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The Side Effects of Psilocybin or ‘Magic’ Mushroom Therapy

All over the world, people see magic mushrooms as a gift from nature with its ability in treating various health conditions, promoting spiritual growth, and producing a positive outlook on life.

Used as a medicinal and spiritual healing tool, magic mushrooms, or mushrooms containing psilocybin, have been used for centuries, and their use is just as present today.

Unfortunately, psilocybin remains illegal in the United States under the Controlled Substances Act. Classified as a Schedule I drug, psilocybin is deemed to have no approved medical use and has a high potential for abuse and addiction.

Clearly, psilocybin shows potential in treating a wide range of medical conditions, particularly mental health disorders. This strict regulation has certainly limited its ability for those who could benefit from it. Not all hope is lost, though – we can help you begin your journey!

Before embarking on your transformative journey with psilocybin, it’s important to be familiar with the potential positive and negative side effects associated with its use.

Today, we will be going over potential drug interactions you should be aware of when using psilocybin, following up with the potential side effects of using psilocybin with or without certain health conditions. To start off, let’s go over what psilocybin is and how it works in the body.

What is Psilocybin?

Magic mushrooms refer to a variety of mushrooms that contain psilocybin, a naturally occurring psychedelic compound present in approximately 200 different fungi species worldwide. Due to the wide variety of fungi species, the potency of psilocybin can vary significantly.

Historical use of psilocybin in religious ceremonies dates back centuries, particularly in South and Central America. However, ancient art depicting the use of psilocybin dates back as far as 9000 BC in North African indigenous cultures.

Modern psychedelic research began in the early 1940s when Albert Hofmann first discovered and synthesized LSD. In 1958, Hofmann was the first to isolate psilocybin and psilocin from the mushroom Psilocybe mexicana.

When ingested, psilocybin is converted into psilocin, the chemical responsible for its psychoactive properties, which can be compared to the effects of LSD and DMT. Psilocin then reacts with the serotonin 2A (5-HT2A) receptor to produce the hallucinogenic effect.

Although magic mushrooms can be eaten raw, the taste of these mushrooms is quite bitter and is often consumed in other ways, such as being brewed into tea, smoked with tobacco, or ground up into capsules.

It’s extremely important to do thorough research before identifying and consuming magic mushrooms gathered from nature, as some poisonous mushrooms look quite similar. Ingesting poisonous mushrooms can lead to severe side effects.

As with any psychedelic drug, psilocybin has a significant impact on all senses and can create visual distortions and alter perceptions of time and space. Psilocybin use can also reduce negative symptoms associated with various health disorders.

While psilocybin has been linked with numerous positive effects and therapeutic outcomes, it still has potential risks that need to be taken into consideration before use.

The Potential Side Effects of Psilocybin

After ingestion, the effects of psilocybin can be felt within 30-60 minutes, with the peak of the experience occurring around 90 minutes. The effects can last up to 6 hours, but some may experience lingering effects beyond this.

It’s important to note that several factors can affect this timeline, including the amount of mushrooms ingested, how the mushrooms were consumed, tolerance levels, body weight, age, and recent food consumption.

Let’s dive into the most common physical/mental side effects that you may experience from magic mushrooms. For a more detailed understanding, read on to explore how psilocybin can affect specific medications and health conditions, along with the benefits it has to offer.

Positive Effects

    • Enhanced visual acuity
    • A lightweight feeling
    • Eureka moments
    • Vivid dreams
    • Reduced anxiety
    • Reduced depression
    • Relaxation
    • Mood enhancement
    • Increased creativity
    • Increased empathy for self and other
    • Increased quality of life
    • Deepened introspection
    • Extra dimensional consciousness
    • Connection to a higher power
    • Deepened appreciation for the planet
    • Constructive self awareness

Negative/ Uncomfortable Effects

    • Nausea
    • Vomiting
    • Drowsiness
    • Dry mouth
    • Headache
    • Increased heart rate
    • Increased blood pressure
    • Body temperature fluctuations
    • Continuous yawning
    • Anxiety
    • Nervousness
    • Paranoia
    • Confusion

In rare, severe cases:

    • Delirium 
    • Seizures (Occurs most commonly in those with a family history of epilepsy)
    • Hallucinogen Persisting Perception Disorder (HPPD)

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For harm-reduction purposes, we provide links to online psilocybin vendors, local stores, delivery services, and spore vendors for growing your own medicine at home.

