Psilocybin-assisted therapy (Hopkins, NYU, Imperial)

1. Introduction

Version followed: the Johns Hopkins safety frame (Johnson, Richards & Griffiths 2008, "Human hallucinogen research: guidelines for safety") as the shared session structure; the NYU cancer-distress trial (Ross et al. 2016) as its authors and therapists describe it; and the Imperial College London depression trials with the ACE model (Accept, Connect, Embody; Watts & Luoma 2020; Murphy et al. 2022). Where the three differ, the guide says so. Dosing, administration and medical procedures are left out on purpose: they belong to the prescribing and medical team.

Source status. The structure of the ACE model comes from the ACBS abstract of Watts & Luoma 2020 and a secondary summary of the full paper; no public ACE manual is available in these sources, so the ACE exercise steps in 4.5 are [synthesis]. The NYU psychotherapy description comes from Ross et al. 2016 and a 2019 interview with Anthony Bossis; the NYU therapist manual and the paper's Supplementary Methods are not used here [uncertain]. The July 2025 UK government response is taken from the Home Office's published response; UK scheduling and the licensing burden come from Drug Science and the University of Manchester; COMP360's FDA status comes from Compass Pathways releases and an SEC filing of April to August 2026, which are company sources, not FDA pages [uncertain]. The Yale Manual (Guss, Krause & Sloshower 2020) is a Yale protocol, not NYU's, and is not used for content here.

What it is. Psilocybin-assisted therapy is a protocol, not a stand-alone psychotherapy. A screened participant has preparation meetings with a therapist pair, then one or more supervised psilocybin sessions in a calm, home-like room with eyeshades and music, then integration meetings. It has been used in two ways. Johns Hopkins and Imperial used it for major or treatment-resistant depression. NYU and Johns Hopkins used it for anxiety, depression and existential distress in people with life-threatening cancer. [source: Johnson et al. 2008; Ross et al. 2016; Murphy et al. 2022; Davis et al. 2021]

End-of-life use is psychological support only. It sits alongside oncology and palliative care. It is never a treatment for cancer, and it never replaces medical care. NYU therapist Jeffrey Guss called it "chemotherapy for the fear of cancer", which is a metaphor, not a claim about the disease. [source: ASCO Post 2015]

How change is thought to happen.

• Hopkins: a good outcome depends mainly on psychological factors (preparation, trust, setting and interpersonal support), not only on the drug. In the cancer and depression trials, the authors link benefit to intense, often mystical-type or emotionally significant experiences. [source: Johnson et al. 2008]
• NYU: the authors describe a "supportive and integrative psychotherapy treatment model" with an existential and spiritual focus. Patients reported less fear of death, more self-compassion and a sense of separation from the disease ("I am not my cancer"). NYU likens the approach to the historical "psychedelic-peak" model and contrasts it with psycholytic approaches. [source: Malone et al. 2018; ASCO Post 2015]
• Imperial: the authors describe a move from experiential avoidance and disconnection towards acceptance of difficult emotion and connection to self, others, values and the body. This is a psychological-flexibility account taken from Acceptance and Commitment Therapy (ACT). [source: Watts & Luoma 2020; Murphy et al. 2022]

Legal and regulatory status. As of the Drug Science review dated June 2026:

• US: federal access is limited to research and exceptional pathways. Oregon and Colorado have regulated state programmes created by ballot measure. Utah has a three-year pilot limited to designated health systems, and New Mexico has a Department of Health pathway.
• Australia: a federal Authorised Prescriber framework applies.
• Canada: limited federal access; Alberta has a provincial framework.
• Czech Republic: prescription for some mental disorders under strict conditions from 1 January 2026.
• Germany: a 2025 compassionate-use programme for treatment-resistant depression, which is not marketing approval.
• Switzerland and New Zealand: individual exemptions or approvals only.

[source: Drug Science 2026]

UK. Psilocybin is in Schedule 1 of the Misuse of Drugs Regulations 2001, the most tightly controlled schedule. Research needs a Home Office domestic licence, which the sources describe as a significant financial and bureaucratic barrier. In December 2023 the ACMD recommended exempting universities and hospitals, and trials that already have MHRA, HRA or ethics approval, from that licence. On 16 July 2025 the government agreed to both points in principle: for universities and hospitals subject to operational feasibility and through a pilot scheme, and for studies with MHRA, HRA or research ethics approval by first creating an exemption for administering Schedule 1 drugs within those studies. [source: Home Office, government response to the ACMD's report on barriers to research, part 2, 16 July 2025] This is a licensing exemption, not a move to Schedule 2. These sources report no MHRA-approved psilocybin medicine [uncertain: check the MHRA's current product information]. COMP360 holds UK Innovative Licensing and Access Pathway (ILAP) designation for treatment-resistant depression. [source: Drug Science 2025; University of Manchester impact page; Compass Pathways, April 2026]

US federal and FDA. Psilocybin is still investigational at federal level. Compass Pathways' COMP360, a synthetic psilocybin formulation, has FDA Breakthrough Therapy designation for treatment-resistant depression. Compass reports two positive phase 3 trials (COMP005 and COMP006). In April 2026 the FDA granted rolling submission and review of its New Drug Application (NDA) and selected COMP360 for the Commissioner's National Priority Voucher programme, which offers a review of 1–2 months once the NDA is filed. As of 5 August 2026, some NDA modules had been submitted and Compass expected to complete the filing in Q4 2026; its 7 July 2026 SEC filing gives the same timing and a planned launch in the first half of 2027, subject to FDA approval and DEA rescheduling. Launch would need both FDA approval and DEA rescheduling. No FDA approval of a psilocybin product had been reported by then. [source: Compass Pathways, April and August 2026; Compass Pathways Form 8-K, 7 July 2026] [uncertain] Later events (completion of the filing, an FDA decision, DEA rescheduling) and other sponsors' designations are not covered here. Check them before advising anyone.

