Who Should Avoid Psilocybin? Psilocybin Contraindications and Screening

Published on: January 5, 2026

Contraindications for Psilocybin: Understanding Medications, Conditions, and Screening

While psilocybin proves beneficial for many people, some should avoid using this psychedelic (as well as the other psychedelics). This is because psilocybin has contraindications, meaning it shouldn’t be used in some situations because there is a risk of harm. Certain physical and psychological conditions as well as medications can increase that risk if psilocybin is used.

In this article, we’ll be taking a look at common psilocybin contraindications and how proper psychedelic screening can help protect users’ well-being, whether this takes place in clinical or retreat settings.

Why Psilocybin Screening Is Essential for Safety and Eligibility

Psychedelic screening involves checking would-be participants' physical and mental health, as well as their use of medications or supplements. Participants may be asked about their physical and mental health history, including historical and current diagnoses. This screening process is important given some of psilocybin’s contraindications.

The risks of psilocybin do not apply equally to all people. Some mental health conditions, for instance, may be worsened by an intense psychedelic experience. And certain medications can lead to physical complications, varying depending on the type of medication that someone uses.

Psilocybin Contraindications Related to Mental Health

A growing body of evidence indicates that psilocybin therapy can offer significant and long-lasting benefits for people with depression, anxiety, PTSD, end-of-life distress, and addiction. In clinical trials of psilocybin therapy for these conditions, researchers also highlight psilocybin’s safety.

Some uncomfortable effects can occur, such as headache, anxiety, dizziness, and nausea, but these effects are typically short-lived and highlight the often surprising physical component of this type of therapy.

The vast majority of participants do not experience persistent negative effects from psilocybin, and serious adverse events are rare. In these rare cases, particularly when the considerations shared in this article aren't properly taken into account, people can experience a range of challenges following a psychedelic experience, such as Hallucinogen Persisting Perception Disorder (HPPD), emotional and mood difficulties, and issues with perception of self and reality.

Prolonged adverse effects are more common in underground or uncontrolled settings. In clinical trials, in contrast, researchers deem psilocybin therapy safe and effective for the treatment of mood dysfunction, for example.

Approaching psilocybin therapeutically can help prevent adverse outcomes, such as experiences of destabilization, depersonalization, and ontological shock. Careful instruction and skilled guidance go a long way in helping participants let go and surrender to the psilocybin therapy experience, which protects them from these post-experience psychological difficulties. Resisting, rejecting, or not being ready for what manifests during these experiences can leave people shaken up following psilocybin. In addition to this, proper preparation and integration should be provided to help support intense altered states of consciousness.

Failing to provide this support can cause participants to fall into what’s been called a “trauma vortex”, as popularized by Peter Levine. The experience of a trauma vortex is often accompanied by overwhelming fear and extreme rumination. People may start to dissociate as a protective mechanism when entering this state. This process is what can leave people coming out of psychedelic experiences feeling destabilized or left with varying degrees of dissociation (also known as depersonalization or derealization, depending on the experience).

Other important preparations include cultivating an informed and ready mindset in participants (e.g., informing them about possible experiences, particularly based on their background), creating a calm, peaceful environment for the experience, and providing therapeutic touch, if and when necessary (which helps participants feel cared for and grounded during the experience).

The high degree of psilocybin safety observed in clinical trials is also due to the rigorous psychedelic screening that takes place.

Screening involves excluding people with certain mental health conditions or mental health histories. This typically includes a current or past history of schizophrenia, bipolar disorder, borderline personality disorder, or other psychotic disorders, such as delusional disorder, paranoid personality disorder, and schizoaffective disorder.

While psilocybin therapy can be helpful for alleviating depressive symptoms, if these symptoms occur alongside psychotic or manic symptoms, the treatment may be too risky. Through this rigorous screening, the risk of experiences like destabilization is minimized.

These psilocybin contraindications mean that if someone with one of the conditions above takes psilocybin, they may be at greater risk of their symptoms being triggered or worsened. This might involve, for instance, a highly distressing psychotic or manic episode.

A Canadian study showed that people who required acute care (a visit to an emergency clinic or hospital admission) after an incident involving hallucinogens were associated with increases in risk of death relative to the general population, particularly from suicide.