Tolerance, Dependence, and Withdrawal

Like any other drug, regular use of psilocybin can lead to tolerance, which occurs when the body becomes familiar with the effects of the drug and therefore requires higher doses to achieve the same effect. Tolerance to psilocybin can be built up in as little as 4 days.

To reset tolerance, discontinuing mushroom use for around a week is recommended, allowing individuals to return to their normal tolerance level.

While psilocybin does not cause physical dependence, regular use may lead to psychological dependence, where users become reliant on its effects.

Because psilocybin is not chemically addictive, physical symptoms will not be present after stopping use. As mentioned above, psychological withdrawal may occur in cases of dependency, making it hard to adjust to reality without the substance.

Can Psychedelic Therapy Cause Psychosis?

Among these potential side effects, the risk of psychosis often weighs heavily on the minds of individuals considering psychedelic therapy.

And although one must recognize the profound entanglement of psychedelic experiences with the study of psychosis, it’s also important to discuss the topic within context.

Historically, these drugs were initially used as tools to model aspects of psychosis, allowing researchers to draw comparisons between drug-induced states and naturally occurring psychological disturbances. 

This entanglement provided unique insights into human consciousness. However, the societal upheaval of the 1960s led to a divergence in these research paths, setting the stage for distinct approaches to psychedelic therapy and psychosis.

The question then arises: Is psychosis itself a risk in this therapeutic context?

The answer is nuanced. While psychedelic therapy may involve experiences that bear some resemblance to psychosis, it’s crucial to differentiate between these states

Psychedelic therapy is typically conducted in a controlled and supportive environment, guided by trained professionals who emphasize compassion and support. In contrast, traditional responses to psychosis often involve medical interventions, restraint, and seclusion.

So, while the therapy itself may involve challenging moments, the key distinction lies in the therapeutic context and support provided. While not without its risks, psychedelic therapy offers unique opportunities for personal growth and healing when administered with care and expertise.

Drug Interactions with Psilocybin

Compared to other medications currently on the market, psychedelics are considered a safer alternative. Current treatments often leave people dissatisfied with their negative side effects.

Like any other drug, psilocybin can interact with other substances, including prescription, over-the-counter, and other recreational drugs. These interactions can lead to potentially dangerous side effects and should be taken seriously.

Some of the most common drug interactions with psilocybin include:

1. Antidepressants

Selective serotonin reuptake inhibitors (SSRIs) work by increasing the levels of serotonin in the brain. As psilocybin also affects serotonin receptors, taking this combination together can lead to a potentially life-threatening condition known as serotonin syndrome.

The adverse effects of serotonin syndrome typically come on within 24 hours and may include nausea, vomiting, agitation, insomnia, rapid heart rate, high blood pressure, high fever, confusion, fainting, or seizures. If left untreated, severe serotonin syndrome may lead to death.

Another type of antidepressant classified as monoamine oxidase inhibitors (MAOIs), works by blocking the action of monoamine oxidase, which is an enzyme that breaks down serotonin and other neurotransmitters. Again, a combination of these drugs could lead to serotonin syndrome.

Other types of antidepressants include serotonin-norepinephrine reuptake inhibitors (SNRIs), serotonin partial agonist/reuptake inhibitors (SPARIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), and atypical agents.

Antidepressants are also known to blunt the effects of psychedelics. To learn more about these drug interactions in depth, make sure to check out our article on antidepressants and psilocybin interactions.

2. Mood Stabilizers

Mood stabilizers, such as lithium, can treat psychiatric disorders such as bipolar disorder. Mixing mood stabilizers and psilocybin can lead to an increased risk of seizures, psychosis, and ‘bad trips‘.

3. Stimulants

The use of stimulants, like cocaine or amphetamines, and psilocybin can lead to an increase in heart rate, blood pressure, and body temperature. Additionally, there is a much higher risk of cardiovascular complications, such as heart attack or stroke, when using these drugs together.

Stimulants can also increase the intensity of the psilocybin experience, which could worsen the negative side effects, including anxiety and panic.

4. Alcohol

Similar to stimulants, using alcohol and psilocybin together can worsen the negative side effects and increase the intensity of the psychedelic experience, leading to a potential loss of control and being at a higher risk for accidents.

Both substances can cause dehydration as well, which can lead to an increased risk of nausea, vomiting, and dizziness.

5. Antihistamines

Antihistamines are commonly used to treat allergies and insomnia, which explains why their main side effect is drowsiness and sedation. When taken with psilocybin, the risk of sedative effects and impaired coordination is greatly increased.

