6 ms·

The world of medecine is degenerate. Sustainable, non addictive and non neurotoxic anxiolytics exists: the #1 being opipramol the sigmaergic. emoxypine (which b

The world of medecine is degenerate. Sustainable, non addictive and non neurotoxic anxiolytics exists: the #1 being opipramol the sigmaergic. emoxypine (which btw cure hangover) and guanfacine are worth mentioning. Maybe beta blockers to some extent. NMDA antagonists such as memantine have side effects but are not neurotoxic to my knowledge and there are milder ones such as mg-lthreonate. afobazole is interesting but its pharmacology is too weird to be sure. Etifoxine is revolutionnary, it double axon length growth rate so ironically a great cure to benzo neurodamage. its acts on the mitochondria benzodiazepine receptor. It's unclear to me wether it is subject to a tolerance effect and if so if it is lower. Also etifoxine can interact badly with other drugs on the liver. Note that there exists ultra-atypical mechanisms, such as inositol megadose or tofisopam but they are not firstline. So yeah, basically opipramol and guanfacine should be what humans take as first line. Glycine is a nice obvious augmentation (kinda absurd that people forget about the second inhibitor neurotransmitter in the brain, especially since the effect feel nice and doesn't really lead to tolerance). if you have benzo neurodamage, take magnesium lthreonate which is a very potent synaptotrophic. also fun fact: the benzo cartel was so strong it was the most prescribed drug in the world, all classes, in the 70s