Outside a licensed trial or a regulated programme, a clinician's role is assessment, harm reduction and integration only, never facilitation (see 4.6).

2. Framework

The core structure is the same at all three sites: screening → preparation → psilocybin session(s) → integration → follow-up. [source: Johnson et al. 2008; Watts & Luoma 2020]

Phase 0: Screening and eligibility.

• Goal: exclude people for whom the risk is unacceptable.
• Format: psychiatric interview and medical work-up. Hopkins lists medical history, physical examination, ECG, blood tests and urinalysis, done by medical staff.
• Published psychiatric exclusions: current or past psychotic disorder or bipolar I or II disorder, and a first- or second-degree relative with these (Hopkins). In the Hopkins depression trial, also a serious suicide attempt or a past psychiatric hospitalisation (Davis et al. 2021).
• Other Hopkins exclusions: severe depression or anxiety needing immediate medication, including active suicidal ideation; pregnancy or no reliable contraception; blood pressure outside set limits; and some medications and supplements (Hopkins names lithium, tricyclic antidepressants and some serotonergic drugs and supplements). Medication questions are for the prescriber.
• Inclusion: NYU required life-threatening cancer plus an anxiety-related diagnosis, and patients were not taking psychotropics at enrolment. Hopkins depression required a major depressive disorder diagnosis and no current antidepressant.
• Moving on: clear medical and psychiatric screening, plus informed consent.

[source: Johnson et al. 2008; Davis et al. 2021; Ross et al. 2016]

Phase 1: Preparation.

• Goal: trust and rapport, informed consent, knowing what may happen and how to meet it, practical safety, and intentions.
• Format by site:
  • Hopkins: at least four meetings totalling at least eight contact hours, usually over about a month. The lead monitor attends all of them and the second monitor at least one. Some take place in the session room.
  • NYU: three two-hour sessions, including a full personal history.
  • Imperial: about five hours, plus a check-in call 7–10 days before the session about practicalities and music.
• Moving on: proceed only when trust is sufficient. If it is not, Hopkins adds contact hours or cancels. Bossis (NYU): "Without that rapport and trust, we wouldn't go to the dosing session."

[source: Johnson et al. 2008; ASCO Post 2015; Murphy et al. 2022]

Phase 2: Psilocybin session(s).

• Goal: a safe, contained, inward-focused experience.
• Format: a full day in a living-room-like room with two therapists or monitors present throughout and a physician available. Medical monitoring is done by medical staff.
• Not given here: the number, timing and spacing of drug sessions, which the protocol and medical team set.
• Moving on: the session ends only when the acute effects have resolved. The participant then goes home with a briefed companion or stays overnight on site.

[source: Johnson et al. 2008; ASCO Post 2015; Murphy et al. 2022]

Phase 3: Integration.

• Goal: make sense of the experience, check stability and translate insight into daily life.
• Format by site:
  • Hopkins: a meeting usually the next day, with more if difficulties persist.
  • NYU: three integration sessions after each drug session.
  • Imperial: a two- to three-hour in-person session the morning after, plus optional weekly one-hour calls with the main guide as clinically indicated. A three-month check-in was reported, after which the relationship ended.
• Hopkins depression trial: about 11 hours of supportive psychotherapy in total across the course.
• Moving on: psychological stability, no persisting perceptual or psychiatric problems, and a planned ending or onward referral.

[source: Johnson et al. 2008; ASCO Post 2015; Murphy et al. 2022; Baker Jones 2022; Davis et al. 2021]

Phase 4: Follow-up. Outcome assessments continue for months, about six months at NYU. Ask specifically about persisting perceptual changes. [source: ASCO Post 2015; Johnson et al. 2008]

Staffing.

• Hopkins: at least two monitors; lead monitors were clinical psychologists or clinical social workers. Mixed-gender teams are preferred where possible. Both monitors should not be the opposite gender to the participant unless a same-gender staff member who knows them can come quickly. A clinical psychologist or psychiatrist should be available for consultation.
• Imperial: two guides, mostly trained or training clinical psychologists, psychotherapists or psychiatrists, all with experience of non-ordinary states. One main guide attended all six face-to-face visits. Monthly group supervision was run by a consultant psychiatrist and psychotherapist.