This is why psychedelic screening at retreats must factor in these conditions, as adverse events involving psychedelics can happen.

People at risk for suicide, which might be indicated by suicidal ideation that includes a plan, means, or intent, or suicidal behaviors like a recent suicide attempt, must also be excluded from psychedelic therapy for the time being. This does not eliminate the risk of increased suicidal ideation following psilocybin therapy, as one case study underscores, but it does significantly reduce this risk.

It’s important to keep in mind that there are ways to prevent these adverse events or suicidal ideation following a psychedelic experience.

As we’ve outlined above, issues related to preparation, guidance, integration, or a lackluster screening process can leave people in a highly negative state following a psychedelic experience.

By promoting and practicing thorough therapeutic standards across all levels of psychedelic therapy, we can decrease the odds of these unfortunate outcomes.

Medical Contraindications to Psilocybin Use

Most psilocybin contraindications are related to increased psychological distress, but some are related to physical harm. The main physical concerns related to psilocybin safety are transient increases in heart rate and blood pressure.

This means that serious or uncontrolled cardiovascular conditions are psilocybin contraindications, and so people with these conditions should usually be excluded from clinical trials, psychedelic therapy, and psilocybin retreats.

Antidepressant and Psychiatric Medication Interactions with Psilocybin and the Associated Risks

Clinical trials often require the tapering of antidepressant medications before someone is deemed suitable for taking psilocybin. However, research has not found that using an SSRI antidepressant at the same time as psilocybin increased heart risk or serotonin syndrome.

The latter condition – when an excessive level of serotonin accumulates in the body, which is potentially life-threatening – can occur when taking two drugs that increase serotonin levels in the body. Both antidepressants and psilocybin boost serotonin levels, but there’s little evidence that SSRI antidepressants, in combination with psilocybin, increase the risk of serotonin syndrome.

Case studies have found an increased risk of serotonin syndrome when psilocybin is used in combination with non-SSRI antidepressants. But this link remains an area of ongoing investigation. As it stands, a scientific review concluded that the combined use of antidepressants and psychedelics is safe, although the authors acknowledge limitations and gaps in knowledge in studies on the potential risks.

The risks that do exist are relative to the type of antidepressant used. For example, MAOI (monoamine oxidase inhibitors) prevent the metabolism of serotonin, which could lead to dangerous levels of serotonin when combined with psilocybin or other psychedelics. MAOI antidepressants are riskier to use at the same time as psilocybin compared to SSRI antidepressants.

The main risk we have seen in combining antidepressants with psilocybin therapy, and why we require our guests to wean off their antidepressants with their prescribing professional before arriving, is that the presence of antidepressants in a person’s system will make it difficult to determine a safe therapeutic dose. Antidepressants diminish the strength of psychedelic effects, often to widely varying degrees based on factors such as which exact antidepressants the person is taking, how long they have been taking them, medication dosage(s), and their unique biochemistry.

These factors create uncertainty about determining an appropriate therapeutic dose of psilocybin that accounts for these variables.

In addition to safety considerations, there is also a high likelihood that people engaging with psilocybin therapy while still on SSRI or SNRI antidepressants will be left underwhelmed as a result of the dampening effects that these medications have on the psychedelic experience. As a result, the presence of these medications will often mute the therapeutic potential of psilocybin therapy.

However, one clear contraindication between a psychiatric medication and psilocybin is when the medication lithium is involved. A high percentage of lithium users (47%) reported seizures in their psychedelic reports in a self-reported study.

Given that lithium is most often prescribed as a mood stabilizer, people taking lithium also likely have the very mental health conditions (i.e., bipolar disorder) that would typically preclude them from receiving psilocybin therapy after completing a proper screening protocol.

