Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?

Posted on March 30, 2016 by David

“The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia.

Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders.

Of particular interest is the primary nonpsychoactive constituent cannabidiol (CBD).

Unlike Δ9-tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1) receptor but has many other receptor targets that may play a role in psychiatric disorders.

Here we review preclinical and clinical data outlining the therapeutic efficacy of CBD for the treatment of motivational disorders such as drug addiction, anxiety, and depression.

Across studies, findings suggest promising treatment effects and potentially overlapping mechanisms of action for CBD in these disorders and indicate the need for further systematic investigation of the viability of CBD as a psychiatric pharmacotherapy.”

http://www.ncbi.nlm.nih.gov/pubmed/27023732

The role of carbon monoxide on the anti-nociceptive effects and expression of cannabinoid 2 receptors during painful diabetic neuropathy in mice.

Posted on March 30, 2016 by David

“The activation of cannabinoid 2 receptors (CB2R) attenuates chronic pain, but the role played by carbon monoxide synthesized by the inducible heme oxygenase 1 (HO-1) on the anti-nociceptive effects produced by a selective CB2R agonist, JWH-015, during painful diabetic neuropathy remains unknown.

The activation of HO-1 enhanced the anti-nociceptive effects of JWH-015 in diabetic mice, suggesting that coadministration of JWH-015 with CORM-2 or CoPP might be an interesting approach for the treatment of painful diabetic neuropathy in mice.”

http://www.ncbi.nlm.nih.gov/pubmed/27020787

Prohedonic Effect of Cannabidiol in a Rat Model of Depression.

Posted on March 25, 2016 by David

“Accumulating evidence suggests that cannabidiol (CBD) may be an effective and safe anxiolytic agent and potentially also an antidepressant.

These findings extend the limited knowledge on the antidepressant effect of CBD, now shown for the first time in a genetic animal model of depression. These results suggest that CBD may be beneficial for the treatment of clinical depression and other states with prominent anhedonia.”

http://www.ncbi.nlm.nih.gov/pubmed/27010632

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

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

Posted on March 24, 2016 by David

“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

Medical marijuana use in head and neck squamous cell carcinoma patients treated with radiotherapy.

Posted on March 24, 2016 by David

Supportive Care in Cancer

“The purpose of the study was to better understand why patients with history of head and neck cancer (HNC) treated with radiotherapy are using medical marijuana (MM).

RESULTS:

There was a 100 % response rate. Median time from treatment was 45 months (21-136 months). Most patients smoked marijuana (12 patients), while others reported ingestion (4 patients), vaporizing (3 patients), and use of homemade concentrated oil (1 patient). Six patients reported prior recreational marijuana use before diagnosis. MM provided benefit in altered sense, weight maintenance, depression, pain, appetite, dysphagia, xerostomia, muscle spasm, and sticky saliva.

CONCLUSIONS:

HNC patients report MM use to help with long-term side effects of radiotherapy.”

http://www.ncbi.nlm.nih.gov/pubmed/27005465

https://link.springer.com/article/10.1007%2Fs00520-016-3180-8

The effect of cannabinoids on the stretch reflex in multiple sclerosis spasticity.

Posted on March 24, 2016 by David

“The aim of this observational study was to assess the efficacy of a tetrahydrocannabinol-cannabidiol (THC : CBD) oromucosal spray on spasticity using the stretch reflex in patients with multiple sclerosis (MS).

Numeric rating scale (NRS) for spasticity, modified Ashworth scale (MAS), and the stretch reflex were assessed before and during treatment in 57 MS patients with spasticity eligible for THC : CBD treatment.

A significant reduction in stretch reflex amplitude as well as significant reductions of NRS and MAS scores were observed. There was a low concordance between the three measures (stretch reflex, NRS, and MAS), likely related to the different aspects of muscle hypertonia assessed.

Stretch reflex responders were taking a significantly higher number of puffs, whereas no differences were found in the responders by the other scales, suggesting that a higher dosage would add benefit if tolerated.

The present study confirms the efficacy of cannabinoids in reducing spasticity in patients with MS, suggesting a higher sensitivity and specificity of the stretch reflex compared with other measures. As an objective and quantitative measure of spasticity, the stretch reflex is particularly useful to assess the effects of cannabinoids on spinal excitability and may play a role in future pharmacological studies.”

http://www.ncbi.nlm.nih.gov/pubmed/27003093

Cannabidiol and epilepsy: rationale and therapeutic potential.

