Special Access to Medicinal Marijuana for Compassionate Use: Policies and Perspectives in Canada and the US By Philipp Novales-Li, DMedSc, PhD, DPhil, RAC

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Medical use of marijuana is legal in only a limited number of countries. Even though the legality of its use for therapeutic purposes is an ongoing political and ethical debate, basic and clinical research in this field has burgeoned in the past two decades alone. Since this topic is a cause célèbre, this article is not another polemic on whether marijuana should be legalized, but focuses on the special access programs for medicinal marijuana use available in the US and Canada. Similarities and differences in policies and perspectives between the two neighboring countries are highlighted.

Historical Use Marijuana (scientific name: Cannabis sativa) has been widely used for medicinal purposes for the past 12,000 years. In ancient China, marijuana was used as an anesthetic and to treat vomiting, infections and parasitic hemorrhaging. In fact, marijuana is one of the fundamental herbs recognized in traditional Chinese medicine. The ancient Egyptians also used the hemp of marijuana as suppositories for relieving hemorrhoid pain. Ancient Indian texts document the use of marijuana for various illnesses, such as insomnia, headaches, pain and gastrointestinal disorders. Further, the ancient Greeks used marijuana for both veterinary and human medicine, such as healing wounds and sores on horses, and to treat inflammation and pain caused by ear obstructions. From the late 19th to the early 20th centuries, marijuana was commonly used throughout the world as a primary pain reliever, well before aspirin was introduced. A British physician, W.B. O’Shaughnessy, who learned about marijuana while stationed in India, is credited for introducing marijuana to Western medicine in the early 19th century. In fact, cannabis remained listed in the US Pharmacopeia until 1942, and several pharmaceutical companies sold cannabis in powdered or tincture forms as painkillers, antispasmodics, sedatives and exhilarants. Eventually, the advent of more-stable and -effective medicines as well as the availability of modern hypodermic syringes (to deliver soluble opiates that have faster pain-relieving effects) contributed to the decline of marijuana use. Further, in the early 1900s, most US states outlawed marijuana because of its association with violent crime and psychosis, as well as its use by Mexican migrant workers in the West and African Americans in the South, which associated it with racial and ethnic fears. In 1937, the US federal government deemed marijuana a substance of abuse and its use was made illegal, over the objections of the American Medical Association.1

Pharmacology Marijuana is known to contain more than 60 cannabinoids and several hundred other chemical substances. The mature flowering heads of female cannabis plants have been shown to

contain the highest concentration of medicinal compounds. Delta-9-tetrahydrocannabinol (THC), however, is the main cannabinoid component and has the most prominent psychoactive function. As a practical matter, TCH determines the potency of dried marijuana. Cannabidiol is another major component of medical marijuana that represents 40% of the extract’s chemistry. Cannabidiol is known to have anticonvulsant properties and is also claimed to play a role in relieving inflammation, anxiety and nausea and in inhibiting cancer cell growth. Another important compound is ß-Caryophyllene, which is present in cannabis essential oil at concentrations of about 12%–35%. ß-Caryophyllene is a selective activator of a cannabinoid receptor (CB2), thus explaining its role in reducing tissue inflammation. Finally, cannabigerol is a medicinal compound found in marijuana that does not have psychoactive properties but has been shown to help lower blood pressure in experimental animals.2

Potential Clinical Applications In the past 30 years, there has been a surge in basic and clinical research that has increased our understanding of the medical benefits of marijuana and its various compounds. Just a cursory review of the medical literature would reveal a plethora of peer-reviewed articles on medicinal marijuana, covering a wide spectrum of pathologies. The following key areas are among the most productive avenues for research on clinical applications for marijuana:3 • Cachexia: Marijuana has been shown to increase appetite and weight gain, as well as serve as an appetite stimulant. • Chemotherapy-induced nausea and vomiting: THC may treat the symptoms and side effects of cancer treatment, such as nausea and vomiting. • Neurological and movement disorders: Marijuana has demonstrated anticonvulsant properties and is particularly effective in generalized and partial tonic-clonic seizures. In addition, various studies have shown antispasmatic and anti-tremor properties of marijuana. • Glaucoma: There is evidence that marijuana (or its components) can reduce intraocular pressure, which is a major factor in glaucoma, to prevent further optic nerve damage. • Brain tumors: Animal studies have shown that cannabinoids can inhibit tumor angiogenesis, which may be linked to THC’s effect on the vascular endothelial growth factor (VEGF) pathway. Tumor growth is stymied when formation of new blood vessels is stopped.

