Could Psilocybin Be Helpful In Bipolar Depression? Is it Safe?

on November 18, 2021
Could Psilocybin Be Helpful In Bipolar Depression? Is it Safe?


Watch our recent Q&A event on psychedelics & bipolar disorder, featuring Dr. Josh Woolley.

Watch on YouTube

One of the most difficult aspects of living with bipolar disorder is the impact of depression on one’s life. While mania is often cited as the symptom that has the most destructive effects, research into the disorder has shown that depression can be as bad or worse on the day-to-day functioning for people with bipolar disorder.1 Unfortunately, treatment providers are often hesitant to prescribe antidepressant medications (such as SSRIs or tricyclics) to individuals. This is likely because they’re afraid of activating a manic episode – a phenomenon called a “Treatment Emergent Affective Switch,” or TEAS.2 Because of this medication treatment options for depression in bipolar disorder are often limited to mood stabilizers such as lithium.

Psilocybin – a breakthrough treatment of depression

A major recent development in the treatment of depression and treatment-resistant depression has been the use of psychotherapy-assisted psilocybin. Psilocybin is the active chemical in ‘magic mushrooms’ and several clinical trials have recently shown that just one high dose of psilocybin, along with a few sessions of psychotherapy in a structured setting, can have enormous benefits.3,4 In fact, the Food and Drug Administration has recently designated psilocybin as a breakthrough treatment of depression.

Given this, it would make a lot of sense if people suffering with bipolar depression were to look to psilocybin as a possible treatment option. However, up to this point, all modern clinical trials testing psilocybin have excluded individuals with bipolar disorder or individuals with a family history of bipolar disorder.

The main question is, why have researchers been so cautious to explore psilocybin as a treatment for bipolar disorder?

Surprisingly, the answer is not quite clear. Most studies refer to the exclusion of people with bipolar disorder but do not include a rationale. One reason may be related to the powerful serotonergic activation associated with psilocybin. That is, it is possible that the increased serotonin from a high dose of psilocybin could activate a TEAS, or a manic episode, in individuals with bipolar disorder. Given that people have been using psilocybin and related substances for decades and beyond, we decided to ask the question: what is the evidence for psilocybin activating mania, or a serious adverse event, in people living with bipolar disorder?

A picture of mushrooms and psilocybin

Existing evidence that psychedelics are unsafe in bipolar disorder

In a recent paper, we evaluated this question. We looked to both the existing research literature and to published case studies of adverse events. While all modern clinical trials have left out individuals with bipolar disorder, there have still been many studies in this area, and so it stands to reason that individuals who have not been diagnosed yet have been in these studies. Some researchers have looked at this.

For example, in an analysis of 227 laboratory-based psilocybin administration sessions, researchers did not find any examples of prolonged psychosis, or mania in any participant.5 Recent research since this time has also not indicated any known incidences of mania being activated in these controlled research trials. While the absence of evidence does not imply evidence of absence, this is one data point to consider.

It is also certainly the case that people with bipolar disorder (or at risk of developing bipolar disorder) have used hallucinogens recreationally. In one large-scale survey of more than 130,000 participants, researchers found that hallucinogen use (in approximately 22,000 individuals) was not a predictor for mania, psychosis, or the need for mental health treatment.6 In another large-scale survey of over 190,000 participants, individuals who had used psychedelics were at reduced odds of psychological distress and suicidality, while other recreational drug use increased these odds.7 From these and other studies, there is not a lot of evidence that (at least recreationally) psychedelics induce mania in the general population.

Dr. David E. Gard

Published case studies

Given the limited scientific data on the impact of psychedelic use for people with bipolar disorder, we decided to look at the case study research, which goes back more than 60 years. Case studies are write-ups of outcomes of individuals that researchers and clinicians put together. They are used to help clinicians and others understand things such as diagnoses, substances, interactions of the two, and more.

We carefully reviewed more than 250 published case studies where a psychedelic substance was involved. In these studies, we looked specifically for cases where individuals who had bipolar disorder took a psychedelic substance and had a bad outcome, and cases where someone took a psychedelic substance and developed symptoms of mania. We found 17 cases that met these criteria.

When we analysed these 17 cases, we discovered many themes. These included that most cases were not of people with a previous diagnosis of bipolar disorder; several involved polysubstance use; many negative outcomes occurred after repeated uses of the substance; and all but two cases were in unstructured or recreational settings. This last point is crucial, given the care and structure that is involved in modern clinical trials.

Importantly, even though these case studies have many limitations, the fact that cases were found where mania appeared after taking a psychedelic substance does highlight the need for caution in working with bipolar disorder and psychedelics.

What to make of all this?

While the broader epidemiological and other research does not imply a great deal of risk for the use of psilocybin in controlled clinical trials with bipolar disorder, our findings in the published case study literature highlight that there can and have been negative outcomes associated with bipolar disorder and psilocybin. In other words, the picture is fairly complicated and more clarity is needed.

One issue is certain–there is not a lot of research in this area and more work clearly needs to be done. Perhaps the best way to test this is through a carefully controlled prospective clinical trial. We,8 and others,9 are currently developing such a study, structured to reduce potential risks so that we can test both the safety of psilocybin in bipolar disorder and its potential effectiveness in treating bipolar depression.

More Posts About Bipolar Disorder & Magic Mushrooms
A cluster of small brownish mushrooms are in the foreground, towards the right of the image, against a purple background. In large white letters, the title of the post (written below) is shown.
Study Update: Phase 2 of the Bipolar Psilocybin Project
We have officially closed the survey and are moving forward to the next phase of the study.
A poster with a orange psychedelic-looking mushrooms against a vibrant purple background. 'Bipolar and mushrooms: helpful or not?' is written on it in big letters.
Survey Update: Risks and benefits of “magic mushrooms” in bipolar disorder
An early release of the very first study results is available in this short blog post.

Follow us on social media: