Cannabinoids in late-onset Alzheimer’s disease.

“Given the lack of effective treatments for late-onset Alzheimer’s disease (LOAD) and the substantial burden on patients, families, healthcare systems, and economies, finding an effective therapy is one of the highest medical priorities.

The past few years have seen a growing interest in the medicinal uses of cannabinoids, the bioactive components of the cannabis plant, including the treatment of LOAD and other physical conditions that are common in older people.

Several in vitro and in vivo studies have demonstrated that cannabinoids can reduce oxidative stress, neuroinflammation, and the formation of amyloid plaques and neurofibrillary tangles, the key hallmarks of LOAD.

Also, in population-based studies, cannabinoids reduced dementia-related symptoms (e.g., behavioral disturbances).

The current article provides an overview of the potential of cannabinoids in the treatment of LOAD and related neuropsychiatric symptoms in older people.

We also discuss the efficacy, safety and pharmacokinetics of cannabinoid-based drugs in older people with dementia.”

http://www.ncbi.nlm.nih.gov/pubmed/25788394

http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

Cannabidiol, a non-psychoactive cannabinoid, leads to EGR2-dependent anergy in activated encephalitogenic T cells.

“Cannabidiol (CBD), the main non-psychoactive cannabinoid, has been previously shown by us to ameliorate clinical symptoms and to decrease inflammation in myelin oligodendrocyte glycoprotein (MOG)35-55-induced mouse experimental autoimmune encephalomyelitis model of multiple sclerosis as well as to decrease MOG35-55-induced T cell proliferation and IL-17 secretion. However, the mechanisms of CBD anti-inflammatory activities are unclear…

Our data suggests that CBD exerts its immunoregulatory effects via induction of CD4(+)CD25(-)CD69(+)LAG3(+) cells in MOG35-55-activated APC/TMOG co-cultures. This is accompanied by EGR2-dependent anergy of stimulated TMOG cells as well as a switch in their intracellular STAT3/STAT5 activation balance leading to the previously observed decrease in Th17 activity.”

http://www.ncbi.nlm.nih.gov/pubmed/25779454

Cannabinoid Replacement Therapy (CRT): Nabiximols (Sativex) as a novel treatment for cannabis withdrawal.

“Cannabis is a common recreational drug that is generally considered to have low addictive potential.

However an increasing number of cannabis users are seeking treatment for dependence on the drug.

There is interest in using agonist (substitution) pharmacotherapies to treat cannabis dependence and here we outline a novel approach involving a buccal spray (Nabiximols) that contains tetrahydrocannabinol (THC) and cannabidiol (CBD).

We review recent research with Nabiximols and highlight findings relevant to clinical practice.”

http://www.ncbi.nlm.nih.gov/pubmed/25777582

Cannabis in cancer care.

“Cannabis has been used in medicine for thousands of years prior to achieving its current illicit substance status.

Cannabinoids, the active components of Cannabis sativa, mimic the effects of the endogenous cannabinoids (endocannabinoids), activating specific cannabinoid receptors, particularly CB1 found predominantly in the central nervous system and CB2 found predominantly in cells involved with immune function.

Delta-9-tetrahydrocannabinol, the main bioactive cannabinoid in the plant, has been available as a prescription medication approved for treatment of cancer chemotherapy-induced nausea and vomiting and anorexia associated with the AIDS wasting syndrome.

Cannabinoids may be of benefit in the treatment of cancer-related pain, possibly synergistic with opioid analgesics.

Cannabinoids have been shown to be of benefit in the treatment of HIV-related peripheral neuropathy, suggesting that they may be worthy of study in patients with other neuropathic symptoms.

Cannabinoids have a favorable drug safety profile, but their medical use is predominantly limited by their psychoactive effects and their limited bioavailability.”

http://www.ncbi.nlm.nih.gov/pubmed/25777363

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

Cost-effectiveness of Sativex in multiple sclerosis spasticity: new data and application to Italy.

“This study aims to evaluate the cost-effectiveness of Sativex® (9-delta-tetrahydrocannabinol plus cannabidiol oromucosal spray) when used as add-on therapy for management of resistant MS-related spasticity in the context of the Italian healthcare system…

Sativex can be regarded as a cost-effective treatment option for patients with MS-related spasticity in Italy.”

http://www.ncbi.nlm.nih.gov/pubmed/25771713

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Cannabinoid receptors as therapeutic targets for dialysis-induced peritoneal fibrosis.

