Cannabis and the Treatment of Neuropathic Pain Barth

Cannabis and the Treatment of Neuropathic Pain Barth Wilsey MD VANCHCS Pain Clinic Department of Physical Medicine and Rehabilitation UC Davis Medical Center

Disclosure I have no relevant financial interest/arrangement or affiliation with any organizations related to commercial products or services to be discussed at this program

Educational Objectives · To describe the history of medical marijuana in the US from the 19 th Century to present day · To recognize partial legalization versus full legalization of marijuana · To understand the contributions of the UC Center for Medicinal Cannabis Research (CMCR) · To discuss opportunities for research

• Listed in U. S Pharmacopeia 1850 -1941 – marijuana & hashish extracts were the 1 st, 2 nd, or 3 rd most prescribed meds in the US from 1842 -1890 s

• • • • neuralgia gout rheumatism tetanus hydrophobia epidemic cholera convulsions chorea hysteria mental depression delirium tremens insanity uterine hemorrhage

Prohibition 1937

California's Proposition 215 1996 • First statewide medical marijuana ballot initiative to pass in the USA – allow possession and cultivation of cannabis for ‘debilitating’ medical conditions if recommended by a physician • provide a defense against prosecution under state criminal laws

Who are medical marijuana patients? • patient survey – pain, insomnia, and anxiety • Reinarman C, Nunberg H, Lanthier F, Heddleston T. Who are medical marijuana patients? Population characteristics from nine California assessment clinics. J Psychoactive Drugs. 2011; 43: 128 -135 • physician survey – 94% of patients receiving medical marijuana have chronic pain, and 17% have muscle spasms • Kondrad E, Reid A. Colorado family physicians' attitudes toward medical marijuana. J Am Board Fam Med. 2013; 26: 52 -60.

Legal Marijuana, Coming to a Vending Machine Near You

Colorado – requires the legislature to address • product labeling • security requirements for wholesale and retail marijuana establishments • workplace drug policies • marijuana impairment while driving • integrating the existing medical marijuana system into the new commercial market • 15 percent excise tax on wholesale marijuana sales

Washington • State Liquor Control Board given the assignment for devising a system • licensing • regulating • taxing marijuana growers, processors and retail stores

US Attorney General Response • Prevent: – distribution of cannabis to minors – revenue from going to criminal enterprises, gangs, and cartels – diversion of cannabis from states where it is legal under state law to other states – use as a cover or pretext for the trafficking of other illegal drugs or other illegal activity – violence and the use of firearms in the cultivation and distribution of cannabis – drugged driving and the exacerbation of other adverse public health consequences associated with cannabis use – growing of cannabis on public lands – cannabis possession or use on federal property Cole, J. Guidance Regarding Cannabis Enforcement August 29, 2013, Deputy Attorney General. http: //www. justice. gov/iso/opa/resources/3052013829132756857467. pdf

Educational Objectives · To describe the history of medical marijuana in the US from the 19 th Century to present day · To recognize partial legalization versus full legalization of marijuana · To understand the contributions of the UC Center for Medicinal Cannabis Research (CMCR) · To discuss opportunities for research

Full vs Partial Legalization • full legalization has the potential to substitute underground economies with legitimate businesses • pharmaceutical companies • agribusiness

Full vs Partial Legalization • alternatives to full legalization • in the Netherlands, the use and sale of small quantities is permitted while production and wholesale distribution is banned • penalties for possession of small amounts of marijuana could be reduced and treated as civil rather than a criminal matter (so-called “decriminalization”) • production, sale, and use could be permitted but only for medical purposes

Medical Marijuana Laws Get Tougher

Illinois Proposed Medical Marijuana Bill cancer; glaucoma; HIV/AIDS; hepatitis C; amyotrophic lateral sclerosis (ALS); Crohn's disease; agitation of Alzheimer's disease; cachexia/wasting syndrome; muscular dystrophy; severe fibromyalgia; spinal cord disease, including but not limited to arachnoiditis; Tarlov cysts; hydromyelia; syringomyelia; spinal cord injury; traumatic brain injury and post-concussion syndrome; multiple sclerosis; Arnold Chiari malformation and Syringomyelia; Spinocerebellar Ataxia (SCA); Parkinson’s disease; Tourette’s syndrome; Myoclonus; Dystonia; Reflex Sympathetic Dystrophy (RSD); Causalgia; Neurofibromatosis; Chronic Inflammatory Demyelinating Polyneuropathy; Sjogren’s syndrome; Lupus; Interstitial Cystitis; Myasthenia Gravis; Hydrocephalus; nail patella syndrome; or the treatment of these conditions

