Could a Notorious Party Drug Be the Next Psychiatric Breakthrough?

Originally appearing here. MDMA is a drug that’s typically associated with youth culture and dance parties — but it’s increasingly attracting the attention of psychologists and cognitive therapists. Also known as ecstasy, the drug has shown effectiveness in treating a number of mood disorders. But are the potential health risks worth it? Since its introduction less than 50 years ago, recreational use of MDMA (3,4-methylenedioxy-N-methylamphetamine, “ecstasy,” “molly”) has skyrocketed. In the U.S. alone there are an estimated 2.6 million users. It’s an amphetamine drug that elevates mood. In its “pure” form, MDMA tends to take on a crystalline or powder state, often with the color and consistency of nutmeg. Over the past several decades, the drug has become a fixture at raves and dance clubs. It’s currently illegal in most countries on account of its empathogenic effects; users experience feelings of reduced anxiety, euphoria, and a heightened sense of interpersonal intimacy. The drug works by decreasing activity in the amygdala, a part of the brain associated with the fear response. It also increases activity in the prefrontal cortex, the region responsible for higher-level brain processing. And indeed, some users report a heightened sense of awareness and verbal articulateness. MDMA ≠ Ecstasy? It’s important to note, however, that what’s often touted as ecstasy does not always equate to MDMA. This is why some users have started to use the term “molly” in its place. Ecstasy is often quite impure — multi-colored tablets that contain chemicals (namely adulterants) other than MDMA. Chemical analyses of “ecstasy” often reveal added compounds like caffeine, ephedrine, pseudoephedrine, salicylates, dextromethorphan (DXM), amphetamine, methamphetamine, paracetamol, and ketamine. And indeed, this is a very serious point that warrants clarification; the consequences of misunderstanding the distinction can be quite severe — if not fatal. Early last year, eight Albertans died after taking what they thought was ecstasy, but were instead given pills laced with high levels of paramethoxymethamphetamine (PMMA), a notoriously toxic amphetamine often called “Dr. Death.” What’s more, these added adulterants have also posed a problem for scientists and medical practitioners trying to understand this amorphous thing called “ecstasy.” Writing in Popular Science, Shaunacy Ferro explains: Ecstasy’s toxicity is a scientific mystery because it lacks a clear “dose and response effect,” according to [Edward] Mills — one person might get sent to the hospital after one pill, while someone else can take 50, no problem. How many people actually die a year from ecstasy-related causes is hard to pin down, but according to the Substance Abuse and Mental Health Services Administration, there were 22,816 MDMA-related emergency room visits in 2009. So, are these emergency room visits the result of MDMA, or laced ecstasy pills? Aware of this problem, scientists over the last several years have made a concerted effort to use MDMA in its pure form when conducting experiments. Psychiatrist Michael Mithoefer, for example, uses MDMA produced by a university lab, that’s 99% pure. And interestingly, the only side-effects he’s been able to chronicle have been things like dizziness, impaired balance, and some anxiety. And Canadian Health Officer Perry Kendall recently referred to the perceived risks of MDMA as “overblown,” noting that the the drug has been proven safe in controlled clinical trials by psychiatrists, and that the type of ecstasy sold on the street is laced with potentially dangerous chemicals. Back in 2009, the UK’s Home Office drug advisor David Nutt remarked that ecstasy “is no more dangerous than riding a horse.” Now, all that said, the jury is still out on MDMA’s long-term effects. There simply hasn’t been enough work done. And troublingly, contradictory evidence does indicate some rather serious health risks. Which we’ll get into in just a bit. Given this ambiguity, and the fact that MDMA works extraordinarily well as a mood-altering drug, mental health professionals are starting to wonder if it should be used to treat such conditions as post traumatic stress disorder (PTSD), anxiety, depression, and even autism. Here’s what the early evidence is indicating. MDMA in the therapeutic setting A recent pilot study showed that MDMA, in conjunction with psychotherapy, reduced PTSD symptoms without inducing drug abuse or neurocognitive decline in the long-term (upwards of three years after treatment). The researchers suspect that MDMA