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

Smoking Marijuana Impairs Cognitive Function in MS Patients

February 14, 2008

Science Daily/American Academy of Neurology

People with multiple sclerosis (MS) who smoke marijuana are more likely to have emotional and memory problems, according to new research.

"This is the first study to show that smoking marijuana can have a harmful effect on the cognitive skills of people with MS," said study author Anthony Feinstein, MPhil, PhD, of the University of Toronto. "This is important information because a significant minority of people with MS smoke marijuana as a treatment for the disease, even though there are no scientific studies demonstrating that it is an effective treatment for emotional difficulties."

Feinstein noted that MS itself can cause cognitive problems. "In addition, cognitive problems can greatly affect the quality of life for both patients and their caregivers," he said.

For the study, researchers interviewed 140 Canadian people with MS. Of those, 10 people had smoked marijuana within the last month and were defined as current marijuana users. The marijuana users were then each matched by age, sex, the length of time they had MS, and other factors to four people with MS who did not smoke marijuana.

The researchers then evaluated the participants for emotional problems such as depression, anxiety and other psychiatric disorders. They also tested the participants' thinking skills, speed at processing information, and memory.

The study found marijuana smokers performed 50 percent slower on tests of information processing speed compared to MS patients who did not smoke marijuana. There was also a significant association between smoking marijuana and emotional problems such as depression and anxiety.

People with MS have higher rates of depression and suicide compared to the general population. "Since marijuana can induce psychosis and anxiety in healthy people, we felt it was especially important to look at its effects on people with MS," Feinstein said.

This research was published February 13, 2008, in the online edition of Neurology®, the medical journal of the American Academy of Neurology. The study was supported by a grant from the Canadian Institutes for Health Research.

https://www.sciencedaily.com/releases/2008/02/080213160851.htm

University of Saskatchewan Research Suggests Marijuana Analogue Stimulates Brain Cell Growth

October 16, 2005

Science Daily/University of Saskatchewan

A synthetic substance similar to ones found in marijuana stimulates cell growth in regions of the brain associated with anxiety and depression, pointing the way for new treatments for these diseases, according to University of Saskatchewan medical research published today in The Journal of Clinical Investigation.

Xia Zhang, an associate professor in the U of S neuropsychiatry research unit, led the team that tested the effects of HU-210, a potent synthetic cannabinoid similar to a group of compounds found in marijuana. The synthetic version is about 100 times as powerful as THC, the compound responsible for the high experienced by recreational users.

The team found that rats treated with HU-210 on a regular basis showed neurogenesis – the growth of new brain cells in the hippocampus. This region of the brain is associated with learning and memory, as well as anxiety and depression.

The effect is the opposite of most legal and illicit drugs such as alcohol, nicotine, heroin, and cocaine.

“Most ‘drugs of abuse’ suppress neurogenesis,” Zhang says. “Only marijuana promotes neurogenesis.”

Current theory states that depression may be sparked when too few new brain cells are grown in the hippocampus. It is unclear whether anxiety is part of this process, but if true, HU-210 could offer a treatment for both mood disorders by stimulating the growth of new brain cells.

But Zhang cautions that HU-210 is only one of many cannabinoids. His previous work with marijuana shows that while the plant may contain medicinal compounds, they come in the same package as those that cause symptoms such as acute memory impairment, addiction, and withdrawal. Also, the HU-210 used in the study is highly purified.

“This is a very potent cannabinoid oil,” Zhang says. “It’s not something that would be available on the street.”

Marijuana has been used for recreational and medicinal purposes for centuries, evoking public interest and controversy along the way. As a medicine, the plant is used to ease pain in multiple sclerosis patients, combat nausea in cancer patients, and stimulate appetite in people afflicted with AIDS. It has also been used to treat epilepsy and stroke.

