Magic mushrooms: A magic cure for depression?

The last few weeks have seen magic mushrooms and their potential to treat depression spotlighted in the media.

This is just another of the latest instalments highlighting the changing perception of the media (and the public) on the valid use of psychedelic substances.

The study that birthed these news-bites was conducted at the Imperial College London, in the labs of the esteemed psychedelic scientist, David Nutt and was led by his protégé; Robin Carhart-Harris. This is the same team that brought you the equally publicised cardinal LSD imaging study earlier this year.

The study is titled “Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study” and was published in The Lancet Psychiatry, one of the most revered journals in psychiatry.

Over recent years, more and more psychedelic studies are being published in high-impact journals. The esteem of the journal can imply two things to a reader:

1)           The findings of the study are novel and exciting.
2)           The wider scientific community is starting to accept the use of psychedelic drugs as medicines

About time right?

So where do mushrooms fit on the societal landscape?

Magic Mushrooms – Public Policy and Other Dissociated Realities

Although it may seem irrational to ban a naturally occurring substance, magic mushrooms, and the active ingredient psilocybin, are recognised as a Schedule 1 substance as soon as they are picked from the earth.

Schedule 1 is home to substances that: 1) have a high potential for abuse, 2) are unsafe and 3) have no medical use.

The growing and established scientific evidence does not support the scheduling of psilocybin into this category.

Not only does psilocybin hold no potential for abuse or addiction, rather if you input  the search terms ‘psilocybin’ and ‘addiction’ into a journal database, what you are likely to find are a range of pilot studies and reviews like this, and this, describing the therapeutic potential of psilocybin in treating addiction.

We failed to find any scientific evidence of harms from psilocybin when used in a safe setting. In fact, a recent study has shown that use of psilocybin is associated with reduced risk of suicide. This may be because psilocybin is able to increase positive moods, whilst stimulating spiritual experiences.

In fact a study at Jon Hopkins has shown the magnitude of a spiritual experience on psilocybin to be directly proportional to the efficacy and duration of therapeutic effect.

Suggesting that the therapeutic effect is embedded within the psychedelic experience

The range of potential medical range from not only addiction, but also in alleviating near death anxiety, the treatment of autism and now, as described in this study, to alleviate treatment-resistant depression.

None of this coming as any surprise to experienced psychonauts.

The Hype

As always, even when the media gets it right the results are distilled with that thrilling ring of hyperbole.

This particular study has spurred many mainstream media articles to publish about this study, describing how “magic mushrooms beat severe depression”.

They go on to describe how 12 patients were given magic mushrooms.

With all 12 participants showing reductions in depression after 1 week!

With “the majority still showing effects after 3 months”.

However, even as psychonauts who have experienced the anxiolytic, mood enhancing effects of psilocybin we cannot allow ourselves to succumb to the all too easy pitfall of positive bias.

We have to be careful of the hype and learn to interpret the findings for what they are.

The Study

Participants of the study show a drop in depression measured after 1 week from a single therapeutic session under the influence of a strong dose of psilocybin (25mg; see figure below taken from Carhart-Harris et al, 2016).

However, do not mistake this for clinical significance, with 8 of the 12 participants in remission after one week.

This is still a great result, considering classic antidepressants (SSRIs, eg. Zoloft, Prozac) take 2-3 weeks to exhibit therapeutic effects.

Furthermore, these effects were seen in treatment-resistant patients, meaning they showed no response to at least 2 different prior treatments.

After 3 months, 5 of the 12 participants were in remission. This is approximately equal to the effect SSRIs being used daily over the same time period.

Psilocybin exerted its therapeutic effects from a single dose. In contrast, SSRIs are prescribed for a minimum of 3-6 months and very often for years, if not decades.

Additionally, SSRIs are known to cause many undesirable side-effects.

carhart-harris (2016) psilocybin depression image high res

Figure 1. Levels of depression over time. All participants show a drop in depression one week after being treated with psilocybin, with 8 out of 12 in remission. Three months after a single dose of psilocybin, 5 of 12 participants remain in remission.

 

The Limitations

We have to be careful of positive bias when talking about psychedelics… actually, any science.

Not all articles present an overly optimistic picture, such as this article from vice, because it notes the limitations of the study as well as the realistic positive effects. This is something i have noticed many other reports have left out of their assessment. I think to gain acceptance and respect from the wider community, we have to be honest about the results. Some limitations of the current study include:

1) Sample size – There are only 12 participants. This is not enough to determine if the therapeutic effect of psilocybin is likely to be “real”. Hence, why the study is categorised as a “proof-of-concept” trial.

2) Selection bias – Only one participant had not previously used psilocybin to treat their depression. Furthermore, most participants were self-referred. This indicates they had a belief that psilocybin was likely to be beneficial, either due to previous experience, or due to expectation. Previous positive experience with psilocybin is likely to lead to a positive selection bias of psilocybin, because people who did not have success with self-treatment are unlikely to volunteer to be in the study. Furthermore, those who seek to participate are likely to have some expectation of the effect of psilocybin, leading to a stronger placebo effect.

3) Placebo effects – There was no control group, and given psilocybin has such a noticeable effect on perception and cognition, this is likely to create a large placebo effect.

 

What does this mean?

 

Given this study is so small and the effects may be attributed to placebo or selection bias, we can not conclude on the clinical significance of psilocybin for treating depression. However, the strength of the effect after only one week is quite striking, and if these effects were to be real they could revolutionise the treatment of depression. Thus, this “proof-of-concept” trial is successful in providing a rationale for a larger, double-blind, randomized, placebo-controlled study. We are quietly excited about the results, but are yet to hold judgment on the use of psilocybin as an antidepressant.