Imperial College London
Centre for Psychedelic Research
“Trial of Psilocybin versus Escitalopram for Depression”
Carhart-Harris RL, Giribaldi B, Watts R, et al.
New England Journal of Medicine · 2021
The science
The science behind psychedelic transformation.
I read these studies so you can see what they found. Every claim names its source, and I state the limits in plain English.
Written by Austin Mao. Last reviewed: October 2026
The three pillars
How healing happens.
Three things shape an experience. Research has studied the first the most and the last the least.
Pillar 1, Pharmacology
What the molecule does
Psilocybin binds 5-HT2A receptors in cortical neurons. Human fMRI shows changes in brain-network integration, and rodent studies show new dendritic spines. Whether these explain clinical benefit is still being studied.
Pillar 2, Set & setting
What the conditions create
Mindset entering ceremony and the safety of the container shape the experience. Clinical trials standardize preparation, the room and the therapist relationship, though none has isolated their individual effects.
Pillar 3, Integration
What our practice adds
Ceremonia's approach pairs ceremony with practice: IFS parts work, somatic regulation, journaling, community accountability. This is our practice, not a research finding. No trial has tested whether integration support lengthens benefits.
Our Colorado retreat center
The default mode network
The brain's self-narrating engine.
The default mode network is a cluster of midline brain regions (medial prefrontal cortex, posterior cingulate, precuneus) that activates when you are not focused on a task. It is linked to the running inner monologue, autobiographical memory, and self-referential thought.
The DMN has been linked to rumination, though the pattern in depression is more complicated than simple overactivity. fMRI studies from Imperial College London reported reduced blood flow and reduced medial prefrontal–posterior cingulate coupling during the psilocybin state in 30 healthy volunteers (Carhart-Harris et al., PNAS 2012), and increased global integration with reduced modularity about three weeks later in patients with depression (Daws et al., Nature Medicine 2022). Whether these changes explain therapeutic benefit remains exploratory.
People in these studies often describe rumination softening and ego boundaries becoming porous during the acute effects, which last a few hours.
Neuroplasticity
What the research says about new wiring forms.
Ly et al. (Cell Reports, 2018) reported that psychedelics increased neurite growth, dendritic spines and synapse number in cultured rodent neurons and in rodent cortex, dependent on 5-HT2A, TrkB and mTOR signaling. In mice, one psilocybin dose raised spine density and size by about 10% within 24 hours, and the change persisted at one month (Shao et al., Neuron 2021). These are rodent and cell-culture findings.
Researchers sometimes call this a “plasticity window,” but no study has measured one in humans. In mice, a social-reward-learning critical period stayed open at two weeks after psilocybin and had closed by three weeks (Nardou et al., Nature 2023). In patients, fMRI measured increased global brain integration about three weeks after treatment (Daws et al., Nature Medicine 2022). Human structural plasticity has not been measured directly.
These are indirect markers from small studies, so the practical reading is modest: the evidence does not show that a molecule installs change, and no trial has tested whether integration support lengthens benefits. Ceremonia treats integration as load-bearing, not aftercare, as a matter of its own practice rather than a research finding.
Our Colorado retreat center
Modality comparison
Three medicines. Different doors.
Same underlying pharmacology, partial 5-HT2A agonism, but the phenomenology, time course, and integration demand vary considerably. Choosing the right modality for a given person is its own discipline.
The most studied
Psilocybin
- Mechanism
- Prodrug for psilocin. Partial agonist at 5-HT2A. Human fMRI shows reduced default-mode network integrity during the acute state; increased dendritic spine density has been shown in rodents.
- Clinical evidence
- Breakthrough Therapy designation for COMPASS (TRD) and Usona (MDD) programs; not FDA-approved. In a phase 2b trial in treatment-resistant depression (n=233), 25 mg psilocybin lowered MADRS scores by 12.0 points at week 3 vs 5.4 for 1 mg (Goodwin et al., NEJM 2022).
- Typical experience
- 4–6 hour journey. Vivid imagery, ego softening, autobiographical insight. Body load typically light to moderate.
DMT + harmala MAOIs
Ayahuasca
- Mechanism
- DMT (5-HT2A agonist) made orally active by beta-carboline MAOIs in B. caapi.
- Clinical evidence
- Palhano-Fontes et al. (Psychol Med 2019): in 29 people with treatment-resistant depression, single-dose ayahuasca lowered MADRS scores more than placebo at days 1, 2 and 7. It remains a single small randomized trial, and no large trial has been located.
- Typical experience
- 4–6 hour ceremony. Strong somatic and visionary content; purging is common.
Brief, non-dual
5-MeO-DMT
- Mechanism
- Endogenous tryptamine. Strong 5-HT1A and 5-HT2A activity. Triggers a short, often non-dual altered state with reduced narrative content.
- Clinical evidence
- Early-stage trials only (AtaiBeckley, GH Research); company-reported results are not independently peer-reviewed. Reckweg et al. (Front Psychiatry 2023) reported a phase 1/2 trial of vaporized 5-MeO-DMT in treatment-resistant depression. Shown for education; Ceremonia does not offer 5-MeO-DMT.
- Typical experience
- 10–30 minutes. Frequently non-dual: dissolution of subject/object boundary. Minimal visual content; high integration demand afterward.
How we cite
Each study on this page is named with its authors, year and journal. Click any citation to read the original paper. If a study is paywalled, the DOI is the permanent identifier; it will resolve at any institutional library you have access to.
We do not paraphrase results to make them friendlier. Where a figure comes from a company press release or a trial registry rather than a peer-reviewed paper, we label it as sponsor-reported. Where a mechanism comes from animal work, we say so.
How we read a study →The research
Where the evidence comes from.
Three flagship trials. Public DOIs. Read them yourself.
Johns Hopkins Medicine
Center for Psychedelic & Consciousness Research
“Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer”
Griffiths RR, Johnson MW, Carducci MA, et al.
Journal of Psychopharmacology · 2016
MAPS Public Benefit Corporation
Multidisciplinary Association for Psychedelic Studies
“MDMA-assisted therapy for severe PTSD: a randomised, double-blind, placebo-controlled phase 3 study”
Mitchell JM, Bogenschutz M, Lilienstein A, et al.
Nature Medicine · 2021
What's in trial
The active registry.
A snapshot of the late-stage trials moving toward regulatory review, last reviewed October 2026. Sourced from ClinicalTrials.gov and sponsor disclosures, so company figures are sponsor-reported rather than independently peer-reviewed. Verify current status before citing.
COMPASS Pathways
COMP360 (synthetic psilocybin, 25 mg)
Treatment-resistant depression
Phase 3 reportedCOMP005 complete; COMP006 active, not recruiting
Sponsor-reported: both trials met their primary endpoints (week-6 MADRS difference -3.6 in COMP005, -3.8 in COMP006; modest absolute differences). Rolling NDA under way, final submission expected Q4 2026. Not FDA-approved.
Resilient Pharmaceuticals (formerly Lykos Therapeutics)
MDMA-assisted therapy
Severe PTSD
Phase 3 completeNot approved
FDA issued a Complete Response Letter on 2024-08-09. A resubmission was reported in August 2026 by MAPS and trade press; FDA has not announced acceptance.
Usona Institute
Psilocybin
Major depressive disorder
Phase 3Enrollment complete
NCT06308653: randomized, double-blind; results not yet public. Breakthrough Therapy designation (2019).
AtaiBeckley (Beckley Psytech)
BPL-003 (5-MeO-DMT)
Treatment-resistant depression
Phase 2b completePhase 3 expected 2026
Randomized, double-blind, three-arm design; sponsor-reported MADRS reduction of 11.1 (12 mg) vs 5.8 (0.3 mg comparator) at day 29. Company-reported: Phase 3 (ReConnection-1/2) expected to start in 2026, with the 8 mg dose selected. Shown for education only; Ceremonia does not offer 5-MeO-DMT.
How it works
What happens in the brain.
Default Mode Network softens
Human fMRI studies report reduced default-mode network integration during the acute effects, the network linked to self-referential thought and rumination.
Functional connectivity rises
In patients with depression, fMRI measured increased global brain integration about three weeks after psilocybin therapy (Daws et al., Nature Medicine 2022).
