Treatment Protocols

Comprehensive psychiatric evaluation using CAPS-5 (Clinician-Administered PTSD Scale). Full medical screening including ECG, liver function tests, complete blood count, and thyroid panel. Psychiatric evaluation to rule out exclusionary diagnoses. If currently on SSRIs or SNRIs, a supervised medication washout period of 2-4 weeks is required with psychiatrist oversight.

Duration: 1-2 weeks

Building therapeutic alliance with the co-therapist pair. Psychoeducation about MDMA pharmacology, expected effects, and timeline. Discussing the trauma narrative at the participant's own pace. Establishing a safety plan and grounding techniques. Introducing the concept of 'inner healing intelligence' — the idea that the psyche has an innate drive toward healing when given the right conditions. Setting intentions without rigid expectations.

Duration: 3 sessions, 90 min each

Initial dose of 80-120mg MDMA administered orally with an optional supplemental dose of 40-60mg offered at the 1.5-2 hour mark. Conducted in a comfortable, aesthetically designed room. Participants wear eyeshades and listen to a curated music playlist. A male-female therapist pair remains present throughout. The protocol follows: blood pressure check at baseline, dosing, 30-45 minute onset period, music begins, inner-directed experience with minimal but supportive therapist guidance, supplement offered at 1.5 hours, peak experience at 2-3 hours, gradual return at 4-6 hours, integration discussion at 6-8 hours. Vital signs (BP, HR) monitored every 30 minutes. Temperature and hydration tracked. Overnight stay with a night attendant provided.

Duration: 8 hours + overnight

Three integration sessions following each medicine session. Processing experiences and emotions that arose during the MDMA session. Connecting new insights and perspectives to the trauma narrative. Building new cognitive frameworks and narratives around traumatic material. Homework includes journaling, body-based practices (yoga, somatic exercises), and creative expression. Preparing emotional readiness for the next medicine session.

Duration: 3 sessions, 90 min each

Same protocol as Session 1. Often deeper trauma processing occurs as the therapeutic alliance is stronger and the participant understands the experience. Dose may be adjusted based on response to the first session. Many participants report accessing previously unreachable emotional material.

Duration: 8 hours + overnight

Continued integration work. Assessment of progress using CAPS-5 interim measures. Determination of whether a third medicine session is clinically indicated based on symptom reduction and therapeutic judgment.

Duration: 3 sessions, 90 min each

Third session follows the same protocol if clinically indicated. For some participants, this is the session where the most profound shifts occur after two sessions of gradual deepening.

Duration: 8 hours + overnight

Final integration block followed by long-term follow-up assessments. CAPS-5 administered at 2 months post-treatment, then at 12 months. In the MAPP1 trial, 67% of participants no longer met diagnostic criteria for PTSD at the primary endpoint. Relapse prevention strategies, ongoing self-care practices, and community support connections are established.

Duration: 3+ sessions

PHQ-9 and MADRS depression assessment. Full medical screening including MRI if clinically indicated. Supervised medication taper: minimum 2 weeks off SSRIs (6 weeks for fluoxetine due to long half-life), 2 weeks off SNRIs, washout of MAOIs, lithium, and antipsychotics. Psychiatric evaluation to confirm MDD diagnosis and rule out psychotic features, active suicidality, bipolar I, and seizure disorders.

Duration: 2-6 weeks

Building rapport with the two trained guides who will be present during sessions. Discussing expectations and setting intentions. 'Flight instructions' — practical guidance for navigating the experience: what to do if overwhelmed, how to engage with difficult content, the importance of surrender over resistance. Teaching the 'TRY' framework: Trust the process, Relax your body and mind, Yield to the experience rather than fighting it. Familiarization tour of the treatment room (living-room-like environment with couch, art, plants). Challenging experience protocol discussed in advance.

Duration: 2-3 sessions, 2 hours each

Dose: 25mg/70kg psilocybin (moderate-to-high dose). Setting: living-room-like environment with a comfortable couch, eyeshades, and the Johns Hopkins Psilocybin Research playlist (curated classical and ambient music designed to support the arc of the experience). Two trained guides present throughout. Protocol: light breakfast on the morning of, dosing with water, 30-minute onset period, eyeshades on as effects begin, music plays through high-quality speakers, inner experience unfolds with guides available but maintaining a non-directive stance, peak at 2-3 hours, eyeshades removed when participant is ready, gentle discussion, light meal offered.

