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

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[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.