Does any DMT variant work here? Since you mentioned psilocybin working, and most people mean NN-DMT when they say “DMT”. Since some DMT variants have lighter psychedelic effects. Claude 4.5 Sonnet, when pressed, claims that 4-AcO-DMT would be the least disruptive.
(I’m a bit worried that psychedelics enthusiasts are a very exited about using psychedelics to treat this hellish condition, and might not be maximally balanced in evaluating the evidence.)
4-AcO-DMT is converted to psilocin (4-HO-DMT) in the body, the same way psilocybin (4-PO-DMT) does, so it’s not particularly different.
DMT is already mild when taken in doses required for this condition. If you want something even milder, 5-MeO-DALT pops up in discussions, but my impression it’s because it’s legal in many jurisdictions.
Re: psychedelic enthusiasts.overstating effects. I recommend going for the primary sources and looking up testimonials from cluster headache patients!
Re: psychedelic enthusiasts.overstating effects. I recommend going for the primary sources and looking up testimonials from cluster headache patients!
Yeah… I’m trying to beware surprising and suspicious convergence here. “Local psychedelics enthusiasts discover that psychedelics are the cure to the worst conditions known to humanity, more at 11.”
This is, in some sense, a cheap and kind of mean heuristic, but I wanted to flag the suspicion. I might go and read some testimonials, but nothing beats a good ol’ RCT[1]. I don’t want to be the person who’s like “you need more research before you advocate” and I’m looking forward to putting DMT-variants head-to-head in an experiment with known medical treatments for cluster headaches.
Actually not true, we could & should try to design successors to the RCT, but they’ll go in the direction of “Thompson-sample from the posterior distribution in some bandit setup” as opposed to “more anecdata”.
I don’t think there was an RCT for DMT vs triptans. It’d be great to have one but I don’t think anyone ran one. There are also legal barriers to running one (which are definitely possible to overcome, but still).
Testimonials and surveys of patients are the best thing we have currently.
On a similar note, I wonder if a more promising angle of attack is chemical research to find another compound that might be even more effective.
Given that sumatriptan and DMT are pretty similar, and the psychedelic effects of DMT are apparently not relevant, it’s plausible that there might be an even better molecule out there.
If that molecule did not have psychedelic effects, that would be ideal in terms of quick widespread adoption.
4-AcO-DMT and most other psychedelics also last on the order of 8 hours (or more), while inhaled / injected DMT lasts ~20 minutes.
Normally, ingested DMT has no pharmacological activity because monoamine oxidase (MAO) in the body will break it down before it has any effect. The likely reason is that DMT is endogenous.
Ayahuasca is an ingested DMT extract that also contains a natural MAO-inhibitor. (“Pharmahuasca” is an analogue of it that uses ingestion of purified DMT plus an MAO-inhibitor in pill form).
A sub-impairment dose of DMT sounds like the least invasive treatment for this in particular.
Does any DMT variant work here? Since you mentioned psilocybin working, and most people mean NN-DMT when they say “DMT”. Since some DMT variants have lighter psychedelic effects. Claude 4.5 Sonnet, when pressed, claims that 4-AcO-DMT would be the least disruptive.
(I’m a bit worried that psychedelics enthusiasts are a very exited about using psychedelics to treat this hellish condition, and might not be maximally balanced in evaluating the evidence.)
4-AcO-DMT is converted to psilocin (4-HO-DMT) in the body, the same way psilocybin (4-PO-DMT) does, so it’s not particularly different.
DMT is already mild when taken in doses required for this condition. If you want something even milder, 5-MeO-DALT pops up in discussions, but my impression it’s because it’s legal in many jurisdictions.
Re: psychedelic enthusiasts.overstating effects. I recommend going for the primary sources and looking up testimonials from cluster headache patients!
Yeah… I’m trying to beware surprising and suspicious convergence here. “Local psychedelics enthusiasts discover that psychedelics are the cure to the worst conditions known to humanity, more at 11.”
This is, in some sense, a cheap and kind of mean heuristic, but I wanted to flag the suspicion. I might go and read some testimonials, but nothing beats a good ol’ RCT [1] . I don’t want to be the person who’s like “you need more research before you advocate” and I’m looking forward to putting DMT-variants head-to-head in an experiment with known medical treatments for cluster headaches.
Actually not true, we could & should try to design successors to the RCT, but they’ll go in the direction of “Thompson-sample from the posterior distribution in some bandit setup” as opposed to “more anecdata”.
I don’t think there was an RCT for DMT vs triptans. It’d be great to have one but I don’t think anyone ran one. There are also legal barriers to running one (which are definitely possible to overcome, but still).
Testimonials and surveys of patients are the best thing we have currently.
On a similar note, I wonder if a more promising angle of attack is chemical research to find another compound that might be even more effective.
Given that sumatriptan and DMT are pretty similar, and the psychedelic effects of DMT are apparently not relevant, it’s plausible that there might be an even better molecule out there.
If that molecule did not have psychedelic effects, that would be ideal in terms of quick widespread adoption.
4-AcO-DMT and most other psychedelics also last on the order of 8 hours (or more), while inhaled / injected DMT lasts ~20 minutes.
Normally, ingested DMT has no pharmacological activity because monoamine oxidase (MAO) in the body will break it down before it has any effect. The likely reason is that DMT is endogenous.
Ayahuasca is an ingested DMT extract that also contains a natural MAO-inhibitor. (“Pharmahuasca” is an analogue of it that uses ingestion of purified DMT plus an MAO-inhibitor in pill form).
A sub-impairment dose of DMT sounds like the least invasive treatment for this in particular.