[source: Johnson et al. 2008; Murphy et al. 2022]

3. Guiding principles

• The frame is the treatment. Plan preparation, setting and support as carefully as any clinical procedure. [source: Johnson et al. 2008]
• Safety comes before procedure. Hopkins: "Volunteer safety must take priority over scientific procedures." Pause assessments or any agenda when the person needs support. [source: Johnson et al. 2008]
• Trust is a precondition. If trust is not there, do not proceed: add preparation hours or stop. [source: Johnson et al. 2008; ASCO Post 2015]
• Participation stays voluntary. Rapport must never become pressure to continue. Say plainly that withdrawal at any point will be supported. [source: Johnson et al. 2008]
• The participant is never alone. One monitor stays in the room at all times, including toilet trips (with the door unlocked or the key held by staff). [source: Johnson et al. 2008]
• Be non-directive. Follow the participant's process rather than steering content. Imperial guides worked "in a non-directive and open manner" with unconditional positive regard, as a "warm, nondirective, embodied presence." [source: Murphy et al. 2022; Baker Jones 2022]
• Approach, don't avoid. Prepare and support the person to move towards frightening or painful material rather than away from it. [source: Johnson et al. 2008; Murphy et al. 2022]
• Turn attention inward. Eyeshades and music support an inward focus. Encourage the person to collect the experience now and talk about it later. [source: Johnson et al. 2008; Murphy et al. 2022]
• Reassure; don't argue reality. Respond to fear with calm, empathy and orientation, not with reality-testing ("talking down"). [source: Johnson et al. 2008]
• Agree touch in advance and keep it limited. Discuss supportive touch (hand-holding, a hand on the arm or shoulder) in preparation and practise it. Use it only as agreed. [source: Johnson et al. 2008; Murphy et al. 2022] [synthesis] Document the agreement, re-check consent on the day, and treat any change of mind as final.
• Avoid shaping expectations. Hopkins describes the range of effects verbally and avoids giving published trip accounts to read. [source: Johnson et al. 2008]
• Treat everyone with respect. Every staff member the participant meets, from reception to security, is part of the setting. Being treated "like a guinea pig" is named as a risk. [source: Johnson et al. 2008]
• Each site works in its own framework. NYU's is existential and spiritual. Imperial's is ACE and psychological flexibility. Hopkins's is supportive and centred on safety. Work within the framework of the protocol you are delivering. [source: Ross et al. 2016; Watts & Luoma 2020]
• Respect beliefs. Explore the participant's philosophical and spiritual beliefs. Treat their interpretations as theirs and do not endorse or impose a metaphysics. [source: Johnson et al. 2008] [synthesis for the non-imposition point]
• Medical decisions belong to medical staff. Therapists provide psychological support. The responsible physician makes any decision about medical intervention. [source: Johnson et al. 2008]

4. Intervention inventory

This inventory covers only the psychotherapeutic and safety procedures. It gives no drug quantities, administration details or medical procedures. In an approved trial or regulated programme, the medical and prescribing staff handle those. The items are grouped by phase: 4.1 preparation, 4.2 the psilocybin session, 4.3 integration, 4.4 end-of-life adaptations, 4.5 ACE-specific work (Imperial) and 4.6 the clinician's role outside regulated settings.

4.1 Preparation

4.1.1 Rapport-building and life-history meetings

• Purpose: build the trust that makes the session safe, and learn the material likely to come up during it. Use this in every case, before anything else. [source: Johnson et al. 2008; ASCO Post 2015]
• Steps:
  • Hold the minimum preparation contact your protocol sets (Hopkins: at least four meetings and eight hours; NYU: three two-hour sessions; Imperial: about five hours).
  • Cover childhood, family, romantic life, friendships, and philosophical or spiritual beliefs.
  • In cancer care, also cover how the illness has affected the person's life (NYU).
  • The lead therapist attends every meeting. The second therapist meets the participant at least once, because they may be alone with them on the day.
  • Hold at least one meeting in the session room.
  • Review together whether trust is enough to go ahead.
• Example language (illustrative): "Before the session day, I'd like to understand your story: the people who matter to you, the hard times, and what you believe about life. Whatever comes up on the day, we'll already know each other."
• Watch for: guardedness, people-pleasing, or a feeling of being obliged to continue. If trust is thin, add hours or stop (Hopkins). Signs it is working: the person can name fears openly and can say how they would ask for help.

4.1.2 Informed-consent conversation

• Purpose: genuine, plain-language consent to an experimental or regulated treatment.
• Steps:
  • Explain the possible experiences: changes in perception, time and space; strong emotion, including anxiety, fear, panic and paranoia; and possible loss of the usual sense of self.
  • Explain the time course in general terms and what is known about toxicity.
  • Explain the rare lasting risks: psychosis, mood or anxiety disorder, and persisting perceptual disorder.
  • Explain the study status and blinding.
  • Repeat that withdrawal is possible and will be supported.
  • [synthesis] Explain the touch agreement (4.1.6) and the escort and supervision rules (4.2.6) as part of consent.
• Example language (illustrative): "Most people find parts of this hard as well as meaningful. Rarely, problems last afterwards, and I want you to know about them now. You can stop taking part at any stage, and we'll support you if you do."
• Watch for: minimising of the risks, or consent driven by desperation (terminal illness, long-standing depression). Check understanding by asking the person to describe the risks in their own words [synthesis].

[source: Johnson et al. 2008]

4.1.3 Describing the range of experiences without scripting them

• Purpose: prepare the person without planting expectations.
• Steps:
  • Describe in your own words the range of possible experiences: bodily sensations, intense emotion, loss of the sense of self, and mystical-type experiences.
  • Hopkins avoids giving published accounts to read.
  • In controlled trials, give every arm identical preparation, because suggestion is a confound.
• Example language (illustrative): "Some people meet vivid images or memories, some feel mainly bodily sensations, and some find it subtle. None of these is the right experience."
• Watch for: the person fixing on a hoped-for mystical experience. Reframe: the aim is to meet whatever comes [synthesis].

