A public health scientist’s response to the US Food and Drug Administration regarding their failed marijuana policy
This response is to the Food and Drug Administration (FDA) Docket FDA-2018-N-3685
“International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; ADB–FUBINACA; ADB–CHMINACA; Cyclopropyl Fentanyl; Methoxyacetyl Fentanyl; para-Fluoro Butyrfentanyl; Tramadol; Pregabalin; Cannabis Plant and Resin; and Eight Additional Substances; Request for Comments” October 10, 2018 Federal Register notice with the invitation to comment
The FDA notice scopes the invitation for comments to the abuse potential, actual abuse, medical usefulness, trafficking, and impact of scheduling changes on availability for medical use of 16 drug substances. As required under the Controlled Substances Act (the CSA), comments will be considered in preparing a response from the United States to the World Health Organization (WHO) regarding the abuse liability and diversion of these drugs. WHO will use this information to consider whether to recommend that certain international restrictions be placed on these drugs.
By Elizabeth Porter, MSSM
My comments focus on the need to remove botanical cannabis from the Controlled Substances Act (CSA) and secondarily on the overall destructive social consequences the CSA. The CSA is a costly and ineffective law. Pharmaceutical and chemical regulation would be better achieved using another legislative tool that is based more on evidence and public health, and measured by outcomes and risk-based indicators. Botanical cannabis should never have been scheduled in the CSA. It needs to be removed from the schedule of drugs under the CSA authority.
Drug policy, with the CSA as the primary regulatory authority to implement drug policy rules, resulted in decades of destructive policies that bred contempt of government and public health while inflicting greater harm via abysmal public health outcomes related to drug misuse. Under the CSA, the nation faced an increase in substance misuse related morbidity and mortality, and the seeming lack of policy effectiveness in stemming importation of novel pharmaceutical compounds used in drugs of abuse. Fundamentally the CSA is a policy failure and this country and allies in the UN need to revisit if and how drugs and other substances are regulated to protect the public interest and health without infringement into personal liberty and choice.
My comments summarized input provided in April 2018 to FDA regarding botanical cannabis are from the perspective of a public health systems scientist and former federal regulator.
1. The FDA should recommend removal (“de-scheduling”) of the cannabis plant and derivatives from the CSA.
The FDA has authority under the CSA to make recommendations concerning scheduling (Section 201 (c), [21 U.S.C. § 811 (c)]). The FDA should recommend removal (“de-scheduling”) of the cannabis plant and derivatives from the CSA.
2. The Controlled Substances Act is not an effective law and should be replaced with regulatory mechanisms that are based on science and relative harm principles to ensure safety and to better address the public health problem of substance abuse.
An invitation to comments on the CSA begs the question of the effectiveness of this law to protect public health and ensure public safety. The CSA is the legal foundation for the “War on Drugs”. The intent of the law was to combat substance abuse from a supply-sided approach as enforced by the DEA. Its unintended consequences regarding decisions to schedule cannabinoids most restrictively has likely exacerbated the country’s drug crisis rather than combating it, by placing less restrictive controls on more harmful substances.
As a public health scientist, I view the Controlled Substances Act as an utter public health policy failure. As we approach the fifty-year anniversary of the CSA, our country is mired in the deadliest drug epidemic in its history (from drugs or drug combinations, in many cases scheduled less restrictively than the cannabinoids), the demand for treatment for substance misuse disorders far outpaces current treatment capacity, our country tops the world in legal and illicit drug consumption, our country incarcerates more of its citizens (largely due to drug-related crimes), and yet we spend more money per capita to obtain these poorest health outcomes.
The CSA, which has a criminal law enforcement focus to combating drug abuse, is the center piece of this heavy handed and unbalanced policy and is simply the wrong public health approach.
The scheduling system is not truly risk-based, as evidenced from the abysmal public health outcomes involving drug abuse and harms. Additionally, laws like the CSA, that are not based in sound science nor the public interest, seed distrust in the public sector – as they support concerns that special interests (e.g., big pharma, big legal/prison industries), not sound science or citizen interests, control decisions that profoundly impact every day Americans’ lives. The distrust of government consequent to bad policy is a particularly distressing trend in public health – from fear of the integrity of the US vaccine supply, the legitimacy of the FDA or CDC, to the efficacy and safety of the US pharmaceutical supply.
