Tag Archives: tetrahydrocannabinol

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

Sativex in the management of multiple sclerosis-related spasticity: An overview of the last decade of clinical evaluation.

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Multiple Sclerosis and Related Disorders Home

“Spasticity is a common symptom of multiple sclerosis (MS) affecting about 80% of MS patients. Numerous lines of evidence suggest that spasticity due to its complexity is not adequately managed with conventional anti-spastic therapies. Therefore, in order to improve the outcomes for the majority of MS patients, alternative approaches are needed to be discovered. Over the last years, the use of cannabinoid compounds as a potential treatment for MS-related symptoms has aroused great interest, owing to encouraging preclinical and clinical studies. To date, Sativex, an oromucosal spray containing tetrahydrocannabinol and cannabidiol in approximately 1:1 ratio, is the only commercially available formulation containing cannabinoids used as add-on therapy for treatment of spasticity in adult MS patients who are not responding to conventional antispastic therapies.

METHODS:

Here, by performing a literature search, we provided an overview of the last decade of clinical evaluations as well as post-marketing studies about effectiveness and safety of Sativex in the management of MS-related spasticity.

RESULTS:

Sativex was proven effective in treating spasticity and also in improving the patient’s quality of life. In addition, a low incidence of adverse reactions Sativex-related supports the good safety profile and its tolerability.

CONCLUSION:

This review by recognizing the clinical effectiveness of Sativex in spasticity management, opened a new opportunity for many patients with spasticity resistant to common antispastic drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/29055461

http://www.msard-journal.com/article/S2211-0348(17)30148-7/fulltext

THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: a pilot prospective study.

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“Lower urinary tract dysfunctions (LUTDs) are commonly reported in multiple sclerosis (MS) patients and are mainly related to neurogenic overactive bladder (OAB).

The aim of this observational study was to assess the effect of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray on resistant OAB by means of clinical and instrumental tools.

The THC/CBD treatment successfully reduced the OAB symptoms.

THC/CBD oromucosal spray has shown to be effective in improving overactive bladder symptoms in MS patients demonstrating a favorable impact on detrusor overactivity.”

https://www.ncbi.nlm.nih.gov/pubmed/29052091

Cannabis sativa Extract Reduces Cytoskeletal Associated Proteins in Breast Cancer Cell Line

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Human serum albumin: A modulator of cannabinoid drugs.

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International Union of Biochemistry and Molecular Biology

“The endocannabinoid system is a unique neuromodulatory system that affects a wide range of biological processes and maintains the homeostasis in all mammal body systems. In recent years, several pharmacological tools to target endocannabinoid neurotransmission have been developed, including direct and indirect cannabinoid agonists and cannabinoid antagonists. Due to their hydrophobic nature, cannabinoid agonists and antagonists need to bind specific transporters to allow their distribution in body fluids. Human serum albumin (HSA), the most abundant plasma protein, is a key determinant of drug pharmacokinetics. As HSA binds both the endocannabinoid anandamide and the active ingredient of Cannabis sativa, Δ-9-tetrahydrocannabinol, we hypothesize that HSA can be the most important carrier of cannabinoid drugs. In silico docking observations strongly indicate that HSA avidly binds the indirect cannabinoid agonists URB597, AM5206, JZL184, JZL195, and AM404, the direct cannabinoid agonists WIN55,212-2 and CP55,940, and the prototypical cannabinoid antagonist/inverse agonist SR141716. Values of the free energy for cannabinoid drugs binding to HSA range between -5.4 kcal mol-1 and -10.9 kcal mol-1 . Accounting for the HSA concentration in vivo (∼ 7.5 × 10-4 M), values of the free energy here determined suggest that the formation of the HSA:cannabinoid drug complexes may occur in vivo. Therefore, HSA appears to be an important determinant for cannabinoid efficacy and may guide the choice of the drug dose regimen to optimize drug efficacy and to avoid drug-related toxicity. ”

https://www.ncbi.nlm.nih.gov/pubmed/28976704

http://onlinelibrary.wiley.com/doi/10.1002/iub.1682/abstract

Is cannabis an effective treatment for joint pain?

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“Cannabis has been used to treat pain for thousands of years.

However, since the early part of the 20th century, laws restricting cannabis use have limited its evaluation using modern scientific criteria. Over the last decade, the situation has started to change because of the increased availability of cannabis in the United States for either medical or recreational purposes, making it important to provide the public with accurate information as to the effectiveness of the drug for joint pain among other indications.

The major psychotropic component of cannabis is Δ9-tetrahydrocannabinol (THC), one of some 120 naturally occurring phytocannabinoids. Cannabidiol (CBD) is another molecule found in herbal cannabis in large amounts. Although CBD does not produce psychotropic effects, it has been shown to produce a variety of pharmacological effects. Hence, the overall effects of herbal cannabis represent the collective activity of THC, CBD and a number of minor components.

The action of THC is mediated by two major G-protein coupled receptors, cannabinoid receptor type 1 (CB1) and CB2, and recent work has suggested that other targets may also exist. Arachidonic acid derived endocannabinoids are the normal physiological activators of the two cannabinoid receptors.

Natural phytocannabinoids and synthetic derivatives have produced clear activity in a variety of models of joint pain in animals. These effects are the result of both inhibition of pain pathway signalling (mostly CB1) and anti-inflammatory effects (mostly CB2). There are also numerous anecdotal reports of the effectiveness of smoking cannabis for joint pain.

Indeed, it is the largest medical request for the use of the drug. However, these reports generally do not extend to regulated clinical trials for rheumatic diseases. Nevertheless, the preclinical and human data that do exist indicate that the use of cannabis should be taken seriously as a potential treatment of joint pain.”

https://www.ncbi.nlm.nih.gov/pubmed/28967368

Efficacy and Tolerability of Phytomedicines in Multiple Sclerosis Patients: A Review.

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 CNS Drugs “Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder of the central nervous system (CNS) that can cause cognition, mobility, and sensory impairments. It is considered one of the most common non-traumatic causes of disability in the world. The aim of the present article was to review the clinical evidence related to medicinal plants in the management of MS symptoms. Electronic databases, including the Cochrane Library, Pubmed, and Scopus, were searched for entries from 1966 to February 2017. Only clinical studies were included in this review. Different medicinal plants have positive effects on MS, including Andrographis paniculata, Boswellia papyrifera, Ruta graveolens, Vaccinium spp., Camellia sinensis, Panax ginseng, Aloysia citrodora, Ginkgo biloba, Oenothera biennis, and Cannabis sativa. C. sativa had the highest level of clinical evidence, supporting its efficacy in MS symptoms. Proanthocyanidins, ginkgo flavone glycosides, ginsenosides, epigallocatechin-3-gallate, cannabinoids (including delta-9-tetrahydrocannabinol and cannabidiol), boswellic acid, and andrographolide were presented as the main bioactive components of medicinal plants with therapeutic benefits in MS. The main complications of MS in which natural drugs were effective include spasticity, fatigue, scotoma, incontinence, urinary urgency, nocturia, memory performance, functional performance, and tremor. Herbal medicines were mostly well tolerated, and the adverse effects were limited to mild to moderate. Further well-designed human studies with a large sample size and longer follow-up period are recommended to confirm the role of medicinal plants and their metabolites in the management of MS.” https://www.ncbi.nlm.nih.gov/pubmed/28948486
https://link.springer.com/article/10.1007%2Fs40263-017-0466-4
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