Mixed findings regarding quality of evidence supporting benefit of medical marijuana
June 23, 2015
Science Daily/JAMA - Journal of the American Medical Association
In an analysis of the findings of nearly 80 randomized trials that included about 6,500 participants, there was moderate-quality evidence to support the use of cannabinoids (chemical compounds that are the active principles in cannabis or marijuana) for the treatment of chronic pain and lower-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, sleep disorders, and Tourette syndrome, according to a study in the June 23/30 issue of JAMA.
Medical cannabis refers to the use of cannabis or cannabinoids as medical therapy to treat disease or alleviate symptoms. In the United States, 23 states and Washington, D.C., have introduced laws to permit the medical use of cannabis; many other countries have similar laws. Despite the wide us of cannabis and cannabinoid drugs for medical purposes, their efficacy for specific indications is not clear, according to background information in the article.
Penny F. Whiting, Ph.D., of the University of Bristol, Bristol, United Kingdom, and colleagues evaluated the evidence for the benefits and adverse events (AEs) of medical cannabinoids by searching various databases for randomized clinical trials of cannabinoids for a variety of indications. The researchers identified 79 trials (6,462 participants) that met criteria for inclusion in the review and meta-analysis.
The researchers found that most studies suggested that cannabinoids were associated with improvements in symptoms, but these associations did not reach statistical significance in all studies. There was moderate-quality evidence to suggest that cannabinoids may be beneficial for the treatment of chronic neuropathic or cancer pain and spasticity due to multiple sclerosis (sustained muscle contractions or sudden involuntary movements). There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV, sleep disorders, and Tourette syndrome; and very low-quality evidence for an improvement in anxiety. There was low-quality evidence for no effect on psychosis and very low-level evidence for no effect on depression.
There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. There was no clear evidence for a difference in association (either beneficial or harmful) based on type of cannabinoids or mode of administration. Only 2 studies evaluated cannabis. There was no evidence that the effects of cannabis differed from other cannabinoids.
"Further large, robust, randomized clinical trials are needed to confirm the effects of cannabinoids, particularly on weight gain in patients with HIV/AIDS, depression, sleep disorders, anxiety disorders, psychosis, glaucoma, and Tourette syndrome are required. Further studies evaluating cannabis itself are also required because there is very little evidence on the effects and AEs of cannabis," the authors write.
Editorial: Medical Marijuana
"If the states' initiative to legalize medical marijuana is merely a veiled step toward allowing access to recreational marijuana, then the medical community should be left out of the process, and instead marijuana should be decriminalized," write Deepak Cyril D'Souza, M.B.B.S., M.D., and Mohini Ranganathan, M.D., of the Yale University School of Medicine, New Haven, Conn., in an accompanying editorial.
"Conversely, if the goal is to make marijuana available for medical purposes, then it is unclear why the approval process should be different from that used for other medications. Evidence justifying marijuana use for various medical conditions will require the conduct of adequately powered, double-blind, randomized, placebo/active controlled clinical trials to test its short- and long-term efficacy and safety. The federal government and states should support medical marijuana research. Since medical marijuana is not a life-saving intervention, it may be prudent to wait before widely adopting its use until high-quality evidence is available to guide the development of a rational approval process."
https://www.sciencedaily.com/releases/2015/06/150623113152.htm
Medical marijuana may ease some MS; Little evidence for other complementary or alternative therapies
March 24, 2014
Science Daily/American Academy of Neurology (AAN)
A new guideline from the American Academy of Neurology suggests that there is little evidence that most complementary or alternative medicine therapies (CAM) treat the symptoms of multiple sclerosis (MS). However, the guideline states the CAM therapies oral cannabis, or medical marijuana pills, and oral medical marijuana spray may ease patients' reported symptoms of spasticity, pain related to spasticity and frequent urination in multiple sclerosis (MS). The guideline, which is published in the March 25, 2014, print issue of Neurology®, the medical journal of the American Academy of Neurology, states that there is not enough evidence to show whether smoking marijuana is helpful in treating MS symptoms.
