Author Topic: POIS paper treatment summary  (Read 4121 times)

Hopeoneday

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Re: POIS paper treatment summary
« Reply #15 on: November 25, 2020, 05:21:14 PM »
Nice work.
Dr-pois.

Muon

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Re: POIS paper treatment summary
« Reply #16 on: November 27, 2020, 09:15:57 AM »
Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders

"In addition, hypnotherapy, which increases vagal tone (213), has been effective in the treatment of IBD"

Jacob (Psychotherapy, hypnotherapy, holotrophic breathing, meditation)

Hmm hypnotherapy could be something to get my breathing frequency under control...taking a note here.

Dumping this here:
Pyridostigmine Protects Against Diabetic Cardiomyopathy by Regulating Gut Microbiota and Branched-Chain Amino Acid Catabolism to Attenuate Mitochondria Dysfunction

I wonder whether cutting the vagus nerve solves POIS instantly...

Who were the POISers that used vagus nerve stimulators with partial succes? I can add those to the list. Also post any treatment for vagus nerve dysfunction/modulation if you see any.
« Last Edit: November 27, 2020, 10:53:44 AM by Muon »

Muon

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Re: POIS paper treatment summary
« Reply #17 on: December 08, 2020, 01:19:19 PM »
Placed CFS community recovery stories under the 'other conditions'---> CFS--->recovery stories. More ideas.
List of ME/CFS Recovery and Improvement Stories

Muon

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Re: POIS paper treatment summary
« Reply #18 on: December 09, 2020, 12:00:27 PM »

Muon

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Re: POIS paper treatment summary
« Reply #19 on: December 12, 2020, 01:55:21 PM »
Dumping this here.

"different things work for different people, and recovery is often a matter of trial, error, and blind luck." Ref

https://forums.phoenixrising.me/threads/dr-jay-goldsteins-rapid-remission-me-cfs-treatments.34516/

"I took a 10 mg tablet of isosorbide dinitrate (Isordil)"

https://forums.phoenixrising.me/threads/betrayal-by-the-brain-jay-goldstein-md-has-anyone-read.20051/page-7

"I was a patient of Dr. Goldstein in 1998-1999. I tried at least two dozen pharmaceuticals he prescribed. My symptoms resolved completely for 6 weeks on Nimodipine but I developed a tolerance and it stopped working. A few other drugs resolved or reduced symptoms for as long as a week but they all stopped working."

http://www.cfstreatmentguide.com/dr-jay-goldstein-a-z-treatments.html

https://www.ncf-net.org/forum/jay.htm

Books:

Betrayal by the brain: The Neurologic Basis of Chronic Fatigue Syndrome, Fibromyalgia Syndrome, and Related Neural Network Disorders (1996)

Tuning the Brain: Principles and Practice of Neurosomatic Medicine (2004)

Chronic Fatigue Syndrome: A Treatment Guide, 2nd Edition, 1st edition free here (1997)

Q: "Is there anywhere in his books where Goldstein provides a flow diagram to follow, for systematically testing out the effects on a patient of the various drugs he recommends for ME/CFS?"

A: "Yes; at the back of Tuning the Brain, Dr. Goldstein provides such a chart. It contains far fewer than the total of 140 drugs, but it does contain a few dozen of the most common ones. All the drugs he uses are listed in the pages after this chart. They're merely listed in alphabetical order, but after a while, you get a feel for how the whole process works, and the chart is not so important. Also, it's not 100% correct, as Dr. Goldstein acknowledges; the workings of the human brain are far too complex to be summarized in a simple chart."

Q: "is the book Tuning the Brain that you are reading more useful than the book Betrayal by the Brain, in terms of an ME/CFS patient trying to follow Goldstein's treatment protocol? Or are both books similar?"

A: "The two books really form a single conceptual volume. Both are necessary to understand his work. Receptor profiling, which is what replaced the list of 23 medicines and what allowed him to know which of his 140 medicines were most likely to help a patient, is explained only in Tuning the Brain. This book is about twice the size of Betrayal by the Brain, and I find that I use it a lot more in my treatment based on this protocol"

Goldstein's Decision Tree (2004)

Goldstein's Decision Tree

How to use Goldstein's Decision Tree

Receptor Profiling as a Guide to Treatment


Copying some in case sites are down:

A Typical Neurosomatic New Patient Treatment Protocol (1996 protocol from 'Betrayal')

The purpose of his treatments was essentially to reset the brain, specifically the limbic system, via pathways going to the brain.
Typically, when Dr. Goldstein saw new patients, he would test them sequentially with minute quantities of many psychoactive drugs in order to 1) identify the source of the problem, and 2) establish which drugs would be most effective. This method allowed Dr. Goldstein to assess the patient rapidly, and at minimal cost. Dr. Goldstein halted sequential trials when the patient was “virtually asymptomatic.” Dr. Goldstein claimed that using this protocol most patients were dramatically improved in one or two office visits.

