Contraindications and Concomitant Medications and Supplements

While psilocybin is generally considered safe in a clinical setting (Little book of psychedelics), there always exist the possibility of interactions with other medications or adverse effects for clients with existing conditions or predispositions for certain conditions.

Health professionals should be mindful of possible interactions and consult a physician or pharmacist on the possibility of interactions. Any change in medication should be overseen by a licensed medical provider. Use of psychedelic medicines other than ketamine in a clinical setting is very new and has for many years been limited to highly controlled clinical trials. Not all concomitant medications have been studied.

Contraindications

The following conditions are contraindications for psilocybin administration.

Absolute Contraindications

Under no circumstances should a client use psilocybin if they have one of these conditions.

  • Ongoing therapy with a medication that has a potential interaction with psilocybin, including most types of psychiatric medications, where the medication cannot be tapered (see concomitant medications)

  • Present suicide risk that makes psilocybin-assisted psychotherapy unsafe (though history of remote suicide attempts may not be an exclusion)

  • Active or unstable substance use disorder that is not the indication for treatment will be evaluated on a case-by-case basis by the screening physician

  • Have received Electroconvulsive Therapy (ECT) within 12 weeks

  • Unwillingness to abstain from use of psychoactive substances (with the exception of nicotine and caffeine) for 24 hours prior to treatment

  • Unwillingness to abstain from the use of any non-prescription medicines or herbal supplements not approved by the treating care provider

  • First-degree relatives with any psychotic disorders or bipolar disorders

  • History of (or current) primary psychotic or mental health disorder which may include bipolar affective disorder type 1, major depressive disorder with psychotic features, or current dissociative identity disorder (DID)

  • Have a diagnosis of uncontrolled essential hypertension

Absolute Contraindications

Under no circumstances should a client use psilocybin if they have one of these conditions.

  • Seizure disorder or history of seizures

  • History of unstable or uncontrolled cardiovascular disease (coronary artery disease, heart failure, clinically significant ECG abnormality)

  • History of significantly impaired hepatic function

  • History of major central nervous system disease (history of cerebrovascular accident, masses, aneurysm)

  • History of uncontrolled obstructive airway disease or significant respiratory compromise

  • History of uncontrolled thyroid disease

  • History of narrow-angle glaucoma

  • Gastrointestinal conditions which may affect psilocybin absorption (i.e., stenosing peptic ulcer, pyloroduodenal obstruction)

  • Clients who are pregnant, breastfeeding, or planning/attempting to become pregnant during treatment period and are not practising an effective means of contraception. Breastfeeding clients are encouraged to abstain from breastfeeding for a minimum of 48 hours (and up to 96 hours) following treatment

Additional Scenarios

In addition to the contraindications, if the client meets any of the following criteria, psilocybin-assisted therapy is not recommended.

  • Are not able to give adequate informed consent

  • Lack of fluency in the language of the treating health professionals

  • Lack of stable living situation or lack of supportive family/network

  • Have any current problem which, in the opinion of the health professionals or supervising physicians, might interfere with participation in treatment

Concomitant Medications and Supplements

There are myriad more potential drug interactions between psilocybin and other substances. The following are selected based upon commonality or potential for severe risks in combination.

Drug Interaction
Serotonin reuptake blocking antidepressants (SSRIs) Reported to reduce effects of psilocybin in some, others have preserved effects of psilocybin while using this class of antidepressants (Becker et al., 2021). There is emerging evidence to suggest psilocybin’s efficacy is maintained with concurrent SSRI use and the risk of treatment-emergent adverse effects are negligible (including symptoms associated with serotonin toxicity) (NIH, 2021; Malcolm & Thomas, 2021).
Lithium

Increases the risk of seizures drastically with classic psychedelics such as psilocybin and should be avoided in combination (Nayak et al., 2021).
Monoamine Oxidase Inhibitors

Intensifies psychological effects of psilocybin, while long-term use of MAOIs diminishes them.
Typical Antipsychotics

May increase adverse psychological effects of psilocybin, while 5HT2A blocking or atypical antipsychotics (e.g., risperidone, chlorpromazine) decrease psychological effects (Vollenweider, 1998; Keeler, 1967).
Buspirone

Diminishes effects of psilocybin (Pokorny et al., 2016)

Several drugs with psychiatric indications including benzodiazepines and mood stabilizers (VPA) as well as NSAIDs may inhibit glucanosyltransferases and introduce hypothetical pharmacokinetic interactions, although data is lacking to confirm clinical significance (Liston et al., 2001).

