Severe depression eased by single dose of synthetic ‘magic mushroom,’ study finds
The randomized, double-blind clinical trial, which authors called “the largest of its kind,” compared results of a 25-milligram dose to a 10-milligram and 1-milligram dose of a synthetic psilocybin, COMP360, that was administered in the presence of trained therapists.
Results of the study, published Wednesday in The New England Journal of Medicine, found “an immediate, fast, rapid-acting, sustained response to 25 milligrams (of COMP360),” said study coauthor Dr. Guy Goodwin, a professor emeritus of psychiatry at the University of Oxford in the United Kingdom.
“This drug can be extracted from magic mushrooms, but that is not the way our compound is generated. It’s synthesized in a purely chemical process to produce a crystalline form,” said Goodwin, who is the chief medical officer of COMPASS Pathways, the company that manufactures COMP360 and conducted the study.
Experts in the field found the study findings promising.
“They clearly found a dose effect and clinically meaningful improvement in just three weeks,” said Dr. Matthew Johnson, a professor in psychedelics and consciousness at Johns Hopkins Medicine in Baltimore. He was not involved in the new study.
“If you were in the 25-milligram group, you were nearly three times as likely to respond than if you were in the 1-milligram group,” said Johnson, who coauthored safety guidelines for psychedelic research in 2008.
The rapid response to treatment was notable as well.
“The maximum effect (was) seen the day after receiving the treatment. This contrasts with standard antidepressants, which take several weeks to reach maximum effect,” said Dr. Anthony Cleare, a professor of psychopharmacology and affective disorders at King’s College London, in a statement. He was not involved in the study.
However, there are a number of issues that need further study before this drug would be available for clinical use, experts said.
“The effects did start to wear off by three months, and we need to know how best to prevent the depression returning,” Cleare said, adding that not enough is yet known about potential side effects.
“While the safety profile seems encouraging overall, great care is obviously needed when using psychoactive substances such as psilocybin. Larger studies are on the way that we hope will help answer these issues,” he said.
The clinical trial occurred at 22 sites in the United States, Canada, the UK and seven countries in Europe. The study was designed to test the safety of different dosages of the proprietary version of psilocybin.
The 233 study participants had treatment-resistant depression, which can only be diagnosed after a person fails to respond to two courses of antidepressants. Of the 9 million people in the US with medically treated depression, 3 million patients are resistant to treatment, studies have estimated. Globally, some 100 million people have treatment-resistant depression, Goodwin said.
People with the condition are at a high risk of physical illness, disability, hospitalization and suicide, the study said.
Any study participants on antidepressants were required to wean themselves from those medications prior to the start of the trial. Psychedelic treatment doesn’t work on people who are actively taking antidepressants — the receptors where psychedelics attach in the brain are already flooded with serotonin from their current mood-altering drugs.
“Participants were requested to remain off antidepressant treatment during the first 3 weeks after the trial-drug administration; however, these medications could be started at any time during the trial if deemed clinically necessary by a physician investigator,” the study said.
Depression severity for each person was assessed the day before treatment using a psychological scale widely used by clinicians. Counselors trained to offer psychological support were present during the psychedelic trips, which lasted between six and eight hours. Participants were also given two more therapy sessions in the first week, the study said.
Depression levels were documented the day after the “trip” and another five times over a 12-week period. About 37% of people who took the 25-milligram dose showed improvement. In fact, 29% were considered to be in remission at week three, the study found.
By week 12, however, the positive impact on depressive symptoms had waned and no longer reached a level of statistical significance, the study found.
“The incidence of sustained response at week 12 was 20% in the 25-mg group, 5% in the 10-mg group, and 10% in the 1-mg group,” wrote psychobiologist Dr. Bertha Madras, director of the laboratory of addiction neurobiology at Harvard Medical School’s McLean Hospital in Belmont, Massachusetts, in an accompanying editorial. She did not participate in the study.
“This is not a spectacular response rate for a psychiatric treatment … and we would only expect this to worsen over a longer follow-up period,” said Dr. Ravi Das, an associate professor of educational psychology research methods and statistics at University College London via email. He who was not involved with the study.
In addition, “there were an uneven number of severely depressed patients in each group; with significantly fewer severely depressed people in the apparent ‘effective’ (25mg) dose group,” Das said in a statement. “This does not appear to be acknowledged in the paper.”
Headache, nausea, fatigue and dizziness plagued 77% of the study participants and occurred at all dosage levels, which experts say is a typical response on the day of psilocybin administration.
A small number of people in all three dosage groups experienced suicidal thoughts or injured themselves over the 12-week follow-up period, the study found. Within the first three weeks alone, two people in the 25-milligram group thought about suicide and two intentionally injured themselves. Two people in the 10-milligram group were suicidal, one self-injured and one was hospitalized for severe depression, the study reported.
Those behaviors are “common in treatment-resistant depression studies — most cases occurred more than a week after the COMP360 psilocybin session,” the company said.
“Remember that this is in people who were assessed not to be at significant risk of suicide when they entered the trial. The numbers were fairly small, but this is something that will need to be taken carefully into account in any later-stage trials,” said Kevin McConway, professor emeritus of applied statistics at The Open University, a British public research university.
The study results are promising, but many questions remain and it’s unknown if this drug would be successful for different types of depression, said McConway, who was not involved in the study.
“They can’t tell us how effective this psilocybin plus therapy treatment is in comparison with other existing drug or non-drug treatments for depression,” said McConway, noting that as a next step for follow-up trials.
