Wednesday, October 3, 2012

The Army's on Ecstasy: Marching toward an ethical drug policy

Post-traumatic stress disorder (PTSD) among American soldiers returning from Iraq and Afghanistan has reached epidemic proportions, affecting between 75,000 to 225,000 veterans. In fact, suicide is now the leading cause of death in the army, with more soldiers dying by suicide than in combat. Frustratingly, existing treatments for PTSD are limited and ineffective for between 25-50% of patients. Last year a clinical trial using MDMA (i.e. Ecstasy) in conjunction with psychotherapy was shown to ameliorate PTSD symptoms far more effectively than any other known treatment. Despite these promising results, it could be ten years or more before MDMA is approved for use in treating PTSD, and even then clinicians will face additional hurdles until our nation’s drug policy is seriously overhauled. Given the public health imperative for effective PTSD treatment, it’s high time to rethink our stance toward illegal drugs and create an ethical drug policy that paves the way for expedient psychedelics research while providing honest education, harm reduction measures, and on-demand treatment for drug addiction.

PTSD is a chronic, debilitating mental illness. People with PTSD are hyperaroused, repeatedly re-experience their trauma in the form of nightmares, panic attacks, and flashbacks, and often suffer from comorbid depression and drug abuse. The army's own research illustrates that trauma is widespread and long-lasting: around 25% of Vietnam veterans remain symptomatic, even decades after the end of their service. The army is fully aware of this growing issue, and has taken many steps over the years to address it, including the formation of the National Center for PTSD within the US Department of Veterans Affairs, which has emerged as the world’s leading research and educational center on PTSD. The Obama administration has also increased funding for mental health services at the VA by 39% since 2009. Despite these and other efforts, the statistics are alarming: about 18 veterans take their lives each day.

PTSD treatment typically involves pharmacotherapy, psychotherapy, or some combination of both. To date, the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine are the only two FDA-approved drugs to treat PTSD, although others are prescribed off-label. Meta-analyses, which pool data from dozens of randomized clinical trials (RCTs) to try to assess drug efficacy, have found SSRIs to be slightly more effective than placebo, with about 50% of RCTs finding medication to be more effective than placebo in reducing PTSD symptoms. However, SSRIs take several weeks to begin working, often have undesirable side-effects, and many patients fail to respond at all. Psychotherapeutic approaches for PTSD include cognitive behavioral therapy (CBT) and psychodynamic psychotherapy, which are often effective, although attrition rates are high and many never respond. Clinicians and researchers alike recognize the need for more treatments, and the army is scrambling to find them, even exploring mindfulness-based therapies, such as loving-kindness meditation.
MDMA-assisted psychotherapy offers hope for those suffering from PTSD, but the US' fear-based approach to drug policy and education has delayed its development into an approved medicine. (credit: www.maps.org/)

The trick to successful PTSD psychotherapy is to hit the “window of tolerance,” wherein the patient is neither over- nor under-aroused while revisiting his past trauma. Within this sweet spot, the patient can work through difficult emotions without overwhelming anxiety (hyperarousal) or numbing detachment (underarousal). Finding this zone is tricky, requiring the establishment of a trusting patient-therapist relationship, a degree of introspective awareness by the patient, and massive amounts of courage. This may sound simple, but many veterans have spent months, years, or even decades in silence, repressing and suffering through their traumatic memories and emotions. Additionally, therapy within the optimal arousal zone must be ongoing; it’s not a one-shot deal. If therapists or scientists could devise a means by which patients with PTSD could widen, maintain, and more quickly establish this openness, therapy sessions could deliver results more quickly and effectively. And this is exactly where MDMA comes in.

MDMA, known by its street name, Ecstasy, is a psychoactive drug that produces feelings of euphoria, a sense of intimacy with others, and diminished anxiety. It belongs to a class of drugs known as “empathogens,” or “entactogens,” implying that its effects (typically 4-6 hours in duration) increase one’s ability to empathize or feel. MDMA was first synthesized a hundred years ago, but was popularized by the organic chemist, Alexander Shulgin, in the 1970’s. Shulgin himself experimented with the drug and shared it with colleagues and friends, some of whom began using it in psychotherapy sessions. Among underground psychotherapists, MDMA developed a reputation for enhancing communication during clinical sessions, reducing patients’ psychological defenses, and increasing capacity for therapeutic introspection. By the early 1980’s, an estimated 500,000 doses of underground MDMA had been consumed under the code name "Adam," with the media and drug enforcement agencies taking no notice of that use, as sessions were conducted in private settings and didn't produce problems (see Rosenbaum & Doblin for an historical account).

