Short-acting programs are built on the bet that they can match the durability of a six-hour psilocybin session in a fraction of the time. But do they buy as much benefit per dosing day?
This analysis compares six depression programs based on two parameters: 1. how long a patient stays in the clinic on a dosing day, and 2. how long the benefit held per dosing day.
1. A Longer Trip Could Buy Longer Relief, but the Data Cannot Confirm It Yet
Short-acting programs, those where most patients leave the clinic within two hours (GH001 and BPL-003, both 5-MeO-DMT), have shown up to 8 weeks of benefit per dosing day. Long-acting programs, those with sessions of four to eight hours (COMP360, DT120 and HLP003), have mostly shown 12 or more. That fits the idea that a longer session buys longer benefit.
Only one program, GH001, was followed long enough to see how often patients needed another dose: roughly every six weeks. That is sooner than any long-session program has shown, which fits the idea that session length matters.
All the other psychedelic programs were still holding when their blinded trials ended: BPL-003 at 8 weeks, DT120 at 12, and COMP360 at 26. HLP003 was followed for a year, but mostly open-label, after a blinded phase of only three weeks. So we don’t know how long any of these four programs really lasts. If BPL-003 turns out to hold for months, the case that session length matters gets weaker.
Two other problems make it hard to compare short and long sessions. The short-session programs both use the same molecule, 5-MeO-DMT, so we can’t tell whether their shorter benefit comes from the session length or from the drug itself. And the programs were tested in two different groups of patients, TRD (treatment-resistant depression) and MDD (major depressive disorder), and benefit tends to last longer in MDD.
The durability figures are also not measured the same way. For COMP360 they describe only the 25 to 39% of patients who improved by at least 25% at week 6, and for HLP003 a handful of patients followed open-label for a year. For BPL-003 and DT120 they describe the whole treated group. Two of the three long-acting programs are therefore measured on their best patients, which flatters the long-acting side.
2. Most Blinded Windows Closed Before the Benefit Wore Off
Let's compare the hours in clinic against weeks of benefit per dosing day across the 6 following programs:
Program: Spravato (esketamine nasal spray, J&J)
Population: TRD
Stage: Approved
Hours in clinic: At least 2 of observation (visits typically 2 to 3)
Dosing days: 34 to 56 a year on the label schedule
Blinded window: Not applicable
Benefit per dosing day: 1 to 2 weeks
Program: GH001 (inhaled 5-MeO-DMT, GH Research)
Population: TRD
Stage: Phase 2b
Hours in clinic: About 1 to 2 for most patients, up to about 3 with all three doses (effects last 9 to 14 minutes per inhalation; doses given an hour apart)
Dosing days: Mean of 4 over the 6-month study, including the first treatment day
Blinded window: 1 week, then 6-month open label
Benefit per dosing day: About 4 to 8 weeks
Program: BPL-003 (nasal 5-MeO-DMT, Eli Lilly)
Population: TRD
Stage: Phase 3
Hours in clinic: 1.5 to 2 (most patients discharge-ready at 90 minutes)
Dosing days: 1
Blinded window: 8 weeks
Benefit per dosing day: At least 8 weeks
Program: HLP003 (deuterated psilocin analogue, Helus Pharma)
Population: MDD
Stage: Phase 3
Hours in clinic: 4 to 6 (company-reported duration of acute effects, not a measured discharge time)
Dosing days: 2
Blinded window: 3 weeks, then open follow-up to 52 weeks
Benefit per dosing day: At least 26 weeks in the 5 of 10 patients given two 12 mg doses who were in remission at 12 months
Program: DT120 (LSD, Definium)
Population: MDD
Stage: Phase 3
Hours in clinic: 5.8
Dosing days: 1
Blinded window: 12 weeks
Benefit per dosing day: At least 12 weeks
Program: COMP360 (psilocybin, Compass Pathways)
Population: TRD
Stage: Phase 3
Hours in clinic: 6 to 8
Dosing days: 1 to 2 in COMP005; 2 to 3 in COMP006 (through week 26)
Blinded window: 26 weeks
Benefit per dosing day: About 9 to 26 weeks in the 25 to 39% of patients who improved by at least 25% at week 6
“GH001 is the only program here followed long enough to see when patients needed another dose.”
3. What Each Program Actually Measured
Spravato (esketamine nasal spray, Johnson & Johnson): not a classic psychedelic, but it shows what a two-hour session buys today. The label calls for at least two hours of observation per session, twice weekly for weeks 1 to 4, weekly for weeks 5 to 8, then weekly or every two weeks from week 9. Each visit buys one to two weeks, and the benefit is sustained only by repeat dosing. That figure is the interval the label sets, not a durability measured after dosing stopped, so it is a different kind of number from the other five.
GH001 (inhaled 5-MeO-DMT, GH Research): each inhalation’s effects last 9 to 14 minutes, and patients can receive up to three in one day, an hour apart. Most needed only one or two and were ready to leave about an hour after dosing, so a typical visit lasts two hours or less (HCPLive, 2026a; GH Research, 2025). The placebo-controlled part of the trial lasted only one week. After that, patients could be redosed over six months whenever their depression scores called for it. On average they received four treatments in total, and the median time to the first redose was about six weeks (JAMA Psychiatry, 2026; HCPLive, 2026a). Michael Thase, the study’s senior author, expects patients will need a dose every six to eight weeks in practice (HCPLive, 2026b). This makes GH001 the only program followed long enough to see when patients needed another dose.
