Health & Wellness

Review of CAM Therapies Offers Mixed Results: CAM Therapies in Multiple Sclerosis -- 2014 ANN Guidelines

By Vijayshree Yadav, MBBS, MCR and Pushpa Narayanswami
Despite the availability of several FDA-approved, disease-modifying therapies for multiple sclerosis, there appears to be a significant gap in the care of people with MS in regards to their MS symptoms. Some of the disabling MS symptoms include fatigue, pain, stiffness, abnormal sensory feelings, muscle spasms, mood and memory problems, tremor, imbalance, bladder dysfunction, and constipation. Having one or more of these symptoms can lead to poor quality of life
Many people with MS explore complementary and alternative medical (CAM) treatment options for these symptoms. CAM therapies are defined as nonconventional forms of medical therapies that are not prescribed by a conventional medical provider. Examples of CAM therapies include use of over-the-counter, nutritional dietary supplements such as omega-3 fatty acids, gingko biloba, ginseng, vitamins, and antioxidants; diets; herbs such as cannabis; mind-body techniques such as mindfulness-based stress reduction, yoga, and tai chi; and medical practices such as naturopathy and homeopathy, among others. The limitations associated with CAM for most chronic medical conditions include the lack of necessary medical supervision needed for its use and the lack of objective information about the scientific evidence behind efficacy of these therapies.
Reviewing the Data
To address this gap, in 2007, the American Academy of Neurology (AAN), the largest professional society in the world for neurologists and neuroscientists, convened a panel of experts to review the literature about CAM therapies in MS so that evidence-based information about use of CAM in MS can be provided to patients, healthcare providers, and other MS stakeholders. In March 2014, the comprehensive review emerging from this literature search was published as the AAN guidelines.  
The AAN guidelines included review of relevant MS and CAM therapy articles published between 1970 and September 2013. 115 studies that met the stringent criteria developed by the AAN Guideline Development Subcommittee underwent data extraction and inclusion in the guidelines. Table 1 (below) shows the key CAM therapies that were included in the literature search.
Table 1: CAM therapies included in the review
Category of CAM therapy Examples 
Mind–body medicine
Music therapy
Mindfulness training
Biologically-based practices Herbs: 
  • Padma 28
  • Ginkgo biloba
  • Cannabis
Dietary supplementation:
  • Low-fat diet with omega-3 supplementation
  • Linoleic acid
  • Creatine
  • Acetyl-l-carnitine
  • Inosine
  • Lofepramine plus phenylalanine with vitamin B12 ( Cari Loder regime)
  • Threonine
  • Glucosamine sulfate
  • LDN
Other biologically-based practices:
  • Bee venom treatment
  • Transdermal histamine
  • Hyperbaric oxygen
Manipulative and body-based practices Reflexology
Massage therapy
Progressive muscle relaxation
Energy medicine Magnetic therapy
Neural therapy
Other medicine Naturopathic medicine
Each study that met the inclusion criteria for the review was classified into Class I, II, III or IV according to a well-defined AAN guideline development therapeutic classification system. Class I studies are considered most scientifically sound and class IV the least. The resultant data then forms the basis of strength of recommendation for practice for individual CAM therapy. There can be four levels of recommendations (Level A, B, C and U) for any given condition for an individual therapy based on the class of studies available (Table 2, below). 
Table 2: Levels of recommendation per AAN guideline development therapeutic classification system
Level of Recommendation Implication on recommendation on individual therapy
A Establishes the therapy as effective, ineffective, harmful, or useful.
B Establishes the therapy as probably effective, ineffective, harmful, or useful.
C Establishes the therapy as possibly effective, ineffective, harmful, or useful.
U Data as available is inadequate or conflicting; thus, the therapy is unproven.
Hits and Misses
Details of the key CAM therapies and their level of evidence for effectiveness or ineffectiveness for various MS symptoms are described in Table 3. Level A recommendations were available only for medical marijuana in pill form (oral cannabis extract) and ginkgo biloba. The guidelines reviewed 19 studies on various forms of cannabis, including in a pill, oral spray (spray taken by mouth), or smoked form. This review found that medical marijuana pills and oral medical marijuana spray may ease patients’ reported symptoms of spasticity and pain related to spasticity in MS. Medical marijuana oral spray may also help treat frequent urination in MS. With current data, there is not enough evidence to show whether smoking medical marijuana is helpful in treating MS symptoms. The review also found that ginkgo biloba does not help treat memory and thinking problems; however, it might help treat fatigue. 
Other key findings from the guidelines were that magnetic therapy can help lessen fatigue but not depression, and reflexology might help lessen paresthesia (tingling, numbness, and other unusual skin sensations). The Cari Loder regimen (regimen consisting of an antidepressant, Lofepramine, combined with L-phenylalanine and intramuscular vitamin B12), a low-fat diet with fish oil, and bee sting therapy did not help MS symptoms.
Table 3: Evidence of effectiveness of CAM therapies
CAM therapy Indication of use Level of evidence Number of studies Therapy established as Duration of study