Zhang’s work is the latest product of the U of S Neural Systems and Plasticity Research Group (http://www.usask.ca/neuralsystems/group.htm), a multidisciplinary effort by researchers from the Colleges of Arts and Science, Engineering, Kinesiology, Medicine, Pharmacy and Nutrition, and Veterinary Medicine. The group collaborates to study the function of neural systems, from nerves to brain, in living organisms. In particular, they look at how these systems change over time with experience.

Zhang’s research is supported by a grant from the Canadian Institutes of Health Research (CIHR), as well as a CIHR New Investigator Award. The Saskatchewan Health Research Foundation provided funding support to establish the Neural Systems and Plasticity Research Group, as well as post-doctoral fellowship awards to research team members Wen Jiang and Shao-Ping Ji.

https://www.sciencedaily.com/releases/2005/10/051016083817.htm

New insights into the neural risks and benefits of marijuana use

Compounds in cannabis can impair or improve memory depending on age, disease

November 6, 2018

Science Daily/Society for Neuroscience

Research released today underscores both the dangers and the therapeutic promise of marijuana, revealing different effects across the lifespan. Marijuana exposure in the womb or during adolescence may disrupt learning and memory, damage communication between brain regions, and disturb levels of key neurotransmitters and metabolites in the brain. In Alzheimer's disease, however, compounds found in marijuana, such as the psychoactive compound delta-9-tetrahydrocannabinol (THC), may improve memory and mitigate some of the disease's symptoms.

Research released today underscores both the dangers and the therapeutic promise of marijuana, revealing different effects across the lifespan. Marijuana exposure in the womb or during adolescence may disrupt learning and memory, damage communication between brain regions, and disturb levels of key neurotransmitters and metabolites in the brain. In Alzheimer's disease, however, compounds found in marijuana, such as the psychoactive compound delta-9-tetrahydrocannabinol (THC), may improve memory and mitigate some of the disease's symptoms. The findings were presented at Neuroscience 2018, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.

Marijuana is the most commonly used illicit drug in the United States and its popularity is expected to rise as it is legalized in more places. It is also the illegal drug most commonly used by pregnant women, despite the potential for long-term harm to the fetus. Many people start using marijuana as teenagers -- a particularly vulnerable time as the brain is still developing -- when there is evidence for increased risk. At the same time, a growing number of people are turning to marijuana for the relief of symptoms of chronic diseases such as epilepsy and multiple sclerosis. These use patterns highlight the need to better understand the long-term effects of marijuana, particularly in sensitive populations such as unborn children and adolescents.

Today's new findings show that:

·     Prenatal exposure to THC in rats has lasting effects on metabolites in the brain, making the animal more vulnerable to stress later in life (Robert Schwarcz, abstract 609.12).

·     Rats exposed to synthetic compounds that are similar to THC during fetal development show impaired formation of the neural circuits involved in learning and memory as adolescents (Priyanka Das Pinky, abstract 424.17).

·     Cannabinoid use by adolescent rats boosts activity in brain pathways responsible for habit formation (José Fuentealba Evans, abstract 602.07).

·     In adolescent rats, cannabinoids may disturb the development of a protein lattice important for balancing excitatory and inhibitory activity in a brain region involved in decision-making, planning, and self-control (Eliza Jacobs-Brichford, abstract 645.09).

·     Long-term cannabinoid use alters metabolism and connectivity of brain regions involved in learning and memory in adult mice (Ana M. Sebastião, abstract 778.08).

·     Treating Alzheimer's disease mice with the psychoactive compound found in marijuana improves memory and reduces neuronal loss, suggesting a possible therapy for the human disease (Yvonne Bouter, abstract 467.14).

"Today's findings lend new understanding of the complex effects that cannabis has on the brain," said press conference moderator Michael Taffe, PhD, of Scripps Research Institute and an expert in substance abuse research. "While it may have therapeutic potential in some situations, it is important to get a better understanding of the negative aspects as well, particularly for pregnant women, teens, and chronic users."

https://www.sciencedaily.com/releases/2018/11/181106150418.htm