New psychedelic treatment shows early promise against postpartum depression

A single day of inhaled psychedelic treatment may relieve postpartum depression symptoms, with effects lasting for a week, early research suggests.

Postpartum depression is a severe mood disorder that affects women after giving birth. Symptoms can include extreme sadness, anxiety, changes in sleep and eating habits and difficulty bonding with a baby.

The condition affects up to one in five mothers globally. If untreated, it can have lasting effects on a mother’s psychological wellbeing and a child’s cognitive development.

Standard antidepressants, including selective serotonin reuptake inhibitors, a common type of antidepressant, often take four to six weeks to start working.

They can also cause side effects including weight gain, nausea and sexual dysfunction.

The only medication specifically approved by the US Food and Drug Administration for postpartum depression is zuranolone. It works faster than standard antidepressants but requires a 14-day daily course and carries warnings about drowsiness.

Researchers are exploring psychoactive compounds as possible alternatives for faster relief.

Mebufotenin, also known as 5-MeO-DMT, is a psychedelic compound that acts on serotonin receptors in the brain. Serotonin is a chemical messenger involved in functions including mood, sleep and digestion.

Previous early-stage trials found that an inhaled synthetic formulation called GH001 produced very rapid 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 investigated whether the treatment could safely help women with severe postpartum depression.

The trial assessed its safety, side effects and impact on maternal functioning. It was funded by GH Research, the company developing the drug.

Researchers enrolled 10 women aged 18 to 45. All had major depressive disorder that began shortly before or after giving birth and were at least four weeks postpartum.

Participants also had to score at least 28 on a standard depression questionnaire, indicating moderate to severe depression.

Treatment was given on a single day using a specialised vaporisation system, with patients inhaling the medication from a collection balloon.

Doses were adjusted according to each woman’s response.

Participants first received 6mg. Those who tolerated the drug but did not experience a sufficiently intense psychoactive effect could receive 12mg one hour later, followed by 18mg after another hour if needed.

Researchers used a specialised scale to assess the intensity of the psychedelic experience, including feelings of losing control and how profound the experience felt.

Further doses were stopped once participants reached a predefined score.

Patients were monitored for changes in vital signs, psychiatric symptoms and overall comfort.

The psychedelic effects lasted for an average of around 20 to 25 minutes after each dose.

Participants also had to arrange for a trusted adult to care for their baby while they received treatment.

The main measure was the change in depression scores between the start of the study and day eight. Researchers also measured symptoms two hours after the final dose and on day two.

Four participants were lactating, allowing researchers to test their breast milk and assess how quickly the drug was eliminated from their bodies.

All 10 women experienced at least a 50 per cent reduction in depression symptoms two hours after their final dose.

By day eight, average depression scores had fallen by around 96 per cent and every participant met the study criteria for remission, meaning they no longer met the clinical threshold for depression.

Participants also reported improvements in maternal functioning.

Scores on a questionnaire assessing psychological wellbeing, self-care and mother-child interaction improved by around 56 per cent by day eight, with gains seen across almost all areas measured.

No serious adverse events were reported.

The most common side effect was mild to moderate headache, experienced by five of the 10 women.

The treatment did not cause lingering sedation and all participants were able to return home on the day they received it.

Among the four lactating women, levels of the drug and its byproducts in breast milk peaked around one hour after the final dose and fell below detectable levels after about 10 hours.

Researchers said this suggests mothers may only need to pause breastfeeding for a relatively short period on the day of treatment, although further research is needed before firm clinical recommendations can be made.

The trial was open-label, meaning both participants and researchers knew the active drug was being given.

There was no placebo comparison group, making it impossible to rule out the possibility that expectations about the treatment influenced the reported improvements.

The sample was also small and lacked demographic diversity, with nine of the 10 participants identified as white.

Almost none of the women were taking other psychiatric medications during the trial, meaning the findings may not reflect how a broader and more diverse group of mothers with postpartum depression would respond.

Researchers followed the women for only one week after treatment, leaving questions about how long the antidepressant effects may last.

Future studies will need to follow patients for several months to assess whether depression returns or additional doses are needed.

Larger trials will also need to randomly assign participants to receive either the active treatment or a placebo.

These studies will be needed to confirm the treatment’s safety and determine whether the drug itself is responsible for the rapid reduction in symptoms.