Psilocybin compound in Hallucinogenic Magic Mushroom Relieves Depression

A small study by Johns Hopkins Medicine researchers of adults with major depressive disorder (MDD) showed that two doses of a psychedelic compound found in "magic mushrooms," when administered with supportive psychotherapy, can produce significant reductions in depressive symptoms. 24 patients diagnosed with MDD who were not using any antidepressant medications during the trial were included in the randomised, waiting list controlled clinical trial. The findings showed that psilocybin-assisted therapy contributed to changes in most patients, with remission achieved by half of the participants in the study over the four-week follow-up period.

Alan Davis, PhD, adjunct assistant professor of psychiatry and behavioural sciences at the Johns Hopkins University School of Medicine, said the size of the impact we saw was about four times greater than what clinical trials have shown with standard antidepressants on the market. Because most other depression therapies take weeks or months to function and could have adverse consequences, if these results hold up in potential placebo-controlled 'gold-standard' clinical trials, this may be a game changer. Reporting on their analysis in JAMA Psychiatry, the researchers propose that psilocybin could be beneficial in the far broader population of patients suffering from major depression than has been previously seen. Their article is titled "Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder. A Randomized Clinical Trial"

The authors wrote that "major depressive disorder (MDD) affects more than 300 million people worldwide and is a" substantial public health issue. "In the United States, over the past 12 months, nearly 10% of the adult population has been diagnosed with MDD, and the annual economic cost of MDD is estimated at $210 billion."

The researchers went on to suggest that existing drug therapies for depression have limited effectiveness and are associated with adverse side effects, which may cause patients to avoid taking them. Most of the commonly used medications, including selective serotonin reuptake inhibitors (SSRIs), raise levels of serotonin and norepinephrine brain neurotransmitters. More recently, growing evidence has indicated that through their effects on glutamate neurotransmission, newer, ketamine-like drugs have therapeutic efficacy in MDD. Ketamine, however, has a high responsibility for violence, the team pointed out, and its use can be correlated with a mild physiological risk that needs to be controlled. Much further research into drugs with rapid and sustained antidepressant effects is required, considering the public health impact of MDD. "New antidepressants with fast and lasting mood and cognitive effects could be a breakthrough in depression treatment and could possibly boost or save lives."

For several hours after ingestion, psilocybin, a compound found in magic mushrooms, induces visual and auditory hallucinations and profound changes in consciousness. Johns Hopkins Medicine researchers first reported in 2016 that psilocybin therapy in people with a life-threatening cancer diagnosis substantially relieved existential anxiety and depression under psychologically supported conditions. Combined serotonergic and glutamatergic activity is demonstrated by the drug, and early evidence of its antidepressant effects indicates the potential for psilocybin-assisted therapy as a novel approach to depression treatment, the team commented. "In addition, relative to ketamine, psilocybin has a lower liability for addiction and toxic effects and is usually not associated with long-term visual, cognitive or neurological impairment."

The team recruited 24 people with a reported long-term history of depression for the new study, most of whom had recurrent symptoms for nearly two years before enrolling in the study. The average age of the participants was 39 years; 16 women were participants. In order to ensure safe exposure to this experimental therapy, participants had to taper off their use of all other antidepressants before the study, with the aid of their personal physician.

Immediately after induction and after planning sessions, thirteen participants received psilocybin medication, and 11 participants received the same preparation and treatment after an eight-week break. The treatment consisted of two doses of psilocybin administered by two clinical monitors who gave advice and reassurance. Between August 2017 and April 2019 at the Johns Hopkins Bayview Medical Center Behavioral Biology Research Building, the doses were administered two weeks apart. Each therapy session lasted approximately five hours, in the presence of the monitors, with the client lying on a couch wearing eyeshades and headphones that played music.

The GRID-Hamilton Depression Rating Scale, a standard depression evaluation tool, was provided to all participants when they participated in the experiment, and then one week and four weeks after completion of their treatment. A score of 24 or more shows extreme depression on the scale, 17-23 shows moderate depression, 8-16 mild depression, and 7 or less no depression. At registration, participants had an average depression scale score of 23 but had an average depression scale score of 8 one week and four weeks after treatment. Most patients showed a significant decline in their symptoms following therapy, and almost half were in remission from depression during follow-up. Until undergoing the psilocybin drug, participants in the delayed group did not display reductions in their symptoms. 67 percent reported a more than 50 percent decrease in depressive symptoms at the one-week follow-up and 71 percent at the four-week follow-up for the whole group of 24 participants. Overall, 54 percent of patients were declared in remission four weeks after therapy, meaning they no longer identified as depressed.

Since there are many forms of major depressive disorders that can affect how people respond to treatment, I was surprised that most of the participants in our study considered the treatment of psilocybin to be successful,' said Roland Griffiths, PhD, Oliver Lee McCabe III Professor of Consciousness Neuropsychopharmacology at the Johns Hopkins University School of Medicine, and dire Griffiths, whose psilocybin studies began in the early 2000s, indicated that when compared with the "reactive" type of depression in patients they observed in a 2016 cancer trial, the major depression treated in the current study could have been different. He further noted that because of the much greater potential public health impact, his team was urged by public health officials to investigate the effects of psilocybin in the wider population of people with major depressive disorder.

For a year after the analysis , the researchers say they will monitor the participants to see how long the antidepressant effects of the treatment with psilocybin last, and will publish their results in a later publication. The authors concluded, "This randomised clinical trial recorded the major rapid and lasting antidepressant effects of psilocybin-assisted therapy in MDD patients." "The present study showed that psilocybin administered in the form of supportive psychotherapy (approximately 11 hours) induced large, rapid and sustained antidepressant effects. The efficacy of psilocybin therapy after a single or just a few administrations is another significant benefit over widely used antidepressants requiring regular administration."

The team agreed that their research had some drawbacks, including short-term follow-up and limited sample size, and said that more studies with broader, more diverse patient populations, longer-term follow-up, and placebo control would be needed to better investigate the safety (including psilocybin abuse potential, suicide risk, and psychosis emergence) and efficacy of psilocybin. They nonetheless wrote. These data extend the results of previous research involving cancer and depression patients as well as treatment-resistant depression patients by showing that psilocybin could be beneficial in the much larger MDD population. Additional studies with active treatment or placebo controls and in larger and more diverse populations are required.