Returning the "magic" - The Quest

[SpinKing]

As well as Upregulating (increasing the number of 5 HT2 receptors, which seems extremely undesirable), can the sensitivity of the individual receptors (or the pathways leading the serotonin to the receptor) be altered?

SpinKing added 23 Minutes and 26 Seconds later...

http://www.nevdgp.org.au/info/topics/img/fig1_f.jpg
If you could downregulate in some parts of the brain, would a prominence of higher brain functions be felt more regularly?
could learned control of raphe nuclei affect distribution of serotonin in brain and alter natural emphasis?
http://en.wikipedia.org/wiki/Raphe_nuclei

[KyleM]

Originally Posted by SpinKing

As well as Upregulating (increasing the number of 5 HT2 receptors, which seems extremely undesirable), can the sensitivity of the individual receptors (or the pathways leading the serotonin to the receptor) be altered?

SpinKing added 23 Minutes and 26 Seconds later...

http://www.nevdgp.org.au/info/topics/img/fig1_f.jpg
If you could downregulate in some parts of the brain, would a prominence of higher brain functions be felt more regularly?
could learned control of raphe nuclei affect distribution of serotonin in brain and alter natural emphasis?
http://en.wikipedia.org/wiki/Raphe_nuclei

The sensitivity of an individual receptor most likely cannot be altered and it's best not to think of it that way. It's better to think of it in terms of how sensitive the entire neuron is to serotonin, which is determined by the number of receptors.

It depends on what receptors are downregulated and where they are located. Lower or higher brain functions could be experienced depending on that.

In regards to distribution of serotonin, I don't know how learned control could be possible, it seems the brain merely reacts to what happens to you in life and what is absorbed into your body. The rest is most likely genetics.

[Synesthesiac]

It aint just us humans, scientists have very recently discovered that mice lose 'the magic' if they use it too much too.


Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats - Progress in Neuro, Volume 32, issue 4, 15 May 2008

Abstract

The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4 × 5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT1A agonist 8-OH-DPAT (250 µg/kg but not 125 µg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT1A receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA.

So they still don't quite know the answer, they find no difference to the main 5-HT1A receptor system, but still find a lower social effect after frequent use, so they it suggests that "other neuroadaptations may underlie the lasting social deficits caused by MDMA" If only they were allowed to self administer and study themselves, they would certainly know what the magic that gets lost with frequent use is then. And no doubt they'd be a hell of a lot more up for finding it out

Swim finds the only way to fully return the magic is to use three monthly, one month isn't even enough for swim, probably because he abused in the past. Swim finds that using MDMA after doing too regularly you still feel great, you get all the physical aspects, you do increase your confidence, want to dance your ass off, but theres just something missing from your buzz, that complete utter breakdown of all social barriers does not seem to happen, and its a much less spiritual experience than if you haven't done it in ages. So something in your brain is definately still replenishing over this time.

Just thought; anyone tried preloding with melatonin? or anyone tried preloading with oxytocin (the loooove drug)?



Synesthesiac added 19 Minutes and 16 Seconds later...

Just read another rather interesting observation from a similar recent MDMA study. But this one looks at oxytocin as a player too, as opposed to purely the serotogenic HT receptors.

Neural correlates of MDMA (“Ecstasy”)-induced social interaction in rats - Social Neuroscience, 23 May 2008

...snip...

These results indicate that a moderate dose of MDMA given in a social context causes considerably greater brain activation than the same dose given to solitary rats. This activation involves specific neural circuits that are known to regulate affiliative behavior, perhaps by modulating the incentive value of social stimuli. A possible role for the neuropeptide oxytocin in mediating the prosocial effects of MDMA is discussed.

Its known that peoples brain only releases oxytocin when around people they have warm feelings for, which becomes very strong when people are in love and almost stops completely around people who hate each other, and it especially releases it after touch with another person. Probably why touching feels so good on MDMA. When on MD you are generally happy to be around people, so more oxcytocin is released, making it a far more enjoyable experience.

The oxytocin system isn't really my area, so if anyone here (kyle?) has any ideas about what you would need to take to replenish this system, I think this is a very good contendor for returning the magic.



Synesthesiac added 12 Minutes and 7 Seconds later...

They just keep coming. I'm thinking oxytocin could be the magic molecule (would be spirit, but thats already taken). This one looks like its govenment funded by the title, but may still have some good info.