[source: Johnson et al. 2008]

4.1.4 Navigation guidance for the experience

• Purpose: give the person a stance they can recall when the experience gets difficult. [source: Johnson et al. 2008; ASCO Post 2015; Murphy et al. 2022]
• Steps:
  • Teach the Hopkins points: trust that the body will keep functioning without conscious control, and trust that ordinary consciousness will return.
  • Teach the person to surrender to the experience when frightening material arises.
  • Teach approach rather than escape. Hopkins's example is turning towards a frightening image, such as a monster, and asking why it is there.
  • Teach the person to turn into uncomfortable bodily sensations, such as nausea, with curiosity rather than fight them.
  • NYU asked participants to set the ego aside and follow where the mind leads.
  • Imperial emphasised moving towards difficult experiences and painful content.
  • Rehearse the stance with the person's own likely fears.
• Example language (illustrative): "If something frightening appears, see if you can turn towards it and ask what it wants to show you. Your body will keep breathing. We'll be right here, and this will pass."
• Watch for: a person who plans to stay in control. Explore that fear in preparation rather than on the day.

4.1.5 Intention setting

• Purpose: link the session to the person's reasons for coming, without turning it into a task. [source: Murphy et al. 2022]
• Steps:
  • Help the person put one or more intentions into words (Imperial included this in preparation).
  • [synthesis] Keep intentions open ("to understand my grief") rather than outcome demands ("to cure my depression").
  • [synthesis] Agree to hold the intentions lightly on the day.
• Example language (illustrative): "What would you most like to understand or meet? Let's hold that loosely. The experience may take you somewhere else, and that's fine."
• Watch for: rigid or perfectionistic intentions, which can become another way of controlling the experience [synthesis].

4.1.6 Agreeing supportive touch and asking for help

• Purpose: make non-verbal grounding available with clear consent, and make it easier to ask for help. [source: Johnson et al. 2008; Murphy et al. 2022]
• Steps:
  • Talk through how the person feels about asking for help (Imperial).
  • Describe the limited forms of touch the protocol allows: holding a hand, or a hand on the arm or shoulder.
  • Demonstrate hand-holding in preparation (Hopkins).
  • [synthesis] Agree a signal for help and a signal for "stop touching". Document the agreement and re-confirm it on the day.
• Example language (illustrative): "Some people find it steadying to hold a hand. Would you like that option? Show me how you'd let me know, and how you'd tell me to stop."
• Watch for: a trauma history involving touch, or ambivalence about touch. Default to no touch unless consent is clear [synthesis].

4.1.7 Music and personal choices

• Purpose: give the session structure and support emotional processing. [source: Murphy et al. 2022; Johnson et al. 2008]
• Steps:
  • Explain that a pre-selected playlist will play through headphones. Imperial's was informed by music research.
  • Invite the person to add a few personal choices (Imperial allowed three).
  • Note any music they dislike [synthesis].
• Example language (illustrative): "The music is there as a support you can lean into. Are there pieces you'd like included, or any you'd want left out?"
• Watch for: music tied to traumatic memories [synthesis].

4.1.8 Visualisation and body-attunement exercises (Imperial)

• Purpose: rehearse attuning to the body, moving towards difficult emotion, and connecting with self and others. [source: Murphy et al. 2022; Baker Jones 2022]
• Steps:
  • Guide a short eyes-closed exercise that brings attention to bodily sensation.
  • One named exercise is "Diving for Pearls". It frames fears and pain as spiky oyster shells that may hold something of value. Invite the person to imagine approaching a shell rather than swimming away.
  • Debrief what the exercise was like.
  • [uncertain] Imperial's full scripts are not published in the sources used. Write your own wording and do not attribute it to Imperial.
• Example language (illustrative): "Imagine diving down towards something spiky and uncomfortable. What happens if you stay close to it for a moment?"
• Watch for: dissociation or flooding during the exercise. This is useful information for planning the session day.

4.1.9 Practical safety planning

• Purpose: prevent avoidable harm on and after the session day. [source: Johnson et al. 2008]
• Steps:
  • Agree arrival and end times, the protocol's diet and medication restrictions (set by the medical team), and who will collect the person.
  • Explain that phones are handed in before the session. Hopkins records a case where a phone call contributed to someone leaving the site.
  • Explain the no-driving rule for the rest of the day.
  • Brief the companion to offer support while giving space.
  • Give an after-hours contact number.
• Example language (illustrative): "On the day, your phone stays with us. Someone you trust will take you home, and you won't drive until the next day."
• Watch for: an unreliable companion. Arrange an overnight stay where the protocol allows it.

4.2 Psilocybin session day (psychological support only)

4.2.1 Preparing the setting

• Purpose: provide a safe, non-clinical, contained space. [source: Johnson et al. 2008; ASCO Post 2015]
• Steps:
  • Use a living-room-like room: comfortable couch, rugs, soft lighting and artwork. NYU borrowed original artwork for its room.
  • Keep out white-coat cues and visible medical equipment.
  • Remove sharp or fragile objects and secure the windows.
  • Keep no phone in the room.
  • Have a private toilet nearby. If it is shared, keep the participant from contact with other people.
  • Have eyeshades and headphones ready.
  • Hopkins routinely video-recorded sessions and saw no rise in paranoia.
• Watch for: interruptions and unfamiliar staff. Only the monitors, or staff the person has already met, should interact with them.

