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The Current Research on Psychedelics & Bipolar Disorder

Ever wake up some days just not feeling it? Or perhaps you can recall a time you’ve sprung out of bed, ready to take on the day, only to have your mood ruined by coffee-stained jeans? Or is that just me? 

Everyday we experience a range of thoughts, feelings, and emotions– all of which play important roles in our cinematic perception of life. Sometimes these emotions can be fleeting, and other times they can linger. When a feeling persists, this is often referred to as mood

Mood acts as a filtering effect on our internal experience, as well as our external behavior. Extreme polarities in emotions, with rapid shifts from severe lows or to extreme highs, are markers for diagnosing mood disorders.  

For those experiencing severe lows, such as depression, psychedelic-assisted therapy is emerging as a novel treatment. Psychedelics are serotonergic, meaning they help produce serotonin in the brain, helping to elevate mood. 

So what happens when our moods fluctuate so quickly and intensely? In many cases, these drastic variations in mood are functions of bipolar disorder (BD). Can psychedelics have therapeutic effects on BD? Do psychedelics interact with the bipolar brain differently than they do with healthy brains? 

In today’s article, we’ll be discussing exactly what BD is, the various types of BD, along with the current treatments available. Those with BD are often excluded from clinical trials with psychedelics, so definitive claims about how psychedelics work in the bipolar brain cannot be made. 

That being said, we will be providing a hypothesized framework to investigate how psychedelics may work in the bipolar brain, and how psychedelic-assisted therapy may benefit or harm people with BD. To do this, we’ll review the neurological abnormalities in the bipolar brain, then cross reference that with research on how psychedelics act in those parts of the brain. 

Although clinical studies are limited, reviews of individual case studies can provide vital information– much of which we will be presenting in this article. We’ll also review anecdotal reports submitted by Psychedelic Passage survey respondents who have BD and have used psychedelics. 

Lastly, we will discuss the potential contraindications of bipolar disorder and psychedelics, and what should be considered when taking these substances. 

DISCLAIMER: We are not medical professionals, this article is only for harm reduction purposes. Please consult a medical professional when considering the use of psychedelics.

What is Bipolar Disorder?

Bipolar disorder is a mental illness that results in atypical changes in mood, concentration, energy, and activity levels, as well as the ability to complete daily tasks.

Different from the normal changes in mood, the symptoms of bipolar disorder are severe. Untreated bipolar disorder can result in poor job or school performance, damaged relationships, and even severe cases, suicide.  

Within the diagnosis of bipolar disorder, there are three categories; Bipolar I, Bipolar II, and Cyclothymic Disorder (also referred to as Cyclothymia). Sometimes an individual may experience symptoms of bipolar disorder that do not necessarily fall into one of these categories, in which case the diagnosis is deemed as “other specified and unspecified bipolar and related disorders” or (BP-NOS). 

Within a diagnosis of BD, individuals may experience Rapid Cycling Bipolar Disorder (RCBD), which is defined as four or more affective episodes (depression, mania or hypomania) within 1 year. 

RCBD has a high point of prevalence (from 10% to 20% among clinical bipolar samples) and is associated with greater severity, longer illness duration, worse global functioning and higher suicidal risk, but there is no current consensus on treatment option (Bourla et al., 2022).

The unifying factor though for all of these disorders is that they involve irregular changes in mood. Someone with bipolar disorder may experience extremely elevated moods, feeling elated, energized, or more irritable– manic or hypomanic episodes, coupled with rapid shifts to extremely depressed, sad, or hopeless periods– depressive episodes. 

What differentiates one diagnosis from another is the duration and intensity of mood shifts. Bipolar I Disorder is defined by manic episodes that last at least 7 days (most of the day, nearly every day) or by manic symptoms that are so severe that the person requires immediate hospital care. Usually, depressive episodes occur as well, typically lasting at least two weeks. 

Bipolar II Disorder is defined by a pattern of depressive episodes and hypomanic episodes, but the episodes are less severe than the manic episodes in Bipolar I Disorder. 

Cyclothymia is defined by recurrent hypomanic and depressive symptoms that are not intense enough or do not last long enough to qualify as hypomanic or depressive episodes, but persist for at least two years.

Bipolar disorder also has a high comorbidity rate, meaning that many people with BD also have other mental disorders or conditions such as anxiety, attention-deficit/hyperactivity disorder (ADHD), eating disorders, and others. 

Sometimes people who have severe manic or depressive episodes also have symptoms of psychosis, such as hallucinations or delusions, that tend to associate with the person’s extreme mood.

The Current Treatments For Bipolar Disorder

Typically diagnosed during early adulthood, bipolar disorder can be chronic (persistent or constantly recurring) or episodic (occurring occasionally and at irregular intervals), and usually requires lifelong treatment. 

Although the exact cause of bipolar disorder is still unknown, there is research being conducted regarding genetics, brain structure, nutrition, and the role of the gut-brain connection, along with many more aspects that may play a part in the development of the disorder. 

