atb-style up in this bitch.

i know this is probably disorganized, my apologies. i am inattentive.

doom3q:


I wonder how we would go about preventing this -- without sacrificing the focus.

The line right now is that methylphenidate (more zombifying than amphetamine for most?) tends to be a less effective treatment for the inattentives than amphetamine.

Is the stimulation of prefrontal focus, in some ways, in opposition to limbic creativity and joy? Clearly an oversimplification, but perhaps there is something there.

If anyone sees this post, I'd be interested in knowing what might have worked for them.

Frangible talks about the early limbic effects and mood-boost from amphetamine, which rapidly develops tolerance. He opposes this to his consideration of the therapeutic focusing action, which can last much longer and sensitize.

It's a weird thing. For me, I almost feel as if these early effects are more therapeutic. My focus seems to be less of a problem then my lack of motivation, joie de vivre. My zombie state. Those first few days are like an expansion of my whole being. Colors richer. It's not a straight mood lift, in the sense that sadness too becomes richer. Stronger emotions. A fuller life.

In my normal state, it's just blankness. And with methylphenidate, and eventually amphetamine in time, this problem remains, or may even be worsened. I can focus, but I also don't really give a shit. Creativity gone.

Depression, one might say, but the current lineup of antidepressants doesn't seem to work too well, for one reason or another.

Here again I get theoretical, but an issue that has been raised is the difference between those with hyperactive attention problems, and the inattentives. There's the British study which notes that hyperactivity may resolve with time, even aided by the stimulants, and this is seen in plastic changes to the brain. Those with hyperactivity may eventually develop the skills required to focus. Could we say that the deficit with hyperactives is prefrontal?

If we did, we might say that inattentives face a more troublesome problem. Their underdeveloped/understimulated structures, dopaminergic tone in deficit, may be more global. They lack limbic dopamine (I say dopamine, although it is more complex) as well as prefrontal dopamine. If hyperactives can train their focus, inattentives might have a harder time doing this, because there's still this problem of ... emptiness.

Right now on a few forums there's a revival of the discussion of the prevention of amphetamine tolerance via NMDA antagonists, like memantine. We have one guy who couldn't take amphetamine for more than two days without "poop-out", but has now taken it for many years with 30mg of nightly memantine (a dose that I would expect produced cognitive impairment, but it doesn't seem to be the case for him.)

I assume that what they're really referring to is the early mood-lift. Does memantine prevent tolerance to this effect? Some people are pointing to a relationship between glutamate overactivity and desensitization of dopamine receptors in the ventral tegmental area, a piece of the limbic system.

Again, I'm sorry if this doesn't make any sense, or is just completely stupid. I'm true that I'm in kind of a bad mood. I'm just fishing for thoughts and leads. I'm just a nerd dissatisfied with my condition, and complaining. Thoughts?

another effect of the early days of amphetamine is that my posts on the internet are a lot less irritatingly weak-willed

Am I the only one who has found a residual loss of oomph to life because of stimulant experimentation in the past and would like to get that oomph back even in daily life?

Yeah, i think thats possible. We are squeezing the dopamine out of the reward system like twisting a half-empty tube of toothpaste. Cant be good for the system in the long term.

What defines your 'stimulant experimentation'? Therapeutic dosages of pharmaceuticals or abuse dosages of pharmas and/or illicit substances?

http://en.wikipedia.org/wiki/Mesocortical_pathway should be some interesting reading for you.

Though what you describe sounds like comorbid depression to me.

That depends on your approach to supplementation and augmentation of lifestyle. I think there is good reason to adopt a supplement routine and several habits if you are going to be using stimulants like amphetamines daily--and if you do it correctly I don't think there is going to be much along the lines of long-term consequences.

Also, I think a large majority of problems people experience with loss of effect from amphetamine/consequences of use are from magnesium "deficiency". Not enough Mg = problems with Ca 2+ influx into NMDA receptors. Modern lifestyles are hard on Magnesium levels and stimulants only make it worse. Looking at the kind of people who routinely use/abuse stimulants and their lifestyles...yeah...these problems are on several levels of magnitude above even the average person (who probably doesn't have enough Mg either). Just a theory of mine though. (but I still experience the mood lift/ flow state thing for most of the day, a month after starting AMP, after reducing dosage to roughly 60% of what I started with.)

"
Right now on a few forums there's a revival of the discussion of the prevention of amphetamine tolerance via NMDA antagonists, like memantine. We have one guy who couldn't take amphetamine for more than two days without "poop-out", but has now taken it for many years with 30mg of nightly memantine (a dose that I would expect produced cognitive impairment, but it doesn't seem to be the case for him.)
"
As far as Memantine/DXM goes, if you feel comfortable taking NMDA antagonists every day go right ahead. I'll pass though.

