Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving cannabinoid receptor CB2.

Posted on January 30, 2016 by David

“Chronic pain is commonly and closely correlated with inflammation.

Both cannabinoid signaling and mesenchymal stem cells (MSCs) have been demonstrated to reduce inflammatory pain.

Although cannabinoid signaling is essential for mesenchymal stem cell survival and differentiation, little is known about its role in modulatory effect of MSCs on inflammation and pain sensitivity. Here we showed that mouse bone-marrow derived MSCs (BM-MSCs) expressed both cannabinoid receptor type 1 and 2 (CB1 and CB2). CB2 expression level in BM-MSCs increased with their maturation.

In addition, we found that tetrahydrocannabinol (THC) activated CB2 receptor and ERK signaling, consequently enhancing the modulation of MSCs on inflammation-associated cytokine release from lipopolysaccharides-stimulated microglia.

Consistent with in vitro data, THC pretreatment enhanced the immunomodulatory effects of BM-MSC on thermal hyperalgesia and mechanical allodynia in chronic constriction injury model, by decreasing the release of pro-inflammation cytokines.

Our study revealed the crucial role of THC in promoting the immunomodulatory effects of MSCs and proposed a new strategy to alleviate pain based on stem cells therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/26824325

Dronabinol increases pain threshold in patients with functional chest pain: a pilot double-blind placebo-controlled trial.

Posted on January 30, 2016 by David

“Noncardiac chest pain is associated with poor quality of life and high care expenditure. The majority of noncardiac chest pain is either gastresophageal reflux disease related or due to esophageal motility disorders, and the rest are considered functional chest pain (FCP) due to central and peripheral hypersensitivity. Current treatment of FCP improves 40-50% of patients.

Cannabinoid receptors 1 (CB₁ ) and 2 (CB₂ ) modulate release of neurotransmitters; CB₁ is located in the esophageal epithelium and reduces excitatory enteric transmission and potentially could reduce esophageal hypersensitivity.

We performed a prospective study to evaluate its effects on pain threshold, frequency, and intensity in FCP.

Dronabinol increased pain thresholds significantly (3.0 vs. 1.0; P = 0.03) and reduced pain intensity and odynophagia compared to placebo (0.18 vs. 0.01 and 0.12 vs. 0.01, respectively, P = 0.04).

Depression and anxiety scores did not differ between the groups at baseline or after treatment.

No significant adverse effects were observed.

In this novel study, dronabinol increased pain threshold and reduced frequency and intensity of pain in FCP. Further, large scale studies are needed to substantiate these findings.”

http://www.ncbi.nlm.nih.gov/pubmed/26822791

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

Posted on January 23, 2016 by David

“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/

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

Posted on January 15, 2016 by David

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/26764336

The Role of the Brain’s Endocannabinoid System in Pain and Its Modulation by Stress.

Posted on December 8, 2015 by David

“Stress has a complex, bidirectional modulatory influence on pain. Stress may either reduce (stress-induced analgesia) or exacerbate (stress-induced hyperalgesia) pain depending on the nature, duration, and intensity of the stressor.

The endogenous cannabinoid (endocannabinoid) system is present throughout the neuroanatomical pathways that mediate and modulate responses to painful stimuli.

The specific role of the endocannabinoid system in the brain in pain and the modulation of pain by stress is reviewed herein.

We first provide a brief overview of the endocannabinoid system, followed by a review of the evidence that the brain’s endocannabinoid system modulates pain.

We provide a comprehensive evaluation of the role of the endocannabinoid system supraspinally, and particularly in the rostral ventromedial medulla, periaqueductal gray, amygdala, and prefrontal cortex, in pain, stress-induced analgesia, and stress-induced hyperalgesia.

Increased understanding of endocannabinoid-mediated regulation of pain and its modulation by stress will inform the development of novel therapeutic approaches for pain and its comorbidity with stress-related disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26638768

Self-Medication of Somatic and Psychiatric Conditions Using Botanical Marijuana.

Posted on November 28, 2015 by David

“As a complement to research evaluating botanical marijuana as a medical therapy for various somatic and psychiatric conditions, there is a growing body of research assessing marijuana users’ self-reports of the symptoms and conditions for which they use marijuana without a physician’s recommendation.

As part of two larger web-based surveys and one in-situ survey at an outdoor marijuana festival, we asked regular marijuana users if they consumed the drug without a physician’s recommendation and, if so, to describe (or select from a checklist) the conditions for which they used marijuana as a medication.

