Will psychedelics for depression be just another false dawn?

Mind-bending street drugs are increasingly being hailed as potent antidepressants. Will they live up to the claims, ask Colin Hendrie and Alasdair Pickles
By Colin Hendrie and Alasdair Pickles

The current global crisis of depressive illness has a simple root cause: a failure of treatment. This is the result of a broken scientific process that has for nearly 70 years fallen short in delivering the drug therapies it was set up to provide.

Given existing antidepressants don’t work for many people, the excitement surrounding the development of a new class of treatments from recreational drugs such as magic mushrooms is understandable. But there are strong reasons to doubt they will have the kind of impact hoped for. Instead, we are more likely to be seeing the latest episode in a long-running saga of repeated disappointment.
Can magic mushrooms treat depression? Learn more in our expert talk at New Scientist Live

This saga began when antidepressant use became widespread in the 1950s and 1960s. It was hoped they would have the same transformative effect on mental illness that antibiotics had on non-viral infectious diseases.

As it turned out, antidepressants were only of value to some people with depression. Studies involving thousands of people with the condition reveal that the proportion seeing a clinically significant response to antidepressants is often very similar to that seen with a placebo, which is about 40 per cent. In double-blind, placebo-controlled studies, antidepressants don’t fare well.

This helps to explain why, by the end of the 20th century, Big Pharma was floundering over the development of new drugs for depression. In 2010, many companies stopped such work.
Hallucinogenic drug

Today, the observation that recreational drugs with hallucinogenic properties seem to have an effect on depression is attracting renewed optimism. Of 12 people with “treatment-resistant” depression who were given the active ingredient of magic mushrooms – psilocybin – five (42 per cent) were in remission three months later. Of 16 that were given ketamine, seven (44 per cent) were in remission six months later.

While these figures are good news for the individuals involved, they are very similar to what would be expected with a placebo. The headlines hailing a “cure” for depression could prove optimistic.

Aside from the lack of supporting evidence in double-blind, placebo-controlled studies, we also don’t know how antidepressants or psychedelics-based treatments work. The hypothesis drawn up to explain antidepressants – that they address insufficient levels of neurotransmitters called monoamines – has long lacked supporting biological evidence.

What’s more, the drug discovery process built on these foundations sought only to find variations of the first antidepressants. Given their shortcomings, this approach meant any real progress was effectively blocked.

This failed process has cost us the best part of 70 years so far. Assuming we can identify the biology behind depression, the final cost is likely to be nearer to a century, given the lead time in developing new drugs.

Policy-makers and researchers must heed the errors of the past, so that we don’t repeat them over and over again.