood, and management of other chronic symptoms.

Our findings suggest that occasional use of marijuana for these or other purposes may not be associated with adverse consequences on pulmonary function.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840897/

https://jamanetwork.com/journals/jama/fullarticle/1104848

“A common misconception about medical marijuana is that if inhaled, it will have detrimental effects on the patient’s lungs. However, according to a 2012 study published in the Journal of the American Medical Association (JAMA), this notion is simply untrue; in fact, this study points to an idea quite the opposite: that medical marijuana just might improve lung health under certain conditions.” HTTPS://AGRIMEDINDUSTRIES.COM/2018/06/08/STUDY-SHOWS-MARIJUANA-HAS-A-POSITIVE-IMPACT-ON-LUNG-HEALTH-UNDER-CERTAIN-CONDITIONS/

Cannabis smoking and serum C-reactive protein: A quantile regressions approach based on NHANES 2005-2010.

Posted on December 28, 2014 by David

“In this epidemiological study, we aim to present estimates on suspected cannabis-attributable immunomodulation as manifest in serum C-reactive protein (CRP) levels as non-specific inflammatory markers with interpretable clinical values…

Extending pre-clinical research on cannabis-attributable immunomodulation, this study’s CRP evidence points toward possible anti-inflammatory effects of cannabis smoking…”

http://www.ncbi.nlm.nih.gov/pubmed/25529540

Drug discovery strategies that focus on the endocannabinoid signaling system in psychiatric disease.

Posted on December 11, 2014 by David

“The endocannabinoid (eCB) system plays an important role in the control of mood, and its dysregulation has been implicated in several psychiatric disorders.

Targeting the eCB system appears to represent an attractive and novel approach to the treatment of depression and other mood disorders.

…the review provides discussion on compounds and drugs that target this system and might prove to be successful for the treatment of mood-related psychiatric disorders.

The discovery of increasingly selective modulators of CB receptors should enable the identification of optimal therapeutic strategies.

It should also maximize the likelihood of developing safe and effective treatments for debilitating psychiatric disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/25488672