Methylphenidate has something else ..

[resorcinol]

.. in common with cocaine besides also being a DNRI stimulant

*Note: (cocaine is more euphoric most likely because 1)it enters the brain more quickly 2)it also mildly blocks the serotonin transporter; MPH does not 3)it has significantly less body load than MPH and 4)although DNRI action predominates with MPH, it also shows MINOR signs of having the amphetaminergic action of releasing DA and NE although the DNRI mechanism clearly dominates -- and it's conjectured that mixing these two mechanisms can result in drug oddities (ie, common sense would tell you that a DNRI stimulant would BLOCK a DA/NE releaser stimulant, but that does not appear to be entirely true in actual practice since DA/NE releasers don't require the transporter to enter the cell; diffusion directly into the cell and into the storage vesicles for DA and NE is another mechanism - the result is that having a DNRI stimulant present in serum results in a dose of a DA & NE releaser stimulant having less psychoactive effect at any given dose than it would if given alone, but its effects are not even close to entirely blocked [in contrast to SSRIs which DO very significantly block MDMAs 5-HT release mechanism, but keep in mind, SSRIs bind very very tightly to the 5-HT transporter while DNRIs tend to bind to DAT and NET more weakly, giving some amphetamine molecules a chance to sneak in ... and EVEN with SSRIs a large enough MDMA dose will elicit a mild entactogen/empathogen effect, the marker of 5HT release, showing that some MDMA sneaks in through the transporter / displaces the SSRI when MDMA conc is high in the CNS and probably that diffusion accross the cell membrane occurs with MDMA too as a secondary mech of entry into the sending serotonin neuron]). The slight ampetaminergic, minor secondary mech of action for causing psychomotor stimulation, is likely partially responsible for the relative unpredictability in MPH liking from person to person ... these two mechs of action which intuitively seem incompatible don't really cancel each other like they would if DAT and NET transporter plugs totally made the transporters inaccesable to a drug with amphetaminergic-like DA & NE release through transporter reversal. The DAT and NET aren't plugged so strongly and as such a DA & NE releaser will indeed have additive effects when taken with a DNRI, but the added effect won't be the full stimulatory potential of the DA & NE releaser alone (ie 10 mg adderall will only add say 5 mg worth of adderall stimulation when taken with a DNRI). Since MPH has the amphetaminergic method of stimulation as a minor secondary mech of action, shit can get weird with MPH and that may be behind the widely varying opinions on the drug. We can all agree that it's no amphetamine or cocaine and should probably be CIII and not CII, but the thing is in some individuals (like me) it actually deserves the CII ranking because, while short acting compared to Adderall, I can get just as speeded up and euphoric if I take enough.

It is less pro-social than Adderall, but so is cocaine -- I believe the lack of serotonergic RELEASE with both COC and MPH (the SRI of coke does not count for social empathetic feelings since for some reason SRI does NOT create the warm, lovey feelings that 5HT release does -- basically 5HT is an oddball monoamine compared to DA and NE. With DNRI drugs a different euphoric stimulation (subjectively) than DA & NE releasers is elicited, but the stimulant effect is still euphoric. This is not so with selective SRIs -- the do NOT cause effects anything REMOTELY like MDMA, and I'm PERSONALLY still not sure why this is. In fact, SSRIs make me feel awful, and MDMA sounds wonderful. Granted, MDMA very-probably would not be what it is if it did not also release DA, but drugs very selective for 5HT (serotonin) release like MDEA STILL cause empathogenic / entactongenic effects that are pleasureable (just less so than those of MDMA). This is something I'd love to get to the bottom of, and if anyone who REALLY knows their pharmacology has an idea, let me hear it because I'm bothered by this).

Back to my point: cocaine and MPH are both DNRI type stimulants, but they have another somewhat uncommon trait in common. MPH, like cocaine, has an ester bond in its structure that is very vulnerable to metabolic attack. In fact, the ester bond in both is methanol bonded by dehydration to a carboxylic acid group in the molecule:

Cocaine:
http://upload.wikimedia.org/wikipedia/commons/thumb/9/90/Cocaine-2D-skeletal.svg/220px-Cocaine-2D-skeletal.svg.png

Methylphenidate:
http://upload.wikimedia.org/wikipedia/commons/thumb/7/7b/Methylphenidate-2D-skeletal.svg/175px-Methylphenidate-2D-skeletal.svg.png