Spine growth in mice
In mice, one dose raised dendritic spine density about 10% within 24 hours, and it persisted at one month (Shao et al., Neuron 2021). This has not been measured directly in humans.
How long it lasts
A mouse critical period stayed open at two weeks and had closed by three (Nardou et al., Nature 2023). Human markers range from about three weeks to one month. No human plasticity window has been established.
Published research
What the major trials found
−3.6 and −3.8
COMPASS phase 3, sponsor-reported
MADRS point difference at week 6 in the two phase 3 trials of psilocybin for treatment-resistant depression. Modest absolute differences; not yet fully peer-reviewed.
−12.0 vs −5.4
Dose finding
MADRS points at week 3 for 25 mg vs 1 mg psilocybin in treatment-resistant depression (n=233). The 10 mg dose did not differ significantly from 1 mg.
p = 0.17
Psilocybin vs escitalopram
No significant difference on the primary outcome (n=59) between two psilocybin doses and six weeks of escitalopram. Several secondary outcomes favored psilocybin but were not corrected for multiple comparisons.
~4%
Serious adverse events
Share of trial participants with neuropsychiatric disorders who had a serious adverse event, in a systematic review of 214 studies (114 with analyzable data, 3,504 participants). None were reported in healthy participants.
These are research findings from controlled settings; they do not describe outcomes at a retreat. Full citations: see the published studies above.
Frequently asked, briefly answered
Is psychedelic therapy evidence-based?
In part. Controlled trials of psilocybin and MDMA-assisted therapy have reported positive results in specific clinical populations, while other findings are modest, mixed or still preliminary. No psychedelic product is FDA-approved yet. Three things to know when you read the evidence:
Peer-reviewed
The trials and papers cited on this page were published in peer-reviewed journals. Company press releases and trial-registry entries are labelled as sponsor-reported.
Mixed durability
Several imaging groups have reported acute changes in default-mode network integrity after psilocybin. Spine growth has been shown in rodents, and a plasticity "surge" in humans has not been established. How long benefits last varies across trials.
Not yet approved
FDA granted Breakthrough Therapy designation to COMPASS's psilocybin for treatment-resistant depression (2018) and to Usona's psilocybin for major depressive disorder (2019). That is a development-pathway status, not approval: no psilocybin or MDMA product is FDA-approved.
Frequently asked
The questions people search for.
Is psychedelic therapy FDA approved?
No. As of October 2026, no psilocybin or MDMA product is FDA-approved. FDA granted Breakthrough Therapy designation to COMPASS Pathways' psilocybin (COMP360) for treatment-resistant depression in 2018 and to Usona Institute's psilocybin for major depressive disorder in 2019; that is a development-pathway status, not approval. COMPASS has reported positive phase 3 results (sponsor-reported) and has begun a rolling submission to FDA. For MDMA-assisted therapy for PTSD, FDA issued a Complete Response Letter on 2024-08-09, and it is not approved. Esketamine (Spravato), a ketamine-related medicine, is FDA-approved for treatment-resistant depression.How do psychedelics work in the brain?
Classical psychedelics (psilocybin, LSD, DMT) are partial agonists at the 5-HT2A serotonin receptor on cortical pyramidal neurons. Human fMRI studies report reduced default-mode network integrity during the acute effects and increased global integration weeks later in patients (Carhart-Harris et al., PNAS 2012; Daws et al., Nature Medicine 2022). In rodent neurons and cortex, psychedelics increased neurite growth and dendritic spines via 5-HT2A, TrkB and mTOR signaling (Ly et al., Cell Reports 2018). A BDNF surge after psilocybin has not been shown in humans.Can psychedelics help with PTSD?
Phase 3 trials of MDMA-assisted therapy showed roughly two-thirds of severe PTSD participants no longer met diagnostic criteria after three sessions paired with structured therapy (Mitchell et al., Nature Medicine 2021; DOI 10.1038/s41591-021-01336-3). In the Mitchell trial (n=90), 28 of 42 (67%) in the MDMA group no longer met PTSD criteria at 18 weeks vs 12 of 37 (32%) on placebo. Results have not translated into FDA approval: the agency issued a Complete Response Letter on 2024-08-09, functional unblinding and therapist-misconduct concerns were central to the decision, and three related MDMA papers were retracted in 2024 (the Nature Medicine paper was not).Are psychedelics addictive?
