Techniques and technologies for the bioanalysis of Sativex®, metabolites and related compounds.

“Sativex® is an oromucosal spray indicated for the treatment of moderate-to-severe spasticity in multiple sclerosis and is also an effective analgesic for advanced cancer patients.

Sativex contains Δ9-tetrahydrocannabinol (THC) and cannabidiol in an approximately 1:1 ratio.

The increasing prevalence of medicinal cannabis products highlights the importance of reliable bioanalysis and re-evaluation of the interpretation of positive test results for THC, as legal implications may arise in workplace, roadside and sports drug testing situations. This article summarizes published research on the bioanalysis of THC and cannabidiol, with particular focus on Sativex.”

http://www.ncbi.nlm.nih.gov/pubmed/27005853

Cannabis in Pain Treatment: Clinical & Research Considerations.

“Cannabinoids show promise as therapeutic agents, particularly as analgesics, but their development and clinical use has been complicated by recognition of their botanical source, cannabis, as a substance of misuse. While research into endogenous cannabinoid systems and potential cannabinoid pharmaceuticals is slowly increasing, there has been intense societal interest in making herbal (plant) cannabis available for medicinal use; 23 U.S. States and all Canadian provinces currently permit use in some clinical contexts. Whether or not individual professionals support the clinical use of herbal cannabis, all clinicians will encounter patients who elect to use it and therefore need to be prepared to advise them on cannabis-related clinical issues despite limited evidence to guide care. Expanded research on cannabis is needed both to better determine the individual and public health effects of increasing use of herbal cannabis and to advance understanding of the pharmaceutical potential of cannabinoids as medications. This paper reviews clinical, research and policy issues related to herbal cannabis in order to support clinicians in thoughtfully advising and caring for patients who use cannabis and it examines obstacles and opportunities to expand research on the health effects of herbal cannabis and cannabinoids.

PERSPECTIVE:

Herbal cannabis is increasingly available for clinical use in the U.S despite continuing controversies over its efficacy and safety. This paper explores important considerations in the use of plant Cannabis to better prepare clinicians to care for patients who use it and to identify needed directions for research.”

http://www.ncbi.nlm.nih.gov/pubmed/26961090

Combined treatment with morphine and Δ9-tetrahydrocannibinol (THC) in rhesus monkeys: antinociceptive tolerance and withdrawal.

“Opioid receptor agonists are effective for treating pain; however, tolerance and dependence can develop with repeated treatment. Combining opioids with cannabinoids can enhance their analgesic potency…

These results demonstrate that antinociceptive tolerance is greater during treatment with the mixture, and although treatment conditions were sufficient for dependence to development on morphine, withdrawal was not markedly altered by concurrent treatment with THC.

Thus, THC can enhance some (antinociception, tolerance) but not all (dependence) effects of morphine.”

http://www.ncbi.nlm.nih.gov/pubmed/26937020

A Single Intrathecal or Intraperitoneal Injection of CB2 Receptor Agonist Attenuates Bone Cancer Pain and Induces a Time-Dependent Modification of GRK2.

“The objective of this study was to explore the potential role of G-protein-coupled receptor kinase 2 (GRK2) in the progression of cannabinoid 2 receptor (CB2) agonist-induced analgesic effects of bone cancer pain.

The results affirmed CB2 receptor agonists might serve as new treatment targets for bone cancer pain.

Moreover, spinal GRK2 was an important regulator of CB2 receptor agonist-analgesia pathway.”

http://www.ncbi.nlm.nih.gov/pubmed/26935064

Development and Pharmacological Characterization of Selective Blockers of 2-Arachidonoyl Glycerol Degradation with Efficacy in Rodent Models of Multiple Sclerosis and Pain.

“We report the discovery of compound 4a, a potent β-lactam-based monoacylglycerol lipase (MGL) inhibitor characterized by an irreversible and stereoselective mechanism of action, high membrane permeability, high brain penetration evaluated using a human in vitro blood brain barrier model, high selectivity in binding and affinity-based proteomic profiling assays, and low in vitro toxicity.

Mode-of-action studies demonstrate that 4a, by blocking MGL, increases 2-arachidonoylglycerol, and behaves as cannabinoid (CB1/CB2) receptor indirect agonist.

Administration of 4a in mice suffering from experimental autoimmune encephalitis ameliorates the severity of the clinical symptoms in a CB1/CB2-dependent manner. Moreover, 4a produced analgesic effects in a rodent model of acute inflammatory pain, which was antagonized by CB1 and CB2 receptor antagonists/inverse agonists. 4a also relieves the neuropathic hypersensitivity induced by oxaliplatin.

Given these evidences, 4a, as MGL selective inhibitor, could represent a valuable lead for the future development of therapeutic options for multiple sclerosis and chronic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/26888301

Quantification of pain in sickle mice using facial expressions and body measurements.

“Pain is a hallmark feature of sickle cell disease (SCD). Subjects typically quantify pain by themselves, which can be biased by other factors leading to overtreatment or under-treatment. Reliable and accurate quantification of pain, in real time, might enable to provide appropriate levels of analgesic treatment.

The mouse grimace scale (MGS), a standardized behavioral coding system with high accuracy and reliability has been used to quantify varied types of pain. We hypothesized that addition of the objective parameters of body length and back curvature will strengthen the reproducibility of MGS.

We examined MGS scores and body length and back curvature of transgenic BERK sickle and control mice following cold treatment or following treatment with analgesic cannabinoid CP55,940. We observed that sickle mice demonstrated decreased length and increased back curvature in response to cold. These observations correlate with changes in facial expression for the MGS score.

CP55,940 treatment of sickle mice showed an increase in body length and a decrease in back curvature concordant with MGS scores indicative of an analgesic effect. Thus, body parameters combined with facial expressions may provide a quantifiable unbiased method for objective measure of pain in SCD.”

http://www.ncbi.nlm.nih.gov/pubmed/26852657

http://www.thctotalhealthcare.com/category/sickle-cell-disease/

Clinical/Therapeutic Approaches for Cannabinoid Ligands in Central and Peripheral Nervous System Diseases: Mini Review.

“Cannabinoids, the components of Cannabis sativa Linnaeus, interact with CB1 and CB2 receptors, which are located both in the central nervous system and in the periphery and thus may exert a widespread biological activity in the body.

The main medicinal properties of cannabinoids include analgesic, anti-inflammatory, antitumor, appetite stimulation, antiemesis, and muscle relaxation effects.

This mini review aims to explore existing clinical trials that investigated the use of cannabinoids in diseases affecting the nervous system.

There is evidence that cannabinoid-based drugs may effectively control some symptoms associated with nervous system dysfunction, especially various types of pain and neurologic disorders, although studies are limited.

The efficacy of cannabinoid drugs in the treatment of nervous system diseases should be verified in future large-scale randomized clinical trials.”

http://www.ncbi.nlm.nih.gov/pubmed/26818043

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

Marijuana For Migraines

 

 

“Our brain’s own endogenous marijuana-like chemicals produce analgesia by modulating the entry of pain signals into the brain at the level of our spinal cord.

Future generations of pain relievers will likely be developed based upon the action of marijuana in the body.

The advantage of targeting the endogenous marijuana system is that only noxious or painful signals are blocked; normal touch sensation is normal.

This study may lead to the development of more effective migraine prevention and treatment.

The challenge will be to find a dose of marijuana that produces pain relief without disturbing normal cognitive function.”

 https://www.psychologytoday.com/blog/your-brain-food/201309/marijuana-migraines

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

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