m_a_g 4y ago
I've been seeing your comments on HN and you seem very well-read. Is there a drug/supplement stack you recommend or use? I've seen you recommend magnesium l-threonate and skq1 several times and I was wondering if there are more drugs/supplements that are worth mentioning.
- ineedasername 4y ago
  Not sure what the parent post would recommend, but l-theanine is supposedly well tolerated and moderately effective as an anxiolytic. Annecdotal personal experience supports this.
rhexs 4y ago
Emoxypine doesn't seem to have any English studies, or has incredibly few. So it may or may not be useful, but I sure as heck can't tell.
- SemanticStrengh 4y ago
  here's 438 studies for you https://pubmed.ncbi.nlm.nih.gov/?term=Emoxypine&sort=date https://pubmed.ncbi.nlm.nih.gov/?term=Emoxypine&sort=date the marketing name is mexidol. Emoxypine is a wonder drug for health, it is one of the most potent superoxide antioxidant and has an incredible range of body protective effetcs see e.g. https://en.wikipedia.org/wiki/Emoxypine#Mechanism_of_action https://en.wikipedia.org/wiki/Emoxypine#Mechanism_of_action look at the pictures and admire the amount of saved brain volume https://www.researchgate.net/publication/221738761_Evaluation_of_Effects_of_Histochrome_and_Mexidol_on_Structural_and_Functional_Characteristics_of_the_Brain_in_Senescence-Accelerated_OXYS_Rats_by_Magnetic_Resonance_Imaging https://www.researchgate.net/publication/221738761_Evaluatio...
  - rhexs 4y ago
    Interesting. What's the quality of Russian medical research versus western? What journals are considered prestigious? (Not trying to troll -- I honestly have no idea and can't judge it accurately).
    - SemanticStrengh 4y ago
      I have much more respect for russian papers in pharmacology in general than for your average american study. There are many reasons to this: 1) a lot of their research is public. They don't have broken incentives, e.g. they can study the tech that the body use, such as peptides. Big pharma can't leverage endogenous peptides because they're not patentable, a true tragedy that considerably sets back medecine progress. 2) they study outside of the boxe things, they are not afraid to do human trials, they have expertise in gerontology (oxidative stress, bioenergetics, etc) which are often very lacking in american studies. also, those russian researches are generally validated by non-russian working groups. as an example, many of the favorites nootropics people experience have been discovered in russia (racetams, bromantane, etc)
      - rhexs 4y ago
        Thanks, interesting to get this perspective. I have seen a lot of interesting research chemicals and nootropics redditors are using, most of which are prescription drugs in Russia (semax, selank, probably others). Shame there doesn't seem to be any pharmaceutical crossover, would love to see some studies done in the West. I'd be too scared to experiment on myself.
sph 4y ago
I have a hard time believing that while the current status quo is suboptimal, there's some little known compounds that are, as you say, revolutionary and with little side effects. Pharmacological research is a constantly moving target, there is no scientific nor economic reason that a supposedly "perfect" remedy remains unknown. Sounds too much like thinly veiled conspiracy, or perhaps they're not as perfect as you're suggesting. That said, it's not my area of competence, so if you know _why_ opipramol and guanfacine are ignored compared to benzos and other anxiolytic, you should probably explain that. EDIT: re: guanfacine, I know it's a second-line treatment for ADHD, it was previously used to treat hypertension, but this is the first time I hear it might be applicable as an anxiolytic. It does certainly have side effects, though not as bad as being neurodegenerative like benzodiazepines. https://en.wikipedia.org/wiki/Guanfacine https://en.wikipedia.org/wiki/Guanfacine
- gavinray 4y ago
  I have personal experience with Guanfacine (and Clonidine), beta blockers (Propanolol/Labetalol), Etifoxine, Phenibut, and a myriad of benzos. Long history of RX for anxiety disorders, which I eventually tapered off of and quit due to dependence. Can attest to Etifoxine being effective without side effects, guanfacine and clonidine being mildly effective. Beta blockers never did much for me but YMMV.
  - ineedasername 4y ago
    After all of those, what did you settle on for managing anxiety long term? Was it the Etifoxine?
    - gavinray 4y ago
      I keep Etifoxine on hand for acute panic attacks and take l-Theanine + Ashwagandha daily for general anxiety. The over-the-counter supplements don't do much but it's better than nothing.
      - SemanticStrengh 4y ago
retrac 4y ago
Anecdotally, I can attest to the surprising efficacy of alpha blockers. I have used prazosin as a sleep aid for the last decade, a few times a month. There were some limited studies that suggest it is effective in helping sleep quality in people with nightmares and PTSD. Now, I don't have PTSD, but I do have a mind that will not shut off at night, running in useless circles that jolt me back awake. It does nothing for the racing mind, but my body's physiological reaction to my emotional state is lessened. I physically relax, quite literally in smooth muscle activation terms, and apparently that lets me get to sleep. Beta blockers are probably a bit more heavy duty, but they do appear to be quite effective at treating performance-related anxieties from another small study. Shakes? Chills? Dizziness and blood pressure spikes? From the discussion I had with my psychiatrist, I think the working hypothesis is that treating the physical symptoms of anxiety is an effective intervention here, as the discomforting experiences that the initial anxiety triggers, creates a feedback cycle. (Oh god, now I'm sweating and flushed, everyone's gonna notice...!)
- SemanticStrengh 4y ago
  Good to hear! Glycine 3 gram before sleep can be useful as a combination. it relaxes the body too and relaxe the mind also. There are interesting studies showing positive effects on sleep and no tolerance. magnesium l threonate before sleep, the lthreonate variant penetarte the brain far more than regular magnesium, and it acts as a mild NMDA antagonist, which means it decrease maximal excitation. it is also a great synaptotrophic.
  - voldacar 4y ago
    > the lthreonate variant penetarte the brain far more than regular magnesium How is this possible? Don't the magnesium ions fully dissociate once they come in contact with water, so that there's just free floating Mg+ and threonate?
    - SemanticStrengh 4y ago
      > How is this possible? I don't know, that's a good question I somehow the bond must mostly break in the brain but I don't know why. I have made extensive research on magnesiusm forms in the past, there was a great study comparing the amount of magnesium that crossed the blood brain barrier per form. Between a form and another the difference had a lot of variation. Magnesium taurate (not threonate) was the one with the highest crossing. however this study included all forms except threonate.. threonate is known to cross the brain much more than the others and it shows in studies, the effect on synaptogenesis/ gained IQ points is huge and incomparable with other forms. The unknown is how threonate and taurate compare. I'm not aware of comparative studies for threonate but you can see e.g. https://pubmed.ncbi.nlm.nih.gov/31806980/ https://pubmed.ncbi.nlm.nih.gov/31806980/ for absolute values. As to why? I don't know.
blantonl 4y ago
also fun fact: the benzo cartel was so strong it was the most prescribed drug in the world, all classes, in the 70s "Mother's little helper" was a term coined during the 60s and 70s (Diazepam - aka Valium)
- deleted 4y ago
  [deleted]
gavinray 4y ago
Etifoxine can be purchased from other countries and has studies showing comparable effects to classic benzodiazepines for acute panic attacks, but without being addictive. Personal experience, it doesn't have noticeable psychoactive effects like benzos do but does block stress response + panic. https://en.wikipedia.org/wiki/Etifoxine https://en.wikipedia.org/wiki/Etifoxine
bin_bash 4y ago
don't forget buspirone!
- SemanticStrengh 4y ago
  buspirone works great, when it works.. which is for what ? 20% of the population?
nickstinemates 4y ago
remedies and compounds that work widely have a name: medicine.
markdown 4y ago
> Sustainable, non addictive and non neurotoxic anxiolytics exists: the #1 being opipramol You misspelled kava.
kall 4y ago
Opipramol is a weird one. It's among the most prescribed anti-depressants in Germany (and other European countries), yet apparently non existent in the US.