Taking too high of a dose of an antihistamine, such as Benadryl or Claritin, has been linked to hallucinations. So, when using these drugs with psilocybin, the risk of hallucinations is even greater.

6. Other Drugs

Other recreational drugs, such as cannabis and MDMA, can also interact with psilocybin. These interactions can lead to unpredictable effects, such as increased heart rate and blood pressure, hallucinations, and seizures.

It’s important to note that this is not an exhaustive list of drug interactions with psilocybin. If you currently take any medications, it’s important to talk to your healthcare provider before using psilocybin.

Your doctor may taper you off your medication, which could come with some nasty side effects. Some have found relief by microdosing psilocybin through this process. Again, make sure to consult with your doctor before microdosing psilocybin.

If you find it hard to remember what types of drugs and combinations can cause negative effects, just remember that any drug that works with your serotonin system could interact negatively with psilocybin. 

Psilocybin & Health Conditions: What They Can Treat

As you’ve heard before, psilocybin has shown great potential in treating various health conditions through its actual effects on the brain and subjective experiences. Listed below are just a few health conditions that psilocybin can help treat.


While depression affects millions of Americans each year, a new and improved treatment is needed now more than ever. Luckily, psilocybin is here to do that.

A major benefit of psilocybin is its fast-acting nature. Medications used to treat depression often take weeks before the user starts to feel any sort of effect. For some, no relief is ever felt.

People with treatment-resistant depression have exhausted all treatment options and often feel like there is no hope, which could unfortunately lead to suicide.

For those with depression, psilocybin essentially works by rewiring the brain. When ingested, psilocybin binds to 5-HT2A receptors, which results in altered neural connections. 

Because psilocybin reduces the activity of the brain’s default mode network (DMN), individuals may experience an increased perception of their surroundings with an open mind.

Additionally, psilocybin promotes neuroplasticity, which is the brain’s ability to reorganize and form new connections, in regions involved in mood regulation and emotional processing.

Beyond its work in the brain, the actual psychedelic experience has also been shown to increase emotional well-being in people with depression.

Because depression often coexists with other psychiatric disorders, like bipolar disorder, it’s important to know the potential risks before using psilocybin. For your benefit, we’ve published an article on who should not use psychedelics.


Anxiety is one of the most common mental health conditions that affect millions of people each year. Although current treatments for anxiety exist, like antidepressants, many don’t experience relief and some may feel worse off.

Psilocybin interacts with 5-HT2A receptors, which are involved in mood regulation. By binding to these receptors, psilocybin influences neural activity patterns, further contributing to its anxiolytic effects.

Additionally, psilocybin has been shown to be effective in treating both anxiety and depression in end-of-life patients. These stresses can be a lot to handle, so being able to improve the quality of life is essential. And luckily, the effects of psilocybin can be long-lasting.

Because psilocybin use can induce feelings of paranoia and increase anxiety, microdosing psilocybin is a favorable option for those seeking anxiety relief. Microdosing reduces anxiety without the hallucinogenic experience.

Obsessive-Compulsive Disorder (OCD)

OCD is a psychiatric condition characterized by intrusive and persistent thoughts, fears, and compulsive behaviors that can significantly impact daily life. Whether you worry about cleanliness or repeating routines, these uncontrollable thoughts can cause distress.

When psilocybin reaches the brain, brain activity is decreased in the medial prefrontal cortex, which is associated with obsessive thinking. Repeated doses of psilocybin have been shown to influence serotonin-binding activity, leading to a reduction of OCD symptoms.

Psilocybin can alter or reset functional connectivity between or within various brain regions, which is why psilocybin is helpful for those who have OCD. The psychedelic experience alone can lead to improved well-being and a reduction in stress.

More importantly, psilocybin has shown promising potential as a fast-acting alternative to current OCD treatments on the market, which tend to provide little relief.

Post-Traumatic Stress Disorder (PTSD)

PTSD is a psychiatric disorder that can be triggered by experiencing or witnessing a terrifying event. Individuals with PTSD often experience intense and disturbing thoughts and feelings related to their traumatic experience, lasting long after the event occurred.

Symptoms of PTSD may include sadness, anger, fear, intrusive thoughts, detachment from others, and vivid flashbacks and nightmares that make them feel like they are reliving the event.

These symptoms can interfere with everyday life, making it hard to perform daily functions. It’s estimated that 1 in 11 people will be diagnosed with PTSD during their lifetime.

