How Risky Are Psychedelics for People With Bipolar Disorder?

Disclaimer: The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Chemical Collective or any associated parties.

People with a personal or family history of bipolar disorder (a condition marked by extreme mood swings) are typically excluded from being participants in psychedelic clinical trials. While research continues to show that psychedelic therapy, such as psilocybin therapy, is helpful for depression (which is an aspect of bipolar disorder), the mania that bipolar patients experience is why they are excluded from these trials. There is a concern that psilocybin will trigger or worsen manic symptoms.

However, while this risk is present, some researchers are starting to challenge the absolute exclusion of bipolar patients from participating in psychedelic clinical trials. There is also growing evidence that psychedelics may, for some patients, help alleviate the symptoms of bipolar disorder. But a certain level of wariness is needed; this research involves controlled, supervised psychedelic sessions with trained mental health professionals present. The level of risk is different when taking psychedelics outside of this context, especially on one’s own for the purposes of self-medication.

(In the following article, ‘psychedelics’ will refer to classic psychedelics like psilocybin; there is more evidence on the efficacy and safety of using ketamine – a non-classic psychedelic – for the treatment of bipolar, although this treatment, too, is not without its risks.)

Mixed Views on Psychedelics and Bipolar Disorder in the Medical Community

Dr Bryan Roth, a pharmacology professor at the University of North Carolina at Chapel Hill, told The New York Times, “Anybody with a serious psychiatric disorder — like schizophrenia, bipolar disorder — should not take psychedelics.” This view fits in with the strict exclusion of bipolar patients from trials on psilocybin therapy. Nonetheless, the authors of a 2022 study published in the Journal of Psychopharmacology note, “The rationale for supporting these exclusions, however, is rarely provided and appears to be anecdotal as no systematic study of psychedelic use in people with BD has been reported.”

Roth, for the same piece in The New York Times, says, “I had many patients that would give me the story that they were more or less fine, they took LSD, and they’ve had schizophrenia since. My guess is they had some underlying predisposition to schizophrenia and it sort of tipped them over the edge.” Dr Charles Nemeroff, chair of the Department of Psychiatry and Behavioral Sciences at the University of Texas at Austin Dell Medical School, offers the same view: “I think the issue with these very powerful medications [psychedelics] is that there are probably people who are genetically vulnerable to a major psychiatric illness, but they haven’t reached the threshold yet. And then what these medications might do is unleash it.”

This view applies not just to those with a family history of schizophrenia but also to those who have a family history of bipolar disorder. Bipolar is frequently inherited; studies estimate that genetic factors account for 60–80% of the cause of the condition. In fact, bipolar is considered to be the most heritable mental health condition. This doesn’t mean that if one or both of your parents are diagnosed with bipolar disorder you are destined to have the condition yourself. But this does increase your genetic vulnerability to the condition. It means you stand a higher chance of developing bipolar disorder than someone without a family history of the condition.

Suppose you have a family history of bipolar disorder but haven’t yet shown symptoms of the condition. In that case, it’s possible that environmental factors (e.g. stressful life events) could trigger the onset of those symptoms. Roth and Nemeroff worry that psychedelics could be one of these triggers, thus justifying the exclusion of those with a family history of bipolar from clinical trials on psychedelics.

However, other medical professionals believe this strict view may be unjustified and unhelpful. In a 2024 paper published in Psychedelic Medicine, a group of researchers propose that there are relative risks (rather than absolute risks) when considering whether those with a family history of bipolar disorder should undergo psychedelic therapy. They write:

Balancing the need for effective treatments against the potential for serious adverse events in those undergoing psilocybin therapy with a family history of BD [bipolar disorder], we argue for caution in psychedelic clinical trials but not outright exclusion of these individuals. Our risk stratification tool allows for more nuanced inclusion and exclusion criteria.

These views matter because, along with published research, they will influence whether bipolar patients will be considered for legal, regulated psychedelic therapy in the future.

The Research on the Effects of Psychedelics on Bipolar Disorder is Mixed

When it comes to the research on how psychedelics affect people with bipolar disorder, the picture is also mixed (although this is related to the kind of study we’re looking at, i.e. whether it is a clinical trial on psychedelic therapy or survey-based data). Findings are also mixed within the same study.