The guideline looked at CAM therapies, which are nonconventional therapies used in addition to or instead of doctor-recommended therapies. Examples include oral cannabis, or medical marijuana pills and oral medical marijuana spray, ginkgo biloba, magnetic therapy, bee sting therapy, omega-3 fatty acids and reflexology.
"Using different CAM therapies is common in 33 to 80 percent of people with MS, particularly those who are female, have higher education levels and report poorer health," said guideline lead author Vijayshree Yadav, MD, MCR, with Oregon Health & Science University in Portland and a member of the American Academy of Neurology. "People with MS should let their doctors know what types of these therapies they are taking, or thinking about taking."
For most CAM therapies, safety is unknown. There is not enough information to show if CAM therapies interact with prescription MS drugs. Most CAM therapies are not regulated by the Food and Drug Administration (FDA). Dronabinol and nabilone are synthetic forms of key ingredients in marijuana. The FDA approved both drugs as treatments for nausea and vomiting associated with cancer chemotherapy that do not respond to standard treatments. Dronabinol also is approved for loss of appetite associated with weight loss in patients with AIDS.
The guideline found that certain forms of medical marijuana, in pill or oral spray form only, may help reduce patients' reported spasticity symptoms, pain due to spasticity, and frequent urination but not loss of bladder control. The therapy may not help reduce tremor. Long-term safety of medical marijuana use in pill or oral spray is not known. Most of the studies are short, lasting six to 15 weeks. Medical marijuana in pill or oral spray form may cause side effects, some of which can be serious. Examples are seizures, dizziness, thinking and memory problems as well as psychological problems such as depression. This can be a concern given that some people with MS are at an increased risk for depression or suicide. Both doctors and patients must weigh the possible side effects that medical marijuana in pill or oral spray form can cause.
Among other CAM therapies studied for MS, ginkgo biloba might possibly help reduce tiredness but not thinking and memory problems. Magnetic therapy may also help reduce tiredness but not depression.
Reflexology might possibly help ease symptoms such tingling, numbness and other unusual skin sensations. Bee sting therapy, a low-fat diet with fish oil, and a therapy called the Cari Loder regimen all do not appear to help MS symptoms such as disability, depression and tiredness. Bee stings can cause a life-threatening allergic reaction and dangerous infections.
Moderate evidence shows that omega-3 fatty acids such as fish oil likely do not reduce relapses, disability, tiredness or MRI brain scan lesions, nor do they improve quality of life in people with MS.
https://www.sciencedaily.com/releases/2014/03/140324181258.htm
Cannabis constituent has no effect on multiple sclerosis progression
July 23, 2013
Science Daily/University of Plymouth
The first large non-commercial clinical study to investigate whether the main active constituent of cannabis (tetrahydrocannabinol or THC) is effective in slowing the course of progressive multiple sclerosis (MS), shows that there is no evidence to suggest this; although benefits were noted for those at the lower end of the disability scale.
The study is published in The Lancet Neurology.
The CUPID (Cannabinoid Use in Progressive Inflammatory brain Disease) study was carried out by researchers from Plymouth University Peninsula Schools of Medicine and Dentistry. The study was funded by the Medical Research Council (MRC), the Multiple Sclerosis Society and the Multiple Sclerosis Trust, and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership.
CUPID enrolled nearly 500 people with MS from 27 centres around the UK, and has taken eight years to complete. People with progressive MS were randomised to receive either THC capsules or identical placebo capsules for three years, and were carefully followed to see how their MS changed over this period. The two main outcomes of the trial were a disability scale administered by neurologists (the Expanded Disability Status Scale), and a patient report scale of the impact of MS on people with the condition (the Multiple Sclerosis Impact Scale 29).
Overall the study found no evidence to support an effect of THC on MS progression in either of the main outcomes. However, there was some evidence to suggest a beneficial effect in participants who were at the lower end of the disability scale at the time of enrolment but, as the benefit was only found in a small group of people rather than the whole population, further studies will be needed to assess the robustness of this finding.
