Novel, Fast-Acting Psychedelic May Provide New Avenue for the Treatment of Postpartum Depression

Following decades of prohibition, psychedelic drugs – often associated with 1960s counterculture – are attracting newfound attention for their potential to treat a variety of behavioral health disorders, including depression, anxiety and addiction.

Hoping to increase their therapeutic understanding of these compounds, Cleveland Clinic researchers have launched a new study to evaluate a novel, single-dose psychedelic for the treatment of postpartum depression (PPD), a serious psychological condition that afflicts as many as 1 in 7 new mothers.

Now in its second phase, the multicenter trial is focused on RE104 – a proprietary drug similar to psilocybin – for the treatment of PPD, which can cause a persistently low mood, sleep disturbances, feelings of inadequacy or guilt, and a sense of detachment from the newborn. It is not uncommon for patients to harbor feelings of self-harm (~19%) and even thoughts of infanticide.

“The birth of a new baby incites a cascade of emotional, environmental and hormonal changes, all of which can be fertile ground for depression,” explains Cleveland Clinic psychiatrist and chief investigator Brian Barnett, MD. “Unfortunately, there are a number of factors – including persistent stigma – that can stand in the way of effective treatment. Our hope is that this study will help provide a safe, alternative path forward for patients struggling with PPD.”

Importantly, he notes that PPD should be distinguished from the “baby blues,” a transient and far more common condition evidenced by frequent crying, irritability, restlessness and anxiety.

An Unmet Need

Historically, there have been few therapeutic options for new mothers with moderate or severe PPD. Although the current standard of care consists of selective serotonin reuptake inhibitors, these agents are not specifically approved for the treatment of PPD and are associated with several disadvantages, including slow response times and potential risks to breast milk production and supply.

Although newer drugs like brexanolone have been approved for the treatment of PPD, most are hindered by long administration times that may require the patient to be away from their baby for several days.

“The big advantage of psychedelics is that they work very quickly, which allows women to get back to their lives at a time when they’re needed most.” Dr. Barnett says. “Every parent wants to be on their feet when they bring a new baby home, but the potential side effects of current PPD treatments can stand between patients and their infants. We’re hopeful that the pharmacodynamic effects of RE104 will result in rapid, ongoing symptom relief after only one dose – and with no risk to the neonate.”

Most women can return to breastfeeding within 24 hours of taking the drug, Dr. Barnett says. In addition, he notes that the short duration of the psychoactive experience demands fewer healthcare resources than traditional PPD treatments, with less time required to monitor patients in the clinical setting.

Study specifics

Prior to receiving a single-dose subcutaneous injection of RE104, study participants will undergo a battery of physical and psychological tests and are given several opportunities to get to know the research team.

On dosing day, the patient will be paired with a monitor who will remain present for the duration of treatment (approximately 2 hours). After the session, the patient will be monitored for an additional 6 hours and evaluated by a psychiatrist prior to dismissal. Several follow-up visits will be scheduled over the next four weeks to measure the severity of the participant’s symptoms.

Promising future

Psychoplastogens like psylocibin work by targeting serotonin receptors within the brain, enhancing sensory input and eliciting the hallucinations and sense of connection many users report. By promoting structural and functional plasticity, psychedelics may be capable of disrupting the neural networks implicated in the development of depression.

When administered in a therapeutic setting by a trained provider, these potent agents may help relieve certain psychiatric symptoms by enabling patients “to learn new ways of interacting with the world,” Dr. Barnett says.

“Postpartum depression has not received the attention it deserves, but the medical field is beginning to sharpen its sights on the unique mental health concerns of new mothers, for whom standard therapies may be inadequate,” he adds. “We want to help these patients get back to the people and things that are most important to them, and we believe this study may be a meaningful step in the right direction.”