Posted on March 19, 2016 by David

“Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remains still poor. Unfortunately, besides several advantages, these new AEDs have not satisfactorily reduced the number of refractory patients. Therefore, the need for different other therapeutic options to manage epilepsy is still a current issue.

To this purpose, emphasis has been given to phytocannabinoids, which have been medicinally used since ancient time in the treatment of neurological disorders including epilepsy.

In particular, the nonpsychoactive compound cannabidiol (CBD) has shown anticonvulsant properties, both in preclinical and clinical studies, with a yet not completely clarified mechanism of action.

However, it should be made clear that most phytocannabinoids do not act on the endocannabinoid system as in the case of CBD.

In in vivo preclinical studies, CBD has shown significant anticonvulsant effects mainly in acute animal models of seizures, whereas restricted data exist in chronic models of epilepsy as well as in animal models of epileptogenesis.

Likewise, clinical evidence seem to indicate that CBD is able to manage epilepsy both in adults and children affected by refractory seizures, with a favourable side effect profile.

However, to date, clinical trials are both qualitatively and numerically limited, thus yet inconsistent. Therefore, further preclinical and clinical studies are undoubtedly needed to better evaluate the potential therapeutic profile of CBD in epilepsy, although the actually available data is promising.”

http://www.ncbi.nlm.nih.gov/pubmed/26976797

[Role of cannabinoid receptors in renal diseases].

Posted on March 13, 2016 by David

“Chronic kidney disease remains a major challenge for public health systems and corresponds to the replacement of renal functional tissue by extracellular matrix proteins such as collagens and fibronectin. There is no efficient treatment to date for chronic kidney disease except nephroprotective strategies.

The cannabinoid system and more specifically the cannabinoid receptors 1 (CB1) and 2 (CB2) may represent a new therapeutic target in chronic kidney disease.

Experimental data obtained in models of diabetes and obesity suggested that CB1 blockade and CB2 stimulation may slow the development of diabetic nephropathy.

In human kidneys, CB1 expression is increased in various chronic nephropathies and correlates with renal function. Moreover, endogenous CB1 and CB2 ligands are greatly increased during renal fibrogenesis. A microarray analysis performed in an experimental model of renal fibrosis found that the gene encoding for the CB1 receptor was among the most upregulated genes. We also demonstrated that renal fibrogenesis could be reduced by CB1 inhibition and CB2 stimulation in an experimental model through a direct mechanism involving CB1 on myofibroblasts, which are the major effector cells during renal fibrosis.

Therefore, CB1 blockers may represent a novel therapeutic target in chronic kidney disease and diabetes.”

http://www.ncbi.nlm.nih.gov/pubmed/26968477

Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.

Posted on March 12, 2016 by David

“Recent reports have shown that cannabinoid 1 receptors (CB1Rs) are expressed in pancreatic β cells, where they induce cell death and cell cycle arrest by directly inhibiting insulin receptor activation. Here, we report that CB1Rs regulate the expression of the anti-apoptotic protein Bcl-2 and cell cycle regulator cyclin D2 in pancreatic β cells. Treatment of MIN6 and βTC6 cells with a synthetic CB1R agonist, WIN55,212-2, led to a decrease in the expression of Bcl-2 and cyclin D2, in turn inducing cell cycle arrest in G0/G1 phase and caspase-3-dependent apoptosis. Additionally, genetic deletion and pharmacological blockade of CB1Rs after injury in mice led to increased levels of Bcl-2 and cyclin D2 in pancreatic β cells. These findings provide evidence for the involvement of Bcl-2 and cyclin D2 mediated by CB1Rs in the regulation of β-cell survival and growth, and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and growth in diabetes.”

http://www.ncbi.nlm.nih.gov/pubmed/26967640

Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings.

Posted on March 5, 2016 by David

“There is currently no pharmacological treatment approved for cannabis dependence. In this proof of concept study, we assessed the feasibility/effects of fixed and self-titrated dosages of Sativex (1:1, Δ⁹-tetrahydrocannabinol (THC)/cannabidiol (CBD)) on craving and withdrawal from cannabis among nine community-recruited cannabis-dependent subjects.

The results found in this proof of concept study warrant further systematic exploration of Sativex as a treatment option for cannabis withdrawal and dependence.”

http://www.ncbi.nlm.nih.gov/pubmed/26925704