Tag Archives: treatment

The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: clues for other neuroinflammatory diseases.

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“Multiple sclerosis is the most common inflammatory demyelinating disease of the central nervous system, caused by an autoimmune response against myelin that eventually leads to progressive neurodegeneration and disability. Although the knowledge on its underlying neurobiological mechanisms has considerably improved, there is a still unmet need for new treatment options, especially for the progressive forms of the disease.

Both preclinical and clinical data suggest that cannabinoids, derived from the Cannabis sativa plant, may be used to control symptoms such as spasticity and chronic pain, whereas only preclinical data indicate that these compounds and their endogenous counterparts, i.e. the endocannabinoids, may also exert neuroprotective effects and slow down disease progression.

Here, we review the preclinical and clinical studies that could explain the therapeutic action of cannabinoid-based medicines, as well as the medical potential of modulating endocannabinoid signaling in multiple sclerosis, with a link to other neuroinflammatory disorders that share common hallmarks and pathogenetic features.”

https://www.ncbi.nlm.nih.gov/pubmed/29097192

http://www.sciencedirect.com/science/article/pii/S0301008217300709

THC inhibits the expression of ethanol-induced locomotor sensitization in mice.

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“The motivational circuit activated by ethanol leads to behavioral changes that recruit the endocannabinoid system (ECS). Case reports and observational studies suggest that the use of Cannabis sp. mitigates problematic ethanol consumption in humans.

Here, we verified the effects of the two main phytocannabinoid compounds of Cannabis sp., cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), in the expression of ethanol-induced locomotor sensitization in mice.

Our findings showing that phytocannabinoid treatment prevents the expression of behavioral sensitization in mice provide insight into the potential therapeutic use of phytocannabinoids in alcohol-related problems.”

https://www.ncbi.nlm.nih.gov/pubmed/29084627

http://www.sciencedirect.com/science/article/pii/S0741832916302877?via%3Dihub

The Potential of Cannabidiol Treatment for Cannabis Users With Recent-Onset Psychosis.

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Schizophrenia Bulletin

“A major factor associated with poor prognostic outcome after a first psychotic break is cannabis misuse, which is prevalent in schizophrenia and particularly common in individuals with recent-onset psychosis. Behavioral interventions aimed at reducing cannabis use have been unsuccessful in this population.

Cannabidiol (CBD) is a phytocannabinoid found in cannabis, although at low concentrations in modern-day strains. CBD has a broad pharmacological profile, but contrary to ∆9-tetrahydrocannabinol (THC), CBD does not activate CB1 or CB2 receptors and has at most subtle subjective effects.

Growing evidence indicates that CBD acts as an antipsychotic and anxiolytic, and several reports suggest neuroprotective effects. Moreover, CBD attenuates THC’s detrimental effects, both acutely and chronically, including psychotogenic, anxiogenic, and deleterious cognitive effects. This suggests that CBD may improve the disease trajectory of individuals with early psychosis and comorbid cannabis misuse in particular-a population with currently poor prognostic outcome and no specialized effective intervention.”

https://www.ncbi.nlm.nih.gov/pubmed/29083450

https://academic.oup.com/schizophreniabulletin/article/doi/10.1093/schbul/sbx105/4080751/The-Potential-of-Cannabidiol-Treatment-for

N-Arachidonoyl Dopamine: A Novel Endocannabinoid and Endovanilloid with Widespread Physiological and Pharmacological Activities.

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Mary Ann Liebert, Inc. publishers

“N-arachidonoyl dopamine (NADA) is a member of the family of endocannabinoids to which several other N-acyldopamines belong as well. Their activity is mediated through various targets that include cannabinoid receptors or transient receptor potential vanilloid (TRPV)1. Synthesis and degradation of NADA are not yet fully understood. Nonetheless, there is evidence that NADA plays an important role in nociception and inflammation in the central and peripheral nervous system. The TRPV1 receptor, for which NADA is a potent agonist, was shown to be an endogenous transducer of noxious heat. Moreover, it has been demonstrated that NADA exerts protective and antioxidative properties in microglial cell cultures, cortical neurons, and organotypical hippocampal slice cultures. NADA is present in very low concentrations in the brain and is seemingly not involved in activation of the classical pathways. We believe that treatment with exogenous NADA during and after injury might be beneficial. This review summarizes the recent findings on biochemical properties of NADA and other N-acyldopamines and their role in physiological and pathological processes. These findings provide strong evidence that NADA is an effective agent to manage neuroinflammatory diseases or pain and can be useful in designing novel therapeutic strategies.”

https://www.ncbi.nlm.nih.gov/pubmed/29082315

http://online.liebertpub.com/doi/10.1089/can.2017.0015

Anti-Inflammatory Activity in Colon Models Is Derived from Δ9-Tetrahydrocannabinolic Acid That Interacts with Additional Compounds in Cannabis Extracts.

