Psychedelic research timeline
Depressive Disorders: the psychedelic research timeline
From ketamine’s rapid antidepressant signal to the first pivotal psychedelic programmes, this is the deliberately selective history of how several compounds reopened the depression question.
Milestones are editorially selected from Blossom’s research catalogue. Future markers are limited to important trials with dated public guidance and are shown as planned, not promised.
Hover any marker to preview its callout on the canvas, then click to pin it. Pinned is what stays open, fills this panel with the full context and links, and is what an export captures. Landmarks stay labelled on the canvas so the exported image reads on its own.
Download the artifact
Exports rasterise the live SVG, so whatever you have toggled is what you get.
A rapid signal
1997 to 2013Ketamine changes the timing of the antidepressant question.1997-01
Yale University
Berman’s Yale crossover trial
Seven patients, a saline placebo, and depression scores falling within hours rather than weeks.
A tiny randomised, double-blind, placebo-controlled crossover pilot at Yale. Seven patients. Published in Biological Psychiatry in February 2000, it is now the most-cited paper in Blossom’s entire ketamine set at over 3,800 citations.
What made it startling was speed. Conventional antidepressants take four to six weeks to separate from placebo, and the field had largely accepted that as a property of how depression lifts. Ketamine moved scores within hours, which implied the delay was a property of the drugs, not the illness.
Hold two things at once here. This result reoriented an entire subfield and remains the origin point for everything below it on this canvas. It was also seven people in a crossover design, and a single small trial is a hypothesis rather than a finding. It took six more years for anyone to replicate it properly.
2004-07
National Institute of Mental Health (NIMH)
NIMH opens the replication programme
Carlos Zarate’s intramural study runs for thirteen years and produces the trial that made the field believe.
The National Institute of Mental Health put its intramural programme behind replicating Berman, and the 2006 readout is the moment the antidepressant claim stopped being a curiosity. Government money, not industry money, did that work.
The registry record runs to 2017, which tells you something about how these programmes actually operate. It is a long-running platform study rather than a single readout, and the famous result comes from an early slice of it.
The economics here are worth stating plainly. Ketamine was already generic in 2004, so no company had a patent worth defending and no company was going to fund the pivotal work. Public funding filled the gap. When you reach the esketamine thread below, notice that the compound which attracted commercial development was the one that could be patented.
2010-08
Archives of General Psychiatry
Randomised add-on trial in bipolar depression
The NIMH group extends the finding past unipolar depression, in Archives of General Psychiatry.
Bipolar depression is harder to treat and easier to destabilise, because antidepressants can tip some patients into mania. Showing a rapid effect there, in a randomised add-on design, widened the claim considerably.
A replication in Biological Psychiatry followed in 2012. Two independent randomised results in the harder population is a meaningfully stronger position than one, and this is roughly the point at which clinicians outside research settings started asking how to get hold of it.
2012-01
University of São Paulo, Ribeirão Preto
The first clinical trial opens in Brazil
An open-label study gives a single dose of church-prepared ayahuasca to patients with recurrent depression, with SPECT imaging before and after.
The formal clinical record starts here, 161 years after the first European note and roughly two decades after the Hoasca Project. It is a small, unregistered, single-arm study: seventeen patients, one dose, symptom scales out to three weeks, and brain perfusion imaging to see whether anything changed physically.
Depression scores fell quickly and stayed down over the follow-up, and perfusion increased in regions associated with emotional processing and interoception. In an open-label design with no control group, none of that separates drug effect from expectation, and the authors said so. What the study established was feasibility: that this could be done at all, in a hospital, with a preparation obtained from a church and its alkaloid content verified.
The preliminary report appeared in 2015 and the imaging paper in 2016. Both are among the most cited ayahuasca papers in Blossom, which is itself a comment on how thin the interventional literature is.
2013-11
Janssen Pharmaceuticals
Breakthrough Therapy designation for treatment-resistant depression
The FDA grants esketamine its expedited-development status for treatment-resistant depression, and does so again in 2016 for depression with imminent suicide risk.
Breakthrough Therapy designation is a promise of closer regulatory attention and a faster review, granted when preliminary evidence suggests substantial improvement over available therapy. It is not an approval and it is not a judgement that the drug works.
