Issue Date: June 20, 2016
Pressure is on the U.S. to relax marijuana’s legal status
The legal marijuana industry in Colorado is fed up with state and local government officials seizing and destroying their crops and marijuana-infused products. The state has seen dozens of recalls of contaminated pot this year, triggered by positive tests for pesticides banned for use on marijuana in Colorado.
Businesses say they have no way to challenge the test results before their products are removed from commerce. Two Denver-based businesses—EdiPure, which sells marijuana-infused edibles, and Organa Labs, which makes marijuana products for vaping—are appealing recalls by the city of Denver. They claim that the city relied on shoddy tests results from an uncertified laboratory.
The tension between businesses and state and local officials over pesticides on marijuana has been growing rapidly since the governor of Colorado declared last year in an executive order that marijuana contaminated with unlawful pesticides “constitutes a threat to the public safety.”
The Colorado Department of Agriculture and other state agencies are struggling to identify safe levels of pesticides on marijuana. They are getting no help from the Environmental Protection Agency, which normally evaluates pesticides for safety, because the federal government considers marijuana a dangerous controlled substance.
Medical marijuana activists, environmental groups, and some U.S. lawmakers are urging the Drug Enforcement Administration to downgrade marijuana, also known as cannabis, from the federal Schedule I category, a list of the most dangerous drugs with a high potential for abuse. The change would allow the U.S. federal government to assess the hazards of pesticides used on marijuana and to ensure the safety of the drug. It would also make it easier for scientists to study the therapeutic properties of the cannabis plant.
DEA is expected to respond to three petitions to reclassify marijuana under the Controlled Substances Act by the end of this month. One of the petitions was filed in 2009 by medical marijuana activist Bryan Krumm of New Mexico. The other two were filed in 2011 by the then-governors of Washington and Rhode Island.
The petitions argue that marijuana should not be classified as a Schedule I drug because drugs in that class, which includes heroin and lysergic acid diethylamide (LSD), have no accepted medical use in the U.S. They point to the fact that some two dozen states; Washington, D.C.; and Canada have legalized marijuana for medical purposes, and more states are expected to do so this year.
But the odds aren’t good that DEA will respond favorably to the three petitions: The agency has rejected three other similar petitions in the past. Experts predict that if DEA decides to change marijuana’s classification, it is likely to do so only for specific marijuana chemical components, such as cannabidiol (CBD), rather than the entire marijuana plant.
Worldwide, only 10 countries permit the use of marijuana for medical purposes, according to the Medical Cannabis Declaration, an online platform that aims to promote the safe use of medical marijuana globally. An additional 20 countries have “established regulations that make cannabis as medicine accessible only in a few special cases, while in more than 150 countries, legal access to this treatment remains unavailable,” the group says.
Cannabidiol interest surges
Driving much of the excitement about medical marijuana are reports about the potential of CBD to reduce seizures in children with severe forms of epilepsy. Unlike Δ9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, CBD does not induce a euphoric high. Researchers are investigating CBD and other endogenous cannabinoids in marijuana for their potential to treat cancer, pain, anxiety, neuromuscular disorders, and a wide range of other ailments.
Drugs containing botanical marijuana or compounds extracted from it have never gotten approval from the Food & Drug Administration, nor has the agency found any such products to be safe and effective for any indication. But FDA has approved two drugs that contain synthetic cannabinoids: Marinol, which contains synthetic THC, and Cesamet, which contains a synthetic chemical similar in structure to THC called nabilone. Both are used to treat nausea and vomiting caused by cancer drugs. And Insys Therapeutics is carrying out a Phase III clinical trial on a synthetic CBD product for severe pediatric epilepsies such as Dravet syndrome and Lennox-Gastaut syndrome.
Pharmaceutical companies are also conducting clinical trials on a few drug candidates derived from marijuana plants. One of the furthest along is a Phase III trial conducted by GW Pharmaceuticals. The study is testing the efficacy of a purified CBD extract called Epidiolex for treating Dravet syndrome.
GW also has high hopes for Sativex, a drug that contains roughly equal amounts of naturally derived THC and CBD. Twenty-seven countries have approved the oral spray for treating spasticity due to multiple sclerosis. It is currently being sold in 15 countries, including the U.K., Spain, Italy, and Germany, according to GW. Sativex has yet to be approved for any indication in the U.S., but GW is testing it in a Phase III clinical trial in the U.S. for the treatment of cancer pain.