Agents tried sequentially (Start at top and work your way down)

Drug | Time to Onset of Action | Duration of Action

(1) Naphazoline HCL 0.1% eye drops | 2 - 3 seconds | 3 - 6 hours
(2) Nitroglycerin 0.04 mg sublingual | 2 - 3 minutes | 3 - 6 hours
(3) Nimodipine 30 mg oral | 20 - 40 minutes | 4 - 8 hours (Click here for overview of trials in ME)
(4) Gabapentin 100 to 800 mg oral | 30 minutes | 8 hours
(5) Baclofen 10 mg | 30 minutes | 8 hours
(6) Oxytocin 5 to 10 U intramuscular, or twice daily;
OR: Syntocinon 1 or 2 puffs three times a day | 15 minutes - 72 hrs | 12 - 24 hours
(7) Pyridostigmine 30 to 60 mg oral | 30 minutes | 4 - 6 hours
(8] Hydralazine 10 to 25 mg oral | 30 - 45 minutes | 6 - 12 hours
(9) Mexiletine 150 mg oral | 30 - 45 minutes | 6 - 8 hours
(10) Tacrine 10 mg | 30 minutes | 4 - 6 hours
(11) Risperidone 0.25 to 0.5 mg | 45 - 60 minutes | 8 - 12 hours
(12) Pindolol 5 mg twice a day | 15 minutes - 7 days | 12 hours
(13) Lamotrigine 25 to 50 mg four times a day | 30 - 45 minutes | 24 hours
(14) Sumatriptan 3 - 6 mg subcutaneous | 15 - 30 minutes | 16 hours
(15) Ranitidine 150 mg twice a day | 1 hour - 1 week | 12 - 24 hours
(16) Doxepin HCL elixir 2 - 20 mg at bedtime | 1 hour | variable
(17) Sertraline 25 to 50 mg every day before noon;
OR: Paroxetine 10 to 20 mg every day before noon | 1 hour - 8 weeks | 1 - 2 days
(18) Bupropion 100 mg three times a day | 30 minutes - 8 weeks | 8 - 24 hours
(19) Nefazodone 100 to 300 mg twice a day | 2 - 8 weeks | 24 hours
(20) Venlafaxine 37.5 to 75 mg twice a day | 1 - 4 weeks | 24 hours
(21) Glycine powder 0.4 grams per Kg of body weight daily in juice;
OR: Cycloserine 15 to 20 mg four times a day | 1 hour | 24 hours
(22) Felbamate 400 mg | 30 minutes | 6 - 8 hours
(23) Lidocaine 200 to 300 mg

A-Z Treatments (Comments are by Dr. Goldstein)

Acetazolamide (Diamox): This drug is a carbonic anhydrase (CA) inhibitor which is routinely used as a cerebral vasodilator in nuclear medicine. Patients will occasionally have a reduction in symptomatology with acetazolamide. Acetazolamide 250 mg eliminated the pain of a 41-year-old female patient with post-traumatic fibromyalgia, helped her feel very relaxed, and markedly reduced her other symptoms.

Acetyl-L-Carnitine: In theory, a good drug. It should work as an acetyl group donor to increase acetylcholine, and the carnitine has already been shown to be effective in a double-blind experiment by the Drs. Plioplys. Acetyl-L-carnitine also increases the levels of nerve growth factor (which are four times normal in the spinal fluid of FMS patients) and increases other transmitters like adenosine and ATP. In practice, a semi-dud.

Adderall: An amphetamine combination that a few patients find more energizing than plain dexedrine. Only about a third of CFS patients have a good response to stimulants, which act by squeezing dopamine (DA) and norepiniphrine (NE) out of neurons and glia. If these transmitters are much too low already, giving stimulants will further lower the signal-to-noise ratio and increase symptoms.

Amantadine: A weak NMDA antagonist. Helpful for a few patients. Doses higher than the PDR recommends may be more effective, but there is an increased risk of adverse drug reactions when exceeding this dose. Israelis have given 100 mg IV with good results in neurogenic pain. IV amantadine is not available in the USA. Amantadine, ketamine, dextromethorphan, and a new MNDA antagonist, memantine, can be used in trigger point injections as well as gel applications for local pain.

