(CNN) -- MDMA -- the active ingredient in the banned street drug ecstasy -- is safe and enhances the treatment of post-traumatic stress disorder when administered during psychotherapy, according to a new clinical trial.
More research is needed to fully assess the drug, caution the authors of the US Food and Drug Administration-approved experiment. The study included just 26 patients, all of them veterans, firefighters and police officers who developed PTSD as a result of trauma in the line of duty.
MDMA -- or 3,4-methylenedioxymethamphetamine -- has been illegal in the United States since 1985.
"MDMA has some stimulant effects as well as psychoactive effects," said Dr. Michael C. Mithoefer, lead author of the study and a psychiatrist in the department of psychiatry and behavioral sciences at the Medical University of South Carolina.
The drug is sometimes described as an "empathogen" or "entactogen," he added, because it "rarely causes hallucinations or disorientation and tends to increase feelings of empathy and trust and increased awareness of inner experience."
"We obtained FDA approval for our first clinical trial in 2001," Mithoefer said. "We began our first phase two clinical trial here in Charleston in 2004 treating mostly crime-related PTSD such as childhood abuse or rape in individuals who had failed to respond to psychotherapy and medications."
Promising results from previous trials led to the new study, published Tuesday in the journal The Lancet Psychiatry, he said.
Search for new therapies
PTSD, a disorder that develops in some people who have experienced a shocking or dangerous event, affects about 8 million American in any given year.
Continuing symptoms, including flashbacks and frightening thoughts, may lead to substance abuse, unemployment, family disruption and even suicide. Existing treatments for PTSD include various forms of psychotherapy, such as exposure therapy and cognitive processing therapy, and/or prescription drugs, such as antidepressants.
Up to 72% of veterans who receive psychotherapy retain their PTSD diagnosis and frequently drop out of their treatment programs, according to a previous unrelated study.
The need for improved PTSD therapies is clear, Mithoefer and his co-authors say, adding that the "development of new treatments should address the common reasons for treatment avoidance, failure, and dropout."
The Multidisciplinary Association for Psychedelic Studies, a nonprofit research organization, funded Mithoefer's study of 22 veterans, three firefighters and one police officer, all with service-related PTSD lasting longer than six months.
"We only included people who had received prior treatment but still had clinically significant PTSD," Mithoefer said of the study, which followed the FDA's strict guidelines for a phase two trial.
All 26 participants received a course of treatment that consisted of about 13 hours of non-drug psychotherapy plus two eight-hour sessions of MDMA-assisted psychotherapy. Participants were randomly assigned to receive MDMA (orally) in one dose of either 30, 75 or 125 milligrams for each of the two MDMA-assisted psychotherapy sessions.
One month after the second MDMA session, 68% of patients in the two higher-dose groups no longer qualified for a diagnosis of PTSD, while the same was true of 29% of patients in the lowest-dose group. One year later, 67% of all participants no longer qualified for a diagnosis of PTSD, the study results indicate. Those participants who still met the criteria for PTSD experienced a reduction in symptoms, the researchers noted.
Experts disagree on findings
The most frequently reported immediate side effects of MDMA were anxiety, headache, fatigue and muscle tension. One week after treatment, some participants experienced anxiety, fatigue and insomnia. Four serious side effects were reported during the course of the study, though three of these events -- suicide ideation, major depression and appendicitis -- were not attributed to MDMA.
One participant experienced premature ventricular contractions -- extra beats in one chamber of the heart -- at the outset of the study and during the study. After an overnight stay in a hospital, the patient recovered fully, the researchers reported.
Dr. Neil Greenberg, a professor of defence mental health at King's College London, said the study may be "interesting" but does not "fundamentally change" the services offered for PTSD treatment.
Greenberg, who was not involved in the study, noted that 22 of the 26 participants had been recruited from the internet, "and one has to assume they were interested in taking a psychedelic drug." He also said that some of the participants received prior treatments that were either not evidence-based or known to be effective with PTSD; a sample "bias" such as this weakens the quality of any analysis.
Overall, he said, future research of the effects of MDMA on patients with PTSD might be watched with interest, but he does not recommend any stronger actions, "given the controversial nature of the medication, the risk of serious side effects and the small and biased sample" of participants.
But David Nutt, a professor of neuropsychopharmacology at Imperial College London, said the new study is "the biggest breakthrough in medicinal PTSD treatment for two decades" and "opens a potential new era in the treatment of PTSD."
According to Nutt, who was not involved in the study, the results suggest that "MDMA should be fast-tracked to clinical acceptance" since the evidence is now sufficient to warrant its wider use in treating PTSD.
In his own research, Nutt explored the neurological effects of MDMA in healthy participants. His work showed that MDMA "reduces fear responses, which probably explains how it works to aid psychotherapy in PTSD," he said.
Nutt will be conducting a study of MDMA in alcoholics who drink in an attempt to deal with prior trauma.
Not a 'daily drug'
MDMA was first synthesized in 1912 by a German pharmaceutical company that intended to use it as a blood clotting agent. In the 1970s, a small number of psychotherapists made use of it in couples' therapy, where it was shown to help traumatized clients address repressed emotional memories "without being overwhelmed by the negative effect that usually accompanies such memories," Nutt wrote in a report. In the 1980s, MDMA lost its legal status around the world under a United Nations agreement, having fallen into disrepute as a street drug.
However, some scientists remained convinced of its potential and persisted in their research. In the early 1990s, the FDA approved experiments in which MDMA was used as an adjunct to psychotherapy. Ongoing research in a similar vein resulted in the new study, among others, in addition to the FDA agreeing in 2017 to expedite its review of MDMA-assisted psychotherapy for PTSD.
Phase three clinical trials of MDMA-assisted psychotherapy for PTSD, involving 200 to 300 participants across 16 sites in the United States, Canada and Israel, will begin in the summer, according to Mithoefer. If these trials demonstrate sufficient efficacy and an acceptable safety profile, FDA approval of the treatment is expected by 2021.
"Unlike most other drug studies, MDMA is not being used as a daily drug," Mithoefer said. Using the drug as a catalyst to psychotherapy means it is used only a few times, at monthly intervals, which is appealing to psychiatrists, he noted. "Taking it only a few times decreases side effects compared to daily dosing," he said, and it "eliminates the possibility of abuse, since it is administered directly by the therapists."
"If it is approved by FDA for clinical use, it will likely be restricted to specialized clinics with properly trained therapists, not as a take-home medicine that people get from the pharmacy," Mithoefer said.
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