The buspirone challenge test clearly distinguishes ME/CFS patients from healthy controls: why is it not being developed and deployed?

[Peter T]

Still I think it’s just an idea from 100,000ft, no evidence to say reducing prolactin helps at all.

I still find it counter intuitive that we want to rush to a treatment, before understanding any underlying mechanisms. Though I won’t turn down a drug that helped, many drug trials feel like playing the lottery.

But this phenomenon is well worth investigating. Still, various possibilities. It would be a potentially useful starting point if we found that prolactin responses varied with severity of ME/CFS or were even associated with PEM.

 

[V.R.T.]

I still find it counter intuitive that we want to rush to a treatment, before understanding any underlying mechanisms. Though I won’t turn down a drug that helped, many drug trials feel like playing the lottery.

But this phenomenon is well worth investigating. Still, various possibilities. It would be a potentially useful starting point if we found that prolactin responses varied with severity of ME/CFS or were even associated with PEM.

I don't see how it's counter intuitive. I don't see any dichotomy between wanting good quality basic research to pinpoint the mechanism and also wanting treatment trials based on what we hypothesise might be wrong now.

Also if this antibody was approved (it isn't) and the buspirone stuff inc patients feeling worse was replicated in a larger study it would be a good therapeutic experiment. If more prolactin makes patients feel worse, does reducing levels make them feel better? If it did then we not only have a treatment option but we have a big clue to the mechinism of MECFS.

There are also hypotheses where we cannot currently sample or image the pathological cells/tissue currently so a theraputic experiment would be the only way to confirm a mechanism.

We are currently trying to make up for decades of neglect and get people in dire straits help as fast as feasibly possible. We don't want to rush and make mistakes, or blow all our funding on exploratory clinical trials, but a sense of haste is appropriate.

 

[SugarSquared]

Also if this antibody was approved (it isn't) and the buspirone stuff inc patients feeling worse was replicated in a larger study it would be a good therapeutic experiment. If more prolactin makes patients feel worse, does reducing levels make them feel better? If it did then we not only have a treatment option but we have a big clue to the mechinism of MECFS.

The thing that makes prolactin being the culprit less likely is that no studies found prolactin to be higher than controls at baseline.

There could be a question of if PEM is a state of elevated prolactin. I think that would have been found out by now, but I haven’t looked at the research to see if this has been investigated. As a personal anecdote, I do sometimes experience a mix of nausea and lightheaded when I overdo it and will feel carsick much more easily. So, there being some kind of connection would not be the most surprising to me given that patients also felt nausea after the buspirone administration. Still, I don’t think it’s that likely or at least the only thing going on in PEM.

 

[V.R.T.]

The thing that makes prolactin being the culprit less likely is that no studies found prolactin to be higher than controls at baseline.

There could be a question of if PEM is a state of elevated prolactin. I think that would have been found out by now, but I haven’t looked at the research to see if this has been investigated. As a personal anecdote, I do sometimes experience a mix of nausea and lightheaded when I overdo it and will feel carsick much more easily. So, there being some kind of connection would not be the most surprising to me given that patients also felt nausea after the buspirone administration. Still, I don’t think it’s that likely or at least the only thing going on in PEM.

No I agree I think it's unlikely to be that simple sadly. I was more talking in generalities. It might be worth a shot though.

 

[Axel]

I can’t remember was there any anecdotal experiences with the more common prolactin small molecule drug cabergoline?

Here the link to the discussion on dopamine modulators, interesting to this discussion (though there are no personal accounts regarding cabergoline) :

Thread 'Dopamine modifying agents'

Jun 5, 2026

I’ve been thinking and reading more about dopamine. Partially because of interest in PD but also now in relation to eccentric medium spiny neurons aka eccentric spiny projection neurons (which have both D1 and D2 receptors).

Dopamine receptors are subdivided into D1-like (D1, D5) and D2-like (D2, D3, D4) receptor subclasses

And from what I’ve read D1 generally excites the post-synaptic neuron while D2 generally dampens firing.

The most studied dopamine signaling pathway is the modulation of cyclic AMP production, with D1-like receptors activating cyclic AMP...

• hotblack
• dopamine
• Replies: 45
• Forum: Drug and supplement treatments

• 

 

[Sid]

Just an interesting mention of buspirone on Phoenix Rising:

I remember this post (and the discussion) because it seemed like one of the few credible findings in ME/CFS ever. Could never understand why no one else continued this line of research.

 

[SugarSquared]

Forgive me if someone already mentioned this, but has anyone looked into if there are hormonal shifts around the age of onset peaks (about 16 and 37) that McGrath et al. 2026 identified? If there’s some changes in estradiol or other sex hormones, it could be really interesting and perhaps lend credence to the sex hormone theory of elevated prolactin.