Bipolar disorder, like any mental illness, is uniquely experienced by each individual- with specific symptoms, their own goals, needs, abilities, and limitations regarding care. Thus, treatment must be specialized for each individual. 

That being said, treatment of bipolar disorder conventionally focuses on acute stabilization, in which the goal is to bring a patient to a sense of balance and mood stability, prevent relapse, reduce symptoms and enhance overall functioning. Bipolar disorder is typically treated with a combination of psychosocial treatments and therapies along with pharmacotherapy. 

Psychosocial treatments are based on the idea that psychosocial stressors, such as negative life occurrences, family distress, accelerated goal attainment, and events that disrupt sleep cycles, are associated with relapses and worsening symptomatic states. 

The main goal of psychotherapy treatment for bipolar disorder is to educate patients, and caregivers whenever possible, regarding strategies for stress management, identifying early signs of recurrence, and guidance on how to maintain consistent lifestyle habits, such as regular sleep and exercise. 

The implementation of adjunctive psychosocial intervention, including Cognitive Behavioral Therapy (CBT), Functional Family Therapy (FFT), and interpersonal and Social Rhythm Therapy (IPSRT), has shown to significantly decrease BD-related hospitalizations, depressive relapses, and severity of manic episodes, while improving social functioning and quality of life. 

While some studies do confirm this, others have observed no significant differences in relapses or symptom severity from psychosocial intervention. In one study, even when patients received CBT for up to 33 months, there was no significant change.

Oftentimes, pharmaceutical medication such as mood stabilizers, antipsychotics, antidepressants, and anticonvulsants are also used in order to try and achieve stability. The efficacy of mood stabilizers, such as lithium, have been replicated in various studies. 

One study showed that long term lithium use may help to reduce the risk of both manic relapses (by 38%) and depressive relapses (by 28%), as well as reduce the risk of suicide (by 50%). 

Still, lithium treatment typically only achieves success rates of 40 to 50%.

Other medications have shown benefits as well, such as antipsychotics for treating acute mania, and anticonvulsants for depressive phases and overall mood stabilization. 

Antidepressants can be helpful in treatment of bipolar disorder, but tend to be used conservatively due to their potential to induce mania or rapid cycling. As we can see, managing bipolar disorder with medications can be quite complex. 

Because of the condition’s contrasting phases– mania and depression, treatment is often more complicated than prescribing mood stabilizers.

The same treatments that can help alleviate depression can actually induce mania, hypomania, or rapid cycling, and the treatments that reduce mania might induce rebound depressive episodes. 

Each of these medications also comes with its own side effects. Side effects are common and vary by medication, but some frequently observed changes include weight fluctuations, metabolic dysregulation, sedation/somnolence, and akathisia (an inability to remain still). 

Another aspect that makes bipolar disorder challenging to treat is treatment non-adherence. About half of the patients diagnosed with bipolar disorder become non-adherent during long-term treatment. Treatment non-adherence is an important challenge to consider when treating bipolar disorder. 

What exactly causes treatment non-adherence is yet to be fully understood, as it’s a complex phenomenon determined by a multitude of influences– such as demographics, illness-related factors, and personal beliefs regarding treatment.

Overall, with bipolar disorder, adherence to treatment and treatment efficacy is just as complex and individualized as the disorder itself, which can prove a challenge for both patients and practitioners alike. 

How Psychedelics Act on The Bipolar Brain

Psychedelics, or serotonergic hallucinogens, are incredibly powerful psychoactive substances that have the ability to profoundly alter perception, mood, and behavior, and affect numerous cognitive processes. Psychedelics can induce ecstatic states with persistent positive personality change (Nichols, 2016). 

But how do psychedelics work exactly? Psychedelic mechanisms vary based on their unique chemical structure and effect. The neurological effects they produce, as well as your mindset and the environment a journeyer is in, influences the trajectory of the experience. This means that no single psychedelic trip can be exactly replicated.

Psychedelics and their effect on the brain can be classified by their chemical structure and mode of action (what they do in the brain), and fall under the following categories:

  • Serotonergic hallucinogens: a class of psychedelic drugs strongly linked to the neurotransmitter serotonin (5-HT)– which is linked to mood, social behavior, sexual desire, memory, sleep, appetite and digestion among many other things. The class includes LSD, psilocybin, MDMA, DMT, 5-MeO-DMT, mescaline, DOI, and ketamine and cannabis are often included, too.
  • Psychedelic or dissociative anesthetics: commonly associated with distorted sensory perceptions and feelings of being disconnected from oneself and the environment (i.e. detached from reality). They include PCP and ketamine.
  • Entactogens: produce psychedelic-like effects, but typically don’t produce hallucinations. Entactogens are typically associated with feelings of oneness, emotional communion, and emotional relatedness. Includes: MDMA, MDE

In this article, since research is still fairly limited, we’ll be focusing on psychedelics categorized as of serotonergic hallucinogens. Unfortunately, patients with bipolar disorder have been excluded from most psychedelic clinical trials due to safety concerns. 