Ambien: The best sleeping pill. Does not cause dependence except in unusual circumstances.

Aricept: A cholinesterase inhibitor marketed for Alzheimer's disease. Has the advantage of once-a-day dosing and no requirement for liver function test. Does not work as well as Cognex, perhaps because it is not a potassium channel blocker. Cognex has several effects on neurotransmitters relevant to CFS/FMS.

Ascorbic Acid (Vitamin C): Recent research into the role of ascorbic acid in the brain (which has the highest concentrations of this substance in the entire body) has shown that this agent may be beneficial in certain patients with CFS. Ascorbate has been found to be neuroprotective, particularly by inhibiting the redox site of the NMDA receptor and diminishing calcium influx. Trials of high-dose oral ascorbic acid have been generally disappointing. Administration of ascorbic acid is done via IV doses of 25 to 50 grams diluted in half-normal saline of Ringer's lactate over a period of about 90 minutes. Adding magnesium sulfate is recommended because ascorbic acid can cause magnesium shifts from extracellular to intracellular compartments. It is beneficial to add 500 mg of calcium gluconate since ascorbic acid is a calcium chelator and could possibly lower serum calcium. Responders to IV ascorbic acid generally feel considerably better in most respects the day after treatment.

Baclofen: A greatly under used medication. A GABA-B agonist with few ADRs, it has an immediate onset of action and is still in my top 10.

Vitamin B12: Besides being vital to transmethylation (which helps to synthesize NE), B12 2g. orally in AM decreases inappropriate daytime melatonin secretion, thereby aiding in the treatment of the delayed sleep-wake cycle many CFS patients experience. Very large doses (10 g) may aid transmethylation.

BuSpar: The ideal anxiolytic in all respects except efficacy. Best used as an SSRI augmentation agent, especially combined with Visen (not generic Pindolol). Augmentation strategies, of which there are many, do not work nearly as well in CFS as they do in major depression disorder.

Clonidine: Another greatly underused drug. Can be good for central pain, ADD, anxiety. Helps all symptoms in some patients. Eliminates nightmares. Safe and cheap. Comes in a patch that lasts all day. Better than Zanaflex, another alpha-2 agonist. Tolerance and depression have not been much of a problem. Adverse drug reactions to clonidine can be reversed by yohimbine, an alpha-2 antagonist. Guanfacine (Tenex) is a less sedating alpha-2 antagonist with a 24-hour duration of action.

Dexedrine: An effective stimulant. Makes some patients calm also. May synergize with Ultram. Desoxyn may be better but has neurotoxicity. Many patients like Adderall more.

Depakote: In the CFS population its only value is in migraine prophylaxis, for which it is excellent.

Dilantin: Useless in every CFS patient I have treated with it.

DHEA: Theoretically excellent, it is a neurosteroid which is a GABA antagonist, not necessarily a good thing for some patients. Pregnenolone should be the best neurosteroid (low in PMS).

Felbamate (Felbatol): Not used much because of requirement for hematologic and liver function test monitoring. Should be tried in every treatment-resistant patient. May work when nothing else does, especially for intractable headaches. It may cause headaches, however. There's no free lunch.

Gabapentin (Neurontin): Gabapentin, an antiepileptic drug with a novel mechanism of action, has become one of my five favorite medications (the others are oxytocin, nimopidine, baclofen, and intravenous lidocaine) to treat neurosomatic disorders.

Gabitril: The only GABA reuptake inhibitor (like Prozac is a serotonin reuptake inhibitor). Very effective and very safe if you follow PDR dosing suggestions. Increase the dose too rapidly and the patient may get delirious or manic. Effects are reversible with flumazenil if necessary.

Gingko Biloba: Useful only for sexual dysfunction induced by serotonin reuptake inhibitors (SRIs). Inhibits platelet aggregation. Rare reports of brain hemorrhage. This adverse reaction raises the risk/benefit ratio.

Ginseng Saponins: Works a little like nitroglycerin, which converts to nitric oxide. Increases energy slightly.

Gotu Kola: A mild stimulant with no apparent adverse reactions.