Substance Use and Addiction as Psilocybin Contraindications

Those with current alcohol or substance abuse, occurring in the past year, may also be excluded from psilocybin therapy. This is due to several reasons:

• Impairment and Suppression: Mixing psilocybin with alcohol or opioids can increase the risk of injuries and accidents due to confusion or impaired judgment and coordination. Substances such as alcohol and opioids may be used as avoidance mechanisms by those who are addicted to them, which will suppress psilocybin’s ability to catalyze any sort of real therapeutic state. As a result, someone who is currently addicted to another substance or engages in avoidance behaviors is most likely unprepared for psychedelic therapy.
• Greater unpredictability: Active substance use introduces a potentially more unpredictable ‘set’ (or mindset), which can increase the risk of negative psychological reactions. For example, one study found that many psychedelic users who had challenging experiences combined psychedelics with alcohol and cannabis.
• Underlying medical conditions: Chronic substance and alcohol use can lead to liver, kidney, and heart conditions. Since psilocybin transiently increases heart rate and blood pressure, this can pose a risk to people with pre-existing or unstable cardiovascular issues related to regular substance use.
• Withdrawal symptoms: Quickly and suddenly quitting alcohol or a drug to which someone is dependent – to access psychedelic therapy – can lead to withdrawal symptoms, which may be physical or psychological in nature, or both. At worst, weaning off so suddenly is simply unsafe. Assuming a person is physically able to participate in psilocybin therapy, such a rapid shift will likely create a negative ‘set’ in which to have a psychedelic experience, and it would increase the chances of distressing experiences.

However, this doesn’t mean that substance use, which doesn’t meet the criterion of addiction, is excluded from psilocybin therapy.

Psilocybin safety also isn’t usually jeopardized if someone currently smokes, so a current smoking habit is not an exclusion criterion. In fact, researchers have shown that psilocybin therapy is safe and effective for the treatment of tobacco addiction.

Age Requirements and Brain Development in Psilocybin Screening

To participate in a psychedelic clinical trial, currently, you typically need to be aged 18 or over. In legal psychedelic therapy and psychedelic retreats, the age requirement is usually 21 and over (such as in Oregon), although many retreats (and even some clinical trials) exclude those younger than 25 years old.

One major reason for these age requirements is that the brain has not fully developed until the age of 25. (This is a bit of an oversimplification: the brain continues to change after the age of 25, including in significant ways, but a lot of the rewiring or pruning process in the brain does occur before the age of 25.)

Age requirements in psychedelic screening are based on concerns about longer-lasting negative effects, due to the brain being more malleable before the age of 25. In addition, the prefrontal cortex is still developing in adolescence (it matures much later than the limbic system, which processes emotions). The prefrontal cortex is important for emotional regulation. Psychedelic experiences can, at times, be challenging. So, if someone under 18 takes psychedelics, it is thought that they may have a harder time managing or processing intense or challenging psychedelic experiences.

However, it is not automatically risky to use psychedelics before the age of 25, as many cultures involve psychedelic use earlier in life than this. Researchers are also exploring the potential of safely administering psychedelic therapy to adolescents.

The risk of administering psychedelics to those younger than 25 may relate more to psychological readiness and support systems than brain development. Many of the adverse effects of adolescent substance use may be less from the consumption of a particular substance, but rather from many of the same factors we have outlined above (screening/suitability, preparation, set, and setting).

For example, in cultures in which psychedelic use among adolescents is normalized – such as the Santo Daime church, Amazonian ayahuasca sects, the Bwiti tradition, and the Huichol people of Mexico – psychedelics are approached in a prepared, ritualized, communal way. Psychedelics are also treated with the utmost respect. This cultural framework helps make the experiences safer.

The Psilocybin Therapy Screening Process Explained

The following screening process for psilocybin therapy usually involves the following steps or considerations. This is the screening process that we at MycoMeditations, after integrating the protocols from psychedelic clinical trials with our decade-plus of experience administering psilocybin therapy, have found to be the most effective in ensuring psychedelic safety and readiness:

• Application submitted: The application must be comprehensive and cover everything from reasons for attending a psilocybin retreat to mental health information, family mental health information, cardiovascular health, general health, medications, supplements, allergies, and understanding previous psychedelic experiences. This serves as a full-spectrum evaluation to identify any contraindications to taking psilocybin. This part of the psilocybin screening process also involves taking the participant’s support system, life stability, and readiness for psychedelic therapy into account.
• Initial consultation: The participant has an introductory conversation with a psilocybin therapist, facilitator, or retreat organizer. This involves discussing the client’s mental health history, current symptoms, and therapeutic goals. The aim is to establish initial eligibility.
• Further psychological, medical, and physical assessments: If the application and discussion raise any red flags, this stage of the screening process is an opportunity to follow up in the appropriate areas to safely approve that this participant can safely engage in psilocybin therapy.
• Informed consent: Potential participants are informed of the risks, benefits, procedures, and any unknowns associated with psilocybin therapy. Participants must provide written consent and are informed that they can withdraw from treatment at any point.
• Establishing rapport: During these initial interactions in the psychedelic screening process, the client and psilocybin therapy provider begin to establish a sense of trust and rapport, which is a key component of safety in psilocybin therapy. A participant needs to feel safe, prepared, and supported when enrolling in psilocybin therapy.

