Depression is the leading psychiatric disorder globally, causing significant personal and economic burden. While over 30 FDA-approved antidepressants exist, a systematic review and meta-analysis of 22 antidepressants found they are only modestly more effective than placebo in adults with major depressive disorder and come with many side effects. Because of this therapeutic gap, the hallucinogens psilocybin and LSD are being reconsidered as potential medications decades after their use was discontinued.
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.