So, to briefly summarize: Been off stimulants (adderall) for 10 years, started again to complete boring exam via a horribly-written text and am on disability for ADHD. Current regimen is ALA, vitamins C and E, ashwaghanda, Magnesium Glycinate, Alprazolam, Inderal, and Memantine (currently titrating to 20mg/day from 15), oh and 5-HTP. Initial dosage was only 5mg dex, titrated now to prescribed dosage of 10mg morning/5 afternoon, with frequent days off, as I don't wish to waste the 10 years I was off stimulants, though I would like to add that I consider ADHD a disorder of society, yet my efforts off stimulants have failed.
As suggested in "Treatment of the Psychostimulant-Sensitized Animal Model of Schizophrenia" (retrievable here: http://www.sendspace.com/file/w2vf6v I titrated up to about 10 mg/day memantine before beginning dex, which I know is a low dose of memantine. Am now at 15mg, 10 in morning, 5 evening. However, my problems are not with tolerance, but with sensitization.
I will feel the calm focus for a fleeting moment when the dex kicks in, but it is soon replaced with what I can only describe as "hypofrontality". Signs are flattened affect, what I feel are indistinguishable from the negative symptoms of schizophrenia, and visual anomalies; I know no one's out to get me nor do I see things that aren't real, rather, I experience phenomenon analogous to staring at a light-bulb and the vision remaining when you shift focus; Some paragraphs on the computer seem to be highlighted with faint color, but when I look at the paragraph this disappears. Additionally, I initially feel the impulse to engage in reasonable tasks (studying for an exam), but after a few seconds of this feeling, I can only stare at the page like a zombie. I feel a "heaviness" frontally. Like I can't contextualize the information, maybe a circuit with the hippocampus is not right along with something frontal, perhaps mediated by raphe nuclei and 5-ht3? Again, my sleep is adequate, although my circadian cycle is currently precessing to join the normal world.
I feel something is amiss with my serotonin, and am pushing to have a 5-HT3 antagonist prescribed. The visuals are like what I've heard is experienced in LSD, that is, I will have healthy sleep, and yet I feel, even on this low dose of dex, with my sensitization, something is amiss with my 5-HT signaling, due to the sensitization, which persists after 10 years. I have taken 5-HTP but the only agent that can alleviate this is alprazolam. Then (with alprazolam) on the same low dose of dex(10 mgs or 5 mgs, summed to a maximum of 15 mgs per "on" day (I intersperse with at least 2 off days), I clean &etc, but studying is pointless. The need for the BZD prohibits my use of the stimulant for it's intended purpose: studying and memorizing boring shit. Moreover, when the dex works, my body temperature increases, which has been demonstrated to be caused by, but not only by so far as I know, 5-HT3 agonism, and an increased startle response, and tachyardia in dogs administered a 5-HT3 agoninst (blocked by 5 day zofran pretreatment). I also have tinnitus on the dex, although I restate that I take a low dose (15 mgs max/day with at least two day breaks every week). Even on the low dose, without the benzos, I feel psychotically depressed, like agitated, crying . . as newer generations of antipsychotics target the 5-HT system, I feel confident that a 5-HT3 antagonist (Zofran or Ondansetron) may help, but I appeal to this board for input or alternatives on this ambition.
I respect the purpose of ADD, so I will summarize my questions thus and any moderator has my permission to move to the forum he or she deems most fitting.
My questions are:
1.) Could the glycinate anion in the Mg supplement be interfering with the NMDA blockage/attenuation of tolerance. (glycine is a co-factor for NMDA permeability)
2.) Referring to the above-referenced "Treatment of the Psychostimulant-Sensitized Animal Model of Schizophrenia", memantine along with the stimulant will reverse tolerance, and, so much as we can tell, cure schizophrenia in rats. This paper went to to demonstrate, again in rats, that co-administration of a 5-HT3 antagonist blocks EXPRESSION of sensitization to stimulants- not reversal, but blockade. Sensitization and schizophrenia display similar results in mice testing. Memantine, in vitro, is an antagonist of 5-HT3 with an affinity roughly equal to it's affinity at NMDA channels, though this equal affinity is debated in vivo. I have a feeling in vivo, it is insignificant.
2a.) Do my peers feel I could be on the right track with a 5-ht3 antagonist (zofran). Is this readily obtained for idiopathic nausea, which I do technically have right now? My Pdoc hasn't capitulated and I want it now.
-and-
2b.) Do my peers feel my antioxidant regimen is sufficient to counter oxidative stress,
which I do feel I am more susceptible to, being sensitized and having that sensitization last 10 years?