Much has been written and documented about the political history of the CSA and how in particular the scheduling decision for cannabis was not based on public health science, but rather it was crafted to reinforce cultural-political bias (Aggarwal, 2015). By measure of results and outcomes, the CSA is not an effective way to control pharmaceutical contraband or drug abuse in the US. The FDA needs to assume regulatory oversight of these substances under the Food Drug and Cosmetic Act or other science-based authorization.
3. The CSA definition of “Abuse” and “Abuse Potential” needs to realistically incorporate relative risk to be meaningful.
In January 2017 FDA CDER released guidance on the “Assessment of Abuse Potential of Drugs”. The notice invites comments on abuse potential for five cannabinoid substances, therefore review of the definition provided on drug abuse is relevant.
“Drug abuse is defined as the intentional, non-therapeutic use of a drug product or substance, even once, to achieve a desired psychological or physiological effect. Therefore, abuse potential refers to the likelihood that abuse will occur with a particular drug product or substance with CNS activity. Desired psychological effects can include euphoria, hallucinations and other perceptual distortions, alterations in cognition, and changes in mood.” FDA Guidance on Abuse Potential Assessment, 2017
The guidance emphasizes that if a drug has rewarding properties and induces physical dependence or tolerance, these factors increase its overall abuse potential. Cannabis is a substance with CNS activity that clearly has rewarding properties, as supported by both animal research and social surveys of human use. However, both sugar and coffee meet these rewarding criteria as well (and are associated with adverse events and significant adverse health impacts, and these substances are not subject to CSA scheduling). Strict schedule I control of substances like coffee or sugar likely would elicit the same negative behaviors attributed to cannabis abuse, regarding substance seeking and trafficking, if these substances were controlled and prohibited liked cannabis. Some potentially harmful substances still are used and appropriately regulated (as a food, supplement, or drug) and have manageable safety risks or adverse health impacts from a societal perspective.
Drugs that produce dependence or have significant safety concerns are not necessarily regulated under the CSA. Medications that are not associated with abuse, such as antidepressants, betablockers, and centrally acting antihypertensive drugs are not scheduled and are not subject to the restrictions of the CSA; yet these can produce physical dependence and/or tolerance after chronic use. Some of these dangerous substances have been approved for over the counter sales. For example, antihistamines like Benadryl, that are regulated as over the counter drugs, have lethal doses close to the therapeutic doses, and are even more dangerous in combination with other CNS acting drugs, and can significantly impair the consumer in tasks needing psychomotor skills and attention, like driving.
The public perception is that product safety is the key to scheduling, and when the public sees highly lethal drugs outside the Schedule, even “abusable”, highly lethal drugs scheduled at a less restrictive level, it breeds contempt for law, the FDA and public health.
4. The FDA should not discount comparisons with other drugs or substances on or off the CSA schedule when evaluating cannabis. Comparisons are key to the public perception of consistent and fair evaluations.
The 2016 DEA/FDA Scheduling Recommendation to retain cannabis in Schedule One completely discounted the justification for reduced scheduling through risk comparisons of other less restrictively regulated substances made by the 2009 and 2011 rescheduling petitioners’. The FDA claims that these are “difficult, because of the pharmacologically dissimilar actions of substances in Schedule Two of the CSA.” The comparisons were not an attempt to compare pharmacology, but rather an obvious observation of relative risk, especially when morbidity and mortality are key indicators. The FDA reply was suggestive of an agency looking to dodge the obvious – that cannabis is exceedingly safe when compared to many lesser scheduled, unscheduled and over-the-counter substances.
5. Botanical cannabis has medical usefulness and to deny this is intellectually dishonest.
FDA continues to state that there is no evidence that there’s a consensus among qualified experts that marijuana is safe and effective for use in treating a specific recognized disorder even though the evidence is plentiful. The response to the de-scheduling petitions further states that only “qualified experts” as deemed by the FDA can make this determination. This is again skirting reality through semantic gaming. Furthermore, by determining that cannabis has no accepted medical use, and then stating that all non-medical use would equate to abuse, the CSA considers all use of cannabis as substance abuse. This circular reasoning does not facilitate sound public health decisions.
6. Removal of botanical cannabis and derivatives from Schedule One will reduce trafficking as trafficking is a byproduct of prohibition.
The CSA helped nurture a valuable illicit commodity that exceeds the value of most other US agricultural products – prohibition of botanical cannabis created an environment for trafficking and likely created a product array less safe than if the agency had effectively regulated this as an herbal supplement. Sound regulation truly crafted in the public interest will protect consumers and not nurture illicit activities.