Honey Bee Venom: As with any "natural product," bee venom has a multitude of ingredients. Patients should be skin tested for bee venom allergy first. Major constituents from my point of view are phospholipase A2 (PLA2), which makes arachidonic acid, the precursor to eicosanoids (prostaglandins, leukotrienes, etc.), dopamine and NE. When it works, the patient often feels like he has been injected with rocket fuel. Effects last about one to two weeks. Has made three patients worse, two of whom were father and daughter. Patients should have an Epi-Pen (if available) and an antihistamine with them at all times. Plaquenil antagonizes PLA2. Arachidonic acid combines with effianolamine in the brain to make anandamide, an endogenous cannabinoid (like marijuana).

H2 Receptor Antagonists: The first treatments I developed for CFS were cimetidine and ranitidine. I based this therapy on my successful experience treating acute infectious mononucleosis with cimetidine. When a CFS patient responds to an H2 antagonist (I use ranitidine), the onset of action is similar to that seen in acute infectious mononucleosis, i.e. one or two days at a dose of 150 mg b.i.d. Usually all symptoms are ameliorated. Some patients are unable to take any does of ranitidine because it makes them “hyper.”


Hydergine: The most underused effective medication in the PDR. Extremely safe. A dopamine and acetylcholine agonist. There is nothing else like it. Other dopamine agonists seem to be restricted in action to the nigrostriatal dopaminergic tract, which is not important in CFS symptoms. Not the case with Hydergine, which is quite helpful for alertness, especially in those sedated by Baclofen. As with most medications listed, it can sometimes help all symptoms.

Oxytocin: Oxytocin has a wide range of behavioral effects. Oxytocin neurons project to many areas of the limbic system, as well as to the frontal cortex. Oxytocin is involved in maternal behavior, female and male sexual behavior, feeding, social behavior, and memory. It also has effects on cardiovascular, autonomic, and thermoregulatory processes. Approximately one-fifth of my patients have a good response to IM oxytocin after failing to respond to numerous oral agents. Cognitive clarity is the most responsive symptom, with fibromyalgia and pain being second.

Kava-Kava: One of the two best "natural products" for CFS. May take up to eight weeks to have an effect. No adverse drug reactions.

Ketamine: The best single agent for CFS/FMS and all other neurosomatic disorders. Known best as an NMDA receptor antagonist (the NMDA receptor is one of the several receptors for the excitatory amino acid glutamate), it increases dopamine in the limbic system, a very important objective in CFS. I administer it by slow intravenous infusion or in PLO gel for transdermal (through the skin) absorption. The intravenous route is more effective, but transdermal application can be done daily, and if effective, can obviate peaks and valleys and need for IVs. I have seen no cases of Ketamine abuse among my patients. Ketamine is one component of my "resurrection cocktail," for patients who have been bedridden for more than a year and whom I may only see once. The others are IV ascorbate, IV lidocaine, IV thyrotropin- releasing hormone (which raises all biogenic amines plus acetylcholine), Nimotop, and Neurontin (still the most effective oral agent but is being pushed by Tasmar). I am doing trials with Ketamine eyedrops.

Klonopin: The benzodiazepine to use if you are going to use one. Affects neurosteroid biosynthesis.

Kutapressin: I don't know how this drug works, but some patients have immediate symptomatic improvement after 2 ml IM. I don't usually prescribe it otherwise since there are so many immediate-acting options. It does increase bradykinin, and adverse drug reactions may be treated with drugs like Vasotec (ACE inhibitors).

Lamictal: One of the new anti-epileptic drugs. All of them increase GABA, and most of them are N-methyl-d-aspartate (NMDA) antagonists. Works immediately. The main adverse drug reaction is a rash, which can be minimized by gradual dosage escalations. Affects all symptoms. 50-100 mg of Larnictal and 800-1200 mg of Neurontin have rendered euthymic in 30 minutes every patient with acute manic excitement I have treated. Zyprexa and Rilutek could be added to this cocktail if necessary. Lamictal is also an antidepressant and may also work over four weeks or so.

IV lidocaine: In addition to its actions mentioned in Betrayal by the Brain, it also acts as an NMDA antagonist. It is the second best treatment. I have given it about a thousand times without a serious adverse drug reaction. Patients have come with great difficulty from other states or countries with the common lament of "If you can't help me I'm going to kill myself' (I hear this about twice a week). At least two patients, achieving complete symptomatic relief with IV lidocaine, returned home and could not find a physician or nursing service to administer it. Since they could not move to southern California, they were again bedridden and had to crawl to the bathroom. Not able to live this way any longer, they committed suicide, a worse outcome than the lidocaine toxicity, which never happens. Many physicians will not prescribe any of the medications I use, even if they help their patients a lot. Some medium-sized cities have not one physician who will care for CFS patients. I must treat them from afar, a hazardous practice medicolegally.