Two designations, three years apart, tell you how the programme was positioned. Treatment-resistant depression is where the unmet need argument is strongest, and acute suicidality is where nothing else acts fast enough. Both are populations for which the regulator was willing to accept a thinner evidence base than usual.
It is also where the commercial logic becomes visible. The designations attach to esketamine, not to ketamine, even though the underlying evidence at that point came almost entirely from racemic ketamine trials. The molecule that got the regulatory momentum was the one with a patent behind it.
Psychedelics return
2014 to 2018Small studies reopen several compound paths.2014-02
Federal University of Rio Grande do Norte
The randomised placebo-controlled trial
A trial in Natal randomises patients with treatment-resistant depression to a single dose of ayahuasca or an inert placebo, with response measured to seven days.
This is the study the rest of the canvas points at. Randomised, parallel-group, with a placebo built to match the taste and colour of the brew, in patients who had already failed at least two antidepressants. Depression scores were significantly lower in the ayahuasca group at one, two and seven days, and the effect was large enough to show up in a sample this size.
Three limitations belong next to that result and are stated in the paper. The sample is small, so the confidence intervals are wide. The follow-up is seven days, which says nothing about durability. And blinding almost certainly failed, because a substance that produces vivid visual imagery and vomiting is not hard to distinguish from mineral water; the placebo arm improved substantially too, which tells you the comparison was not psychologically inert.
It has been cited more than eight hundred times and it remains, a decade later, the only adequately powered randomised placebo-controlled ayahuasca trial for a psychiatric indication in this database. Compare the compounds that have a pharmaceutical sponsor: psilocybin went from a first randomised readout to multi-site Phase 3 in under a decade. Ayahuasca produced a positive randomised result in 2018 and nothing has been built on it, because there is nobody whose job it is to build on it.
2015-01
Imperial College London
Imperial opens the depression question
An open-label feasibility study in treatment-resistant depression at Imperial College London.
Robin Carhart-Harris and colleagues run a small open-label study in patients whose depression had not responded to existing treatment. No control arm, no blinding, twelve patients. The results, published in Lancet Psychiatry in 2016, showed large symptom reductions that persisted at six months in some participants.
Open-label results in depression should always be read carefully, because expectation alone moves depression scores and these participants knew exactly what they had taken. The study was designed to establish feasibility, and it did. What it also did was give every commercial programme further down this canvas a number to point at when raising money.
2015-08
Janssen Pharmaceuticals
The three TRANSFORM trials run
Three Phase 3 short-term studies in treatment-resistant depression open within a fortnight of each other. One of the three separates from placebo on its primary endpoint.
TRANSFORM-1 tested fixed doses in 346 adults, TRANSFORM-2 tested flexible doses in 236, and TRANSFORM-3 tested the same design in 139 elderly patients. All three added intranasal esketamine to a newly started oral antidepressant and compared it against the antidepressant plus a placebo spray.
TRANSFORM-2 met its primary endpoint. TRANSFORM-1 and TRANSFORM-3 did not. Approval on one positive short-term trial out of three is unusual, and the FDA accepted it on the strength of the relapse-prevention data and the designation status rather than on a clean replication.
The effect size in the trial that did work was modest: roughly four points of separation on the MADRS depression scale, which is real but sits close to the threshold at which clinicians start arguing about whether patients would notice. Read next to the hours-not-weeks framing of the 2000 result, the pivotal data are considerably less dramatic than the story around them.
There is also the blinding problem, which is not a technicality for this drug. Esketamine produces obvious dissociation within minutes and the comparator was a saline spray with a bittering agent. Most participants and most raters could reasonably guess who got what, and a later analysis of dissociation as a predictor of response is one of several attempts to work out what that does to the estimates.
2016-05
Nature
The metabolite result, in Nature
Zanos and colleagues report antidepressant actions from a ketamine metabolite that does not block the NMDA receptor.
For sixteen years the explanation had been NMDA receptor blockade (ketamine switching off a particular glutamate receptor). This paper argued that hydroxynorketamine, a downstream metabolite, produced antidepressant effects in mice without doing that at all.