You can clearly see a carboxylic acid group in the structure of both that has been esterified with methanol -- resulting in a methyl group attached to the single bonded oxygen as occurs in methanol - organic acid esters. This feature is the REASON why both cocaine and MPH have no legs. Since cocaine actually has ANOTHER ester bond (between the benzoic acid and methylecognine [the "alcohol"] it has two weak spots that are readily attacked by metabolism and has an even shorter T-1/2 than methylphenidate. More weak spots for metabolism to deactivate the drug compound by super-easy reactions, the less time it will continue to have the desireable effects. MPH is hydrolyzed to methanol (very very small amounts, in the mgs as we dose MPH in the mgs even in extreme abuse, so it's not like drinking methanol where the desperate drink 80000 mg of methanol) and "ritalinic acid" (its structure is just like the above minus the methyl group on the C-O-Me part of the ester moiety and plus a hydrogen in place of the Me group to give a normal carboxylic acid group, and ritalinic acid is inactive, that methyl group is essential for activity as a DNRI).

Cocaine is metabolized by hydrolysis into methanol (again, tiny amounts, even extreme abuse like crack binges will never get harmful levels of methanol metabolite into the bloodstream), benzoyl-ecognine, ecognine, and benzoic acid. It has more metabolites because it's hydrolyzed at two different spots.

Finally to my point. Cocaine and MPH have this methyl ester in common, and have similar behavior when alchohol (ethanol, drinking kind, booze) is consumed alongside either drug. When this happens, transesterification enzymes in the liver give the OH in ethanol to the leaving methyl group of cocaine or MPH, the ethyl group which results that is freed of its -OH replaces the methyl group that was esterified onto the carboxyl group of either drug. The result is that the C-O-Me moiety is changed to a C-O-Et moiety. This occurs when ethanol and either cocaine or methylphenidate are present in the serum at the same time, especially when high doses of both are present (ethanol and COC or MPH).

Almost every druggie has heard that this happens with cocaine / crack. They call this ethyl ester "cocaethylene" and it is more potent and more selective for DAT than cocaine itself (unfortunately, more cardiotoxic than cocaine itself also).

What some may not know is this also happens with methylphenidate. The product is ethylphenidate and is formed in exactly the same way as cocaethylene. More interestingly, the pharmacodynamic differences are similar too. Like cocaethylene v cocaine, EPH vs MPH is more selective for DAT and slightly more potent. The one difference is that neither MPH or EPH are cardiotoxic in the way that cocaine is (cocaine blocks sodium channels, disrupting normal sinus heart ryhthm -- neither MPH nor EPH are local anaesthetics that block sodium channels). All stimulants are cardiotoxic in that they cause sinus tachycardia or even ventricular tachycardia in overdose though.

So MPH and booze go hand-in-hand much in the way cocaine and booze do (however I do not recommend either drug be used with booze ... this little transesterification makes for a fun time, but the combo is dangerous for either of these stimulants and booze -- booze make it harder to tell when you've had too much stimulant and your heart will not forgive you for your brain getting mixed up due to upper-downer mixes).

Final note: Dexmethylphenidate is a better drug than racemic methylphenidate. If you don't like Ritalin, don't just write off Focalin. I'm sure it's still no cocaine, but I can say having tried both that the chirally pure d-MPH is MUCH cleaner a stim than d,l-MPH. 2x more potent, significantly lower body load, and more euphoric (I feel this is because the unwanted peripheral ephinephrine and norepinephrine released by the nasty l-MPH isomer which cause the nasty body load aren't there to detract from the central DNRI euphoria of the d-MPH, which is the actual active drug -- l-MPH doesn't bind DAT or NET, all it does is cause unpleasant side effects). These phenethylamine stimulants, with about all of them, the levo isomer is just bad news; it's side effects heaven. I gather that l-MPH is particularly nasty (l-amp is useless but maybe not as nasty as l-MPH as few people complain about its presence in adderall) ... l-propylhexedrine is a nasty one too; if that Benzedrex cotton was not racemic but rather pure d-propylhexedrine I don't think it would stay OTC very long at all. I'd take d-MPH over cocaine even if (and it surely is... it's the prototype DNRI, only starting to be challenged by RC DNRI substances) it is better still than d-MPH because cocaine is 1)Just too damn short a high due to the rapid metabolic attack 2)The expense. WTF on charging prices like 40 bucks a gram for a drug that is dosed in 50 mg lines that last a half hour each ... talk about throwing money away; coke wins the grand prize in blowing lots of money for little reward.

