Criterion 2: Coexisting conditions

Learning Objectives

By the end of this module, the trainee will be able to:

• State the boundary of the facilitator's role in this criterion: to recognize coexisting conditions and route them to the right professional, not to diagnose or treat them.
• Explain the mechanism of serotonin syndrome as it arises from ayahuasca combined with serotonergic medication, at the level of monoamine oxidase A inhibition and synaptic serotonin.
• Apply the Hunter Serotonin Toxicity Criteria to recognize serotonin toxicity, and state why clonus is the most discriminating sign.
• Describe the cardiac liability of ibogaine at the level of the QT interval and the mechanism of torsades de pointes, and state the screening and monitoring it requires.
• Use a medication interaction framework to identify the drug classes that most often change or halt a plan, including selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, lithium, and tramadol.
• Distinguish pharmacodynamic from pharmacokinetic interactions, and give an example of each as it applies to psychedelic work.
• Identify the medical comorbidities that require clearance before proceeding, and distinguish psychiatric conditions that are contraindications from those that are indications.
• Distinguish the interaction profiles of the major compound classes, classic serotonergic psychedelics, MDMA, ketamine, ayahuasca, and ibogaine, well enough to know what a medication review is protecting against in each case.
• Apply the medical-intervention threshold, distinguishing medical care that is separable from the administration (often lawful, and best routed through the client's own treating team) from care that is inseparable from it (which cannot be made lawful and safe together, and is a stop), and route the legal question to counsel (see Criterion 41).
• Complete a structured coexisting-conditions review and a defensible referral, coordinated with the prescriber.

Key Terms

The medical-intervention threshold. The rule that where safe participation requires a medical intervention (ECG and cardiac monitoring, electrolyte management, intravenous access, a prescriber-supervised washout), that requirement is the practice of medicine, which an unlicensed facilitator may not provide. Whether a clinician may lawfully provide it turns on separability. Taught in full at Criterion 41.

Separable and inseparable medical care. Separable care stands on its own clinical footing and does not require the clinician to handle or administer the substance (pre-session cardiac clearance, a prescriber managing the client's own medication, a contracted clinician on site for emergency response), and is frequently lawful and often the right arrangement. Inseparable care functions only if delivered during and as an integral part of the administration (continuous cardiac monitoring with IV access through an ibogaine session), which makes the clinician a participant in an unlawful act where the substance is Schedule I. Even separable arrangements can carry clinician exposure, which is a question for counsel.

Coexisting condition. Any medical, psychiatric, or pharmacological factor present alongside the person's reason for seeking the work that alters risk or requires additional expertise to manage safely.

Serotonin syndrome (serotonin toxicity). A potentially fatal state of serotonergic excess marked by autonomic instability, neuromuscular hyperactivity, and altered mental status, which can arise when serotonergic agents are combined (Ruffell et al., 2020). The preferred diagnostic framework is the Hunter Serotonin Toxicity Criteria (Dunkley et al., 2003).

Hunter Serotonin Toxicity Criteria. A validated decision rule for diagnosing serotonin toxicity in a person with known serotonergic exposure, built on neuromuscular and autonomic signs, with clonus as the central discriminating feature. It is more sensitive and specific than the older Sternbach criteria (Dunkley et al., 2003).

Clonus. Rhythmic, involuntary muscle contractions elicited by sudden stretch (inducible), occurring without a trigger (spontaneous), or seen in the eyes (ocular). It is the single most discriminating sign of serotonin toxicity (Dunkley et al., 2003).

Monoamine oxidase inhibitor (MAOI). A drug that blocks the enzyme monoamine oxidase, raising synaptic monoamine levels. The harmala alkaloids in ayahuasca act as reversible MAO-A inhibitors, which is what renders oral DMT active (Ruffell et al., 2020; Halman et al., 2024).

QT prolongation. A lengthening of the cardiac QT interval, the time from ventricular depolarization to repolarization, that raises the risk of the ventricular arrhythmia torsades de pointes. Ibogaine is a known QT-prolonging agent (Cherian et al., 2024).

Torsades de pointes. A polymorphic ventricular tachycardia that can arise on a prolonged QT interval and can degenerate into ventricular fibrillation and sudden cardiac death. It is the specific arrhythmia the ibogaine cardiac precaution is designed to prevent.

Pharmacodynamic interaction. An interaction in which two agents act on the same physiological system, producing an additive, synergistic, or opposing effect, for example two serotonergic drugs combining toward serotonin syndrome.