In order to analyze the bipolar brain in relation to psychedelics, we will first describe specific neurological abnormalities noted in people with BD, then describe how psychedelics act on brain systems associated with BD abnormalities, and later, hypothesize how psychedelics may impact those specific brain functions in people with BD.  

As mentioned earlier, the exact causes of BD are yet to be fully understood. The exact pathophysiology is still being studied. May it be noted that in our review or BD studies, we found the conditions to often be generalized.

It is rarely specified whether the study participants were diagnosed with Bipolar I, Bipolar II, Cyclothymic Disorder, BP-NOS, or RCBD. That being said, there are certain abnormalities confirmed in association with BD, including biochemical, neurological, and physical differences in the brain.    

Bipolar Disorder, Psychedelics, & The Serotonergic System

Serotonin is an important neurotransmitter that plays a key role in mood, sleep, digestion, nausea, wound healing, bone health, blood clotting and sexual desire. Serotonin levels that are too low or too high can cause physical and psychological health problems. 

Studies have shown decreased levels of serotonergic neurotransmission for those with BD in major depressive episodes. During manic episodes, the data appear to be less clear. 

Some studies indicate the main metabolite of serotonin (5-Hydroxyindoleacetic acid) as decreasing, some increasing, and some find no difference in the levels between manic and depressed patients. 

That being said, serotonin plays a vital role in mood, and is still speculated to play a key role in BD. One of the main reasons this is important is because selective serotonin reuptake inhibitors (SSRIs), or anti-depressants, have been associated with triggering manic episodes

In regards to lithium– a popular mood stabilizing compound used to treat BD, it’s thought to exert many of its beneficial effects via an enhancement of serotonergic function. 

Yet, through tryptophan depletion (which lowers serotonin levels), studies have founds that there was still recurrence of symptoms while using lithium, suggesting that other mechanisms of the drug, besides its serotonergic function, may be more important. 

When a serotonergic psychedelic enters one’s system, it can act as an agonist or partial agonist at the brain’s serotonin 5-hydroxytryptamine 2A (5-HT2A) receptors. What does this mean? 

Well first, an agonist is a drug or chemical agent that acts by binding to a particular receptor and producing a physiological effect, typically one similar to that of the body’s own neurotransmitter at that receptor. 

In this case, the serotonergic psychedelic compound can trigger a range of intracellular pathways similar to serotonin, helping to produce the euphoric feelings they commonly sought for. 

Since psychedelics work on various pathways in the brain, and the exact mechanisms behind their function are still being fully understood, we cannot make conclusions about how they may affect systems with a certain mental disorder. 

However, since serotonin plays a key role in mood, psychedelics may be beneficial for those with BD when experiencing depleted serotonin levels. It’s important to consider one’s own serotonin levels, not just where our current emotions are. 

Prospective journeyers with BD should always consider the frequency and presence of their manic episodes, as well as their reactions to SSRIs. While serotonin is an important neurotransmitter in the well-being of all individuals, when it comes to bipolar disorder, balance is key. 

Bipolar Disorder, Psychedelics, & The Noradrenergic System

Investigation supports the presence of noradrenergic (NE) system abnormalities in BD. Norepinephrine, also known as noradrenaline, is a neurotransmitter that plays an essential role in the regulation of arousal, attention, cognitive function, and stress reactions. 

An overactivated NE system can result in increased arousal and emotional reactions to stress, insomnia, anxiety, irritability, emotional instability, and exaggerated fear or aggressiveness (hyperarousal symptoms). When under-activated, decreased arousal and insensitivity to stress can occur.   

Some studies have found an increase in NE turnover in various brain regions of those with bipolar disorder. Others have found that a major metabolite of NE is lower in those with bipolar depression (when depressed), compared to those with unipolar (or major) depression. These same metabolites have also been found to be higher in people who are in a manic state of BD. 

While more studies need to be conducted, and findings need to be replicated, it’s suspected that there could be an abnormality or altered sensitivity of adrenergic receptors in those with mood disorders. Since psychedelic research is still developing, the exact role of psychedelics on the noradrenergic system in humans is limited. 

There was one study conducted on rats which found that psychedelics such as LSD and psilocybin reduced the noradrenaline content of the rat’s hypothalamus. Other studies have been inconclusive as to whether psilocybin increases or decreases norepinephrine levels. 

Because psychedelics work on various pathways in the brain, and the exact mechanisms behind their function are still being fully understood, we cannot make conclusions about how they may affect systems with bipolar disorder. 

That being said, it could be hypothesized that because psychedelics may affect norepinephrine levels, they might affect the experience of depression and/or mania in those with bipolar disorder, depending on their current NE levels.

