Up and down regulation of serotonin receptors

[KyleM]

SWIM does not think that will produce the results SWIY is looking for. The idea is to emulate chronic, unavoidable stress, not just a few extremely stressful events. SWIM's recommendation would be to take it for at least twice that length of time, but every other day instead. Dexamethasone should last 2 days in SWIY's system anyway, just remember to taper off and not abruptly discontinue. Stress alone will take a toll on the body as will artificial stress, but as SWIM said in the past, it all depends on how badly someone wants to roll and SWIM also assumes SWIY will extensively research this before trying this. SWIM's own order of dexamethasone was seized at U.S. customs apparently, so hopefully it's easier to obtain in the U.K.

And again make serotonin levels are adequate just prior to MDMA otherwise receptors will have no use.

[Fantasian]

SWIF is doing all the research he can now on dexamethasone, the side effects do seem unpleasent. Dexamethasone is available to SWIF as he has pharmacutical access, as are all presently prescribed Uk drugs.

Once SWIF has a better idea of his plan you mind if he runs it over with you. You seem very knowledgeable in the area.

[KyleM]

Yeah run it by, but keep in mind SWIM was unable to experiment personally with dex and can only go off of online research meaning SWIY would be the guinea pig on trying this one.

[Fantasian]

Originally Posted by KyleM

Yeah run it by, but keep in mind SWIM was unable to experiment personally with dex and can only go off of online research meaning SWIY would be the guinea pig on trying this one.

Yeah SWIF understands this, but from the limited medical knowledge he has he shouldnt be doing anything irreversable and this kind of treatment is done commonplace as a use for various things in the short term.

SWIF is so interested in this theory as his first 10 experiences with MDMA were Life changing and he believes this to be due to the Post traumatic stress disorder than he endured for 2 years prior to any use. SWIF went through a hell of alot including opiate withdrawal prior to any serotogenic drug use and he thinks possibly that would explain his unusually profound effects.

[KyleM]

Yeah of course, SWIM had depression for 7 years and took MDMA, it was absolutely outstanding. SWIM had other friends without that history try and while they seemed to enjoy it, most did not have the "nothing in life is better" experiences that SWIM enjoyed. SWIM did take notice that there were certain individuals that seemed to enjoy it most, ones that had a harder life before ever trying drugs.

Just think of drugs needing a natural opposite to allow its full potential. Examples being: someone with chronic pain will probably enjoy narcotics more than someone just trying to get high; someone who is chronically tired and slow cognitively will enjoy stimulants more than those without those problems. MDMA should be no different, it's the most effective antidepressant known to man.

A naturally depressed person will still have a large amount of serotonin relative to someone who has used MDMA, but will be lower than normal. A frequent MDMA user will most likely have such a low supply of serotonin that receptor number does not matter; this is a different case than natural depression and should be taken into consideration. SWIY will not have a roll like his first few unless the brain chemistry is similar, so SWIY should attempt to achieve a natural amount of serotonin storage, but below a naturally, non-depressed person. This would be difficult to calculate obviously.

Another misconception is that serotonin takes only 2 weeks to replenish after MDMA. That could not be more false. There is no way to measure how much serotonin is available in storage vesicles in a living human. The 2 weeks thing most likely means that synaptical serotonin levels along with serotonin metabolites are at or near control levels. MDMA needs serotonin from storage vesicles that probably built up their supply over years worth of creating it faster than it can be matabolized, therefore taking years to replenish the vesicles naturally.

