The Holy Grail: Searching for a Cure for PSSD

Print Friendly, PDF & Email
June 21, 2022 | 47 Comments


  1. My PSSD has been particularly bad the last two months.

    Genital numbness, pleasure less orgasms, zero libido, emotional numbness, day in, day out.

    I have been feeling suicidal again, and to be honest, I don’t know how much longer I can endure this existence.

    I have suffered for almost 15 years now, and there is only so much more I can take.

    I feel left behind, and all my peers, and family; have moved on to have relationships, marriages, children, and normal lives.

    I have had nothing. I can’t even enjoy pleasuring myself.

    I have been left to rot, by the mental health team that so badly betrayed me, and actively worked so hard to deny what has happened to me.

    I am estranged from most of my family, and a big part of why, is because of PSSD.

    In fact the only family I talk to is my mother, who is now quite elderly.

    God knows how I am going to cope once she is gone, as she is the only person that really cares about me.

    I have few friends, and most of the friends I do have, are fellow PSSD sufferers; as they are the only ones, who really understand what it is like to live with this hell.

    I am struggling to see any light at the end of the tunnel.

    Please find a cure for PSSD, as I can promise you, it truelly is a form of hell on earth!

  2. PSSD from ashwagandha supplements.
    I experienced PSSD symptoms from ashwagandha a year ago and still have loss of libido and penile numbness.

    The brain fog and anhedonia symptoms went away with time and by fixing my gut by taking candibactin.

    The vagus nerve controls the gut brain axis and DNPR may help with this just like it helps with CFS.
    Please research more about the gut brain axis and how CFS and PSSD are related.
    FMT has also cured multiple people.

    • What was the reason behind taking Candibactin?

      All the improvements I got disappeared within days of diarrhea which hasn’t resolved after many months now.

      The problem with FMT is that most people I’ve read and talked to say only a temporary improvement happened after it which disappeared after a while.

  3. Dear Mr. Healy & Co.

    The emotional problems, cognitive problems (memory), vision problems, skin problems (dry skin), partial loss of smell, dry eyes, GI problems, altered tacktile and thermo sensation in body, altered autonomic function (blood pressure, skin temperature, loss of sweating) should be considered. In my opinnion it is very harmful that our condition with as wide spectrum of severe symptoms as they have in PFS and PAS is still named as PSSD (…Sexual dysfunction). We people are really sick in every aspect. For many the sexual symptoms are not the most severe ones. Some of us can’t feel even our heart pumping, lungs when breathing, or a thing when urinating or defecating. Our nervous system is destroyed and we have also pains. We are living in a hell where it is not possible to even cry properly, no matter how hard you try. We should also remember that altered neurosteroids are linked to autism-like behaviour and flat feelings, anhedony and severe depression as well as many severe neurological conditions.

    IS the theory of Small fiber neuropathy and autonomic dysfunction totally ruled out?

    You are the biggest hope to us who rapidly lost everything to SSRI:s…

    • The SFN and autonomic dysfunction are not ruled out. They are very much alive. But we have to find which protein or enzyme within small fibres has been knocked out.

      The reason to focus on sex and numb genitals is that this offers us a very clear target – explain this and we likely have the answer to everything else. Having some people look at eyes, some at hearts and some guts is a recipe for diluting our efforts.


      • Yes this is right and totally agree! As so many PSSD sufferer have clearly autonomic dysfunction / at least problems with it, so do we know if it is progressive and are these people in danger getting worse? Do we have cases of death due to autonomic dysfunction caused by SSRI?

        I am sure Dr. Guerrini’s findings are extremely valuable for the future. This new research could be way to many new findings on medicine.

      • This really did demand reading and re-reading. Thank you.

        The Holy Grail: Searching For A Cure for PSSD certainly did inspire hope.
        ‘- explain this and we likely have the answer to everything else’.
        The ‘everything else’ is vast in terms of the enduring and evolving SSRI/SNRI/Atypical-ADs and other psychotropic drug injuries which affect so many different tissues, physiological functions, (hypothalamic functions??) and multiple organs. All of these in addition to PSSD and PGAD, endured by so many who comment here.
        I have been distressed to watch a multiplicity of atypical symptom-complexes arise in our loved one over the last 9 years free of all medication. There is destruction of thermo-regulation (heat intolerance). Multi-site deep bone pain, limiting exercise. Low back/sacral pain limiting pronged sitting. Destruction of normal patterns of micturition. Destruction of Sleep/Wake Cycle. There have been thyroid changes. Atypical chest pain. Extreme vulnerability to atopic reactions – topical eczema – resulting from ‘gentle’ cosmetics and deodorants.
        All of this adversity has been endured with a resilience which has been inspirational, yet heart breaking.
        There are other symptoms, and none are likely to be understood by a primary care physician. A ‘diagnosis’ of functional neurological disorder and/or inappropriate presumption of ‘Underlying/Emerging/Revealed M. H. Disorder’ remains a constant threat; even an enduring terror. This alone is a lifelong disability in a person whose iatrogenic disability will never be acknowledged or compensated. Tragic. The cavalier and injudicious, enforced use of such widely toxic psychiatric drugs surely merits questioning from within my profession: But, like the decades of AKATHISIA DENIAL, few are prepared to question the status quo. Meanwhile, priceless years of youth, attractiveness and reproductive opportunity have passed by in lonely, enduring isolation and medical/societal rejection. Even more tragic? This takes a toll on the entire family, in addition to the injured loved-one.

        A recent television program identified the courage of a medical whistleblower.
        His words (as I recall them) were immensely moving:
        ‘I was appointed to care for my patients, not for my colleagues’. The context implied was apparently referring to alleged cover-up.

        How much longer can these cascades of life-destroying ADRs to psychotropic drugs be denied, ignored or covered up?

        When we are able (via RxISK) to explain everything, how might we then achieve prescriber awareness, prescriber understanding, and realise our need to end the rejection of such suffering?

