Monday, April 29, 2013

MDMA, "Drugs Live," and a life update.

It's been a while.

Last summer, I became inspired to write an article about the potential benefits of the club drug, MDMA, otherwise known as Ecstasy or Molly. The blog post got turned into an article for my alma mater's science magazine, The Synapse, and was published a few months ago. With permission, I am cross-posting it here.

A quick life update for anyone who is interested will be at the bottom of this post.

In Europe and the United States, the drug known as ecstasy is the magic bullet that loosens the inhibitions of many dancers at all-night dance parties known as “raves.” Ecstasy—or “Molly” in its allegedly purer form—is a psychedelic drug with a signature high that produces an intense sensory experience coupled with feelings of euphoria and closeness with others. However, ecstasy's tendency to raise body temperatures and dehydrate users in over-packed, sweltering clubs creates a dangerous situation that troubles parents and politicians alike.

Though ecstasy has been the culprit behind some tragic deaths since its popularization in the mid-eighties, death and injury from ecstasy are relatively rare compared to other drugs scheduled I or II by the DEA. The number of emergency room visits per year resulting from the use of ecstasy are tens of thousands fewer than those due to the use of cocaine, heroin, and marijuana. Every year, the number of deaths from ecstasy are miniscule relative to tobacco- and alcohol-related deaths. Some experts believe that MDMA, the primary chemical constituent behind the ecstasy high, isn't the real danger of ecstasy. Instead, they believe that it is the crowded, hot dance floors combined with the effects of the many other substances ecstasy is famously adulterated with that puts users in danger.

Despite the risks, MDMA's signature high has not only beguiled party-goers. The drug has also intrigued many scientists with its potential therapeutic benefits. In hushed sessions behind closed doors, therapists in the seventies and eighties began to explore the drug's ability to release patients from painful emotions attached to traumatic experiences and to strengthen the therapist-patient alliance. Although the anecdotal evidence was in favor of MDMA as a therapeutic drug, no placebo-controlled clinical trials had been performed by 1985, which was when MDMA was on the table for scheduling by the DEA. Due to the lack of clinical data, and MDMA's perceived dangers in the club scene, the drug was labeled as Schedule 1: a harmful drug with no medical benefits. All research on the therapeutic effects of ecstasy were halted for the next two and a half decades.

Nevertheless, MDMA has only become more ubiquitous among young people since 1985, and the cries to research the actual effects of MDMA on the human body have gradually swelled to a dull roar. However, the US and British governments have little to no precedent for funding studies on MDMA in humans. In 2010, Channel 4 in London endowed Professors David Nutt and Val Curran with funding to begin the first fMRI study of MDMA's effects in the human brain. The results of the study were broadcast live in a TV special called Drugs Live: The Ecstasy Trial late last September.

In the trials, conducted in September 2011, 25 volunteers came in for testing twice. Each time a volunteer came in, they received either an 83 milligram dose of MDMA or a placebo. The study was double-blind, so neither the administrators nor the subjects knew which drug they were getting. 30 minutes after they took the pill, the volunteers entered a fMRI scanner, where they were monitored for 90 minutes while answering questions about their subjective experiences. Throughout this process, volunteers were also asked to recall positive and negative memories from their lives. After the volunteers came out of the scanner, they performed a task in which they rated the trustworthiness of various faces, testing their feelings of closeness with others.

Drugs Live features the experiences of five volunteers: an ordained priest, an ex-soldier, a journalist, an actor, and a former member of Parliament. The show itself consists of clips of the five volunteers' trials on ecstasy, interviews with them and members of the audience, a debate between David Nutt and his loudest dissenter, Andrew Parrott, short videos of recreational MDMA users out dancing or just enjoying a night in with friends, and a video of an illegal therapy session with MDMA. The program is punctuated by fleeting explanations of the results of the study, described by Nutt and host Jon Snow with the aid of a giant, plastic brain with flashing lights indicative of the various structures within.

The first major discovery presented in episode 1 is MDMA's effects on the neural circuit between the posterior cingulate cortex and the prefrontal cortex. This circuit is known to become overactive in people suffering from anxiety disorders and depression, and is believed to lead to the excessive rumination characteristic of mood disorders. Normally, the two nuclei fire in sync with one another, but MDMA releases a deluge of serotonin and causes the two nuclei to start firing out of line, hushing the circuit between them and alleviating anxiety, which leads to the characteristic euphoria of the drug.

After a clip showing a therapy session, in which a woman talks through her feelings towards her recently deceased, abusive father, Nutt walks toward the giant brain to explain how MDMA is helping this woman work through her traumatic memories. When a person recalls a traumatic memory, there is an activation of the amygdala and the prefrontal cortical region. According to Nutt, the prefrontal cortical region modulates the emotions associated with a particular memory, and MDMA works to dampen the firing of that region. Without the chatter of the emotional overlay, patients are better equipped to engage with and process those memories, making MDMA a particularly exciting potential therapy for post traumatic stress disorder.

Though the program opened with a claim of being politics-free, “unvarnished science,” many viewers felt that Drugs Live was more of a “pro-drugs” circus than a lucid exposition of the science behind MDMA. Indeed, there was little discussion of the negative aspects of MDMA, including the “Tuesday blues” experienced by one volunteer in the study and the overall negative experience the ex-soldier had during the trials. There was also little air time for the debate between Nutt, Curran, and Parrott, which some viewers with a scientific background were particularly interested in.

Perhaps the positive bias in Drugs Live is unsurprising to those who know David Nutt for famously suggesting that drugs like cannabis, ecstasy, and LSD were less dangerous than alcohol and tobacco while on the Advisory Council on the Misuse of Drugs. His comments were largely responsible for his subsequent firing from the Council.

Regardless of Nutt's personal opinions on illicit substances, the study performed in Drugs Live is still an exciting contribution to a sparse body of research on the effects of MDMA in humans. Many other studies on MDMA are funded by government agencies such as the National Institute on Drug Abuse (NIDA). These studies tend to be performed on animals with the intention of finding the harmful neurological effects of MDMA. Such studies have shown significant depletion of neurons that produce serotonin that lasts for years after a single round of MDMA administration. However, these single doses are given intravenously over the course of three or four days. Critics say such dosages are not representative of how the drug would be administered in therapy (a low dose taken orally once or twice in a patient's lifetime), nor do they reflect how most recreational users take ecstasy (taken orally once or twice a month.)

Studies on humans are often relegated to surveying cognitive faculties in recreational users of ecstasy, using hair and urine drug tests to determine what sorts of drugs subjects have been taking. There are many criticisms of these studies as well, many citing poor control for subjects who have taken ecstasy in combination with other drugs or alcohol. However, these studies still show many deficits in memory, as well as higher levels of anxiety in current and former ecstasy users. Theseresults foster skepticism for the therapeutic benefits of MDMA.

A viewer watching Drugs Live likely wouldn't catch the troublesome findings of such research on MDMA just from watching the few short minutes where Andrew Parrott attempted to explain it. This was one of many issues that commenters brought up about Drugs Live after it aired. Some criticized Channel 4 for not giving enough credit to its viewers for being able to hold their attention on scientific facts for more than a few seconds. It seemed as though the content of Drugs Live wasn't much different from that of ecstasy found on the street: very little though potent science adulterated with an abundance of questionable filler.

Life update: For anyone who is wondering what I've been up to this past year, I'm still writing! I have also been working a lot waiting tables to save up for graduate school. I will be beginning the science communication graduate program at University of California Santa Cruz in the fall. In addition, I have been writing for The Synapse, and I will be posting my newest article once it comes out in print!