If it holds, it means the therapeutic effect and the dissociation can be separated, and every company on this canvas trying to build a non-dissociating ketamine has a mechanistic story to point at. Blossom’s set has it at over 1,500 citations, second only to Berman.
It has not gone unchallenged. Replication has been contested and the field has not settled, which is a useful reminder that a Nature paper is a strong claim rather than a closed question. Gilgamesh’s GluN2B-selective programme and Ketabon’s dissociation-free oral formulation are both, in effect, bets on this line of reasoning being right.
From studies to programmes
2019 to 2024Approvals, comparisons and the first pivotal trials.2019-01
COMPASS Pathways
COMPASS opens the largest psilocybin trial yet
A 233-participant Phase 2b of COMP360 in treatment-resistant depression, the first industry-scale study of the compound.
COMPASS Pathways runs a randomised, controlled Phase 2b in treatment-resistant depression across ten countries. At the time it is by a wide margin the largest psilocybin trial ever conducted, and it is the moment the field acquires an industrial scale it had never had.
Scale changes what a trial can show. A 233-participant study can detect a modest effect and can surface adverse events too rare for a 12-patient academic pilot to catch. Both of those turned out to matter when the results published in 2022.
2019-03
Janssen Pharmaceuticals
FDA approves Spravato
Esketamine nasal spray is cleared for treatment-resistant depression, the first genuinely new antidepressant mechanism in decades, under a restricted distribution programme.
Janssen took the S-enantiomer, delivered it intranasally, and got the patent protection that racemic ketamine could never offer. That is the whole commercial logic of the programme, and it worked. Thirty-two years after fluoxetine, psychiatry had an approved antidepressant that did not act on monoamines.
Approval came with a REMS, a risk evaluation and mitigation strategy: administration in a certified clinic, direct observation while the dose is taken, two hours of monitoring afterwards, and no take-home supply. Those conditions exist because of the dissociation, the sedation and the blood-pressure rise, and they are defensible on safety grounds.
They are also the product’s central commercial problem. Two hours of monitored clinic time per dose, twice a week during induction, is expensive to staff and awkward to schedule, and the reimbursement often does not cover the chair time. Several later markers on this canvas exist because somebody is trying to get rid of that requirement.
The uncomfortable framing, which deserves to be stated rather than hinted at: this is a patented enantiomer of a cheap generic that any licensed prescriber could already use off-label. That is a commercial strategy as much as a pharmacological one. The fair counter is that nobody else was going to fund a 1,500-patient registration programme for a compound with no exclusivity, and without one there would be no approved, quality-controlled, labelled product at all. Both things are true.
2019-11
GH Research
Phase I/II in depression
The first patient study of GH001, running nearly two years through the pandemic.
The first time the compound is given to patients rather than healthy volunteers, which is the step where a programme starts generating evidence about benefit rather than safety alone.
The near-two-year run reflects pandemic recruitment conditions as much as protocol design. Read trial durations on this canvas with that caveat: the bars measure elapsed time, not effort or difficulty, and 2020 stretched almost everything.
2019-11
Usona Institute
FDA Breakthrough Therapy for Usona
The regulator grants Breakthrough Therapy Designation to a non-profit’s psilocybin programme for major depression.
Breakthrough Therapy Designation is the FDA signalling that a treatment may offer a substantial improvement over what exists, and committing to more intensive guidance in return. Usona receives one for major depressive disorder in November 2019, a year after COMPASS received one for treatment-resistant depression.
The detail worth pausing on is that Usona is a non-profit medical research organisation, not a venture-backed biotech. Its results are intended to reach the literature and the regulator without a commercial licensing layer sitting on top. On a canvas where the money lane fills up rapidly after this point, that is a genuinely different model rather than a rhetorical one.
2021-04
Small Pharma Ltd
The commercial thesis enters the clinic
Small Pharma opens a Phase 1/2a of SPL026, an intravenous DMT fumarate, in healthy volunteers and patients with major depressive disorder.
Here is the argument the whole commercial lane rests on. A psilocybin session occupies six to eight hours, two therapists and a dedicated room, and that cost is the reason psychedelic therapy is hard to fit into a health system. An intravenous DMT session lasts minutes. If the antidepressant effect survives the compression, the economics change completely.