Bipolar Disorder, Psychedelics, & The Dopaminergic System

Evidence points to the role of dopamine systems in mood disorders. Dopamine plays a crucial role in the neural circuitry of reward and/or incentive motivational behavior. Loss of motivation is one of the key features of depression, and thus a deficiency of dopaminergic (DA) systems is assumed to be linked with depression. 

Dopaminergic treatments– treatments that increase dopamine levels, have been used by those with bipolar depression, and evidence backs their efficacy. 

Interestingly, there is also pharmacological evidence that both dopaminergics and antidopaminergics can improve bipolar depressive symptoms. Hence, it is speculated that actions at other receptors may reconcile these findings. 

The mania aspect of BD is heavily associated with dysfunction in the dopaminergic system. An increase in motivation and reward centers in the brain, along with feelings of elation (mania symptoms) are linked with an increase in dopamine. 

Pharmacological and imaging studies support the hypothesis that a state of hyperdopaminergia underlies mania. Most current anti-manic antipsychotics are all dopamine D2 receptor blockers. Hence, their use for mania has long supported the involvement of dopamine in mania. 

After analyzing studies on the role of dopamine in both manic and depressive states, it can be speculated that a lack of homeostasis in dopamine receptors– or an inability for dopamine production to remain balanced, may play a role in the pathology of BD. 

There is little research to determine the exact effect of serotonergic psychedelics on the dopaminergic system. Some have postulated, in rat studies, that hallucinogens like LSD decrease dopamine-firing activity. 

Others theorize that compounds like psilocybin increase dopaminergic neurotransmission, which is beneficial for motivation and fear extinction. 

Theories have been postulated regarding dopamine and psychosis, suggesting that hyperactivity of dopamine in the mesolimbic pathway can cause psychosis.

This being said, the dopamine pathway also involves other interconnected pathways with other neurotransmitters, leading scientists to believe that more than one of these pathways is involved in psychosis. 

Depending on the psychedelic substance, whether it be psilocybin, LSD, or something else completely, its impact on dopamine may vary. Depending on its exact effect on dopamine, which is still being studied, this will most likely impact its effect on those with bipolar disorder. 

It will also have varying effects on the body depending on how much dopamine is already present in an individual, whether they have a deficit, or overactivation of dopamine could determine whether they feel more or less balanced after receiving a substance that affects these neurotransmitters. 

Thus, it’s important to note the levels of dopamine in one’s body, their previous experiences with mania (which have been hypothesized to be aggravated by increased dopamine levels), and how the substance interacts with these systems.   

Bipolar Disorder, Psychedelics, & Grey Matter

Grey matter is made of a high concentration of neuronal cell bodies which form the outermost layer of the brain. Grey matter plays a very significant part in allowing humans to function normally. 

Various studies have reported that early-onset BD is associated with deficits in temporal cortical gray matter, which is involved in the control of attention. One study analyzed the MRI scans of 6,503 individuals, including 2,447 adults with bipolar disorder and 4,056 healthy controls.

Findings showed a thinning of gray matter in the brains of patients with bipolar disorder when compared with healthy controls. The greatest deficits were found in parts of the brain that control inhibition and motivation; the frontal and temporal regions. 

Another study used differential brain mapping to show structural grey-matter abnormalities in patients with bipolar disorder and bipolar disorder type I, which were mainly present in the prefrontal cortex and insula. 

They also found that patients’ mood state can affect grey-matter alterations. However, it’s important to note that abnormalities in regional grey-matter volume could be correlated with patients’ specific demographic and clinical features. 

A 2016 meta-analysis found a significantly lower volume of grey matter in the brains of people with bipolar disorder compared with those of people without the condition. This was also true for people with major depressive disorder.

Clinical research with rodents has examined lithium’s effect on grey matter, revealing that chronic lithium significantly increases total grey matter content in the human brain of patients with BD. The study hypothesized that the observed increases in grey matter content are likely due to neurotrophic effects associated with lithium treatment. 

Psychedelics have been associated with increased neuroplasticity and neurogenesis. Various studies have analyzed the cellular and molecular neuroplasticity effects after single and repeated administrations of psychedelics. 

The ability to promote both structural and functional plasticity in the prefrontal cortex (PFC) is beneficial to brain health, since the atrophy of these neurons plays a key role in depression and related disorders. 

While results do vary depending on the substance, dosage, and number of doses, studies suggest that psychedelics may cause an increase in neuroplasticity– the nervous system’s ability to change in response to stimuli, related to learning processes. 

Serotonergic psychedelics alter the expression of genes that contribute to synaptic plasticity, providing physiological evidence that these compounds cause persistent changes in the brain that may underlie their therapeutic effects. 

Studies mentioned previously have demonstrated how those with BD typically have a lower volume of grey matter, or thinning grey matter, compared with healthy individuals.

Lithium has been helpful in increasing grey matter in patients with BD, as it is neurotropic. Psychedelics have also been known to be neurotrophic, as they initiate adaptations in the prefrontal cortex. 