“Long-term exposure to bioincompatible peritoneal dialysis solutions is frequently complicated with peritoneal fibrosis and ultrafiltration failure.

As cannabinoid receptor (CBR) ligands have been reported to be beneficial to ameliorate the process of liver fibrosis, we strove to investigate their therapeutic potential to prevent peritoneal fibrosis…

Intraperitoneal administration of CBR ligands (CB(1)R antagonist and CB(2)R agonist) offers a potential therapeutic strategy to reduce dialysis-induced peritoneal fibrosis and to prolong the peritoneal survival in peritoneal dialysis patients.”

http://www.ncbi.nlm.nih.gov/pubmed/23296044

Cannabinoid receptor 1 is a major mediator of renal fibrosis.

“Chronic kidney disease, secondary to renal fibrogenesis, is a burden on public health.

There is a need to explore new therapeutic pathways to reduce renal fibrogenesis.

To study this, we used unilateral ureteral obstruction (UUO) in mice as an experimental model of renal fibrosis and microarray analysis to compare gene expression in fibrotic and normal kidneys.

The cannabinoid receptor 1 (CB1) was among the most upregulated genes in mice, and the main endogenous CB1 ligand (2-arachidonoylglycerol) was significantly increased in the fibrotic kidney.

Interestingly, CB1 expression was highly increased in kidney biopsies of patients with IgA nephropathy, diabetes, and acute interstitial nephritis. Both genetic and pharmacological knockout of CB1 induced a profound reduction in renal fibrosis during UUO. While CB2 is also involved in renal fibrogenesis, it did not potentiate the role of CB1. CB1 expression was significantly increased in myofibroblasts, the main effector cells in renal fibrogenesis, upon TGF-β1 stimulation.

The decrease in renal fibrosis during CB1 blockade could be explained by a direct action on myofibroblasts. CB1 blockade reduced collagen expression in vitro. Rimonabant, a selective CB1 endocannabinoid receptor antagonist, modulated the macrophage infiltrate responsible for renal fibrosis in UUO through a decrease in monocyte chemoattractant protein-1 synthesis.

Thus, CB1 has a major role in the activation of myofibroblasts and may be a new target for treating chronic kidney disease.”

http://www.ncbi.nlm.nih.gov/pubmed/25760323

Risk of emergency medical treatment following consumption of cannabis or synthetic cannabinoids in a large global sample.

“Synthetic cannabinoids (SCs) have become increasingly popular in recent years. Often marketed to reflect their similar effects to cannabis, their use has been associated with a range of negative health effects. We sought to determine the relative risk of seeking emergency medical treatment (EMT) following use of SCs and natural cannabis.

The relative risk associated with the use of SCs was 30 (95% CI 17.5-51.2) times higher than that associated with cannabis. Significantly more symptoms (p=0.03) were reported by respondents seeking treatment for SCs than for cannabis.

CONCLUSIONS:

Whilst these findings must be treated with caution, SCs potentially pose a greater risk to users’ health than natural forms of cannabis. Regulation is unlikely to remove SCs from the market, so well-informed user-focused health promotion messages need to be crafted to discourage their use.”

http://www.ncbi.nlm.nih.gov/pubmed/25759401

Safety and Pharmacokinetics of Oral Cannabidiol When Administered Concomitantly With Intravenous Fentanyl in Humans.

“Objectives: Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects.

Conclusions: Cannabidiol does not exacerbate adverse effects associated with intravenous fentanyl administration. Coadministration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse.”

http://journals.lww.com/journaladdictionmedicine/Abstract/publishahead/Safety_and_Pharmacokinetics_of_Oral_Cannabidiol.99700.aspx

Emerging targets and therapeutic approaches for the treatment of osteoarthritis pain.

“Osteoarthritis is a complex and often painful disease that is inadequately controlled with current analgesics. This review discusses emerging targets and therapeutic approaches that may lead to the development of better analgesics…

Aberrant excitability in peripheral and central pain pathways drives osteoarthritis pain, reversing this via modulation of nerve growth factor, voltage-gated sodium channel, voltage-gated calcium channel and transient receptor potential vanilloid one activity, and increasing inhibitory mechanisms through modulation of cannabinoid and descending modulatory systems hold promise for osteoarthritis pain therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/25730180

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