Pharmacokinetic interaction. An interaction that changes the absorption, distribution, metabolism, or excretion of a drug, altering its concentration and duration, for example competition at cytochrome P450 enzymes (Halman et al., 2024).

Washout. A prescriber-supervised period during which an interacting medication is discontinued and cleared before a session, timed to the drug's elimination and, for irreversible enzyme effects, to the recovery of the affected enzyme.

Scope of practice. The set of activities a practitioner is trained, competent, and authorized to perform. Recognizing the edge of one's scope and referring beyond it is the core skill of this criterion.

Core Teaching

The facilitator's role: recognize and route

This criterion defines a boundary as much as a task. A facilitator is not being asked to diagnose or treat coexisting conditions. They are being asked to recognize them and route the person to the professional who can. The most dangerous errors in this field cluster at exactly this point: a facilitator either fails to detect a condition that changes the risk profile or detects it and proceeds anyway rather than referring. The pharmacology here is unforgiving, and it does not care about good intentions. This module pairs with Criterion 1, which surfaces these conditions during readiness screening; Criterion 2 is the discipline of routing them correctly.

The interaction that kills: serotonin syndrome

The single most important interaction to understand involves ayahuasca and serotonergic medication. Ayahuasca combines a plant containing N,N-dimethyltryptamine with a source of harmala alkaloids that act as reversible inhibitors of monoamine oxidase A. That inhibition is not incidental. Oral DMT is ordinarily destroyed in the gut and liver by monoamine oxidase before it can act, with a half-life on the order of minutes, so the MAO inhibition is precisely what allows the DMT to reach the brain and produce effects (Halman et al., 2024). The mechanism has a direct clinical consequence. Monoamine oxidase A is also the principal enzyme that catabolizes serotonin. When its activity is suppressed, synaptic serotonin rises. A person already taking a serotonergic drug, most commonly a selective serotonin reuptake inhibitor, and then dosing an MAO inhibitor stacks two serotonergic mechanisms on top of one another: reduced reuptake from the SSRI and reduced breakdown from the harmala alkaloids. Serotonin accumulates, and the result can be serotonin syndrome (Ruffell et al., 2020).

Ayahuasca has genuine clinical interest, which is part of why this hazard matters rather than being academic. A randomized placebo-controlled trial reported rapid antidepressant effects of ayahuasca in treatment-resistant depression (Palhano-Fontes et al., 2019). People will seek this work, and some will arrive on antidepressants. The facilitator who does not obtain and review the full medication list, by name, is not competent to sit with ayahuasca, because the hazard is a property of the pharmacology and no amount of ceremony changes it.

Recognizing serotonin toxicity: the Hunter criteria

Recognition is the facilitator's job; management belongs to the emergency system. Serotonin toxicity is a clinical diagnosis, since serum serotonin levels do not track severity, and the most accurate tool is the Hunter Serotonin Toxicity Criteria, which are more sensitive and more specific than the older Sternbach criteria (Dunkley et al., 2003). The Hunter rule requires known serotonergic exposure plus at least one of a short list of findings, and clonus, rhythmic involuntary muscle contraction, is the central discriminating sign. In a person with serotonergic exposure, any one of the following is sufficient: spontaneous clonus; inducible clonus with agitation or diaphoresis; ocular clonus with agitation or diaphoresis; tremor with hyperreflexia; or hypertonia with a temperature above 38 degrees Celsius together with ocular or inducible clonus (Dunkley et al., 2003). Onset is typically rapid, within hours of the interacting exposure. The severe form, marked by rapidly rising temperature and rigidity, is a medical emergency that can progress to multi-organ failure. The facilitator must recognize it early and activate emergency medical care.

The cardiac liability: ibogaine and the QT interval

Ibogaine carries a separate and equally severe risk that is cardiac rather than serotonergic. It prolongs the QT interval, the electrocardiographic measure of the time the ventricles take to depolarize and repolarize. A prolonged QT interval is the substrate for torsades de pointes, a polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation and sudden death. This is the specific pathway from an abnormal tracing to a fatal event, and it is why the QT number is not a formality. In a prospective observational study of magnesium-ibogaine therapy in veterans with traumatic brain injury, magnesium was given with the intention of reducing cardiac risk, alongside screening and monitoring (Cherian et al., 2024). Without a control group, the study cannot establish that magnesium prevented QT prolongation or cardiac complications. The operational consequence is strict. Any program working with ibogaine that lacks pre-treatment cardiac screening, continuous cardiac monitoring during administration, and genuine emergency capability is operating outside the bounds the evidence permits. This is not a setting a facilitator improvises.

