A study of 53 patients who had used psilocybin or LSD found that “twenty-two of 26 psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin users and 7 of 8 LSD users reported cluster period termination; 18 of 19 psilocybin users and 4 of 5 LSD users reported remission period extension” (Sewell et al., 2006). Another online survey of 270 cluster headache sufferers revealed that 68% of respondents who used tryptamines had a 4 or 5 out of 5 relief, with 5 being “completely eliminated the cluster headaches” (Frerichs, 2019).
While these are very promising effect sizes, the methods are of low quality (e.g. high risk of bias). I would suggest a properly powered RCT before concluding that psychedelics are really that effective.
If you put all the existing evidence together – which is much more than just those two studies – even with the risks of bias, it really is overwhelming. See, for example, Fig. 2 in our policy paper, based on a paper by Schindler et al. https://www.preventsuffering.org/wp-content/uploads/2020/11/Legalising-Access-to-Psilocybin-for-Cluster-Headaches-Policy-Paper.pdf, and also some of the patient testimonials. The usual standards for determining the effectiveness of new medications are understandably more rigorous than for other kinds of situations, but in the case of cluster headaches, the huge number of patient reports claiming the efficacy of psychedelics (while other substances like cannabis are generally ineffective), including chronic cluster headaches that end after a few doses of psychedelics, essentially excludes the possibility that there is no causal relationship. And the extreme pain means that patients have the right to access them even if there were any doubts. We’re actually preparing a case series for submission, with a Zurich-based neurologist who can legally prescribe psychedelics, on the results obtained with her patients.
Thanks! It’d be great if someone (maybe myself, but ideally someone with more experience in the field) published a summary of the existing literature (more research here). Having spent so many hours reading up on the topic these past few months, I’m optimistic about the efficacy. I think funding and/or running a large scale RCT in particular for N,N-DMT (in a country where it is legal) would be a great use of EA money/time.
There’s a real need for large clinical trials. There have been a few on psilocybin and LSD as preventatives. The big obstacles are recruiting a sufficient number of patients and obtaining funding to study substances that aren’t directly patentable. Demonstrating the efficacy of DMT as an abortive compared to placebo could be done on very few patients and reach high statistical significance. Demonstrating greater efficacy than Sumatriptan—a standard abortive—would be more difficult, as the latter is also fast-acting and effective in the short term. Sumatriptan is widely believed among patients to cause rebound attacks and to lose effectiveness over time, so a proper comparative study would probably need to follow patients over a period of months. I don’t think that DMT would have to be legal (e.g. for personal use) to be studied as a controlled substance—just authorisation would be needed.
To what extent are the legal restrictions on psychedelics also obstacles to running trials with them in major pharmaceutical R&D countries like the US?
There was a small trial that was recently completed at Yale. The administrative hurdles are greater, including DEA approval in the US, but certainly not insurmountable. It might be easier in some other countries with more permissive laws and where psychedelics have already been legally prescribed, like Canada and Switzerland, but approval is still necessary.
While these are very promising effect sizes, the methods are of low quality (e.g. high risk of bias). I would suggest a properly powered RCT before concluding that psychedelics are really that effective.
If you put all the existing evidence together – which is much more than just those two studies – even with the risks of bias, it really is overwhelming. See, for example, Fig. 2 in our policy paper, based on a paper by Schindler et al. https://www.preventsuffering.org/wp-content/uploads/2020/11/Legalising-Access-to-Psilocybin-for-Cluster-Headaches-Policy-Paper.pdf, and also some of the patient testimonials. The usual standards for determining the effectiveness of new medications are understandably more rigorous than for other kinds of situations, but in the case of cluster headaches, the huge number of patient reports claiming the efficacy of psychedelics (while other substances like cannabis are generally ineffective), including chronic cluster headaches that end after a few doses of psychedelics, essentially excludes the possibility that there is no causal relationship. And the extreme pain means that patients have the right to access them even if there were any doubts. We’re actually preparing a case series for submission, with a Zurich-based neurologist who can legally prescribe psychedelics, on the results obtained with her patients.
Thanks! It’d be great if someone (maybe myself, but ideally someone with more experience in the field) published a summary of the existing literature (more research here). Having spent so many hours reading up on the topic these past few months, I’m optimistic about the efficacy. I think funding and/or running a large scale RCT in particular for N,N-DMT (in a country where it is legal) would be a great use of EA money/time.
There’s a real need for large clinical trials. There have been a few on psilocybin and LSD as preventatives. The big obstacles are recruiting a sufficient number of patients and obtaining funding to study substances that aren’t directly patentable. Demonstrating the efficacy of DMT as an abortive compared to placebo could be done on very few patients and reach high statistical significance. Demonstrating greater efficacy than Sumatriptan—a standard abortive—would be more difficult, as the latter is also fast-acting and effective in the short term. Sumatriptan is widely believed among patients to cause rebound attacks and to lose effectiveness over time, so a proper comparative study would probably need to follow patients over a period of months. I don’t think that DMT would have to be legal (e.g. for personal use) to be studied as a controlled substance—just authorisation would be needed.
To what extent are the legal restrictions on psychedelics also obstacles to running trials with them in major pharmaceutical R&D countries like the US?
There was a small trial that was recently completed at Yale. The administrative hurdles are greater, including DEA approval in the US, but certainly not insurmountable. It might be easier in some other countries with more permissive laws and where psychedelics have already been legally prescribed, like Canada and Switzerland, but approval is still necessary.