[tinytom]

SWIM would like to share his best E experience

it was xmas day and he took 1 ecstasy tab he was going to a large dance event the next day so he took it easy.
swim could feel the effects but as he had been usin E quite alot recently he was not rolling hard.

swim got up the next day and went shopping he bought some 5-HTP he took 120mg at around 4pm o`clock
swim took another 120mg at around 6pm.

swim went to the rave he was in a slightly subdued state because of the night before but he ate some sugary sweets and a packet of crisps.

anyway

swim is still holding off as he wants to party well into the next day

at 10.30pm swim swallows one pill then a few mins later puts one between his gums and cheek
at around 12.30 swim takes another pill the last two took a while to hit but were coming on strong now.
3.00am swim takes another pill he is rolling very hard now he has a few interesting conversations with strangers, but its not till he gets into the taxi that swim realises how bad he is, swim cannot remember very much and cannot hold a conversation, swim tries to write but cant remember how, he can remember the phone number but cannot physically write it down.

when swim gets back to the appt he parties hard and smokes many joints.

swim then starts to hallucinate, not small ones either the toilet was crawlling with slugs,
a persons face melts and turns to maggots other people appear to be actually buzzing but under close inspection they were actually made out of tiny pins.

swim laughed at these sights he didnt have a care in the world,

he felt 4 years old again

it took him 45min to set up a joint.
he still could not hold a conversation and would randomly say phrases not relevent to the situation.

anyway got abit carried away there with swims story,

but this was swims best E experience.

could the reason of been because the receptors were down regulated?

did me preloading with 5-htp fool my head into thinking that seretonin was infact not released the night before?


swim is still trying to understand downregulation and the likes.

it has been 1 month since swims last roll he is going to do the exact same thing as last time, 1 pill on the friday, load with 5-htp that NIGHT then take 3-4 pills that night.

he will report back

[KyleM]

SWIM has just completed his experiment with St. John's Wort (hypericum) to upregulate cortical 5-HT2A and bring back magic.

Experiment went as follows: SWIM consumed 10 pills of SJW each morning and each night (6000mg/day) for 2 months. He discontinued use about 10 days prior to planned MDMA experience. Results were outstanding!

SWIM had minor luck 6 months ago using 12000mg piracetam/day for 1 month in returning the magic in which he struggled for 2 years to return.

This experiment however, resulted in a complete noticeable turnaround in his ability to roll. This was the best experience he has had since spring of 2005. He has failed to roll the slightest bit after almost 10 attempts over a 2-year span and now rolled so hard it was shocking. It was also the 1st time in years that SWIM received orgasmic sexual pleasure rushing in his brain and down his body, like his 1st few experiences. SWIM can credit it only to the SJW.

Reputation Comments on this post:

great experiment to undergo

[RaverHippie]

Congratulations for persistence. It will be interesting to see in the future, if spaced correctly, If SWIY could roll again normally or if all that SJW was only useful for one body-shaking orgasmic roll...

[experimenter]

Originally Posted by KyleM

SWIM has just completed his experiment with St. John's Wort (hypericum) to upregulate cortical 5-HT2A and bring back magic.

Experiment went as follows: SWIM consumed 10 pills of SJW each morning and each night (6000mg/day) for 2 months. He discontinued use about 10 days prior to planned MDMA experience. Results were outstanding!

SWIM had minor luck 6 months ago using 12000mg piracetam/day for 1 month in returning the magic in which he struggled for 2 years to return.

This experiment however, resulted in a complete noticeable turnaround in his ability to roll. This was the best experience he has had since spring of 2005. He has failed to roll the slightest bit after almost 10 attempts over a 2-year span and now rolled so hard it was shocking. It was also the 1st time in years that SWIM received orgasmic sexual pleasure rushing in his brain and down his body, like his 1st few experiences. SWIM can credit it only to the SJW.

SWIM wanted to thank you for the information in this thread, very interesting. But I have a question for you, I was doing some reading on seretonin syndrome on Wiki. http://en.wikipedia.org/wiki/Serotonin_syndrome for reference.

Now it says that seritonin syndrome can be contributed to by taking St. John's wart, reading that, I remebered your experience with upregulating with SJW. Were you worried that this much SJW may cause seritonin syndrome? Any idea how much SJW would cause seretonin syndrome.