The medical-intervention threshold: when the required safeguard cannot lawfully be supplied

Everything this criterion requires has an uncomfortable implication that should be stated plainly, because a facilitator who follows the workup faithfully will otherwise walk into it unprepared. Look at what the safeguards in this criterion actually are. A baseline electrocardiogram and an assessment of the QT interval is a medical investigation. Cardiology clearance and continuous cardiac monitoring during administration is medical care. Correcting and maintaining electrolytes, and holding intravenous access against a possible arrhythmia, is medical care. A washout of a serotonergic antidepressant before an ayahuasca-type brew is medication management, directed by a prescriber, and it is medical care. Each of these is the practice of medicine rather than an adjunct to a ceremony, and none of them may lawfully be performed by an unlicensed facilitator. That, by itself, is why this criterion routes rather than manages. The harder point sits one step further on. In the United States, a licensed clinician cannot lawfully administer, dispense, or prescribe a Schedule I substance outside federally authorized research, which includes psilocybin, MDMA, the DMT in ayahuasca, and ibogaine. So when the workup in this criterion identifies a client whose safe participation depends on a medical intervention, the intervention that would make them safe cannot lawfully be attached to the substance they are seeking. An unlicensed facilitator who supplies it is practicing medicine without a license. And a licensed clinician who administers the substance, or whose care is delivered as an integral part of administering it, is working with a Schedule I substance unlawfully, and risks the protection of the credential that made them competent to help, together with their professional liability cover. The safeguard that would make the client safe cannot simply be arranged in the way an ordinary medical referral can.

That statement needs a distinction, because in practice the picture is less uniform than a flat prohibition suggests, and the distinction is the one a facilitator should actually reason with. The question is whether the medical care is separable from the administration of the substance. Separable medical care stands on its own clinical footing and does not require the clinician to handle, administer, or participate in giving the substance. A cardiologist who evaluates a client and assesses their QT interval is practicing ordinary medicine. A prescriber who manages a client's antidepressant, or who supervises a taper for legitimate clinical reasons the patient independently has, is practicing ordinary medicine. A physician or paramedic contracted to be on site and to respond to a medical emergency, as they would at any gathering, is providing emergency care rather than administering a controlled substance. Care of this kind is frequently lawful and is often the right answer, and organizations do contract clinicians on precisely this basis. Inseparable medical care is different in kind. Continuous cardiac monitoring with intravenous access and electrolyte management through an ibogaine session is not standby emergency cover; the safeguard only functions if it is delivered during the administration and as an integral part of it, which makes the clinician a participant in the administration rather than a bystander to it. Where the safeguard is inseparable from the unlawful act, the claim that the clinician never touched the substance is thin cover, and the exposure is real.

Two honest qualifications belong with that distinction. The first is that separability mitigates the problem rather than dissolving it. A clinician who provides care in and around a setting where a Schedule I substance is being administered may still face exposure that this workbook is not competent to adjudicate, including questions of aiding and abetting, professional licensing-board discipline, and the exclusion of unlawful activity from professional liability coverage. Whether a given arrangement is defensible is a legal question with real consequences for the clinician, and it belongs with an attorney rather than with a facilitator's judgment, which is the raise-and-route discipline taught in Criterion 41. The second qualification is more constructive, and it points to what a facilitator should generally do. Where a client has a medical condition or a medication that bears on their safety, the most appropriate route is frequently to bring the client's own treating team into the process: the prescriber who knows their psychiatric medication, the cardiologist who knows their heart, the physician who manages their blood pressure. That care is separable by nature; it is already lawful, it is already established, and it improves the quality of the decision rather than merely satisfying a form. Coordinating with the client's existing providers, with consent, is the same care-coordination discipline the workbook builds elsewhere, and it is the version of medical involvement that is both lawful and genuinely protective. What remains true after all of this is the core of the threshold: where the safeguard a client needs can only be delivered as part of the administration itself, and the substance is Schedule I, there is no arrangement that makes that lawful and safe together, and the finding is a stop and a routing to a lawful setting rather than a logistics problem to be solved. The full legal structure, and the duty to convey it to clients, is taught in Criterion 41. What belongs here, in the screening function, is the recognition that a required medical safeguard is a gate, that separable care can often be arranged lawfully and should be, and that inseparable care cannot be.

