Testing Psilocybin against a placebo for psychological distress

Exclusion

• −Current or previously diagnosed, or first-degree relative with, psychotic or bipolar disorder
• −Previously deemed eligible for MAiD with intention to proceed with MAiD regardless of study intervention effectiveness (this criteria is meant to exclude patients who would be unlikely to complete follow-upFollow-upContinued check-ins after the treatment part is finished.Read more → - those considering or being assessed for MAiD will still be eligible)
• −Documented or suspected delirium in the past 3 months without a clearly defined reversible cause (e.g. opioid toxicity, infection) and resolution
• −Documented moderate or severe dementia diagnosis
• −Inability to provide first-person informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more →
• −Inability to complete assessments via telephone or video-conferencing platform
• −Severe or unstable physical symptoms based on the judgment of the palliative care provider
• −Palliative Performance Scale (PPS) \<50%\*
• −Cancer with known central nervous system (CNS) involvement or other CNS disease
• −Use of high-dose psychedelic substances in the past year
• −Taking lithium at any dose
• −Taking tramadol at any dose
• −Taking tapentadol at any dose
• −Taking any monoamine oxidase inhibitor at any dose \[American Hospital Formulary Service (AFHS) group 28:16.04.12 or 28:36.32, including, but not limited to, moclobemide, tranylcypromine, phenelzine, selegiline, rasagiline\]
• −Taking any atypical antipsychotic (aripiprazole, asenapine, brexpiprazole, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone)
• −a. Note: patients can be included if their atypical antipsychotic is stopped or, if appropriate, substituted with haloperidol 48 hours prior to the start and for the duration of the intervention period and follow-up.
• −No enteral route of drug administration available
• −Does not apply to the open-labelOpen-labelEveryone knows which treatment is being given — nothing is hidden.Read more → access or open-label extension phases (since participants are expected to decline in overall health and function from baselineBaselineYour starting measurements, taken before treatment begins.Read more → due to natural disease progression towards the end of life).
• −Individuals with dementia (assessed at baseline by the treating team - no formal screeningScreeningThe checks done before joining, to see whether a study fits.Read more → of dementia will be done during the intervention or follow-up period) or delirium are excluded. While the safety and effects of psilocybin have not previously been studied in these populations, it can be reasonably assumed that hallucinogenic substances could exacerbate or lead to worsening of delirium or dementia symptoms common among people at the end of life (e.g., confusion, agitation).
• −The use of selective serotonin reuptake inhibitors (SSRIs) and antipsychotic medications (other than atypical antipsychotics) is a relative contraindication. For participants taking either an SSRI or an antipsychotic medication, there are several conditions for participation: (1) the palliative care provider must approve their participation in the study; (2) the SSRI/antipsychotic medication dose cannot change for the duration of the intervention trial and follow-up, and; (3) the patient must not be taking more than the maximum allowable trial dose for each SSRI.
• −The decision to not include SSRI and antipsychotic medications as an absolute contraindication was three-fold. Firstly, there is no empirical evidence from psilocybin microdosing literature that supports these medications as absolute contraindications. Risks related to serotonin syndrome are theoretical in nature for microdosing protocols, with no actual cases being observed. Secondly, the physician investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → team has estimated the risk to participants of rebound syndrome and associated symptoms from being taken off SSRIs and/or antipsychotics to be similar to or greater than that of serotonin syndrome. Lastly, to safely have participants stop taking SSRIs and/or antipsychotic medications, this would require a relatively long period of time (weeks to months) to taper the medication, which is not feasible for palliative care and end-of-life populations.
• −All trial participants must agree to not take any other psychedelic substance for the duration of the clinical trialInterventional studyA study where participants are given something to see what happens.Read more → and follow-up, and to notify the investigative team of any medication changes during intervention or follow-up. Participants must also notify the investigative team if any cannabis products are consumed during the treatment days. Participants must also agree not to take their benzodiazepine or antipsychotic medication, if applicable, within 12 hours (6 hours pre and 6 hours post) of taking their study dose. Participants must also agree not to drive or operate any heavy machinery on any treatment day after taking the drug (psilocybin or placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more →) for the duration of the 2-week intervention. Lastly, for patients in the community setting, participants must agree not to take the study dose alone for the first week of the intervention; at least one individual must stay with the participant at the time they take their dose and for at least 2 hours following dose administration. This is to ensure participants are not alone in the event of a serious adverse drug reactionSide effectAn unwanted effect thought to be caused by the treatment itself.Read more →.
• −Pregnancy or lactation