SPL026 was the first serious test of that proposition. Small Pharma ran it as an integrated programme rather than a single study: healthy-volunteer safety first, then patients, then a follow-on asking whether the effect survives concurrent SSRI treatment, which matters enormously because most people with depression who would be offered this are already taking one.
The proposition remains unproven, and it is worth naming what could break it. Antidepressant response to psychedelics may depend on the duration of the experience rather than merely on its occurrence. A shorter session leaves less room for the psychological work that most protocols treat as the active ingredient. Nobody has yet run the head-to-head study that would settle it.
2021-04
New England Journal of Medicine
Psilocybin fails to beat escitalopram on the primary endpoint
The first head-to-head against a standard antidepressant publishes in the New England Journal of Medicine. The primary endpoint is not met.
Imperial College London runs psilocybin directly against escitalopram, a widely prescribed SSRI, in moderate-to-severe depression. On the primary endpoint, the difference between the two is not statistically significant. Several secondary measures favoured psilocybin, and the trial was not powered for the comparison it is most often quoted for.
This trial is routinely reported as a psilocybin win and routinely reported as a psilocybin failure, depending on who is doing the reporting. Both readings are selective. The honest summary is that a 59-participant study could not distinguish the two treatments on its pre-specified measure, which is a real result and a genuinely underpowered one.
A six-month observational follow-up published in 2024 found the groups had converged further. Head-to-head comparisons against active treatment are the hardest test a new psychiatric drug can face, and this remains the only one psilocybin has attempted.
2022-06
Neuropsychopharmacology
First depression data reach print
An exploratory report covers dose-related safety, tolerability and efficacy of intravenous DMT in healthy volunteers and in major depressive disorder.
This is the paper that made the short-duration case look plausible rather than merely clever. It reports dose-related safety and tolerability alongside an efficacy signal in patients, which is what a Phase 1/2a is supposed to produce and what most compounds at this stage fail to.
Exploratory is the operative word. Small samples, open questions about blinding, and an efficacy read that was never powered to be definitive. In psychedelic research the gap between a promising early signal and a controlled replication has repeatedly turned out to be wide, and treating an exploratory readout as proof of concept is how the field keeps disappointing itself.
A companion pharmacokinetic paper published the same year characterised how DMT fumarate behaves in the body, and a 2023 modelling study went on to derive infusion rates that hold the experience at a target intensity. That kind of work is unglamorous and it is what turns a drug into a dosing protocol.
2022-11
New England Journal of Medicine
COMP360 Phase 2b publishes in the NEJM
A 25 mg dose beat a 1 mg comparator at three weeks. The separation had largely faded by twelve weeks, and adverse events clustered in the high-dose arm.
The largest psilocybin trial to that date reports in the New England Journal of Medicine. A single 25 mg dose produced a significantly greater drop in depression scores than a 1 mg comparator at three weeks. By week twelve the gap between arms had narrowed considerably.
The safety findings drew as much attention as the efficacy ones. Suicidal ideation and self-injurious behaviour were reported more often in the 25 mg group than in the 1 mg group. In a treatment-resistant population with a high baseline risk this is difficult to interpret, and the trial was not designed to settle it.
This is the paper that turned psilocybin from a promising story into a regulatory proposition, and it is also the paper that set the bar sceptics have been pointing at ever since. A durable single-dose effect was the commercial premise. Three weeks of clear separation is not obviously that.
2022-11
COMPASS Pathways
The first psilocybin Phase 3
COMP005 opens, the first pivotal trial of psilocybin anywhere, followed by the repeat-dose COMP006 three months later.
COMPASS opens COMP005, a single-dose pivotal study in treatment-resistant depression, and follows it in February 2023 with COMP006, which tests two administrations. Together they are the registration package.
Fifty-two years after Schedule I and twenty-one years after Moreno restarted human research, psilocybin finally enters pivotal trials. It is the longest run-up of any compound on Blossom.
COMP005 completed in October 2024 and topline results were reported in mid-2025. The reported difference against the 1 mg comparator was statistically significant but modest in absolute terms, and the share price reaction suggested investors had expected more. COMP006, the repeat-dose study, is where the durability question is actually being tested.
2023-03
GH Research
ended earlyPostpartum depression (terminated)
A Phase II in postpartum depression is terminated. The results were still published in 2026.