Other medication interactions that change the plan

Beyond those two, several drug classes recur as decision points. Lithium combined with classic psychedelics has been associated with seizures and warrants specific inquiry rather than a general medication question (Johnson, Richards, & Griffiths, 2008; Halman et al., 2024). Monoamine oxidase inhibitors prescribed for depression carry the same serotonin syndrome logic as the harmala alkaloids in ayahuasca. Tramadol, which has serotonergic properties and lowers the seizure threshold, is a frequently overlooked entry precisely because people do not always think of an analgesic as a psychiatric drug. At the pharmacokinetic level, interactions also run the other way: selective serotonin reuptake inhibitors can blunt or shorten the psychedelic response through receptor downregulation and adaptation, and agents that inhibit or induce cytochrome P450 enzymes can alter the concentration and duration of compounds metabolized by those pathways, including LSD (Halman et al., 2024; Nichols, 2016). The systematic review of these interactions documents effects at both the pharmacodynamic and pharmacokinetic levels, some of which blunt the response and some of which potentiate and prolong it (Halman et al., 2024).

Pharmacodynamic and pharmacokinetic: why the distinction is practical

The two interaction types demand different responses, which is why the distinction is worth noting. A pharmacodynamic interaction is a collision of effects on the same system. The SSRI-plus-MAOI serotonin stacking is pharmacodynamic: two drugs pushing serotonin in the same direction, and the danger scales with their combined serotonergic load. The response is to prevent the combination, through a prescriber-supervised washout. A pharmacokinetic interaction changes how much drug is present and for how long. A cytochrome P450 inhibitor slowing the clearance of a psychedelic is pharmacokinetic: the compound is not more intrinsically dangerous, but its concentration and duration shift, which can turn an expected experience into a longer or more intense one. The response is a medical or pharmacy review of dose and timing. A facilitator who can place an interaction in the right category asks the right next question and refers to the right professional.

Medical comorbidities that require evaluation

The medical conditions that most often require clearance before proceeding are cardiovascular disease and uncontrolled hypertension, given the sympathomimetic load these compounds place on the system (Johnson, Richards, & Griffiths, 2008); seizure disorders, given the lowered threshold some combinations produce; and hepatic or renal impairment, given their effect on drug clearance. Metabolism is not an abstraction here. Psilocybin is a prodrug, rapidly dephosphorylated to its active form psilocin, which is then cleared hepatically, so significant hepatic impairment can alter exposure and duration (Nichols, 2016). Pregnancy is a standard exclusion in the absence of safety data. None of these findings is the facilitator's to manage alone. Each is a trigger for medical evaluation.

Psychiatric comorbidities: contraindication or indication

The psychiatric read requires a distinction that is easy to state and consequential to miss. A personal or first-degree family history of a primary psychotic disorder, and bipolar disorder with a history of mania, function as serious contraindications because these compounds can precipitate or worsen psychosis and mania (Johnson, Richards, & Griffiths, 2008). By contrast, depression, anxiety, and post-traumatic stress are frequently the reason a person seeks the work, and are conditions in which supervised psychedelic and entactogen therapy has shown benefit rather than reasons to exclude (Davis et al., 2021; Mitchell et al., 2021). The facilitator's task is to recognize which category a presentation falls into and to route the contraindications and the ambiguous cases to psychiatric evaluation. This mirrors the psychiatric read in Criterion 1; here the emphasis is on the routing decision that follows.

A note on compound classes

The interactions above are not uniform across every substance, because the compounds are not pharmacologically identical, and a medication review is only protective if the reviewer knows what class they are working with. The classic serotonergic psychedelics, psilocybin, LSD, DMT, act primarily through 5-HT2A agonism. MDMA is an entactogen that acts largely by releasing serotonin, dopamine, and norepinephrine, which gives it a heavier serotonergic load than the classic agonists and its own 5-HT2B considerations relevant to cardiac and valvular risk (McIntyre, 2023); a recent analysis comparing repeated low-dose exposure to known cardiotoxins argues the theoretical valvular risk of chronic 5-HT2B agonism should not be dismissed (Rouaud, Calder, & Hasler, 2024). Ketamine is a dissociative NMDA receptor antagonist with a different interaction profile entirely, weighted toward blood pressure, bladder, and dependence considerations rather than serotonergic ones. Ayahuasca adds the MAO-A inhibition discussed above. Ibogaine adds the QT liability. A facilitator does not need to be a pharmacologist, but they do need to know which class they are working with and which interactions that class carries, because the medication review is only as good as the questions the reviewer knows to ask.

