Low doses of MDMA do not appear to cause negative effects in rodent models of addiction and depression, according to new research published in Psychopharmacology. But doses higher than 3 mg/kg result in observable impairments.
MDMA (3,4-Methylenedioxymethamphetamine, also known as ecstasy) shows promise as an adjunct to psychotherapeutic treatment for conditions such as posttraumatic stress disorder. But the researchers behind the new study were concerned by the lack of dose response data, which is needed to determine which MDMA doses are both safe and effective.
“I became generally interested in psychology and neuroscience as an undergraduate. I was most interested in how the brain and behavior functioned under abnormal conditions, such as under the influence of drugs or in mental health conditions,” said study author Maddie Pantoni, a Weill Neurohub Postdoctoral Fellow in the Translational Psychedelic Research Program at UC San Francisco.
“As I dove further into my studies of psychopharmacology, more and more research came out suggesting that psychedelics may have remarkable therapeutic effects. I found it incredible that some patients who did not respond to any other traditional treatments showed dramatic improvements following psychedelic-assisted psychotherapy. I was also very drawn to the unique history and unorthodoxy of the field of psychedelic research.”
For their study, the researchers systematically examined the effects of 0.01, 0.05, 0.1, 0.5, 1, 3, and 10 mg/kg of MDMA on Pavlovian fear conditioning, additive-like behavior, and depressive-like symptoms in 184 male and female mice.
Pantoni and her team found that high doses of MDMA produced fear memory impairments and addiction-related behaviors. But these memory impairments and addiction-related behaviors were not apparent in lower doses. The researchers also observed MDMA-induced antidepressant effects at high doses but not at lower doses.
“Dose is everything,” Pantoni told PsyPost. “The dose of a drug can dramatically influence its effects on the brain and behavior. In the case of MDMA, high doses (≥ 3 mg/kg) produced adverse memory-impairing and addiction-related effects in our rodent studies, but lower doses (< 3 mg/kg) did not. Low and slow is the way to go to reduce the probability of these adverse effects.”
While animal models are an important starting point, there is still much to learn about the proper doses for humans.
“One big question is whether MDMA produces therapeutic effects (like prosocial effects) at much lower doses than this 3 mg/kg threshold,” Pantoni said. “Also, we still don’t know exactly how these findings translate to humans, including in recreational or therapeutic settings.”
“Despite the current excitement about psychedelic therapies, there is still much more to be learned, especially in regards to safety,” Pantoni added. “In the grand scheme of things, we know very little about how these drugs work and who they will be safe and beneficial for. Additional support for psychedelic research is critical!”
The study, “MDMA and memory, addiction, and depression: dose-effect analysis“, was authored by Madeline M. Pantoni, Jinah L. Kim, Kaitlin R. Van Alstyne, and Stephan G. Anagnostaras.