Psychedelic Drugs for Mental Illness: A Scientific Guide

HBR

While the research on psychedelic medicine for mental illness is still considered new and emerging, some studies have shown compelling results.

Psilocybin

In one study published in 2023 that involved a randomized placebo-controlled trial, participants who received a single dose of psilocybin saw a rapid and sustained reduction in major depressive disorder symptoms when compared to a placebo. Participants in both the psilocybin and placebo groups also received psychological support as part of the trial. Additionally, no trial participants experienced serious adverse events as a result of psilocybin treatment. Based on the results, the researchers remarked that psilocybin showed promise as a treatment for depression when used in conjunction with psychological support.

Psilocybin also has potential as a safe and effective treatment for treating mental health conditions among those with life-threatening diseases. In a small study published in 2023, cancer patients with major depressive disorder received a single dose of psilocybin as well as individual and group therapy before, during, and after dosing. As a result, 80 percent of patients saw some form of sustained response to psilocybin treatment, and 50 percent showed full remission of depressive symptoms for at least eight weeks after dosing. There were no serious adverse events related to treatment.

In addition, the National Cancer Institute has several ongoing clinical trials to explore the safety and efficacy of psilocybin treatment for mental health conditions in cancer patients.

According to a double-blind randomized clinical trial published in 2022, psilocybin may be effective at treating alcohol use disorder when used in conjunction with psychotherapy. The researchers found that those who received psilocybin reported a smaller percentage of heavy drinking days after treatment compared to those who received a placebo.

LSD

LSD-assisted psychotherapy — meaning a combined intervention of therapy and medication — may lessen feelings of anxiety among people with life-threatening illnesses who are anxious about their illnesses, according to a small study with 12 participants. Follow-up research with participants one year after treatment found that those decreases in anxiety had lasted.

A review of 11 randomized-controlled clinical trials found that LSD has therapeutic potential, especially in the short term, to reduce symptoms of alcohol use disorder, anxiety, depression, and other psychosomatic diseases. Most of the studies focused on alcohol use disorder, and that is where researchers reported the greatest positive effects of LSD treatment.

Ketamine and Esketamine

Research published in 2023 on the long-term safety and efficacy of esketamine nasal spray found that participants’ scores on a common depression symptom rating scale decreased by an average of 12.8 points after four weeks of treatment. (The average depression rating at the beginning of the study was a little less than 30 points.) After almost four years of treatment, this average decrease in symptom severity was maintained, with about 46 percent of patients in remission. Throughout the study, participants were also prescribed an antidepressant medication.

And in a study published in 2022, researchers found that among 537 people who received intravenous ketamine therapy in a clinical setting between 2016 and 2020, more than half experienced improvement in their symptoms, and nearly 30 percent achieved remission. And 73 percent of people with suicidal thoughts and behaviors saw a decrease in these symptoms. The researchers noted that 8 percent of people experienced worsened depression after starting ketamine therapy, and 6 percent reported increased suicidal thoughts or behaviors.

MDMA

Some of the most compelling results for MDMA as a treatment for mental illness have come from clinical trials involving people with PTSD. A randomized, placebo-controlled trial published in 2023 studied 104 participants with moderate or severe PTSD for three treatment sessions over 18 weeks. It found that 71 percent of those who received MDMA-assisted therapy no longer met common diagnostic criteria for PTSD at the end of treatment compared to 48 percent of those who received a placebo in conjunction with therapy. In addition, 46 percent of those who received MDMA achieved remission compared to 21 percent of the placebo group.

That said, almost all participants in both groups experienced at least some adverse side effects, the most common of which were muscle tightness, nausea, decreased appetite, and excessive sweating. About 9 percent of the MDMA group and 4 percent of the placebo group experienced a severe adverse event due to treatment (defined as being unable to perform normal daily activity). No recorded adverse event was life-threatening or required inpatient hospitalization.

Supportive Therapy Is Essential, Too

Although the research on psychedelic medicine is promising, it’s important to note that these studies involved very careful administration of these drugs in a clinical setting under the supervision of doctors. Currently available research consists of very small, short-term studies, many of which are performed in specific groups of patients (such as people with life-threatening illnesses, for instance). This means that the findings from these studies may not apply to everyone being considered for psychedelic therapies.

In addition, most studies also included supportive care in the form of psychotherapy.

“For clinical indications, psychotherapy appears to be necessary to support and facilitate change,” says Danovitch.

He adds that therapy protocols typically involve the following phases:

  • Assessment Phase During this phase, a mental health professional and the patient set goals for therapy.
  • Preparation Phase This phase is intended to get patients physically and emotionally ready for treatment.
  • Experience Phase During this phase, health professionals monitor patients carefully as they take the medication.
  • Integration Phase This phase focuses on helping patients reflect and learn from the experience after treatment with the psychedelic has ended.

O’Donnell says this type of support, including preparing the patient for what will happen when taking the medication, is vital for successful treatment.

“If someone has no idea what they’re in for and someone gives them a psychedelic, that can be a really traumatic experience,” O’Donnell says. “A lot of people have the idea that it’s a one-and-done and your life is transformed forever, and that’s really not the case. That takes it out of the context of a therapeutic relationship, which is so important.”

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