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“Inflammatory bowel diseases (IBDs) include Crohn’s disease, and ulcerative colitis. Cannabis sativa preparations have beneficial effects for IBD patients. However, C. sativa extracts contain hundreds of compounds. Although there is much knowledge of the activity of different cannabinoids and their receptor agonists or antagonists, the cytotoxic and anti-inflammatory activity of whole C. sativa extracts has never been characterized in detail with in vitro and ex vivo colon models.

Material and Methods: The anti-inflammatory activity of C. sativa extracts was studied on three lines of epithelial cells and on colon tissue. C. sativa flowers were extracted with ethanol, enzyme-linked immunosorbent assay was used to determine the level of interleukin-8 in colon cells and tissue biopsies, chemical analysis was performed using high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance and gene expression was determined by quantitative real-time PCR.

Results: The anti-inflammatory activity of Cannabis extracts derives from D9-tetrahydrocannabinolic acid (THCA) present in fraction 7 (F7) of the extract. However, all fractions of C. sativa at a certain combination of concentrations have a significant increased cytotoxic activity. GPR55 receptor antagonist significantly reduces the anti-inflammatory activity of F7, whereas cannabinoid type 2 receptor antagonist significantly increases HCT116 cell proliferation. Also, cannabidiol (CBD) shows dose dependent cytotoxic activity, whereas anti-inflammatory activity was found only for the low concentration of CBD, and in a bell-shaped rather than dose-dependent manner. Activity of the extract and active fraction was verified on colon tissues taken from IBD patients, and was shown to suppress cyclooxygenase-2 (COX2) and metalloproteinase-9 (MMP9) gene expression in both cell culture and colon tissue.

Conclusions: It is suggested that the anti-inflammatory activity of Cannabis extracts on colon epithelial cells derives from a fraction of the extract that contains THCA, and is mediated, at least partially, via GPR55 receptor. The cytotoxic activity of the C. sativa extract was increased by combining all fractions at a certain combination of concentrations and was partially affected by CB2 receptor antagonist that increased cell proliferation. It is suggested that in a nonpsychoactive treatment for IBD, THCA should be used rather than CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/29082314
http://www.liebertpub.com/manuscript/can

Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients.

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“Treatment of neuropathic pain (NP) symptoms associated with multiple sclerosis (MS) is frequently insufficient. Yet, cannabis is still rarely offered for treatment of pain. This clinical trial aimed at showing the positive benefit-risk ratio of dronabinol. Two hundred forty MS patients with central NP entered a 16-weeks placebo-controlled phase-III study followed by a 32-weeks open-label period. One hundred patients continued therapy for overall up to 119 weeks. Primary endpoint was change of pain intensity on the 11-point Numerical Rating Scale over a 16-weeks treatment period. Safety was assessed on the basis of adverse reactions (ARs), signs of dependency and abuse. Pain intensity during 16-weeks dronabinol and placebo treatment was reduced by 1.92 and 1.81 points without significant difference in between (p = 0.676). Although the proportion of patients with ARs was higher under dronabinol compared to placebo (50.0 vs. 25.9%), it decreased during long-term use of dronabinol (26%). No signs of drug abuse and only one possible case of dependency occurred. The trial results demonstrate that dronabinol is a safe long-term treatment option.” https://www.ncbi.nlm.nih.gov/pubmed/29073592

“Overall, this trial demonstrated the long-lasting therapeutic potential, the good tolerability and favourable safety profile of dronabinol – especially in terms of drug abuse and dependency. Based on the presented results, there is no special focus on the harm caused by dronabinol treatment. Although the statistical proof of efficacy for dronabinol versus placebo treatment is pending, physicians should consider the potential benefits of the multifactorial effects of dronabinol.” https://www.karger.com/Article/FullText/481089

Medical cannabis for the treatment of chronic pain and other disorders: misconceptions and facts.