Marinol: Marinol-deta-9-tetrahydrocannobinol is a medication I use rarely, because of the medicolegal implications. Among other things, it is a dopamine agonist in the limbic system (at the nucleus accumbens, a key structure in CFS), but an indirect one. It is also a calcium channel blocker. A few patients get total symptomatic relief with Marinol when one hundred other medications have failed. One such patient is applying for disability only because she cannot afford it. It is one of the last and best options for treating the diffuse pain of FMS, and is good for atypical facial pain. In five years it should be used routinely in many situations.

Methadone: Another drug I don't use very often, and for the same reason, although California has passed a law that physicians cannot be prosecuted for using opioids responsibly to treat chronic pain. Thus, it is less risky for me. Physicians in some states are afraid to prescribe it. It is the opioid of choice. Besides being an agonist at the mu opioid receptor, it is an NMDA receptor antagonist (like Ketamine), and blocks the serotonin transporter (like SRIs). I described its use as an antidepressant about 15 years ago in the medical literature. It is very cheap, does not produce much opioid euphoria, and often ameliorates all neurosomatic symptoms.

Nicotine Patch or Gum: I have been prescribing nicotine in these forms for a long time. Nicotine is analgesic, probably by virtue of its stimulating secretion of dopamine and norepinephrine. It binds to the nicotinic cholinergic receptor and can also have profound effects on mood, energy, and cognition. An occasional patient will have worsening of symptoms with nicotine.

Papaverine SA: Marketed many years ago as a vasodilator, this medication will probably be discontinued shortly. It is the only drug available that inhibits adenylate cyclase, thereby increasing cyclic AMP, which you may recall from biology class as being pretty important. There is an experimental antidepressant, rolipram, which has a similar mode of action. It preferentially affects energy, alertness, and cognition, and has very few adverse drug reactions. It is a top-10 drug (cheap, too).

Pentazocine (Talwin):Occasionally, an extremely treatment-resistant individual has felt much better after taking pentazocine plus naloxone (Talwin-Nx).

Spironolactone (Aldactone): Spironolactone (a mineralocorticoid receptor antagonist) has been used for several years to treat premenstrual syndrome. My experience with spironolactone is that it helps only occasionally, but the effect is rapid (30 minutes or so), and thus can be assessed while the patient is in the office.

St. John's Wort (Hypericum): The other good "natural" remedy for CFS.

Tasmar (Tolcapone): Neither an exotic location on the Silk Road nor a Mafia-run turnpike in Chicago, Tasmar is a unique agent. It inhibits the enzyme catechol-ortho-methyltransferase (COMT), one of the two enzymes (monomine oxidase is the other) that metabolizes dopamine and norepinephrine. Tasmar degrades them in the synaptic cleft. I have been waiting for this drug for years. It is marketed for Parkinson's disease, and most physicians have not heard of it yet. It can work as monotherapy, either acutely or after four weeks or so. It may be more effective (immediately) when combined with a dopamine agonist such as Requip (quinpirole) or a reversible inhibitor of monoamine oxidase (RIMA) such as meclobemide, which due to the wisdom of the FDA is available in every other industrialized country in the world but the USA. The package insert advises against combining it with irreversible MAOIs such as Nardil and Pamate, so I have not done so. This combination would leave reuptake as the only mechanism to terminate the post-synaptic effect of catecholamines, although rats do quite well on the two drugs. An accountant, unable to work for three years, is back to work now on meclobemide and Tasmar. Adding Sinemet may enhance the action of Tasmar, since it is metabolized to dopamine. Sinemet may be given instead of Requip or Mirapex, or concomitantly. Requip and Mirapex are useful in that they are D3 agonists also. The D3 receptor is located primarily in the limbic system. Since COMT is a methyl group acceptor, it may work better by combining it with S-adenosylmethionine (SAMe), a methyl group donor with no adverse drug reactions, effective in FMS and depression. SAMe is available in many other countries, and certain buyer's clubs will supply you with it. Tasmar inactivates COMT, allowing SAMe to transfer methyl groups to precursors so that more norepinephrine can he formed. This process is termed "transmethylation" and is too complicated to discuss further in this column. Interested readers may consult the work of John R. Sinythies and R.J. Baldessarini and go from there.