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Analgesia: Numerous studies have supported the effect of marijuana on relieving neurogenic pain. This may be due to its effect on neuromodulation in ascending and descending pathways.

US and Canadian Regulatory Landscape Under its Marihuana Medical Access Regulations (MMAR), which came into effect on 30 June 2001, Health Canada has provided Canada’s healthcare system with a legal framework to enable the use, cultivation and storage of marijuana for medicinal purposes (Note: Canada spells “marijuana” differently.) The MMAR came about as an offshoot of a court of appeals ruling, which mandated the creation of new regulations on medicinal marijuana use. The court stipulated that if the Canadian government failed to develop policies on this matter, the Ontario courts would not prosecute as illegal the use, growth or storage of marijuana. By 2001, MMAR was ratified, and in response to concerns from stakeholders, was amended in December 2003 to streamline the application process, enable police to have access to the program’s database and move the program toward a more traditional healthcare model. In brief, the MMAR has three main components: authorization to possess dried

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marijuana; license to produce marijuana, which encompasses personal-use production licenses and designated person production licenses; and access to the supply of dried marijuana or marijuana seeds. Despite the special access regulations for marijuana under the provisions of the MMAR, marijuana is still categorized as a controlled substance in Canada, and the regulation does not address the issue of legalization. In fact, Health Canada has not issued a Notice of Compliance for marijuana for medicinal purposes. In short, the Therapeutic Products Directorate of Health Canada has not issued a letter of approval to indicate that marijuana has been assessed for its safety, efficacy and quality as a drug.4,5 In the US, the federal government considers marijuana a controlled substance. It is classified as a Schedule I drug, the strictest classification, which is shared by heroin, LSD and Ecstasy. Under the Controlled Substances Act, use of marijuana is deemed illegal and physicians are prohibited from prescribing Schedule 1 drugs. In contrast, numerous psychoactive and opiate derivatives are classified as Schedule II drugs, allowing prescription use. Conversely, 13 states have ratified laws that legalize the special access of marijuana for medicinal use. However, during the administrations of Presidents George H.W. Bush and Bill Clinton, the US Justice Department nullified state medicinal marijuana laws (since

Table 1. US States With Medical Marijuana Regulations and Approved Conditions of Use State

State Regulations

Approved Diseases

Alaska

Ballot Measure 8 (Effective: 4 March 1999)

cachexia, cancer, chronic pain, epilepsy (and other seizure disorders), glaucoma, HIV/AIDS, multiple sclerosis (and other muscle spasticity disorders) and nausea; other conditions are revised on a case-by-case basis

California

Proposition 215 (Effective: 6 November 1996)

AIDS, anorexia, arthritis, cachexia, cancer, chronic pain, glaucoma, migraine, persistent muscle spasms (including those associated with multiple sclerosis), seizures (e.g., epilepsy), severe nausea and other chronic/persistent medical symptoms

Senate Bill 420 (Effective: 1 January 2004) Colorado

Ballot Amendment 20 (Effective: 1 June 2001)

cancer, glaucoma, HIV/AIDS, cachexia, severe pain, severe nausea, seizures (epilepsy) and persistent muscle spasms (multiple sclerosis); other conditions are reviewed on a case-by-case basis

Hawaii

Senate Bill 862 (Effective: 14 June 2000)

cancer, glaucoma, HIV/AIDS, chronic/debilitating disease or condition (or its treatment) that causes cachexia, severe pain, severe nausea, seizures (epilepsy), severe/persistent muscle spasms (multiple sclerosis) and Crohn’s disease

Maine

Senate Bill 611 (Effective: 2 April 2002)

epilepsy (seizures), glaucoma, multiple sclerosis (muscle spasticity), nausea and vomiting (as a result of AIDS or cancer chemotherapy)

Michigan

Proposal 1 (Effective: 4 December 2008)

cancer, glaucoma, HIV, AIDS, hepatitis C, amyotrophic lateral sclerosis, Crohn’s disease, agitation of Alzheimer’s disease, nail-patella, cachexia or wasting syndrome, severe/chronic pain, severe nausea, seizures, epilepsy, muscle spasms and multiple sclerosis

Montana

Initiative 148 (Effective: 2 November 2004)

cancer, glaucoma, HIV/AIDS or treatment of these conditions; chronic/ debilitating disease/condition (or its treatment) that produces cachexia (or wasting syndrome), severe/chronic pain, severe nausea, seizures (epilepsy) or severe/persistent muscle spasms (multiple sclerosis or Crohn’s disease); other conditions as adopted by rule