Do explain more...



I agree with that, in theory. In practice, I have found that Magnesium supplementation fucks me up. It makes me real dull and sedated. Higher dosages that is. I took Jarrow Magnesium Optimizer once (100mg mg citrate + potassium + taurine) and that threw me for a loop. I felt sedated like I had a few drinks. Except... not as fun...

Same goes for other times Ive tried Mg supplementation. Blunted the hell outta me.

Any thoughts on that?

Magnesium supplementation is best, IMO after a nightly meal. Taking Mg with stims or when you are trying to do shit can be counterproductive. This is anecdotal and I can't really give an explanation in terms of plasma levels of Mg or metabolism but...yeah . YMMV, and how much and when you should be taking Mg is definitely something you have to experiment with.

As far as supplementation/etc. for stims, here are my general ideas:

-Mag

-Supps important to the adrenal system. Vitamins C, the Bs, etc. If you are stressed, especially chronically, or have negative schizoid symptoms then occasional DHEA can help.

Speaking of DHEA, big fan, but best used sparingly and dosed on an individual basis. There is a ton of interesting shit on how DHEA and DHEA-S interact with catecholamines, the limbic system and the sigma-1 receptor on pubmed. Also check out the DHEA and schizophrenia thread where Frangible and ATB rock out. Loosely speaking, it appears a generalization that stress and social defeat result in increased DHEA because it's effects help coping. It could be postulated that when the body does not/cannot produce enough DHEA in these cases, negative schizoid symptoms can result. Thus, why supplemental DHEA helps in these cases.

I also saw a study once (can't find it but will try to dig it up) where they studies the effects of AMP on DHEA and DHEA-S levels. Acute administration increased DHEA and DHEA-S but this effect diminished with time. Could it be that this is tied in with the above concepts of stress and DHEA secretion, and possible the diminishing of AMPs subjective 'good' effects with time? I dunno, but I think it is possible.


-A lot of these supps are important to dose at the correct time. Acidic supps and mag should be taken later in the day, because they will weaken your AMP effects (Mg will anecdotally, acidic supps will increase rate of AMP metabolism/secretion IIRC). This can be a good thing, as it can help prevent sleep disturbances, which is also VERY important here.

-Making sure plasma levels are as low as possible at bedtime. Acidic supps/food, dosing titration schedule, possible inclusion of a -racetam to enable a lowering of dosage are all things to consider here. Sleep is good for your brain, kids.

-NAC. As already mentioned, used with stimulants it is good for DAT and has anti-addictive/sensitization properties. I think it could be argued that this is not necessarily good if you have ADD, but I like it. Also a strong anti-oxidant, so any possible brain damage AMP causes is being combated here.

-Exercise, meditation, sleep. Goes without saying. Aerobic exercise and anaerobic exercise should be included to get the full range of benefits on the dopaminergic system etc.

Also, I know this is fast and loose to a certain extent. I will look up cites and be more specific with reasoning upon request, but I am very busy and posting on here when I want a break from studying

Also, as far as DHEA and stims go, every anecdotal report I have seen indicates a synergy and decreased crash.

Pregnenolone also has this "synergy". I'm interested to know more about NAC + amphetamine, I guess I'll have to try this out by myself. I just started taking magnesium again after running out of it for a while a do notice reduced tolerance to the more pleasant effects of amphetamine (I had drive to do maths earlier today, and was much more productive than usually). I heard about ppl mixing small doses of DXM with amphetamine to kill the tolerance from these effects.

From what I've seen Pregnenolone's synergy is likely due, at least to a large degree, to DHEA conversion.

I'm not too hot on DXM everyday. I think that making sure Mg is up to par is almost as good for tolerance reduction/prevention, and the idea of taking compounds like that everyday irks me.

Also, you won't have to bother with magnesium as much if you have a good diet. Eat a lot of spinach. Bannanas are also good food for people who use stimulants.

I've done meth twice, snorted, basically half a line the first time, a line and a half the next.

I've taken methylphenidate probably 40 different times over a span of 15 years (had a supply of it for a while). Never took more than maybe 20mg at one sitting.

I've taken mdma probably 8 times.

Adderall maybe six.

Ephedrine too many times to count although I can't go near the stuff anymore.