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“Recently, many countries have enacted new cannabis policies, including decriminalization of cannabis possession, medical cannabis legalization, and legalization of recreational cannabis.  In this context, patients and their physicians have had an increasing number of conversations about the risks and benefits of cannabis.  While cannabis and cannabinoids continue to be evaluated as pharmacotherapy for medical conditions, currently, the best evidence exists for the following medical conditions: chronic pain, neuropathic pain, and spasticity resulting from multiple sclerosis.  We also reviewed the current state of evidence for cannabis and cannabinoids for a number of other medical conditions while addressing the potential acute and chronic effects of cannabis use, which are issues that physicians must consider before making an official recommendation on the use of medical cannabis to a patient.  As patient requests for medical cannabis increase, physicians must become knowledgeable on the science of medical cannabis and open to a discussion about why the patient feels that medical cannabis may be helpful to them.”

https://www.ncbi.nlm.nih.gov/pubmed/29067992

http://pamw.pl/en/issue/article/29067992

The use of cannabidiol for seizure management in patients with brain tumor-related epilepsy.

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“Epilepsy, commonly encountered by patients with brain tumors, is often refractory to standard therapies. Our aim was to examine the safety and efficacy of pharmaceutical grade cannabidiol (CBD; Epidiolex, GW Pharmaceuticals) in those patients with epilepsy with concomitant tumors enrolled in The University of Alabama at Birmingham CBD Program (NCT02700412 and NCT02695537). Of the three patients with refractory seizures and a history of a primary brain tumor, two had improvement in seizure frequency and all three had improvement in seizure severity. These pilot results suggest that CBD should be further studied for the treatment of brain tumor-related epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/29063814

http://www.tandfonline.com/doi/abs/10.1080/13554794.2017.1391294?journalCode=nncs20

The Synthetic Cannabinoid WIN 55,212-2 Elicits Death in Human Cancer Cell Lines.

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“Studies have revealed that cancer might be treated with cannabinoids since they can influence cancer cell survival. These findings suggest an alternative treatment option to chemo- and radiotherapy, that are associated with numerous adverse side-effects for the patients.

MATERIALS AND METHODS:

Viability staining was conducted on lung cancer, testicular cancer and neuroblastoma cells treated with different concentrations of the synthetic cannabinoid WIN 55,212-2 and the percentage of dead cells was compared. Activity of apoptosis-related enzymes was investigated by the presence of DNA ladder in gel electrophoresis.

RESULTS:

Treatment with different WIN 55,212-2 concentrations led to a significant dose-dependent reduction of cell viability. A DNA ladder was observed after WIN 55,212-2 treatment of testicular cancer and lung cancer cells.

CONCLUSION:

The application of WIN 55,212-2 was found to trigger cell death in the investigated cell lines. The decline in lung cancer and testicular cancer cell viability seems to have been caused by apoptosis. These findings may contribute to development of alternative cancer therapy strategies.”

https://www.ncbi.nlm.nih.gov/pubmed/29061818

Medical Cannabis in Parkinson Disease: Real-Life Patients’ Experience.

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“The use of medical cannabis (MC) is controversial. Support for its benefits is based on small clinical series.

OBJECTIVE:

The aim of this study was to report the results of a standardized interview study that retrospectively assessed the effects of MC on symptoms of Parkinson disease (PD) and its adverse effects in patients treated for at least 3 months.

METHODS:

The survey used telephone interviews using a structured questionnaire based on subjective global impressions of change for various parkinsonian symptoms and yes/no questions on adverse effects.

RESULTS:

Forty-seven nondemented patients with PD (40 men) participated. Their mean age was 64.2 ± 10.8 years, mean disease duration was 10.8 ± 8.3 years, median Hoehn and Yahr (H&Y) was stage III. The duration of MC use was 19.1 ± 17.0 months, and the mean daily dose was 0.9 ± 0.5 g. The delivery of MC was mainly by smoking cigarettes (38 cases, 80.9%). Effect size (r) improvement for falls was 0.89, 0.73 for pain relief, 0.64 for depression, 0.64 for tremor, 0.62 for muscle stiffness, and 0.60 for sleep. The most frequently reported adverse effects from MC were cough (34.9%) in those who used MC by smoking and confusion and hallucinations (reported by 17% each) causing 5 patients (10.6%) to stop treatment.

CONCLUSIONS:

Medical cannabis was found to improve symptoms of PD in the initial stages of treatment and did not cause major adverse effects in this pilot, 2-center, retrospective survey. The extent of use and the reported effects lend support to further development of safer and more effective drugs derived from Cannabis sativa.”

https://www.ncbi.nlm.nih.gov/pubmed/29059132

https://insights.ovid.com/crossref?an=00002826-900000000-99616