Terminated trials usually vanish. Nobody publishes them, so the field never learns what went wrong, and the same idea gets tried again by someone else.
This one did not vanish. The Phase 2a results were published in the Journal of Clinical Psychiatry in June 2026, three years after the trial stopped. Both events sit on this canvas because both are true, and a timeline that showed only the successes would be marketing rather than evidence.
Termination is also not the same as failure. Trials stop for recruitment problems, funding, or strategic reprioritisation as often as for safety or futility, and the registry record rarely says which.
2023-05
GH Research
Phase II TRD completes
The anchor study in treatment-resistant depression reads out.
With the postpartum and bipolar arms stopped, this becomes the study GH Research’s case rests on. It is also the closest comparator for the BPL-003 programme running one lane below, which matters for reading the acquisition that follows.
Two sponsors, the same compound, different routes of administration and different corporate outcomes. GH Research completed its Phase II first, and went on to publish the only randomised placebo-controlled trial on this canvas. AtaiBeckley was the one Lilly bought.
2023-09
JAMA
Usona Phase 2 publishes in JAMA
A single 25 mg dose beat an active placebo over six weeks in 104 participants with major depression.
Usona’s PSIL201 study reports a rapid and sustained antidepressant effect against a niacin active placebo, in the general major-depression population rather than the treatment-resistant one. It is the strongest evidence supporting the Phase 3 that follows six months later.
The trial has an awkward companion record. Its long-term follow-up study was terminated in October 2022, which means the durability question the original trial raised was not answered by the study designed to answer it. Terminations rarely come with an explanation, and this one does not.
2023-10
New England Journal of Medicine
ESCAPE-TRD beats quetiapine
A head-to-head against an established augmentation drug, published in the New England Journal of Medicine.
Esketamine plus an antidepressant outperformed quetiapine extended-release plus an antidepressant on remission at week eight, in 676 randomised patients. Beating an active comparator that guidelines already recommend is a stronger claim than beating placebo, and this is the best single result in the esketamine dossier.
It is open-label, which for a drug producing obvious dissociation is a real limitation rather than a technicality. Patients knew whether they were spraying something that made the room feel strange or swallowing a sedating tablet, and both they and their clinicians rated the outcomes.
The follow-on literature is unusually complete for once: sensitivity analyses, a long-term extension published in 2026, work-productivity costings and a cost-per-remitter analysis. Payers read those rather than the NEJM paper, and the economic case is where this trial has done most of its work.
2023-10
Nature Mental Health
ended earlyKetamine masked by surgical anaesthesia: no difference
Given to patients already unconscious for surgery, so nobody could tell who received it, ketamine did not beat placebo.
The cleverest trial design on this canvas, and the most uncomfortable result. Patients undergoing surgery were randomised to ketamine or placebo while already under general anaesthesia, which makes the blind genuinely airtight. Neither patients nor raters could tell.
Both groups improved substantially. Neither improved more than the other.
One interpretation is that a meaningful part of ketamine’s antidepressant effect in ordinary trials comes from expectation, made powerful by the unmistakable experience of having received something. Another is that a patient who is unconscious cannot have the experience that does the therapeutic work. A third is that the trial was small, in a surgical population, and does not generalise.
Nobody knows which is right, and a 2026 systematic review of blinding integrity across psychedelic trials suggests the problem is not confined to ketamine. This is the strongest existing challenge to the whole edifice above it, so it belongs here at full weight rather than in a footnote.
2024-03
Cybin
Breakthrough designation for an analogue
The FDA grants Breakthrough Therapy Designation to CYB003, the first for an adjunctive psychedelic therapy in major depression.
CYB003 is a deuterated psilocin analogue rather than psilocybin itself: chemically modified to shorten the session and make the dose more consistent between patients. The designation covers its use alongside an existing antidepressant rather than in place of one.
Adjunctive positioning is a quiet but important strategic choice. It sidesteps the head-to-head comparison that produced an ambiguous answer for Imperial in 2021, and it fits how depression is actually treated, since most patients are already on something. It also means a positive result would show psilocybin-class treatment adding to standard care, which is a narrower claim than the one the field usually makes for it.