Participants reported using marijuana to self-medicate a wide variety of both somatic conditions (such as pain, diabetes, and irritable bowel syndrome) and psychiatric conditions (such as depression, anxiety, and insomnia).

Because fewer than half of the American states, and only a few countries, allow physicians to recommend medicinal marijuana, these findings may be of interest to clinicians as they treat patients, to lawmakers and policymakers as they consider legislation allowing physicians to recommend botanical marijuana for somatic and psychiatric conditions, and to researchers evaluating conditions that individuals elect to self-medicate using botanical marijuana.”

http://www.ncbi.nlm.nih.gov/pubmed/26595140

Cannabinoids in the management of chronic pain: a front line clinical perspective.

Posted on November 19, 2015 by David

“Chronic pain is an escalating public health problem. Currently available treatments are inadequate to control chronic pain conditions, and there is a critical need for novel treatments.

Over a half century of elegant preclinical research has identified the presence of a sophisticated endocannabinoid system that is part of our natural pain and immune defense network.

Convergent work has supported the significant potential to exploit this system to decrease pain and inflammation.

Although the clinical research remains in its infancy, recent systematic reviews have found that 25 of 30 randomized controlled trials have demonstrated a significant analgesic effect.

The authors concluded that cannabinoids currently available for clinical use demonstrate a modest analgesic effect and are safe for the management of chronic pain.

There is a critical need for more translational research so that the excellent work of Dr. Itai Bab and our basic science colleagues around the world can move forward in providing novel cannabinoid-based medicines.

This should include more potent analgesics that are limited in side effects with several routes of delivery. Our patients deserve additional agents for pain control with a novel mechanism of action, and cannabinoids are the new frontier.”

http://www.ncbi.nlm.nih.gov/pubmed/26581068

The prescription of medical cannabis by a transitional pain service to wean a patient with complex pain from opioid use following liver transplantation: a case report.

Posted on October 29, 2015 by David

Canadian Journal of Anesthesia/Journal canadien d'anesthésie

“The purpose of this case report is to describe a patient with a preoperative complex pain syndrome who underwent liver transplantation and was able to reduce his opioid consumption significantly following the initiation of treatment with medical cannabis.

CLINICAL FEATURES:

A 57-yr-old male with a history of hepatitis C cirrhosis underwent liver transplantation. Preoperatively, he was taking hydromorphone 2-8 mg⋅day-1 for chronic abdominal pain. Postoperatively, he was given intravenous patient-controlled analgesia through which he received hydromorphone 30 mg⋅day-1. Our multidisciplinary Transitional Pain Service was involved with managing his moderate to severe acute postsurgical pain in hospital and continued with weaning him from opioid medications after discharge. It was difficult to wean the patient from opioids, and he was subsequently given medical cannabis at six weeks postoperatively with remarkable effect. By the fifth postoperative month, his use of opioids had tapered to 6 mg⋅day-1 of hydromorphone, and his functional status was excellent on this regimen.

CONCLUSION:

Reductions in opioid consumption were achieved with the administration of medical cannabis in a patient with acute postoperative pain superimposed on a chronic pain syndrome and receiving high doses of opioids. Concurrent benefits of initiating medical cannabis may include improvements in pain profile and functional status along with reductions in opioid-related side effects. This highlights the potential for medical cannabis as an adjunct medication for weaning patients from opioid use.”

http://www.ncbi.nlm.nih.gov/pubmed/26507533

https://link.springer.com/article/10.1007%2Fs12630-015-0525-6

Peripherally Restricted Cannabinoids for the Treatment of Pain.

Posted on October 27, 2015 by David

“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

Medical Cannabis Effective for Chronic Pain, Other Indications

Posted on September 28, 2015 by David

“According to this study:

* Moderate-quality evidence supports the use of cannabinoids for the treatment of chronic pain and for the spasticity related to multiple sclerosis.

* Low-quality evidence suggests that cannabinoids may be effective for chemotherapy-induced nausea and vomiting and other indications.”

http://journals.lww.com/ajnonline/Abstract/2015/10000/Medical_Cannabis_Effective_for_Chronic_Pain,_Other.31.aspx

https://www.researchgate.net/publication/282153137_Medical_Cannabis_Effective_for_Chronic_Pain_Other_Indications

“Medical Cannabis Effective for Chronic Pain, Other Indications. According to this study.” http://www.ncbi.nlm.nih.gov/pubmed/26402288

“Cannabinoids for Medical Use: A Systematic Review and Meta-analysis” http://jama.jamanetwork.com/article.aspx?articleid=2338251