        • Tim, this is for you –

          This was the ‘Keynote Lecture’ as given at the International Congress of the Royal College of Psychiatrists, Monday 20 June 2022:

          As far as I can see, this summary slide, from the keynote lecture of the RCPsych International Congress 2022, fails to mention AKATHISIA: a widely recognised potential consequence of all psychiatric drugs [particularly when starting , reducing, or changing dose].

          Yet another opportunity to “improve safety” seems to have passed by.

          Who is wagging the dogs tail?

          On Monday of this week [20 June 2022] I peacefully protested outside the 2022 International Congress of the Royal College of Psychiatrists:

          Peter has put together a few thoughts on his visit to Edinburgh, his posts can be found after each composition.

          I hope you will have a good pour over them, as I did.

          • Thank you Annie,
            ‘Yet another opportunity to “improve safety” seems to have passed by’.
            Surely two fundamental tenets of ethical medical practice are:
            The prevention of harm.
            Ensuring that patients are told the truth.
            It would appear that both of these principles have been compromised by some 40 years of AKATHISIA DENIAL. It must be hoped that the AKATHISIA AWARENESS advertisements placed on the London Underground in April may have afforded the opportunity for some families to recognise this common and devastating ADR. They may have been enabled to recognise what was happening to their loved ones and prevent the suffering described above.
            Surely, the denial of akathisia, and the apparent prevention of prescriber awareness and understanding, demands formal investigation and urgent remediation.
            Continued akathisia denial would appear analogous to allowing prescribers to believe that penicillin cannot cause anaphylaxis.

      • How close are we to figuring this out ? I think it may be some sort of autoimmune condition that the medications triggered. I developed an autoimmune condition right after getting PSSD and lots of people who have one autoimmune condition have another . Please let me know if there is any chance at any leads towards solving this. I already have one suicide attempt and the one person who speaks to me and understands is my mother . I’m seriously dying here

  4. Rxisk says ‘Those of you who are affected are the greatest research resource any researchers could have.’ This could be a chance of enlightning readers of thebmj by making more responses. No need for any kind of ;professional ;qualifications to make a response by the way.

    Re above ‘Research’ Donations are made to Centre for Data Based Medicine, a registered charity in England and Wales. (See link in article )where J K Aronson works
    His response says:-
    Re: A system reset for the campaign against too much medicine Kamran Abbasi. 377:doi 10.1136/bmj.o1466
    Dear Editor

    The Editor of the BMJ is justified in calling for more scrutiny of harms [1], as did one of his predecessors: “Think harms always” [2]. The term “practices of no net benefit” has been suggested [3], stressing the need to consider the balance of benefits and harms, not merely one or the other [4].

    However, there is ambiguity in the term “Too much medicine”. “Medicine” means “the science or practice of the diagnosis, treatment, and prevention of disease” (Oxford English Dictionary). However, in that sense the word is sometimes used to differentiate medicine and surgery. And “medicine” can also mean a medicinal product, a drug. In that case, the implication is that the harm from “too much medicine” is an adverse drug reaction, whereas all forms of medical practice are potentially harmful as well as potentially beneficial.
    In fact, we could be said to have too much of [almost] everything:

    Too many diagnostic tests (if used inappropriately)
    Too much technology (enabling too many tests)
    Too many guidelines (if used inappropriately)
    Too many “diseases” (inappropriate labels)
    Too many biomarkers (incomplete understanding of how to use them)
    Too much monitoring (if used inappropriately)
    Too much therapy (if used inappropriately)
    Too much cost (too little money)
    Too much enthusiastic hype (too little reproducibility)
    Too much poor science (overreliance on observational studies, poor quality RCTs)
    Too much licensing of medicinal products (too speedy licensing, too slow withdrawal, when indicated)

    Competing interests: JKA has taught, lectured, and written articles about overdiagnosis and adverse reactions to drugs and devices, and has edited textbooks on adverse drug reactions.

    21 June 2022
    Jeffrey K Aronson
    Consultant Physician and Clinical Pharmacologist
    Centre for Evidence Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford
    Nuffield Dept of Primary Care Health Sciences, The Radcliffe Observatory Quarter Woodstock Road

    Respond to this article
    Read all responses to this articleRe: A system reset for the campaign against too much medicine Kamran Abbasi. 377:doi 10.1136/bmj.o1466

  5. When I read how peoples lives have been impacted by these medicines, it makes me want to scream at the top of my lungs.
    You are all worthy of life, irrespective of how/what/why/when!
    Blood rushes to my head when I acknowledge and fully appreciate that:
    1. Some people don’t give a damn about your circumstances
    2. The system and some professionals don’t care
    3. Some family members are judgmental and make a mockery of you
    4. You feel all alone
    5. Some people lie to ruin you. Stay away from people who do not genuinely/sincerely care about you
    If I had my way, I would make those who do harm, pay for all the damages and more…………!
    Changing the mindset is the biggest hurdle.
    Forgiving is part of the process however, forgetting is the hardest part.
    Try to find ‘the spark within’ that makes you happy.
    Anything that puts a spring in your step.

  6. As campaigners know this drug is not only used for epilepsy, She is a regular writer in thebmj so should have known this and used the opportunity to alert those who take others including antipsycholtics.
    It cannot be the only drug which will ‘potentially’ effect future generations. It’s still being prescribed to women …..
    Valproate: UK regulator looks into possible transgenerational effects
    BMJ 2022; 377 doi: (Published 22 June 2022)
    Cite this as: BMJ 2022;377:o1531

    The UK’s medicines regulator is examining animal data that show that the epilepsy drug sodium valproate could trigger genetic changes that are passed on to future generations.

    The Medicines and Healthcare Products Regulatory Agency (MHRA) said that as part of its ongoing review of the safety of sodium valproate it has sought independent advice from the Commission on Human Medicines about animal data that show changes to the testes in juvenile male animals and transgenerational effects in mice.