Nevada

Ballot Question 9 (Effective: 1 October 2001)

AIDS, cancer, glaucoma; any medical condition or treatment that produces cachexia, persistent muscle spasms or seizures, severe nausea or pain; other conditions are subject to approval

Assembly Bill 453 (Effective: 1 October 2001) New Mexico

Senate Bill 523 (Effective: 1 July 2007)

severe chronic pain, painful peripheral neuropathy, intractable nausea/ vomiting, severe anorexia/cachexia, hepatitis C, Crohn’s disease, posttraumatic stress disorder, Lou Gehrig’s disease (ALS), cancer, glaucoma, multiple sclerosis, damage to nervous tissue of the spinal cord with intractable spasticity, epilepsy, HIV/AIDS and hospice patients

Oregon

Ballot Measure 67 (Effective: 3 December 1998)

cancer, glaucoma, positive HIV/AIDS, or treatment for these conditions; cachexia, severe pain, severe nausea, seizures (epilepsy) or persistent muscle spasms (multiple sclerosis); other conditions are revised on a case-by-case basis

Senate Bill 1085 (Effective: 1 January 2006) House Bill 3052 (Effective: 21 July 1999) Rhode Island

Senate Bills 0710 and 791 (Effective: 3 January 2006)

cancer, glaucoma, positive HIV/AIDS, hepatitis C (or treatment of these conditions); cachexia, wasting syndrome, severe/debilitating/ chronic pain, severe nausea, seizures (epilepsy), severe/persistent muscle spasms (multiple sclerosis or Crohn’s disease) or agitation of Alzheimer’s disease; other conditions are reviewed on a case-by-case basis

Vermont

Senate Bill 76 and House Bill 645 (Effective: 1 July 2004)

cancer, AIDS, positive HIV, multiple sclerosis (or treatment of these conditions if the disease or treatment results in severe, persistent and intractable symptoms); or a disease, medical condition or its treatment that is chronic, debilitating and produces severe, persistent and one or more of the following symptoms—cachexia (or wasting syndrome), severe pain, nausea or seizures

Washington

Senate Bill 6032 (Effective: 2 November 2008)

cachexia, cancer, HIV, AIDS, epilepsy, glaucoma, intractable pain (i.e., pain unrelieved by standard treatment or medications), multiple sclerosis, Crohn’s disease or hepatitis C (with debilitating nausea or intractable pain); other diseases (including anorexia) that result in nausea, vomiting, wasting, appetite loss, cramping, seizures or muscle spasms (or spasticity) when such conditions are unrelieved by standard treatments or medications

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reinstated) and the federal government periodically raided and prosecuted dispensaries or individuals claiming to comply with state medicinal marijuana laws. This, however, changed under the Obama administration. A crucial policy reversal was quietly instituted in February 2009 (and highly publicized in October 2009), which signaled a new approach—the federal government no longer conducts drug raids and prosecutions of dispensaries or individuals in compliance with state medicinal marijuana laws. This is a watershed development, arguably akin to the 21st Amendment that repealed the prohibition on alcoholic beverage sales. A list of the 13 states in which medical marijuana use is legal, and their laws, is presented in Table 1. Most of these laws started out as ballot initiatives that were then transposed into law. The majority of these state laws abolished criminal penalties for the use, possession and cultivation of marijuana by patients who need special access to this “drug” for medicinal purposes. Also, two other states have passed laws favorable toward medicinal marijuana but have not legalized its use. Specifically, Arizona allows physicians to prescribe marijuana, and Maryland allows a plaintiff to claim medical use as a defense in court.6 Finally, another 15 states are considering legislation or ballot initiatives on legalizing medicinal marijuana.

Scope of Approved Symptoms/ Illnesses Under Canada’s MMAR, there are two categories of patients who can apply to possess marijuana for medicinal purposes. Category 1 comprises patients with any symptoms that can be treated within the context of compassionate end-of-life care or that are covered under specific medical conditions listed in the statutes. These are: severe pain and/or persistent muscle spasms from multiple sclerosis, spinal cord injury or spinal cord disease; severe pain, cachexia, anorexia, weight loss and/or severe nausea from cancer or HIV/ AIDS; severe pain from severe forms of arthritis; and seizures from epilepsy. Patients under Category 1 can provide a declaration from a physician to support their application. The provider need not be a specialist. Category 2 covers patients who have debilitating symptoms due to medical conditions not covered under Category 1. Patients can apply for an authorization to possess dried marijuana for medicinal purposes if conventional treatments have failed or are deemed inappropriate to relieve symptoms of the disease. An assessment of the patient’s medical condition must be done by a specialist, but the treating ­physician, whether a specialist or not, can sign the application form.7,8 In the US, the diseases or symptoms covered under a special access program for medicinal marijuana vary from state to state. Table 1 lists the approved medical conditions for each state where medicinal marijuana can be legally used. Most include debilitating illnesses where the medical use of marijuana can be recommended by a physician. Also, most states allow special access to marijuana for other medical conditions, subject to review on a case-by-case basis.9