m_a_g 4y ago

I've been seeing your comments on HN and you seem very well-read. Is there a drug/supplement stack you recommend or use? I've seen you recommend magnesium l-threonate and skq1 several times and I was wondering if there are more drugs/supplements that are worth mentioning.

ineedasername 4y ago
Not sure what the parent post would recommend, but l-theanine is supposedly well tolerated and moderately effective as an anxiolytic. Annecdotal personal experience supports this.

rhexs 4y ago

Emoxypine doesn't seem to have any English studies, or has incredibly few. So it may or may not be useful, but I sure as heck can't tell.

SemanticStrengh 4y ago
here's 438 studies for you https://pubmed.ncbi.nlm.nih.gov/?term=Emoxypine&sort=date https://pubmed.ncbi.nlm.nih.gov/?term=Emoxypine&sort=date the marketing name is mexidol. Emoxypine is a wonder drug for health, it is one of the most potent superoxide antioxidant and has an incredible range of body protective effetcs see e.g. https://en.wikipedia.org/wiki/Emoxypine#Mechanism_of_action https://en.wikipedia.org/wiki/Emoxypine#Mechanism_of_action look at the pictures and admire the amount of saved brain volume https://www.researchgate.net/publication/221738761_Evaluation_of_Effects_of_Histochrome_and_Mexidol_on_Structural_and_Functional_Characteristics_of_the_Brain_in_Senescence-Accelerated_OXYS_Rats_by_Magnetic_Resonance_Imaging https://www.researchgate.net/publication/221738761_Evaluatio...
- rhexs 4y ago
  Interesting. What's the quality of Russian medical research versus western? What journals are considered prestigious? (Not trying to troll -- I honestly have no idea and can't judge it accurately).
  - SemanticStrengh 4y ago
    I have much more respect for russian papers in pharmacology in general than for your average american study. There are many reasons to this: 1) a lot of their research is public. They don't have broken incentives, e.g. they can study the tech that the body use, such as peptides. Big pharma can't leverage endogenous peptides because they're not patentable, a true tragedy that considerably sets back medecine progress. 2) they study outside of the boxe things, they are not afraid to do human trials, they have expertise in gerontology (oxidative stress, bioenergetics, etc) which are often very lacking in american studies. also, those russian researches are generally validated by non-russian working groups. as an example, many of the favorites nootropics people experience have been discovered in russia (racetams, bromantane, etc)
    - rhexs 4y ago
      Thanks, interesting to get this perspective. I have seen a lot of interesting research chemicals and nootropics redditors are using, most of which are prescription drugs in Russia (semax, selank, probably others). Shame there doesn't seem to be any pharmaceutical crossover, would love to see some studies done in the West. I'd be too scared to experiment on myself.

sph 4y ago

I have a hard time believing that while the current status quo is suboptimal, there's some little known compounds that are, as you say, revolutionary and with little side effects. Pharmacological research is a constantly moving target, there is no scientific nor economic reason that a supposedly "perfect" remedy remains unknown. Sounds too much like thinly veiled conspiracy, or perhaps they're not as perfect as you're suggesting. That said, it's not my area of competence, so if you know _why_ opipramol and guanfacine are ignored compared to benzos and other anxiolytic, you should probably explain that. EDIT: re: guanfacine, I know it's a second-line treatment for ADHD, it was previously used to treat hypertension, but this is the first time I hear it might be applicable as an anxiolytic. It does certainly have side effects, though not as bad as being neurodegenerative like benzodiazepines. https://en.wikipedia.org/wiki/Guanfacine https://en.wikipedia.org/wiki/Guanfacine

