Medicinal cannabis.

“A number of therapeutic uses of cannabis and its derivatives have been postulated from preclinical investigations.

Possible clinical indications include spasticity and pain in multiple sclerosis, cancer-associated nausea and vomiting, cancer pain and HIV neuropathy.

Controversies lie in how to produce, supply and administer cannabinoid products.

Introduction of cannabinoids therapeutically should be supported by a regulatory and educational framework that minimises the risk of harm to patients and the community.

The Regulator of Medicinal Cannabis Bill 2014 is under consideration in Australia to address this.

Nabiximols is the only cannabinoid on the Australian Register of Therapeutic Goods at present, although cannabidiol has been recommended for inclusion in Schedule 4.”

http://www.ncbi.nlm.nih.gov/pubmed/26843715

“There is some evidence of therapeutic benefit for cannabis products in defined patient populations.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674028/

[Efficacy, tolerability and safety of cannabinoids for chronic neuropathic pain : A systematic review of randomized controlled studies].

“Recently published systematic reviews came to different conclusions with respect to the efficacy, tolerability and safety of cannabinoids for treatment of chronic neuropathic pain.

Cannabinoids were marginally superior to placebo in terms of efficacy and inferior in terms of tolerability.

Cannabinoids and placebo did not differ in terms of safety during the study period.

Short-term and intermediate-term therapy with cannabinoids can be considered in selected patients with chronic neuropathic pain after failure of first-line and second-line therapies.”

http://www.ncbi.nlm.nih.gov/pubmed/26830780

http://www.thctotalhealthcare.com/category/neuropathic-pain/

The selective monoacylglycerol lipase inhibitor MJN110 produces opioid sparing effects in a mouse neuropathic pain model.

“Serious clinical liabilities associated with the prescription of opiates for pain control include constipation, respiratory depression, pruritus, tolerance, abuse, and addiction.

A recognized strategy to circumvent these side effects is to combine opioids with other antinociceptive agents.

The combination of opiates with the primary active constituent of cannabis, Δ9-tetrahydrocannabinol, produces enhanced antinociceptive actions, suggesting that cannabinoid receptor agonists can be opioid sparing…

Here, we tested whether elevating the endogenous cannabinoid 2-arachidonylglycerol (2-AG) through the inhibition of its primary hydrolytic enzyme monoacylglycerol lipase (MAGL), will produce opioid sparing effects…

These findings, taken together, suggest that MAGL inhibition produces opiate sparing events with diminished tolerance, constipation, and cannabimemetic side effects.”

http://www.ncbi.nlm.nih.gov/pubmed/26791602

http://www.thctotalhealthcare.com/category/pain-2/

The endocannabinoid system and neuropathic pain.

“The research of new therapeutic strategies for neuropathic pain represents a major current priority.

Important drawbacks to advance in the development of these therapies are the limited translational value of the animal models now available and the elucidation of the complex neuronal and immune pathophysiological mechanisms underlying neuropathic pain.

One of the neurotransmitter systems participating in neuropathic pain control that has recently raised a particular interest is the endocannabinoid system.

This system is highly expressed in neurons and immune cells, and it plays a crucial role in the development of neuropathic pain.

Preclinical studies have provided important findings, revealing the potential interest of the endocannabinoid system for the treatment of neuropathic pain.

These studies have reported the analgesic effects of cannabinoid agonists in multiple neuropathic pain models, and they have identified specific targets within this system to develop more effective and safe analgesic compounds.

Several clinical studies suggest that cannabinoids significantly reduced neuropathic pain…

http://www.ncbi.nlm.nih.gov/pubmed/26785153

Evaluating Sativex® in Neuropathic Pain Management: A Clinical and Neurophysiological Assessment in Multiple Sclerosis.

“Pain is a common symptom of MS, affecting up to 70% of patients.

Pain treatment is often unsatisfactory, although emerging drugs (including cannabinoids) are giving encouraging results.

 The aim of our study was to better investigate the role of Sativex® in improving pain in multiple sclerosis (MS) patients by means of either clinical or neurophysiological assessment.