Duration: 6-8 hours

Next-day session focuses on immediate processing of the experience. What stood out, what was challenging, what felt meaningful. Second session one week later focuses on meaning-making and connecting insights to the experience of depression. Journaling strongly encouraged as homework. No interpretation is imposed by guides — participant-led sense-making.

Duration: 2 sessions over 2 weeks

Same protocol as Session 1, conducted 2 weeks after the first session. Dose may be adjusted to 30mg/70kg if the first session was well-tolerated but insufficiently deep. Participants often report different thematic content: while the first session may focus on emotional release, the second often involves deeper existential or relational insights.

Duration: 6-8 hours

Processing the second experience. Establishing lasting behavioral changes and new coping strategies. Outcome assessment using PHQ-9 and MADRS at 1 week, 4 weeks, 3 months, 6 months, and 12 months post-treatment. In Phase 2 trials, 71% showed clinically significant response and 54% achieved full remission at the 4-week primary endpoint.

Duration: 2-4 sessions over 4 weeks

Confirmation of treatment-resistant depression (failure of 2 or more adequate antidepressant trials). Comprehensive medical clearance including cardiac screening (ECG, blood pressure baseline), hepatic and renal function tests. Anesthesia risk assessment. Review of medication interactions, particularly with MAOIs, benzodiazepines (which may blunt response), and lamotrigine. Fasting requirement of 4-6 hours before each infusion. Baseline MADRS/PHQ-9 and dissociation scale (CADSS) assessment.

Duration: 1-2 sessions

Standard dose: 0.5mg/kg IV administered over 40 minutes via infusion pump, 3 times per week for 2 weeks (Monday-Wednesday-Friday schedule typical). Each session involves: IV line placement, baseline vital signs, infusion start with gradual titration, check at 10 minutes, check at 20 minutes, infusion completion at 40 minutes, followed by a 30-60 minute observation period before discharge with an escort. Continuous pulse oximetry monitoring. Blood pressure measured every 10 minutes during infusion. Dissociation monitored using CADSS scale. Common side effects include dissociation (resolves within 1-2 hours), nausea (20%), transient hypertension, and perceptual changes. Response typically begins after infusion 3-4.

Duration: 6 infusions over 2-3 weeks

MADRS and PHQ-9 reassessment after the 6th infusion. 50-70% of patients show significant response within hours to days. Approximately 30-40% achieve full remission. If no response after 6 infusions, treatment is typically discontinued. For responders, a maintenance schedule is established.

Duration: After infusion 6

Maintenance infusions tapered to every 2-6 weeks based on individual response duration. Some patients achieve sustained remission and can extend intervals. Monitoring for tolerance development is important. Concurrent psychotherapy enhances and sustains ketamine response. The esketamine (Spravato) intranasal variant follows a different schedule: 56mg or 84mg self-administered under clinical supervision, twice weekly for 4 weeks, then weekly for 4 weeks, then weekly or biweekly as maintenance.

Duration: Ongoing: every 2-6 weeks

Medical screening focusing on cardiovascular health, liver function, psychiatric history. Critical: screening for SSRI/SNRI/MAOI use — ayahuasca contains MAO inhibitors, creating a potentially fatal interaction with serotonergic drugs. Minimum 2-week washout from SSRIs (6 weeks for fluoxetine). 'Dieta' preparation: 1-2 weeks of restricted diet eliminating tyramine-rich foods (aged cheese, fermented foods, cured meats, red wine), reducing salt, sugar, spicy food, caffeine, alcohol. Sexual abstinence traditionally observed. Intention setting and journaling.

Duration: 2-4 weeks before ceremony

Light vegetarian meal at noon — no food after that. Group meeting with facilitator to discuss intentions, set group agreements, review safety protocols. Medical team performs vitals check. Ceremony space is prepared (maloca or ceremonial room with mattresses arranged in a circle, purge buckets, blankets, water).

