New Hope For Treatment-Resistant Severe Depression

Medical Reviewer

For those with mild to moderate depression, a standard treatment of psychotherapy combined with antidepressant medication is enough to start feeling better. It’s a different story, however, for patients who have severe depression. While they tend to be most responsive to antidepressants, a significant number still aren’t able to recover as well as some of their counterparts. And it’s when a patient fails to gain relief after two treatments or two antidepressants that they’re considered to have what’s called treatment-resistant depression. It’s estimated that roughly a million people fall into this category.

Current treatment options

All antidepressants work differently, and doses can vary - so unresponsive patients are often encouraged to try alternative approaches. For example, if one medication doesn’t work, an alternative may be prescribed and possibly augmented with others.

And when all else fails, a more invasive procedure such as electroconvulsive therapy (ECT) can be considered. ECT involves the patient being put under anesthesia so that a carefully calibrated electrical current can be passed through the brain to induce a seizure. While the treatment works much more quickly than antidepressants, it comes with some serious side effects such as headaches and memory loss.

The Magic Mushrooms study

However, the results of a newly published study in the prestigious medical journal, The Lancet, has given reason for cautious optimism. A group of resistant-depression patients in the clinical trial who were given two highly refined and controlled doses of psilocybin, the active substance in magic mushrooms, all reported a reduction of symptoms for a period of three weeks. And in the case of five other volunteers, they experienced a lift that lasted for as a long as three months.

The use of medicinal plants isn’t uncommon in modern day medicine. In fact, up to 50 percent of approved drugs between 1981 and 2010 were plant derivatives (2). However, there’s one huge caveat for anyone thinking of self-medicating themselves through using magic mushrooms: In 2011, the John Hopkins Medical Institutions reported that a single high dose of psilocybin was sufficient to bring about measurable personality changes that lasted at least a year(3).

It’s long been shown to be a potent hallucinogenic, and the researchers used extreme caution, making sure to test volunteers using low doses to assess negative reactions. The volunteers were even talked through their hallucinations in the presence of two psychiatrists in a carefully controlled environment. In each case, the psychedelic experience lasted no more than 5 hours.

The Future

Researchers are still uncertain whether the positive effects on depression came about as a result of chemical changes or from the hallucinations. More rigorous follow-up studies are needed to better examine the therapeutic potential of this approach.

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(1) Tartakovsky, M. (2015). What You Need to Know About Treatment-Resistant Depression. Psych Central. Retrieved on May 18, 2016, from

(2) Newman, D.J., Cragg, G.M. (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. Journal of Natural Products 2012 Mar 23; 75(3): 311-35

(3) Johns Hopkins Medical Institutions. "Single dose of 'magic mushrooms' hallucinogen may create lasting personality change, study suggests." ScienceDaily. ScienceDaily, 29 September 2011. <>

Dr. Jerry Kennard is a Chartered Psychologist and Associate Fellow of the British Psychological Society. Jerry's clinical background is in mental health and, most recently, higher education. He is the author of various self-help books and is co-founder of