    In April new figures showed that valproate was still being prescribed to women of childbearing age.1

    • Because the Prize Fund is still acting as a stimulus to get people to do things.
      There have been many proposals – all interesting but none that seem likely to be right.

      A number of people though have come up with really good ideas, leading to our interest to fund these to make them happen. Hence the new Research Fund.


      • The prize money has stopped growing for quite some time. If rxisk decided to change direction by transferring the prize money towards the new research fund in order to speed up the process, could it physically be accomplished?
        Raising money in this pssd community will take a very long time to reach $50,000.

        • I guess that the total will not have to be reached before the researchers begin to be supported by the Fund? It’s up to all of us to get cracking and make this work.

    • Will, may I share with you the way that I see things. As so many others did also, I worked really hard to raise funds for the Prize Fund and to share the reason it was needed. Not only is it to be given for a cure for PSSD but, and this is where my interest lies, IT COULD PROVIDE ANSWERS FOR MANY OTHER REASONS FOR THE SUFFERING connected to these prescribed drugs. THAT is the Prize’s purpose and. as such, MUST remain there, awaiting a cure to be found.
      The Research Fund, I perceive as being “a means to an end”, a support for those who feel that they’re really onto something extremely exciting and worthy of further investigation. Research is expensive. People cannot afford to do it for free. Hence the Fund – to provide a little support to ensure that the progressive work now established does not go to waste simply because of a lack of funds.
      Those of us who supported the Prize Fund should now be wholeheartedly behind this new Fund to ensure progress is possible. The “Prize”, when eventually handed out , would not disappear into anyone’s personal pocket – it would be used to further the work already accomplished.
      We need both trust and hope here. Trust in the knowledge that our monies in the Prize Fund are safe for its purpose and Hope that the support we provide through the Research Fund bears fruit as quickly as is absolutely possible. Many out there are crying out for an answer to this, and many other, problems.

  7. This is a fantastic post. I love how it keeps an open mind. That’s what research is all about.

    The questions about weather the physiological drive the psychological or the other way around, so to speak, are interesting. I’m not sure the two are even different. Chemicals affect how we perceive things, i.e. our psychology, but the mind also affects the body.

    On that note, I’ve had some success with meditation. It’s somewhat like the mind has forgotten to focus on certain things, but that it can, to some limited extent anyway, be taught to refocus.

    • I believe the prize money is not an incentive to find a cure. As you mentioned, “Research is expensive and people cannot do it for free”. To find a cure will cost way more money that what the prize fund has raised over a 10 year period? Where is the incentive for new researchers to look into pssd ?

      The prize Money which is already in our possession could be working for us to find a cure. I strongly believe the prize funds will continue to sit there for years to come.

      I would love to be given the opportunity to transfer my prize funds over to new research fund.

      (1) THAT is the Prize’s purpose and. as such, MUST remain there, awaiting a cure to be found.
      (2) Research is expensive. People cannot afford to do it for free. Hence the Fund – to provide a little support to ensure that the progressive work now established does not go to waste

  8. With all honesty, the research should be done before these medicines go out on the market.
    What is the point in investing in something, that does not promise/yield results?
    They have research for this; research for that however, they never really come up with substantial cures that eradicate health issues that some medicines/vaccines induce.
    If this was the case, no one would be in research if they came up with cures.
    I believe many of these medicines/vaccines induce health issues immediately or with time.
    Before a medicine goes out on the market, it should go through vigorous research upon research so that people do not get harmed or death results.
    The prize money should go to anyone who can make changes in the Laws regarding these medicines/vaccines.
    All the negative clinical data trials should be out there for all to see before a pen is put to the script.
    Perhaps, one day this will be reality.

  9. Some of us donated to the RxISK Prize fund under the assumption that it was a publicity stunt to gain more attention for PFS, PSSD, and PAS/PRS, and with the understanding that it would eventually be disbursed “to support the most innovative research proposal or donate it to the PFS Foundation who are already undertaking some elegant research.”

    The “most innovative/elegant research proposal” is debatable. The fact that the above statement quoted was published by RxISK in regards to the RxISK Prize is not.

    It’s been around 5 years since the RxISK Prize was launched and it would be great if RxISK/DBM could refund contributors or offer to dispense donations, by proxy, to university-level research the donors are supportive of as a show of good faith.

  10. My pleasure senses and cognitive symptoms was recovering. My mind was sharp again. My blank mindedness was reversed to normal. Music was like usual again. My skin numbness was also gone in some parts of body.

    Then had re-activation of stomach pain which caused me diarrhea for 3 weeks.

    For the first 3 days of the diarrhea I was dizzy and my vision got cloudy. Then the feeling of pleasure was replaced with a tingling sense in the back of my brain. Now for the past months I’ve lost all the improvements I had gained.

    I believe diarrhea somehow has reversed improvements but I’m not sure what to do to reverse what diarrhea has done. I’ve done all things I was doing right before my improvements with no help.

  11. Dear Mr. Healy & Co.

    Has a link between the immune system and PFS/PSSD/PSI ever been considered ?I have an hypothesis to propose to you, I detail my reasoning below (while having some knowledge in biology, I have no expertise in the field so I ask my readers to be indulgent) :


    First of all, many medication may elicit an immune response : streptomycin, aspirin, the sulfonamides, some anesthetics (e.g., succinyl choline), and some opiates … A known case study is penicillin which react to protein to create a penicilloyl-protein which behaves as a hapten-carrier conjugate eliciting an allergic reaction (mediated by IgE). In some patients, such drug-protein complexes induce formation of antibodies (mediated IgG, IgM), which then bind to the adsorbed drug on red blood cells, inducing complementmediated lysis and thus progressive anemia. Other drugs like hydralazine can also cause a syndrom, drug-induced lupus, which include clinical features of systemic lupus erythematosus . None of the processes above would explain all of the symptoms in people with PFS/PSSD/PIS, as the symptoms usually improve once the drug is withdrawn. I just wanted to emphasize that a link between the immune system and drugs is not necessarely far fetched.


