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A single dose of psylocibin along with psychological support proves to be a promising alternative treatment for Major Depressive Disorder according to a 2023 study, “Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial,” published in JAMA Network.

The study consisted of 104 participants with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) diagnosis of MDD. Participants had at least a 60-day diagnosis duration with moderate or greater symptom severity. Individuals who had a history of psychosis, mania, active substance abuse, active suicidal ideation with intent or suicidal behavior in the last 12 months were excluded from participating in the study. Exclusion criteria also included individuals who used a psychedelic drug at some point over the past 5 years or those who used psychedelics more than 10 times throughout the duration of their lifetime. The ages of the participants ranged from 21 to 65 years old, all of which were medically healthy adults.

Participants were divided between two groups where they would receive either a 25 mg dose of psilocybin or a placebo of 100 mg of niacin. Niacin was used as the placebo due to its ability to produce an acute physiological response that would seem similar to psilocybin. Both the psilocybin and placebo also appeared in identical capsules to avoid participants being able to detect one from the other. All doses were administered with psychological support as well. When researchers evaluated participants from baseline to day 43 (a 6-week period), they found a statistically significant reduction in depressive symptoms for those who were administered the psilocybin compared to those who received the placebo.

Improvements were seen in participants within just 8 days of receiving the single dose of psilocybin compared to those who received the placebo. The psilocybin group of participants also showed sustained improvements throughout the 6-week period. These findings suggest that a single dose of psilocybin leads to a rather quick antidepressant response and has the ability to maintain its effects in comparison to prescribed antidepressant medication. The study found no serious adverse effects from taking psilocybin for the treatment of MDD, suggesting that psilocybin seems to be a promising treatment option.

“These findings suggest that a single dose of psilocybin leads to a rather quick antidepressant response and has the ability to maintain its effects in comparison to prescribed antidepressant medication.”

Researchers used the Montgomery-Asberg Depression Rating Scale (MADRS) score to evaluate the effect each dosage had on the participants. The MADRS is a widely used clinical 10 item assessment to measure symptoms and severity of depression, focused on mood, thoughts, and physical symptoms. The 25 mg dose of psilocybin, compared to the 100 mg dose of niacin, showed a significant reduction in MADRS scores. The study further showed a reduction in Sheehan Disability Scale (SDS) scores for those who received the psilocybin treatment compared to those who received the placebo. The SDS is a short 5 item assessment that measures the functional impairment of individuals in their work, school, social, and family lives.

While prescribed anti-depressant medications have been effective in the treatment of depression for some, many do not experience the benefits without side effects, or they will experience no relief at all. Only two-thirds of those who are diagnosed with MDD and prescribed antidepressant medications see a reduction in their symptoms. New alternative interventions for the treatment of MDD are essential for finding a solution for those who have not benefited from taking prescribed anti-depressant medication. Even for those who see a benefit, it can take months of treatment before they are able to see a significant change. In these circumstances, doctors will end up attempting to prescribe additional medication in hopes of finding their MDD patients a lasting response. This causes patients to be more on more medication which could possibly lead to more unwanted side effects and possibly lead to more health complications.

“New alternative interventions for the treatment of MDD are essential for finding a solution for those who have not benefited from taking prescribed anti-depressant medication.”

When patients who were prescribed antidepressants decided to stop taking their medications, many experienced negative symptoms due to withdrawal. Unfortunately, even those who experience no reduction in their depressive symptoms when taking prescribed antidepressant medication may experience negative symptoms of withdrawals when they decide to stop the use of medication. Withdrawal symptoms can range from more physical symptoms such as dizziness, nausea, and headaches to mental health struggles such as anxiety, insomnia, and suicidal ideations. Additionally, prescription antidepressant medications may not offer a long-term solution. On average, around 50% of individuals who were taking prescribed antidepressant medication will experience a relapse within a year of remission.

Beyond the findings that the psilocybin group of participants experienced a significant reduction in depressive symptoms, the overall well-being of these participants had been positively impacted without additional negative side effects that are common for one to experience while taking prescribed antidepressant medication. Researchers measured participants using a variety of differentiation assessments such as the Clinical Global Impressions Scale, Hamilton Anxiety Rating Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, and Symptoms of Major Depressive Disorder Scale. They used the Oxford Depression Questionnaire to evaluate emotional blunting. Unlike many antidepressant medications, the use of psilocybin did not result in side effects such as emotional blunting. Emotional blunting makes it difficult for one to feel their emotions and reduces affect display. This feeling of being emotionally numb may impact an individual’s close relationships as well as their overall social and professional life. Based on the researchers’ evaluations, the psilocybin treatment resulted in less anxiety, improved functioning, and increased quality of life for participants.

“Unlike many antidepressant medications, the use of psilocybin did not result in side effects such as emotional blunting.”

It is important to note that there are potential drawbacks to this research and more studies will need to be done before utilizing psilocybin as a standard treatment for depressive symptoms in those with MDD. While psilocybin showed to have an effective antidepressant response, more studies are needed to understand the ability of the substance to have a clinically significant effect when it comes to remission of depressive symptoms. Additionally, the exclusion criteria of the study left out many people in the general population who are diagnosed with MDD. Anyone with a history of psychosis, mania, active substance abuse, or active suicidal ideation with intent were unable to participate in the study.

“Psilocybin is a promising alternative option for the treatment of individuals with a diagnosis of MDD.”

Despite the need for more research, this study demonstrated that a single 25 mg dose of psilocybin administered with psychological support may be a promising novel treatment option for MDD patients as participants showed a clinically significant decrease in depressive symptoms. Along with the reduction in symptoms, patients who were given psilocybin experienced a more sustained reduction in their depressive symptoms. Since there were no adverse side effects reported and an absence of withdrawal symptoms, psilocybin has the potential to be an even safer option for MDD patients seeking treatment. Furthermore, the rapid and sustained antidepressant response suggests that it may be more effective than prescribed antidepressant medications. Psilocybin is a promising alternative option for the treatment of individuals with a diagnosis of MDD.