increases a person’s likelihood of detecting positive expressions and finding them rewarding, while reducing the chance of the opposite. “These effects may combine to increase the effectiveness of psychotherapy for PTSD, by increasing self-acceptance, promoting interpersonal trust with therapists and catalyzing the effective processing of emotionally-distressing material,” the researchers write. It’s worth noting that two participants out of the 12 relapsed, and three didn’t answer the questionnaire; so the treatment may not work for everyone. An independent report from Norwegian researchers made the case that MDMA should be used to treat PTSD, and this is why: 1) MDMA increases oxytocin levels, which may strengthen the therapeutic alliance; 2) MDMA increases ventromedial prefrontal activity and decreases amygdala activity, which may improve emotional regulation and decrease avoidance and 3) MDMA increases norepinephrine release and circulating cortisol levels, which may facilitate emotional engagement and enhance extinction of learned fear associations. Thus, MDMA has a combination of pharmacological effects that, in a therapeutic setting, could provide a balance of activating emotions while feeling safe and in control, as described in case reports of MDMA-augmented psychotherapy. Consequently, the researchers suggest that MDMA should be considered for any kind of anxiety disorder. And in fact, MDMA is being seriously considered for treating anxiety in people with advanced stage cancer (two different studies, here and here). An informal study has also indicated that MDMA could be used to treat depression. As noted, MDMA increases prosocial feelings, like friendliness, lovingness and playfulness. This has led some mental health practitioners to suggest that the drug could be used to promote intimacy among people who have difficulty feeling close to others. It could be used, for example, to treat social and empathy disorders. Or even as part of relationship counselling. And recently, the U.S. FDA approved the first study of ecstasy-assisted therapy for adult autistic patients. The drug could be used to help autistics overcome their social anxiety — though this has the potential to be very controversial. The risks Unfortunately, while the scale may be tipping in favor of MDMA’s safety and efficacy, there’s a tremendous amount of evidence indicating the exact opposite. In fact, some studies show that MDMA produces the exact same effects its promoters are trying to counter. For example, studies have shown that ecstasy users have increased levels of serotonin-2A receptors, and that higher lifetime use of the drug (taken at higher doses) correlate with higher serotonin receptor levels (which can lead to depression). These findings are consistent with experiments on animals, in which receptor levels have increased to compensate for the loss of serotonin. Researchers have also found that ecstasy increases brain activation in those areas associated with visual processing, suggesting a loss in brain efficiency. MDMA has also been linked to sleep apnea, acute hyperthermia (the raising of core body temperature), and heart
problems like cardiac valvulopathy (more on this here and here). In terms of neurocognitive deficits and neurotoxicity, the data is conflicting. One review has shown that MDMA use can cause a number of neurocognitive deficits, including in attention/information processing speed and episodic memory. It’s interesting to note, however, that, “To date, the neurocognitive deficits observed in MDMA users were not linked to functional deficits, such as employment status or treatment outcome.” On the other hand, some studies have shown that no cognitive impairment arises from ecstasy use — at least if there’s minimal exposure to other drugs. This study concluded the same thing. But in response to that last one, Andrew Parrott noted that, “MDMA is clearly damaging to humans, with extensive empirical data for both structural and functional deficits.” This is clearly an area that needs more work. Because if proven safe and effective, MDMA could become an integral part of many different types of behavioral therapies. In the meantime, psychiatrists should consider the well-being of their patients. People suffering from debilitating anxiety, whether it be caused by PTSD or the threat of a terminal illness, may benefit greatly from MDMA’s effects. io9 dives deep into the history of MDMA in therapeutic contexts, focusing on the explosion of research into new treatment methods for PTSD, depression, anxiety, and social anxiety for autistic adults using MDMA as part of therapy.