If you would like some abstracts, I will amend this upon request, however I presume you all frequent pubmed often and are familiar with the 5-HT3 subtype.
Thank You Most Sincerely,
Monoamine
As suggested in "Treatment of the Psychostimulant-Sensitized Animal Model of Schizophrenia" (retrievable here: http://www.sendspace.com/file/w2vf6v I titrated up to about 10 mg/day memantine before beginning dex, which I know is a low dose of memantine. Am now at 15mg, 10 in morning, 5 evening. However, my problems are not with tolerance, but with sensitization.
I will feel the calm focus for a fleeting moment when the dex kicks in, but it is soon replaced with what I can only describe as "hypofrontality". Signs are flattened affect, what I feel are indistinguishable from the negative symptoms of schizophrenia, and visual anomalies; I know no one's out to get me nor do I see things that aren't real, rather, I experience phenomenon analogous to staring at a light-bulb and the vision remaining when you shift focus; Some paragraphs on the computer seem to be highlighted with faint color, but when I look at the paragraph this disappears. Additionally, I initially feel the impulse to engage in reasonable tasks (studying for an exam), but after a few seconds of this feeling, I can only stare at the page like a zombie. I feel a "heaviness" frontally. Like I can't contextualize the information, maybe a circuit with the hippocampus is not right along with something frontal, perhaps mediated by raphe nuclei and 5-ht3? Again, my sleep is adequate, although my circadian cycle is currently precessing to join the normal world.
I feel something is amiss with my serotonin, and am pushing to have a 5-HT3 antagonist prescribed. The visuals are like what I've heard is experienced in LSD, that is, I will have healthy sleep, and yet I feel, even on this low dose of dex, with my sensitization, something is amiss with my 5-HT signaling, due to the sensitization, which persists after 10 years. I have taken 5-HTP but the only agent that can alleviate this is alprazolam. Then (with alprazolam) on the same low dose of dex(10 mgs or 5 mgs, summed to a maximum of 15 mgs per "on" day (I intersperse with at least 2 off days), I clean &etc, but studying is pointless. The need for the BZD prohibits my use of the stimulant for it's intended purpose: studying and memorizing boring shit. Moreover, when the dex works, my body temperature increases, which has been demonstrated to be caused by, but not only by so far as I know, 5-HT3 agonism, and an increased startle response, and tachyardia in dogs administered a 5-HT3 agoninst (blocked by 5 day zofran pretreatment). I also have tinnitus on the dex, although I restate that I take a low dose (15 mgs max/day with at least two day breaks every week). Even on the low dose, without the benzos, I feel psychotically depressed, like agitated, crying . . as newer generations of antipsychotics target the 5-HT system, I feel confident that a 5-HT3 antagonist (Zofran or Ondansetron) may help, but I appeal to this board for input or alternatives on this ambition.
I respect the purpose of ADD, so I will summarize my questions thus and any moderator has my permission to move to the forum he or she deems most fitting.
My questions are:
1.) Could the glycinate anion in the Mg supplement be interfering with the NMDA blockage/attenuation of tolerance. (glycine is a co-factor for NMDA permeability)
2.) Referring to the above-referenced "Treatment of the Psychostimulant-Sensitized Animal Model of Schizophrenia", memantine along with the stimulant will reverse tolerance, and, so much as we can tell, cure schizophrenia in rats. This paper went to to demonstrate, again in rats, that co-administration of a 5-HT3 antagonist blocks EXPRESSION of sensitization to stimulants- not reversal, but blockade. Sensitization and schizophrenia display similar results in mice testing. Memantine, in vitro, is an antagonist of 5-HT3 with an affinity roughly equal to it's affinity at NMDA channels, though this equal affinity is debated in vivo. I have a feeling in vivo, it is insignificant.
2a.) Do my peers feel I could be on the right track with a 5-ht3 antagonist (zofran). Is this readily obtained for idiopathic nausea, which I do technically have right now? My Pdoc hasn't capitulated and I want it now.
-and-
2b.) Do my peers feel my antioxidant regimen is sufficient to counter oxidative stress,
which I do feel I am more susceptible to, being sensitized and having that sensitization last 10 years?
3.) Am I ignoring my adrenals, insulin, other biochemical effects and looking to closely at neurotransmission?
If you would like some abstracts, I will amend this upon request, however I presume you all frequent pubmed often and are familiar with the 5-HT3 subtype.
Thank You Most Sincerely,
Monoamine