While companies such as GW are going through the slow and costly drug approval pathway in the U.S., other manufacturers are getting their marijuana-derived products to market faster by selling them as dietary supplements or nutraceuticals.
CBD can’t legally be marketed as a dietary supplement in the U.S. because “it has been authorized for investigation as a new drug for which substantial clinical investigations have been instituted,” FDA says. Furthermore, no CBD products were marketed as dietary supplements or as a food before the new drug investigations were authorized, the agency claims. If they had been, they could have stayed on the market.
Nonetheless, the U.S. market for botanical CBD extracts and oils is rapidly growing. These products, which are typically ingested or vaped, often claim to be made from hemp—a type of cannabis that contains less than 0.3% THC. Typically marijuana contains from 1% to more than 10% THC.
Botanical CBD products are popping up in all sorts of stores as well as medical marijuana dispensaries. The legality of these products falls into a gray area, says Jordan Wellington, an attorney with the Colorado-based law firm Vicente Sederberg LLC, which specializes in marijuana litigation.
FDA has sent warning letters to companies that sell CBD products as dietary supplements on the internet or in more than one state, claiming that the companies are breaking interstate commerce laws. But FDA has not cracked down on CBD products that are only sold within one state, leaving it up to each state to set and enforce its own requirements.
As a result, the purity and potency of CBD products vary widely, and in some cases, CBD products have been found to contain no CBD at all, say patient advocates and some U.S. senators.
For more than a year, Sens. Chuck Grassley (R-Iowa) and Dianne Feinstein (D-Calif.) have urged the federal government to address the lack of quality control for CBD products. They also want the agencies to evaluate CBD in terms of its abuse potential, pharmacology, and adverse effects to determine whether there is a scientific basis for changing DEA’s classification of CBD—making it separate from marijuana. Such a move could make it easier for researchers to study the chemical.
“Given that many individuals suffer from serious medical conditions that may be alleviated by cannabidiol, it is critical that this evaluation be completed expeditiously,” Grassley and Feinstein wrote in a May letter to Attorney General Loretta Lynch and Health & Human Services (HHS) Secretary Sylvia Mathews Burwell. The letter comes nearly a year after the agencies agreed to conduct the evaluation at the request of the two lawmakers.
“There’s still much we don’t know about CBD and its effect on the human body, especially on children,” Grassley said at a hearing in the summer of 2015. “But in recent years, as word of its potential medical benefit has spread, more and more parents, out of understandable desperation, have turned to what is essentially a black market to get it.”
Both cell culture and animal models have shown CBD may have “antiseizure, antioxidant, neuroprotective, anti-inflammatory, analgesic, antitumor, antipsychotic, and antianxiety properties,” testified Nora D. Volkow, director of the National Institute on Drug Abuse (NIDA), which is part of the National Institutes of Health. But “rigorous clinical studies are still needed to evaluate the clinical potential of CBD for specific conditions,” she said.
One reason why there haven’t been more clinical trials of CBD is the extra regulatory requirements associated with research on a Schedule I substance, including the need for institutional review board approval, Volkow added.
In addition, many CBD products available to researchers are not produced under current Good Manufacturing Practices, conditions required for testing compounds in human clinical trials to ensure their quality and safety, she said. “Furthermore, the opportunity to gather important information on clinical outcomes through practical—nonrandomized—trials for patients using CBD products available in state marijuana dispensaries is complicated by the variable quality and purity of CBD from these sources.”
Last summer’s hearing prompted eight senators to question DEA, HHS, and the White House Office of National Drug Control Policy about government efforts to reduce regulatory barriers to medical marijuana research.
In a December 2015 letter to the agencies, the senators said the regulatory scheme “is outdated and in desperate need of serious and immediate review.” They added, “Problems are exacerbated by a lack of coordination between the agencies and states.”
The senators pointed to the limited supply of marijuana available for scientific investigation as a significant barrier to research concerning its potential medical value. The University of Mississippi is the only facility authorized by DEA to grow marijuana for research purposes, under an exclusive contract with NIDA.
