SMI-6 as Monotherapy: my outcome and results.

Gegen

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Hello guys. I wanted to share you my experience of using SMI as monotherapy for 6 months ( from +/- 06/15/2021 to 12/13/2021 ). I post it on the research subforum as it is the most visited subforum and as the subject is about an experimental drug. My discord pseudonyme is Sc0tt1sh.

APRIL
- I started SMI few days after receiving it ( we had to figure out what vehicle we had to use ). This was approximately in mid april. For one month, wich I don't count in my journey, I used a PEG400 - Ethanol based vehicle. It didn't work because of the lack of penetration.
- At the same time, I was using minoxidil 5% topically since 3 years, and I microneedled regularly, about once every two weeks.

- I started with 0.2mL on each temple at 0.625% once then twice a day.

MAY
- Then, in the middle of May, we figured out that we needed a DMSO/Ethanol dominant vehicle for SMI to penetrate skin layers. So I changed my 50/45/5 - PEG400/Ethanol/Tween80 vehicle to a 40/45/10/5 - DMSO/Ethanol/PEG400/Tween80 one. And then results started to come one month after these changes.
- Parallely, I stopped Minoxidil and dermarolling few days following this vehicle reformulation.

- I switched to a 1.25% concentration.

JUNE
- Results started to come out in the end of June. Before photo wasn't good but we could see a difference.
Here is my before Photo, around middle of May : https://zupimages.net/up/21/50/0ngh.jpg You can see a little point that served as a reference to compare pics.
Here is the first pics I done, the 02 and 09 of June
: https://zupimages.net/up/21/50/pi2b.jpg
And the most interesting pic of June, where we started to see the early changes : https://zupimages.net/up/21/50/r7uq.jpg
As you can see, vellus were elongating more than thickening, and it started to fill some areas that were uncovered by hair since 1/2 years. My phone has a shitty objective, details aren't visibles, but I can assure you that there was a real cosmetical difference by the end of june.

- My shedding almost stopped.

JULY
- This month was the greatest when it comes to regrowth. My vellus were thickening and growing.
Pic : https://zupimages.net/up/21/50/3n9m.jpg


AUGUST
- It continued to bring some growth. I took a pic the 8th august : https://zupimages.net/up/21/50/i31k.jpg

- Then, it started to limp. I think it was due to 2 things. I became less consistent and, more importantly, I changed my ethanol source, I came from a 99% pure ethanol to 70%, I didn't have the choice. I think it had some bad impact on the dilution of smi, it made some weird vesicles in the batch, probably because of the presence of water in the 70% ethanol.
- Then, I started to shed again. It's not relevant to talk about September, nothing happened unless shedding.


OCTOBER
- I restarted using a proper vehicle with 99% pure Ethanol, and continued with 1.25% concentration solution.
- I took a new baseline. Right side
: https://zupimages.net/up/21/50/q5m0.jpg and Left Side: https://zupimages.net/up/21/50/6and.jpg
- As you can see, I lost almost all my gains.

NOVEMBER
- I increased the concentration to 2.5%.
- Took new pics : Right: https://zupimages.net/up/21/50/uqcq.jpg Left: https://zupimages.net/up/21/50/k8mn.jpg
- *painful*


DECEMBER
- I continued with the 2.5% concentration.
- Pics: Right : https://zupimages.net/up/21/50/fpmp.jpg Left : https://zupimages.net/up/21/50/83c9.jpg

- It gets worse and worse.

So,
given the fact SMI doesn't work as monotherapy, I just added WAY at 0.4% concentration yesterday and restartde to microneedle today. I will probably add other things, but I'm pretty sad it didn't work. I knew it was risky to try SMI as monotherapy, but I really wanted to see if inhibiting prlr with a little inhibitor like smi could halt hairloss by isolating this drug. It is probably too weak, given his nature of competitive inhibitor and the fact it doesn't have a really strong affinity to PRLr compared to Prolactin.

Also, my experiment doesn't show that prlr inhibition isn't going to work. It shows that a "weak" inhibitor of these prlr is not sufficient to silence the PRL signalling efficiently. Some hypothesis (from @pegasus2 and others on the discord servers) suggest that we need to silence almost 100% of the PRL signalling to promote hair regrowth substancially. It seems to be the case.