gavinray 4y ago
I have personal experience with Guanfacine (and Clonidine), beta blockers (Propanolol/Labetalol), Etifoxine, Phenibut, and a myriad of benzos. Long history of RX for anxiety disorders, which I eventually tapered off of and quit due to dependence. Can attest to Etifoxine being effective without side effects, guanfacine and clonidine being mildly effective. Beta blockers never did much for me but YMMV.
- ineedasername 4y ago
  After all of those, what did you settle on for managing anxiety long term? Was it the Etifoxine?
  - gavinray 4y ago
    I keep Etifoxine on hand for acute panic attacks and take l-Theanine + Ashwagandha daily for general anxiety. The over-the-counter supplements don't do much but it's better than nothing.
    - SemanticStrengh 4y ago

retrac 4y ago

Anecdotally, I can attest to the surprising efficacy of alpha blockers. I have used prazosin as a sleep aid for the last decade, a few times a month. There were some limited studies that suggest it is effective in helping sleep quality in people with nightmares and PTSD. Now, I don't have PTSD, but I do have a mind that will not shut off at night, running in useless circles that jolt me back awake. It does nothing for the racing mind, but my body's physiological reaction to my emotional state is lessened. I physically relax, quite literally in smooth muscle activation terms, and apparently that lets me get to sleep. Beta blockers are probably a bit more heavy duty, but they do appear to be quite effective at treating performance-related anxieties from another small study. Shakes? Chills? Dizziness and blood pressure spikes? From the discussion I had with my psychiatrist, I think the working hypothesis is that treating the physical symptoms of anxiety is an effective intervention here, as the discomforting experiences that the initial anxiety triggers, creates a feedback cycle. (Oh god, now I'm sweating and flushed, everyone's gonna notice...!)

SemanticStrengh 4y ago
Good to hear! Glycine 3 gram before sleep can be useful as a combination. it relaxes the body too and relaxe the mind also. There are interesting studies showing positive effects on sleep and no tolerance. magnesium l threonate before sleep, the lthreonate variant penetarte the brain far more than regular magnesium, and it acts as a mild NMDA antagonist, which means it decrease maximal excitation. it is also a great synaptotrophic.
- voldacar 4y ago
  > the lthreonate variant penetarte the brain far more than regular magnesium How is this possible? Don't the magnesium ions fully dissociate once they come in contact with water, so that there's just free floating Mg+ and threonate?
  - SemanticStrengh 4y ago
    > How is this possible? I don't know, that's a good question I somehow the bond must mostly break in the brain but I don't know why. I have made extensive research on magnesiusm forms in the past, there was a great study comparing the amount of magnesium that crossed the blood brain barrier per form. Between a form and another the difference had a lot of variation. Magnesium taurate (not threonate) was the one with the highest crossing. however this study included all forms except threonate.. threonate is known to cross the brain much more than the others and it shows in studies, the effect on synaptogenesis/ gained IQ points is huge and incomparable with other forms. The unknown is how threonate and taurate compare. I'm not aware of comparative studies for threonate but you can see e.g. https://pubmed.ncbi.nlm.nih.gov/31806980/ https://pubmed.ncbi.nlm.nih.gov/31806980/ for absolute values. As to why? I don't know.

blantonl 4y ago

also fun fact: the benzo cartel was so strong it was the most prescribed drug in the world, all classes, in the 70s "Mother's little helper" was a term coined during the 60s and 70s (Diazepam - aka Valium)

deleted 4y ago
[deleted]

gavinray 4y ago

Etifoxine can be purchased from other countries and has studies showing comparable effects to classic benzodiazepines for acute panic attacks, but without being addictive. Personal experience, it doesn't have noticeable psychoactive effects like benzos do but does block stress response + panic. https://en.wikipedia.org/wiki/Etifoxine https://en.wikipedia.org/wiki/Etifoxine

bin_bash 4y ago

don't forget buspirone!

SemanticStrengh 4y ago
buspirone works great, when it works.. which is for what ? 20% of the population?

nickstinemates 4y ago

remedies and compounds that work widely have a name: medicine.

markdown 4y ago

> Sustainable, non addictive and non neurotoxic anxiolytics exists: the #1 being opipramol You misspelled kava.

kall 4y ago

Opipramol is a weird one. It's among the most prescribed anti-depressants in Germany (and other European countries), yet apparently non existent in the US.