Sorry if im compleyely off here flawed, is still trying learn the ins and outs of this subject. Thanks.

[Fantasian]

This brings real hope to some. SWIF will copy your experiment to see if it works for him too! Could you PM me the details of the supplementation for the 2months please so that SWIF may follow it relegiously. He'd prefer to try this before going to something like Dexamethasone.

To answer the question above Serotonin syndrome would only be a problem if one didnt discontinue the hypercium 2 weeks prior to adminstering the MDMA. I think.

[KyleM]

The idea is to use the SJW to upregulate receptors, then wait until it is completely out of SWIY's system, then take MDMA. SJW would interefere with it anyway if taken together, causing diminished effects for the MDMA.

Serotonin syndrome is caused by combining serotonergic drugs such as SSRIs and MAOIs, not by taking an excessive amount. There is probably not too much concern for SJW, but for now just avoid combining with other drugs that could fall in those categories. SWIM has taken 13,000mg of SJW at once with no symptoms of serotonin syndrome and another time took 10,000mg of 5-HTP with no symptoms as well. SWIM isn't necessarily endorsing that practice, but it just shows that they are relatively safe supplements.

[Fantasian]

Originally Posted by KyleM

SWIM has taken 13,000mg of SJW at once with no symptoms of serotonin syndrome and another time took 10,000mg of 5-HTP with no symptoms as well. SWIM isn't necessarily endorsing that practice, but it just shows that they are relatively safe supplements.

Was there any side effects noted with taking dosages this high or even as high as 6000 mgs a day. SWIF has will start tommorrow with the experiment to see if it can be repeated but would like to be aware of sides. Also SWIF takes a side supplement of ginseng but only in normal dosage, assuming this is ok to take as normal?

[KyleM]

With the 6000mg/day SWIM had minor photosensitivity which subsided after SJW supplementation ceased. With doses above 6000mg/day SWIY will probably get the shits, as did SWIM.

[Alfa]

Maybe this should be made clear in the rules then. Though I do not feel that this is something to give infractions for.
I just encounter a lot of problems from the use of such abbreviations. There was no offence meant, but at the same time it is something that needs to change on this board.

[KyleM]

"MDL 11,939 and SR 46349B are currently the only 5-HT2A receptor antagonists that have been demonstrated to up-regulate the 5-HT2A receptor in vivo"

The article goes much more into detail.
http://jpet.aspetjournals.org/cgi/co...ull/299/3/1066 (abstract)
http://www.neuroscience.iastate.edu/...utics_2001.pdf (full)

http://www.learnmem.org/cgi/content/full/10/5/355 (whole article is interesting, but find section called "Implications of Inverse Agonism for Associative Learning And Psychopathology" It discusses upregulation for MDL 11,939



The way that they will interfere with binding is that they are antagonists, meaning they bind to the receptor preventing biological effects from that receptor and reduce agonist effects at the receptor. So if one wanted to use these substances for MDMA, concurrent use would prevent or dampen the agonist effects of serotonin on the receptors involved. Just like an SSRI (a serotonin reuptake transporter antagonist) will prevent MDMA from binding to a transporter (SERT) because the SSRI is in the way of the MDMA molecule, just as the antagonist is in the way of the agonist trying to bind the the receptor (in layman's terms). If one were to utilize the upregulating effects, then discontinue use until the MDL 11,939 and/or SR 46349B was cleared out of SWIY's body, then theoretically SWIY should be left with increased receptors to be used by MDMA-induced serotonin.

Reputation Comments on this post:

Much obliged

[Alfa]

It would be very interesting to see if that theory is a reality. And also if there are any adverse effect to this.

Thanks for the info.

[KyleM]

SR46349B (eplivanserin) is currently being tested right now by Sanofi-Aventis research company (FDA phase 3) so we may see it available within the next couple years.

http://clinicaltrials.gov/show/NCT00253968

http://en.sanofi-aventis.com/index.asp (company's website)