Sativex for the management of multiple sclerosis symptoms.

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Abstract

“Sativex (R) is a cannabis-based pharmaceutical product containing delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a 1:1 ratio, delivered in an oromucosal (mouth) spray. It has been approved as adjunctive treatment for neuropathic pain in patients with multiple sclerosis (MS). It is being investigated for the management of other MS symptoms, such as spasticity. THC:CBD spray is regulated as a narcotic. Five randomized controlled trials (RCTs) compared the benefits and harms of THC:CBD spray with placebo. A total of 368 patients with various neurological conditions (including MS) were recruited. In some trials, THC:CBD spray significantly reduced neuropathic pain, spasticity, muscle spasms and sleep disturbances. The most common adverse events (AEs) reported in trials were dizziness, sleepiness, fatigue, feeling of intoxication and a bad taste. Long-term safety and the potential for dependence, abuse, misuse and diversion are unknown.”

http://www.ncbi.nlm.nih.gov/pubmed/16317825

Sativex: clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain.

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Abstract

“Sativex is one of the first cannabis-based medicines to undergo conventional clinical development and to be approved as a prescription medicine. It is an oromucosal spray that allows flexible, individualised dosing. Patients self titrate their overall dose and pattern of dosing according to their response to and tolerance of the medicine. This usually results in the administration of approximately 8-12 sprays/day. Each spray delivers tetrahydrocannabinol 2.7 mg and cannabidiol 2.5 mg, giving an approximate average dose of tetrahydrocannabinol 22-32 mg/day and cannabidiol 20-30 mg/day. Development has concentrated on the treatment of symptoms of multiple sclerosis, notably spasticity and neuropathic pain, as well as the treatment of neuropathic pain of other aetiologies. Positive results in placebo-controlled trials of the use of Sativex as an add-on therapy in these indications demonstrate that Sativex is efficacious and well tolerated in the treatment of these symptoms. Sativex has been approved for use in neuropathic pain due to multiple sclerosis in Canada. If ongoing studies replicate the results already observed, further approvals for the treatment of spasticity in multiple sclerosis and for neuropathic pain are likely.”

http://www.ncbi.nlm.nih.gov/pubmed/16553576

THC and CBD oromucosal spray (Sativex®) in the management of spasticity associated with multiple sclerosis.

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“People with multiple sclerosis may present with a wide range of disease symptoms during the evolution of the disease; among these, spasticity can have a marked impact on their well-being and quality of life. Symptom control, including spasticity, remains a key management strategy to improve the patient’s well-being and functional status. However, available drug therapies for spasticity sometimes have limited benefit and they are often associated with poor tolerability.

 Sativex is a 1:1 mix of 9-delta-tetrahydrocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, which is available as an oromucosal spray. Clinical experience with Sativex in patients with multiple sclerosis is accumulating steadily. Results from randomized, controlled trials have reported a reduction in the severity of symptoms associated with spasticity, leading to a better ability to perform daily activities and an improved perception of patients and their carers regarding functional status when Sativex was added to the current treatment regimen. Adverse events such as dizziness, diarrhea, fatigue, nausea, headache and somnolence occur quite frequently with Sativex, but they are generally of mild-to-moderate intensity and their incidence can be markedly reduced by gradual ‘uptitration’.

 In summary, initial well-controlled studies with Sativex oromucosal spray administered as an add-on to usual therapy have produced promising results and highlight encouraging avenues for future research.”

http://www.ncbi.nlm.nih.gov/pubmed/21456949

Clinical efficacy and effectiveness of Sativex, a combined cannabinoid medicine, in multiple sclerosis-related spasticity.

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Abstract

“Multiple sclerosis (MS) is associated with a wide range of disease symptoms and amongst these, spasticity is one of the most disabling and has the greatest impact on patient well-being and quality of life. Until now, available drug therapies for spasticity appear to have limited benefit and are often associated with poor tolerability. In a recent Spanish survey it was noted that multidrug therapy and a low control rate were common features for a large proportion of patients with MS-related spasticity, suggesting that currently available monotherapies lack significant activity. Sativex is a 1:1 mixture of δ-9-tetrahydrocannabinol and cannabidiol derived from Cannabis sativa chemovars, which is available as an oromucosal spray. Clinical experience with Sativex in patients with MS-related spasticity is steadily accumulating. Results from randomized, controlled trials have reported a reduction in the severity of symptoms associated with spasticity, leading to a better ability to perform daily activities and an improved perception of patients and their carers regarding functional status. These are highly encouraging findings that provide some much needed optimism for the treatment of this disabling and often painful symptom of MS.”

http://www.ncbi.nlm.nih.gov/pubmed/22509985

Cannabis linked to ‘prostate cancer cure’

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“Cannabis helps combat prostate cancer, scientists revealed yesterday.

But patients were warned not to use the drug even though active chemicals halted the spread of the disease.

Cannabis also helped reduce the size of tumours when tested on mice, according to researchers at Spain’s University of Alcala.

But Cancer Research UK’s Dr Lesley Walker said: “This opens a new avenue to explore potential drug targets but it is at a very early stage – it absolutely isn’t the case that men might be able to fight prostate cancer by smoking cannabis.

“Research suggests that prostate cancer cells might stop growing if they are treated with chemicals found in cannabis but more work needs to be done to explore the potential of these cannabinoids in treatment.”