The verdict years
2025 onwardsCompeting formulations approach consequential readouts.2025-04
Definium Therapeutics
Phase 3 opens in major depression
Emerge takes the same formulation into a second and much larger indication.
Depression is a far bigger market than generalised anxiety and a far more crowded one, with two decades of failed novel mechanisms behind it. Opening a second pivotal indication before the first has read out spreads the risk and raises the stake at the same time.
A second MDD study, Ascend, began in May 2026 and runs to mid-2028.
2025-04
Neuropsychopharmacology
Vaporised DMT reports an antidepressant signal
A Phase 2a in treatment-resistant depression reports rapid and sustained antidepressant effects from vaporised DMT, the first efficacy readout for the compound itself.
Five years after the first registered trial, DMT has an efficacy result. It is Phase 2a, so it is small and exploratory, and it reports both rapid onset and effects that persist beyond the day of dosing, which is the pattern the whole field is looking for and rarely finds in a single study.
Treatment-resistant depression is a demanding population and a forgiving one at the same time. Demanding, because these patients have already failed several adequate trials of standard treatment. Forgiving, because expectancy runs high in people who have exhausted the alternatives and know they are receiving something novel, and an unblinded psychedelic maximises that.
A companion randomised double-blind study of vaporised DMT published two months later gives the safety and subjective-effects picture from a controlled design. Read together, the two make a reasonable case for proceeding, and no case at all for concluding.
2025-08
Reunion Neuroscience
RE104 hits its endpoint in postpartum depression
A 23.0-point depression score reduction at day seven against 17.2 for the control arm, with an effect visible from day one.
Reunion Neuroscience reports positive topline results from RECONNECT, a Phase 2 of luvesilocin (RE104, a psilocin prodrug) in postpartum depression across 38 US sites. The 30 mg arm reached a 23.0-point reduction on the depression scale at day seven against 17.2 for the 1.5 mg control, with no serious adverse events reported.
Postpartum depression is a well-chosen indication. It affects roughly one in seven women after birth, it has an existing rapid-acting comparator in the approved neurosteroids, and the regulatory path is sympathetic. The FDA granted Breakthrough Therapy Designation in February 2026 and, after an end-of-phase-2 meeting, indicated that a single additional pivotal trial could support a filing.
The control arm is worth noticing. A 17.2-point improvement in the low-dose group is a large response to something intended as a comparator, which is the blinding problem showing up again in the numbers rather than in the discussion section.
2025-09
University of Basel
Basel depression trial: a near miss
61 patients, high dose against low dose. The clinician-rated difference was significant until baseline severity was accounted for, and then it was not.
The honest reading of this result is that it is inconclusive. Self-rated depression scores favoured the high dose but missed significance (p = 0.059). Clinician-rated scores reached significance (p = 0.023) and then lost it once baseline severity was adjusted for (p = 0.086).
The authors called for a larger Phase 3, which is the correct conclusion and also the one that keeps a programme alive. It is worth naming what this study cannot tell us: with 61 patients and a low-dose comparator rather than placebo, it was never going to settle the question.
It sits directly below the MM120 depression programme on this canvas, which is running two pivotal trials on a related premise with far more money behind it and no published depression result of its own.
2025-10
AbbVie
AbbVie acquires the bretisilocin programme
Up to $1.2bn for Gilgamesh’s GM-2505, the largest psychedelic drug deal on record.
AbbVie completes its acquisition of Gilgamesh Pharmaceuticals’ bretisilocin programme, announced in August 2025, in a deal worth up to $1.2bn. Bretisilocin is a short-acting serotonin 5-HT2A agonist designed to compress the dosing session, which is where most of the delivery cost in psychedelic therapy sits.
The evidence behind the deal is one Phase 2a: a 21.6-point improvement on the depression scale against 12.1 for a 1 mg comparator, no serious adverse events. That is a strong signal from a small study against an active comparator rather than a placebo.
Read this next to Otsuka paying CAD $80m for a whole company two years earlier and the pattern is clear. Big pharma is not buying psilocybin. It is buying short-acting engineered analogues with defensible patents and shorter clinic time, and it is paying roughly fifteen times more for them. The compound that generated all the evidence on the left of this canvas is not itself the asset.