Duration: Afternoon of ceremony day

The ceremony begins at nightfall. The curandero opens sacred space with prayers and/or icaros (traditional healing songs). Participants receive an individually dosed cup of ayahuasca brew (DMT content varies, typically 25-35mg DMT equivalent). Onset in 30-45 minutes. The experience unfolds over 4-6 hours with purging (vomiting, sometimes diarrhea) being a common and traditionally valued part of the process ('la purga'). The curandero sings icaros throughout, sometimes visiting individual participants for focused healing. Medical staff monitors for severe reactions. A second dose may be offered at the 2-hour mark if effects are mild. The experience includes vivid visions, emotional processing, somatic sensations, and often a sense of contact with non-ordinary intelligence or ancestral wisdom.

Duration: 4-6 hours (evening, starting ~8-9pm)

Morning-after sharing circle where participants describe their experiences in a structured, non-judgmental group format. Light breakfast. Individual integration sessions available. Continued dieta for 1-3 days post-ceremony recommended. Longer-term integration through journaling, therapy, body practices, and community support over following weeks.

Duration: Next morning + ongoing

Selecting source material and establishing consistent dosing. For dried mushrooms, grinding to powder and weighing with a precision scale (0.01g accuracy) is essential for consistency. Typical starting dose: 0.1g dried Psilocybe cubensis (roughly 1mg psilocybin). The dose should be sub-perceptual — no visual distortions, no impairment. If noticeable effects occur, reduce dose. Begin with a test dose on a free day to calibrate. Setting up a tracking journal for mood, energy, creativity, sleep quality, and any side effects.

Duration: 1-2 weeks

Developed by Dr. James Fadiman. Schedule: Day 1 — microdose day; Day 2 — transition day (afterglow, often reported as the most productive day); Day 3 — normal baseline day; Day 4 — microdose day (cycle repeats). Take dose in the morning with food. Do not microdose on consecutive days to prevent tolerance buildup. Run for 4-8 weeks, then take a 2-4 week break to reset tolerance and reassess effects. Track mood, creativity, focus, social ease, and sleep daily.

Duration: 4-8 weeks cycle

Developed by mycologist Paul Stamets. The 'stack' combines psilocybin microdose with lion's mane mushroom (500-1000mg) and niacin (vitamin B3, 100-200mg). Niacin causes a flush that theoretically distributes the compounds peripherally, and lion's mane provides nerve growth factor support. Schedule: 4 days on, 3 days off. Run for 4 weeks, then 2 weeks off. This protocol is more aggressive than Fadiman and may cause more tolerance issues. The niacin flush can be uncomfortable but is not dangerous.

Duration: 4 weeks on, 2 weeks off

After the first cycle, review the tracking journal. Are there measurable improvements in mood, focus, or creativity? Any negative effects (increased anxiety, sleep disruption, headaches)? If benefits are clear, continue with regular break periods. Long-term safety data is limited. Known risks include mild cardiac valve concerns at chronic high-frequency 5-HT2B agonism (theoretical, not proven at microdose levels). Recommended: annual cardiac check-up for chronic microdosers.

Duration: Ongoing

CRITICAL cardiac screening is the most important step. 12-lead ECG to measure QTc interval — ibogaine is absolutely contraindicated if QTc >450ms (males) or >470ms (females). Comprehensive cardiac workup: echocardiogram, stress test if indicated, electrolyte panel (magnesium, potassium, calcium — must be optimized). Liver function tests (ibogaine is hepatically metabolized via CYP2D6). Opioid use history: dose, duration, last use. Short-acting opioids must be last used 12-24h before treatment; long-acting (methadone) requires 72h+ washout. Blood toxicology screen. Psychiatric evaluation. HIV/hepatitis screening.

Duration: 1-2 weeks before

Admission to clinic. IV line placed for hydration and emergency access. Electrolytes rechecked and supplemented if needed (IV magnesium is common). Light meal, then fasting from midnight. Continuous cardiac telemetry monitoring begins. Psychological preparation: discussing intentions, reviewing what to expect during the experience (which is typically very different from classical psychedelics — more visionary/dreamlike, with a distinct 'life review' quality).

Duration: Day before treatment

Treatment typically begins in the morning. A test dose of 50-100mg ibogaine HCl is given first to check for allergic reaction or extreme sensitivity (30-60 min observation). If tolerated, the flood dose is administered: typically 15-20mg/kg ibogaine HCl, given in 2-3 divided doses over 1-2 hours. Onset within 1-2 hours. The acute visionary phase lasts 4-8 hours and involves a powerful, often dream-like experience with vivid autobiographical imagery (the 'life review'). Participants are supine with continuous cardiac telemetry (ECG, pulse oximetry, BP). The evaluative/processing phase follows for 8-12 hours — less intensely visionary, more cognitive/reflective. Residual effects continue for 24-72 hours. Withdrawal symptoms are typically dramatically reduced or eliminated within hours of the visionary phase onset.