4.2.2 Opening the day

• Purpose: settle the person and re-establish the alliance. [source: Johnson et al. 2008; ASCO Post 2015]
• Steps:
  • Greet the person warmly. Hopkins assigned a separate staff member to handle morning logistics.
  • Briefly revisit the person's intentions and the navigation stance.
  • Re-confirm the touch agreement and the help signal [synthesis].
  • Leave all medical steps to the medical staff.
• Example language (illustrative): "We're both here all day. Remember: trust, turn towards whatever comes, and let us know if you need anything."

4.2.3 Supporting inward focus

• Purpose: let the experience unfold without interference. [source: Johnson et al. 2008; Murphy et al. 2022; ASCO Post 2015]
• Steps:
  • Invite the person to lie down with eyeshades and headphones on and the music playing.
  • Encourage them to "collect experiences" and save discussion for later. Gently discourage analysis or a lot of talking while the effects are strong.
  • Later in the day, time without eyeshades is usual, with the music continuing as structure (Hopkins).
• Example language (illustrative): "You don't need to explain anything to us now. Just notice, and we'll talk about it later."
• Watch for: repeated removal of the eyeshades or restlessness, which may signal anxiety. Check in (4.2.4).

4.2.4 Periodic gentle check-ins

• Purpose: monitor wellbeing without breaking the process. [source: Johnson et al. 2008; ASCO Post 2015]
• Steps:
  • Check in quietly from time to time. Hopkins gives the example: "Would you like to describe where you find yourself?"
  • NYU therapists checked in roughly hourly with a gentle touch on the shoulder (where agreed).
  • Offer water, food or a toilet break as needed.
  • Accept a non-verbal answer.
• Watch for: the person's facial expression, breathing, crying and posture. These are part of the observation; any medical concerns go to the medical staff.

4.2.5 Responding to anxiety or a challenging experience

• Purpose: help the person through fear, panic or paranoia, which are the main acute psychological risk. [source: Johnson et al. 2008]
• Steps (Hopkins first-line sequence):
  1. Reassure strongly; convey calm and security.
  2. Empathise with how intense it is.
  3. Do not "talk down" with reality-testing.
  4. Remind the person of the agreed stance: surrender and turn towards the experience.
  5. Offer supportive touch as agreed (hand on arm or shoulder).
  6. Orient them: they are in a study or programme, they took a substance, and they will return to normal.
  7. Offer to hold their hand ("interpersonal grounding").
• If this does not settle them: the responsible physician and the team decide whether medical intervention is needed. Hopkins treats the emergency department as a "last resort" and aims to handle difficulties "in the session context".
• Outcomes reported: in the Hopkins series of 54 volunteers, reassurance alone was enough for all acute distress. NYU needed no rescue intervention.
• Example language (illustrative): "This is very intense, and you're safe. We're right here. Breathe and let it move through you. It will pass."
• Watch for: escalating paranoia, attempts to leave, or a loss of contact with the guides. Call in the physician early.

[source: Johnson et al. 2008; Ross et al. 2016]

4.2.6 Escorting and preventing departure

• Purpose: prevent dangerous behaviour, especially leaving the site. Hopkins treats this as the critical risk. [source: Johnson et al. 2008]
• Steps:
  • Stay close whenever the person moves, with a light hold on the arm or shoulder.
  • Escort them to the toilet and wait just outside, with the door unlocked or the key held by staff.
  • If they try to leave, redirect them to the room compassionately but firmly.
  • If an unplanned event forces you outside (Hopkins describes a fire alarm), stay in contact and reframe it gently. In that case the walk outside was presented as a chance to enjoy nature.
• Example language (illustrative): "I hear you want to go. Let's go back to the room together. It's the safest place for you right now, and I'll stay with you."
• Watch for: the cases Hopkins cites, such as feeling imprisoned, a sense of a grand mission, or fleeing a site.

4.2.7 End-of-session sharing and release

• Purpose: give a gentle close and a safe handover. [source: Johnson et al. 2008; ASCO Post 2015; Murphy et al. 2022]
• Steps:
  • As the effects wane, invite the person to share if they wish (Imperial and NYU).
  • Confirm with the medical staff that the acute effects have resolved.
  • Hand over to the briefed companion, or arrange the overnight stay.
  • Restate the no-driving rule and the contact number.
• Example language (illustrative): "Would you like to tell us anything about where you've been today? There's no need to make sense of it yet."
• Watch for: lingering confusion, agitation or distress. Do not release the person until it has resolved [synthesis, consistent with Hopkins].

4.3 Integration

4.3.1 Next-day integration session

• Purpose: check stability, help the person tell the experience and make meaning of it, and assess persisting effects. [source: Johnson et al. 2008; Murphy et al. 2022]
• Steps:
  • Meet the next day. Imperial held this in person for two to three hours.
  • Invite the whole narrative before interpreting anything.
  • Listen openly and attentively, with compassion. Recognise the insights or changes the person names.
  • Ask about sleep, mood and any persisting perceptual changes.
  • Schedule more meetings if difficulties persist.
• Example language (illustrative): "Take me through it from the beginning, at whatever pace suits you. What stands out most this morning?"
• Watch for: destabilisation, ongoing fear, grandiosity or new perceptual symptoms. These call for more support and psychiatric review.