To each his own though -- I just find the whole idea of cocaine (at these prices at least) absurd. I've heard it's even more astronomically expensive in europe and australia (makes since, harder to smuggle in since there's no land route / short sea route like there is for the USA). I'd probably snort a free line if somebody offered just to add to my resume, but I'd never buy the shit. D-mph certianly doesn't last all that long either, but it's dirt cheap and lasts 2 hr v. 1/2 hour.

[EleusisII]

Not much of a discussion here ;) Just wanted to say that I sure enjoy your little drug-symposiums!

[Paregoric Kid]

l-methylphenidate does bind to norepinephrine and very slightly to dopamine receptors. obviously, like levo-amphetamines, it produces more PNS effects than CNS effects.
and while ritalin is good, focalin is definitely better. although with the racemic mix the l-methylphenidate might slow down the metabolism of d-methylphenidate which might make it last longer.

[Morphus]

I would agree cocaine is more euphoric than methylphenidate when the cocaine is injected or smoked, and the mph is eaten; however I think the euphoria of eaten mph is about the same, qualitatively and quantitatively versus snorted cocaine. BUT, the crash/comedown of mph is much worse than that of snorted cocaine, but then again when one snorts cocaine it only lasts about an hour, while a single dose of mph lasts about 2.5 hours before the crash starts. YMMV

[resorcinol]

I've never had cocaine so I can't agree, disagree, or compare & contrast my experiences.

I will say though, that pharmacologically, it makes sense that some individuals who enjoy cocaine also enjoy MPH, and some who enjoy cocaine do not like MPH very much. It might partially reduce to how much an individual needs "rushiness" in their stimulant high and how much they need an effect on all three monoamines.

Cocaine is primarily a DNRI, but also a weak SRI. While SRI is NOT associated with feelings that are pleasant (SSRIs are NOT recreational in any way) -- it may be that a small amount of SRI activity ALONG WITH a much stronger NRI and DRI activity increases the pleasurable sensations by boosing sociability and perhaps smoothing out the pure dopaminergic "MORE MORE MORE" feelings, which are completely selfish --- very PURE stimulants are nothing like MDMA as they cause more feelings that are selfish than feelings that are empathetic. I'd even say that OPIOIDS cause more feelings that could be considered "loved up" feelings than very PURE stimulants like dextroamphetamine or dextromethylphenidate. This is why I don't agree with considering MDMA a "stimulant" at all --- it's its own class, entactogen/empathogen (with other members in the class; like MDMC/methylone/bk-MDMA, MDA, MDEA, etc).

As for the other factor, rushiness, cocaine enters the brain faster than methylphenidate, although they BOTH enter the brain rapidly (which is why they're both capable of causing an INTENSELY pleasurable rush when injected via IV... for methylphenidate, particularly the pure d-MPH isomer ... I've heard that IV Focalin has a rush so intense that only cocaine beats it from quite a few people ... this may be why Focalin is CII --- orally maybe Adderall is an overall more addictive high than Focalin, but for IV use, I think Focalin kicks Adderall's ass [and even crystal methamphetamine's ass also] since amphetamine type stimulants do not cause a tremendous, OH MY FUCKING HOLY SHIT THIS FEELS GOOOOODDDDD!!!!!, RUSH ... while DNRI stimulants that rapidly enter the brain DO cause this type of intense rush (cocaine and dexmethylphenidate in particular are rated as the most intense rushes of all when used intraveinously). IMO, when we start talking about a RUSH part of a high, the line between STIMULANT and OPIOID effects becomes very blurred as BOTH are EXTREMELY intense feelings of pleasure BURSTING throughout the mind and body, often described as being accompanied by roaring, distorted sounds and ringing ears. I actually believe that opioid and stimulant rushes are BOTH caused by RAPID increases in neuronal action potential firing in the nucleus accumbens due to rapidly increasing dopamine release in this region ... the mechanisms for causing dopamine to rapidly accumulate in the synapses of the NAc differ, but from the perspective of the receiving neurons in the NAc I don't think it matters during the "RUSH" part of an opioid or DNRI stimulant high. After the rush settles down, the differences between the highs become clear: opioids are .. well .. opioids, neither stimulants nor depressants IMO. DNRIs become clearly "stimulant" when the rush is finished. IMO, amphetamines, even methamphetamine, cannot cause a rush such as that of cocaine, dexmethylphenidate, or any strong rapid acting opioid -- even when used via IV -- because amphetamines take longer to start heaving dopamine into the synapses in the NAc (they .. amphetamines .. have to bind DAT and unbind it once permitted into the cell at which point dopamine present is accidentally bound and permitted to enter the synapse ... DAT is tricked to work in reverse but this takes more time than DNRIs or opioids [I'll explain in a sec] .. the second thing amphetamines do, which is diffuse directly into dopamine neurons across the cell membrane and into the storage vesicles for dopamine, where they take up space and force dopamine out of the neuron into the synapse, also takes time [not a whole lot of time, and neither does the DAT reversal take a whole lot of time, but it takes too long to provide an INTENSE rush]).