Duration: 24-36 hours

Ibogaine has a very long half-life (noribogaine, the active metabolite, persists for days to weeks). Continued cardiac monitoring for at least 48-72 hours post-dose. Gradual reintroduction of food. Rest and sleep recovery (sleep is often disrupted for 24-48h). Nutritional supplementation. Begin psychological integration work. Daily ECG checks until QTc returns to baseline. Most patients report complete elimination of opioid withdrawal and significantly reduced cravings.

Duration: 3-7 days in clinic

The 'window of opportunity' after ibogaine treatment typically lasts 3-6 months — a period of reduced craving and increased neuroplasticity. This is the critical period for establishing new habits, support networks, and coping mechanisms. Recommended: ongoing psychotherapy, support group participation, lifestyle changes (exercise, nutrition, sleep hygiene). Booster microdoses of ibogaine (50-200mg) are sometimes used at monthly intervals. Without aftercare, relapse rates increase significantly after the 3-6 month window.

Duration: 3-12 months ongoing

Structured clinical interview to confirm OCD diagnosis (DSM-5 criteria). Y-BOCS baseline assessment (minimum score of 16 required for moderate OCD). Medical screening: ECG, CBC, LFTs. Medication review: SSRIs/SRIs should be tapered under supervision (minimum 2-week washout). Psychiatric evaluation to rule out comorbid psychotic disorders, bipolar I, and active suicidality.

Duration: 1-2 weeks

Building therapeutic rapport. Psychoeducation about psilocybin effects and the dose-escalation design. Discussion of OCD symptom patterns and triggers. Setting intentions around relationship with obsessive thoughts. Teaching acceptance-based strategies: observing thoughts without engaging compulsions.

Duration: 1-2 sessions, 90 min each

The Moreno protocol uses a within-subject dose-escalation design: very low (25 mcg/kg), low (100 mcg/kg), medium (200 mcg/kg), and high (300 mcg/kg) psilocybin doses administered in separate sessions spaced at least 1 week apart. Y-BOCS is administered at baseline, during the session (at peak), and at 24 hours post-session. In the pilot data, all doses produced acute reductions in Y-BOCS scores, with effects persisting for at least 24 hours. The highest dose produced the most robust and sustained effect. Vital signs monitored every 30 minutes. Setting: clinical room, recliner, eyeshades, curated music.

Duration: 4 sessions, 8 hours each, 1 week apart

Integration sessions focusing on insights from the psilocybin experiences and their relationship to OCD patterns. Y-BOCS reassessment at 1 week, 4 weeks, and 8 weeks post-final session. Exploration of whether new cognitive flexibility translates to reduced compulsive behavior. Development of exposure and response prevention (ERP) strategies building on psilocybin insights.

Duration: 4-8 weeks post-treatment

Confirm treatment-resistant depression: failure of at least 2 adequate antidepressant trials in the current episode. Enroll in the Spravato REMS program. Medical evaluation including baseline blood pressure, cardiac history, and hepatic function. Psychiatric assessment to rule out psychotic features. Establish concurrent oral antidepressant (newly initiated or continued). Baseline PHQ-9/MADRS and dissociation scale assessment. Discuss nasal spray administration technique. Cannot eat 2 hours before or drink 30 minutes before dosing.

Duration: 1-2 weeks

Week 1: 56mg esketamine intranasally (2 spray devices, 1 spray per nostril each). Week 2-4: 56mg or 84mg (3 spray devices) based on tolerability and response. Patient self-administers under clinician supervision. Each device delivers one spray per nostril. 5-minute rest between devices. Blood pressure measured pre-dose, at 40 minutes, and before discharge. 2-hour mandatory observation period post-dose: patient must remain in certified healthcare setting. No driving for remainder of dosing day. Common effects: dissociation, dizziness, nausea, sedation, vertigo — typically resolve within 2 hours.