Prostate cancer affects more than 35,000 UK men each year and kills around 10,000.”

http://www.mirror.co.uk/news/uk-news/cannabis-linked-to-prostate-cancer-cure-413459

Cannabis blunts prostate cancer threat: study – ABC News

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“Chemicals in cannabis have been found to stop prostate cancer cells from growing in the laboratory, suggesting marijuana-based medicines could one day help fight the disease, scientists said.

After working initially with human cancer cell lines, Ines Diaz-Laviada and colleagues from the University of Alcala in Madrid also tested one compound on mice and discovered it produced a significant reduction in tumour growth.

Their research, published in the British Journal of Cancer, underlines the growing interest in the medical use of active chemicals called cannabinoids, which are found in marijuana.”

Read more: http://www.abc.net.au/news/2009-08-19/cannabis-blunts-prostate-cancer-threat-study/1396346

Cannabis Chemicals Stop Prostate Cancer Growth

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“ACTIVE chemicals in cannabis have been shown to halt prostate cancer cell growth according to research published in the British Journal of Cancer.

Researchers from the University of Alcala, in Madrid tested the effects of the active chemicals in cannabis called cannabinoids on three human prostate cancer cell lines – called PC-3, DU-a45 and LNCaP.

The prostate cancer cells carry molecular ‘garages’- called receptors- in which cannabinoids can ‘park’.

The scientists showed for the first time that if cannabinoids ‘park’ on a receptor called CB2, the cancer cells stop multipyling.

Dr Walker added: “This research suggest that prostate cancer cells might stop growing if they are treated with chemicals found in cannabis but more work needs to be done to explore the potential of the cannabinoids in treatment.”

To confirm the findings the scientists switched off the CB2 receptors – or ‘closed the garage doors’- on the prostate cells. When cannabinoids were then added to cells without the CB2 receptor, the prostate cancer cells carried on dividing and growing. This suggests that cannabinoids connect with the CB2 receptors on prostate cancer cells to stop cell division and spread.

Professor Ines Diaz-Laviada, study author at the University of Alcala said: “Our research shows that there are areas on prostate cancer cells which can recognise and talk to chemicals found in cannabis called cannabinoids. These chemicals can stop the division and growth of prostate cancer cells and could become a target for new research into potential drugs to treat prostate cancer.”

Read more: http://www.medicalnewstoday.com/releases/161628.php

Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma.

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“PURPOSE:

Recently, functional cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (TRPV1) have been described in human prostate and prostate cancer-derived cell lines where the activation of the receptors resulted in inhibition of cellular growth. We, however, lack the description of the expression of these molecules in human prostate cancer (PCC) and in benign prostate hyperplasia (BPH).

RESULTS:

CB1 was identified in epithelial and smooth muscle cells types of the human prostate, whereas TRPV1 was exclusively localized to the mucosal cells. We also found that the expression of CB1 and TRPV1 (both at the protein and mRNA levels) were significantly up-regulated in PCC. However, while the increased expression of TRPV1 showed a proper correlation with increasing PCC tumor grades, such phenomenon was not observed with CB1. In addition, we also measured markedly elevated CB1 levels in BPH tissues whilst the expression of TRPV1 was not altered when compared to healthy control prostate.

CONCLUSIONS:

Our findings strongly argue for that (1) the CB1 and TRPV1 molecules as well as their ligands may indeed possess a promising future role in the treatment of PCC; (2) TRPV1 may also serve as a prognostic factor in PCC; and (3) CB1 may act as a potential target molecule in the therapeutic management of BPH.”

http://www.ncbi.nlm.nih.gov/pubmed/18830626

The role of cannabinoids in prostate cancer: Basic science perspective and potential clinical applications.

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“Prostate cancer is a global public health problem, and it is the most common cancer in American men and the second cause for cancer-related death. Experimental evidence shows that prostate tissue possesses cannabinoid receptors and their stimulation results in anti-androgenic effects.”

“Cannabis is a bushy plant with palmate leaves and clusters of small green flowers, and it grows wild in regions of tropical weather and can attain up to 3 m height. The genus Cannabis is complemented by sativa which translates to useful. Cannabis has indeed been used throughout history for a variety of purposes, including the production of fiber for paper and textile manufacture. However, its current popularity lies in its use as a recreational drug with psychoactive properties. The plant contains many chemical compounds that have different pharmacological properties, varying in quantity and quality depending on the strain, culture, and storage conditions.”

“The frequently held view of cannabis and its related products as drugs of abuse have slowed progress in the development of studies designed to take advantage of the properties of cannabinoid derivatives for therapeutic purposes…”

“Delta-9-THC is the substance with the greatest psychoactive potency of the natural cannabinoids and exhibits the greatest analgesic activity. Cannabidiol (CBD), another major constituent of the Cannabis sativa plant, has the same therapeutic effects of THC (analgesic, anti-inflammatory, and others), but with a different pharmacologic profile…”

“It is our conclusion that it would be of interest to conduct clinical trials involving medicinal cannabis or other cannabinoid agonists, comparing clinical markers such as PSA with controls, especially in men with bone metastatic prostate cancer, whom would not only benefit from the possible anti-androgenic effects of cannabinoids but also from analgesia of bone pain, improving quality of life, while reducing narcotic consumption and preventing opioid dependence.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339795/