To work safely with psychedelics, it is important to understand fully the potential side effects associated with the substance you are ingesting, and to undergo a thorough mental and physical health risk assessment to reduce the risk of harm.

As we take a look at psilocybin (the active ingredient of magic mushrooms) through a medical lens, it is first important to acknowledge that psilocybin is considered very safe, having the lowest profile of risk according to the Global Drug Survey and accounting for only 0.2% of Emergency Department visits in the US. When evaluating any negative effects from working with psilocybin, hold in mind the risk/benefit ratio from the illness with which the person is suffering. A person who has had chronic debilitating depression for much of their life, or suicidality, is no doubt in extreme mental anguish, and alleviation of their pain through working with psilocybin may be deemed worth the risk of potential side effects. Context is key.

Psilocybin, which has a duration of action of around 5-6 hours is considered a less exhausting psychedelic to work with than LSD, which has a duration of action of around 10-12 hours. LSD has been referred to as the “atomic bomb” of the psychedelic world, while psilocybin is more of a “weapon of conventional strength”. When working with patients in a palliative care setting for example, who are physically very ill, they would probably not have the strength to endure LSD. 

Most importantly in any discussion around working with psychedelics, is know what you are taking, and give due care and attention to having a safe set and setting.  

Set refers to the mindset with which you enter a psychedelic experience; take time to ground yourself, prepare, set intentions, sleep well, prepare your body and mind, nurture yourself. The psychedelic experience begins the moment you decide to go ahead with it, as your conscious and unconscious mind makes plans. Honour this. Be mindful of what you are reading, watching and inputting. Spend time with people who love you and treat you well.  

Setting refers to the environment you are in for the experience; ideally it will feel secure, calm, nurturing, have elements from the natural world, ceremony, music, intention setting, rituals of connection to yourself and your guides. Choose sitters who you trust. When you return home after your experience it is a good idea to create a similar safe space to land and ground, before facing the world fully. Many difficult psychedelic experiences can be prevented with a safe set and setting. 

Psilocybin is a serotonergic agonist targeting the 5-HT2A receptors found in the central nervous system and the gastrointestinal tract. Serotonin is known as the “happy hormone” found in SSRI antidepressants like fluoxetine (prozac), and so some of the physical side effects of psilocybin are similar to those experienced when taking these antidepressant medications. Serotonin makes us feel good, modulates our thinking, learning and memory. It creates feelings of happiness and reward. As 90% of serotonin receptors are in the gastrointestinal tract, side effects from psilocybin can include nausea, diarrhoea and constipation.

Physiologically, serotonin can cause both blood vessel constriction (vasoconstriction) and blood vessel dilation (vasodilation), causing either an increase or decrease in blood pressure. Rarely, stimulation of the 5-HT2A receptor through psilocybin use can cause coronary artery spasm. Psilocybin has been shown increase a person’s blood pressure (BP) an average of 10mmHg. This means a person who has healthy BP of 130/80 may be expected to increase to 140/90. This increase is marginal and probably not dissimilar to “white coat syndrome”, the increase in BP that can commonly be experienced due to anxiety during a trip to the doctor’s office. However, with someone who has a very high baseline BP, this increase may send them into a crisis. Getting a routine BP check before taking psilocybin is a really good idea. 

Psychologically, a person may experience visual disturbances, troubling thoughts, paranoia, panic and mild anxiety when taking psilocybin. They may have hyperawareness of their bodily processes, feeling their heartbeat intensely for example, or feeling their blood flowing. Fear and paranoid delusions can potentially lead to aggressive behaviours towards self and others. That being said, side effects are generally minimal and are more likely influenced by a poor set and setting, and the person’s emotional state. From a research study performed by John Hopkins University, it was found that from a cohort of 1193 participants, only 2.1 percent described having a “bad trip”. A difficult trip should not be written off as a failure, because even difficult experiences can hold significant meaning when integrated properly. 

From the Human Hallucinogen Research Guidelines for Safety, potential exclusions for people to work with psilocybin may include: 

  • personal history of psychosis or severe psychiatric disorders 

  • a first or second degree relative who had psychosis, schizophrenia or bipolar type 1 

  • hypertension (high blood pressure) 

  • a history of cardiac disease 

  • alcohol abuse 

Individual assessment of a participant by a competent practitioner is important when assessing psychiatric history, especially personality disorders. There are different opinions as to what client groups should be excluded from working with psilocybin. Ultimately this work could change a person’s life forever, so immediately excluding them can seem harsh. Professional opinion varies and sits with the individual practitioner.