    It wouldn’t be impossible that the root cause of PSSD could be the immune system targeting a auto-antigen leading to the symptom set of PFS/PSSD/PIS. This is the case in some forms of Addison’s disease in which an enzyme is recognized as non-self. This has been proved in a “breakthrough” study which was the first to prove a link between some form of the Addison disease and a specific auto-antigen : 21-Hydroxylase, a major autoantigen in idiopathic Addison’s disease ( doi : 10.1016/0140-6736(92)91829-w ). The auto-antigen is a steroidogenic enzyme, 21-hydroxylase, which is needed to catalyze a set of reactions necessary for our body to supply us with two major hormones : aldosterone and cortisol. Lack of those hormones leads to a set of symptoms which caracterize the Addison disease : psychiatric symptoms (anxiety, depression …), sexual dysfunction (decreased libido), skin changes (darkening skin), adrenal crisis (which is life threatening). As everyone can see a “small” cause (enzyme being targeted by the immune system) can lead to a very wide range of symptoms (from psychiatric to sexual dysfunction). Other auto-immune diseases, such as the graves disease, involving receptors as an auto-antigen may induce debilitating symptoms (including decreased sexual drive) : anti-TSH receptor induce an overproduction of thyroid hormones. What is striking is that such auto-immune diseases are sometimes conflated with depression or anxiety because of the overlap with symptoms of depression. Why would PSSD/PFS/PIS not stem from an auto-antigen being targeted by our immune system ?


    A cohort study, comparing the cerebrospinal fluid ( concentration of a set of neurosteroid among healthy volunteer with those having PFS, yielded some significant results. In fact despite the small cohorts size the differences were statistically significant for a wide range of neurosteroid. Whether this low level of neurosteroid explain the set of symptoms among PFS/PSSD/PIS patients or not cannot be concluded, but it seems like an interesting lead : what is the cause of such a low level of neurosteroid ? Assuming PSSD/PFS/PIS has an auto-immune explanation we can rephrase the question : What auto-antigen, if targeted by our immune system, can induce such an abnormal profile of neurosteroid that has been observed among PFS patient ? A process similar to that which occurs in Addison’s disease (auto-antigen is a a steroidogenic enzyme), but of course with a different auto-antigen, could be an explanation. it would be interesting to have an enlightened opinion.


    The advantage of such a hypothesis is that it can be “easily” confirmed or invalidated. The protocol is almost the same as the one described in the Addison disease paper above. We perform a western blot analysis among PFS or PSSD or PIS patients : 1) we separate auto-antigen from a mixture of potential auto-antigen, using an electrophoresis, according to their masses 2) we probe each antigen with some PFS/PSSD/PIS sera (containing potential auto-antibodies) 3) by using radiolabeled or enzyme-linked anti-antibody we assess whether auto-antibodies have latched on a potential auto-antigen. We perform the same western blot analysis among a cohort of healthy patients. And we compare both cohorts. I have briefly described the different stages of such a protocol so that everyone can see that it does not require a lot of equipment or funds : it uses a well-known and widespread technique (western blot), in case of postive result it would provide an easy diagnostic tool.


    Of course, a possible autoimmune cause is very speculative. Several symptoms of PFS/PSSD/PIS do not seem to match the usual symptoms of autoimmune diseases:
    – Usually auto immune disease vary between remission phase and acute phase which does not seem the case with people with PFS/PSSD/PIS .
    – inflammation are also pretty common with auto immune disease. I have not heard anyone reporting such symptoms having PFS/PSSD/PIS.
    Although it seems unlikely that such an assumption will turn out to be true, there is a small chance that it will.


    • Johann

      This is a good idea and the kind of thinking that is needed. Luisa Guerrini’s work heads in this direction in two ways. One is that any genetic effect like generating antibodies goes through a set of proteins like p53, p63, p73 so what is being proposed comes close to what you are thinking.

      Second, it looks like the action of thalidomide and SSRIs on these proteins destabilizes what is called the ACE-2 receptor and this blocks the entry of Covid into cells – one of the things Covid appears to do is to produce antibodies to ACE-2 receptors which as I understand them would count as auto-antigens. Again this seems in the same ballpark.

      I doubt if its a frank auto-immune disease though because we have had tardive dyskinesia for 60 years and PSSD for 30 years and I’d imagine someone would have stumbled over a link by now – perhaps finding someone showing huge improvement after a course of plasmapheresis. But that requires people to be curious and alert. If there is an auto-immune component you’d expect inflammatory markers to be raised and there is some evidence for this and changes in steroids in depression but these seem to happen in everyone not just in those with PSSD.

      I have thought along the lines you outline and agree this would be worth doing – or at least checking out with someone who can advise us properly.


  12. Hello Susanne,
    Medicine has turned into a conundrum, filled with so much ambiguity and uncertainty.
    There are simple solutions out there to many diseases however, many are not inclined to think outside the box.
    I love the way you compartmentalize systems/processes and say it the way it is.
    Susanne eloquently stated:

    Too many diagnostic tests (if used inappropriately)
    Too much technology (enabling too many tests)
    Too many guidelines (if used inappropriately)
    Too many “diseases” (inappropriate labels)
    Too many biomarkers (incomplete understanding of how to use them)
    Too much monitoring (if used inappropriately)
    Too much therapy (if used inappropriately)
    Too much cost (too little money)
    Too much enthusiastic hype (too little reproducibility)
    Too much poor science (overreliance on observational studies, poor quality RCTs)
    Too much licensing of medicinal products (too speedy licensing, too slow withdrawal, when indicated)
    Please allow me to add another one to the list:
    – Too much balderdash