Ginkgo biloba Cognition A 2 Class I Ineffective 12 week duration
Ginkgo biloba Fatigue C 2 Class II Possibly effective 4 weeks
OCE Patient reported spasticity symptoms, pain (not the central nerve pain) A 2 Class I, 1Class II
1 Class III
Effective 12-15 weeks
OCE Clinician assessed spasticity B 1 Class I Probably ineffective 15 weeks
Oral THC Patient reported spasticity symptoms, pain (not the central nerve pain) B 1 Class I, 1 Class III Probably effective 15 weeks
Oral THC Clinician assessed spasticity B 1 Class I Probably ineffective 15 weeks
OCE and oral THC Patient reported spasticity symptoms, clinician assessed spasticity C 1 Class II Possibly effective 12 month
OCE and oral THC Tremor B 1 Class I Probably ineffective 15 weeks
Oromucosal cannabinoid spray (Sativex®) Spasticity symptoms, pain, urinary frequency B 1 Class I each for each symptom Effective 5-10 weeks
Oromucosal cannabinoid spray (Sativex) Clinician assessed spasticity measures and urinary incontinence episodes B 1 Class I study for each symptom Probably ineffective 6-10 weeks
Oromucosal cannabinoid spray (Sativex) Tremor C 1 Class II Possibly ineffective 15 weeks
Magnetic therapy Fatigue B 1 Class I Probably effective 12 weeks
Magnetic therapy Depression B 1 Class I, 2 Class II, 3 Class III Probably ineffective 12 weeks
Low-fat diet with fish oil supplementation MS relapses, disability, fatigue, MRI lesions, or quality of life B 1 Class I, 1 Class II, 1 Class III Probably ineffective 24 months
Reflexology Paresthesias C 1 Class I, 2 Class II, 1 Class III Possibly effective 11 weeks
Cari Loder regime Disability, symptoms, depression, fatigue C 1 Class II Possibly ineffective 24 weeks
Bee sting therapy Relapses, disability, fatigue, Brain MRI changes, or quality of life C 1 Class II Possibly ineffective 24 weeks
*OCE: oral cannabis extract; THC: Tetrahydrocannabinol; Grey highlighted therapies have the highest level of evidence – Level A.
CAM therapies that were reviewed in the guideline but were inconclusive about their efficacy or non-efficacy included: Biofeedback, music therapy, mindfulness training, hypnosis, padma 28, linoleic acid, creatine monohydrate, acetyl-l-carnitine, inosine, threonine, glucosamine sulfate, low-dose naltrexone, transdermal histamine with caffeine, hyperbaric oxygen, yoga, hippotherapy, massage therapy, acupuncture, electroacupuncture, progressive muscle relaxation, neural therapy, and naturopathic medicine. 
Remaining Unknowns
In summary, it appears that for most of the CAM therapies, there is little evidence for their effectiveness for treating MS. For some CAM therapies, no studies were available. For other CAM therapies, studies showed evidence for effectiveness or lack of effectiveness. For most CAM therapies, safety is unknown. 
The long-term safety of medical marijuana use in pill or oral spray form is not known. Medical marijuana in pill or oral spray form may cause side effects, some of which can be serious. Both doctors and patients must weigh the possible side effects that medical marijuana in pill or oral spray form can cause. Except for the synthetic THC based formulation, Marinol®, the other cannabis formulations evaluated in the studies are not commercially available in U.S., so people should exercise caution when they consider medical marijuana as a therapy for MS. 
Importantly, there is not enough information to show whether any CAM therapies interfere with prescription drugs used to treat MS. There is no quality control for most CAM therapies, including most forms of cannabis, and lack of U.S. FDA regulation oversight makes safety and efficacy of CAM therapies a challenge. 
Most CAM therapies are not covered by insurance. We suggest working closely with the healthcare professionals to decide whether any CAM therapies would be good choices in a particular situation. If someone with MS is already using CAM therapies, we encourage them to talk to their healthcare professional about whether evidence for those therapies is available.
1. Complementary, alternative, or integrative health: What’s in a name?. Updated 2014.
2. Yadav V, Bever C,Jr, Bowen J, et al. Summary of evidence-based guideline: Complementary and alternative medicine in multiple sclerosis: Report of the guideline development subcommittee of the american academy of neurology. Neurology. 2014;82(12):1083-1092.
3. Clinical practice guideline process manual. 2004th ed. St. Paul, MN: American Academy of Neurology; 2004.

Dr. Vijayshree Yadav is a board-certified neurologist who is fellowship-trained in multiple sclerosis and neuro-immunology, and honored with a masters degree in clinical research from Oregon Health & Science University. She currently is an associate professor of Neurology at Oregon Health & Science University in Portland, Ore. She is currently the Clinical Director of the MS Center at OHSU. As a clinician-scientist, she is very interested in improving health using complementary therapies such as dietary modification and supplements. 

Pushpa Narayanswami is assistant professor of neurology at Harvard Medical School / Beth Israel Deaconess Medical Center in Boston, Mass. She is a clinician, educator, and researcher with sub-specialty training in neuromuscular disorders. She is a member of the Guideline Development, Dissemination and Implementation subcommittee of the American Academy of Neurology. She received her medical degree from Bangalore Medical College in India. She completed her neurology residency at the National Institute of Mental Health and Neuro Sciences in Bangalore, India. She moved to the U.S. in 1995 and completed another neurology residency, followed by a fellowship in neuromuscular diseases at the University of Tennessee in Memphis, Tenn.