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Home , Cannabigerolic acid, Hemp oil

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

• >480 chemical compounds • 60 are compounds • CBN – • CBD – • THC – • CBC – • CBCA - cannabichromenate • CBG – • CBGA – cannabigerolic acid • CBDA – cannabidolic acid • THCA – tetrahydrocannabinolic acid • THCV –

McGovern Medical School

CBD 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 receptor (transient receptor potential cation channel subfamily V member 1 [TRPV1]) • Mediates pain perception, inflammation

McGovern Medical School (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

McGovern Medical School CBD Oils

• 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 in brain (CB1) • Subjective and some objective evidence for benefit in treating pain and spasticity

McGovern Medical School McGovern Medical School