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Uses of CBD in MS

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Uses of CBD in MS Uses of CBD in MS John A. Lincoln, MD, PhD Associate Professor Disclosures • I have received honoraria from Sanofi-Genzyme and Biogen • I currently have grant funding from Sanofi-Genzyme McGovern Medical School Cannabis • >480 chemical compounds • 60 are cannabinoid compounds • CBN – cannabinol • CBD – cannabidiol • THC – tetrahydrocannabinol • CBC – cannabichromene • CBCA - cannabichromenate • CBG – cannabigerol • CBGA – cannabigerolic acid • CBDA – cannabidolic acid • THCA – tetrahydrocannabinolic acid • THCV – tetrahydrocannabivarin McGovern Medical School Cannabinoids Cannabis sativa CBD Oil Marijuana Oil McGovern Medical School Extracting Cannabinoids McGovern Medical School Cannabinoid Extracts Koppel BS, Brust JCM, Fife T, Bronstein J, Youssof S, Gronseth G, et al. Neurology. 2014 Apr 29;82(17):1556–63. McGovern Medical School Cannabinoid Receptors McGovern Medical School THC vs CBD • THC (tetrahydrocannabinol) • Most of the effect through CB1 receptor • Psychoactive effects and increases appetite • Works mainly through GABAergic neurons in hippocampus, amygdala, cerebral cortex • CBD (cannabidiol) • Non-psychoactive • Activates capsaicin receptor (transient receptor potential cation channel subfamily V member 1 [TRPV1]) • Mediates pain perception, inflammation McGovern Medical School Dronabinol (Marinol®) • Synthetic delta-9-THC • FDA-approved since 1985 • Anorexia associated with weight loss in patients with AIDS • Nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments • Several insurances now cover off-label use for patients with MS • 2.5 mg twice daily taken 1 hour before meal • Common side effects • Abdominal pain, dizziness, euphoria, nausea, paranoid reaction, somnolence, abnormal thoughts, vomiting McGovern Medical School CBD Oils McGovern Medical School CBD Oils • Hemp CBD – legal in US • Generally 6.65 mg/ml – 16.67 mg/ml strength • Multiple products that are not regulated • CBD oil (hemp extract) vs hemp oil vs cannabis oil (THC) • Buy from a reputable source and read the label • Start low and go very slow • 2.5 mg – 20 mg gradually increasing dose for efficacy • Common side effects • Vertigo, somnolence, dizziness, diarrhea, nausea, change in appetite or mood, dry mouth McGovern Medical School Clinical Trials Koppel BS, Brust JCM, Fife T, Bronstein J, Youssof S, Gronseth G, et al. Neurology. 2014 Apr 29;82(17):1556–63. McGovern Medical School • Based upon review of 33 of 63 articles • Evaluated effects of marijuana on spasticity, pain and tremor in MS McGovern Medical School Clinical Trial Outcomes – Spasticity Subjective Objective McGovern Medical School AAN Guidelines – Spasticity • Nabiximols (Sativex) – combination THC/CBD • CBD added to reduce psychoactive THC effects • Probably effective for reducing patient-reported symptoms at 6 weeks (1 Class I study) and probably ineffective for reducing objective measures at 6 weeks (1 Class I study) • Oral cannabis extract (CBD) • Effective for reducing patient-reported scores (2 Class I studies), probably ineffective for reducing objective measures at 12–15 weeks (1 Class I study) but possibly effective at 1 year (1 Class II study) • THC • Probably effective for reducing patient-reported scores (1 Class I studies), probably ineffective for reducing objective measures at 15 weeks (1 Class I study) but possibly effective at 1 year (1 Class II study) Koppel BS, Brust JCM, Fife T, Bronstein J, Youssof S, Gronseth G, et al. Neurology. 2014 Apr 29;82(17):1556–63. McGovern Medical School Clinical Trial Outcomes – Pain Subjective McGovern Medical School AAN Guidelines – Central Pain • Nabiximols (Sativex) & THC • THC or nabiximols (1 Class I study each) are probably effective for treating MS-related pain or painful spasms • CBD • Effective for reduction of central pain (2 Class I studies) Koppel BS, Brust JCM, Fife T, Bronstein J, Youssof S, Gronseth G, et al. Neurology. 2014 Apr 29;82(17):1556–63. McGovern Medical School AAN Guidelines – Tremor • Determined using 11-point visual analog scale • THC and CBD are probably ineffective for treating MS-related tremor (1 Class I study) • Nabiximols is possibly ineffective (1 Class II study) Koppel BS, Brust JCM, Fife T, Bronstein J, Youssof S, Gronseth G, et al. Neurology. 2014 Apr 29;82(17):1556–63. McGovern Medical School Conclusions • Dronabinol is an FDA-approved synthetic THC • Nabiximols (Sativex) is a combination THC/CBD with fewer psychoactive effects • Approved in many countries and possibly soon in US • Hemp extract contains cannabidiol (CBD) • Non-psychoactive • Mediates pain perception, inflammation • Subjective and some objective evidence for benefit in treating pain and spasticity • Cannabis extract contains tetrahydrocannabinol (THC) • Psychoactive • Binds to endogenous cannabinoid receptor in brain (CB1) • Subjective and some objective evidence for benefit in treating pain and spasticity McGovern Medical School McGovern Medical School .
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