Duration: 4 weeks, twice weekly

Weeks 5-8: once weekly dosing at 56mg or 84mg. Week 9 onward: once weekly or once every 2 weeks, based on clinical assessment. Continue concurrent oral antidepressant. Periodically reassess need for continued treatment. Same 2-hour monitoring requirement applies for every session. PHQ-9/MADRS monitoring at regular intervals. If response is lost during less frequent dosing, return to weekly schedule.

Duration: Ongoing: weekly to biweekly

Individual screening per standard psilocybin protocol (psychiatric evaluation, medical clearance, medication washout). Group composition is intentional: similar conditions, balanced demographics, no pre-existing relationships (to reduce social dynamics). Group size: 3-6 participants. Participants meet each other in a structured introduction session before the medicine day.

Duration: 2-3 weeks

Group-based preparation conducted by the therapy team. Session 1: Psilocybin psychoeducation, sharing personal stories and intentions, group agreements (confidentiality, respect, non-judgment). Session 2: Practical preparation, challenging experience protocol, establishing trust within the group, discussing boundaries around physical contact during the session.

Duration: 2 sessions, 2-3 hours each

All participants receive their psilocybin dose simultaneously (typically 25mg/70kg). Each participant has their own mattress, eyeshades, blanket, and headphones with individual music. The shared space allows natural interactions while maintaining individual focus. Therapist-to-participant ratio of 1:2 or 1:3. Each participant is periodically checked by a designated therapist. The group setting creates a unique container where participants may be aware of others' experiences (hearing emotions, movement) which can be normalizing and supportive. Vital signs monitored individually.

Duration: 6-8 hours

The morning after: group sharing circle where each participant describes their experience. Facilitated by therapists to ensure equal time and non-judgment. Follow-up group sessions at 1 week and 4 weeks. The group format provides ongoing peer support and shared meaning-making that is not available in individual protocols. Participants often form lasting support connections.

Duration: 2-3 sessions over 4 weeks

Volumetric dosing is essential for LSD microdosing due to the microgram-level precision required. Dissolve a known quantity of LSD in distilled water or alcohol (e.g., 100mcg in 10ml = 10mcg per 1ml). Use amber glass bottles to protect from light degradation. Store in refrigerator. Start with 5mcg on a free day to calibrate — the dose should be fully sub-perceptual. Increase by 2.5mcg increments if no effect is noticed. Typical effective range: 8-15mcg. If visual distortions, body load, or cognitive impairment occur, the dose is too high.

Duration: 1 week

Day 1 (Dose day): Take calibrated microdose in the morning with breakfast. Effects last 8-12 hours — do not dose in the afternoon. Day 2 (Transition): No dose. Many report this as the day with the most noticeable positive effects (afterglow). Day 3 (Rest): No dose. Baseline comparison day. Day 4: Repeat cycle. Morning dosing is critical because LSD's long duration can interfere with sleep if taken too late. Track mood, focus, creativity, energy, sleep quality, and social interactions daily. After 4-8 weeks, take a minimum 2-week break.

Duration: 4-8 weeks

Review tracking journal after first cycle. Key question: are benefits distinguishable from placebo/expectation effects? Consider a self-blinding protocol (Szigeti et al. model) to test. Long-term safety considerations for LSD microdosing include: potential cardiac valve effects from chronic 5-HT2B agonism (theoretical risk, shared with psilocybin), tolerance development, and the risk of dose creep. Unlike psilocybin, LSD also acts on dopamine D2 receptors, which could theoretically contribute to different long-term effects.

Duration: Ongoing

Rigorous medical screening: cardiac evaluation (ECG, BP baseline), respiratory assessment (5-MeO-DMT can cause temporary apnea), and psychiatric evaluation. CRITICAL: screen for MAOI use — 5-MeO-DMT is metabolized by MAO-A, and concurrent MAOIs can be fatal. Screen for SSRI use (serotonin syndrome risk due to potent 5-HT1A and 5-HT2A agonism). Previous psychedelic experience is strongly recommended due to the intensity. Preparation sessions focus on surrendering to the experience, as resistance at these doses can be extremely psychologically distressing.

Duration: 1-2 weeks

Synthetic 5-MeO-DMT is preferred over toad venom for precise dosing and reduced variable compounds. The substance is vaporized and inhaled in a single deep breath, typically at doses of 5-15mg (lower range for first experience). Onset is near-instantaneous (10-30 seconds). The participant lies supine immediately. A trained sitter maintains physical safety — particularly monitoring breathing and body position (recovery position if needed). The experience involves rapid ego dissolution, somatic intensity, potential vocalization/movement, and temporary loss of motor control. Pulse oximetry and BP monitoring throughout. The peak lasts 5-15 minutes, followed by 15-30 minutes of gradual return. A second dose may be offered 30-45 minutes later if the first was sub-threshold.