BPL-003 (nasal 5-MeO-DMT, Eli Lilly): the in-clinic visit lasted about two hours on average, and most patients were discharge-ready at 90 minutes (Eli Lilly, 2026a; Fierce Biotech, 2026). After a single 8 mg dose, benefit was still significant at day 57 (8 weeks), when the blinded core study ended and patients were offered a redose (Fierce Biotech, 2026; AtaiBeckley, 2025). Eight weeks is therefore a floor: the trial cannot say how much longer the effect would have lasted. Lilly completed its acquisition of AtaiBeckley in September 2026, and the Phase 3 program is underway (Eli Lilly, 2026a; 2026b).
HLP003 (deuterated psilocin analogue, Helus Pharma): Helus reports acute effects lasting 4 to 6 hours with onset within 15 minutes, designed to be shorter than psilocybin (Helus Pharma, 2026). That is the duration of the experience rather than a measured discharge time. After two 12 mg doses three weeks apart, 5 of the 10 patients who completed 12-month follow-up were in remission (Cybin, 2024). The 16 mg dose now in Phase 3 did better, with 5 of 7 in remission; we use the 12 mg figure as the conservative case. Both are small Phase 2 cohorts followed open-label. A Phase 3 readout is expected in Q4 2026.
DT120 (LSD, Definium): patients met end-of-session criteria after 5.8 hours on average (median 5.1), close to a psilocybin session despite LSD's longer pharmacology (Definium Therapeutics, 2026). After a single 100 µg dose, DT120 was still 7.3 MADRS points ahead of placebo at week 12, the end of the blinded phase. This is a group mean, not responder durability, and the population is MDD rather than TRD.
COMP360 (psilocybin, Compass Pathways): a session typically lasts six to eight hours, with psychological support throughout (Compass Pathways, n.d.). In COMP005, patients received one dose; in COMP006, two doses three weeks apart. In both trials, they could receive one extra dose before week 26. On the 25 mg dose, 25% of patients in COMP005 and 39% in COMP006 improved by at least 25% by week 6, and on average they held that improvement until week 26, when the blinded phase ended (Compass Pathways, 2026a; 2026b). Depending on how many doses they received, that is about 9 to 26 weeks per dosing day. After week 26, most 25 mg patients who stayed in COMP005 took another dose: 90 people, about half of the 171 who started on that dose (Compass Pathways, 2026c).
4. Three Kinds of Data Would Settle the Question
Matched follow-up: a short-acting Phase 3 that keeps patients blinded for 26 weeks or more with no scheduled redose. Until then, BPL-003's durability is capped by its 8-week design.
Same molecule, different duration: deuteration slows metabolism and can change how long the effect lasts without changing the target. A head-to-head of a deuterated analogue against its own non-deuterated parent is the cleanest test of duration alone. HLP003 against psilocybin does not qualify, because HLP003 is also given as psilocin rather than as the psilocybin prodrug, which changes its pharmacokinetics independently of deuteration.
Comparable intensity data: Few trials report MEQ-30 (Mystical Experience Questionnaire) or 5D-ASC (Five-Dimensional Altered States of Consciousness Rating Scale) scores in the same way, so intensity cannot yet be tested as a driver of durability.
References
- AtaiBeckley (2025). Positive topline data from the Phase 2b open-label extension of BPL-003.
- Compass Pathways (n.d.). About psilocybin therapy.
- Compass Pathways (2026a). Compass Pathways successfully achieves primary endpoint in second Phase 3 trial evaluating COMP360 psilocybin for treatment-resistant depression.
- Compass Pathways (2026b). Six-month data from second Phase 3 trial confirming rapid and durable profile.
- Compass Pathways (2026c). New 52-week topline open-label data from Phase 3 COMP005 trial demonstrates additional benefit from another COMP360 dose in Part C.
- Cybin (2024). CYB003 produces robust and enduring antidepressant effects, 12-month data (ACNP poster).
- Definium Therapeutics (2026). Positive topline results from Phase 3 Emerge study of DT120 ODT in major depressive disorder.
- Eli Lilly (2026a). Lilly to acquire AtaiBeckley to advance therapies for treatment-resistant depression and other mental health conditions.
- Eli Lilly (2026b). Lilly completes acquisition of AtaiBeckley.
- European Psychiatry (2026). Long term efficacy and safety of GH001 in patients with treatment-resistant depression.
- Fierce Biotech (2026). Eli Lilly inks $2.8B AtaiBeckley buyout to challenge J&J in psychedelic mental health market.
- GH Research (2025). Global pivotal program plans and further development updates.
- HCPLive (2026a). Single-day GH001 for TRD shows rapid response, with Michael E. Thase.
- HCPLive (2026b). Maintenance dosing and safety shape GH001 outlook, with Michael E. Thase.
- Helus Pharma (2026). Corporate presentation, March 2026.
- JAMA Psychiatry (2026). GH001 vs placebo in patients with treatment-resistant depression: a randomized clinical trial.
- Janssen. Spravato (esketamine) prescribing information.
Written by Alexandre Stipanovich, with AI-assisted research, fact-checking, and editing (Claude Opus 5.5).
This analysis is for informational purposes and does not constitute investment, medical, or regulatory advice.