Oral MDMA impairs executive function in monkeys for several days, a finding potentially relevant to human MDMA users. The cognitive deficits were reversed by inhibitors of the serotonin transporter (citalopram) and the norepinephrine transporter (desipramine), but not by a dopamine/norepinephrine transporter inhibitor (methylphenidate). MDMA also altered sleep latency. The results implicate the norepinephrine transporter and norepinephrine in MDMA-induced cognitive impairment, suggesting that serotonin deficits alone may not explain the cognitive effects. The study used cynomolgus monkeys trained in a reversal learning task and tested with oral or intramuscular MDMA, with or without transporter inhibitor pretreatments.
Ibogaine, a natural alkaloid, shows potential for treating substance use disorders, trauma, mood disorders, and suicidality, but clinical use is limited by safety concerns and regulatory barriers. Researchers are pursuing two main strategies: developing ibogaine-like compounds that keep broad effects while reducing risks, and creating selective 'bespoke' analogs targeting specific conditions like opioid use disorder, traumatic brain injury, or PTSD. The authors emphasize that the field should avoid oversimplified views that derivatives are uniformly better or interchangeable, and call for greater conceptual clarity and mechanistic humility as ibogaine-based therapies move toward regulated medical use.