Duration: 60-90 minutes (active effects: 15-45 min)

5-MeO-DMT experiences can be profoundly disorienting and require careful integration. The experience often defies verbal description, making integration particularly challenging. Sessions focus on body-based processing, art, and somatic practices. 'Reactivations' (spontaneous re-experiencing of the 5-MeO-DMT state) can occur days to weeks later and should be normalized. Integration therapy should address: existential insights, potential psychological destabilization, changes in worldview, and relationship to self/others post-experience.

Duration: 1-4 weeks

DSM-5 Alcohol Use Disorder diagnosis confirmation (moderate to severe). Timeline Follow-Back (TLFB) assessment of drinking patterns. Medical screening: CBC, LFTs (particularly GGT and MCV as drinking biomarkers), ECG, BP. Psychiatric evaluation: comorbid depression, anxiety, and trauma history are common and not exclusionary. Active alcohol withdrawal requiring medical management is exclusionary — patients must be stable. No requirement for abstinence at enrollment, but must not be in acute withdrawal.

Duration: 1-2 weeks

MET is the psychotherapeutic backbone of the protocol. Based on motivational interviewing principles. Sessions explore ambivalence about drinking, develop personal motivation for change, and establish a change plan. The first 4 MET sessions also serve as preparation for the first psilocybin session: building therapeutic alliance, discussing psilocybin expectations, and setting intentions around the relationship with alcohol.

Duration: 4 sessions over 4 weeks

25mg/70kg psilocybin administered in the standard clinical setting (comfortable room, eyeshades, curated music, 2 trained monitors). The session follows standard psilocybin administration protocols. Participants are encouraged to explore their relationship with alcohol during the experience, though the approach remains non-directive. Vital signs monitored. Integration discussion at the end of the session.

Duration: 8 hours

4 additional MET sessions integrating insights from the first psilocybin experience and preparing for the second. TLFB reassessment of drinking patterns. Second psilocybin session at 25mg/70kg follows the same protocol. Participants often report that the second session deepens insights about the role of alcohol in their lives.

Duration: 4 MET sessions + 1 psilocybin session over 4 weeks

Final 4 MET sessions focus on maintaining changes, relapse prevention, and ongoing integration. TLFB drinking assessment at weeks 12, 24, and 32. In the Bogenschutz trial, the psilocybin group showed 83% reduction in heavy drinking days at 32 weeks, with 48% achieving complete abstinence in the final 8 weeks vs. 24% in the placebo group.

Duration: 4 MET sessions over 8 weeks + follow-up to 32 weeks

Each partner undergoes individual screening: full medical evaluation, psychiatric assessment, CAPS-5 for PTSD, PHQ-9 for depression, and relationship satisfaction measures (DAS-4 Dyadic Adjustment Scale). Both partners must be medically cleared for MDMA. Exclusion of active domestic violence (safety risk when defenses are lowered). Couple assessment: relationship history, communication patterns, areas of trauma impact on the relationship. Both partners must provide fully informed consent and understand they will be in an altered state together.

Duration: 2-3 weeks

Joint therapy sessions establishing communication guidelines, discussing trauma narratives (as appropriate), and learning emotion regulation skills. MDMA psychoeducation including the distinct experience of MDMA with a partner vs. alone. Setting agreements: what happens in the session stays in the session (no using session content as ammunition later). Discussing boundaries around physical contact during MDMA session. Practicing active listening and empathic reflection.

Duration: 3-4 sessions, 90 min each

Both partners receive MDMA simultaneously (75-125mg each, based on body weight). A co-therapist pair facilitates (ideally one male, one female). The session typically begins with individual inner experience (eyeshades, music) for the first 60-90 minutes, then transitions to dyadic interaction when both partners feel ready. The empathogenic window (2-4 hours post-dose) is used for facilitated couple communication: addressing difficult topics, expressing needs and fears, rebuilding emotional connection. Optional supplement dose for one or both partners at 1.5-2 hours. The final hours are for continued conversation and beginning integration.