4.3.2 Continuing integration sessions

• Purpose: turn insights into change in daily life. [source: ASCO Post 2015; Murphy et al. 2022; Malone et al. 2018]
• Steps:
  • Hold the sessions the protocol provides: NYU, three after each drug session; Imperial, optional weekly calls as clinically indicated.
  • Explore the insight into what caused the distress.
  • Support the changes people reported: healthier eating, more exercise, and new non-drug spiritual or meditative practice.
• Example language (illustrative): "You said you saw how much you'd shut people out. What would one small step towards them look like this week?"
• Watch for: idealising the experience or the therapist, or a fading afterglow followed by disappointment [synthesis].

4.3.3 Screening for persisting perceptual change and psychological problems

• Purpose: detect rare lasting adverse effects. [source: Johnson et al. 2008; Ross et al. 2016]
• Steps:
  • At each follow-up, ask specifically about persisting visual or perceptual changes, mood, anxiety and any psychotic-like experiences.
  • Have a psychiatrist or clinical psychologist experienced with altered states available for consultation.
• Example language (illustrative): "Since the session, have you noticed any changes in how things look, or any visual effects that keep coming back?"
• Watch for: symptoms that persist or keep returning. Refer for psychiatric assessment.

4.3.4 Ending and long-term follow-up

• Purpose: a planned ending of an intense, time-limited relationship. [source: Baker Jones 2022; ASCO Post 2015]
• Steps:
  • Mark the ending explicitly (Imperial reported a three-month check-in, after which the relationship ended).
  • Complete the follow-up measures.
  • Arrange onward therapy or care where needed [synthesis].
• Example language (illustrative): "This is our last planned meeting. Let's look at what you'll take forward and who supports you now."
• Watch for: abandonment feelings at the ending, and relapse of depression. Have a referral pathway ready [synthesis].

4.4 End-of-life distress adaptations (NYU, Hopkins cancer trials)

4.4.1 Existentially oriented preparation and integration

• Purpose: address existential and psychospiritual suffering, such as fear of death, loss of meaning and identity merged with illness. This is psychological support alongside oncology and palliative care. [source: Ross et al. 2016; ASCO Post 2015; Malone et al. 2018]
• Steps:
  • In preparation, take the cancer narrative: diagnosis, treatment, losses, and what the person fears most.
  • In integration, explore recurring themes the NYU cases reported: self-compassion and love, acceptance of death, the cycle of life and death, re-emerging trauma memories, and a sense of separation from the disease.
  • Support practices the person chooses to continue, such as meditation.
  • NYU's platform integrated "several" of the "manualized existentially oriented psychotherapies" reviewed by Lemay & Wilson (2008). The main paper names no single model; the full procedures are in its Supplementary Methods, not summarised here. Bossis describes the drug session as "embedded within an interpersonally supportive psychotherapeutic period of preparation and integration". He names meaning-making and transcendence as central for dying patients. [source: Ross et al. 2016; McGill Health e-News 2019] [uncertain] Which existential therapies were used, and how, is not documented here.
  • [synthesis] Coordinate with the oncology or palliative team (with consent) on medical status, fatigue and timing. Never present the therapy as affecting the cancer.
• Example language (illustrative): "You've described feeling that you are more than your illness. How would you like to live the time ahead, given that?"
• Watch for: physical frailty, which limits session length and needs medical judgement. Watch also for re-emerging trauma (one NYU case recalled childhood sexual assault): give trauma-informed support and refer as needed. Respect the person's own spiritual framework.

4.4.2 Supporting family and companions

• Purpose: brief the person who supports the participant at home. [source: Johnson et al. 2008] [synthesis for the end-of-life specifics]
• Steps:
  • Brief the companion to offer emotional support while giving space.
  • [synthesis] With consent, offer a joint meeting about what the participant may want to share. In palliative care, link the family to the palliative team's bereavement support.
• Example language (illustrative): "They may want to talk, or they may want quiet. Follow their lead tonight."

4.5 ACE-informed work (Imperial depression trials)

ACE (Accept, Connect, Embody) is Imperial's adaptation of the ACT psychological flexibility model for preparation and integration. Its authors used it in an Imperial psilocybin trial for major depression. Watts & Luoma regroup the six ACT processes into two triads: an acceptance triad (defusion, present-moment focus, willingness) and a connection triad (self-as-context, values, committed action). [source: Watts & Luoma 2020, ACBS abstract]

A secondary summary of the full paper adds five points. Embodiment runs through both triads rather than being a separate stage. Therapists stay supportive and minimally directive, so ACE is a scaffold, not a prescriptive protocol. In the trial described (Psilodep 2), preparation was four contacts, including one extended face-to-face session, and integration was four to seven sessions plus optional remote ones. Two named exercises, P-ACE (preparation) and I-ACE (integration), use guided imagery and body-focused work. Integration moves through three stages (4.5.4). [source: Blossom summary of Watts & Luoma 2020]

[uncertain] No public ACE manual or published step-by-step description of P-ACE and I-ACE was found; the steps below are the writer's synthesis. The exercises in 4.5.1–4.5.4 are ACT-style applications written as [synthesis], not Imperial's scripts. Therapists emphasise different themes for different clients and sessions [source: Murphy et al. 2022; Baker Jones 2022].