Anyhow, the last time I took methylphenidate I was at a new year's eve party and I remember distinctly feeling as if I wasn't high but like I was 12 again. There was a joy for life and a sense of excitement about things that I remember distinctly feeling almost all the time (actually spent a great deal of effort at times learning how to curb it so as to not seem like a spaz).

And now things are getting better and I'm done with experimenting aside from the occasional mdma with a loving partner sort of exception.

But there's a certain zeal I had for life that seems to be gone since using all this stuff. I know I know, consequences, right? What I'm wondering is if there's any way to get that back (I know Lior! CBT!! Gotcha!).

I think the amygdala might be key also. Like you´re a little too good at fear-processing ?

Well, there's always salvia.

Meh. Act fast though. Just got banned in my state 2 weeks ago dammit. I gotta drive all the way across the border and get a PO box if I want to get some.

Methylphenidate taken with alcohol produces ethylphenidate, which has noticeably different effects. I do think initial effects of MPH can give you that 'zest' for life, but it doesn't last for long.

I'd rather stay on MPH, despite the lack of thrill, as it's kept me calm and organized. MPH has been fantastic for keeping me on task, but it has done nothing to make me enjoy those tasks. Recently I've been combining other drugs to bring back some thrill so I can feel rewarded after completing goals. I'm using a mix of T3, 1,3dimethylamylamine, vitD3, and soy lecithin with decent success. It sounds like a mouthful but all can be obtained very cheaply.

I'd be curious to know exactly which subreceptors are responsible for attention, motivation, and pleasure. I think MPH does increase motivation&attention while reducing pleasure. Then comes the question if MPH is impairing endorphin neurotransmission.

I'm scared of being on an NMDA antagonist at all times too, valuing my cognitive abilities (lack thereof) more than most anything, but the interesting thing about memantine is that it's a "partial antagonist" -- unlike DXM and ketamine -- and the idea is that memantine will buffer excesses of glutamate transmission, but not compromise its healthy functioning.

I have a paper I should write but I'll respond to you guys soon, and update on the memantine-psychostimulant peeps I've been following.

Eclypz, I sort of doubt that (with what you described) your psychostimulant use is responsible for your symptoms, this far down the line ...

I actually really appreciated the afterglow from that stuff. Unfortunately I don't care for the actual effect. It reminds me of my old scotch guard experiments when I was a teen. Dysphoric.

But I decided last night actually to just smoke a little bitty bit, just enough to get the numb feeling and then see if it has any benefit today. I will probably repeat nightly.

Hmm.. some interesting stuff in this study:

http://www.ncbi.nlm.nih.gov/pubmed/1788402...Pubmed_RVDocSum

Antidepressant treatment can normalize adult behavioral deficits induced by early-life exposure to methylphenidate.
Bolaños CA, Willey MD, Maffeo ML, Powers KD, Kinka DW, Grausam KB, Henderson RP.

Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306-4301, USA. bolanos@psy.fsu.edu

BACKGROUND: Methylphenidate (MPH) is prescribed for the treatment of attention-deficit/hyperactivity disorder. Exposure to MPH before adulthood causes behavioral deficits later in life, including anxiety- and depression-like behaviors and decreased responding to natural and drug rewards. We examined the ability of fluoxetine (FLX), a selective serotonin reuptake blocker, to normalize these MPH-induced behavioral deficits. METHODS: Male rats received MPH (2.0 mg/kg) or saline (VEH) during preadolescence (postnatal day [PD] 20-35). When adults, rats were divided into groups receiving no treatment, acute or chronic FLX, and behavioral reactivity to several emotion-eliciting stimuli were assessed. RESULTS: The MPH-treated rats were significantly less responsive to natural (i.e., sucrose) and drug (i.e., morphine) rewards and more sensitive to stress- and anxiety-eliciting situations. These MPH-induced deficits were reversed by exposure to FLX. CONCLUSIONS: These results indicate that exposure to MPH during preadolescence leads to behavioral alterations that endure into adulthood and that these behavioral deficits can be normalized by antidepressant treatment. These results highlight the need for further research to better understand the effects of stimulants on the developing nervous system and the potential enduring effects resulting from early-life drug exposure.


This might or might not be dead on to your situation but it is something to think about. I started on MPH treatment when I was around 7 (I believe) and, now at 20, I do feel a little bit of anxiety and depression (nothing overwhelming but a low grade chronic amount). Decreased 'responding to natural and drug rewards are' are seemingly there, too.

But Ill be damned if I ever take Prozac for it. Too bad thats the only option theyve found/studied so far.



And another one for ya.

http://www.ncbi.nlm.nih.gov/pubmed/1467579...ed_Discovery_RA

Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood.
Bolaños CA, Barrot M, Berton O, Wallace-Black D, Nestler EJ.

Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.

BACKGROUND: Methylphenidate (MPH) is a psychomotor stimulant medication widely used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Given the extent of prescribed use of MPH, and because MPH interacts with the same brain pathways activated by drugs of abuse, most research has focused on assessing MPH's potential to alter an individual's risk for adult drug addiction. Data examining other potential long-term behavioral consequences of early MPH administration are lacking, however. METHODS: We investigated the long-term behavioral consequences of chronic administration of MPH (2.0 mg/kg) during pre- and periadolescent development in adult rats by assessing their behavioral reactivity to a variety of emotional stimuli. RESULTS: The MPH-treated animals were significantly less responsive to natural rewards such as sucrose, novelty-induced activity, and sex compared with vehicle-treated control animals. In contrast, MPH-treated animals were significantly more sensitive to stressful situations, showed increased anxiety-like behaviors, and had enhanced plasma levels of corticosterone. CONCLUSIONS: Chronic exposure to MPH during development leads to decreased sensitivity to rewarding stimuli and results in enhanced responsivity to aversive situations. These results highlight the need for further research to improve understanding of the effects of stimulants on the developing nervous system and the potential enduring effects resulting from early-life drug exposure.




Follow me on this idea though... Do you believe that decreased response to stimuli and being more sensitive to stressful situations leads one to be 'never satisfied' and, even more so, better responsive/adaptive/whatever-word-you-want-to-use to professional and work-related situations.... thus producing a fantastic businessman or entrepreneur or someone who be turned into chemically successful?

Another good one....
http://www.ncbi.nlm.nih.gov/pubmed/1830546...Pubmed_RVDocSum

Methylphenidate Disrupts Social Play Behavior in Adolescent Rats.
Vanderschuren LJ, Trezza V, Griffioen-Roose S, Schiepers OJ, Van Leeuwen N, De Vries TJ, Schoffelmeer AN.

[1] 1Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands [2] 2Department of Anatomy and Neurosciences, Center for Neurogenomics and Cognitive Research, VU University Medical Center, Amsterdam, The Netherlands.

Methylphenidate is the first-choice treatment for attention-deficit/hyperactivity disorder (ADHD), but its mechanism of action is incompletely understood. The cognitive effects of methylphenidate have been extensively studied, but little is known about its effects on spontaneous social behavior. During adolescence, rats display a characteristic, highly vigorous form of social behavior, termed social play behavior, which is of critical importance for social and cognitive development. We investigated the neurobehavioral mechanisms by which methylphenidate affects social play behavior in rats. Methylphenidate (0.3-3.0 mg/kg, s.c. or p.o.) abolished social play behavior, without altering general social interest. This effect of methylphenidate did not depend upon the baseline level of social play and was not secondary to changes in locomotion. Furthermore, the play-suppressant effect of methylphenidate was not subject to tolerance or sensitization. Methylphenidate blocked both the initiation to play and the responsivity to play initiation. The effect of methylphenidate was mimicked by the noradrenaline reuptake inhibitor atomoxetine, which is also used for the treatment of ADHD, and was blocked by an alpha-2 adrenoceptor antagonist. In addition, combined administration of subeffective doses of methylphenidate and atomoxetine suppressed social play. However, blockade of alpha-1 adrenoceptors, beta-adrenoceptors, or dopamine receptors did not alter the effect of methylphenidate. These data show that methylphenidate selectively blocks the most vigorous part of the behavioral repertoire of adolescent rats through a noradrenergic mechanism. We suggest that the effect of methylphenidate on social play is a reflection of its therapeutic effect in ADHD, that is, improved behavioral inhibition. However, given the importance of social play for development, these findings may also indicate an adverse side effect of methylphenidate.

Damn, in the very first study I posted regarding Prozac, in the discussion they go so far as to even say:

"Within this context, it is tempting to suggest that early-life exposure to psychostimulants could serve as a potential model for depression."

Damn. Im torn to see what Prozac treatment might do to me after reading that study. It fits me to a T (MPH treatment in early life, low anxiety and depression in later life, low feelings of natural reward, higher sensitivity to anxious situations versus relaxing ones).

interesting stuff.

Yes, but rats drink sugar water over cocaine, even if they were addicted to the cocaine first, so what the hell do rats know about dopaminergics?

You are not a rat.

Yeah, thats the one drawback to my findings.

And where do you get the sugar water v cocaine theory? I mean, sugar water is some good shit

http://www.plosone.org/article/fetchArticl...al.pone.0000698