With DNRI uppers (provided they enter the brain very quickly due to high lipophilicity, like cocaine and d-MPH) the mechanism is different. When injected by IV, a HUGE amount of DNRI is suddenly plugging up dopamine transporters in the NAc (which prevents re-uptake of dopamine). Action potentials normally occur quite frequently, and since the blockade of DAT is rapid and sudden for drugs like IV COC or MPH, dopamine accumulates in the NAc synapses incredibly quickly, far more quickly than in the blink of an eye does dopamine accumulate to incredibly high levels. Unlike where amphetamine has to molecule by molecule displace dopamine into the synapse, causing a steady, slower come up --- lipophilic DNRIs plug DAT and let normal action potentials do the rest of the work --- before the body can even go "WTF, DUDE?" a shitload of action potentials have fired and only a fraction of the dopamine normally re-uptaken back into the sending neuron is re-uptaken --- so in sharp contrast to the molecule by molecule slow displacement steady come-up of amphetamines, lipophilic DNRIs result in dopamine levels rising staggeringly in the blink of an eye .. many many dopamine molecules accumulate all at once in the synapse ... this causes an intense rush. After the rush is over though, the highs are similar. Eventually with DNRIs each action potential just releases very little dopamine as most of it is already in the synapse stimulating receiving NAc neurons. Likewise with amphetamine, at the "peak", amphetamine has displaced almost all of the dopamine into the synapses of the NAc where it stimulates receiving NAc neurons constantly --- and the storage vesicles for dopamine are filled with amphetamine.

For opioids, they cause an intense rush (provided they're powerful enough as mu agonists and lipophilic enough to enter the brain rapidly) for a reason similar to that of DNRIs -- they, like DNRIs and unlike amphetamines, cause a rapid rise in dopamine concentration in NAc synapses very very rapidly. The whole bind the mu receptor --> reduce GABA(B) mediated inhibition of dopaminergic neuron firing from VTA to NAc --> subsequent surge in number or action potentials reaching the NAc (far above normal) --> subsequent surge in amount of dopamine being dumped into synapse due to excessive action potentials : this all happens just as quickly (almost ... not quite as quickly .... perhaps this is why DNRIs such as cocaine and dexmethylphenidate have the most intense drug rushes although some opioids come close) or almost as quickly as with DNRIs. Instead of relying on normal action potentials and plugging up DAT to suddenly cause a tremendous many many molecule of dopamine at once increase in dopamine in NAc synapses (whole cargos of dopamine at once accumulate, whereas with amphetamine it's more of an exchange, one amphet goes in, one dopamine comes out... course it happens faster than one at a time, much faster, but not in whole "action potential clusters" like with DNRIs... or opioids), opioids simply increase, dramatically, the NUMBER of action potentials reaching the NAc. The dramatically increased number of action potentials reaching the NAc causes many many more "lots" of dopamine to be released into the synapse .... more lots and much faster than DAT can get close to mopping up ... causing, like DNRIs, a rapid, sudden, massive amount of dopamine stimulating receiving neurons' dopamine receptors in the NAc. Rushes are all about sudden dramatic bursts of dopaminergic activity in the NAc, emphasis on sudden -- the dopamine neurotransmission must increase very very rapidly as with lipophilic DNRIs and opioids. Amphetamines cause a high just as pleasant as opioids or DNRI stimulants but they don't increase the amount of dopamine signalling in the NAc QUICKLY enough to cause a "rush" ... at least not an INTENSE one. Amp and methamp are still said to have a "rush" by many users.... but they don't have a "rush" the way DNRIs like cocaine and d-MPH, or opioids like heroin or hydromorphone ... have. Amphetamine "rushes" are more like just a very rapid onset of effects that is more intense than the overall high, whereas DNRI and opioid rushes are a distinct phase of the high, separate from the rest of the high, and quite different feeling ... much more intense than just "rapid onset" of effects that are "more intense than the rest of the high" like with amphetamines. True rushes are something I've only experienced by taking LARGE hits of fentanyl, smoked, at once (this was VERY dangeous, I was at a bad point in my life, I could have easily OD'd taking huge rips of fent like that).... and it was the most intesnely pleasurable thing I've ever felt in my life. It was "sorta" like an orgasm but different.... it was all over the body physically (like every cell was cumming) and accompanied by an overwhelming euphoric emotional blast of joy that isn't really there during an orgasm. So it's different. Also, my rush from a huge hit of smoked fent was probably a MILD rush, albeit a true rush .... IV heroin, cocaine, d-MPH, hydromorphone, oxymorphone, and ketobemidone are probably indescribably pleasurable beyond the imagination.