Clinical and Decision Tools

Tool 1. Medication and substance interaction matrix

Review every entry on the person's medication and supplement list against this matrix. Any High-risk finding halts the process pending prescriber and medical coordination. Shaded rows are hard stops.

Tool 2. Serotonin syndrome recognition (Hunter criteria)

Serotonin syndrome is a medical emergency. Recognition is the facilitator's job; management is the emergency system's job. In a person with known serotonergic exposure, any one grouping below meets the Hunter criteria for serotonin toxicity (Dunkley et al., 2003). Onset is typically within hours.

Tool 3. Compound-specific required workup

Read this tool with the threshold in mind. The required workup states what safety demands. It does not make an unlawful setting safe. Ask whether the medical care is SEPARABLE from the administration. Separable care (cardiac clearance beforehand, a prescriber managing the client's own medication, a contracted clinician on site for emergency response) does not require the clinician to handle or administer the substance, is frequently lawful, and is often the right answer; involving the client's own treating team is usually the best route. INSEPARABLE care (continuous cardiac monitoring with IV access and electrolytes delivered during and as part of an ibogaine administration) makes the clinician a participant in an unlawful act, and there is no arrangement that makes it lawful and safe together. That finding is a stop and a routing to a lawful setting rather than a task to arrange. Even separable arrangements can carry clinician exposure (aiding and abetting, board discipline, liability-cover exclusions), which is a question for an attorney. Ketamine is the contrast: prescribable, so the safeguard and the law coexist. See Criterion 41.

Tool 4. Interaction type and matched response

Sort each flagged interaction into its type to choose the correct next step.

Tool 5. Referral decision guide

Each finding below is a trigger for referral, not for facilitator management. Route with clear reasoning and, with signed release, coordinate with the receiving professional.

Cardiac finding or QT concern: cardiology evaluation and clearance.

Serotonergic or interacting medication: the prescribing clinician, for washout planning or a decision not to proceed.

Psychiatric contraindication or ambiguity: psychiatric evaluation.

Hepatic, renal, or seizure history: primary care or the relevant specialist.

Signs of serotonin toxicity in session: emergency medical services, immediately; this is not a referral for later.

Worked Examples: Completed Coexisting-Conditions Reviews

The following models the reasoning and documentation this criterion should produce. Details are fictional.

Worked Example 1: A serotonergic stop-and-refer

Client: J.T., 47, seeking ayahuasca work for depression and grief.

Medication and supplement review: Reports sertraline 100 mg daily, prescribed for two years. Also takes a magnesium supplement and occasional over-the-counter ibuprofen. No other agents.

Interaction analysis: Sertraline is a selective serotonin reuptake inhibitor. Ayahuasca contains harmala alkaloids acting as MAO-A inhibitors. The combination stacks reduced serotonin reuptake against reduced serotonin breakdown, a pharmacodynamic serotonergic collision that carries a serotonin syndrome risk. This is a hard stop, not a matter for negotiation (Ruffell et al., 2020; Halman et al., 2024).

Medical review: No cardiac history; blood pressure normal on two readings. No hepatic or renal concerns reported.

Psychiatric review: No personal or family history of psychotic or bipolar disorder. Depression and grief are the presenting reasons, not exclusions.

Decision and referral: Do not proceed at this time. Refer to the prescribing clinician to determine whether a supervised sertraline taper and washout is clinically appropriate, recognizing that discontinuing an antidepressant carries its own risks and is the prescriber's decision, not the facilitator's. Re-evaluate only after the prescriber confirms a completed washout and a stable baseline. Rationale documented and, with signed release, shared with the prescriber.

Worked Example 2: An ibogaine cardiac gate

Client: A.R., 39, seeking ibogaine for opioid use disorder after multiple relapses. Highly motivated, reports being in good health.

Medication and supplement review: Takes an over-the-counter proton pump inhibitor for reflux and, on inquiry, an antiemetic obtained abroad whose name they do not know. No prescribed psychiatric medication.