From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use? - British Journal of Pharmacology (2008)

Oxytocin regulates social affiliation and social recognition in many species and modulates anxiety, mood and aggression. Recent evidence suggests that popular party drugs such as MDMA and gamma-hydroxybutyrate (GHB) may preferentially activate brain oxytocin systems to produce their characteristic prosocial and prosexual effects. Oxytocin interacts with the mesolimbic dopamine system to facilitate sexual and social behaviour, and this oxytocin-dopamine interaction may also influence the acquisition and expression of drug-seeking behaviour. An increasing body of evidence from animal models suggests that even brief exposure to drugs such as MDMA, cannabinoids, methamphetamine and phencyclidine can cause long lasting deficits in social behaviour. We discuss preliminary evidence that these adverse effects may reflect long-term neuroadaptations in brain oxytocin systems. Laboratory studies and preliminary clinical studies also indicate that raising brain oxytocin levels may ameliorate acute drug withdrawal symptoms. It is concluded that oxytocin may play an important, yet largely unexplored, role in drug addiction. Greater understanding of this role may ultimately lead to novel therapeutics for addiction that can improve mood and facilitate the recovery of persons with drug use disorders.

I'll see if I have access to these when I can use a suitable computer tomorrow. At the moment I'm only picking out abstracts, but theres no doubt some pretty damn interesting stuff in these new studies now MDMA is being studied much more openly than years back.

Reputation Comments on this post:

great information

[Fantasian]

As you said above time will actually eventually sort out most imbalances so whatever happens there is the hope that the effects wont be too long lasting. Someone else may be able to shed some more light on what you call the enhanced communication on MDMA however i think more than likely your not talking about cognative enhancement your actually talking about the increased empathy while on MDMA which directly relates to oxytocin release. THe so called love hormone, which is what causes MDMA uses to feel a closeness or connection to each other. But so far i know of nothing except abstinance that will upregulate the oxytocin receptor. In my mind this is why people sometimes fall in and out of love and after a period of not loving anyone people can fall in love at first sight. (I dont know of any data proving this but it just makes sense to me ))

Nice info on inositol too.

[chaos69]

i just thought i'd report on swiC's results with this. he tried the SJW thing for about 5 weeks using 3000mg in the morning and at night (6000mg total daily) and about three weeks in he began a 750mg aniracetam twice daily with choline also. around three weeks after finishing the SJW (was intending on two but thats how it played out) and while continuing with the aniracetam he tried a (presumablely) MDMA pill which he was told by freinds to be of good quality. much to his surprise it still did not work! he tried two things similtaniously as well as an unplanned or expected personal tradjedy during the treatment, which can also apparanetly unregulate receptors and still no success. all he got was a very mild body feeling and slight closeness to others but nothing compared to what it used to like for him. no euphoric waves at all. he doesn't know if the pills were just shit but others that had them that night seemed pretty happy with them. at least one person that had them that night did actually say that they were probably onlt 7 out of 10 pills but still. he did get eye wobbles though which he can't remember getting for awhile. perhaps the SJW he used was a shit brand or prehaps he needs to repeat the SJW for longer. he's tried 5-HTP preloading in the past with no success either. any ideas?

[Fantasian]

Re Chaos:

Thats very interesting and shows possibly that the method isnt as effective as it first seemed. Did SWIY find the 3 weeks of abstinance were quite depressing and upsetting? While using the SJW how did SWIY feel? IT's also worth noting that ANY 5HTP use, while enhancing recovery speed does undo much of the good work that SJW does. Had SWIY used 5HTP for long periods prior to this experiment or directly before the use of MDMA?

Re KomodoMK:

Abstinance is definately part of the process, and it's good to see that SWIY's experience supports this. Frequent use of MDMA will definately cause desensitization and the methods listed previously will as i have said before not enable a user to use every week or even every month effectively.

[KyleM]

After the experiment, when SWIY takes MDMA, the experiment may not show it's full benefit. SWIM mentioned previously that for some reason if he takes MDMA a week later also (back to back weeks) without any supplementation before the 2nd session, the benefit of the SJW experiment is evident.

So it should be like this: SJW supplementation for however long, then 7-10 days no supplementation, then MDMA, then wait 7 days, then MDMA.

