MDMA doesn't make me happy, hyper and huggy anymore?

[Jabberwocky]

Scientific proof of isomer debate.....oh yea there is none.

I guess someone should tell these mice that:

[h=1]MDMA (N-methyl-3,4-methylenedioxyamphetamine) and its stereoisomers: Similarities and differences in behavioral effects in an automated activity apparatus in mice.[/h]
Abstract:

"Racemic MDMA (0.3 – 30 mg/kg), S(+)-MDMA (0.3 – 30 mg/kg), R(-)-MDMA (0.3 – 50 mg/kg) and saline vehicle (10 ml/kg) were comprehensively evaluated in fully automated and computer-integrated activity chambers, which were designed for mice, and provided a detailed analysis of the frequency, location, and/or duration of 18 different activities. The results indicated that MDMA and its isomers produced stimulation of motor actions, with S(+)-MDMA and (±)-MDMA usually being more potent than R(-)-MDMA in measures such as movement (time, distance, velocity), margin distance, rotation (clockwise and counterclockwise), and retraced activities. Interestingly, racemic MDMA appeared to exert a greater than expected potency and/or an enhanced effect on measures such as movement episodes, center actions (entries and distance), clockwise rotations, and jumps; actions that might be explained by additive or synergistic (i.e. potentiation) effects of the stereoisomers. In other measures, the enantiomers displayed different effects: S(+)-MDMA produced a preference to induce counterclockwise (versus clockwise) rotations, and each isomer exerted a different profile of effect on vertical activities and jumps. Furthermore, each isomer of MDMA appeared to attenuate the effect of its opposite enantiomer on some behaviors; antagonism effects that were surmised from a lack of expected activities by racemic MDMA. S(+)-MDMA (but not R(-)-MDMA), for example, produced an increase in vertical entries (rearing) and a preference to increase counterclockwise (versus clockwise) rotations; (±)-MDMA also should have induced such effects but did not. Apparently, R(-)-MDMA, when combined with S(+)-MDMA to form (±)-MDMA, prevented the appearance of those increases (from control) in activities. Similarly, R(-)-MDMA (but not S(+)-MDMA) produced increases in episodes (i.e. jumps) and vertical distance that racemic MDMA also should have, but were not, exhibited. Evidently, the presence of S(+)-MDMA in the racemic mixture inhibited the appearance of those increases (from control) in behavior. Taken together, the various and complex effects of MDMA and its stereoisomers are noted and a strategy is suggested for future studies that stresses the importance of steric effects and interplay, probable interaction(s) with various neurotransmitters, and interaction(s) with the particular behavioral or biological event (or action) being measured."


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994347/

 

[Black]

Actually, it is probably the racemic mixture differences in MDMA that cause the experiential differences (assuming real MDMA). More of the r-isomer and you get less stimulation and a more stoned effect, more s-isomer and you get much more stimulation.

Many people seem to forget that MDMA has stereo-isomers that act completely differently --- the r-isomer hits the 5HT2A receptors really hard, while the s-isomer is very stimulating. The s-isomer also has a much shorter half life than the r-isomer and is metabolized differently.

what makes you think that the pure enantiomers appear anywhere on the black market? all usual syntheses give the racemat, everyone knows that a single enantimer doesn't give the full effects and separating the enantiomers is a lot of work, needs special material and quite a bit more chemistry knowledge. it's not as easy as simply follow one of the recipes for synthesizing mdma you find on the internet.

 

[Jabberwocky]

what makes you think that the pure enantiomers appear anywhere on the black market? all usual syntheses give the racemat, everyone knows that a single enantimer doesn't give the full effects and separating the enantiomers is a lot of work, needs special material and quite a bit more chemistry knowledge. it's not as easy as simply follow one of the recipes for synthesizing mdma you find on the internet.

Different people metabolize the isomers differently.

 

[Jabberwocky]

what makes you think that the pure enantiomers appear anywhere on the black market? all usual syntheses give the racemat, everyone knows that a single enantimer doesn't give the full effects and separating the enantiomers is a lot of work, needs special material and quite a bit more chemistry knowledge. it's not as easy as simply follow one of the recipes for synthesizing mdma you find on the internet.

I never said pure enantiomers. I said differences in the racemic mix.

There are also a multitude of other factors that can contribute to different subjective feelings.