Duration: 8 hours

Integration sessions as a couple, facilitated by the therapy team. Processing what was shared during the MDMA session. Building on emotional breakthroughs with practical communication skills. Addressing any difficult material that emerged. Developing a shared narrative about the experience. CAPS-5 and DAS-4 reassessment at 4 and 8 weeks. The integration period is critical: without it, the emotional openness during the session may not translate to lasting relationship change.

Duration: 4-6 sessions over 8 weeks

Psychiatric evaluation and medical clearance (BP screening critical — ketamine raises BP). Establishing therapeutic goals: what specific emotional material or life issues will be explored? Psychoeducation about the psycholytic ketamine experience: different from both IV infusion and recreational use. At psycholytic doses, patients describe enhanced emotional sensitivity, novel perspectives on problems, reduced fear of emotional content, and mild perceptual shifts without full dissociation. Building the therapeutic relationship before introducing the medicine.

Duration: 2-3 sessions

Sublingual route: 100-400mg ketamine lozenge (troche) held under the tongue for 10-15 minutes, then swallowed or expectorated. Onset: 15-20 minutes. Duration: 45-90 minutes. IM route: 0.3-0.5mg/kg intramuscularly. Onset: 3-5 minutes. Duration: 30-60 minutes. The session begins with a brief check-in (10-15 minutes), then ketamine administration. During the ketamine-active period, the therapist conducts psychotherapy — not just monitoring as in IV protocols. Techniques include guided imagery, somatic experiencing, EMDR elements, or emotion-focused exploration. The therapist remains actively engaged, asking questions and guiding attention. A post-session integration discussion (15-30 minutes) occurs as effects wane. BP monitored before, during, and after.

Duration: 90-120 min each, weekly or biweekly

Between KAP sessions, standard therapy sessions (without ketamine) process material that emerged. As therapeutic goals are met, KAP sessions are spaced out and eventually transitioned to maintenance (monthly or as-needed). Some patients benefit from a short intensive course (6 sessions over 3 weeks) followed by monthly maintenance. Assessment at regular intervals using PHQ-9, GAD-7, PCL-5, or other relevant measures.

Duration: Ongoing

AN patients require additional medical screening beyond standard psilocybin protocols due to the physiological effects of malnutrition. Critical assessments: ECG (QTc prolongation from electrolyte imbalance), comprehensive metabolic panel (electrolytes — hypokalemia, hyponatremia, hypomagnesemia common in AN), renal function, phosphorus levels (refeeding syndrome risk), bone density if severely underweight. BMI must be above a minimum threshold (typically BMI >= 15 kg/m2, though this varies by study). Cardiac monitoring for bradycardia and arrhythmias. Patients must be medically stable — active refeeding syndrome is exclusionary.

Duration: 2-4 weeks

AN-specific preparation addresses the unique therapeutic needs of this population. Building trust and safety (AN patients often have high levels of mistrust and control needs). Psychoeducation about how psilocybin may relate to AN cognitions: disrupting rigid thought patterns about food, body, and control. Discussing fears about the experience (particularly around loss of control, which is a core AN theme). Setting intentions: not about eating behavior specifically, but about relationship with the self, emotions, and flexibility.

Duration: 3 sessions, 90 min each

25mg COMP360 synthetic psilocybin administered orally. The session follows the standard COMP360 framework: comfortable room, eyeshades, curated music, 2 trained therapists. AN-specific adaptations: light snacks available post-peak (a therapeutic opportunity to relate to food in an altered state), body-awareness exercises during the experience, and therapist attunement to body image-related distress. Vital signs monitored with particular attention to heart rate (AN patients may have baseline bradycardia). The experience may involve confrontation with body-related themes, emotional processing of restriction behaviors, and potentially novel perspectives on the function of the eating disorder.

Duration: 6-8 hours

Integration sessions focus on translating psilocybin insights into changes in the AN cognitive framework. Eating Disorder Examination (EDE) and EDE-Q reassessment. Monitoring for: changes in cognitive rigidity (WCST or similar), body image disturbance (BIQ), dietary flexibility, and weight restoration trajectory. Integration therapy may incorporate acceptance and commitment therapy (ACT) elements, which align well with psilocybin-induced psychological flexibility. Nutritional counseling concurrent throughout.

Duration: 6-12 weeks