Psilocybin acts by stimulating nerve cell regrowth in the brain regions responsible for emotion and memory, such as the hippocampus. A psychedelic experience with psilocybin can also help create a positive memory to turn to rather than the traumatic memory.

Current treatments for PTSD include talk therapy and medication, as PTSD is commonly coupled with other mental health disorders like depression. These treatments aren’t a solution for everyone, which can lead to substance abuse, anger problems, or suicide.

Studies have shown that psilocybin increases the quality of life, enhances mood, reduces anxiety and fear, and increases energy in people with PTSD.

However, using psilocybin can induce a ‘bad trip’, leading to flashbacks and increased feelings of anxiety and paranoia. Before using psilocybin, it’s important that you are in the right headspace and work with a psychedelic guide or therapist throughout your journey.

Substance Use Disorders (SUD)

Other mental health conditions may increase your risk of developing a substance abuse disorder. SUD is characterized by uncontrolled and compulsive patterns of drug use. In particular, psilocybin has been shown to be effective in treating alcohol and tobacco addiction.

Psilocybin interacts with serotonin receptors in the brain, leading to altered brain activity. Through modulation of the DMN, psilocybin can reduce negative thinking patterns, allowing individuals to gain new perspectives on their addictive behaviors.

With the many benefits of psilocybin use for SUD, such as aiding in the reduction of cravings, the psychedelic experience alone can promote positive emotions and behaviors.

Psilocybin is not a stand-alone treatment for SUD. A combination of talk therapy and psychedelic therapy is the most effective treatment regimen.

Cluster Headaches and Migraines

Cluster headaches, also known as Horton’s syndrome, are one of the most painful types of headaches out there, causing severe pain on one side of the head. Migraines can cause throbbing on one side of the head, sometimes accompanied with sensitivity to light and nausea.

Psilocybin decreases activity in the brain that is well-connected with other areas. Additionally, psilocybin has been shown to reduce blood flow in the hypothalamus, where blood flow is typically increased in this region with cluster headaches and migraines.

Individuals who experience these types of headaches commonly suffer from depression and anxiety as well. And as you’ve learned, psilocybin is very helpful in the treatment of these conditions.

Eating Disorders

Eating disorders are characterized by persistent disturbances in eating behavior, leading to an impairment of both physical and mental health, and affect at least 9% of the world’s population.

Some common types of eating disorders include bulimia, binge eating, avoidant/restrictive food intake disorder, and anorexia, which actually has the highest mortality rate of all psychiatric illnesses.

Eating disorders affect up to 30 million Americans in their lifetime and currently, there are only a few FDA-approved medications for eating disorders. However, these medications don’t always provide relief.

For eating disorders, psilocybin works directly with the root cause rather than just the symptoms. Psilocybin increases the number of neural connections in the brain by creating new insight potential and disconnecting connections responsible for negative thought patterns.

Unlike conventional methods that often fall short in addressing eating disorders, psilocybin can help individuals dissociate from their negative thoughts and develop a new perspective on their bodies, along with newfound self-love.

Eating disorders typically coexist with other mental health disorders, such as anxiety and depression, which can also be treated with psilocybin.


Lastly, but surely not least, psilocybin has shown promise in treating dementia disorders. Dementia is a condition that is characterized by impairment of thoughts, memories, and cognitive abilities. 

Psilocybin has been found to promote neuroplasticity and increase the growth of new brain cells, which is important for those living with dementia, as their cognitive functions are impaired.

People living with dementia often experience anxiety and depression and unfortunately, antidepressants are not typically recommended for those suffering from dementia. Therefore, it’s important that we have another treatment available in these cases, such as psilocybin.

Connect With Local Psychedelic Guides

Although psilocybin has a significant amount of benefits, it is not a ‘magic bullet’. While keeping its benefits in mind, you must also acknowledge the risks and potential side effects you may encounter while using psychedelic substances.

Psilocybin is a powerful tool for therapeutic and spiritual healing, so it’s important that you are completely prepared before beginning your journey. At Psychedelic Passage, we are here to assist in any way possible!

If you feel ready to embark on your psychedelic journey, we invite you to book a consultation with us. We will connect you with one of our knowledgeable psychedelic concierges who can give you access to our pre-vetted network of US-based facilitators.

Hopefully this article covered all the questions you have, but if not, check out our resources page. Have a safe and mindful journey!

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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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