For example, a web-based survey found that one-third of respondents (with a self-reported diagnosis of bipolar disorder) described new or worsened symptoms after taking psilocybin. These symptoms were mostly manic symptoms, difficulties sleeping, and anxiety. No differences in rates of adverse effects were observed in those with bipolar I disorder (cycling between mania and depression) and bipolar II disorder (cycling between hypomania – a less extreme form of mania – and depression). Nevertheless, respondents (even those who experienced adverse effects) felt that their psilocybin experiences were more helpful than harmful. The authors of the study conclude:

The subjective benefits of psilocybin use for mental health symptoms reported by survey participants encourage further investigation of psilocybin-based treatments for BD. Clinical trials should incorporate careful monitoring of symptoms, as data suggest that BD symptoms may emerge or intensify following psilocybin use.

More recent research has echoed some of these findings. In a 2024 study of adolescents, researchers found that while psychedelic use was associated with fewer psychotic symptoms, the authors observe, “Psychedelic use was significantly associated with more manic symptoms for individuals with a higher genetic vulnerability to schizophrenia or bipolar I disorder than for individuals with a lower genetic vulnerability.” This again seems to suggest that, at least in a non-clinical context, psychedelic use poses unique risks to those with diagnosed bipolar disorder or a genetic susceptibility to the condition. 

Conversely, research on the clinical use of psychedelics for bipolar offers a different perspective. A 2023 study found that a single psilocybin session, in conjunction with psychotherapy, was beneficial for patients with treatment-resistant bipolar II disorder. This condition is frequently associated with difficult-to-treat depressive episodes. After participating in this trial, “most participants met remission criteria on the Montgomery-Åsberg Depression Rating Scale 3 weeks after a single 25-mg psilocybin dose, and most remained in remission 12 weeks postdose with no increase in mania/hypomania symptoms or suicidality.”

The treatment-resistant nature of the participants’ condition means, in this context, that they had tried at least two pharmacological treatments that resulted in insufficient benefit. These medications were discontinued at least two weeks before dosing. Therapists met with the patients for three sessions before the psilocybin session; the session involved taking 25 mg of pure psilocybin (sufficient to induce a mystical experience); and there were three integration sessions with the therapists post-session. This study indicates that a strong dose of psilocybin, alongside psychological support, could be safely administered in the treatment of (at the very least) bipolar II disorder.

As we’ve already seen, bipolar II disorder involves less intense manic symptoms than bipolar I disorder. It could be that patients with the latter type of bipolar face a higher degree of risk when taking psychedelics. In this context, there could be a greater chance that the psychedelic experience will trigger or exacerbate manic symptoms.

In any case, it is likely that psychological risks are reduced in the context of psychedelic-assisted therapy, at least as it occurs in the design of a clinical trial. In the study on bipolar II disorder and psilocybin therapy, participants were able to prepare for the upcoming psychedelic session, and they had time after the session to process and make sense of what they experienced. Both of these factors act as harm-reducing and benefit-maximising strategies. They reduce the likelihood of strong negative reactions occurring and they increase the likelihood of positive effects occurring both during and after the session.

In contrast, in the survey-based studies described earlier, respondents likely lack this level of preparation and psychological support during and after the session. These factors may heighten the risk of manic symptoms developing or worsening. Additional factors like a poorly planned setting for the experience can also influence the degree of risk. As the authors of the 2023 study stress,

the present survey was not able to rule out the influence of alternative precipitating factors for adverse events, including polysubstance use, preexisting subthreshold mood elevation and set/setting. The likelihood of adverse events in a more carefully controlled clinical setting may differ from those reported in non-prescribed/recreational use.

Indeed, we don’t know if some of those with bipolar disorder who experienced adverse effects after taking psilocybin mushrooms also added other drugs into the mix. For example, while cannabis may help some people with bipolar, studies have also found an association between cannabis use and the worsening of manic symptoms in those with previously diagnosed bipolar disorder. It’s possible that mixing psychedelics with cannabis – a common drug combination – may be particularly risky for bipolar patients.

Why Would Psychedelics Increase the Risk of Developing Manic Symptoms?