But this soon changed, as MDMA spilled out into the club scene and the US Drug Enforcement Agency (DEA) took notice. In response to impending drug legislation, the medical community presented their research findings to DEA Administrative Judge Francis L. Young, who recommended that MDMA be placed under Schedule III, meaning it had medicinal value but may lead to dependency or abuse (by comparison, Ritalin is a Schedule II substance due to its medicinal value but higher potential for abuse). But in the mid-80’s, Ronald Reagan’s “War on Drugs” was raging, and the DEA placed MDMA under Schedule I, the most restrictive status for a controlled substance. From then until today, federal law states that MDMA has “no currently accepted medical use in treatment” and “a lack of accepted safety for use…under medical supervision.”

This ruling proved devastating for research into the potential therapeutic benefit of MDMA. In spite of the legislation, researchers persisted in their attempts to study the drug’s cognitive and behavioral effects and to prove that it was safe for responsible use by the medical community. But roadblocks to the timely progress of their research were insurmountable. Researchers around the world were pressing for more studies on the potential therapeutic benefits of MDMA in treating psychiatric disorders, such as pain, anxiety, depression, and most importantly, PTSD. Between 1986 and 1988, five different applications for permission to conduct double-blind, controlled studies with MDMA in human subjects were submitted to the US Food and Drug Administration (FDA). All were summarily rejected. Scientists quickly became hip to the fact that securing government approval, obtaining drug licenses, and gaining institutional review board (IRB) support for human studies were both untimely and cost-prohibitive, and so human MDMA research ground to a standstill. Psychiatrists, with their careers and licenses at stake, abandoned their clinical use of the drug. And with that, the hope that MDMA could some day ameliorate the suffering of the many PTSD-afflicted men and women returning home from armed combat disappeared.

Fast-forward to 2001. After sixteen years of sustained effort, Dr. Rick Doblin, founder and director of the Multidisciplinary Association for Psychedelics Research (MAPS), a non-profit research and educational organization that supports scientific research into therapeutic uses for psychedelics, finally obtained FDA approval for an MDMA-assisted psychotherapy study. Nevertheless, it took Dr. Doblin and other investigators three more years of battling with the DEA and Independent Review Boards (IRBs) before the first experimental session with MDMA-assisted psychotherapy was carried out in a PTSD patient (for a brief history, see Check 2004). The study was finally completed in 2008 and its overwhelmingly promising results published in 2010 (see below). That’s a full nine years from FDA approval to results and publication. (Comprehensive information about MDMA-assisted psychotherapy research can be found here.)

The first Phase II clinical trial using MDMA-assisted psychotherapy to treat PTSD finds that 83% of subjects receiving MDMA no longer met PTSD-criteria after two months, compared to only 25% in the placebo group. (Mithoefer et al., 2011. J Psychopharmacol. 25(4):439-52)
 I had the opportunity to speak with Dr. Doblin about why MDMA/PTSD research over the years has been so painfully slow. According to Dr. Doblin, there remains “a delay that takes place with MDMA research because of drug policy.” Doblin explained that as a Schedule I controlled substance, MDMA could take another 10 years before it’s rolled out for use to treat PTSD. He believes that this is largely due to the unscientific, fear-based approach that the National Institute on Drug Abuse (NIDA), DEA, and the Office of National Drug Control Policy (ONDCP) have taken in their drug education and policymaking, and the reticence of scientific researchers to advocate on behalf of a sensible, empirically-driven approach toward drug policy. The government, especially the DEA and NIDA, continues to balk at research that poses, as Doblin puts it, “a threat to NIDA’s educational campaign.”

Doblin believes that this educational campaign is based on the notion that “drug use goes up when the perception of risk goes down.” Consequently, drug education programs exaggerate the risk of any and all illicit drugs, even when the science clearly dictates otherwise. Cannabis is an obvious example. Despite its medicinal applications for patients with cancer, chronic pain, and insomnia, the government has opted to “sacrifice those patients and those benefits because [they] want to tell a story to people” that cannabis is exceedingly dangerous. And the same sacrifice is now being made with MDMA for PTSD. The government’s basic argument is that they “can’t have unfettered scientific explanations because if it proves that some of these drugs are beneficial in some way, that will send the ‘wrong’ message to people. Therefore, they have to block science because there may be some inconvenient findings. Drug abuse prevention should instead be based on honest information. If you can start with that, everything is different, and you’re not scared of research that may show potential benefits.”

The government’s current scheme raises a number of ethical concerns. Obstructing scientific progress or misrepresenting scientific evidence to fit a political agenda harms scientists, patients, and society at large. The mission of mental health scientists in the US, as stated by the National Institute of Mental Health (NIMH) is to “transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure.” However, in the case of developing novel therapies using recreational drugs like MDMA, drug policy prevents scientists from paving that road. This is simply unethical. As Doblin clearly stated, “when scientists see that politics is blocking their research, they have an obligation to point that out.” Scientists should challenge such practices by speaking out in public forums, participating in educational programs that promulgate evidence-based information, and supporting political organizations that advocate drug policy reform, such as the Drug Policy Alliance. Patients, in this case trauma survivors, must also make their voices heard by massively mobilizing against bureaucratic maneuvering that impedes their fair, timely access to effective treatments. For veterans with PTSD, their lives literally depend on it. Those who don’t suffer from PTSD or conduct research using controlled substances must examine the value they place on scientific inquiry, even when it challenges their preconceived social, political, or religious notions. At play here is also the broader issue of cognitive liberty, whether an individual is free to alter the state of his or her consciousness using any method available. This includes stimulants like Ritalin for cognitive enhancement in healthy adults, psychedelics like MDMA for informal psychotherapy, and LSD and psilocybin for spiritual visionaries. Do we really want to live in a society where the limits of human curiosity, creativity, and well-being are restricted? Hopefully, conversations about how best to expand and protect these freedoms while minimizing harm will permeate public dialogue.

In summary, this country is slowly emerging from a dark age in drug policy. Government regulators are just beginning to take a more reasoned approach toward research into stigmatized illegal drugs like MDMA, but a long road lies ahead. Even though the present administration has eschewed the term, the “War on Drugs,” and stated that “drug policies must be rooted in science,” its Director of the Office of National Drug Control Policy, Gil Kerlikowske, still believes that cannabis is “a dangerous drug,” and that the “Just Say No” campaign is one of the “major successes” of drug education. Progress is slow, indeed, and will require a grassroots, coordinated effort to effect significant change. As our service men and women continue to suffer, and the low-hanging fruit of MDMA-assisted psychotherapy remains out of their reach for at least a decade more, it is now our duty to serve them and advocate for a science-based drug policy that clears the path for psychedelics in treating mental illness.


Want to cite this post?
Kohn, J. (2012). The Army’s on Ecstasy: Marching Toward an Ethical Drug Policy. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2012/10/the-armys-on-ecstasy-marching-toward_3.html

2 comments:

Ross Gordon said...

Really great post, Jordan. I've been following this research for the past several months but there's a lot of detail here (the schedule III recommendation, for instance) that I hadn't been aware of.

What do you think about neuroethics' role in discussing MDMA research, and perhaps psychedelic research more generally? I feel like academic discussion of these issues has been pretty muted, which strikes me as odd given that 1) increasingly, popular media outlets like the NYT (and big science names like Oliver Sacks) have been giving psychedelics positive press coverage, and 2) the public health/DARE orthodoxy is that MDMA, LSD, psilocybin, etc. are dangerous drugs with no legitimate uses.

Jordan Kohn said...

Thank you, Ross.

I think many factors have led to the recent surge in media coverage of this issue, including but not limited to shifts in the public's attitude toward illegal drugs and drug policy, cooperation by governmental agencies like FDA as discussed in the article, increasing trauma/suicide rates in the armed forces, disillusionment with our "best" pharmacotherapies, changes in population demographics (younger, more liberal generations), or better access to drug information online. Characterizing these developments and hypothesizing how, why, and to what extent they've shifted everyone's attention would be very interesting.

As far as academic discussion in the literature, it's been pretty lively ever since Ricaurte's 2002 paper in Science reporting that MDMA causes Parkinson's like symptoms in monkeys, which was eventually retracted. This led to a few articles in 2004 in the journal Nature about psychedelics research, and if you look poke around psychiatry journals, there have been murmurings until now. There's a conversation in the British Journal of Psychiatry as well (187:483-90). MAPS has generated a comprehensive list of media and academic articles involving psychedelics research since 2000, which you can access here: http://www.maps.org/media/timeline/.

With respect to academics speaking in public forums, that's where things get trickier. Look to the recent story of David Nutt, chair of neuropsychopharmacology at Imperial College London. As chairman of the UK Advisory Council on the Misuse of Drugs, Nutt was fired due to his scientific panel's findings that cannabis, MDMA, and LSD posed less of a public health threat than alcohol or tobacco, and that policy should be updated to reflect the science. When politics blatantly ignores and trumps science, we have a big problem. We've seen it with climate science, we're seeing it with drugs. As a grad student in neuroscience, I'm frequently instructed to communicate with the public and foster dialogue. But how can scientists be expected to meet this ethical obligation if their careers are put on the line because of it?