Interaction and cardiac analysis: Ibogaine prolongs the QT interval and can precipitate torsades de pointes. The unnamed antiemetic is a specific concern, since several antiemetics are themselves QT-prolonging, which would be additive. No electrocardiogram has ever been done, so the baseline QT is unknown. This is a stop pending cardiac workup (Cherian et al., 2024).

Decision and referral: Do not proceed. Identify the antiemetic by name before anything else. Refer for cardiology evaluation including a baseline ECG and electrolytes. State plainly that ibogaine without pre-treatment cardiac screening, continuous monitoring, and emergency capability is outside the bounds the evidence supports, and that this program will not provide it without those elements in place. Document the reasoning. Note that opioid use disorder is a serious condition in its own right and warrant its own care pathway regardless of the ibogaine decision.

Case Vignettes

Work each vignette through the medication, medical, and psychiatric reviews, decide whether to proceed, defer, or refer, and identify precisely who must be involved. Fillable response sheets are in the companion worksheet PDF.

Vignette A

A person requests an ayahuasca retreat and, during the medication review, mentions they take an antidepressant but cannot remember its name and describes it as mild.

Guided questions: Why is not knowing the name unacceptable here? What is the specific mechanism you are screening for, and which interaction type is it? What has to happen, and who has to be involved, before this person could safely proceed?

Vignette B

On the morning of a psilocybin session, a participant offhandedly mentions a heart condition they did not disclose on their intake form, saying their cardiologist cleared them for exercise years ago.

Guided questions: Is an old exercise clearance sufficient here? What is the physiological concern with an undisclosed cardiac condition? Is this a proceed, defer, or stop, and what documentation do you need?

Vignette C

A person interested in ibogaine for opioid use disorder is highly motivated and reports no health problems, but has never had an electrocardiogram and takes an over-the-counter medication for acid reflux.

Guided questions: What is the specific ibogaine-related risk you must rule out, and what is the pathway from a prolonged QT interval to a fatal event? Why does the electrocardiogram matter here more than with psilocybin? What screening and monitoring are non-negotiable?

Vignette D

A person on an MAOI prescribed for depression asks about a psilocybin session, having read that psilocybin is a classic psychedelic and not an entactogen like MDMA. They reason that since psilocybin is not primarily a serotonin releaser, the MAOI is not a concern.

Guided questions: Is their pharmacological reasoning sound? What serotonergic risk remains when an MAOI is combined with a 5-HT2A agonist? How do you correct the misconception without dismissing their effort to understand, and who decides about the MAOI?

Vignette E

During an ayahuasca ceremony that a colleague is facilitating, roughly two hours after dosing, a participant develops agitation, sweating, a fast heart rate, and, on examination, clonus at the ankles. The participant had stated on intake that they took no medications.

Guided questions: Which Hunter criteria are met, and what does that tell you? What is your immediate action? What does this event reveal about the completeness of the original medication review, and what would you change?

Role-Play and Practice Scripts

Practice in pairs, then switch. The aim is a complete, unhurried review that treats the medication list as a safety instrument rather than a formality.

The complete medication and supplement review

“I need the full list of everything you take, prescription, over the counter, and supplements, including anything occasional. Please tell me the exact names, and if you are not sure, we will look them up together before we go any further. Some combinations with these medicines are genuinely dangerous, so this is one of the most important things we do.”

Pinning down a vague medication

“You mentioned an antidepressant but are not sure of the name. That detail is not optional here, because the specific drug determines whether a combination is safe or dangerous. Let us find the exact name now, from your pharmacy, your prescriber, or the bottle, before we plan anything.” Practice holding the line on specificity without making the person feel interrogated.

Coordinating a washout with a prescriber

“With your permission, I would like to contact your prescriber. Discontinuing an antidepressant is a medical decision that belongs with them, not with me, and I will not ask you to stop or change anything on your own. If they decide a supervised washout is appropriate, we coordinate the timing together.”

Explaining the ibogaine cardiac requirement

“Ibogaine can affect the electrical timing of the heart in a way that, in some people, causes a dangerous rhythm. That is why we require a heart tracing and a cardiologist’s clearance before, and continuous heart monitoring during. A program that skips these is not one I would trust with your safety.” Practice conveying a hard requirement as protection rather than obstruction.

Delivering a stop-and-refer decision

“Based on your medications, I cannot move forward safely right now, and I want to be precise about why. The combination carries a real risk of a dangerous reaction. Here is who needs to be involved, and here is what would have to be true before we could reconsider.”