In collaboration with the treatment physician, prescribed psychiatric medications will be tapered by the referring physician and discontinued at least five half-lives before psilocybin administration if considered safe and reasonable to do so. These medications include, but are not limited to:

  • Tricyclic antidepressants

  • Lithium

  • Selective Serotonin Reuptake Inhibitors (SSRIs)

  • Serotonin-Norepinephrine Reuptake Inhibitor (SNRIs)

  • Monoamine Oxidase Inhibitors (MAOIs)

  • St. John’s Wort

  • First and second-generation antipsychotic medications

  • Mood stabilizers including valproic acid, carbamazepine, topiramate

  • Any other medications viewed by the treatment physician as having potential serotoninergic activity

  • Opioid medications outside of a client’s opioid agonist therapy that is deemed by the treatment physician to present a safety risk or preclude successful participation in treatment

Health Professional Tip

How should you talk to your clients about relative and absolute contraindications when it comes to ketamine-assisted therapy?

Because this is a new treatment, cautions must be taken to ensure there are no underlying mental or physical vulnerabilities that may put the client at a greater risk of adverse side effects or potential harms. Current standard contraindications draw from conditions that have been excluded due to potential for risk in research that has been done to validate the treatment. Also, because psilocybin has psychoactive properties that cause a significant alteration in mood, thought, and behaviour during the acute effects, it’s important for individuals with mental health concerns to be evaluated for risk and appropriateness.

A relative contraindication is like an orange light/caution suggesting further evaluation and careful decision making weighing potential risks and benefits through informed consent.

An absolute contraindication is like a red light, meaning that this treatment is currently not recommend for someone with this particular condition.

As more research is done, inclusion and exclusion criteria typically broaden so that treatments can be proven safe enough for a broader range of people with a greater variety of underlying mental and physical health conditions.

References

Becker, A. M., Holze, F., Grandinetti, T., Klaiber, A., Toedtli, V. E., Kolaczynska, K. E., Duthaler, U., Varghese, N., Eckert, A., Grünblatt, E., & Liechti, M. E. (2021). Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects. Clinical pharmacology and therapeutics, 10.1002/cpt.2487. Advance online publication. https://doi.org/10.1002/cpt.24878.

Keeler, M.H. (1967). Chlorpromazine Antagonism of Psilocybin Effect. International Journal of Neuropsychiatry, 3, 66-71

Liston, H. L., Markowitz, J. S., & DeVane, C. L. (2001). Drug glucuronidation in clinical psychopharmacology. Journal of clinical psychopharmacology, 21(5), 500–515. https://doi.org/10.1097/00004714-200110000-00008

Malcolm, B. & Thomas, K. (2021). Serotonin toxicity of serotonergic psychedelics. Psychopharmacology.

National Institute of Health, U.S. National Library of Medicine. (2021) ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT047398659.

Nayak, S. M., Gukasyan, N., Barrett, F. S., Erowid, E., Erowid, F., & Griffiths, R. R. (2021). Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports. Pharmacopsychiatry, 54(5), 240-245. https://doi.org/10.1055/a-1524-2794

Pokorny, T., Preller, K. H., Kraehenmann, R., & Vollenweider, F. X. (2016). Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 26(4), 756–766. https://doi.org/10.1016/j.euroneuro.2016.01.005

Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F., Bäbler, A., Vogel, H., & Hell, D. (1998). Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport, 9(17), 3897–3902. https://doi.org/10.1097/00001756-199812010-00024