[insanesteveo]

id read more of your posts if there werent so many abbreviations and acronyms. and they werent so long. and i knew what the hell you were talking about.


but i applaud you for trying!!!

[resorcinol]

I'm trying to make more posts & threads that aren't so technical in nature (unless its necessary for a HR posts), but for the ones that are really technical, I don't mind if only a few folks read it and less actually understand what I'm trying to say. When I post these type of posts I'm more doing it because I like talking about nerdy stuff relating to drugs and opiophile is one of the few places where it's OK to be nerdy about OMG DRUGS!

I'm trying though to make other more interesting posts for more folks (or at least will start trying). One example is ... I thought the hypothetical nightmare drug-test thread would be pretty fun for people to ponder about (scary as hell though... I sure hope that tests like the one I described never become common).

Edit: Seriously though, opiophile is fucking amazing. It's just about the ONLY place where people are accepting of everything about me, which is a breath of fresh air among a stifling environment of prejudice and lack of empathy for others.

Only at opiophile is everybody OK that I've / I'm
1)used psychoactive drugs and I'm against the federal war on drugs / prohibition (this one would obviously be totally cool on a HR drug forum)
2)Nerdy (including with drugs)
3)a homosexual guy
4)an atheist
5)a bit of a loner

There are other places where a few of those are accepted, but opiophile is the only place where ALL of those things are OK. This forum is truly a group of genuinely accepting and open minded individuals. And we use drugs (so government, we're scum, eh ... yet we accept people of all different stripes more readily than the vast majority of other groups in the population .... that sounds really scummy doesn't it. Ugh, the gov't pisses me off).

[insanesteveo]

OMG!!!! YOURE GAY!?!?!?!?!?!

just kidding.

but yea, i hear ya. i actually understood your reply in that drug test thread. its more just the acronyms and abbreviations you use. i have no idea what they are referring to so i cant continue reading and have it make much sense. like HR, i dont know what you mean by that. human resources?

im not saying you should type every word out, just type the whole word and then in parentheses write the acronym or abbreviation you are going to use. that would make it much easier, for me at least.

[Morphus]

Ya know, I've heard people try to liken this or that drugs effects to orgasm, and it has never made sense to me. I have injected alot of drugs with intense rushes and at no time did I think the drug rush was anything like an orgasm. In my humble opinion, the orgasm "high" is incredible, a PURE pleasure bomb going off in your head, and no hangover, no crash either. Only down side is it doesn't last too long.

[Morphus]

Resorcinal I think you oughtta try coke at least a couple times for analysis and comparison to your other (extensive) stimulant experiences. If you don't shoot then try smoking some base, I'd be interested how you'd compare the experience to all your other detailed accounts.

[Restharrow]

There is something about Ritalin that I like more than any other stimulant. I love to eat good food and other stims. take away my appetite AND my appreciation for food and the cooking process.

Also I HATE to nod. I want to be wide awake when I take my meds -- reading, TV watching, web surfing, etc. Sleeping after admin. of opiates is a waste. I also think that stimulants INCREASE the pain-killing effect of opiates.

I have more control over re-dosing with Ritalin than Dexedrine.

I also enjoy many of Resorcinal's threads. I do not respond to them because of lack of chemical knowledge.

I do have a question: Offered the choice of 5mg. of Dexmethylphinadate or 20 mg. or Ritalin (both always taken orally), which would you choose. I am in a little bit of that situation now with my pain doctor.

What say you Resorc.?? D-methylphin or DL Methylphin. -- in larger quanity.

Thanks!
Will

[Restharrow]

Edit: Seriously though, opiophile is fucking amazing. It's just about the ONLY place where people are accepting of everything about me, which is a breath of fresh air among a stifling environment of prejudice and lack of empathy for others.
Its really nice to have some place in the world where you can be yourself and NOT have to defend that.

[Thebane]

I appreciate you taking the time to type all this out Res.. Even though I might not have time to read every word of every one of your posts, at least I know where to find a ton of good info on focalin, ritalin, etc.. If I ever happen to stumble upon them. Right now all I have is adderall sadly.