Self-Assessment and Reflection

Knowledge check

1. Explain, at the level of the enzyme, why oral DMT requires an MAO inhibitor to be active, and why that same inhibition creates the serotonin syndrome risk with an SSRI.
2. State the Hunter Serotonin Toxicity Criteria in outline, and explain why clonus is the central discriminating sign.
3. Describe the pathway from a prolonged QT interval to sudden cardiac death, and name the safeguards used in the observational ibogaine study and the limits of what its design can establish.
4. Distinguish a pharmacodynamic from a pharmacokinetic interaction, give one psychedelic-relevant example of each, and state the matched response to each.
5. Give two psychiatric presentations that are indications for the work and two that are contraindications.
6. For each of psilocybin, MDMA, ketamine, ayahuasca, and ibogaine, name the single interaction concern that most defines its required workup.

Reflection

1. Where in your own practice is the temptation strongest to proceed despite a borderline finding rather than refer? What structure would remove that temptation?
2. Do you currently have a vetted referral relationship with a prescriber and a cardiologist? If not, that gap is a safety liability. What is your plan to close it?
3. A participant arrives having under-reported their medications, which you discover only mid-session. What in your intake process could have surfaced it earlier, and what will you change?

Summary

Criterion 2 draws the line between recognition and treatment. The facilitator's job is to detect coexisting medical, psychiatric, and pharmacological conditions and route them to the right professional, not to manage them. Two interactions dominate the safety picture and together form the safety spine of this workbook: the serotonin syndrome risk when ayahuasca's MAO-A inhibition combines with serotonergic medication, recognized clinically through the Hunter criteria with clonus at their center, and the fatal arrhythmia risk when ibogaine prolongs the QT interval and opens the door to torsades de pointes. Lithium, tramadol, and cytochrome P450 interactions round out the medication review, and sorting each interaction into its pharmacodynamic or pharmacokinetic type points to the correct response. Cardiac disease, seizure disorders, and hepatic or renal impairment trigger medical clearance, while the psychiatric read separates the contraindications, primary psychotic disorders and mania, from the conditions that are frequently the reason a person comes. Held correctly, this criterion produces a documented review and a clear referral, and it depends on a facilitator who knows the limits of their own scope and the pharmacology of the class in front of them.

References

Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021). Effects of psilocybin-assisted therapy on major depressive disorder: A randomized clinical trial. JAMA Psychiatry, 78(5), 481–489. https://doi.org/10.1001/jamapsychiatry.2020.3285

Johnson, M. W., Richards, W. A., & Griffiths, R. R. (2008). Human hallucinogen research: Guidelines for safety. Journal of Psychopharmacology, 22(6), 603–620. https://doi.org/10.1177/0269881108093587

McIntyre, R. S. (2023). Serotonin 5-HT2B receptor agonism and valvular heart disease: Implications for the development of psilocybin and related agents. Expert Opinion on Drug Safety, 22(10), 881–883. https://doi.org/10.1080/14740338.2023.2248883

Mitchell, J. M., Bogenschutz, M., Lilienstein, A., Harrison, C., Kleiman, S., Parker-Guilbert, K., Ot’alora G., M., Garas, W., Paleos, C., Gorman, I., Nicholas, C., Mithoefer, M., Carlin, S., Poulter, B., Mithoefer, A., Quevedo, S., Wells, G., Klaire, S. S., van der Kolk, B., … Doblin, R. (2021). MDMA-assisted therapy for severe PTSD: A randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine, 27(6), 1025–1033. https://doi.org/10.1038/s41591-021-01336-3

Nichols, D. E. (2016). Psychedelics. Pharmacological Reviews, 68(2), 264–355. https://doi.org/10.1124/pr.115.011478

Rouaud, A., Calder, A. E., & Hasler, G. (2024). Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins. Journal of Psychopharmacology, 38(3), 217–224. https://doi.org/10.1177/02698811231225609

Cherian, K. N., Keynan, J. N., Anker, L., Faerman, A., Brown, R. E., Shamma, A., Keynan, O., Coetzee, J. P., Batail, J.-M., Phillips, A., Bassano, N. J., Sahlem, G. L., Inzunza, J., Millar, T., Dickinson, J., Rolle, C. E., Keller, J., Adamson, M., Kratter, I. H., & Williams, N. R. (2024). Magnesium–ibogaine therapy in veterans with traumatic brain injuries. Nature Medicine, 30(2), 373–381. https://doi.org/10.1038/s41591-023-02705-w

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