Educational Objectives · To describe the history of medical marijuana in the US from the 19 th Century to present day · To recognize partial legalization versus full legalization of marijuana · To understand the contributions of the UC Center for Medicinal Cannabis Research (CMCR) · To discuss opportunities for research

California State Legislature Medical Marijuana Research Act SB 847 Senator John Vasconcellos 1999

Approval Process 1997 NIH Workshop • Department of Health and Human Services (HHS) • DEA – Schedule I License • FDA – Investigational New Drug Application • NIDA – supplies marijuana grown at University of Mississippi • Research Advisory Panel of California

CMCR Neuropathic Pain Studies • results have been convergent – five studies demonstrated a significant decrease in pain after cannabis administration • the magnitude of effect in these studies, expressed as the number of patients needed to treat to produce one positive outcome, was comparable to current therapies

Educational Objectives · To describe the history of medical marijuana in the US from the 19 th Century to present day · To recognize partial legalization versus full legalization of marijuana · To understand the contributions of the UC Center for Medicinal Cannabis Research (CMCR) · To discuss opportunities for research

Limited Scientific Studies • As the legal landscape evolves, the medical one remains confusing – fewer than 20 randomized, controlled clinical trials of smoked marijuana for all possible uses • these involved around relatively few people in all— well short of the evidence typically required for a pharmaceutical to be marketed in the U. S.

Federal Restrictions on Cannabis Research • Schedule I Controlled Substance • high potential for abuse • no currently accepted medical use in treatment • lack of accepted safety under medical supervision • use and possession is a federal offense

National Institute of Drug Abuse (NIDA) Supplies Researchgrade Cannabis • NIDA does not stock purified (a. k. a. , Good Manufacturing Practice grade) Δ 9 -THC or CBD in their drug supply inventory for use in clinical trials – not the case with other Schedule I drugs like heroin, LSD, and MDMA » which are provided legally by “private U. S laboratories” or easily imported from abroad with federal permission, making marijuana the only Schedule I drug with a single federal provider

Call for Additional Studies • 1997: National Institutes of Health – Workshop on the Medical Utility of Marijuana • 1999: Institute of Medicine – Marijuana and Medicine: Assessing the Science Base

Call for Additional Studies • American College of Physicians – 2008 Position Paper: Supporting Research Into Therapeutic Role Of Marijuana • trod a middle ground between praising and demonizing cannabis – stating it is “neither devoid of potentially harmful effects nor universally effective” – called for “sound scientific study” and “dispassionate scientific analysis” to find the appropriate balance

The Medical Letter Volume 52 (Issue 1330) January 25, 2010 • medical marijuana may be effective for treatment of nausea, anorexia, pain and some other conditions – but published data supporting its efficacy for treating patients with intractable cancer pain are limited – dosage is not well standardized – cannabis is often poorly tolerated, especially by older patients

The Harvard Mental Health Letter Volume 26 Number 10 April 2010 • more is known about the psychiatric risks than the benefits – there is not enough evidence to recommend medical marijuana as a treatment for any psychiatric disorder – the psychiatric risks are well documented, and include addiction, anxiety, and psychosis

Call for Additional Studies • American Medical Association – 2009 House of Delegates Report • supported review of marijuana's Schedule I status – urged an evidence-based review of marijuana's status as a Schedule I controlled substance to determine whether it should be reclassified to a different schedule – NIH support of clinical studies on the utility of medical marijuana

NIH Sponsored Studies THC / Dronabinol / Marinol Efficacy Trial of Oral Tetrahydrocannabinol in Patients With Fibromyalgia at Hadassah Medical Organization, Jerusalem, Israel Nabilone / Cesamet Efficacy and Safety Evaluation of Nabilone as Adjunctive Therapy to Gabapentin for the Management of Neuropathic Pain in Multiple Sclerosis at University of Manitoba, Winnipeg, Canada Nabiximols / Sativex A Study of Sativex® for Relieving Persistent Pain in Patients With Advanced Cancer in the United States, the UK and Germany

NIH Sponsored Studies Cannabidiol (CBD) Cannabidiol for Inflammatory Bowel Disease at Meir Medical Center, Kefar Saba, Israel Smoked / Inhaled Cannabis Comparing the Effects of Smoked and Oral Marijuana in Individuals With HIV/AIDS at New York State Psychiatric Institute, USA. Effects of Vaporized Marijuana on Neuropathic Pain in Spinal Cord Injury at CTSC Clinical Research Center, Sacramento, United States.