Classical psychedelics (psilocybin, LSD, DMT, mescaline) are not considered chemically addictive. Tolerance develops quickly with repeated dosing and recovers in about a week, which discourages frequent use. A review applying the Controlled Substances Act's eight factors concluded that medical psilocybin has low abuse potential (Johnson et al., Neuropharmacology 2018). They are not benign. They can amplify whatever you bring, which is why preparation and integration matter.What is microdosing?
Taking amounts too small to produce a full psychedelic experience, usually on a repeating schedule. Reported benefits include improved mood and focus, but placebo-controlled studies (Szigeti et al., eLife 2021) suggest much of the effect is expectancy. Microdosing is not what Ceremonia practices; we work with full-dose ceremonial protocols. Read the microdosing evidence summary.What is the difference between psilocybin and LSD?
Both are partial 5-HT2A agonists with overlapping subjective effects. Psilocybin lasts 4–6 hours; LSD lasts 8–12. LSD has higher affinity for dopamine receptors and a longer body load. Most modern clinical trials use psilocybin because the shorter duration is logistically more practical and the molecule is found endogenously in fungi.What is set and setting?
Set is the participant's mindset: preparation, intention, current emotional state. Setting is the external container: physical space, music, the people present, and the trust relationship with facilitators. Set and setting are long-standing concepts in psychedelic research; clinical trials standardize preparation, the room and the therapist relationship, but no trial has isolated their individual effects.What is integration after a psychedelic experience?
The structured practice of translating ceremony insight into daily life, such as somatic regulation, IFS parts work, journaling and community accountability. In mice, a single psilocybin dose increased dendritic spine density that persisted at one month (Shao et al., Neuron 2021); in patients, fMRI measured increased global brain integration about three weeks after treatment (Daws et al., Nature Medicine 2022). No human study has measured a plasticity "window", and no trial has tested whether integration support lengthens benefits. Ceremonia treats integration as load-bearing, not aftercare.How long do psychedelic effects last?
Acute effects: psilocybin 4–6 hours, ayahuasca 4–6 hours, LSD 8–12 hours, 5-MeO-DMT 10–30 minutes. In a randomized trial of 51 cancer patients, about 80% still showed clinically significant reductions in depressed mood and anxiety at the 6-month follow-up (Griffiths et al., J Psychopharmacol 2016). In an uncontrolled follow-up of 15 surviving patients from a separate NYU trial, about 60 to 80% still met response criteria at 4.5 years (Agin-Liebes et al., J Psychopharmacol 2020). These are research findings in people with life-threatening cancer, not outcomes of a retreat.Are there people who shouldn't take psychedelics?
Yes. Personal or first-degree-relative history of psychosis, schizophrenia, or bipolar I is the strongest contraindication. Active SSRIs, MAOIs, and lithium interact with serotonergic psychedelics. Cardiac conditions and some other medical conditions require clearance. Ceremonia screens for all of these before accepting any participant; see /safety for the full protocol.
Go deeper
Go deeper into the studies.
The index lists each study with its DOI, who was studied, and what the trial did not show.
Explore the science pages
Pharmacology
Research Index
The studies themselves: Johns Hopkins, Imperial College, and the COMPASS and Usona phase 3 programs, with DOIs and limits.
Neuroscience
The Default Mode Network
A brain network linked to self-referential thought, and what imaging studies report after psilocybin.
Neuroscience
Neuroplasticity
What was measured, in whom, and for how long: preclinical findings in mice and what human imaging has shown.
Pharmacology
Microdosing
What placebo-controlled, self-blinding and survey studies report, and the open safety questions. Education only.
Pharmacology
Ayahuasca and DMT
How DMT becomes orally active, and what the small clinical literature on ayahuasca has found.
Psychology
Trauma-Informed Care
What trauma-informed means, the Window of Tolerance, what the trials found, and why screening comes first.
Framework
Our Method
How we work: our practice, not a research finding. Read it on its own terms.
Begin
Ready to apply this to your life?
The studies can inform your decision. They cannot make it for you. A readiness check is a good place to start, and the masterclass shows how we work.