I tried to make this as short as possible. If you have questions I'll answer it with pleasure.
Thanks for reading.
 

hmmmmmmmm

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Very impressive logging with all relevant context, especially the motivations for each change

lots of dedication to try something like this as monotherapy too, knowing there's a big chance it hurts your hair

Ultimately it was a very bad compound choice with no meaningful chance of success, and this was knowable ahead of time...
but the unique growth seen in the HMI patent made the logic of a moonshot attempt with something similar defensible
 

5minutesbeforemiracle

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Thanks a lot for your report.

Have you considered that quitting minoxidil was a confounding factor for your results? You said you were using minoxidil for 3 years and had been microneedling too. Then 4 months after quitting them (and 5 months into your SMI therapy), you started to shed and lose hair. That seems about the right timeline to lose minoxidil gains. Even if you were maintaining for years on finasteride/min, if you quit the min then there would be hairloss in that scenario, even though we already know that finasteride works.

However, since no one else seems to have positive results on SMI either, then it's possible it really doesn't work.
 

Gegen

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Thanks a lot for your report.

Have you considered that quitting minoxidil was a confounding factor for your results? You said you were using minoxidil for 3 years and had been microneedling too. Then 4 months after quitting them (and 5 months into your SMI therapy), you started to shed and lose hair. That seems about the right timeline to lose minoxidil gains. Even if you were maintaining for years on finasteride/min, if you quit the min then there would be hairloss in that scenario, even though we already know that finasteride works.

However, since no one else seems to have positive results on SMI either, then it's possible it really doesn't work.
I wonder if quitting minoxidil had a big impact or not.
On one hand I was on minoxidil since 3 years wich means I reached the optimal efficacy 2 years before i stopped.

On the other hand it is possible that i was maintaining with minoxidil, then when i quit the hair i maintained started to go away.

And, yes, sadly it seems that using low to mild doses of smi don't do anything. It is also possible that high doses don't work either.
It seems to be a good nootropic though, you'll be able to fight the depression due to your hairloss with it lol.
 

5minutesbeforemiracle

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I wonder if quitting minoxidil had a big impact or not.
On one hand I was on minoxidil since 3 years wich means I reached the optimal efficacy 2 years before i stopped.

On the other hand it is possible that i was maintaining with minoxidil, then when i quit the hair i maintained started to go away.

And, yes, sadly it seems that using low to mild doses of smi don't do anything. It is also possible that high doses don't work either.
It seems to be a good nootropic though, you'll be able to fight the depression due to your hairloss with it lol.
Hmm honestly speaking it was definitely a mistake for you to drop all your treatments just to try SMi monotherapy for only 6 months. You actually were umable to learn anything from that. I think quitting minoxidil likely had a big impact. There's a reason all clinical studies exclude anyone that's been on any other treatments within the past 6 months..
It's too late now, however to actually see if SMI would've worked for you it, it was actually important to keep all of your other treatments the same too. If you hop back on minoxidil and regain most of the hairs that you lost recently, then I'd say that quitting it was also the cause for your hairloss during your 6 month trial.

Anyway, good luck bro. I wish you luck in regaining your hair.
 

Gegen

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Thank you for sharing your experience with SMI. It was definitely worth it to try as a monotherapy imo, now we know it's too weak probably. You did the community a great service.

I'm hyped for UC-514321 though.

@Gegen You going to try UC?
Thanks !

Probably.
It inhibits potently the majority of the prlr signalling downstream the receptor. So no problem of competition with prolactin. I think it worth a try, I'll follow the outcome from those who are participating to the first groupbuy (they'll receive it soon).
And if it works, price will probably lowers as more people, including me, will buy it.
 

John Difool

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Thanks !

Probably.
It inhibits potently the majority of the prlr signalling downstream the receptor. So no problem of competition with prolactin. I think it worth a try, I'll follow the outcome from those who are participating to the first groupbuy (they'll receive it soon).
And if it works, price will probably lowers as more people, including me, will buy it.
We will know in 6 months from end of December.
 

John Difool

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Hmm honestly speaking it was definitely a mistake for you to drop all your treatments just to try SMi monotherapy for only 6 months. You actually were umable to learn anything from that. I think quitting minoxidil likely had a big impact. There's a reason all clinical studies exclude anyone that's been on any other treatments within the past 6 months..
It's too late now, however to actually see if SMI would've worked for you it, it was actually important to keep all of your other treatments the same too. If you hop back on minoxidil and regain most of the hairs that you lost recently, then I'd say that quitting it was also the cause for your hairloss during your 6 month trial.