Topamax: Another new AED, Topamax has a little more affinity for the ANWA glutamate receptor, as well as the NMDA receptor. It has very few adverse drug reactions, and when it works, is quite energizing. Agonists at the third major class of glutamate receptor, the "metabotropic," of which there are of course various subtypes, are being developed as anxiolytics.

Viagra: I don't have enough money to buy stock in anything, but buying Pfizer a few months ago would have been almost as good as buying Microsoft in 1985. This drug works by inhibiting type 5 phosphodiesterase, one of the six known enzymes to degrade cyclic GMP (as important as cyclic AMP, but maybe not covered in biology class). Type 5 is supposed to be specific for the corpus cavemosurn of the penis and probably the clitoris as well. It is not all that specific, though, at least in my patients, who frequently experience flushing and headache. When Viagra works in CFS/FMS, patients experience a reduction in all symptoms. One patient whom I have been treating for 10 years had not responded to one medication until she took Viagra, whereupon she felt almost normal. Nitroglycerin and hydralazine, which stimulate cyclic GMP by different mechanisms, had not helped her.

Zyprexa: One of the new "atypical neuroleptics," with Risperdal and Seroquel, Zyprexa can he used as a sleeping aid, antidepressant, anxiolytic, and of special relevance to my practice, is probably the most effective treatment for borderline personality disorder. You can look up the symptoms in the DSM-IV, personality disorder.
« Last Edit: January 01, 2021, 07:10:05 PM by Muon »

Muon

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Re: POIS paper treatment summary
« Reply #20 on: December 13, 2020, 10:21:58 AM »
Take a look at Goldstein's decision tree. Goldstein used Testosterone as ketamine antagonist and dopamine agonist. Suggestion: POISers could be categorized by profiling drugs in case of limbic deregulation. Limbic deregulation could be one cause among other causes. Diagnostic flow charts could be made alongside treatment flow charts. I've already seen some of the stuff being used on this forum back in this tree. His latest book is >600 pages. No point in reading when I don't have access to prescriptions.

Edit: Send me a personal message if you are interested in the book  ;)
« Last Edit: December 13, 2020, 03:35:27 PM by Muon »

Muon

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Re: POIS paper treatment summary
« Reply #21 on: December 13, 2020, 05:42:32 PM »
Will post some snippets from the book later. I already see a potential reason why some of the personal treatments here work like they do. POIS might be neurosomatic.

Edit: Some snippets about Testosterone:

Androgens such as testosterone increase the secretion of dopamine, probably by decreasing the activity of the dopamine transporter. Ritalin and cocaine also have this action. Androgens also increase DA by interacting with NO.

The amino acid taurine inhibits the dopamine transporter and maywork somewhat like Ritalin. Taurine is an agent I have tried on several of my patients. It did not enhance dopamine effects but may augment lamotrigine in some individuals.

In rats that are testosterone deficient, the density of tyrosine hydroxylase (TH)-immunopositive axons in the prefrontal cortex increases. Tyrosine hydroxylase converts tyrosine to dopa and is usually the ratelimiting enzyme in the biosynthesis of the catecholamines. The dysregulation of TH is attenuated by supplementing rats with testosterone. The effect is mainly on dopamine and not norepinephrine. Testosterone depletion produces a dopamine hyperinnervation in the prefrontal cortex in an attempt to compensate for decreased production of dopamine.

I have stopped using nitroglycerin as much. Too many patients have migraine headaches, and nitric oxide has been found to cause this disorder. With no history of severe headaches, I can opt to try it (one-half of a 0.3 mg tablet). It either works or not. It sometimes acts as an NMDA agonist since it is a retrograde messenger. Those that respond to nitroglycerin will often benefit from testosterone, oxytocin, and agonists of DA, NE, and glutamate, all of which act in the MPOA to produce arousal and orgasm.

I start testosterone gel at 10 mg/ml, particularly in women with decreased libido if they fail on transdermal estrogen. Their testosterone levels are usually very low.

Perhaps the most relevant aspect of the neuroregulatory aspects of gonadal steroids in neurosomatic disorers is that “estradiol enhances and testosterone attenuates novelty stress-stimulated increases in c-Fos mRNA in the hippocampus, with presumed consequent alterations in the transcription regulatory effects of c-Fos” (Roca CA et al., 1999). Until recently, I have been reluctant to use antiestrogen therapy in women except in treatment-refractory bipolar disorder (Goldstein JA, 1986). I have used testosterone only in men who respond to nitroglycerin, since NO increases DA in the medial preoptic area of the brain. I may be liberalizing its use in transdermal treatment trials, however. When effective, it markedly increases alertness.

