Dr Doris Answers the Internet

So, remember how a couple of weeks ago a big-deal study dropped, showing that psilocybin (the stuff in 'magic mushrooms') might be effective in treating depression? (If not, here's a little thing I wrote about it along with the paper itself and other resources.) At the time, the Internet had a lot to say about it. I addressed some of the comments and questions, and then promptly forgot to post my answers.

So here they are now - a bit delayed but nonetheless still useful (I hope).

Do feel free to shoot more questions my way, I love answering the Internet about drugs and brains.

“We have a friend that uses them to self treat his drinking.” / “I have been using them to microdose and I have had really good results with my stress/depression levels.” / “I have a friend who was micro dosing to treat depression. She absolutely loved it as treatment.” / “I am never depressed , probably because of all the LSD I took in the past.”

Not so fast, the Internet. It’s important to keep in mind that there was a very specific treatment programme attached to people’s trips in this study. Patients had 

• Psychological support before, during, and after each session, including a 4-hr preparation session where they talked about their personal history and thoughts on their depression;
• A carefully curated setting with a decorated room, low lighting, a bed, and specifically selected music;
• A known quantity/quality of psilocybin;
• Two psychiatrists around at all times, who allowed for a mostly uninterrupted inner ‘journey’ but also checked in with patients’ feelings regularly;
• A chance to continue processing those feelings in follow-up calls and visits.

In short, the set & setting were carefully controlled and focused on optimising the experience – and that simply doesn’t happen by itself in other cases.

This is not to say that people’s own experiences aren’t valid or don’t get results, I’m sure they do –  but they more than likely don’t recreate the conditions of the study, so can’t really be considered treatment per se. I think it’s important to distinguish between recreational use (including self-medication) and proper clinical use, even if they can have similar results -- and that mixing them up and lumping them together is dangerous, both in terms of people’s own expectations and in terms of  the scientific legitimacy of the research. Otherwise it sounds like we’re encouraging people to find their nearest dealer and give it a go, and that can have serious repercussions for clinical advancement.

So yeah. I'm genuinely tremendously pleased for you if you've found psilocybin helpful in addressing painful/difficult/destructive issues. But let’s please not call it treatment, OK?

“Why no control group?” / “Needs a MUCH bigger sample and a control group.”

Sure does. But this is the first time in modern times that this very controversial and uncertain topic has been broached. Would YOU spend a fortune and eternity on a full-blown, highly-powered, large-scale study if you didn’t even know yet whether you’d see an effect? 

Even if your answer is yes, the reality is that funding agencies won’t – especially when the study is already incredibly expensive due to drugs licenses and permissions and brain scanning costs, and it involves a topic that has yet to gain widespread scientific & funding support.

Drug development works in increments, and this is only the very first step. The authors make a big point of emphasising that this is a very preliminary safety and feasibility trial – which is designed to answer “can we even give psilocybin to depressed patients without causing mayhem?” and, to a lesser extent, “does this even DO anything?” Ultimately of course we’re interested in the 2^nd question, but as far as the clinical trials process is concerned, we’re only after the 1^st for now – and you can do that just fine without a control group or impressive sample size.

Also, it’s quite evident that the authors are fully aware of the study’s shortcomings – just look at them bend over backwards to make sure nobody thinks they consider the results definitive, and to emphasise that they just want to get to the next level right now! (Which no funding body will pay for until they’ve shown results from the current one.)

·       “In this open-label, single-arm pilot study, we sought to examine the feasibility of administering psilocybin to patients as a prelude to a larger randomised controlled trial.”  

·       “Because this was a small-scale feasibility study with an open-label design, strong inferences cannot be made about the treatment’s therapeutic efficacy. However, the data do suggest that further research is warranted.”

·       “Key questions for future research should address why the therapeutic effect observed in the present study is so large, and if it can be replicated when tighter experimental controls are introduced”

·       “Because the treatment consisted of not just two psilocybin administrations but also psychological support before, during, and after these sessions, as well as a positive therapeutic environment for the sessions, the relative effects of these factors need to be determined, which can only be done by conducting further trials with appropriate control conditions.”

·       “That all patients showed some improvement in their depressive symptoms for up to 3 weeks after treatment could be suggestive of an expectancy bias.”

·       “Psychedelics are known to promote suggestibility, which might have further enhanced positive outcomes. Future double-blind randomised controlled trials could address the role of expectancy and suggestibility by measuring and controlling these variables.”

·       “Our findings support the feasibility of this approach, and the magnitude and duration of the post-treatment reductions in symptom severity motivate further controlled research.”

·       “A logical next step would be to carry out a placebo-controlled randomised trial.”

Personally I'm not worried that anyone is trying to pull a fast one on me with a tiny sample and poor controls. It’s not crappy science; it’s preliminary science. The hard work of getting the control studies funded and run and published and accepted by the public is now ahead.

“Why in future? They could start right now!”

Well, not really. Psilocybin right now is classified as a Schedule I drug under international conventions – meaning it has no accepted medical use and is illegal to possess and distribute. Doctors face criminal penalties for prescribing it or running sessions with patients, so until drug policies change, their hands are tied. That’s why this study is such a big deal. It’s the first step in showing that there very much IS therapeutic potential, which would justify a reclassification to a more lenient (and certainly more easily studied) category. 

But then again, science has shown this for cannabis for ages, and that’s still stubbornly kept in Schedule I, so we’ll see about the expediency of this...

“This is not a permanent solution to depression. A lot of people will have fun trying, however, during a certain amount of time.”

I don’t think we have ANY permanent solution to depression, do we? It’s a relapsing disorder - never completely disappearing is its nature. (But that doesn't mean it can't be managed.) Current antidepressant medications are certainly no permanent solution – in fact you have to be on them for weeks to even start working, and then stay on them continuously for months if not years (ideally while building coping skills through talk therapy. Talk therapy is really the most promising thing we’ve got, and psilocybin is meant to supplement it, not replace it. Plus in this study, 2 doses caused an effect that lasted for months. Seems like a much better deal to have to take a drug once every couple of months than to do continuously, no?

“These drugs cause depression in the first place”

I have never seen scientific evidence for this.

To be fair, there IS evidence that many drugs (alcohol, stimulants, opiates, for example) are linked to mental health issues, violence, impulsive behaviour, etc. But not much evidence points to psychedelics falling in that same category. In fact, a recent study showed that in terms of violent behaviour, psychedelics do not behave like other recreational drugs (see my post here for how the authors argue that hallucinogens should not be lumped in with other drugs), and this study flat-out reported NO link between psychedelics and mental illness, and indeed suggested that people who use psychedelics are psychologically better-off than those who don’t.

I'll consider the counter-evidence when I see it.

“Guessin they just figured out that weed can help with appetite loss. Crazy humans...stating the obvious!”

Aw give ‘em a break. I know that for normal people, the scientific process seems unnecessarily arduous and self-evident (and in many ways it is) – but that’s just how you build an evidence base. We can all know something collectively as a culture, but until something has been empirically tested and recorded, it simply doesn’t exist to science. Popular opinion and folk knowledge don’t count as evidence, and they shouldn’t. So you start at the beginning, and show "that" before you go on to study "how" and "why."

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There's more, I'll post that another time.