The reason that psychedelics may pose a greater risk of worsening mania, but not depression, in people with bipolar disorder may be related to how these compounds affect the brain. (This is not to say that psychedelics cannot lead to, or worsen, depression for an extended period of time after the experience – because they can.) According to Robin Carhart-Harris et al.’s entropic brain hypothesis, psychedelics can be helpful for some mental health conditions but not others because they increase ‘entropy’ (a term borrowed from physics), which stands for the level of disorder/disorganisation/chaos in the brain. 

Carhart-Harris et al. characterise experiences like depression, anorexia, and OCD by low levels of entropy. In other words, they are marked by a high degree of order, which manifests as ruminative thinking, or being stuck in the same pattern of thinking. Psychedelics can be particularly helpful for people with these conditions because they create more disorganised brain activity, opening up avenues for new modes of thinking and feeling. In contrast, Carhart-Harris et al. describe psychosis as a brain state high in entropy. On the subjective level, this is associated with various symptoms of psychosis, including delusions, magical thinking, and disordered/confused thoughts and speech. Psychedelics may precipitate or worsen psychotic symptoms because of the way they further disorganise brain activity.

Mania could also be seen as a brain state high in entropy. Revisiting the entropic brain hypothesis in a later paper, Carhart-Harris states,

the hyper-flexible (instable) individual may become vulnerable to mania-related symptoms such as inappropriate elation and grandiosity. It is noteworthy that such symptoms can sometimes be seen acutely and even sub-acutely with psychedelics (e.g. see https://erowid.org/experiences/), perhaps most commonly when the experience has been poorly integrated.

Carhart-Harris, however, is referring to psychedelic users here, in general. In the case of people with a personal or family history of bipolar disorder, the risk of developing manic symptoms is higher. Carhart-Harris recognises that entropy may be elevated in manic states, which would point to the higher degree of risk faced by bipolar patients taking psychedelics. 

It’s important to underline that bipolar disorder, because of the presence of mania, can involve delusions, sometimes similar to the types that occur in schizophrenia. For example, some bipolar patients develop grandiose delusions. These involve the false belief of one’s special status, power, knowledge, or abilities – which may have religious, supernatural, or science fiction themes. They are defined by an exaggerated sense of self-importance or superiority. This type of delusion can occur during a manic episode.

People with bipolar disorder may also experience paranoid or persecutory delusions. These involve extreme levels of paranoia; they are fixed beliefs about being persecuted (e.g. by friends, strangers, demons, aliens, or intelligence agencies). Grandiose and paranoid delusions can be examples of psychotic symptoms present in bipolar disorder. (The latter condition predisposes one to psychosis.) We can characterise delusions as a high entropy state, given that they feature highly flexible (or loose) thinking. The increases in brain entropy following psychedelic use, therefore, may help explain why some bipolar patients experience new or exacerbated manic or psychotic symptoms as a result of psychedelics.

In terms of anecdotal reports, once again, we have a mixed picture. Some people living with bipolar felt that psychedelics (as well as cannabis) precipitated distressing symptoms, including psychotic symptoms, whereas others report that psychedelics led to benefits or at least didn’t worsen their symptoms. Also, many people with bipolar showed symptoms long before trying drugs, and some believe their symptoms led them to drug use (not the other way around).

Nonetheless, these contrasting reports don’t mean that anyone with bipolar has around a 50/50 chance of being helped or harmed by psychedelics. What we need is better data on the benefits and risks of psychedelics for people with a personal or family history of bipolar disorder, as well as how potential benefits and risks might change depending on the type of bipolar and the presence of other symptoms. 

In any case, the narrative surrounding psychedelics and bipolar seems to be shifting. Further research, and reports from people diagnosed with bipolar, may continue to challenge the idea that you should never use psychedelics – including in a therapeutic context – if you’ve displayed symptoms of bipolar or are predisposed to them.

Sam Woolfe | Community Blogger at Chemical Collective | www.samwoolfe.com

Sam is one of our community bloggers here at Chemical Collective. If you’re interested in joining our blogging team and getting paid to write about subjects you’re passionate about, please reach out to David via email at blog@chemical-collective.com