Unlike lithium, which had to be taken chronically to demonstrate similar results, psychedelics changed the expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), after a single administration, resulting in enhanced neuroplasticity. 

While there are still no studies that examine the exact effect of psychedelics on the grey matter of those with BD, it can be hypothesized that their neurotrophic effects could potentially be helpful in increasing grey matter and potentially help BD symptoms associated with lower amounts of grey matter. 

Something interesting to note is that mindfulness practices have also been shown to increase regional brain grey matter density. Systematic research has proven that the ingestion of psychedelics is associated with an increase in mindfulness, specifically relating to domains of acceptance, openness, and aesthetic appreciation. 

Bipolar Disorder, Psychedelics, & The Default Mode Network

It’s been recognized that those with bipolar disorder have alterations in their default mode network (DMN). These alterations are mostly mixed across studies, consisting of both hypo and hyper-connectivity of the DMN during rest states. Serotonergic psychedelics have been found to modulate the DMN. 

The DMN is a grouping of interconnected brain regions thought to be involved in various functions such as the sense of the self, our relation to external stimuli, and ideas regarding the past or future– essentially, it sets our ‘default mode’ of thinking. The fact that psychedelics modulate DMN activity may explain why some tend to experience ego death during psychedelic journeys. 

It’s thought that psychedelics’ modulation of multiple neural networks allows for the reorganization of disordered neural pathways in the default mode network and can help rebalance maladaptive signaling in reward circuitry– which may explain why psychedelics help treat addictions

Functional Magnetic Resonance Imaging or FMRI studies involving psychedelics have shown decreased connectivity and blood flow within the DMN. This is likely related to ego dissolution events and feelings of oneness often reported by journeyers.

Because we still don’t fully understand how exactly the mechanisms behind DMN function, specifically in the bipolar brain, it’s challenging to make a hypothesis about the impact psychedelics may have on this network. 

Whether someone is diagnosed with BP1, BP2, Cyclothymia, RCBD, or BP-NOS, may impact the specific alterations in the DMN. This being said, psychedelics tend to have a modulating effect on the DMN, allowing reorganization of maladaptive signaling in reward circuitry, which may be helpful to some with BD who struggles with feelings of reward and polarizing thought dynamics.

Bipolar Disorder & Other Mechanisms of Psychedelics

Entropy describes the amount of diversity or disorder in a system, and the ability of the brain to process information. Typically, the brain self-organizes under normal conditions into stable configurations. 

Meaning, your thought patterns and ability to process information remain fairly consistent and organized. But with psychedelics, they allow your neural pathways to take routes that they wouldn’t have taken otherwise, allowing for information to be processed in new ways.   

We’ve written about how psychedelics may affect a plethora of conditions. It’s important to reference this information when analyzing the effects of psychedelics on those with bipolar disorder, as the condition is often comorbid with other mental health challenges that could potentially be improved or exacerbated with the use of plant medicine. 

Specifically, unipolar depression, or major depressive disorder, is a mental health condition that has shown great improvement when treated with psychedelics. 

A review of 19 studies on depressed people who were administered psychedelics showed that out of 423 individuals, 335 (79.2%) demonstrated clinician-judged improvement after treatment with psychedelics. 

Unipolar depression is commonly related to bipolar depression symptoms, but some scientists say that unipolar and bipolar disorders are qualitatively different in etiology and phenomenology.  Others claim that they could fall under the same model, with depression conceptualized as the same disorder regardless of the lifetime presence of mania. 

While depression symptoms are observed in both those experiencing unipolar and bipolar depression, studies directly comparing unipolar and bipolar depression are still limited and often inconsistent. 

Hence, it is still unknown whether the treatments that help improve unipolar symptoms would improve the same symptoms experienced by those with bipolar depression. 

Recent Findings on Psychedelics and Bipolar Disorder 

Unfortunately, patients with bipolar disorder have been excluded from most psychedelic trials due to safety concerns, such as the fear of triggering to mania after drug ingestion. 

However, some studies have surfaced on ketamine treatment for BD. Although the matter requires further exploration, findings suggest that ketamine therapy may be beneficial as supplementary treatment to BD. 

In December of 2022, at the Annual Meeting of the American College of Neuropsychopharmacology (ACNP), COMPASS Pathways released investigational data on psilocybin therapy in type II bipolar disorder. 

This study, led by Dr. Scott Aaronson at Sheppard Pratt Baltimore, and is considered to be an independent investigator-initiated, exploratory open-label study of type II bipolar disorder. 

In this release, they explain how 12 out of 14 patients went into remission for three months following a single 25mg dose of COMP360 psilocybin (a stabilized, high-purity polymorphic crystalline synthesized formulation of psilocybin) therapy. 

They found that 86% (12 out of 14) of the participants met response and remission criteria for the Montgomery-Åsberg Depression Rating Scale (MADRS) at 12 weeks after COMP360 psilocybin therapy. 