2026-03
JAMA Psychiatry
GH001 randomised trial in JAMA Psychiatry
GH001 beats placebo in a randomised controlled trial, the strongest evidence on this canvas.
The first randomised, placebo-controlled evidence for any 5-MeO-DMT compound, published in JAMA Psychiatry in March 2026. Randomisation and a placebo arm are what separate a suggestive result from a credible one, and until this point every study on this canvas lacked both.
It belongs to GH Research, not to the programme Lilly acquired. Read the two clinical lanes together and an awkward pattern appears: the sponsor with the stronger published evidence is not the sponsor that got bought.
One caution before treating this as settled. A single randomised trial is a beginning, not a conclusion, and independent replication is what turns it into an approvable claim.
2026-10
Helus Pharma
plannedAPPROACH topline expected
Company guidance puts the first pivotal readout for HLP003 in the fourth quarter of 2026.
The nearest thing to a verdict on this canvas. APPROACH is the first of the two PARADIGM pivotal studies, and Helus guides to topline data in the fourth quarter of 2026. This is company guidance rather than a registry-confirmed date, so treat it as the optimistic case.
What a positive result would and would not establish is worth being clear about now, before the headlines arrive. It would show a deuterated psilocin analogue, given alongside an existing antidepressant, outperforming a low-dose comparator in major depression. It would not show that psilocybin is an approved medicine, and it would not resolve the blinding question that has shadowed every trial above it.
A negative result would be more consequential. Two decades of accumulated signal, and the field’s first properly powered pivotal test, would have failed to converge.
Depressive Disorders
The psychedelic research story across depressive conditions
Research Landscape
What the registered trials connected to Depressive Disorders look like when you line them up. Counts come from Blossom’s trial records as of August 2026.
How fast is Depressive Disorders research growing?
SourcedRegistered trials by recorded study-start year; 55 earlier trials began before 2013. Click a year for the running total.
Don't read as total research effort: only registered trials with a recorded start date are counted (605 of 606 tracked). Recent years under-count because of registration lag; striped bars are still filling in or are planned starts.
What's live right now, and what stopped?
SourcedRegistry status of all 606 Depressive Disorders trials Blossom tracks. Orange marks trials recruiting or opening.
- Recruiting or opening
- 17930%
- Underway, not recruiting
- 325%
- Completed
- 26544%
- Stopped early
- 7312%
- Unknown / other
- 579%
Don't read stopped trials as failures: trials end early for funding, recruitment, and strategy reasons too. Status is as last synced from the registry; some 'recruiting' trials may already have finished.
Which compounds carry the Depressive Disorders research?
SourcedTrials per compound. Orange marks the most-studied compound.
Don't read shares as adding to 100%: a trial testing several compounds counts once per compound, and placebo comparator arms are not shown. Trial volume signals research attention, not evidence quality.
How does Depressive Disorders research split by subtopic?
SourcedTrials per subtopic within the 606 Depressive Disorders trials on this page. Orange marks the largest subtopic.
Don't read shares as adding to 100%: a trial can name several subtopics (MDD and TRD often travel together), and 'no subtopic specified' means the trial is tagged only with this broader category. Each subtopic's own page can show a different total because it also tracks trials outside this set.
Publication Landscape
How the 1,236 papers Blossom links to Depressive Disorders line up by year, compound and journal. This is the psychedelic-relevant literature in Blossom's records as of August 2026, not the condition's full medical literature.
How has Depressive Disorders research grown?
SourcedTracked papers by publication year; 24 earlier papers published before 2012. Click a year for the running total.
Don't read as total output: only the 1,236 of 1,236 tracked papers with a recorded publication date are counted, and these are the psychedelic-relevant papers Blossom tracks, not a complete bibliography. The current year is still filling in.
Which compounds shape Depressive Disorders?
SourcedTracked papers per compound. Orange marks the largest literature.
A paper studying several compounds counts once per compound, and placebo comparator arms are not shown. These are the psychedelic-relevant papers Blossom tracks.
Where is Depressive Disorders research published?
SourcedTracked papers per journal. Orange marks the most-used journal.
Counts the journal recorded on each tracked paper; papers without a journal on file are omitted. Blossom tracks psychedelic-relevant papers rather than each journal's full catalogue.