7. Removal of botanical cannabis and derivatives from the CSA will reduce the illicit development and commerce of stereoisomers of THC as many of these are byproducts of prohibition.
The CSA restrictions helped nurture illicit drug development in the form of “fake marijuana” (spice, fake weed or K2). These are designed to appear to be botanical cannabis, the appeal of the drug is that it is marketed as an equivalent to botanical cannabis. However, in areas where botanical cannabis is prohibited or controlled to the level where it is expensive, these substances are inexpensive and can be easy to obtain as a commercial product through retail stores. A standard drug test will not identify a user of synthetic cannabinoids whereas natural cannabis would be traced. These substances are associated with thousands of adverse events, many of them extremely serious.
Again, this adverse consequence of the CSA and truly not understanding human behavior, has compounded and amplified a public health problem, rather than mitigating it. De-scheduling botanical cannabis and derivatives likely will result in the drop in ‘fake weed’ through basic tenets of economic demand, if the real botanical product (with a much more tolerable safety profile) can be delivered and marketed safely and without costs added in over-regulating and tracking this plant.
8. Removal of cannabis from the CSA will improve the quality, scope and cost of research on safety and therapeutics
The Schedule I status of cannabis has adversely impacted research on safety and therapeutics. Compounding the FDA pronouncement that cannabis has no accepted medical use and all users are abusers, the funding for research has remained concentrated on study of potential adverse effects. Federal funding is a “zero-sum game”. Funds for studies of diversion (largely a consequence of CSA prohibition and mandate) and repeatedly reinvestigating theories of abuse translates directly to not directing sufficient funds to understand health outcomes from conditions treated in state medical cannabis programs, how this substance may substitute for more harmful substances, or any other health index. This leaves a research void that perpetuates the FDA circular reasoning / standard response that more research is needed to justify removal from strict criminal control under the CSA.
9. Fund the uses of cannabis and do not skew research resources on study of abuse and abuse potential of cannabis.
FDA should provide a more balanced approach to studying the risks and benefits of cannabis. Currently the vast amount of research is on the abuse potential of cannabis and not its uses. The vast majority of federal funding towards cannabis is used for studying the risk profile of cannabis and enforcement issues, rather than conducting balanced risk-benefit studies.
Even the state medical marijuana programs, to avoid enforcement under the CSA, place all of their resources studying risks rather than benefits of cannabis.
The botanical innovation in the illicit cannabis market has produced more cultivars and better research quality material than available through the CSA channels. These are so tied up in “red tape” of bureaucratic impediments that despite a pledge to make botanical cannabis easier to access for research, it seems that the FDA is parking the process until the major pharmaceutical interests are ready to capitalize.
This apparent stalling of policy change, timed to assist the pharmaceutical development of cannabinoid drugs, is obvious to most citizens. These maneuvers work in a corrosive manner on public trust.
10. The Prevailing Drug Approval Paradigm Should Be Revised to Better Reflect Clinical Practice
From a public health perspective, the controls offered by the CSA (and the Food and Drug Act) do not adequately address the health and safety issues in the communities we serve. Specifically, the protocols used for drug approval do not realistically model use. Drug trials often are for much shorter duration than typical use, are not conducted in representative target populations, and are typically not studied in situations of polypharmacy – when multiple drugs are used together. Yet these are always touted as the “gold standard” of evidence.
As a scientist, I understand the importance of controlled studies. However, if these do not model realistic scenarios, they are of limited usefulness.
Because botanical cannabis is used differently than other therapeutic agents, it cannot be forced into the current drug approval taxonomy. Moral judgment and medical paternalism creeps in when substances that produce euphoric effects, (this is considered an adverse effect), and the health advantages of social administration of therapeutics, self-administration of medicines is deemed so dangerous it could justify criminal prosecution.
When FDA force fits cannabis into this drug model, they have ample evidence to say it does not work. Rather than rely on the current framework to determine the safety and usefulness, the FDA should adjust the evaluation framework to best protect public health and accommodate the unique and valued properties of this plant.
11. The FDA Should Re-Open the IND Compassionate Use Program to incorporate State Medical Marijuana Programs and to Enable Collection of More Representative Public Heath Indicators
There is no collaboration between the state medical marijuana programs and the Compassionate Use IND program of FDA. This is a missed opportunity to collect outcome data. Again, the CSA Scheduling of botanical cannabis and derivatives have functioned as impediments to effective public health.
