|Credit: GW Pharma|
Despite the financial risks of dealing with a patchwork of laws, regulatory opposition and political uncertainty, medical marijuana appears poised to grow into a bona fide industry. The question is, will the drug fit into conventional healthcare products distribution, or remain a sketchy, wrong-side-of-the-tracks business?
At this point in 2015, there’s no question that medical marijuana—and its fellow traveler, recreational marijuana—are a business. Research commissioned in 2013 by ArcView Group (Oakland, CA; arcviewgroup.com), an investment network seeking to capitalize on legal marijuana, estimated the total US “national legal marijuana market” to grow from $1.53 billion to $2.57 billion by 2014 as more states adopt pro-cannabis laws, to $10.2 billion within five years. National polls from Gallup, CBS News and the Pew Research Center have found rising proportions of the public in favor of dispensing medical marijuana to patients that need it.
Since California’s passage in 1996 of the first US state law allowing some medical marijuana use, however, a steady stream of states have imposed a patchwork of requirements on the cannabis plant and its derivatives. Today, 23 states, the District of Columbia and Guam have laws governing the stuff, with varying limits on the form, amount, usage and source of supply patients or plain-old recreational consumers (in Washington and Colorado) can have.
Federally, inhaled marijuana remains a Schedule I controlled substance—i.e., an illegal drug—while other forms of cannabis are not. For instance, orally ingested Dronabinol (marketed as Marinol by AbbVie and as a generic by Par Pharmaceutical) has been FDA-approved since 1985, regulated as a Schedule III controlled substance. Data from IMS Health indicate that the synthetic cannabinoid class (which includes Marinol, generic Dronabinol and Cesamet, a cannabinoid marketed by Meda Pharmaceuticals) had sales of $133 million in 2014; sales volume has declined by about $9 million since 2009.
States vary in the details. Possession limits range from one ounce (Alaska, Montana, Nevada) to as much as six (Delaware, New Mexico), eight in California and 24 ounces in Washington. Multiple states allow a reasonable quantity of plants to be grown in the home, while a conservative Florida, since last June, has allowed non-smoked cannabis oil with less than 0.8% of the psychoactive compound THC—the part that causes the “high”—and more than 10% cannabidiol, which has been shown to have benefits.
More important than their differences are the similarities between the patchwork of state laws allowing medical marijuana. These laws generally:
- Remove criminal sanctions for the medical use of marijuana and allow some means of access (i.e., dispensaries and/or home cultivation).
- Require a physician to certify that the patient has a specific medical condition or symptom listed in the law to qualify. (Less stringent recommendations are allowed in California, Massachusetts and Maryland.)
- Protect recommending physicians, as well as designated caregivers who may assist patients by picking up medicine.
- Provide patients with a state or county ID card (following an application, fee and doctor’s certification)—with the exception of Washington state, where adults over 21 can legally possess up to one ounce of marijuana for any purpose.
Several more states have laws that recognize some form of medical marijuana benefits, but with the exception of Missouri and possibly Florida, according to the pro-legalization Marijuana Policy Project (www.mpp.org), these laws “are ineffective because they rely on federal cooperation” and don’t include “reasonable means” for patients to obtain the substance.
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The cannabis plant and its components, in various forms, have been found to have benefits in treating neuropathic pain, spasms, seizures, nausea and vomiting, loss of appetite and muscle-mass, and more. Findings of this sort led the American Medical Association (AMA; www.ama-assn.org) to reverse its opposition to medical cannabis, and reaffirm that stance in 2013. Three main points (truncated here) indicate that the AMA:
- “Calls for further adequate and well-controlled studies of marijuana and related cannabinoids;
- “Urges that marijuana’s status as a federal Schedule I controlled substance be reviewed with the goal of facilitating the conduct of clinical research and development of cannabinoid-based medicines,” and
- “Urges NIH, DEA and FDA to develop a special schedule and implement administrative procedures to facilitate grant applications and the conduct of well-designed clinical research…with the goal of facilitating the conduct of clinical research and development of cannabinoid-based medicines, and alternate delivery methods.”
On December 15, 2014, both houses of Congress approved the $1.1-trillion “CRomnibus” bill—the hybrid Continuing Resolution and omnibus spending bill to keep the federal government afloat while the pols continue fighting. It contained two amendments (or riders) concerning medical marijuana. One appears to have reversed Washington, D.C.’s November Initiative Measure 71 referendum to decriminalize pot. The other amendment seems to have offered some protection to state medical marijuana laws. This rider appears to forbid the Justice Department from interfering—or at least spending money to interfere—with the legalized marijuana laws of 23 states (and District of Columbia), as well as 11 more states that have legalized CBD oils.
The Drug Policy Alliance and the Multidisciplinary Association for Psychedelic Studies noted a regulatory Catch-22 in a report last year, The DEA: Four Decades of Impeding and Rejecting Science. It wrote that while arguing for decades “that there is insufficient evidence to support rescheduling marijuana or the medical use of marijuana,” the DEA and the National Institute on Drug Abuse “acted in a manner intended to systematically impede scientific research.” This includes tightly controlling and limiting the quantities, as well as strains of the plant, made available for effective research.
GW Pharmaceuticals (Cambridge, UK) has launched its Sativex product for cannabinoid medicine for treating MS spasticity and cancer pain in 15 countries, and has been approved in 12 more. The drug gained Fast Track designation in 2014 from the FDA for the treatment of chronic cancer pain. Additionally, GW’s Epidiolex investigational drug program to treat orphan syndromes gained FDA orphan drug status for forms of epilepsy. Clinical trials are underway.
No prescription plant-based cannabis is approved in the US currently. “The reason why we’re able to test it in the US is that we go through the FDA and the DEA. It’s onerous, but it’s the proper path to test these medicines,” said Stephen Schultz, VP of investor relations. If approved, these drugs are likely to be regulated as Schedule III, as is AbbVie’s Marinol.