When men have a good response to nitroglycerin, I try transdermal testosterone, which has an effect in 30 to 60 minutes or less. If it works, they feel much more energetic. Testosterone induces the secretion of NO, which in turn increases DA in the medial preoptic area (Du J, Hull EM, 1999), which is the area of the brain that determines an individual’s response to sexual stimuli. I shall discuss the sexual response in neurosomatic disorders in the section on oxytocin. A much lower dose of transdermal testosterone can have a similar effect on women.

The situation in which synaptic fatigue is most obvious is that of sexual arousal and ejaculation in the male with a neurosomatic disorder. Some males relapse after ejaculation. A few relapse, but in a different, milder way, after sexual arousal. Arousal seems to depend on activation of the medial preoptic area by testosterone, which facilitates NO synthase. NO increases the secretion of DA in the POA, which, as has been seen, is associated with anticipation of reward. Arousal can be augmented by dextroamphetamine, which also increases DA, particularly in the NAc. Lesions of the MPOA in animals decrease sexual behavior. Sexual arousal, causing increased DA secretion, can cause relapse. Ejaculation is related to the actions of NE and oxytocin.

If the patient is hypertensive, anxious, has ADHD, or experiences nightmares, guanfacine would be a good choice. If perimenopausal or low in testosterone, hormonal therapy would be helpful. Such patients usually have a good response to nitroglycerin, the active form of which is nitric oxide. Orgasm centrally requires estrogen or testosterone, NO, OXT, and norepinephrine, plus a little dopamine acting atD1 receptors. Arousal requiresDA, OXT, testosterone, and NO. Testosterone induces NO synthesis, which then stimulates DA release in the medial preoptic nucleus, which facilitates arousal and penile erection. Oxytocin is required for penile erection.

Some articles posted earlier on the website regarding PE, NO, DA and Testosterone:

Stimulation of dopamine autoreceptors elicits “premature ejaculation” in rats

Relevance of serum nitric oxide levels and the efficacy of selective serotonin reuptake inhibitors treatment on premature ejaculation: decreased nitric oxide is associated with premature ejaculation

Testosterone Induces Molecular Changes in Dopamine Signaling Pathway Molecules in the Adolescent Male Rat Nigrostriatal Pathway
« Last Edit: December 14, 2020, 11:48:45 AM by Muon »

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Muon

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Re: POIS paper treatment summary
« Reply #23 on: December 17, 2020, 01:59:16 PM »
Muon:

"Hello Dr. Rubin,

 A while ago you mentioned that you had treated 2 POIS patients. Are you going to report this eventually in literature? If not, could you share what you have given to these men? Drug name, dose, duration and the subjective amount of relief these men got as a result? And what other meds you have tried in these men which were unsuccessful. I could add that info to this thread:
"

 https://poiscenter.com/forums/index.php?topic=3551.0

Dr. Rachel S. Rubin MD, IF:

"Thank you for reaching out!

See our abstract attached that we presented to the SMSNA this year
":

Introduction: Postorgasmic illness syndrome (POIS) is a condition that is not well described in the literature. Waldinger and Schweitzer were the first to elaborate on the symptoms, of which the main ones are severe fatigue, intense warmth, and a transient flu-like state. These symptoms have a rapid onset and can last between 2-7 days. The two leading hypotheses regarding the pathophysiology of this condition include immunogenic reactivity to autologous semen leading to a hypersensitivity reaction and a proposition that this is a disorder of the endogenous opioid system. POIS is classified as a rare disorder by the NIH Office of Rare Disease Research, with ~50 cases recorded in the literature over the last 10 years. Historically, patients have been treated with SSRIs, benzodiazepines, and/or antihistamines, but there is no standardized treatment for this condition.

Objective: We describe two patients affected by POIS, their symptomatology, and the treatment methods that were successful in alleviating their symptoms.

Methods: Patient A is a 24 year old male who started having symptoms at age 14. His main symptoms included feeling drained post-orgasm, conjunctivitis, as well as sinus pain, headache, and stomach pains. Patient B is a 32 year old male whose symptoms included post-orgasm fatigue, somnolence, and cold-like symptoms, but the most bothersome was the deep internal fatigue. Both men reported that symptoms persisted weeks after orgasm. Both patients had no significant past medical history, normal genitourinary physical exams, and normal laboratory workups. Patient A was trialed on a combination of pseudoephedrine and hydroxyzine, which led to a marked improvement in his symptoms. He was advised to take 50 mg hydroxyzine nightly and pseudoephedrine 1 hour before orgasm. Patient B was trialed on 25mg tramadol, which he took immediately post orgasm. The tramadol led to a significant improvement of his symptoms, most significantly, the fatigue. Both men were also enrolled in sex therapy as part of their treatment.

