A recent study suggests that "ecstasy," a commonly abused psychedelic drug, may help patients with chronic post traumatic stress disorder (PTSD). Other research suggests that ketamine (an anesthetic drug with similarities to angel dust or PCP) may help patients with treatment-resistant depression. What is going on here? Are we returning to the 1960s and the heyday of the psychedelic movement?
First, it is important to realize that many therapeutic drugs can be misused as recreational drugs. Two examples are the amphetamines (which are used to treat severe ADHD) and opiates (which are used to treat pain). Drugs that influence the brain can be beneficial (but not necessarily without risks) when used for appropriate medical conditions, but they can be dangerous when abused or used recreationally. Also, the same drug can have very different effects depending on how it is administered. Certain oral amphetamine-like drugs can be helpful for ADHD, but when the same drug is dissolved and injected, it has tremendous potential for addiction and adverse effects. Similar statements can be made about various opiate pain medications. Depending on the drug, it may be difficult to determine if the overall benefit from therapeutic use outweighs the detrimental effects of recreational use.
Why is there an interest in therapeutic uses for drugs like ecstasy and ketamine? Over the last decade, there hasn't been much progress in the development of new pharmacologic approaches for psychiatric illnesses. Drug companies have been concentrating mostly on developing drugs that work in ways that are similar to currently available drugs. Thus, most "new" drugs are only slightly different from older drugs. In addition, investing money in new ideas is risky and businesses may not be willing to devote significant resources to risky ventures, especially ones that wouldn't provide significant income for a decade or longer.
Based on animal research, scientists at the National Institutes of Health (NIH) have been examining whether drugs that alter the effects of glutamate, a common and important brain neurotransmitter, have beneficial effects in psychiatric disorders. Recent efforts have focused on the effects of ketamine, a drug that works by blocking the effects of glutamate on a particular type of receptor (called the NMDA receptor). In a small study, these researchers found that ketamine may be able to relieve symptoms of depression temporarily in treatment-resistant patients. This study has lead to considerable interest and more rigorous ongoing studies. In addition, a recent report suggests that ketamine may temporarily diminish symptoms of bipolar depression.
Recently, another group of researchers, some of whom are affiliated with a non-profit organization called the Multidisciplinary Association for Psychedelic Studies (MAPS), demonstrated that MDMA (3,4-methylenedioxymethamphetamine; ecstasy) may have clinically significant beneficial effects in alleviating symptoms of PTSD when used in conjunction with psychotherapy. MAPS funded this published study. The research participants were mostly women who suffered from PTSD that developed after they were victims of violent crimes. About 40% of the volunteer participants had previous exposure to ecstasy.
What is ecstasy? It is an illicit, recreationally abused drug that is said to boost energy, increase empathy, and decrease defensiveness and aggressiveness. Research suggests that it influences the brain's serotonin system as well as the brain's oxytocin system. Oxytocin is a hormone that influences several behaviors including social bonding. There are few if any rigorous studies of the long term risks of ecstasy; most data are anecdotal or based on small numbers of subjects.
So, should the scientific community dismiss this report of ecstasy's potential use in PTSD because ecstasy is a street drug, or because one of the missions of the study's sponsor is to develop psychedelic drugs for clinical use, or because the design of the study has significant weaknesses? Or should the scientific community entertain the possibility that drugs like ecstasy may have therapeutic potential? Is there enough of a signal from this study to argue for a larger, well-designed study by clinical investigators who aren't affiliated with MAPS? We are in the midst of an explosion of veterans who are returning from several battlefronts with severe PTSD. Many of these individuals are also struggling with depression and substance abuse. Even though this pilot study involved PTSD linked to violent crimes and not to war-related trauma, would it be worthwhile to design a careful study that involves war veterans? Could it be funded by the VA or by the National Institutes of Health? If therapeutically helpful, what are the long-term risks of this agent?
How will politics play in such a discussion? Even though there is the possibility that ecstasy might benefit persons with chronic PTSD, what would the political fallout be of having federal research dollars spent on testing a recreationally abused drug in veterans suffering from severe PTSD?
Further research on ecstasy is being supported by MAPS. At what point should the results of this work trigger the interests of other scientists and how would they obtain funding to study the possibility that drugs that influence both serotonin and oxytocin may help persons with severe PTSD? Would a study of oxytocin in the treatment of PTSD be useful? How much political fallout would occur should the government decide to fund studies of ecstasy? These are interesting questions with no easy answers.
This column was co-written by Eugene Rubin MD, PhD and Charles Zorumski MD.