GW manufactures the medicines at its “undisclosed location” in England and imports to the US under DEA license. The company keeps “very detailed records” under FDA’s requirements, as it does for European regulators, which inspect the plant. Schultz expects the FDA will do the same for medicines developed for US approval, during the approval process and beyond.
Insys Therapeutics (Chandler, AZ) is another newsmaker, having received DEA approval to synthetically manufacture its pharmaceutical grade cannabidiol (CBD) last fall. The company had also been granted a quota to produce 15 kg of CBD in 2014, and expects a larger quota in 2015 for its continued clinical studies. The company uses a proprietary sublingual spray technology to market two products: Subsys, a fentanyl sublingual spray for cancer pain, and a generic version of Dronabinol (THC) capsules. A liquid Dronabinol oral solution touted to improve upon soft gel capsules is planned. Also in the pipeline are sublingual sprays and pharmaceutical cannabidiol. In September 2014, FDA granted orphan drug designation Insys’ CBD for the treatment of glioma, which comprises approximately 80% of all malignant brain tumors, according to the company.
Medical Marijuana, Inc. (San Diego, CA), Cannabis Science (Colorado Springs, CO), KannaLife Sciences (Huntington, NY) and AXIM Biotechnologies (New York) are among the publicly-traded companies pursuing refined cannabinoid products, but as OTC rather than prescription products. Some of them, and others, are planning to use compounds derived from hemp (which has been defined as cannabis products that contain less than 0.3% THC).
Pharma approach misses whole-plant synergy
Hundreds of natural constituents have been identified in the Cannabis plant, including tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), cannabichromene (CBC) and cannabinol (CBN). While more research is needed, proponents of medical marijuana say the interaction and synergy of the plant’s components—known as the “entourage effect”—are superior to the typical drug R&D methods seen in traditional pharma and biotech, which tends to isolate single isomers or other components as active ingredients.
But Marinol is only THC, and only one form of it and its effectiveness is questionable according to David Wright, president and CEO of AltMed (Sarasota, FL; www.altmed.co), who says “the pharmaceutical industries will try and step into this arena as medical marijuana becomes more accepted.” He and co-founder R. Michael Smullen previously worked at MedImmune, a bio-pharmaceutical company AstraZeneca acquired in 2007 for $15.6 billion. (They formed the company after Smullen learned of the low-THC cannabis cure known as “Charlotte’s Web,” named for a girl who, like his 15-year-old daughter Kayla, suffered from epilepsy.)
Wright has said that it’s “very unlikely” such products “will ever be as effective as the whole plant,” at least until more research can be done to understand how different plants with their varying levels of THC, CBD, CBN and other substances, affect specific patient conditions.
While R&D efforts continue in traditional pharma labs, Morgan Fox, spokesman for the Marijuana Policy Project (www.mpp.org), says patients deserve access to whole-plant marijuana in any form they see fit, without further ado: “Rather than try to replace marijuana in the pharmacopeia with other substances or isolated compounds, companies should be considering the prospects of new research into whole-plant marijuana and the potential medications that could be produced.”
Beyond the basement
Big Pharma brands will “never” get into the inhaled marijuana business while it’s a Schedule I Controlled Substance, notes John Burke, former president of the National Association of Drug Diversion Investigators, or NADDI (www.naddi.org), whose corporate members include Walgreen Boots Alliance and several pharma companies.
In addition to DEA opposition, the current state-run wholesale channel is very different from the typical national manufacturer-wholesaler-retail pharmacy norm. Stringent state regulations force a patchwork of measures on cultivation, ownership of growing facilities and distance from dispensaries that may not align with pharmaceutical industry business needs.
Assuming the industry someday matures, the retailing side will still require a model in which dispensaries and pharmacies can coexist, compete or combine. The American Pharmacists Assn. (APhA; www.pharmacist.com ) supports research under the industry’s investigational new drug process, but opposes state-by-state laws. While state laws are allowing a network of dispensaries (which of course have no DEA registration), conventional DEA-registered pharmacies cannot sell medical marijuana due to its federal Schedule I status. Except for one state: Connecticut, which is the only one that allows pharmacists to dispense inhaled cannabis for medical use, so this state “could be viewed as a model for other states evaluating the role of pharmacists in dispensing inhaled cannabis for medical use,” according to Michael Ghobrial, associate director of health policy with the APhA.
Similarly, the National Community Pharmacists Association (www.ncpanet.org) “supports the dispensing of all controlled and legend medications, including any legal prescriptions for marijuana, through state board-licensed community pharmacies in accordance with applicable laws, rules and regulations.”
Asked repeatedly for a policy statement on the topic—including Schedule III variants—a spokesperson for the National Association of Chain Drug Stores offered only: “NACDS members cannot sell marijuana because it is still illegal under federal law.”
The Healthcare Distribution Management Assn. (Arlington, VA) declined to comment on interest among its wholesaler members to be involved in medical marijuana.
“Is Big Pharma afraid of cannabis because the efficacy of it is so good that it could potentially replace some of the medications they already have—or is there an opportunity for Big Pharma?” asks Gary Cohen, CEO of the National Association of Specialty Pharmacy (nasprx.org). He believes in the latter, especially for combination drugs “for greater efficacy and brand extensions.” In five to seven years he predicts not dozens but hundreds of clinical trials underway; loosened stances at FDA and DEA; and drugs containing cannabis being routinely prescribed by physicians—and reimbursed by insurers. In the past year, he has participated in setting up two organizations—the National Assn. of Cannabis Pharmacy and the National Assn. of Cannabis-Based Medicine, but neither seems to be progressing beyond a website address in early 2015.