DEA acknowledges in an April letter to the senators, “The current process for initiating research on marijuana or its constituent compounds is time consuming and some researchers have indicated to NIDA that this can be a disincentive to conducting research in this area.” But the agency does not view the current supply of marijuana produced at the University of Mississippi as a barrier to research. The university currently has 185 batches of marijuana with varying levels of THC and CBD, DEA notes in the April letter. The batches vary in size from less than a kilogram to about 17 kg. Last year, NIDA sent just 20 shipments to eight researchers.
Government officials also confirm in their letter that HHS has sent DEA a recommendation on the scientific and medical evidence for rescheduling marijuana. DEA is in the process of reviewing the recommendation and hopes to release its determination “in the first half of 2016,” the letter states.
While patients and their families anxiously wait for DEA’s decision, environmental groups are also putting pressure on the agency to reclassify marijuana as a less dangerous drug. They claim that pesticides are being illegally sprayed on marijuana plants, potentially harming users and the environment.
Growers of legal marijuana are in a two-pronged legal predicament. First, EPA has not assessed the health hazards of any pesticide for use on marijuana, nor has it approved use of any pesticide on cannabis plants because of the drug’s status as a Schedule I controlled substance. Second, application of a pesticide is only legal for the uses listed on the chemical’s EPA-approved labels, thus making use on marijuana crops illicit. As a result, some states are prohibiting the use of all pesticides on marijuana crops. Others are requiring growers to follow organic practices.
Meanwhile, Colorado, Washington, and Oregon—where recreational marijuana is legal—have each provided growers with lists of pesticides that may be used on marijuana in that state. Growers who use pesticides that are not listed risk having their products seized by state officials.
In Colorado, pesticides that are approved by the Colorado Department of Agriculture can be used on marijuana as long as the label allows use on unspecified crops or plants, with wording such as “bedding plants, flowering plants, or other crops.” The pesticide must also be allowed on crops or plants for human consumption.
Colorado recently began enforcing its marijuana pesticide regulations with mandatory inspections. The action follows two consumer lawsuits in 2015 over pesticide-contaminated marijuana and an executive order from Gov. John Hickenlooper (D) last November. The order allows state officials to stop sales of or destroy marijuana products found to be contaminated with banned pesticides. Colorado and the city of Denver have issued numerous marijuana recalls this year because of pesticide concerns. The top chemicals involved in recalls during the past six months are the insecticides abamectin, imidacloprid, and spiromesifen; the fungicide myclobutanil; and etoxazole, used against spider mites.
In Oregon, a pesticide can be used on cannabis if it has been approved for use on other foods, is not subject to a maximum amount allowed on food, and is considered by EPA to be a low-risk pesticide in terms of its potential effects on human health and the environment, according to the Oregon Department of Agriculture. New rules went into effect in June that require Oregon marijuana growers to test their products for nearly 60 specific pesticides.
Washington also implemented new rules this year restricting pesticides on marijuana. The state performs spot inspections of marijuana-growing facilities and requires producers to document on product packaging which chemicals they use.
This patchwork of state laws governing pesticide use on legal marijuana has led to confusion among growers and varying degrees of protection for consumers, says the environmental group Beyond Pesticides.
“It has created quite a bit of a mess” for both state regulators, who are enforcing the rules, and for marijuana businesses, which are caught in an ever-changing regulatory system, says Wellington, the Colorado lawyer. “It creates public safety risks for both employees and consumers.”
Because the marijuana industry covers so many products, it is unclear how to regulate the industry responsibly, Wellington said during a webinar earlier this year. These products include marijuana flowers or buds that are smoked, as well as marijuana-based oils derived through basic extraction techniques or complex manufacturing processes with various solvents and high pressure. There are also marijuana infusions, which are sold in vaping cartridges, baked goods and other edible marijuana products, pills, and tablets.
But federal regulators “don’t want anything to do with marijuana right now because it is a Schedule I controlled substance,” says Robert A. Hendricks, an attorney with the Michigan-based firm Wrigley, Hoffman & Hendricks.
Complex issues revolve around the possibility of federal legalization of marijuana, Wellington added. Federal regulators and everyone else need to step in and do their jobs to ensure that marijuana products are safe, he said. “They all have a role to play.”
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