Anyway, good luck bro. I wish you luck in regaining your hair.
Okay thanks for the advice, Professor Eyebrow. I can't wait to read your book.

It's always easy to criticize something when you know the outcome. I personally think there were a lot of merit to try monotherapy. Would SMI have been able to retain minoxidil hair, you would now sing a different song. And now we know it doesn't, so thats' a big deal.

I for one would like to say good bye to minoxidil and the raccoon eyes it gives me on bad days.
 

5minutesbeforemiracle

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Okay thanks for the advice, Professor Eyebrow. I can't wait to read your book.

It's always easy to criticize something when you know the outcome. I personally think there were a lot of merit to try monotherapy. Would SMI have been able to retain minoxidil hair, you would now sing a different song. And now we know it doesn't, so thats' a big deal.

I for one would like to say good bye to minoxidil and the raccoon eyes it gives me on bad days.
Hmm, I was speaking out of concern for my fellow hairloss sufferer. It would have been better for him as an individual if he'd stayed on minoxidil while trying SMI too. And at the same time, from a "clinical trial" perspective, his sacrifice was really in vain, because it's hard to draw any conclusions from his attempt at SMI monotherapy, for the reasons I stated...
btw, you are a really sour individual!!
 

Gegen

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Hmm honestly speaking it was definitely a mistake for you to drop all your treatments just to try SMi monotherapy for only 6 months. You actually were umable to learn anything from that. I think quitting minoxidil likely had a big impact. There's a reason all clinical studies exclude anyone that's been on any other treatments within the past 6 months..
It's too late now, however to actually see if SMI would've worked for you it, it was actually important to keep all of your other treatments the same too. If you hop back on minoxidil and regain most of the hairs that you lost recently, then I'd say that quitting it was also the cause for your hairloss during your 6 month trial.

Anyway, good luck bro. I wish you luck in regaining your hair.
Thanks.
But an important thing that i didn't precise in my first post is that i wanted to see if smi alone could maintain my minoxidil gains, i was tired to apply topical minoxidil since 3 years.
 

Gegen

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The thing is that theoretically, after 3 years of application, minoxidil didn't have effects on my hair anymore.
So dropping it wouldn't do so much, especially if smi was a potent hairloss drug, it would have counteract the potential effects of minoxidil discontinuation.
But smi isn't potent enough.
 

hmmmmmmmm

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Hmm, I was speaking out of concern for my fellow hairloss sufferer. It would have been better for him as an individual if he'd stayed on minoxidil while trying SMI too. And at the same time, from a "clinical trial" perspective, his sacrifice was really in vain, because it's hard to draw any conclusions from his attempt at SMI monotherapy, for the reasons I stated...
btw, you are a really sour individual!!
I guess if the experiment was "can SMI maintain my minoxidil gains?" then it was a success

in the sense that he got a clear result of "no"

Beyond this you're obviously right that drawing conclusions about how SMI might work in other people or contexts hasn't really been advanced
 

John Difool

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The thing is that theoretically, after 3 years of application, minoxidil didn't have effects on my hair anymore.
So dropping it wouldn't do so much, especially if smi was a potent hairloss drug, it would have counteract the potential effects of minoxidil discontinuation.
But smi isn't potent enough.


I think you need to clarify here: SMI at the dosage and by the route you took it.
 

John Difool

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I guess if the experiment was "can SMI maintain my minoxidil gains?" then it was a success

in the sense that he got a clear result of "no"

Beyond this you're obviously right that drawing conclusions about how SMI might work in other people or contexts hasn't really been advanced
And your view is that it doesn't work at all. Heard that one before. But you don't miss any opportunity to flame anything, do you?
 

Chads don't bald

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Good work on the report @Gegen. Note to the lurkers reading this now; it is for a topical application of SMI-6. Others (including yours truly). are on much higher oral dosage to determine if the drug can be more effective using that route.
Please do update us if you see any results (or lack of results) with the oral route
 

hmmmmmmmm

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And your view is that it doesn't work at all. Heard that one before. But you don't miss any opportunity to flame anything, do you?
Whether I think SMI works or not has nothing to do with the comment you replied to...

It's relevant to point out that you can't draw a stronger conclusion beyond "SMI under those conditions couldn't maintain minoxidil-dependent hairs"

When similar high quality reports from yourself and the many others who tried SMI become available, it will be interesting to see what other conclusions are possible.
 
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