    My theory and experience tell me, that given time, some issues and damages incurred by medicines, will resolve themselves. You have to work hard at researching what benefits you. Hopefully, the damages done to nerves, myelin sheath, the barometer in the brain and multiple body systems will repair themselves eventually without drastic drug/medical interventions. It’s about trying to STOP the war (inflammation) within the body. Trying to undo what medicines have induced is a very tricky situation but I know it can be done. Nothing is impossible! Listening to many naysayers and not having any HOPE for the future is very detrimental to one’s faith. This is why I have chosen a path less travelled. It makes the journey worthwhile : )

  13. Hello David,

    I am intrigued by what you have written:
    – generating antibodies goes through a set of proteins like p53, p63, p7
    – Second, it looks like the action of thalidomide and SSRIs on these proteins destabilizes what is called the ACE-2 receptor and this blocks the entry of Covid into cells – one of the things Covid appears to do is to produce antibodies to ACE-2 receptors which as I understand them would count as auto-antigens.
    Please expand our knowledge. It is all science in a ‘petri dish’ for me.
    Can you please elaborate.
    As for you Johann, are you a scientist?
    Sounds, very impressive.
    I’m no expert in the field. A suggestion I could put forward is also finding a cure that re-generates nerve damage.
    Keeping inflammation at bay within the body is also something that would be beneficial. When the body attacks itself there has to be a remedy that puts this to a halt. Lot of drugs out on the market tend to do this however, long term disadvantages is that they then go to weaken the immune system or burden other organs.
    Input would be kindly appreciated.

    • Hello dr Healy

      We have someone from Germany who showed significant improvement with immunotheresis and have another member heading to Germany for 2 sessions in februrary.

      I will keep you updated.

      Kind regards

  14. Liu’s study
    Molecular and neural basis of pleasant touch sensation
    they genetically modified mice by removing the function of PROK2 neuropeptides and saw that the mice lost the response to pleasant touch (but not to pain/itchiness). PROK2 neuropeptides through the spinal cord send the pleasurable (not specifically “sexual”) sensation from the skin to the brain.

    Heim’s study
    Sensory-Tactile Functional Mapping and Use-Associated Structural Variation of the Human Female Genital Representation Field
    using fMRI imaging and a particular method of clitoral stimulation (puffs of air not such as to arouse sexual arousal) they located the “representation” of the clitoris in the human female brain.

    Georgiadis’s study
    A psychophysical and neuroimaging analysis of genital hedonic sensation in men
    Using neuroimaging, they identified which brain areas in the male brain are activated by the touch of penile skin (vs. forearm) focusing on the pleasant (not strictly sexual) sensation of participants.

    pleasurable vs. sexual and rats vs. human

    after locating the representation of the clitoris in the human brain and the specifically genital pleasurable touch of the penis in the human brain, if tactile stimulation is added that elicits an initial strictly sexual response, one would observe what more “turns on” (do the same districts intensify their activity, or will other districts predominate?), but a complexity of systems would be activated and one would lose sight of the skin as the source.

    of specifically “sexual” in the genital skin there may be corpuscles that have not yet been well studied. however, hypoesthesia in PSSD involves sensation to light touch, sometimes not only at the genital level but of the skin of other parts of the body. it may also be useful to take into account whether in some genital anesthesia by ssri sensations of itching and pain are also lost.

    since I don’t know about neuropeptides and proteins I don’t know if reversibly inhibiting their action (perhaps locally) on a human being with an inhibitor would mean impairing that human being. if it were harmless one could repeat the brain scan studies after deactivating PROK2 or the proteins and hear what the volunteers have to say and see the differences with previous scans.

    complications in locating the pleasurable penile/clitoral touch in the rats’ brains (when they talk, they don’t make themselves understood well).
    in this way we cannot then see whether ablating PROK2 or some protein would keep such brain areas inactive during light touch.
    on the other hand, observing the mating behaviors of rats we would not understand whether their eventual compromission is really due to altered transmission from skin to brain or other systems.

    one can observe whether rats subjected to ssri have an altered reaction to pleasurable touch and then check whether there is an altered presence of PROK2 or some protein. if so, this would not speak to the mechanism that makes symptoms persist but would be an important clue to possible treatments.

    however, I’m not sure how true it is that ssri’s cause almost all people to experience some degree of skin/genital numbness from the first intake (the fact that they help with premature ejaculation is not evidence that the skin has become less sensitive). making it an evidence with a comparative study (before ssri/with ssri) would be relevant and not very complicated and even the media would then say “antidepressants make your genitals numb.”

    I would add a personal observation that could have several interpretations and not necessarily have anything to do with skin function.
    during the months of citalopram, in addition to no longer having genital erogenous sensations (without despairing about it and thinking “if I don’t want to touch myself anymore what’s the problem?”) perhaps it is true that the light touch of the skin on the body had less power, no longer aroused that emotion, thrill, but as if the skin was already satisfed and no longer needed it. it may also have been a consequence of a different psychological state of me.

    there are women who after so many years on the contraceptive pill say things like “I’m off the pill, my libido is back and I’m feeling alive again, I feel every sensation, every touch again, I had forgotten.” several years ago on a women’s forum I used to read the heated complaints of a woman who after the contraceptive pill had never recovered her sexuality (from multi-orgasmic, to anorgasmic on the pill to only one difficult orgasm after discontinuation). there is also a paper that talks about this possible not full reversibility: .2005.00198.x

    • This is very interesting. I have long wondered whether being on the contraceptive pill and then switching straight over to sertraline (both were given for PMS) contributed to me getting PSSD. I guess that contraceptive-induced sexual dysfunction is yet another thing we aren’t warned about

  15. Both paroxetine and finasteride act on the epinephrine enzyme PNMT, newly identified by Melcangi’s team. Epinephrine may have something to do with ongoing (persistent who knows?) erectile dysfunction.