There was no increase in the suicidality score based on the MADRS, no manic symptoms, and no unexpected adverse events or difficulties with the dosing sessions reported throughout the study (COMPASS, 2022). 

This study has yet to be fully published and peer reviewed, and may present a conflict of interest since the company is studying a compound they themselves have patented.

Currently, a clinical trial is being conducted at the University of California on the use of psilocybin in patients with BD II. The study is planned to conclude in the coming months. We’re hopeful that findings will reveal interesting information, currently unknown to science. 

Systematically Reviewed Case Studies on Psychedelics & BD

While the clinical information remains limited, there is still much valid case study information about the psychedelic experience provided by those with BD. In an international web-based survey, 541 people with BD described their experiences with ‘magic’ or psilocybin mushroom consumption. 

The average age of respondents was 34.1 years old, and 46.4% of the respondents were female. One-third of respondents described new/increasing symptoms after psilocybin trips, prominently manic symptoms, difficulties sleeping, and anxiety. There were no significant differences in the rates of overall adverse events observed between individuals with BD I and BD II. 

The use of emergency medical services was rare (3.3%). On average, respondents rated the harmfulness of psilocybin trips as 1.6 out of 5, where 1 is ‘Not at all harmful’ and 5 is ‘Extremely harmful’. 

When rating the perceived helpfulness of psilocybin trips, the average was 4 out of 5. Some saw a reduction in depressive and anxiety symptoms, mood lability or substance use. 

60.6% of participants reported using psilocybin to aid personal development. Over 75% of those indicated that they achieved their personal goal. 53.2% described an intention to treat symptoms of a mental health. About 65% said they achieved this goal.

Some individuals described ongoing mental health symptoms, but an enhanced ability to cope with these. Respondents (even those who experienced adverse effects) indicated that psilocybin use was more helpful than harmful (Morton et al., 2022). 

After this study was conducted, follow-up interviews were conducted a year to two years later in order to elaborate on the experiences of individuals with BD who reported use of psilocybin. Amongst these, there were both mental health benefits and undesired mental health impacts reported. 

Decreased impact and severity of depression, increased emotion processing, development of a new perspective following psilocybin consumption, and greater relaxation and sleep were highly reported. 

Participants remarked on how their psilocybin experiences enabled emotion processing and the development of new perspectives that supported positive changes in mood. 

Experiences of greater relaxation were described by enhanced calmness and grounding that, in some cases, contributed to improved sleep. Undesired mental health impacts included changes in sleep, increased mania severity, hospitalization, and distressing sensory experiences. Sleep changes following psilocybin use were prominent among participant reports. 

Difficulty relaxing or sleeping after their drug experiences led some participants to experience worsening of symptoms, which at times presented as hypo/mania or distressing sensory experiences that led some participants to become hospitalized.

Anecdotal Reports on Psychedelics & Bipolar Disorder

As mentioned earlier, we collected anecdotal reports from Psychedelic Passage survey respondents who have bipolar disorder and have used psychedelics. These reports must be interpreted within reason, as many didn’t report the type of BD they had, journey conditions cannot be confirmed, and every person has a unique reaction to psychedelics.

“I did before I was diagnosed, it was only once and I was on Wellbutrin. Keep in mind I was in a good headspace for a couple of weeks and completely relaxed and with friends I trusted. I can’t speak for everyone but in my experience I did it without thinking about a bad trip.

It was shrooms because it lasts a good 4 hours whereas LSD like lasts 12? If you are going to trip please talk to your healthcare provider for the best harm reduction. Also research if any medications you are on can interact with psilocybin.

Be very cautious and do your research and make sure you are in a safe, comfy environment and NEVER TRIP BY YOURSELF THE FIRST Time. I hope this helps!” -Anonymous Respondent

“I did once and it was a great experience. I don’t think my experience was any different than the others around me due to my bipolar. I’ve tried multiple times since then but I believe my Lamictal makes it impossible. Which is sad, I found it a valuable experience.” -Anonymous Respondent

“I’m bipolar type 2, I was diagnosed two years ago at age 32 and have been very well managed on medications since (200mg Lamictal/ 50mg Seroquel daily). 

I used psilocybin from time to time before I was diagnosed, the first time at 18 and then maybe seven times over the years leading up to diagnosis. Since diagnosis I have used psilocybin several times but also started regularly tripping with LSD.

One thing I know for sure is I’ve never had a low mood in the days after coming down. Or at least not any lower than I have felt consistently and naturally throughout my life. 

Closer to diagnosis I became very mindful of my need to heal from some unidentified trauma and welcomed the process of diving into pain, accepting and nurturing myself, and identifying and changing negative patterns. 

The couple times I used psilocybin after I started my self healing journey but before diagnosis I did not experience the depressing aspect of trips I had consistently experienced prior. I always used 3.5g or less during this period of time.