The OP indicated melty and eyes rolling back --- those are indicative of very high dose and/or very high response to MDMA -- real MDMA -- back in the heyday 1990-2000 there was a consistent meme that MDMA pills had heroin in them... nope that is just what real MDMA does at higher doses/higher response. (at 1.5-2.5 mg/kg)

there is another very important but little known fact about MDMA and it's active metabolites (and all amphetamines/methamphetamines) -- they are slightly basic in solution

This means if the urine is less acidic or more basic -- excretion of MDMA and metabolites in the urine can be reduced by more than an order of magnitude --> higher peak plasma and longer area under the curve

At a urine pH of 5.5 (common in soda drinkers and people who eat little veggies and lots of protein) -- MDMA and metabolites will be excreted much faster than normal

 

[MoodAltar]

I sure don't get the same rocket-like rush that I remember from my first experiences with MDMA in the early 1990s, but I wonder if my drug-adled brain has become low on neuro-trannies, or maybe I have just become jaded, desensitized. However,I found that with repeated use (often daily - up to 250 - 350 mg of nice crystaline sassafras) I lost that warm, serotonin "roll", and retained only the amphetamine aspect of the MDMA. That serotonin which the MDMA causes to flood into the brain needs to be replenished, and it don't seem to do so very quickly. MDMA is a wonderful drug when taken with adequate amounts of sleep, water, nourishment, and serotonin-replenishment intervals. Lack of serotonin once made me burst into tears at a mere diaper commercial - I mean....really. I'd almost rather be dope-sick than suffer through a week of low serotonin.

 

[MoodAltar]

nope that is just what real MDMA does at higher doses/higher response. (at 1.5-2.5 mg/kg)

Indeed, this has been my experience too. Also, Gawd knows what was in some o' them pressed tabs from them early 90s Raver daze...that's the stuff that I remember giving me that rocket-like rush - maybe a little "jib" was thrown in to light that fuse. Nowadays it's more the brown crystal that's around - the Sass'frass - the "real MDMA"

 

[Jabberwocky]

Indeed, this has been my experience too. Also, Gawd knows what was in some o' them pressed tabs from them early 90s Raver daze...that's the stuff that I remember giving me that rocket-like rush - maybe a little "jib" was thrown in to light that fuse. Nowadays it's more the brown crystal that's around - the Sass'frass - the "real MDMA"

Western Canada eh? British Columbia is where most of the real MDMA in north america is currently manufactured.

 

[Black]

I never said pure enantiomers. I said differences in the racemic mix.

but why would anyone go through all the trouble to get a slightly different ratio of the enantiomers when he could just use the racemate he already has? the procedures required to achieve a different ratio of enantiomers are the same you'd need for making pure enantiomers.

There are also a multitude of other factors that can contribute to different subjective feelings.

The OP indicated melty and eyes rolling back --- those are indicative of very high dose and/or very high response to MDMA -- real MDMA -- back in the heyday 1990-2000 there was a consistent meme that MDMA pills had heroin in them... nope that is just what real MDMA does at higher doses/higher response. (at 1.5-2.5 mg/kg)

agreed.

there is another very important but little known fact about MDMA and it's active metabolites (and all amphetamines/methamphetamines) -- they are slightly basic in solution

This means if the urine is less acidic or more basic -- excretion of MDMA and metabolites in the urine can be reduced by more than an order of magnitude --> higher peak plasma and longer area under the curve

At a urine pH of 5.5 (common in soda drinkers and people who eat little veggies and lots of protein) -- MDMA and metabolites will be excreted much faster than normal

yep, but i don't think it makes a difference. well, of course it does, but you get hugely diminishing returns anyway. especially towards the tail end of the roll.
just look at figure 2 of this paper. after a single 150mg dose you'll still have more mdma in your bloodstream after 10 hours than you'll have at the peak after a 100mg dose. yet you're not rolling at all 10h after a single 150mg dose. tachyphylaxis caused by (you're not gonna like this) serotonin depletion is a much bigger factor than differences in excretion due to pH.

 

[Jabberwocky]

yep, but i don't think it makes a difference. well, of course it does, but you get hugely diminishing returns anyway. especially towards the tail end of the roll.
just look at figure 2 of this paper. after a single 150mg dose you'll still have more mdma in your bloodstream after 10 hours than you'll have at the peak after a 100mg dose. yet you're not rolling at all 10h after a single 150mg dose. tachyphylaxis caused by (you're not gonna like this) serotonin depletion is a much bigger factor than differences in excretion due to pH.

1. Apparently you have never observed people extending a roll by 4 -6 hour spaced re-dosing.

2. If MDMA and metabolites are not excreted as normal -- because of a urine pH 6.8 or higher, effects may be significantly sustained and increased.