Special Access Application Process Health Canada’s Marijuana Medical Access Division (+1 866 337 7705 or www.healthcanada. gc.ca/mma) can provide information and an application form for special access to dried marijuana or to obtain a license to produce it, either for those who want to grow their own supply or who plan to designate a person to grow the marijuana for them. The application must be signed by a physician, who completes the medical declaration to state the nature of the symptoms for which marijuana would be used. Two passport-sized photos need to accompany the application, one of which must be signed on the back by a physician, to be used on the identification card. (This identification card can be shown to enforcement agencies as proof that the patient is authorized to possess marijuana.) Priority in application processing is given to terminally ill patients. Once approved, the authorization to possess is valid for a year and can be renewed as needed.10,11

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Table 2. US Statewide Contact Information for Special Access Applications and Possession Limits

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STATE

CONTACT INFORMATION

POSSESSION LIMITS

Alaska

Alaska Bureau of Vital Statistics Marijuana Registry PO Box 110699 Juneau, AK 99811-0699 E-mail : [email protected]

1 oz. usable 6 plants (3 mature; 3 immature)

California

California Department of Public Health Office of County Health Services ATTN: Medical Marijuana Program Unit (MS 5203) PO Box 997377 Sacramento, CA 95899-7377 E-mail: [email protected]

8 oz. usable 18 plants (6 mature; 12 immature)

Colorado

Medical Marijuana Registry Colorado Department of Public Health and Environment HSVR-ADM2-A1 4300 Cherry Creek Drive South Denver, CO 80246-2184 E-mail: [email protected]

2 oz. usable 6 plants (3 mature; 3 immature)

Hawaii

Narcotics Enforcement Division 3375 Koapaka Street (Suite D-100) Honolulu, HI 96819

3 oz. usable 7 plants (3 mature; 4 immature)

Maine

No state registration program has been established.

1.25 oz. usable 6 plants (3 mature; 3 immature)

Michigan

Michigan Medical Marihuana Program Bureau of Health Professions Department of Community Health 611 W. Ottawa Street Lansing, MI 48933 E-mail: [email protected]

2.5 oz. usable 12 plants

Montana

Medical Marijuana Program Montana Department of Health and Human Services Licensure Bureau 2401 Colonial Drive (2nd Floor) PO Box 202953 Helena, MT 59620-2953 E-mail: [email protected]

1 oz. usable 6 plants

Nevada

Nevada State Health Division 1000 E. William Street (Suite 209) Carson City, NV 89701

1 oz. usable 7 plants (3 mature; 4 immature)

New Mexico

New Mexico Department of Health 1190 St. Francis Drive PO Box 26110 Santa Fe, NM 87502-6110 E-mail: [email protected]

6 oz. usable 16 plants (4 mature; 12 immature)

Oregon

Oregon Department of Human Services Medical Marijuana Program PO Box 14450 Portland, OR 97293-0450

24 oz. usable 24 plants (6 mature; 18 immature)

Rhode Island

Rhode Island Department of Health Office of Health Professionals Regulation 3 Capitol Hill (Room 104) Providence, RI 02908-5097

2.5 oz. usable 12 plants

Vermont

Marijuana Registry Department of Public Safety 103 South Main Street Waterbury, VT 05671

2 oz. usable 9 plants (2 mature; 7 immature)

Washington

Department of Health PO Box 47866 Olympia, WA 98504-7866 E-mail: [email protected]

24 oz. usable 15 plants

January 2010

In the US, each state where medicinal marijuana is legalized has designated offices that process applications for special access. Contact details (address and email) are listed in Table 2. Most states charge a fee for processing new and renewal applications. The documents needed for the application vary according to individual state requirements. Most states do require that patients provide an oral or written professional opinion from their healthcare providers, attesting to the “therapeutic” benefit the patient can receive from the use of medicinal marijuana.12 As a side note, from 1976 to 1992 FDA and the National Institute on Drug Abuse (NIDA) supplied marijuana to 13 patients who were part of a compassionate-use investigational new drug program. A research protocol was drawn up for each patient and the marijuana was supplied by the University of Mississippi’s pharmacy school. The program was eventually shut down, but the 13 patients continued to be supported by the program, and of these, four patients are still receiving medicinal marijuana today from the US government under this compassionate-use program.