4.5.1 Accept: willingness towards difficult emotion

• Purpose: reduce experiential avoidance before, during and after the session.
• Steps:
  • In preparation, identify what the person habitually avoids, such as grief, anger or shame.
  • Rehearse willingness: noticing a feeling, naming it and allowing it.
  • Reassure the person that strong feelings can be "held" in the session. Imperial used this with a participant afraid of his anger.
  • In integration, ask what happened when they stopped fighting a feeling.
• Example language (illustrative): "What if the anger could be here for a while, with us next to you, without anything bad happening?"
• Watch for: acceptance used as resignation. Link it to values (4.5.2). [synthesis]

4.5.2 Connect: self, others and values

• Purpose: turn moments of connection into valued action.
• Steps:
  • In integration, ask what or whom the person felt connected to.
  • Clarify the values that experience points to.
  • Plan small committed actions and review them at later sessions.
• Example language (illustrative): "You felt close to your sister in the session. What matters to you about that, and what could you do about it this week?"
• Watch for: over-large plans made in the afterglow. Scale them down. [synthesis]

4.5.3 Embody: somatic awareness

• Purpose: use the body as an anchor and a source of information.
• Steps:
  • In preparation, run brief body-scan or attunement exercises (Imperial used visualisation to attune to the body).
  • In integration, ask where in the body an insight or feeling was located, and invite a short daily practice of checking in with the body.
• Example language (illustrative): "As you remember that moment, where do you notice it in your body now?"
• Watch for: somatic flooding in people with trauma. Titrate exposure and use grounding. [synthesis]

4.5.4 ACE integration in three stages (Imperial)

• Purpose: give integration sessions an order: build a coherent account, draw out what it means, then act on it. The three stages are named in the summary of Watts & Luoma 2020; the how-to below is the writer's synthesis. [source: Blossom summary of Watts & Luoma 2020] [synthesis for the steps]
• Steps:
  • Stage 1, pulling the narrative together: invite the full account of the session, in order, before any interpretation. Fill gaps gently, and accept that parts may stay unclear.
  • Stage 2, distilling insights: ask which moments stand out and what they suggest about avoidance, connection and the body. Help the person put a few insights into their own words.
  • Stage 3, supporting behavioural change: link each insight to a value and a small committed action, then review the actions at later sessions (4.5.2).
  • Hold as many sessions as the protocol provides (four to seven in the trial summarised).
• Example language (illustrative): "Let's first get the whole story down. Then we can look at what it's telling you, and what you might do differently this week."
• Watch for: jumping to stage 3 before the person has a coherent account, and insights turned into rigid rules rather than values. [synthesis]

[source: Murphy et al. 2022; Baker Jones 2022; Watts & Luoma 2020]

4.6 Clients using psilocybin outside trials or regulated programmes [synthesis]

No published protocol describes this role. Everything in this subsection is the writer's synthesis, built from the published screening and safety principles above.

4.6.1 Harm-reduction assessment and safety planning

• Purpose: reduce risk for a client who has decided to use psilocybin, or who already has, without facilitating illegal use.
• Steps:
  • Do not advise on substances, amounts, sourcing or administration.
  • Assess against the published exclusions: personal or family history of psychosis or bipolar disorder, current suicidality, cardiovascular conditions, pregnancy, and medications (lithium and some antidepressants are named exclusions). Advise the client to discuss interactions with their prescriber or a pharmacist.
  • Discuss in general terms the protective factors from the trials: no one using alone, a trusted sober companion, a safe setting, no driving, and a plan for distress.
  • Make a crisis plan.
  • Point to legal routes: trials, or regulated programmes where they exist.
• Example language (illustrative): "I can't help you obtain it or tell you how to use it. I can help you think through the risks for you specifically, and plan for safety."
• Watch for: red-flag history, coercive or unscreened providers, and isolation.

4.6.2 Integration support after an outside experience

• Purpose: help the client process the experience and screen for harm.
• Steps:
  • Use 4.3.1–4.3.3: take the full narrative without judgement, assess stability and persisting perceptual effects, and link insights to values.
  • Refer for psychiatric review if psychotic, manic or persisting perceptual symptoms appear.
  • Ask about any boundary violations by a facilitator and respond as you would to any reported abuse.
• Example language (illustrative): "Whatever happened, I'd like to hear it in your own words, the hard parts as well as the meaningful ones."

5. Handling problems

Insufficient trust or ambivalence in preparation. Add contact hours or cancel. Make sure that rapport does not become pressure to continue, and state plainly that withdrawal will be supported. [source: Johnson et al. 2008] [synthesis] Explore the ambivalence directly. It is information, not resistance to overcome.

Expectation pressure ("this is my last hope"). Common in treatment-resistant depression and terminal illness. [synthesis] Name the hope and also the uncertainty. Reframe the goal as meeting whatever comes. Revisit consent to make sure desperation is not driving it. The Hopkins guidance not to give trip accounts to read also reduces scripted expectations. [source: Johnson et al. 2008]

Acute fear, panic or paranoia in session. Follow the Hopkins sequence in 4.2.5. Avoid reality-testing arguments. If reassurance fails, the physician decides on medical intervention, and the emergency department is a last resort. [source: Johnson et al. 2008]

Attempts to leave, or grandiose "mission" beliefs. Redirect compassionately but firmly. Never leave the person alone. Escort every movement. [source: Johnson et al. 2008] [synthesis] Do not debate the belief. Acknowledge it and postpone action ("we can think about that tomorrow").

A closed, "stuck" or uneventful session. [synthesis] Do not push. Gently invite curiosity about the stuckness itself, or attention to the body (ACE "Embody"). In integration, normalise a quiet session; Tom, an NYU case, found the experience less life-changing than he expected. [source for the case: Malone et al. 2018]

Re-emerging trauma memories. These were documented in an NYU case. [synthesis]

• In session: stay present and grounding, and offer touch only as agreed.
• In integration: work at the person's pace, avoid interpreting memories as literal fact, and refer for trauma-focused therapy.

