Faculty Peer Reviewed
When the New Jersey legislature approved a measure to legalize the use of marijuana for patients with chronic illnesses early this year, multiple sclerosis (MS) patient Charles Kwiatkowski, of Hazlet, N.J., rhetorically asked the New York Times; “The M.S. Society has shown that this drug will help slow the progression of my disease. Why would I want to use anything else?”1 New Jersey was the 14th state in the nation to approve such legislation. Does the drug have a legitimate role in the treatment of MS, or is the hype little more than half-baked?
The main active compound in herbal cannabis (marijuana) is delta-9 tetrahydrocannabinol (THC). THC acts on the same central cannabinoid receptors (CB1) in the brain as endogenous cannabinoids. Activation of these receptors leads to suppression of neurotransmitters concentrated in particular areas in the brain that result in effects on psychoactive, motor, memory, and pain pathways.2,6 Anecdotal reports of MS patients using marijuana have lauded the drug’s ability to relieve pain and spasticity, and small clinical trials have showed a trend toward multi-symptomatic relief.7 As a result, the UK, Canada, and US have all reported MS patient use of marijuana as ranging from 16-33%.7 Excitingly, basic science researchers have joined forces and shown that in addition, cannabinoids may also reduce neuronal damage and promote plasticity.2,6 On the surface, cannabinoid therapy sounds like a slam-dunk in terms of both symptom management and the slowing of disease progression–so what is the clinical evidence?
The largest randomized controlled trial studying the effects of cannabis on MS is the 2003 Cannabinoids for Treatment of Spasticity and other Symptoms Related to Multiple Sclerosis (CAMS) study. 667 patients were randomly assigned to receive oral synthetic THC or placebo, with the primary outcome being a change in spasticity measured on a 4-point scale.4 There was no significant effect based on numeric spasticity scores or disability indices. However, patient reports of perceived improvements in pain, muscle spasms, spasticity, and sleep disturbance as well as a measured benefit of walking time were significant (p value <.05).3,4
In 2005 the 12-month follow-up CAMS study was more promising. Two thirds of the original study patients opted to continue treatment for up to one year. Results showed significant improvements in spasticity of an average 1.8 points on the 4-point scale, and suggested improvement in general disability indices. Subjective symptom improvement remained significant. The authors conceded that the objective differences were small, and also advised that long-term treatment effects be studied.6 The subjective benefits of cannabinoids are undisputed by the CAMS studies as well as by recent reviews compiling evidence from smaller trials performed over the last ten years.7,8 However, objective measures have thus far as a whole failed to provide evidence that matches patients’ subjective experiences.8
The discrepancy in reported patient experiences versus objective outcomes likely has a great deal to do with mode of delivery. Patients who smoke marijuana benefit from the higher bioavailability of THC when smoked versus taken orally. They can also dose their THC intake per session by varying inhalation based on symptom severity.2 Mucosal sprays attempting to get around the issue of bioavailability have shown promise,7 but have yet to match the symptomatic benefit achieved through inhalation. THC’s significant side effect profile is more pronounced with the inhaled form. The most common side effects are anxiety, panic, paranoia, acute psychosis and hallucination, delusions, slight change in motor and cognitive function, and a brief “high” or euphoria.6 These psychotropic effects cannot be ignored in patients with MS, who often suffer from cognitive deficits. The high levels of THC achievable with inhalation could potentially cause more cognitive damage than symptomatic improvement over the long term.
In 2009 the National Multiple Sclerosis Society released recommendations on marijuana as a treatment for MS, stating, “Although it is clear that cannabinoids have a potential for both management of MS symptoms such as pain and spasticity, as well as for neuroprotection,” it can not yet be recommended because “…studies to date do not demonstrate a clear benefit compared to existing symptomatic therapies and…issues of side effects, systemic effects and long-term effects are not yet clear.”6 These recommendations may change with further study. Research is especially needed in the area of drug system delivery, with the goal of achieving positive subjective and objective outcomes without cognitive deficit. Clinical outcomes regarding neuroprotection and improved plasticity are also of utmost importance to determine the potential for THC to affect the progression of disease.
The therapeutic benefit of cannabinoids, be it acute symptom relief and/or neuroprotection, is far more than a half-baked idea. Just ask Scott Ward, a 26-year-old patient with MS who was prescribed marijuana “to alleviate leg cramps so severe that they often felt “like my muscles are tearing apart.” “Now,” he said, “I can do normal things like take a walk and walk the dog.”1
Dr. Madou, Class of 2010, NYU School of Medicine
Peer reviewed by Jacqueline Friedman, MD, Clinical Professor, Department of Neurology at NYU Langone Medical Center and Director of the Multiple Sclerosis Clinic at the Department of Veterans Affairs, New York Harbor Health Care System
Visit the MS Society website for up to date information regarding MS treatment: http://www.nationalmssociety.org/index.aspx
Commentary by Dr. Jacqueline Friedman
Cognitive deficits are increasingly being appreciated as a significant symptom in MS, affecting daily lives and careers. Given the variable and subjective results of cannabis findings thus far, the clear cognitive negative effects, and given that there are alternative treatments for spasticity and pain, including muscle relaxants, botulinum toxin injections, anti-epileptics, and tricyclics, which can be carefully measured and dosed, I see no current place for medical marijuana in our armamentarium at this time.
1. Kocieniewski D. New Jersey Vote Backs Marijuana for Severely Ill. New York Times. January 11, 2010: N.Y/ Region.
2. Iversen L. Cannabis and the Brain. Brain. 2003;126(Pt 6):1252-1270.
3. Goodin D. Marijuana and Multiple Sclerosis. Lancet Neurol. 2004;3(2):79-80.
4. Zajicek JP, Fox P, Sanders H, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet 2003;362(9395):1517-1526.
5. Zajicek JP, Sanders HP, Wright DE, et al; UK MS Research Group. Cannabinoids in Multiple Sclerosis (CAMS) Study: safety and efficacy data for 12 months follow up. J Neurol Neurosurg Psychiatry. 2005;76(12):1664-1669.
6. National Clinical Advisory Board of the National Multiple Sclerosis Society. Recommendations regarding the use of cannabis in multiple sclerosis. National Multiple Sclerosis Society, 2009. www.nationalmssociety.org/download.aspx?id=1023, accessed 1/25/10
7. Thaera GM, Wellik KE, Carter JL, Demaerschalk BM, Wingerchuk DM. Do cannabinoids reduce multiple sclerosis-related spasticity? Neurologist. 2009;15(6):369-371.
8. Lakhan SE, Rowland M. Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. BMC Neurol. 2009;9:59.