Supply Limits Health Canada has contracted with Prairie Plant Systems Inc., to grow, harvest and process marijuana for use in its special access program. For those authorized to purchase dried marijuana from Health Canada, a maximum 30-day supply may be possessed at any given time. For example, if a patient requires a daily amount of 1, 2, 3, 4 or 5 grams, the maximum amount that can be possessed at a give time is 30, 60, 90, 120 or 150 grams, respectively. Those authorized to grow or produce their own marijuana require a production license and precautions must be taken to prevent loss or theft. Marijuana can be grown indoors or outdoors, subject to certain restrictions. For example, if marijuana is grown indoors all year, five plants may be grown and 225 grams may be stored at any given time for a patient who requires 1 gram/day. Other restrictions apply for growing marijuana outdoors (all year versus summer) or indoors (winter).13, 14 In the US, patients who are approved to have special access to marijuana can purchase it from dispensaries. All 13 states enforce a possession limit (see Table 2). Most allow possession of usable marijuana or cultivation of plants by patients (or their designated primary caregivers), subject to certain restrictions. California allows counties and municipalities to approve and/or maintain local ordinances that permit patients to possess larger quantities of medicinal marijuana than is allowed by state law.15

Quo Vadis? Despite the ethical and political issues regarding the legality of medicinal marijuana, it is hard to overlook the fact that clinical research into the therapeutic value of cannabinoids has proliferated

over the past 40 years. Regarding the safety profile of marijuana, there are no recorded cases of overdose fatalities attributed to marijuana, and regardless of quantity or potency, marijuana cannot be fatal. However, marijuana is not a harmless substance, since some populations (e.g., adolescents, pregnant/nursing mothers, patients with heart cardiovascular risk factors, etc.) may be susceptible to increased risks or adverse side effects.16 As with any medication, a physician must decide on a case-by-case basis whether medical use of marijuana is safe and appropriate. Without doubt, Health Canada is ahead of the US in having a national policy that allows special access to medicinal marijuana. FDA still considers marijuana to have a high potential for abuse and a lack of accepted safety profiles for use under medical supervision. Currently, there is no accepted medical use of marijuana in the US. Despite this, two marijuana derivatives have been used to develop drugs (e.g., Nabilone and Marinol) that are approved in both the US and Canada. Over time, it is hoped that sound medical science will be the judge in expanding the special access to medicinal marijuana, not just in other US states, but in other countries as well. Not only does this make sound medical sense, but it also makes sound economic “sense.” As a case in point, California’s medicinal marijuana industry generated almost $100 million in tax revenues in 2008. Hopefully, much of that can be funneled into research to expand our understanding of this herbal medicine. References 1. Aggarwal SK, Carter GT, Sullivan MD, et al. “Medicinal use of cannabis in the US: Historical perspectives, current trends, and future directions.” J Opiod Manag. 2009;5(3):153-168. 2. Ibid. 3. The National Organization for the Reform of Marijuana Laws. “Emerging clinical applications for cannabis and cannabinoids.” http://norml.org/index. cfm?Group_ID=7002. 4. Health Canada. “Frequently asked questions—Medical use of marihuana.” www.hc-sc.gc.ca/dhp-mps/marihuana/ about-apropos/faq-eng.php. 5. Health Canada. “Fact sheet—Medical access to marihuana.” www.hc-sc.gc.ca/dhp-mps/marihuana/law-loi/fact_sheetinfofiche-eng.php. 6. Procon.Org. “13 Legal medical marijuana states.” http://medicalmarijuana.procon.org/viewresource. asp?resourceID=000881. 7. Ibid 4. 8. Ibid 5. 9. Ibid 6. 10. Ibid 4. 11. Ibid 5. 12. Ibid 6. 13. Ibid 4. 14. Ibid 5. 15. Ibid 6. 16. Ibid 3. Disclaimer The views and opinions expressed herein the author’s and in no way represent the views and policies of the author’s past and present affiliations. Author Philipp Novales-Li, DMedSc, PhD, DPhil, RAC, is an associate director of regulatory affairs at Novartis Vaccines and Diagnostics Inc. He is based in the San Francisco Bay area and can be reached at [email protected].

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