The science of antidepressants, is not, as it goes, an exact science. Two patients can react differently to the same drug. For some people, many of the existing drugs won’t have any effect at all.Science is still struggling to work out why certain drugs only work for certain people. According to one study from Chicago’s Northwestern University, doctors treat the causes in a crude way, with drugs “aimed at the wrong target,” often focusing on reducing stress rather than depression itself. Others have suggested that commercial interests are skewing results when antidepressants are being tested. A study in the New England Journal of Medicine found that some drug companies were selectively publishing studies on antidepressants that showed the drugs had a benefit and shelving others that showed there was no overall effect.“There are a distinct proportion of patients who don’t get better despite taking lots of different antidepressants,” says Dr Mark Bolstridge, an honorary research associate at UCL and a clinical psychiatrist. “That’s frustrating as a clinician, that even though we do have a lot of drugs at our disposal, for some people, none of them work.”Bolstridge is already in the process of searching for alternative and unusual treatments. In particular, he’s been looking into the hallucinogenic compound found within magic mushrooms: psilocybin.Bolstridge, alongside David Nutt, president of the British Neuroscience Association and former government drugs advisor, initially applied to run a psilocybin trial in 2013. Nutt had previously conducted small experiments before more stringent regulations around psychoactive substances were put into place. He felt that psilocybin had the potential to alleviate symptoms of depression and wanted to carry out further experiments.Despite getting approval and funding from the UK Medical Research Council, there remained a number of roadblocks in doing the trial, because magic mushrooms were a class A drug. “We had a lot of problems getting the drug itself, because you need a special license to be able to use it… and it had to be imported from Europe,” Bolstridge told us. “Ethics committees tend to wave things through the first time you present your case to them. We had to meet with them three of four times before they were prepared to approve our study.”He says he can see why they were met with resistance. “Your average person on the street is very sceptical of these drugs because they’re classified in the A category, which means, as far as the general person on the street is concerned, they’re dangerous, as they’re the same category as heroin and cocaine.” But the red tape comes from more than just moral panic around class A drugs. Researchers in psychiatric hospitals in the 1950s and 1960s ran many studies linking psychedelic drugs with various therapeutic effects, including the treatment of alcoholism, depression, and even autism. But many of the studies were poorly controlled and controversial, particularly when LSD was given to the children of vulnerable people. “Studies were not performed to the contemporary standard of rigor,” says Bolstridge. “The methodology was a bit suspect.”Since the 1970s, it has been very hard to get approval for LSD-based studies, but Bolstridge and colleagues were able, for the first time in decades, to run a clinical trial testing the effects of psilocybin on depression. They recruited 12 patients with a moderate to severe form of depression, and treated them in a controlled environment.Unlike many clinical trials, there was no financial incentive for partaking in the trial. Bolstridge described how people were motivated to participate by a “sheer desperation,” saying, “Some patients had been on a whole load of different antidepressants, and nothing had worked. And they were still just feeling really shitty and really low, and they weren’t functioning in life. They were severely incapacitated. They weren’t working. Their lives just hadn’t planned out as hoped, as expected.”Kirk Rutter, one of the participants in the trial, agreed to speak with us about his experiences. He told us he participated in the trial because he “thought it might help me clear the grief and get out the emotion.”After his mother’s death, Rutter suffered with ongoing depression that resisted the treatment of antidepressants and psychotherapy. He believes the drugs prescribed to him were designed to “deal with the symptoms, not the problem” and was keen to get his hands on a more effective treatment. He volunteered. After the treatment, Rutter says he felt “very, very positive. In the first week, I felt great. And then I felt like I was moving backward. It was like, Oh crap, you know, that didn’t last long”.