Results: We found that the treatment methods used with these two patients support the two leading theories about the etiology of POIS, namely the disorder of the opioid system and the immune system hypersensitivity theory. Jiang et al posited that orgasm consumes large amounts of u-opioids, and in these patients, leads to symptoms similar to those of opioid withdrawal (flu-like symptoms, anxiety, fatigue). Tramadol, a u-opioid agonist, might allow for the repletion of the u-opioids in this specific subset of patients. In a hypersensitivity reaction, the body releases large amounts of histamine, therefore, it is likely that an antihistamine, such as hydroxyzine, would alleviate the associated symptoms. In patient A, who had many allergy-like symptoms, it was logical to trial pseudoephedrine and hydroxyzine.
 
Conclusions: POIS is a rare disorder that requires more research. POIS is likely underrecognized and underreported in the general population and may have more than one etiology. It is important to consider a multi-dimensional approach to treatment, take note of each patient's specific symptoms, and recognize different options of pharmaceutical treatment.
« Last Edit: December 17, 2020, 03:30:03 PM by Muon »

Muon

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Re: POIS paper treatment summary
« Reply #24 on: December 21, 2020, 12:45:15 PM »
"It should be obvious why neurosomatic male patients, who have NE-dependent ejaculation-related processes, commonly relapse for up to a week after having sex. Because DA is depleted after ejaculation, there is a marked increase in central prolactin concentration, thought to account for the refractory period after orgasm in men (Exton MS et al., 2001). Large volumes of NE are secreted in several areas, including the hypothalamus, thoracolumbar cord, and during intromission and ejaculation (Meston CM, Frohlich PF, 2000)."

Mushnikk

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Re: POIS paper treatment summary
« Reply #25 on: December 22, 2020, 10:47:43 AM »
"It should be obvious why neurosomatic male patients, who have NE-dependent ejaculation-related processes, commonly relapse for up to a week after having sex. Because DA is depleted after ejaculation, there is a marked increase in central prolactin concentration, thought to account for the refractory period after orgasm in men (Exton MS et al., 2001). Large volumes of NE are secreted in several areas, including the hypothalamus, thoracolumbar cord, and during intromission and ejaculation (Meston CM, Frohlich PF, 2000)."

Explain the abbreviations, thank you!

Muon

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Re: POIS paper treatment summary
« Reply #26 on: December 22, 2020, 12:14:46 PM »

Muon

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Re: POIS paper treatment summary
« Reply #27 on: December 27, 2020, 09:54:50 AM »
If you encounter POISers who have tried methods for their symptoms with a certain degree of succes and who aren't listed yet on the first page, then dump a link to that thread or post here so I or can incorporate them into the list. It's easier for everyone to get a proper overview this way. Thank you.

Muon

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Re: POIS paper treatment summary
« Reply #28 on: December 29, 2020, 01:06:03 PM »
There is too much information on all POIS forums combined. I don't have the energy to go through all of it. People on these forums did such a poor job collecting relevant information and centralize it. Spending time on endless fruitless discussions while most clues are being left in the dust, unbelievable. Almost zero documentation. Healthcare is a similar mess. Doctors not exchanging information about POISers with eachother or centralize this to a database. You don't even need extra money, restructering the healthcare system helps a lot to boost efficiency. Rant out.

Muon

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Re: POIS paper treatment summary
« Reply #29 on: December 29, 2020, 10:46:02 PM »
Massive paper about CBD:
Immune Responses Regulated by Cannabidiol (2020)

Some folks can resolve their POIS completely with CBD oil, like Vandemolen. Aside from mast cell stabilisation via CB1/2, it can act through other receptors; "These studies show that CBD acts through the adenosine A2A receptor, especially in microglial cells." Milnacipran in the case of hurray could also act on microglia.

CBD could be inducing Tregs just like TRT, see this post and articles below:

Cannabidiol (CBD) induces functional Tregs in response to low-level T cell activation (2017)

Cannabidiol (CBD) induces functional CD4+ CD25+ FOXP3+ Tregs (2016)

Response to CBD could differ depending on the level of T cell activation.
« Last Edit: December 30, 2020, 10:55:12 AM by Muon »