 One month of drug administration in MS patients with neuropathic pain successfully reduced pain rating and improved quality of life.
Our data suggest that Sativex may be effective in improving MS-related neuropathic pain, maybe through its action on specific cortical pathways.”

Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress.

“Neuropathy is the most common complication of diabetes and it is still considered to be relatively refractory to most of the analgesics. The aim of the present study was to explore the antinociceptive effect of a controlled cannabis extract (eCBD) in attenuating diabetic neuropathic pain.

These findings highlighted the beneficial effects of cannabis extract treatment in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and a specific action upon nerve growth factor.”

http://www.ncbi.nlm.nih.gov/pubmed/19441010

Therapy with a Selective Cannabinoid Receptor Type 2 Agonist Limits Albuminuria and Renal Injury in Mice with Type 2 Diabetic Nephropathy.

“A critical involvement of the endocannabinoid/cannabinoid receptor system in diabetes and its complications has been recognized.

Experimental evidence suggested that activation of the cannabinoid receptor type 2 (CB2), which is expressed in the kidney by podocytes and inflammatory cells, had a protective role in early streptozotocin-induced type 1 diabetes in mice.

In this study, we investigated the effects of a CB2 agonist given at a phase of overt disease on renal functional and structural changes in BTBR ob/ob mice, a model of type 2 diabetic nephropathy.

These results suggest that CB2 agonism is a potential option to be added to the available therapeutic armamentarium for type 2 diabetic nephropathy.”

http://www.ncbi.nlm.nih.gov/pubmed/26646377

Peripherally Restricted Cannabinoids for the Treatment of Pain.

“The use of cannabinoids for the treatment of chronic diseases has increased in the United States, with 23 states having legalized the use of marijuana.

Although currently available cannabinoid compounds have shown effectiveness in relieving symptoms associated with numerous diseases, the use of cannabis or cannabinoids is still controversial mostly due to their psychotropic effects (e.g., euphoria, laughter) or central nervous system (CNS)-related undesired effects (e.g., tolerance, dependence).

A potential strategy to use cannabinoids for medical conditions without inducing psychotropic or CNS-related undesired effects is to avoid their actions in the CNS.

This approach could be beneficial for conditions with prominent peripheral pathophysiologic mechanisms (e.g., painful diabetic neuropathy, chemotherapy-induced neuropathy).

In this article, we discuss the scientific evidence to target the peripheral cannabinoid system as an alternative to cannabis use for medical purposes, and we review the available literature to determine the pros and cons of potential strategies that can be used to this end.”

http://www.ncbi.nlm.nih.gov/pubmed/26497478

Inhaled cannabis for chronic neuropathic pain: an individual patient data meta-analysis.

“Chronic neuropathic pain, the most frequent condition affecting the peripheral nervous system, remains under-diagnosed and difficult to treat.

Inhaled cannabis may alleviate chronic neuropathic pain.

Our objective was to synthesize the evidence on inhaled cannabis for chronic neuropathic pain.

This novel Bayesian individual patient data meta-analysis of five randomized trials suggests that inhaled cannabis may provide short term relief for one in five to six patients with neuropathic pain.

Pragmatic trials are need to evaluate the long-term benefits and risks of this treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/26362106

Cannabinoids blocks tactile allodynia in diabetic mice without attenuation of its antinociceptive effect.

“Diabetic neuropathic pain is one of the most commonly encountered neuropathic pain syndromes.

It is well known that diabetic animals are less sensitive to the analgesic effect of morphine, and opioids are found to be ineffective in the treatment of diabetic neuropathic pain.

Cannabinoids are promising drugs and they share a similar pharmacological properties with opioids.

It has been reported that cannabinoid analgesia remained intact and to be effective in some models of nerve injury.

Thus, we investigated antinociceptive efficacy and the effects of cannabinoids on behavioral sign of diabetic neuropathic pain in diabetic mice by using WIN 55, 212-2, a cannabinoid receptor agonist.

This study suggests that cannabinoids have a potential beneficial effect on experimental diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/15342139