Prolonged trips and acute psychosis from hallucinogens that can last for days or months, is a possibility, although rare. Mostly this has been reported through recreational LSD use, and is minimised in a clinical trial setting. Psychedelic integration psychotherapy, support groups and having a safe person to talk to about your experience, can minimise the harm from prolonged hallucinations. Often, prolonged hallucinations can give a person positive meaning, understanding and new insights about their life, when held and explored safely with a psychotherapist specialising in psychedelics.

In terms of medications that interact with psilocybin, many serotonergic medications, including the most commonly used antidepressants (SSRIs, SNRIs, MOAIs, Tricyclics, St Johns’s Wort, 5HTP), some anti-nausea medication (ondansetron, metaclopramide) and dextromethorphan cough medicine (found in Benylin), may inhibit psilocybin’s effectiveness, potentially giving the person a reduced reaction to psilocybin. Psychostimulants such as ritalin (an amphetamine used to treat ADHD) can increase the stimulant effects of psilocybin, the potential for psychotic symptoms and the cognitive enhancing effects; as opposed to the ego dissolution experience commonly reported when working with psilocybin. While all these medications may inhibit psilocybin’s effectiveness, they are things to be aware of, that may not necessarily be a strict contraindication.

When considering discontinuation of an antidepressant like a SSRI or SNRI, it is important to do it under medical supervision, from a GP or psychiatrist. Risks of SSRI/SNRI discontinuation syndrome can include; flu like symptoms, insomnia, nausea, imbalance, sensory disturbance and hyperarousal. Sometimes it may be worth remaining on these medications whilst working with psilocybin, but the participant probably won’t have such an intense peak experience. It depends on the person’s expectations from their experience and what they are hoping to gain. 

Serotonin syndrome can be a medical emergency when working with some psychedelic medicines, this can occur with concomitant use of serotonergic medications like the antidepressants listed above. However, with psilocybin there is no evidence of this occurring, so it is not a major concern. If the decision is made to wean off a serotonergic antidepressant, the general advice is a period of two weeks to taper down before discontinuation, and six weeks to taper down for fluoxetine (prozac). Seek medical advice for this.

Alcohol use in conjunction with psilocybin is a big contraindication and a red flag. Alcohol reduces the body’s ability to metabolise psilocybin and increases the chance of adverse effects. With most dangerous, major adverse responses to psilocybin, including suicidality, there has been concomitant use of alcohol. Don’t drink alcohol if you are taking psilocybin.

Probably, one of the biggest risk factors for psilocybin use are accidents; driving after an experience, operating heavy machinery, looking after small children and being in a busy, dangerous or chaotic environment ia very bad idea.

To summarise, psilocybin is considered relatively safe but comes with some precautions:

  • know what you are ingesting

  • know your health, get a BP check

  • create a safe environment, before, during and after your experience

  • do a safety and risk assessment for accident prevention during, and for at least 8 hours after your experience

  • don’t drink alcohol before, during and after a psilocybin experience

Final thoughts, research estimates that in order to physically overdose on fresh psychedelic mushrooms you would need to consume 17kg (37.5lbs). That is roughly the weight of a three-year-old child!

I wish you all happy and safe travels 😊

I would like to reference the wonderful C.J. Spotswood, BSN, RN-BC for some of the clinical information in this blog. C.J. is a board certified psychiatric-mental health Registered Nurse who has presented at the American Psychiatric Nurse Association’s National Conference on “Psychedelics in Psychiatry: Exploring the Potential Use of Psychedelics for the Improvement of Persistent and Intractable Mental Health Symptoms”. You can follow C.J. on Facebook at EntheoNurse.

Written by Jo Dice

Psychedelic Integration and Integrative Psychotherapist

For more information on working with psychedelics and psychedelic integration psychotherapy, or if you would like to work with me, please follow me on social media or visit my website to book a free introductory session.

As well as being an experienced psychotherapist who has undergone comprehensive training in navigating psychedelics, I have also been a nurse for twenty years, meaning I bring a wealth of physical and mental health expertise.