One of the other findings of the trial was that MS in the study population as a whole progressed slowly, more slowly than expected. This makes it more challenging to find a treatment effect when the aim of the treatment is to slow progression.
As well as evaluating the potential neuroprotective effects and safety of THC over the long-term, one of the aims of the CUPID study was to improve the way that clinical trial research is done, by exploring newer methods of measuring MS and using the latest statistical methods to make the most of every piece of information collected. This analysis continued for several months and has provided important information about conducting further large scale clinical trials in MS.
Professor John Zajicek, Professor of Clinical Neuroscience at Plymouth University Peninsula Schools of Medicine and Dentistry, said: "To put this study into context: current treatments for MS are limited, either being targeted at the immune system in the early stages of the disease or aimed at easing specific symptoms such as muscle spasms, fatigue or bladder problems. At present there is no treatment available to slow MS when it becomes progressive. Progression of MS is thought to be due to death of nerve cells, and researchers around the world are desperately searching for treatments that may be 'neuroprotective'. Laboratory experiments have suggested that certain cannabis derivatives may be neuroprotective."
He added: "Overall our research has not supported laboratory based findings and shown that, although there is a suggestion of benefit to those at the lower end of the disability scale when they joined CUPID, there is little evidence to suggest that THC has a long term impact on the slowing of progressive MS."
https://www.sciencedaily.com/releases/2013/07/130723113703.htm
Can Cannabis Compounds Slow the Progression of Multiple Sclerosis?
July 21, 2008
Science Daily/The Peninsula College of Medicine and Dentistry
The CUPID (Cannabinoid Use in Progressive Inflammatory brain Disease) study at the Peninsula Medical School in Plymouth has reached an important milestone with the news that the full cohort of 493 people with multiple sclerosis (MS) has been recruited to the study.
CUPID is a clinical trial which will evaluate whether tetrahydrocannabinol (THC), one of many compounds found in the in the cannabis plant (and the main active ingredient) is able to slow the progression of MS.
This is an important study for people with MS because current treatments either target the immune system in the early stages of MS, or are aimed at easing specific symptoms such as muscle spasms or bladder problems. At present there is no treatment which slows progression of the disease.
The CUPID trial follows an earlier study -- Cannabinoids and Multiple Sclerosis (CAMS) -- which suggested a link between THC and the slowing of MS. The CAMS trial saw participants take THC for a year -- the CUPID trial will last for longer and aims to assess the effect of THC on progressive MS.
It has taken two years to recruit the 493 participants who will each take part in the trial for three years, and in some cases three and a half years. After data cleaning and analysis the results should be available by spring/early summer 2012.
Professor John Zajicek from the Peninsula Medical School, who heads the team carrying out the CUPID study, said: "We are delighted to have achieved the correct number of patient participants for this trial. Patients have been recruited from 27 sites across the UK. If we are able to prove beyond reasonable doubt the link between THC and the slowing down of progressive MS, we will be able to develop an effective therapy for the many thousands of MS sufferers around the world."
The CUPID trial is funded by the Medical Research Council, the Multiple Sclerosis Society and the Multiple Sclerosis Trust.
Chris Jones, chief executive of the MS Trust, commented: "The MS Trust is delighted to be supporting this study on behalf of people with MS. The ability to halt progression in MS is what we dream of - the Holy Grail for those whose condition deteriorates year on year. This study should give us the definitive answer as to whether cannabinoids will prove to be such an agent."
Dr Laura Bell, research communications officer for the MS Society, said: "People affected by MS are keen to know whether there's any truth in the suggestion that elements of the cannabis plant can help ease the symptoms and slow down progression of the condition.
"The MS Society is supportive of safe clinical trials investigating the medicinal properties of cannabis and it's great news that this trial is going ahead. We look forward to the results of this exciting study."
https://www.sciencedaily.com/releases/2008/07/080721114608.htm