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Physical activity strengthens your cardiovascular and musculoskeletal systems and can improve your mood, and relieve depression. It also boosts the quality of your sleep, increasing energy levels. Those who exercise regularly have a reduced risk of common cancers, including breast and colon cancer.
Swimming provides the benefits of physical activity while putting less stress on your joints. This activity works your major muscle groups, and because it is a low-impact form of exercise, those with arthritis or joint pain may want to make swimming their workout of choice.
In a 2022 study of adults with lower back pain, participants who completed a three-month aquatic exercise program reported less pain and a better quality of life than those who completed a standard physical therapy regimen. These long-term benefits lasted up to a year.
Dolphin Pools compiled a list of ways swimming as exercise can improve overall health. Read on to learn more about this activity's benefits on your mind and body.
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Swimming can help lower your cholesterol and blood sugar (glucose) levels, reduce your blood pressure, and burn fat—measurements that provide insight into your health.
In a small study published in 2021, a 16-week regimen of swimming for two hours three times per week improved metabolic syndrome risk factors in adults with Type 2 diabetes and hypertension. The participants in the swimming group had significant improvement after 16 weeks in their total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and blood glucose levels compared to those in the control group, who maintained their regular lifestyle. The swimming group also lowered their systolic and diastolic blood pressure, body mass index, and percentage of body fat at the end of the study period.
In another small study conducted in 1997, previously sedentary men and women with mild to moderate hypertension participated in a swimming program, which resulted in participants showing a lower resting heart rate and lower systolic blood pressure at the end of 10 weeks. No changes in resting heart rate or blood pressure were seen in the control group, who did not exercise.
Swimming is a cardio workout that raises your heart rate, improves circulation, and strengthens your heart muscle.
In a 2017 study that followed participants for 20 years, those who swam regularly lowered their risk of death from cardiovascular disease by 41%. And because your body is horizontal in the water, more blood flows back to your heart when you swim, rather than pooling in your legs as it does during land-based forms of cardio exercise.
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Swimming is a low-impact way to work all your major muscle groups. However, it is important to use the most comfortable swimming stroke for your joints.
For example, if you have arthritis in your knees or hips, you might be more comfortable swimming freestyle because you keep your legs relatively straight while swimming freestyle. A stroke such as the breaststroke, where your knees are bent and you kick outward, might be uncomfortable and aggravate any pain you already feel in these joints.
When you exercise, your brain releases endorphins, hormones that can reduce stress and anxiety and improve mood. Both anecdotal and peer-reviewed research have shown that swimming can improve depressive symptoms, mood, and overall well-being.
For example, in a 2020 study published in Lifestyle Medicine, researchers found that participants who completed 10 weeks of outdoor swimming experienced both acute and chronic positive mood increases and improved well-being compared to the control group that did not swim. Similarly, in a case study published in 2018 in the British Medical Journal, a 24-year-old woman with major depressive disorder and anxiety reported a significantly improved mood after a weekly session of cold water swimming—along with a gradual and lasting improvement in depressive symptoms.
More research needs to be done to explain the exact mechanisms that make swimming effective in improving mood, but it's an activity worth trying, nonetheless.
Studies have shown that aerobic exercises—including swimming—can improve the quality of your sleep. Although researchers are not sure how precisely exercise improves sleep, they know that it improves how much slow-wave or deep sleep you get.
Slow-wave sleep gives your body and brain the opportunity to rejuvenate. An Australian study published in 2017 found that significantly fewer pregnant women who participated in a 17-week water exercise program reported poor-quality sleep than those who did not participate in the program.
During exercise, the pituitary gland and hypothalamus in your brain release endorphins, hormones that can improve mood. In a 1992 study, college students who did yoga or swam reported decreased feelings of tension, confusion, anger, and depression than those in the control group who attended a lecture.
The researchers said the fact that those who did yoga reported similar mood benefits as those who swam suggests that both aerobic and anaerobic exercise can benefit mood.
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In a 2016 study published in the International Journal of Aquatic Research and Education, 26 Japanese women, all over the age of 70, participated in water exercises for 60 minutes three times per week for a 12-week period.
Results demonstrated that the water exercise regimen improved functional fitness and balance measures in activities of daily living, or ADLs, which are tasks a person needs to be able to perform in order to live independently and satisfy their daily needs. Improved quality of life was attributed to an ability to perform ADLs and better exercise habits.
Physical activity benefits bone health at any age. In fact, less physical activity may increase your risk of osteoporotic fractures.
In a small Israeli study published in 2008, postmenopausal women who swam for one hour three times a week either maintained or showed an improvement in bone mineral density after seven months. However, participants in the control group, who did not exercise, showed a decline in bone density.
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Exercise can improve cognitive function and social skills and build self-esteem. One 10-week swimming program improved the swimming skills of boys with autism spectrum disorders while improving their behavior toward others. The researchers said that, based on their findings, swimming programs have the potential to help children improve their social skills.
Another study, an independent report commissioned by the U.K.'s governing body for swimming, found that children who regularly take part in swimming lessons develop social skills more quickly than those who do not.
A cardiovascular workout like swimming can improve memory by triggering transient changes in brain function. And exercising regularly over an extended period of time has cumulative effects on the size of the hippocampus, part of the brain responsible for memory processing. Exercises like swimming also improve cognitive function.
A small Tunisian study of children diagnosed with attention-deficit/hyperactivity disorder (ADHD) found that those assigned to a swimming program had improved memory, better impulse control, and a longer attention span compared to those who did not exercise. The researchers said their findings provide preliminary evidence supporting the use of recreational exercise programs as an alternative intervention for children with ADHD.
This story originally appeared on Dolphin Pools and was produced and distributed in partnership with Stacker Studio.