    – Finasteride inhibits epinephrine synthesis in humans: implication for sexual dysfunction

    – Identification of a novel off-target of paroxetine: possible role in sexual dysfunction induced by this SSRI antidepressant drug

    Professors Guerrini and Melcangi both from Milan could collaborate to hunt for enzymes and proteins perhaps with the screening method used in these studies.

  16. Dear Dr Healy

    I have seen your name on various articles and papers when I’ve been looking for answer to my self-diagnosis of PRSD/PAS. The reason it is self-diagnosed is because in the UK, the prescribing dermatologists refute wholeheartedly that sexual dysfunction can be caused by that poison. Primary care/doctors are not diagnosticians, they clueless really, therefore the road to recovery is a dead end.

    The overlap between PFS/PSSD/PRSD is alarming yet only PFS is a syndrome recognised in the medical community. I did read a post about the potential of gene editing using CRISPR. One of the theories which seems to be consistent is that Accuate is likely to have altered the expression of specific genes, resulting in a persistent downregulation after stopping the medication.

    Please, visit this site. The creator is deeply impassioned and seems to have dedicated huge amounts of time to research. Does this sound plausible?

    All I can attest to is how Isotretinoin has ruined my life and the thousands I have spent trying to regain what has been stolen from me. When a woman complains of sexual dysfunction the only root cause given credence is a psychiatric one. Nothing more. A quick prescription of SSRIs is offered and some counselling. The problem isn’t just the ignorance displayed by specialists – to the level of gross neglience – but there is a gender inequality at play as well. We are all suffering the same storm, there is no cure, but there isn’t one protocol for women. Men have a few different treatment options – obviously which doesn’t do a thing – but women?? Well, she might be stressed, or emotional or whatever the excuse IS that’s used to dismiss women – it only serves to perpetuate the very real truth: a woman’s fundamental human right to enjoy sex doesn’t even rank high enough to warrant a raised eyebrow, much less funding.

    Please find a cure.

  17. – Established a comprehensive mice model of persistent genital arousal disorder and investigated the mechanism of VEGF-ERK signal pathing in vaginal microvascular injury
    These researchers believe they have obtained a valid model of PGAD on rats.
    “Microvascular injury can significantly appeared in the model, and the VEGF-ERK signaling pathway is a possible mechanism involved”

    Maybe this VEGF (Vascular endothelial growth factor, a signalling protein that promotes the growth of new blood vessels) is one of those things that would have something to do with anything

    – is expressed and released by endothelial cells (the tissue that lines the inner surface of blood vessels)
    – treatment target in cases of erectile dysfunction with vascular causes
    – potential target for therapeutic intervention in depression
    – overexpression of VEGF has been associated with tumor progression
    – critical player in the neurovascular stem cell niche of the hippocampus
    – SSRIs and SNRIs increase VEGF expression in the hippocampus
    – Finasteride inhibits angiogenesis and expression of VEGF in human
    – Retinoids are potent inhibitors of VEGF/VPF production by normal human Keratinocytes
    – Talidomide is a potent inhibitor of angiogenesis due to direct inhibitory action on VEGF secretion
    – the two major isoforms of the p63 gene exert opposite effects on the VEGF gene expression

    – Off-Target Effects of Antidepressants on Vascular Function and Structure. 2022

    – Impairment of the Retinal Endothelial Cell Barrier Induced by Long-Term Treatment with VEGF-A165 No Longer Depends on the Growth Factor’s Presence. 2022
    This seems to be a process to get to the bottom of what causes the persistence of an iatrogenic effect to the point of targeting a specific protein.

    in cases of stable pssd without the so-called windows of improvement, with erectile dysfunction and the sensation of blood not reaching the genitals as it should despite libido (and this could be why erogenous sensation does not come and genital arousal is not felt) I would not rule out microvasculature damage either, alongside possible small fiber neuropathy with perhaps fibrotic tissue formation, which has been highlighted as a likely cause of persistent ED in PSSD:

    I found from surveys that almost no one who has pssd has had classical neurological exams such as electromyography or evoked potentials (to name a couple), perhaps because “in pssd they are not revealing”, perhaps because they have seen others who have done them unnecessarily… this kind of thinking may keep some people away from relevant findings about their case.

  18. A line from the insensitive nipples in the PSSD

    The sensory innervation of the human nipple (2020)
    – Merkel cells, specialized cells in the skin that are important for proper neural encoding of light touch stimuli
    – PIEZO2, mechanosensitive ion channel

    Glans clitoris innervation: PIEZO2 and sexual mechanosensitivity (2021)
    – PIEZO2 is also present in Merkel discs and isolated Merkel cells
    – PIEZO2 participates in erotic and sexual mechanical sensing

    Effects on tactile transmission by serotonin transporter inhibitors at Merkel discs of mouse whisker hair follicles (W Chang, 2020)
    – a Merkel disc is a main type of tactile end organ located in touch sensitive spots throughout the body but most abundant at the human fingertips and whisker hair follicles of all non-primate mammals
    – serotonin transporters play a role in regulating tactile transmission at Merkel discs
    – serotonin depletion from Merkel cells since methamphetamine can facilitate serotonin release and inhibit serotonin reuptake.
    – serotonin in Merkel cells is released by methamphetamine initially and serotonin in Merkel cells is likely to be depleted following the prolonged methamphetamine treatment.
    – the static phase relies on Merkel cells and the dynamic phase is due to a direct mechanotransduction at Ab-afferent terminals.

    Piezo2 is required for Merkel-cell mechanotransduction (2014)

    Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors (2014)

    Merkel disc is a serotonergic synapse in the epidermis for transmitting tactile signals in mammals (W Chang, 2016)

    Role of microtubules in Piezo2 mechanotransduction of mouse Merkel cells (W Chang, 2020)

    Cellular and Ion Channel Mechanisms Underlying the Sense of Light Touch in Mammal (ongoing)
    they want to understand how chemotherapy causes loss of tactile sensation and how it deals with PIEZO2 and serotonergic transmission, with also the prospect of treatments for hypoesthesia of the skin.