Since starting medications I have used psilocybin several times, still resulting in a positive and beautiful experience. I skip my Seroquel dose the night before tripping because I noticed that my trip was hindered by the antipsychotic otherwise (although I’d still experience some effects). 

The Seroquel doesn’t build up in your system the way some drugs do so one missed dose is enough to allow myself to experience a deeper trip. I always take at least 4g now because I’m not scared of it being more intense since it is intense in a really good way.

I also skip my dose when I plan to use LSD. I tripped on LSD for the first time when I was in the middle of my rapid mental decline I experienced right before diagnosis and that trip was scary because it made everything I had been feeling magnified and I was already feeling like I couldn’t go on the way I always had any longer. 

That was the experience that caused me to seek treatment that resulted in my diagnosis. All of my LSD trips have been beautiful and transforming since. I possibly experience some hypomania after a trip but it could also just be that I feel so high on life after such a positive experience. 

It manifests as a creative energy, as I am an artist. I don’t need sleep for a full day after tripping. I always take 1.5-2 tabs. Overall I have a really good relationship with psychedelics. They’ve shown me things I couldn’t have conceived on my own, the most important being a harmony and spirituality I didn’t recognize before. 

I’ve also experienced ego death during trips and am much more open to accepting people at face value, not internalizing things that I’ve realized have nothing to do with me, and that everything is an experience of being human, that I’m lucky to have the opportunity to experience deep emotion whether it be good or bad.

Psychedelics aside, my sober life with bipolar was impossible to navigate. I wished on every birthday, on every shooting star, that I could just be happy someday. I was mostly depressed with occasional bursts of mania that didn’t last long. 

I was always yearning for those bouts of mania because it was the only time I felt capable, energetic and inspired. Since being medicated I no longer struggle with depression. 

I’m able to exist more comfortably in relationships because I don’t have as much social anxiety and my tendency to worry that I am “too much” or “not enough” has dissipated.

It’s impossible for me to unpack how much of the change in myself has been due to psychedelics, focusing on self healing, or being treated for BD because it all sort of took place at the same time.” -Anonymous Respondent

“BIPOLAR 2: I love shrooms. I do them on rare occasions, but I try to make those occasions as frequent as possible. I get some classic elements in terms of the visuals and sensations and usually an amazing euphoria.

The thing is, apparently my antipsychotic binds to the same receptors, so I have to take what is considered a “heroic”/inadvisable dosage level in order to get that classic experience.

I totally believe that there is treatment potential in shrooms, but I only take them recreationally. I don’t notice longer term effects on my mood, unless “wants to do shrooms again” is a mood. I’ve never lost my grip on reality on any trip.

I’ve had bad trips, but haven’t had any dark thoughts during these trips that I don’t think about daily anyways.” 

-Anonymous Respondent

“I’m on abilify and did shrooms a few weeks back and had the wildest experience. I felt completely disconnected to myself as a person, and I felt like I truly saw myself for the first time, and I didn’t like it.

I broke down sobbing uncontrollably because of how much I hated who I was. It motivated me to get up, be more productive and willing to learn new things.

Honestly I think that change is the only reason I did well in finals week, i was more motivated to do better. I have BP 2 and have been diagnosed for like 8 months” -Anonymous Respondent

“BIPOLAR 2: Salvia extracts, I used it about 50 to 100 times, but I haven’t used it in at least 10 years. Never had a bad experience. It was something I would do every few months or so. It was kind of like a reset button.

I would always get an afterglow for a day or so that was very zenlike. I know most people don’t like it. I would always lie perfectly still and close my eyes. Never moved around or saw anything even remotely frightening. The entities were friendly. 

But it is not something I ever craved doing or looked forward to. It was something that I seemed to know when was the right time to do it. When I was too caught up in the minutiae of life, not seeing the bigger picture, that is when it would seem helpful.”                     –Anonymous Respondent

“Bipolar 2 here, 9 years diagnosed. It definitely has affected my way of life, and thinking, I find some of my mood swings are a lot more prominent, but it’s also a lot easier to keep myself in a stable mood for longer now.

I don’t take any BP medication, none of it has ever had enough of a positive effect for me to continue taking it, but a semi regular dose of mushrooms/lsd with a good set/setting is really all I need when I’m feeling like things are starting to dwindle out of control.” -Anonymous Respondent

I have BP1, but have never had psychosis symptoms outside of drug experiences. [I’ve done] LSD many times (100+ hits?), mushrooms a handful of times, DMT twice.” 

-Anonymous Respondent

Is it Safe to Take Psychedelics if You Have Bipolar Disorder?

If making a decision to engage with psychedelics, you must first be informed of the potential risks to determine if psychedelics are right for you. Specifically, with bipolar disorder, there are certain risks associated with psychedelics, like the potential triggering of a manic episode. 

In a comprehensive evaluation of case studies published through June 2021, multiple authors reviewed a total of 562 cases of psychedelic use, mania, and bipolar disorder. Out of these, only 17 published case studies met all of the selection criteria.