What To Do if Psilocybin Contraindications Are Flagged

If someone finds that their medical history excludes them from participating in psilocybin therapy, this doesn’t mean there are no options available.

For example, while psilocybin therapy risks may be higher now for a particular individual, that doesn’t mean they have to be in the future. At a later time, for instance, someone’s physical or mental health could be improved, or medication or substance use could change, in ways that make them eligible for psilocybin therapy.

But what should people do before they’re eligible for psychedelic treatment, or if, say, it’s unlikely they will be (due to a pre-existing medical or mental health condition)?

Fortunately, there are still other ways to improve mental well-being without psychedelics, including psychotherapy, medication, dietary and lifestyle changes, and social support. While other consciousness-altering activities (such as meditation) may benefit someone with a psychotic disorder, intensive meditation can also trigger or worsen psychotic symptoms.

Some non-classic psychedelics, on the other hand, are often considered safe for many people excluded from therapy involving classic psychedelics, such as ketamine therapy for those with bipolar disorder.

Researchers are also drawing attention to the potential of microdosing, or non-hallucinogenic psychedelics (also known as psychoplastigens), being helpful for those with typically contraindicated conditions such as schizophrenia and bipolar disorder. This is due to increased neuroplasticity while avoiding intense altered states. In the future, there could be ways for those living with schizophrenia or bipolar disorder to benefit from the brain benefits induced by psychedelics without risking the triggering or worsening of symptoms.

Responsible Screening Protects Participants and Preserves the Integrity of Psilocybin Therapy

An ethical psilocybin therapy provider should have a comprehensive psychedelic screening process in place. This is crucial for protecting the physical and psychological safety of potential participants. Without such screening, practitioners increase the risk of physical complications, psychological distress, and more serious and longer-lasting adverse effects.

Psilocybin therapy is not recreational; it is not to be taken lightly. It can pose risks if administered carelessly or unethically. This is why any legitimate psychedelic therapy provider must prioritize psilocybin safety. To better understand what this process should look like, click here to learn how to book a psychedelic retreat safely.

When psilocybin therapy is provided with the proper safety considerations in mind, eligible participants have the opportunity to have supported, transformative experiences that can offer profound and long-lasting benefits.

Psilocybin Contraindications and Screening: FAQs

What conditions make psilocybin unsafe for some people?

Psilocybin contraindications include serious cardiovascular conditions, as well as psychotic disorders, bipolar disorder, and borderline personality disorder. Also, women who are pregnant are advised to avoid psilocybin.

Why is psychological screening critical before psilocybin use?

Psychological screening minimizes the risks of intense psychological distress before and after psilocybin use. It reduces the likelihood that psychotic or manic symptoms will be triggered or worsened.

How do medications interact with psilocybin?

Some medications, such as SSRI antidepressants, increase serotonin levels in the body. Psilocybin does the same. However, there's no conclusive evidence that using an SSRI antidepressant at the same time as psilocybin would lead to serotonin syndrome, or excessive (and dangerous) levels of serotonin in the body. This risk seems to be mostly confined to MAOI antidepressants.

What alternatives exist if psilocybin isn’t appropriate?

If psilocybin isn’t appropriate for someone, less risky alternative treatments include psychotherapy, medication, dietary and lifestyle changes, social support, and meditation (although intensive meditation may involve higher risks for some people). Ketamine is also showing to be a safe alternative for people who may have contraindications with psilocybin due to a personal or familial diagnosis of bipolar disorder.

How do ethical providers assess participant readiness?

Ethical psilocybin therapy providers assess people’s readiness in terms of their awareness of potential risks and benefits, intentions and therapeutic goals, and openness to the wide variety of psychedelic effects that may occur.