SWIM does not know why it works like this, but that's how it seems to be working for some reason. SWIM normally doesn't recommend back to back dosing, but this is the one exception, and this should include months of abstinence beforehand and months afteward. It does work

[KomodoMK]

SWIM lost the magic for (ab)using the drug too much, to the point of acute short term memory loss. SWIM (for that reason) abstained, and after a year his memory not only returned to normal but improved.

SWIM decided to try MDMA again and the magic had certainly come back!!! SWIM prefers MDMA crystals to pills because it's less adulterated.

[Panthers007]

Yes - stop taking anything/everything for a considerable period of time. SWIM can't restore brain-chemistry to normal by adding more foreign molecules into the mix - only make it different. MDMA works fine with a "normal" brain. Tell SWIM to knock off all other molecules for at least 2 months.

[chaos69]

Originally Posted by Fantasian

Thats very interesting and shows possibly that the method isnt as effective as it first seemed. Did SWIY find the 3 weeks of abstinance were quite depressing and upsetting? While using the SJW how did SWIY feel? IT's also worth noting that ANY 5HTP use, while enhancing recovery speed does undo much of the good work that SJW does. Had SWIY used 5HTP for long periods prior to this experiment or directly before the use of MDMA?

when swiC first started the SJW he noticed a significant increase in his social anxiety and anxiety in general and felt occasional hot flushes and tingleing on his skin which was weird. he did have some depression during (and still does) but the three weeks after was no worse for depression however during the SJW threatment he did suffer the loss of someone very close to him so hard to say what caused the depression. he did notice the increase anxeity from the SJW not go away quickly after stopping the SJW. swiC did use some 5-htp for about three days in the week before the MDMA but not on the day or the day before either.

Originally Posted by Panthers007

Yes - stop taking anything/everything for a considerable period of time. SWIM can't restore brain-chemistry to normal by adding more foreign molecules into the mix - only make it different. MDMA works fine with a "normal" brain. Tell SWIM to knock off all other molecules for at least 2 months.

swiC has had periods of a few months with out drugs and still no increase in MDMA effects. whats worse is that MDMA didn't gradually stop working. it just suddenly stopped.

he will try the SJW for a longer period next time with a different brand without aniracetam or anything else and hopefully it will work.

[Fantasian]

Originally Posted by Anon

hi.

i was wondering if SWIFantasian has had any experience with any of the MDMA like RC's such as methylone or mephedrone during their period of lost MDMA magic and if so if this loss also applies to these too.

thanks

Hi, this question could have been asked on the forum so that others may benefit from the answer so ill copy and paste it to there but in case you want to stay anonomous i'll leave your name out of it.

Some of the RC's like M1 and so on will definately change in effect, SWIF has experienced both of the ones you mention above and he never really found much 'magic' so to speak. Possibly due to him using them much after he had experimented with various serotogenic drugs. SWIF just felt while the experience was enjoyable it didnt share the same empathic qualities of MDMA.

Even so M1, MDMA and it's counterparts exert a 3 fold effect on serotonin, dopamine and acetylcholine however M1's action is more spread between the three than MDMA's domination of serotonin therefore if the serotogenic receptors become desensitized it's effects will remain more like the original because the effects on dopamine and acetylcholine remain. That said still the empathic euphoria and other feelings associated with excess serotonin will diminish and regaining receptor density can be achieved by some of the methods listed previously, not that i condone them as i dont think it's worth it.

Feel free to ask anything further if you dont understand or want something explained more clearly.

[KomodoMK]

Little fishy will be posting a huge and in depth report on 4-Methlmethcathinone (or Mephedrone as various forums seem to have named it) very soon. The first part of the report on low test dosages is already been wrote but will not be posted until the main experience has been completed.

So far it seems a far cry from being anything like MDMA, as the MDMA seems so much more powerful, most likely due to the reason Fantasian posted above. Will report back on the larger dosages when my little fishy passes on the report.

KomodoMK added 1438 Minutes and 0 Seconds later...

The report can now be found here:

http://www.drugs-forum.com/forum/sho...6&postcount=65

[Junket]

Swim used to do ecstasty alot, and then one day he stopped for about three months, upon deciding to do it again, it just wasn't the same.

He got high, but he wasn't rolling tough like he used to. He tried with a couple other pills that others really liked, but the magic simply didn't return.

[KomodoMK]

Good informational post Synesthesiac, made very interesting reading. Thanks.

