Context / inspiration: https://forum.effectivealtruism.org/posts/x8P8EGnujSZm6fyMH/emerging-evidence-on-treating-cluster-headaches-with-dmt
Notably: "Currently, there exist no published studies on the efficacy of DMT to treat cluster headaches. The bulk of the evidence comes from testimonials of patients and advocates, which we argue is highly credible and should be weighted heavily"

Study must be peer-reviewed and have a sample size of at least 100.

Questions on timeline of a study being done are thresholds, i.e. a study being published in 2032 resolves (1) NO, (2) and (3) YES.

Questions on effects resolve to the results of the first study conducted that investigate that thing. I.e. if a study investigates short-term effects but not long-term ones, only the short-term question resolves, and the long-term one resolves when a study investigates long-term effects. These resolve N/A if no such study is published by 2040.

Endorsed AI content:

Resolution criteria

This market will resolve based on the publication of a peer-reviewed scientific study investigating the effects of N,N-dimethyltryptamine (DMT) on cluster headaches. The study must have a sample size of at least 100 participants. Publication in a recognized academic journal (e.g., indexed in PubMed or Google Scholar) will serve as verification.

• Study conducted and released by 2030 / 2040 / 2050: These answers will resolve YES if a qualifying study is published by the end of the respective year (December 31, 2030, 2040, or 2050 UTC). If a study is published in 2032, for example, "Study conducted and released by 2030" will resolve NO, while "Study conducted and released by 2040" and "Study conducted and released by 2050" will resolve YES.

• Study that investigates short-term effects of DMT as a treatment has positive findings: This answer will resolve YES if the first qualifying study to specifically investigate short-term effects of DMT on cluster headaches reports statistically significant positive findings in its primary outcome measures (e.g., reduction in attack frequency, intensity, or duration). Short-term effects are generally understood as those observed within weeks following administration, typically up to 3 weeks.

• Study that investigates long-term effects of DMT as a treatment has positive findings: This answer will resolve YES if the first qualifying study to specifically investigate long-term effects of DMT on cluster headaches reports statistically significant positive findings in its primary outcome measures (e.g., sustained reduction in attack frequency, extension of remission periods, or changes in cluster cycles). Long-term effects are generally understood as those observed over a sustained period, typically months (e.g., 3 months or more) or longer.

If a qualifying study does not investigate a specific effect (e.g., only short-term, not long-term), only the investigated effect's answer will resolve. The other effect's answer will resolve when a subsequent qualifying study investigates and reports on it.

Background

Cluster headache is a rare and severely painful neurological condition, often referred to as "suicide headache" due to its intense pain. It affects approximately 0.1% of the population, with patients experiencing excruciating head pain, often accompanied by autonomic symptoms like tearing or nasal congestion. Conventional treatments have limitations, and a significant portion of patients report dissatisfaction with available therapies or experience side effects.

There is growing anecdotal and some preliminary clinical evidence suggesting that psychedelics, particularly psilocybin and LSD, may be effective in treating cluster headaches by aborting attacks or preventing cycles. DMT (N,N-dimethyltryptamine) is a psychedelic compound of the tryptamine family, chemically similar to psilocybin and structurally related to triptans, a class of drugs used for headache relief. While there are no currently published human clinical trials on DMT for cluster headaches that meet the specified criteria (peer-reviewed, sample size ≥ 100), extensive anecdotal reports from patients suggest that DMT, even at sub-perceptual doses, can rapidly abort cluster headache attacks with few reported side effects. Research is ongoing into the acute analgesic properties of DMT in broader pain models, but specific large-scale studies for cluster headaches are yet to be published.

Considerations

The legal status of DMT as a Schedule I controlled substance in many jurisdictions presents significant regulatory hurdles and logistical challenges for researchers, which can delay the initiation and completion of clinical trials. This regulatory environment may influence the timeline for such studies to be conducted and published.