Because the current drug approval paradigm does not fit well for botanical cannabis, the FDA states its support for drugs derived from marijuana, there is no evidence there is any support for allowing whole plant marijuana as an IND-authorized herbal medicinal product. This omission of interest in supporting and studying medicinal botanical cannabis consumption is a public health mistake; herbal cannabis is a therapeutic agent that costs less, is used more, and generally has a better safety profile than derived drugs.
Studying and collaborating with the state programs to administer and collect health outcomes and adverse events would go far to improving the FDA efforts to stay relevant and protect the public health with respect to this substance in all its forms. The CSA has made state and federal health programs at odds, and this is another poor public health trend. State public health agencies administering medical cannabis programs are mandated to address youth illicit use and diversion – leaving little to no resources to study outcomes, overall drug use patterns and substitutions and no positive measures are studied.
From FDA web site (April 2018):
Information from adverse event reports regarding marijuana use is extremely limited; the FDA primarily receives adverse event reports for approved products. General information on the potential adverse effects of using marijuana and its constituents can come from clinical trials using marijuana that have been published, as well as from spontaneously reported adverse events sent to the FDA. Additional information about the safety and effectiveness of marijuana and its constituents is needed. Clinical trials of marijuana conducted under an IND application could collect this important information as a part of the drug development process.
Does the FDA object to the clinical investigation of marijuana for medical use?
A. No. The FDA believes that scientifically valid research conducted under an IND application is the best way to determine what patients could benefit from the use of drugs derived from marijuana.
12. The FDA should respond to the public interest that consumption and commerce of botanical cannabis and derived products are a tolerable societal public health risk.
The FDA-DEA continue to regulate cannabis in a paternalistic manner despite overwhelming public interest to reduce the restrictions on access and use. States that experimented with medical cannabis programs have been harmed by the CSA restrictions. Instead of collecting outcome measures on those who enrolled in these programs to gather public health data, or research into the use of cannabis, states are using their limited health resources tracking measures of diversion and abuse to comply with the restrictions placed via the inappropriate regulation of this substance. This essentially places the risk benefit analysis of the substance at a distinct negative bias when only data on risks are funded and collected.
The recent (and much heralded) approval of Epidiolex, the first botanical-based cannabis drug, can trace its support for development to patients who advocated through efforts within states to allow for safe access to cannabis as a therapeutic agent. This was despite the efforts of the nation’s premier public health regulatory agency, not because of FDA support.
It is frankly semantic gaming, and an embarrassment to my past career as a federal regulator and public health scientist, when I read the materials and memos from FDA (2015) that provided a “justification” for continued schedule I listing (released in 2016) of marijuana (botanical cannabis). It looked more like a convoluted exercise in hiding from the public interest rather than addressing it. Again, this action is confirmatory to the lack of public confidence in our drug and health system, when the FDA’s only movement on ending the over-restrictive handling of cannabis is when ample economic stakeholders from the pharmaceutical industry are ready to capitalize on the plant’s pharmaceutical constituents.
It is similarly faulty to state, as FDA did in its 2015 CSA analysis of marijuana scheduling, that cannabis did not have accepted medical uses nor an acceptable measure of safety. The analyses truly looked like the regulators began with the conclusion and worked their way back to justify the restrictive scheduling.
I believe the FDA can do better than this. We are clearly in the midst of a great public health experiment with the reintroduction of cannabis into modern medicine, a food, fiber, “nutraceuticals”, supplements, cosmetics. The FDA seems to want to pretend that this will go away. We are also in the midst of a great public health crisis with opioid and other legal and illicit narcotics, of which the CSA has shown to be ineffective policy at stopping or even slowing the trend.
FDA has an important role in the regulation of the US food and drug supply. They need to step up to this responsibility, be responsive to the public interest, and ensure that these products protect consumers and ensure that the risks from using and “normalizing” these substances are well managed and mitigated.
Since the FDA does not have the authority to replace the CSA, and since botanical cannabis does not fit into the current drug paradigm, it would be a first step towards a more public health-oriented drug policy to de-schedule botanical cannabis and derivatives.
-Elizabeth Porter, MSSM
Ms. Porter is a consultant with 30+ years in public health and program analysis, in research and development, public policy and planning, and as a federal regulator.