    [No notable search results for finasteride/isotretinoin + PIEZO2 /Merkel cells]

    Identification of touch neurons underlying dopaminergic pleasurable touch and sexual receptivity (2021)
    – Mas-related G protein-coupled receptor B4 (MrgprB4): rare subpopulation of unmyelinated, nonpeptidergic sensory fibers that exclusively innervate hairy skin.
    – Transdermal optogenetic activation of Mrgprb4-lineage neurons in the skin surrounding female genitalia is sufficient to induce dopamine release in the NAc (nucleus accumbens), representing the first demonstration of molecularly defined somatosensory neurons triggering activation of a brain reward center. Moreover, Mrgprb4-lineage neurons are required for this same dopamine release during male mounts.
    – Mrgprb4-lineage neurons are the first neurons of a skin-to-brain circuit encoding the rewarding quality of social touch.

    [however the genitals and nipples are not hairy skin..]

  19. On p53:

    p53/p63/p73 in the epidermis in health and disease (2014)
    – Although p53 has long been known as the “guardian of the genome” with a role in tumor suppression in many tissues, the discovery of two p53 ancestral genes, p63 and p73, more than a decade ago has triggered a considerable amount of research into the role of these genes in skin development and diseases. In this review, we primarily focus on mechanisms of action of p53 and p63, which are the best-studied p53 family members in the skin. The existence of multiple isoforms and their roles as transcriptional activators and repressors are key to their function in multiple biological processes including the control of skin morphogenesis, regeneration, tumorigenesis, and response to chemotherapy. Last, we provide directions for further research on this family of genes in skin biology and pathology.

    Proteins from the DNA Damage Response: Regulation, Dysfunction, and Anticancer Strategies (2021)
    – The genome is constantly harmed by spontaneous damage caused by endogenous factors produced by normal cellular physiological conditions such as bases alteration, aberrant DNA enzyme function or oxidation, and by a large variety of exogenous genotoxic factors [1]. Cells have evolved a complex network of hundreds of proteins, named the DNA damage response (DDR), to ensure genome integrity and the expression of dedicated proteins to each cell type.
    – in the last decade as part of anti-cancer therapy have been designed inhibitors of proteins that play a role as DDRs: DNA damage response inhibitors
    – among these proteins, P53 plays a central role in managing cell proliferation, inducing cells with damaged DNA to apoptosis (death) and autophagy (eating parts of itself)

    The Role of the p53 Protein in Stem-Cell Biology and Epigenetic Regulation (2016)
    – The p53 protein plays a passive and an active role in stem cells. The transcriptional activities of p53 for cell-cycle arrest and DNA repair are largely turned off in stem cells, but there is some indication that long-term stem-cell viabilitymay require other p53-regulated functions. When p53 is activated in stem cells, it stops cell division and promotes the commitment to a differentiation pathway and the formation of progenitor cells. In the absence of any p53 activity, stem-cell replication continues and mistakes in the normal epigenetic pathway occur at a higher probability. In the presence of a functionally active p53 protein, epigenetic stability is enforced and stem-cell replication is regulated by commitment to differentiation.

    p53: key conductor of all anti-acne therapies (2017)
    – This review based on translational research predicts that the transcription factor p53 is the key effector of all anti-acne therapies. All-trans retinoic acid (ATRA) and isotretinoin (13-cis retinoic acid) enhance p53 expression. Tetracyclines and macrolides via inhibiting p450 enzymes attenuate ATRA degradation, thereby increase p53. Benzoyl peroxide and hydrogen peroxide elicit oxidative stress, which upregulates p53. Azelaic acid leads to mitochondrial damage associated with increased release of reactive oxygen species inducing p53. p53 inhibits the expression of androgen receptor and IGF-1 receptor, and induces the expression of IGF binding protein 3. p53 induces FoxO1, FoxO3, p21 and sestrin 1, sestrin 2, and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the key inducer of isotretinoin-mediated sebocyte apoptosis explaining isotretinoin’s sebum-suppressive effect. Anti-androgens attenuate the expression of miRNA-125b, a key negative regulator of p53. It can thus be concluded that all anti-acne therapies have a common mode of action, i.e., upregulation of the guardian of the genome p53. Immortalized p53-inactivated sebocyte cultures are unfortunate models for studying acne pathogenesis and treatment.
    – isotretinoin via increased p53 signalling apparently depletes the number and survival of p63-regulated sebocyte progenitor cells.

    Isotretinoin treatment upregulates the expression of p53 in the skin and sebaceous glands of patients with acne vulgaris (2022)
    – Biopsies from back skin of patients taken before and after isotretinoin treatment show that the treatment significantly increased the nuclear expression of p53 in sebaceous glands, the p53 protein and gene expression significantly increased in the skin after isotretinoin treatment
    – isotretinoin induces both p53-mediated autophagy as well as p53-induced apoptosis, depending on the dose and duration of isotretinoin exposure and the resulting magnitude of p53 expression.
    – isotretinoin-induced expression of p53 not only promotes sebocyte apoptosis in human sebaceous glands as the predominant sebum-suppressive effect bit is also responsible for isotretinoin´s adverse effects [such as..]

    I see that there is now the possibility of stem cell treatments for erectile dysfunction in centers that offer them at a high price as if they were infallible, but few opinions from people who have done it and perhaps little scientific evidence as well…

  20. Are there any legitimate new leads to how to cure this ? I will sell my house thats worth over 500k if someone can figure this out . I have literally every symptom and already one suicide attempt . How can I volunteer to be part of a CRISPR trial on how to rid of this . I already have one suicide attempt . What should I do/not do to help my chances of recovery

  21. Cameron. I feel your pain but I do believe that help is on the way. The recent media storm over the Julia Moncrieff’s rebuffal of the serotonin hypothesis suggests the media are less afraid to criticise the pharmaceutical model. This provides the opportunity to raise awareness of the terrible consequences that these drugs can have. I am writing to every media outlet who covered the story to alert them to this public health catastrophe. With public concern comes research funding.

