By Mason Marks

Last year more than 64,000 Americans died of drug overdose, which is “now the leading cause of death” in people under 50. Opioids kill an estimated 91 Americans each day and are responsible for most drug-related deaths in the US. This public health crisis requires solutions that are supported by science and reason instead of emotion and political ideology. In Part I of this three-part series, I discuss how the President’s Commission on Combating Drug Addiction and the Opioid Crisis misinterpreted scientific studies and used data to support unfounded conclusions. In this second part of the series, I explore how the Opioid Commission ignored medical interventions that are used successfully in the U.S. and abroad. In Part III, I will discuss non-medical interventions such as drug checking and safe injection sites. The Commission’s failure to consider these options is likely driven by emotions such as fear and disgust rather than a careful review of scientific evidence.

Medical marijuana is currently accepted in 29 U.S. states and the District of Columbia. It is also permitted in at least 10 countries. However, the Opioid Commission outright rejected calls to consider the use of medical marijuana as an alternative to opioids for managing pain. Prior to the Commission’s first meeting, it solicited input from industry and members of the public on how to address the opioid crisis. In response, it received over 8,000 public comments. According to VICE News, which obtained the documents by submitting a Freedom of Information Act (FOIA) request, most comments were submitted by individuals urging the Commission to “consider medical marijuana as a solution to the opioid epidemic.” A spokesman for the Office of National Drug Control Policy, a body of the Executive Branch that provides administrative support to the Opioid Commission, reports receiving “more than 7,800 public comments relating to marijuana.” Despite these comments, in its final report, the Commission dismissed the notion that marijuana should play a role in treating chronic pain and opioid addiction. Its report cited a recent study from the American Journal of Psychiatry, which concluded that marijuana use was associated with an increased risk of opioid abuse. However, this study relied on data that was collected over twelve years ago. One of its authors, Columbia Medical School Professor Mark Olfson, told CNN that if the data were collected today, they could yield different results.

It should be noted that the connection between marijuana and opioid abuse found by Olfson and his colleagues is one of association rather than causation. When viewed in light of other studies on marijuana using more recent data, the reported association becomes less compelling. For example, last year, one of the most comprehensive studies on marijuana consumption was published by the National Academies of Sciences, Engineering, and Medicine. The authors concluded that “in adults with chronic pain, patients who were treated with cannabis or cannabinoids are more likely to experience a clinically significant reduction in pain symptoms.” According to the National Institute on Drug Abuse, the availability of medical marijuana may be associated with a decrease in opioid prescriptions and opioid related deaths. One study found that states with legally-protected medical marijuana dispensaries showed statistically significant reductions in opioid-related deaths and admission to opioid treatment programs. Specifically, states with dispensaries experienced a 16 to 31 percent reduction deaths due to prescription opioids and a 28 to 35 percent reduction in admission rates than they would have without the dispensaries. These observed effects grew larger the longer the dispensaries had been present in the state. A 2017 study published in the American Journal of Public Health found that since recreational marijuana use was legalized in Colorado, statewide deaths due to opioids have steadily declined.

Instead of delving into the complexities of marijuana research, the Opioid Commission cherry-picked a single study on twelve-year-old data and reflexively dismissed the growing body of research that supports the use of medical marijuana to treat pain and reduce opioid-related deaths. Though the available data on the benefits of medical marijuana do not definitively prove that marijuana should be used to treat pain, at the very least, it supports further exploration of its potential and should eliminate any notion that marijuana should be outright dismissed as a tool to combat the opioid crisis.

While testifying before the House Oversight Committee on November 28, 2017, Governor Christie said “175 people are dying per day… the most powerful analogy is that this means that we have a September 11th every two and a half weeks.” Christie asked if American opioid-related deaths were due to the actions of a terrorist group, what price would we be willing to pay to stop it? This sentiment was also present in the Commission’s final report in which it argued that on 9/11, the country banded together and used every tool available to prevent additional American deaths. However, with respect to the opioid crisis, the Commission’s report did not consider every available tool available to treat opioid abuse.

Among the over 8,000 public comments submitted to the Commission was a letter submitted by the Multidisciplinary Association for Psychedelic Studies (MAPS), a non-profit organization that sponsors FDA-sanctioned clinical trials. MAPS is conducting Phase 3 clinical trials on the use MDMA-assisted psychotherapy for treating PTSD. In its letter, MAPS urged the Commission to recommend that the federal government pursue research on the use of the West African plant Tabernanthe iboga (see Fig. 1 below) to combat opioid abuse. Iboga has been consumed in Gabon by members of the Bwiti religion for centuries. Its active compound ibogaine is used to fight addiction in several countries including Canada, New Zealand, South Africa, and Brazil. In the United States, ibogaine is a Schedule I controlled substance, which means the U.S. Drug Enforcement Agency (DEA) deems it to have no currently accepted medical use. However, in 2017, two MAPS sponsored studies on ibogaine were published in the American Journal of Drug and Alcohol Abuse. In one study involving 30 subjects with opioid dependence, the authors observed that 50% of participants had consumed no opioids thirty days after ibogaine administration. These effects persisted to a variable extent for up to twelve months. In another study with 14 participants, the authors reported that a single dose of ibogaine resulted in sustained abstinence from or reduced consumption of opioids over a one-year period. However, despite this evidence and MAPS’s plea to consider the beneficial uses of ibogaine, the Opioid Commission made no mention of the compound in its final report.