Romie1985: My little fishy abused for a long period (>1.5 year) and then suffered the loss of magic, short term memory impairment and only amphetamine like effects. He abstained for over a year and his memory improved (actually seems better than before) and the magic did come back, but only to an extent.

Little fishy thinks that a crucial part of the 'magic' is the learning phase of using MDMA. Once you know what to expect and understand the drug inside out the novelty wears off, and as with anything, over a prolonged period of time it becomes normal.

Little fishy would go as far as to say that many people may never experience the same level of magic or around those first 5 times without a truly exceptional mindset, set and setting.

[Fantasian]

Re: Synesthesiac - Im almost certain oxytocin has a massive part to play and somewhere else on the forum SWIM's are experimenting with that exact hormone. In terms of messing with it in the brain though is a very shifty area. If it truely is the hormone that affects bonding, love and association then a tolerance to that would truely be horrible wouldnt it? Because of the secondary oxytocin release in MDMA it's possible that people become tolerant to oxytocin itself in a similar way one can become tolerant to serotonin. Either way it's not something to which SWIF wants to play with but any experience at altering sensativity to oxytocin would be welcome assuming it wasnt at the cost of ones health.

One of the biggest problems that SWIF has read in terms of oxytocin administration directly is that it doesnt pass the blood brain barrier.

[chaos69]

just thought i'd share swiC's recent experience. swiC was out on the weekend and was offered a pill. he thought he'd give it and shot and this time it did work! not to the full extent with euphoric head rushes but the loved up feelings and body feelings were there which was much much more than he has got since his magic loss. also others that had the same pills also didn't get head rushes so its likely that was just the strength of the pills. swiC has not had any SJW in between MDMA trials but did change from aniracetam to piracetam. also since swiC's last experiment (the unsucessful one) he has found out that the people that were strongly effected by the pills that night had actually double dropped! so there's a fair chance they weren't not the best of pills to start with.

swiC plans to acquire known strong pills or MDMA powder and try this again some time soon and also plans to try the SJW thing again sometime after new years most likely for a full 8 weeks this time.

[tupac15]

SWIM took 5-htp once or twice daily for a month and a week bfore i rolled at a rave and honeslty it didnt really work. i took 5 ills and i did not get the same effects as the first time. but, 5htp defintley changed my emotions. im a more happier person. im gonna try the hypercium diet before i go to together as one.

[Synesthesiac]

Originally Posted by tupac15

SWIM took 5-htp once or twice daily for a month and a week bfore i rolled at a rave and honeslty it didnt really work.

swim found this too. If anything the 5-htp blunted the buzz.

Swim is currently taking tianeptine, which he thinks may work in enhancing the MDMA buzz. SSRI's like prozac are known to completely blunt the Buzz of MDMA, but tianeptine is a somewhat paradixical antidepressant as it does the exact opposite to SSRI's, instead of inhibiting the uptake of serotonin it is a selective serotonin uptake enhancer. Swim also hasn't done any MDMA in two months, so he'll probably get a nice buzz anyway. He'll try another dose within a week of the first to see if theres any restoration of the magic over a quicker time than usual.

[Fantasian]

@Synesthesiac - Thats an interesting concept and I've never considered tianeptine as an enhancer, tbh i know very little about it, please report results when you can and Ill try and do some more reading

@tupac - I think if one is going to use 5HTP to supplement their roll then there are very specific ways to do it, but Im in no doubt that it definately causes a faster tolerance effect due to downregulation. As does using it on a supplementary basis too. There is a thread somewhere where SWIF used it to potentiate MDMA and it worked very sucessfully but once again uses much higher doses than on the side of the bottle. If i remember correctly Kylem also has some experience with this. When taken in much smaller 'normal' dosages it just blunts the high because of receptor downregulatory effects.

[scored]

Swim is enjoying this thread, so much identification and possible solutions, but he feels his jury is still out on this one. Came close last week on a rectal admin experiment with a tiny bit of mud.

