Psilocybin tested in bipolar II depression

Fourteen people, no control arm, no mania — encouraging but nowhere near an answer.

Weekly Science Digest, 19 Sep 2026 to 25 Sep 2026. 40 papers read, 6 preprints, 1 new trials.

1. A population trials usually exclude

Psilocybin was tolerated in 14 people with bipolar II depression, with no mania reported.

The open-label, single-arm trial started at 10 mg and escalated to 25 mg if symptoms persisted, with therapy around each session. Cardiovascular changes were transient; the primary depression endpoint came 21 days after the final dose.

2. Designing the valve risk out of psychedelics

Cryo-EM structures guided compounds that activate 5-HT2A while blocking 5-HT2B.

Comparing the orthosteric pockets of the two receptors yielded a pharmacophore model and two compound series, confirmed by five further receptor-ligand structures. Selected compounds showed antidepressant-like effects in rodents.

3. Mechanism and acute-state work

Intranasal DMT plus harmine made EEG microstate sequences shorter and less random.

In a 25-person double-blind crossover, the DMT/harmine formulation cut microstate duration and raised occurrence and complexity versus harmine alone or placebo; Markov analysis showed transitions became less random, not more.

4. What trial participation costs participants

A bioethics cluster asks whether psychedelic trials adequately disclose employment risk.

The target case is a chronic pain trial; commentaries extend it to military personnel and to whether psychedelics get treated as ethically exceptional. Drug testing, security clearances and licensure can all be jeopardised by documented enrolment.

5. In brief

6. In the clinic

How much weight it carries: Trial registry movements: what is being attempted, not what was found. (Registry, Plans, not results)

7. On the preprint servers

How much weight it carries: Not peer reviewed. Early results that may not hold up. (Preprint)

—
Node—
Statuslive
Throughput—