3. Like I have said before serotonin depletion is a myth -- do levels in the vesicle drop? sure, acutely after dosing -- by then the brain is bathed in it -- and continues to be for a long time; however one can drop a tab of acid or take 2-CB the day after MDMA use and have a completely unattenuated experience

 

[MoodAltar]

That's right - Vancouver Island in fact, 15 mins drive from the site of what was, in the 1980s, one of the largest MDA labs in the world. Drug culture is alive and well in BC - we certainly don't go without - first-rate heroin, reasonably clean methamp, molly, and all manner of psychs - incl wild mushrooms - and marijuana dispensaries on every corner. I even ran across some (supposedly) organic DMT recently.

 

[Mazzab]

Thanks for the Rat study from 9 years ago....

 

[nightElf]

I think this video gives you a good idea why you are feeling like this:

 

[Black]

1. Apparently you have never observed people extending a roll by 4 -6 hour spaced re-dosing.

2. If MDMA and metabolites are not excreted as normal -- because of a urine pH 6.8 or higher, effects may be significantly sustained and increased.

3. Like I have said before serotonin depletion is a myth -- do levels in the vesicle drop? sure, acutely after dosing -- by then the brain is bathed in it -- and continues to be for a long time; however one can drop a tab of acid or take 2-CB the day after MDMA use and have a completely unattenuated experience

1. of course you can redose, but that's beside the point.

2. not necessarily. mdma it a potent inhibitor of the enzymes that degrade it. that's a much more important factor here.

3. yes, acutely after dosing. that's what i mean here. 2c-b and lsd also seem to work at any time after rolling. not just 24h later.

 

[Jabberwocky]

2. not necessarily. mdma it a potent inhibitor of the enzymes that degrade it. that's a much more important factor here.

MDMA is not a significant MAO Inhibitor (although inhibition of MAO B protects against supposed neurotocity in rodents)

you mean synthesizes it (tryptophan hydroxylase)

only max 50% inhibition at 12.5 mg/kg dose intraperitoneal in rats

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1617070/

antioxidant supplementation seems to ameliorate the inhibition as it is due to oxidative mechanisms

 

[Brenner]

I still say its a difference between modern produced MDMA and older stuff (90s). Just look at the pills from back then, they only needed to contain around 60mg which lasted you all night, compared to todays 200+mg which only lasts about 3 hours...

 

[Jabberwocky]

I still say its a difference between modern produced MDMA and older stuff (90s). Just look at the pills from back then, they only needed to contain around 60mg which lasted you all night, compared to todays 200+mg which only lasts about 3 hours...

60 mg is barely over threshold effects -- not even 1 mg/kg

 

[scarlet_tunic]

Nightelf, I have a friend who rolls every day, and this video just made me so sad thinking about her
It actually makes me really sad for anyone with drug abuse problems.. I completely understand this innocence to experience journey that drugs create, whether you started with a glass of wine on Sundays only to end up with a five beers every night or a couple of 'fun' mollies only to end up rolling all of the time. And this isn't just about molly, even though you posted that video here. This is about ALL drugs, and the experience with drugs / alcohol (substance abuse in general) that many of us experience. Some people who come from cultures where intoxication isn't common or where it's against their religion will never undergo the journey this bird does, and it makes me think that our Western society is very indulgent. Thank you for posting that video... it made me sad as I drink this cup of kratom that I've been having every night for almost a week :[

I like how the bird goes from enjoying his life without the yellow substance and walking happily to the world becoming darker and darker, and him running faster and faster to reach it. How common is this story for many of us? From the first time we got drunk, we think 'wow, I want to do this again!' The human brain is so fallible, so liable to weakness.

This reminds me of William Blake's poetry, the Innocence to Experience series, where he talks about the journey from innocence to experience.. it's not specifically drug-related but it can definitely be used as a metaphor for all of our 'journeys' with drugs (whether we ended up in rehab or whether we ended up craving a beer every night or whether we wait anxiously for the weekend to come to get drunk with our friends).

But we shouldn't be sad... we've taken our brains to unique levels. We should just be wary that reality is NOT drugs.

 

[lifeisbeautiful]

Wonderful video, says it all.

 

[nightElf]

Nightelf, I have a friend who rolls every day, and this video just made me so sad thinking about her

Send this video to her
Perhaps it will help her see that what she's doing is destroying her life, and instead of being something fun, it will turn into nightmare, and it will be harder and harder to get out.

 

[scarlet_tunic]

nightElf, watching this video actually sort of changed my life... I realized I need to curb my kratom habit and stop doing it nightly. I realized that I love doing it so much, and that I just wait until the evening sometimes so I can do it. Today is my second night of not doing it and I feel fine Mind you, kratom is not nearly as addictive as other drugs.

I agree about my friend; she says it helps her with back pain, but wouldn't it also mess up your back?