Tag Archives: treatment

Cannabidiol and epilepsy: rationale and therapeutic potential.

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“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].

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“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.

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“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.

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“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

Effects of cannabinoid receptor activation by CP55,940 on normal bladder function and irritation-induced bladder overactivity in non-awake anaesthetised rats.

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“CP55,940 is a synthetic analogue of tetrahydrocannabidiol, which is a psychoactive ingredient of the Cannabis plant.

This study was designed to evaluate the effects of CP55,940 on normal bladder function in vivo and examine whether it suppresses urinary frequency induced by nociceptive stimuli in the bladder.

CP55,940 decreases bladder activity and urinary frequency induced by nociceptive stimuli, probably by suppression of bladder afferent activity. Effects of CP55,940 were abolished by both CBR antagonists. This data implicates a role for the endocannabinoid system in bladder mechanoafferent function in rats. In addition, our results show that CP55,940 reverses urinary frequency exemplified in an overactive bladder model, suggesting it could be an effective treatment for patients with lower urinary tract symptoms.”

http://www.ncbi.nlm.nih.gov/pubmed/26942594

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

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“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

Role of cannabinoids in gastrointestinal mucosal defense and inflammation.

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“Modulating the activity of the endocannabinoid system influences various gastrointestinal physiological and pathophysiological processes, and cannabinoid receptors as well as regulatory enzymes responsible for the synthesis or degradation of endocannabinoids represent potential targets to reduce the development of gastrointestinal mucosal lesions, hemorrhage and inflammation.

Direct activation of CB1 receptors by plant-derived, endogenous or synthetic cannabinoids effectively reduces both gastric acid secretion and gastric motor activity, and decreases the formation of gastric mucosal lesions induced by stress, pylorus ligation, nonsteroidal anti-inflammatory drugs (NSAIDs) or alcohol, partly by peripheral, partly by central mechanisms.

Similarly, indirect activation of cannabinoid receptors through elevation of endocannabinoid levels by globally acting or peripherally restricted inhibitors of their metabolizing enzymes (FAAH, MAGL) or by inhibitors of their cellular uptake reduced the gastric mucosal lesions induced by NSAIDs in a CB1 receptor-dependent fashion.

Dual inhibition of FAAH and cyclooxygenase induced protection against both NSAID-induced gastrointestinal damage and intestinal inflammation.

Moreover, in intestinal inflammation direct or indirect activation of CB1 and CB2 receptors exerts also multiple beneficial effects.

Namely, activation of both CB receptors was shown to ameliorate intestinal inflammation in various murine colitis models, to decrease visceral hypersensitivity and abdominal pain, as well as to reduce colitis-associated hypermotility and diarrhea.

In addition, CB1 receptors suppress secretory processes and also modulate intestinal epithelial barrier functions. Thus, experimental data suggest that the endocannabinoid system represents a promising target in the treatment of inflammatory bowel diseases, and this assumption is also confirmed by preliminary clinical studies.”

http://www.ncbi.nlm.nih.gov/pubmed/26935536

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

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“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

Cannabinoids: Medical implications.

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“Herbal cannabis has been used for thousands of years for medical purposes.

With elucidation of the chemical structures of tetrahydrocannabinol (THC) and cannabidiol (CBD) and with discovery of the human endocannabinoid system, the medical usefulness of cannabinoids has been more intensively explored.

While more randomized clinical trials are needed for some medical conditions, other medical disorders, like chronic cancer and neuropathic pain and certain symptoms of multiple sclerosis, have substantial evidence supporting cannabinoid efficacy.

While herbal cannabis has not met rigorous FDA standards for medical approval, specific well-characterized cannabinoids have met those standards.

Where medical cannabis is legal, patients typically see a physician who “certifies” that a benefit may result.

Physicians must consider important patient selection criteria such as failure of standard medical treatment for a debilitating medical disorder. Medical cannabis patients must be informed about potential adverse effects, such as acute impairment of memory, coordination and judgment, and possible chronic effects, such as cannabis use disorder, cognitive impairment, and chronic bronchitis.

Novel ways to manipulate the endocannbinoid system are being explored to maximize benefits of cannabinoid therapy and lessen possible harmful effects.

Key messages The medical disorders with the current best evidence that supports a benefit for cannabinoid use are the following: multiple sclerosis patient-reported symptoms of spasticity (nabiximols, nabilone, dronabinol, and oral cannabis extract), multiple sclerosis central pain or painful spasms (nabiximols, nabilone, dronabinol, and oral cannabis extract), multiple sclerosis bladder frequency (nabiximols), and chronic cancer pain/neuropathic pain (nabiximols and smoked THC).

Participating physicians should be knowledgeable about cannabinoids, closely look at the risk/benefit ratio, and consider certain important criteria in selecting a patient, such as: age, severity, and nature of the medical disorder, prior or current serious psychiatric or substance use disorder, failure of standard medical therapy as well as failure of an approved cannabinoid, serious underlying cardiac/pulmonary disease, agreement to follow-up visits, and acceptance of the detailed explanation of potential adverse risks.

The normal human endocannabinoid system is important in the understanding of such issues as normal physiology, cannabis use disorder, and the development of medications that may act as agonists or antagonists to CB1 and CB2.

By understanding the endocannabinoid system, it may be possible to enhance the beneficial effects of cannabinoid-related medication, while reducing the harmful effects.”

http://www.ncbi.nlm.nih.gov/pubmed/26912385

Plant-Derived and Endogenous Cannabinoids in Epilepsy.

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“Cannabis is one of the oldest psychotropic drugs and its anticonvulsant properties have been known since the last century.

The aim of this reveiw was to analyze the efficacy of cannabis in the treatment of epilepsy in adults and children. In addition, a description of the involvement of the endocannabinoid system in epilepsy is given in order to provide a biochemical background to the effects of endogenous cannabinoids in our body.

General tolerability and adverse events associated with cannabis treatment are also investigated. Several anecdotal reports and clinical trials suggest that in the human population cannabis has anticonvulsant properties and could be effective in treating partial epilepsies and generalized tonic-clonic seizures, still known as “grand mal.”

They are based, among other factors, on the observation that in individuals who smoke marijuana to treat epilepsy, cessation of cannabis use precipitates the re-emergence of convulsive seizures, whereas resuming consumption of this psychotropic drug controls epilepsy in a reproducible manner.

In conclusion, there is some anecdotal evidence for the potential efficacy of cannabis in treating epilepsy.

Though there has been an increased effort by patients with epilepsy, their caregivers, growers, and legislators to legalize various forms of cannabis, there is still concern about its efficacy, relative potency, availability of medication-grade preparations, dosing, and potential short- and long-term side effects, including those on prenatal and childhood development.”

http://www.ncbi.nlm.nih.gov/pubmed/26892745

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