Criteria included several factors– the individual must have taken a psychedelic drug, the individual experienced persistent adverse effects from the substance, the individual’s experience met the DSM-5 criteria for the duration of a manic or hypomanic episode, or lasted at least 4 days, or involved hospitalization for the adverse effects, or involved effects that were clearly severe in nature.

There were 17 cases that describe the possible activation of a manic episode (or a psychotic episode that may have had manic elements) after psychedelic use. 

Of those cases, two appeared to be people who may have had a bipolar disorder diagnosis prior to taking the substance, and five had a family history of bipolar disorder. 

Other important themes that our case review indicates is that polysubstance use and the use of psychedelics multiple times over a short time period, are risk factors for adverse psychiatric outcomes. 

Together, this suggests that several factors related to psychedelic use may contribute to the risk of a manic episode in this population (Gard et al., 2021). 

The following are contraindicated medications often taken by those with mood disorders, but these are not the only compounds that can interact with psychedelics. 

It is important to consult with a health professional before consuming psychedelic compounds, as they can interact with various medications and health. 

Lithium Salts

Almost half of all online psychedelic experience reports involving lithium and a classic psychedelic (a non-microdose of LSD or psilocybin) involved seizures (47%) and 18% involved otherwise negative experiences. 

Furthermore, 39% of these reports involved emergency medical treatment. Lamotrigine was not seen to have impacted the experience of the psychedelic drug in 64.7% of psychedelic experiences (Nayak et al., 2021)

Serotonergic Pharmaceuticals 

There is risk of serotonin toxicity (ST) when using a serotonergic drug in combination with a serotonergic psychedelic. ST typically occurs with a serotonergic drug overdose or when a drug that can increase intrasynaptic serotonin is combined with a monoamine oxidase inhibitor (MAOI). 

Serotonergic psychotropics that do not contain MAOIs show lower risk in combination with psychedelics that do contain MAOIs. Signs and symptoms warranting immediate medical attention include myoclonus, extreme and fluctuating vital signs, agitation or comatose mental state, muscle rigidity, pronounced hyperthermia (fever), and/or seizure activity (Malcom and Thomas, 2022).

Potential Directions For Future Research 

Although there are some cases suggesting that there is a potential risk for activating a manic episode, the data is still somewhat lacking. Excluding people with bipolar disorder all together from clinical trials with psychedelics because of this potential risk is also excluding them from the potential benefits. 

To further explore the potential of psychedelics as a treatment, the need is high for trials that use modern methods, focus on appropriate ‘set’ and ‘setting’, and target those at lowest risk for mania in the bipolar spectrum (e.g., bipolar 2 disorder).

Should You Take Psychedelics if You Have Bipolar Disorder?

Every individual is unique, with their own symptoms and biochemistry. Bipolar disorder can come in many forms, and is still to be fully understood. It’s recognized that certain brain abnormalities are associated with bipolar disorder and that psychedelics may have an impact on these functions. 

There are currently effective treatments for BD, but each comes with its own pros and cons, thus treatments that work for some, may not work for others. One treatment that is still being explored is the use of psychedelic therapy. 

Although there are case studies and some preliminary research regarding psychedelics and bipolar disorder, we cannot make a generalization as to whether or not the use of psychedelics will be beneficial for people with BD. 

It’s important to consider the recurrence of manic episodes, as well as any current medications or other substances that you may be taking. Again, note that we are not medical professionals. 

This article is for harm reduction purposes. We encourage you to talk to your mental healthcare provider, and consult one of our qualified facilitators before making a decision. 

Ready to Embark on Your Healing Journey?

At Psychedelic Passage, we see you as a unique individual with unique needs. Facilitators may work with clients who have BD on a case-by-case basis. 

Since bipolar disorder is a complex condition, and its relationship to psychedelics is still being clinically understood, the process may require extra screening to determine baseline stability between screening sessions. 

But don’t let this shy you away, we are more than happy to discuss potential treatment options with you. If you’re interested in the potential healing that a psychedelic journey may provide, you can book a consultation to schedule a health screening with a facilitator near you, to ensure this is a safe option for you. 

We’ve made it our mission to curate a network of the nation’s most experienced and therapeutically-equipped psychedelic facilitators, so you no longer have to guess who’s qualified and who isn’t. 

If you’re interested in learning more about psychedelics, you can always reference our resources page for an extensive bibliotheca of information on all-things-psychedelic. That’s all for now, friends. Safe and mindful journeying!

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At Psychedelic Passage, we offer professional 1-on-1 guidance and companionship on your journey of healing. We simply can't sit back and let Americans continue to sit in silent suffering trying to battle mental health issues within a broken health care system, all while knowing that effective alternatives exist. We stand for the sacred, at-home, ceremonial use of psychedelics for consciousness exploration, which we believe to be a fundamental human right.


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