    This awful condition may be very simply reversible. We just can’t know without the research.

    I’ve found it helpful to channel my grief and anger into raising awareness and donating to research funds.

  22. I have just contacted Helen Fisher

    She is a researcher and writter focused in the link between brain and LOVE

    You can ASK her for getting involved in her webpage


  23. Perhaps the prize fund should be used to secure a lawyer to sue these companies.
    I was on Zoloft for 2 years – came off it October 2008. Nowhere in my literature did it say PSSD forever. After coming off, I had hyper arousal for several weeks, which started to disappear, I was so relieved. But then it went the other way, bit by bit, it was like the lights were going out, one by one. To now 2022, I feel numb everywhere, including genitals, fingers toes, arms legs. No sensation, outside or in. Orgasms are a joke. I have no desire and am single raising my son, who is leaving for Uni next year. Should be a me time, sort of time. But the fact is, would a new partner understand or want to even take it on? Every single Doc I have spoken too, has either not heard me, or suggested other issues. I am not heard, no-one understands and I still have 1/2 my life to live. It sucks. I was living in Canada when this started and now reside in the UK. All the chats with Docs have been with UK Docs to no avail.

  24. Dear Mr Healy,

    first of all, thanks for your commitment to find a cure for PSSD (plus other side-effects, better: unwanted effects of SSRIs)!
    We are a group of sufferers and you are a person who gives us hope and confidence.
    I appreciate a lot.

    I am no doctor or research worker but I am a sufferer of almost all persistent side-effects of the SSRI Escitalopram.
    I have taken only one single pill of this poison and all the problems began immediately and lasting for three years now.

    After a long personal research I actually came to the conclusion, a very simple conclusion, that all side-effects are only caused by too much serotonin in the synaptic gap.
    Whereby this is the sense of all SSRI (selective serotonin reuptake inhibitors), that means you can call them unwanted effects.

    So, the question is not about the side-effects per se but the persistence of them.

    The SSRIs are switching off the gene SLC6a4 by gene silencing, so the SERT (serotonin transporter), a product of this gene, can not be encoded and this product/enzyme originally resumes the serotonin from the synaptic gap back into the presynapse.
    (This should be ended after 24h to 36h after taking the pill and because of this you have to take the next one and so on).
    So the serotonin reuptake remains inhibited and there is too much and long lasting action of serotonin in the synaptic gap, human body.
    This is causing the persistent, long lasting side-effects like PSSD, insomnia, akathisia etc…

    How does gene silencing work?

    You have to put a methyl group (CH3-Group) on the gene you want to switch off.
    In this case the SLC6a4 gene. (the gene which encodes the SERT)
    Now look at the chemical structure of a SSRI, for example Escitalopram: there you can find CH3-groups.
    For why?
    To look good or to switch off a gene?
    Understand what I mean?

    Switch off SLC6a4 => no SERT (serotonin transporter) => no reuptake of serotonin from synaptic gap into presynapse => more and long lasting serotonin in the synaptic gap => PSSD and others!!

    Maybe 95% (I do not know) of the people taking SSRI do not have persistent side effects but maybe 5% do have. Maybe these 5% can not break down methyl groups, maybe there is a loss of something in their body, maybe something like a poor metabolizer of a special enzyme.

    Now I have read about CRISPRoff/CRISPRon.

    This tool can remove methyl groups (CH3 groups) off genes in an easy, fast and cheap way.
    If this actually works, then you can free the gene SLC6a4 off the methyl group (CH3-group) and it is working again, it is switched on, and the serotonin could be resumed from the synaptic gap into the presynapse and the persistence of the side effects like PSSD is over.
    I would be a volunteer in testing this, there would be many sufferers who would volunteer.

    Maybe the CRISPRoff/CRISPRon tool is also working for PFS and PAS sufferers.
    (have a look on the chemical structure of these meds who lead to this)

    To all PSSD/PFS/PAS sufferers: hold on, together we are strong.

  25. Part of what has always held the topic back is a kind of primitive obsession with the phallic side of a proper erection, and not enough talk or even precise localisation of numbness. Some even go so far to say, “I’m cured, I get a proper erection, even though I’m still numb – but I don’t care about that”. Although an erection is the most mechanical, treatment responsive, understood, and least “experiential” part. (Alternatively there has been a reasonable enough obsession with orgasm, although that is itself in a way just an extension of numbness, which some spinal research confirms.) Anyway.

    More than that also various cult dogmas and structures have been regressive and oppressive.

    Nonetheless, it seems too likely that in the most severe and persistent cases some kind of damage is at the root of it, unfortunately.

  26. Dear Dr Healy,

    I believe you can update this page for a clinical trial for 2023 by WinSanTor for the treatment of reduced penile sensation and/or orgasmic dysfunction. WinSanTor has been working on a cure for peripheral neuropathy. Their agent WST-057, is topical pirenzipine, an anti-muscarinic receptor agonist approved for use for the treatment of peptic ulcer, was found to promote axonal growth.

    I for one was left solely with genital anaesthesia, and the cause of that can either lie in the CNS or the PNS. Most of the research projects you listed above ultimately are tied to systemic receptor up or down regulation, in the CNS, which is perplexing that such dysfunction will result in neuropathy of as specific an area as the genitals.

    In my view, WinSanTor’s solution could be the most promising yet!

    • S

      While some of the key features of PSSD are peripheral and topical pirenzepine might help – if it works in diabetic neuropathy and doesn’t cause problems, the disorder is also all pervasive and some of its features likely stem from an autonomic neuropathy – see a new post on kisspeptin and PSSD due next week for some insight on this. So we would need a pirenzepine pill – there is one but it stays in the stomach and gut rather than gets absorbed.


Leave a Reply