A fast-acting psychedelic shows promise for postpartum depression

A single day of treatment with an inhaled psychedelic compound called mebufotenin helped relieve symptoms of postpartum depression in a small trial of new mothers. Within two hours of receiving the therapy, patients experienced a near-total reduction in depressive symptoms that lasted for the weeklong duration of the study. The research was published in The Journal of Clinical Psychiatry.

Postpartum depression is a severe mood disorder affecting women after giving birth. Symptoms often include extreme sadness, anxiety, changes in sleeping and eating habits, and difficulty bonding with the newborn. The condition affects up to one in five mothers globally. If left untreated, it can cause long-lasting harm to the psychological well-being of the mother and the cognitive development of the child.

Standard antidepressant pills, such as selective serotonin reuptake inhibitors, often take four to six weeks to begin working. They can also cause persistent side effects like weight gain, nausea, and sexual dysfunction. The only medication specifically approved by the United States Food and Drug Administration for postpartum depression is zuranolone. This oral medication works faster than standard antidepressants but still requires a fourteen-day daily regimen and comes with warnings about drowsiness.

Medical researchers are exploring psychoactive compounds as potential alternatives for rapid relief. Mebufotenin, also known as 5-MeO-DMT, is a potent psychedelic molecule that acts directly on the brain’s serotonin receptors. Serotonin is a chemical messenger that helps regulate mood, sleep, and digestion. In previous early-stage trials, inhaling a synthetic version of mebufotenin called GH001 produced extremely fast antidepressant effects in people with treatment-resistant depression.

Lead authors Martin Johnson of St. Pancras Clinical Research and Kristina M. Deligiannidis of the Feinstein Institutes for Medical Research wanted to test if this formulation could safely help mothers experiencing severe postpartum depression. They organized a clinical trial to evaluate the compound’s safety, side effects, and impact on maternal functioning. The trial was funded by GH Research, the company developing the drug.

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The researchers enrolled ten women between the ages of eighteen and forty-five. All the participants had a confirmed diagnosis of major depressive disorder that began shortly before or after giving birth. The mothers had to be at least four weeks postpartum to participate. To qualify, the women had to score at least twenty-eight on a standard questionnaire used to measure depression severity, which indicates moderate to severe depression.

On the day of the treatment, the researchers administered the drug using a specialized vaporization system. The patients inhaled the medication from a collected balloon. The dosing was individualized for each patient based on how they responded to the drug.

Participants received an initial six-milligram dose of the compound. If they tolerated it well but did not achieve an intense psychoactive peak experience, the medical team gave them a higher twelve-milligram dose one hour later. A third dose of eighteen milligrams was given an hour after that if the intense psychedelic effects were still not reached.

The researchers used a specialized scale to determine if a patient had reached a peak experience. This assessment measured the overall intensity of the psychoactive effects, any feelings of a loss of control, and how profound the experience felt to the patient. Once a patient reached a high score on this assessment, the medical team stopped administering further doses.

The researchers monitored the patients’ vital signs, psychiatric symptoms, and overall comfort during the treatment day. Because mebufotenin acts very quickly in the brain, the psychedelic effects lasted an average of about twenty to twenty-five minutes per dose. The trial required patients to have a trusted caregiver at home to look after their infant while they participated.

The primary goal was to see how the patients’ depression scores changed from the beginning of the study to day eight. The researchers also measured depression scores two hours after the final dose and on day two. Four of the women were lactating, so the team tested their breast milk to see how quickly the drug was eliminated from their bodies.

The results of this small study showed immediate reductions in depression scores. Two hours after the final dose, all ten patients saw a reduction in symptoms of at least fifty percent. By day eight, the average depression score dropped by about ninety-six percent. Every single participant reached full remission, meaning they no longer met the clinical criteria for depression.

The patients also reported major improvements in maternal functioning. By day eight, their scores on a questionnaire assessing psychological well-being, self-care, and mother-child interaction increased by about fifty-six percent. These gains were observed across almost all areas of maternal behavior measured by the researchers.

The inhaled medication was well tolerated by the participants. No serious adverse events occurred. The most common side effect was a mild to moderate headache, which affected half of the women. Unlike some other depression medications, the treatment did not cause lingering sedation, allowing all patients to go home on the same day.

The breast milk analysis for the lactating mothers showed that the drug and its byproducts were eliminated from their systems very quickly. The chemical traces peaked around one hour after the final dose and fell below detectable levels by about ten hours. This suggests that mothers might only need to pause breastfeeding for a brief window on the day of treatment.

As an open-label trial, both the patients and the researchers knew that the active drug was being administered. There was no placebo group for comparison. This design makes it impossible to rule out the placebo effect, where a patient’s expectation of getting better influences their actual symptoms.

The sample size of ten patients is quite small, and the group lacked demographic diversity. Nine of the ten participants were white. Almost none of the patients were taking other psychiatric medications during the trial. The results might not represent how the broader, more diverse population of mothers with postpartum depression would respond to the drug.

The study only tracked the women for one week after the treatment. This short timeframe leaves unanswered questions about how long the antidepressant effects might last. Future studies will need to follow patients over several months to see if the depression returns or if additional doses are required.

Later stages of research will involve larger groups of patients who are randomly assigned to receive either the active drug or a placebo. Those trials will be necessary to confirm the safety profile and to verify that the drug itself is directly responsible for the rapid relief of symptoms.

The study, “Inhaled Mebufotenin (GH001) for Adult Patients With Postpartum Depression: A Phase 2a Open-Label Clinical Trial,” was authored by Martin Johnson, Pau Aceves Baldo, Emilio Arbe, Brian Brennan, Sem E. Cohen, Kelly Doolin, William Gann, David Gregory, Sarah Keady, Katerina Kriger, Rachael MacIsaac, Stuart Ratcliffe, David R. Rubinow, Claus Bo Svendsen, Theis H. Terwey, Dan Tully, Velichka Valcheva, Jasper B. Zantvoord, and Kristina M. Deligiannidis.