- Research has begun to examine medical uses of psilocybin mushrooms, which are hallucinogens used for recreational purposes.
- Psilocybin-assisted therapy refers to the administration of psilocybin under medical supervision for the treatment of psychiatric conditions.
- Psilocybin-assisted therapy appears to be a promising treatment for reducing moderate-severity depression.
Before discussing the study’s methods and findings, I will briefly discuss the recreational and clinical uses of psilocybin.
Uses of Psilocybin (Magic Mushrooms)
Psilocybin mushrooms, also called magic mushrooms or “shrooms,” are considered psychedelics and hallucinogens. They are typically consumed orally (e.g., raw, dried, brewed into a tea). Depending on various factors—the dosage, the strength of the mushrooms, the person’s physical and mental health, previous history of substance use, state of mind, and setting—taking this drug might be associated with different physical and psychological effects.
Neutral or positive effects may consist of sedation, relaxation, a sense of well-being, feelings of lightness or heaviness, time distortion, perceptual changes (e.g., greater sensitivity to music or light), the experience of profound insights, and mystical experiences. Negative effects may include sweating, anxiety, tremors, dangerous changes in blood pressure and heart rate, paranoia, nausea, vomiting, and disturbing hallucinations and flashbacks (occurring even days/months later). When people experience very bad reactions, like intense and terrifying hallucinations, they are said to be having a “bad trip.”
The effects of psilocybin usually begin less than an hour after consumption and can last up to six hours, and sometimes more.
Though psilocybin mushrooms are usually consumed for recreational purposes, there has been a growing interest in their use for the treatment of mental health conditions like tobacco addiction, alcohol use disorder, and especially treatment-resistant depression. The research reviewed below examined the effects of psilocybin-assisted therapy for moderate-severity depression.
Investigating Psilocybin for Depression
The investigation—a randomized, waiting-list controlled trial—was conducted in Baltimore, at the Johns Hopkins Center for Psychedelic and Consciousness Research. The characteristics of the sample: 24 participants: 16 female, 22 White; average age of 40 years with an average of 22 years of depression.
Of the 27 participants initially enrolled, 24 completed the treatments and assessments; of them, 13 had been randomly assigned to an immediate treatment group and 11 to a waitlist condition. After eight weeks, the participants in the waitlist condition received the same treatment as those in the treatment group. The waitlist condition was used as a way to control for symptom improvement unrelated to the psilocybin intervention.
The treatment lasted eight weeks and included two daylong psilocybin administrations (about 1.6 weeks apart). The doses used were 20 mg/70 kg and 30 mg/70 kg.
During these psilocybin-assisted therapy sessions, participants were instructed to lie down and try to focus on their inner experiences. Sleep masks and music were used to facilitate inward reflection.
Assessments included medical history, electrocardiogram, and blood tests. In addition, measures of personality (Personality Assessment Inventory), depression (e.g., Beck Depression Inventory II, Patient Health Questionnaire), and anxiety (e.g., Hamilton Anxiety Rating Scale) were obtained.
The main outcome measure was the GRID Hamilton Rating Scale for Depression (GRID-HAMD), which assesses different aspects of depression, like depressed mood, anxiety, guilt, sleep and appetite disturbances, and suicidal tendencies. Scores on this measure indicate the severity of depression.
A clinically significant response to psilocybin was defined as a decrease of 50% or more in GRID-HAMD scores from the baseline. Symptom remission was defined as a score of no higher than 7 (which indicates no depression). Note: Scores of 8-16 on GRID-HAMD indicate the presence of mild depression, scores of 17-23 signify moderate depression, and scores higher than 24 suggest severe depression.
Psilocybin-Assisted Therapy for Depression: Results
The average baseline GRID-HAMD score of participants in this study was 22.8 (with a 3.9 standard deviation), which suggests high moderate depression.
In the immediate treatment group, the average GRID-HAMD scores dropped from 23 to 8.0 and 8.5 (indicative of very mild depression), one and four weeks after the treatment, respectively.
The effect sizes obtained were quite large:
- Week 1 post-treatment: D = 2.5; 95% confidence interval, 1.4-3.5; P < 0.001.
- Week 4 post-treatment: D = 2.6; 95% confidence interval, 1.5-3.7; P < 0.001.
To compare, the depression scores in the waitlist condition did not change significantly from the baseline (i.e., high moderate depression).
A considerable proportion of participants in the treatment group achieved a clinically significant response: 71 percent, one week after the psilocybin session, and 71%, four weeks after the psilocybin session. In terms of the remission of depressive symptoms, the percentages were 58 percent and 54 percent, respectively.
Similar results were found using secondary outcomes (e.g., anxiety scores), showing statistically significant differences between the treatment and waitlist groups.
In summary, this study found that psilocybin-assisted therapy for depression was associated with significant and enduring antidepressant effects.
Though this was a small investigation, the effect sizes were large—more than four times the effect sizes of typical antidepressants—suggesting that psilocybin-assisted therapy for depression is an area worthy of greater research attention.
This is important because conventional treatments for depression—selective serotonin reuptake inhibitor (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and psychotherapies like cognitive behavioral therapy (CBT)—do not help all patients with depression. Indeed, treatment-resistant depression is common.
Let me end with a brief comparison of psilocybin with ketamine, a dissociative drug that, like psilocybin, is receiving research attention lately for its potential use in the management of treatment-resistant depression.
How do they compare? Not only does psilocybin have a lower addiction potential than ketamine, but psilocybin’s antidepressant effects appear to occur just as rapidly, while also lasting considerably longer.
Specifically, unlike the antidepressant effects of ketamine, which generally last less than two weeks, the antidepressant effects of psilocybin in this investigation appeared to last at least four weeks. Indeed, over 70 percent of participants were still showing a clinically significant response at that time.
The good news is that both of these drugs seem to help relieve symptoms of depression. Whether psilocybin is a better choice for other types of depression and other groups of patients, too, and whether its potential long-term benefits outweigh its risks and side effects are questions for future research.
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