Can't help feeling there are other factors to recreate that magic, certianly state of mind at the onsett, company sharing the experience, obviously quality of said substances. Swim is sure that the chemicals are not the same as the late 80's/90's guess this backed up by every one he talks to. Back then you popped a pill and that was it, twisted for most of the night, it's hard to compare the drugs of today to an experience of nearly 20 years ago, it's all different, well it is for my monkey,..... yet alcohol, the taste, the hit, the rush, the feeling, the meaningless dribble that has not changed in the test of time. Coke? not the same, though swim hasn't been too thorough there, he means freebase or IV.
Not complaining, coming back to rec drug use after 10 or so year break he is enjoying it..... just looking for a bit of that 'Summer of love' feeling

[RaverHippie]

Originally Posted by tupac15

SWIM took 5-htp once or twice daily for a month and a week bfore i rolled at a rave and honeslty it didnt really work. i took 5 ills and i did not get the same effects as the first time. but, 5htp defintley changed my emotions. im a more happier person. im gonna try the hypercium diet before i go to together as one.

Please go check out this thread. http://www.drugs-forum.co.uk/forum/s...ad.php?t=37552 It may help explaining the SWIM thing to you better since you attempted but almost got it right. Because in your post it says you consumed 5 pills containing illegal chemicals and I'm sure that didn't happen since illegal, incriminating activities aren't allowed to be discussed here.

5HTP is often touted as an herbal remedy for depression and it seems like it worked for SWIY.

[Fantasian]

@scored - The tolerance of posative effects of MDMA cant really be compared to cocaine or alcohol for a whole variety of reasons. I do accept that setting, enviornment, company and potency of drug all play an integral role in the experience but regardless these variables alone arn't the only reason. Users of MDMA have been struggling with the problem of a loss of magic through the 80 and 90's, it isnt a new phenomenon, it's also fair to assume people have been in a brilliant environment with great company and very potent pure MDMA and still notice a lack of what they once had. If this problem was very isolated and linked to smaller groups it would be debatable but the way that nearly all users eventually notice a decrease in euphoric effects over time, especially those that use regularly would suggest there is something chemical, biological and physiological in it's nature. Of course noone really knows as this is all trial and speculation otherwise this thread wouldnt exist

[inorbit]

What I have found that seems to work well for Marmoset, is a combination of different pills and potions as a ‘harm minimisation programme’. In turn it does seem to help with returning the magic.
Here’s my list of my ‘harm minimisation’ ingredients.

5htp (helps to ‘top up’ serotonin)
Macuna Pruriens (full of l-dopa, helps to ‘top up’ dopamine)
Vitamin B6 (needed to metabolise 5htp and l-dopa)
Choline (helps to ‘top up’ acetylcholine)
Inositol (helps to modulate serotonin activity)
Piracetam (improves blood flow within the brain and improves communication between the left and right hemispheres)

Piracetam is widely documented as an agent that can be used to improve the effectiveness of mdma and other similar substances and, reduce the comedown. In my experience it does work quite well. Follow this link to find out more http://www.drugs-forum.com/forum/showthread.php?t=5593

[RaverHippie]

^^Actually there's a good thread in the nootropics forum describing Choline as not being metabolized into acetylcholine like one would think. http://www.drugs-forum.com/forum/showthread.php?t=74167

[jamboree117]

Another important and well documented mechanism of drug tolerance that one should consider is CYP enzyme up regulation. MDMA is primarily metabolized by the 2D6 enzyme so constant use will likely induce your body to create more of that enzyme. So the more one uses it, the more 2D6 their body will produce, and the faster that enzyme will break down MDMA.

Its possible that St. Johns wort makes one roll harder not because of seretonin receptor upregulation but because of its effects on CYP enzymes(it inhibits many of them). One can try taking SJW 1 hour before rolling(but no SJW during the week prior) and if they roll harder then it is because of CYP enzymes. Seretonin receptor upregulation would require days(at the minimum) of continuous SJW use.

A possible experiment one could run would be to take Ranitidine(Zantac) with MDMA. Ranitidine is a 2D6 inhibitor so it would increase blood levels of MDMA and as an added bonus it would reduce stomach acidity which should increase absorption(since MDMA is a weak base<---might wanna check that).

As a last side note: SWIM hates to be preachy but SWIM would feel irresponsible not to recommend everyone to limit MDMA to <6 per year(SWIM tries to stay <2) because it makes ones neuronal dendrites shrink and most but not all of them will grow back. Chronic use compounds this effect. Take vitamin C or other antioxidants when rolling. SSRI's have a neuroprotective effect with MDMA but will make you roll less so is good for neurotic ppl.

Reputation Comments on this post:

	informative, thanks
	Some good ideas...