The use of medical marijuana remains a hot topic in the United States. Although twenty states and the District of Columbia have enacted laws to legalize medical marijuana, in the majority of the country, marijuana is still an illicit drug. In the MS community, the patient advocacy organizations are generally neutral on the subject: acknowledging the benefits, warning of the risks, and avoiding recommendation of an activity which may be illegal based on where you live. But it is encouraging that research into the benefits of cannabis-based products is ongoing.
What is Cannabis?
The Cannabis sativa L plant contains at least 60 active cannabinoids including the non-psychoactive component, Cannabidiol (CBD), and the primary psychoactive element, tetrahydrocannabinol (THC). Cannabis plants are bred to contain different levels of these compounds to enhance their "get high" factor or their medicinal use. Cannabis products include marijuana (dried flowers and leaves), hashish (plant resin pressed into blocks), and hash oil (potent oil made from hashish).
Synthetic THC [Marinol ® (dronabinol) or Cesamet ® (nabilone)] has been used for the treatment of nausea, vomiting, and loss of appetite in chemotherapy and AIDS patients for years. Only one cannabis extract containing CBD [Sativex ® (nabiximols)] has been approved for moderate to severe treatment-resistant spasticity in multiple sclerosis. Sativex contains equal amounts of THC and CBD in an oromucosal mouth spray and is approved for use in the treatment of MS spasticity in 24 countries, including Canada and 17 countries in Europe, but not in the United States (Leussink, 2012).
Cannabis in Clinical Trials
In more than 100 controlled clinical trials since 1975, different cannabis preparations have demonstrated antispastic, analgesic, antiemetic (anti-nausea), neuroprotective, and anti-inflammatory actions, and are effective against certain psychiatric diseases (Grotenhermen, 2012; SÃ¡nchez, 2012). The makers of Sativex have sponsored a number of trials in MS (list available). Additional research, some of which is sponsored by the National MS Society, can be found listed at ClinicalTrials.gov.
Medical Marijuana and MS Symptoms: Spasticity, neuropathic pain, bladder dysfunction
A number of studies have indicated improvement in MS symptoms, particularly for muscle stiffness and spasms, neuropathic pain and sleep and bladder disturbance, in patients with MS treated with cannabinoids. Trials evaluating other symptoms such as tremor and nystagmus have not demonstrated any beneficial effects of cannabinoids. Safety profiles of cannabinoids seem acceptable, although a slow prolonged period of titration improves tolerability. No serious safety concerns have emerged (Zajicek, 2011).
Recent case reports included in a German study indicate that THC:CBD oromucosal spray is useful in individual patients with moderate to severe spasticity resistant to existing therapies. Researchers were excited to note that improvements in Quality of Life and Activities of Daily Living in some patients with resistant MS spasticity allowed them to engage back in physical and social activities (Koehler, 2014).
A phase III clinical trial investigating the effects of Sativex in over 500 people showed that 48% of participants had 20% or more improvement in their spasticity. Amongst those who responded, about three quarters had an improvement of greater than 30% in their spasticity score within four weeks when compared with those taking a placebo (Novotna, 2011). Combined analysis of three clinical trials confirmed the effectiveness of Sativex (Wade, 2010).
Animal studies have demonstrated that cannabinoids have immunomodulatory and neuroprotective properties. Through activation of CB2 receptors primarily found on immune cells, cannabinoids modulate peripheral blood lymphocytes, interfere with migration across the blood-brain barrier and control microglial/macrophage activation (SÃ¡nchez, 2012). CB2 select agonists are not psychoactive and could promising therapies against autoimmune and inflammatory diseases, such as MS (Rieder, 2010).
Risks of Cannabis
Although no safety concerns have arisen in clinical trials with MS patients, the use of medical cannabis is not without risk. Cannabinoids have been linked with depression, paranoia and hallucinations; people prone to mental illness may have more serious mental and emotional effects. Physical side effects can include low blood pressure, fast heartbeat, dizziness, slow reaction time and heart palpitations.
A recent study at the University of Toronto measured cognitive function in 25 people with MS who regularly smoked or ingested street cannabis, compared to 25 people with MS who did not use cannabis (age-matched groups were controlled for differences in terms of disease course and duration). Cannabis users performed significantly more poorly than nonusers on measures of information processing speed, working memory, executive functions, and visuospatial perception. They were also twice as likely as nonusers to be classified as cognitively impaired (Honarmand, 2011).
People who consider using street cannabis (i.e. marijuana) or medical cannabis (i.e. Sativex) to improve MS symptoms, such as pain, spasticity, sleep disturbance, or bladder dysfunction, should carefully weigh the benefits against the associated cognitive side effects.
Related HealthCentral posts:
Corey-Bloom J, Wolfson T, Gamst A, et al. Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. CMAJ. 2012 Jul 10;184(10):1143-50. doi: 10.1503/cmaj.110837. Epub 2012 May 14.
Grotenhermen F, MÃ¼ller-Vahl K. The therapeutic potential of cannabis and cannabinoids. Dtsch Arztebl Int. 2012 Jul;109(29-30):495-501. Epub 2012 Jul 23.
Honarmand K, Tierney MC, O’Connor P, Feinstein A. Effects of cannabis on cognitive function in patients with multiple sclerosis. Neurology. 2011 Mar 29;76(13):1153-60. doi: 10.1212/WNL.0b013e318212ab0c.
Kavia RBC, Ridder DD, Constantinescu CS, et al. Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Mult Scler. 2010 Nov;16(11):1349-59. doi: 10.1177/1352458510378020. Epub 2010 Sep 9.
Koehler J. Who Benefits Most from THC:CBD Spray? Learning from Clinical Experience. Eur Neurol. 2014 2014;71 Suppl 1:10-5. doi: 10.1159/000357743. Epub 2014 Jan 22.
Leussink VI, Husseini L, Warnke C, et al. Symptomatic therapy in multiple sclerosis: the role of cannabinoids in treating spasticity. Ther Adv Neurol Disord. 2012 Sep;5(5):255-66. doi: 10.1177/1756285612453972.
Novotna A, Mares J, Ratcliffe S, et al. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex( ®) ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol. 2011 Sep;18(9):1122-31. doi: 10.1111/j.1468-1331.2010.03328.x. Epub 2011 Mar 1.
Rieder SA, Chauhan A, Singh U, et al. Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression. Immunobiology. 2010 Aug;215(8):598-605. doi: 10.1016/j.imbio.2009.04.001. Epub 2009 May 20.
SÃ¡nchez AJ, GarcÃa-Merino A. Neuroprotective agents: cannabinoids. Clin Immunol. 2012 Jan;142(1):57-67. doi: 10.1016/j.clim.2011.02.010. Epub 2011 Mar 21.
Smith PF. New approaches in the management of spasticity in multiple sclerosis patients: role of cannabinoids. Ther Clin Risk Manage. 2010:6 59-63. Epub 2010 Mar 3.
Wade DT, Collin C, Stott C, Duncombe P. Meta-analysis of the efficacy and safety of Sativex (nabiximols), on spasticity in people with multiple sclerosis. Mult Scler. 2010 Jun;16(6):707-14. doi: 10.1177/1352458510367462.
Zajicek JP, Apostu VI. Role of cannabinoids in multiple sclerosis. CNS Drugs. 2011 Mar;25(3):187-201. doi: 10.2165/11539000-000000000-00000.