Distress about touch, or a rupture over boundaries. [synthesis]

• Stop touch immediately at any sign of discomfort.
• Name and repair the rupture in integration.
• Report boundary violations according to your professional code. Use two-person teams and video as the published safeguards. [source for two monitors and video: Johnson et al. 2008]

Destabilisation after the session (low mood, anxiety, insomnia, perceptual effects).

• Hold extra integration meetings. Hopkins adds meetings when difficulties persist.
• Probe for persisting perceptual disorder.
• Refer to a psychiatrist experienced with altered states.

[source: Johnson et al. 2008] [synthesis] Increase contact, review suicide risk using standard structured assessment, and involve the prescriber.

Suicidality. Current suicidal ideation was an exclusion at Hopkins. [source: Johnson et al. 2008; Davis et al. 2021] [synthesis] If suicidality emerges during the course, do a standard risk assessment and safety planning, including lethal-means counselling on safe storage or removal, and give it priority over the protocol.

Non-adherence (medication restrictions, the companion, the no-driving rule). Re-explain the safety reason. If a safety requirement cannot be met, postpone the session. [synthesis, based on Johnson et al. 2008 logistics]

The afterglow fades, or depression relapses. [synthesis] Prepare for this explicitly. Keep the ACE values-and-action work going (4.5.2). Arrange onward therapy. Do not offer or imply further drug sessions outside the protocol.

Idealisation of the experience or the therapist; spiritual over-interpretation. [synthesis] Respect the person's meaning-making. Gently check how it fits their wider life and relationships, and keep boundaries clear when the relationship ends. Treat metaphysical interpretations as the participant's own.

Grief and ending. [synthesis] Imperial's relationship ended after a three-month check-in [source: Baker Jones 2022]. Plan the ending from the start and have a referral ready.

End-of-life specific. [synthesis]

• Physical deterioration may limit participation. Defer to the medical team.
• Family members may hope for a "cure". Restate that this is psychological support only.
• Coordinate with palliative care on anticipatory grief and bereavement support.

Clients using unregulated providers. [synthesis] Use the harm-reduction stance in 4.6. Do not refer to illegal services. Screen against the published exclusions and offer integration support without judgement.

Blinding and "I got the placebo" disappointment in trials. [synthesis] Validate the disappointment, explain the protocol's next steps (for example a crossover or open-label phase, if one exists), and continue supportive work. [uncertain] The sources cited do not address this.

Sources

Sources used:

• OPEN Foundation abstract: Human hallucinogen research guidelines for safety
• Malone et al. 2018, Individual experiences in four cancer patients following psilocybin-assisted psychotherapy (Frontiers in Pharmacology)
• ASCO Post 2015: Researchers discuss pilot study on hallucinogenic therapies for cancer anxiety
• Murphy et al. 2022, Therapeutic alliance and rapport modulate responses to psilocybin assisted therapy for depression (Frontiers in Pharmacology)
• Watts & Luoma 2020, The use of the psychological flexibility model to support psychedelic assisted therapy (abstract, ACBS)
• Baker Jones 2022, Walking each other home (MIND Foundation)
• OPEN Foundation summary: Davis et al. 2021, Effects of psilocybin-assisted therapy on major depressive disorder
• Drug Science 2026: Psilocybin regulation
• Yale Manual for Psilocybin-Assisted Therapy of Depression (ACBS landing page)

Further sources:

• Watts & Luoma 2020 (ACBS publication page)
• Blossom summary: The use of the psychological flexibility model to support psychedelic assisted therapy
• McGill Health e-News 2019: Four burning questions with Anthony Bossis, PhD
• Drug Science 2025: UK government supports ACMD plan
• University of Manchester: Influencing policy change, re-scheduling psilocybin
• Compass Pathways, April 2026: FDA grants NDA rolling review and National Priority Voucher (PDF)
• Compass Pathways, August 2026: Second quarter and first half 2026 results (BioSpace)
• Government response to the ACMD's report on barriers to research: part 2 (Home Office, GOV.UK, 16 July 2025)
• Compass Pathways plc, Form 8-K, 7 July 2026: COMP006 26-week results (SEC EDGAR)
• Ross et al. 2016, PubMed record (abstract)

Books and papers cited:

• Johnson, M. W., Richards, W. A., & Griffiths, R. R. (2008). Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology, 22(6), 603–620.
• Ross, S., Bossis, A., Guss, J., et al. (2016). Journal of Psychopharmacology, 30(12), 1165–1180.
• Watts, R., & Luoma, J. B. (2020). Journal of Contextual Behavioral Science, 15, 92–102.
• Davis, A. K., et al. (2021). JAMA Psychiatry (Johns Hopkins major depressive disorder trial).
• Guss, J., Krause, R., & Sloshower, J. (2020). The Yale Manual for Psilocybin-Assisted Therapy of Depression (PsyArXiv). A Yale protocol, not NYU's; not used for content here.

Not used for content [uncertain]: the full text of Watts & Luoma 2020 and any ACE manual; the NYU Supplementary Methods and therapist manual; Lemay & Wilson 2008; Griffiths et al. 2016 (Hopkins cancer trial); the full Imperial treatment-resistant depression trials; primary MHRA and FDA pages (apart from the Home Office response, regulatory status comes from the secondary and company sources listed above).