Psychedelics are powerful substances that alter perception, mood, and cognition. Psychedelic use has been a part of human history for thousands of years – for both spiritual and recreational practices – and they have been the focus of intense debate. Now, psychedelic drugs – once the symbol of a 1960s subculture – are being evaluated to treat depression.

A new study, published in Lancet Psychiatry, reports a small trial of psilocybin (a psychedelic substance naturally found in some mushroom species) for treatment-resistant depression. A total of 12 patients with moderate to severe unipolar depression received 2 doses of psilocybin 1 week apart along with psychological support. (A 10-mg dose was given as a test dose and a 25-mg dose was given as the therapeutic dose 7 days later.) The patients had experienced symptoms of depression for an average of nearly 18 years that had not responded to traditional therapies. Symptoms of depression were improved at 1 week and 3 months after psilocybin administration with no unexpected adverse events. Anxiety and anhedonia also improved.

The patients (6 men and 6 women) received each psilocybin dose while resting in a relaxation-inducing treatment room. Two psychiatrists were present in the room during the entire process. The onset of the acute psychedelic effects was between 30 and 60 minutes and the peak was approximately 2 to 3 hours after the dose. The drug was undetectable after 6 hours, and the patients were released at this time. Symptoms were assessed with the 16-item quick inventory of depressive symptoms from 1 week to 3 months after high-dose treatment.

There was no control group in this study, and the patients who participated knew they would be taking the psychedelic. Most of the patients were actively seeking treatment for their depression and 5 of the 12 patients had used psilocybin in the past. All of these factors could have influenced the positive findings.

Overall, the drug was well tolerated, with no serious or unexpected adverse effects; confusion and thought disorders were the most common effects. Some patients experienced nausea and headache. All of the side effects were short-lived and – in the opinion of the participants and researchers – paled in comparison to the long-lived benefits. The single, moderate, but therapeutic, dose of psilocybin had a 3-month antidepressant effect. In fact, the depression symptom scores 1 week after the first low dose of psilocybin were also decreased, suggesting that high-dose therapy may not be required to achieve benefits.

Psilocybin is a serotonin receptor agonist that targets the same pathway that existing antidepressants do, though through a different mechanism. Psilocybin shifts emotional biases away from negative and toward positive stimuli, partly through reductions in activity in the amygdala. Several studies have evaluated the use of the compound for cancer-related stress, end-of-life anxiety, obsessive compulsive disorder, and smoking and alcohol dependence.

Supporters of the new research proclaim the safety and effectiveness of psilocybin and encourage future studies with more rigorous designs. People against the use of psychedelics for medical purposes cite beliefs that psychedelics have negative impacts on mental health. However, no evidence has confirmed this, and some research actually points to decreased psychological distress and suicidal thoughts compared to users of other recreational drugs. Psychedelics, especially psilocybin, also have a low risk of dependence or compulsive use. Overall, psychedelics are considered physiologically safe. Still, any use of once primarily recreational substances in traditional medicine would face massive regulatory, practical, and criminal justice obstacles.

Depression affects nearly 7% of American adolescents and adults. Despite the plethora of drugs available to treat depression, as well as long-standing success with cognitive behavioral therapy, 20% of patients do not respond to treatment and many relapse. There is a need for new, longer-lasting therapies for depression, and psychedelics may be the door (or the looking glass) through which researchers must travel to find effective medications.

References

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Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, & Nutt DJ (2016). Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The lancet. Psychiatry PMID: 27210031

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