 

[ScoutB]

Btw, an interesting result from june, in case this hasn't already been posted here/the doc:

RNA sequencing identified seven differentially expressed genes at adjusted p < 0.05, including MIR205HG , FEZF1 , HLA-DMB , SLC1A2 , SYT13 , GALNT4 , and SLC2A14 . Pathway analysis identified 73 differentially expressed pathways, of which 96% were downregulated in ME/CFS MP cells.

Quotes forestglip highlighted on that thread:

MIR205HG is a non-long coding gene that regulates the prolactin expression, primarily through its modulatory effects on transcriptional and post-transcriptional signalling pathways [30]. [...]

Previous studies have reported heightened prolactin responses to serotonergic and dopaminergic challenge tests in ME/CFS patients, despite baseline prolactin levels being typically normal. [...]

It is possible that reduced MIR205HG expression diminishes its regulatory control over prolactin synthesis or release, contributing to the heightened sensitivity of the prolactin axis seen in ME/CFS.

 

[obeat]

I've sent the prolactin PDF and blog to a few people. A reply

Dear Olivia,

Thanks for getting in touch and sharing this evidence summary. Our original hypothesis was that the effect of oestrogen we see on long COVID and ME/CFS symptoms was mediated by the immune system, but you’re right there’s potentially an effect for the dopaminergic system. This would also fit in with some of the emerging evidence on the effects of oestrogen on ADHD.

As an immunologist, dopamine signalling isn’t my area of expertise. I have a colleague in endocrinology who works on prolactin, who I will be seeing in a couple of weeks’ time. I will share this with her and see if she has any thoughts on moving it forward.

Best wishes,

Viki

Associate Professor in Reproductive Immunology
Imperial College London

 

[Andy]

I've introduced the PDF and blog post to the members of PRIME, no obvious take up at the moment but it might lead somewhere.

 

[forestglip]

I really wanted the in-text reference numbers in my PDF to link to the bibliography for easy access. This led me to learn how to create a document using LaTeX software.

In the process, I also reworded significant portions, added a section related to gonadal disorder findings, and added an abstract and more complete introduction. I think it looks much more polished now.

I uploaded here, but also replaced the document at the GitHub link.

 

[Peter T]

A trivial point but when referring to figures and tables in the text shouldn’t the numbers be in the same font size and colour to the rest of the text, unlike the references’ numbers and footnotes?

 

[forestglip]

A trivial point but when referring to figures and tables in the text shouldn’t the numbers be in the same font size and colour to the rest of the text, unlike the references’ numbers and footnotes?

I'm not sure what common practice is, but I think the coloring helps indicate that the number is clickable to go straight to the table. I just checked a PDF from an article in a Nature journal, and they seem to also color the figure number blue.

 

[Utsikt]

Yeah, please colour anything you can interact with - that’s the universal sign for saying this is something to click on.

 

[Peter T]

I'm not sure what common practice is, but I think the coloring helps indicate that the number is clickable to go straight to the table. I just checked a PDF from an article in a Nature journal, and they seem to also color the figure number blue.

There weren’t hyperlinks back when I was involved in drafting articles, but then shouldn’t the words ‘figure’ or ‘table’ be included as well as the number as the link.

 

[Robert 1973]

Looks really good @forestglip

A couple of trivial points:

1. Under the title it says “forestglip*” but I can’t find where the other * is which presumably give more info. I’m reading in my phone so apologies if it’s obvious.

2. There is an indent at the beginning of the abstract paragraph which shouldn’t be there.

 

[forestglip]

There weren’t hyperlinks back when I was involved in drafting articles, but then shouldn’t the words ‘figure’ or ‘table’ be included as well as the number as the link.

Seems like MDPI is another journal where just the number is blue. So that seems to be how the pros do it.

1. Under the title it says “forestglip*” but I can’t find where the other * is which presumably give more info. I’m reading in my phone so apologies if it’s obvious.

It's at the bottom left of the first page. It just says "Independent researcher" and gives an email address just in case anyone wants to chat.

2. There is an indent at the beginning of the abstract paragraph which shouldn’t be there.

Ah yes, thank you, I'll get that sorted.

 

[ScoutB]

Seems like MDPI is another journal where just the number is blue. So that seems to be how the pros do it.

Yeah these sorts of things are stylistic choices and in some fields (and publishers) they'll have it one way or another. It's been a while, but from memory this is the kind of thing where you could have a command/macro along the lines of \fig{1} and depending on what publisher you're sending it to you pick the formatting of \fig{1} and it comes out their preferred way.

Anyway I think it looks fantastic.

 

[SugarSquared]

I really wanted the in-text reference numbers in my PDF to link to the bibliography for easy access. This led me to learn how to create a document using LaTeX software.

In the process, I also reworded significant portions, added a section related to gonadal disorder findings, and added an abstract and more complete introduction. I think it looks much more polished now.

I uploaded here, but also replaced the document at the GitHub link.

Gorgeous! It looks very professional and well-organized.

 

[forestglip]

Looks really good @forestglip

Anyway I think it looks fantastic.

Gorgeous! It looks very professional and well-organized.

Thank you! I really appreciate it.