The Commission also made no reference to mitragyna speciosa, also known as kratom (see Fig. 2 below), which is gaining popularity in the U.S. as a means of controlling pain and easing symptoms of opioid withdrawal. Kratom is a plant native to Southeast Asia and has been consumed for centuries in Thailand, Indonesia, and Malaysia. Unlike marijuana and ibogaine, kratom is not a Schedule I controlled substance, however, it is at risk of being placed in this category. On August 30. 2016. The DEA announced its intention to temporarily categorize kratom in schedule I “to avoid an imminent hazard to public safety.” The announcement sparked outcry from kratom users and advocacy groups such as the American Kratom Association, which argued that the DEA’s claims lacked scientific support. These groups were joined by members of Congress who wrote bipartisan letters urging the DEA to reconsider. In response to these efforts, on October 12, 2016, the DEA announced it had withdrawn its emergency scheduling order to allow time for additional research and public comment.

For the time being, the future status of kratom is unknown. However, on November 14, 2017, the FDA issued an advisory on kratom to warn the public of deadly risks associated with the drug. The FDA reports it is aware of 36 deaths associated with kratom. However, at least some of these may be attributed to co-consumption of kratom and other substances such as alcohol, benzodiazepines, or opioids. An article published in the Journal of Analytical Toxicology reported that adulteration of kratom with a potent synthetic opioid O-desmethyltramadol likely contributed to nine kratom-associated deaths in Sweden. According to Jack Henningfield, a clinical pharmacology expert who has advised the FDA and worked for the National Institute on Drug Abuse, kratom has low toxicity. Though there is some potential to develop a dependence on kratom, Henningfield likens it to the reliance on caffeine developed by many Americans. At a press conference held by the American Kratom Association, Henningfield argued that no deaths have been definitively attributed to kratom, and he contended that categorizing kratom in Schedule I would harm public health. According to Henningfield, users would be forced to acquire kratom through illegal black markets, which could increase exposure to dangerous adulterants. Many users could revert to opioid consumption, which would result in preventable opioid-related deaths.

Though ibogaine and kratom-associated deaths have been reported, the risks of consuming these drugs must be viewed in the proper context. Even common substances that are currently accepted as safe have been associated with death and serious side effects. For example, one study analyzed 51 deaths associated with caffeine poisoning. An article published in 2006 reported that there are an estimated 458 deaths associated with acetaminophen consumption each year. One study reported multiple deaths due to overconsumption of vitamin D. Current medical treatments for opioid abuse are also associated with numerous annual deaths. For example, as shown in Figure 1 (see above) methadone is thought to have contributed to over 3,000 deaths in 2016. The failure of the Opioid Commission to consider all available pharmacologic options for combating the opioid crisis is a missed opportunity especially because there is scientific support for their use, or at a bare minimum, to increase research on their risks and potential benefits. In its final report, the Commission urged the President to instruct the National Institutes of Health (NIH) to invest in the development of new MAT options and non-opioid pain relievers. Yet it instead of recommending development of existing options such as ibogaine and kratom, which are inexpensive and readily available, the Commission advocated for the development of entirely new drugs. In a forthcoming article, I argue that the schedule I status of ibogaine raises social, economic, and regulatory barriers to research on the drug. Similarly, if kratom is categorized in Schedule I, it will become extremely difficult to obtain for research. Instead of ignoring the potential benefits of ibogaine and kratom, the Opioid Commission could have recommended that the DEA reduce barriers to ibogaine research and refrain from categorizing kratom in Schedule I until its potential risks and benefits can be thoroughly evaluated.

Regulators may fear endorsing the use of marijuana to treat pain. They may be disgusted by the thought of studying mysterious West African and Southeast Asian plants such as iboga and kratom to combat addiction. However, if the evidence shows that they can reduce opioid dependence, and they are associated with fewer adverse events than current treatments such as methadone, then any trepidation or disgust should be overcome. Lawmakers must be fearless as they contemplate solutions to the opioid crisis. The availability of marijuana and other non-opioid treatments for pain and addiction should give them hope and the courage to fight the opioid crisis head-on.