As a long-term, responsible user of low-dose stimulants, I've come to the realization that the benefit they add to my life (in productivity and focus) is significant. It seems as though at responsible doses, they can have profoundly positive effects, however I know that nothing is without a downside.
Many studies have proven a solid link between meth/d/l-amphetamine neurotoxicity at high and/or recreational doses, however I have seen very few studies detailing the long-term effects of repeated, low-dose administration.
There is already an excellent thread on this board detailing many options for reducing amphetamine-related neurotoxicity, however I'm hoping this thread will veer more towards the holistic perspective in developing a routine of supplements and habits that will allow for long-term therapeutic use of amphetamines without causing permanent and irreversible brain damage.
Objectives
- Achieve the long-term benefits of therapeutic amphetamine administration without the neurotoxic implications
- Prevent neurotransmitter down-regulation to avoid any increase in dose or dosing frequency
Regimen: 10mg Adderall (mixed Amp. salts) [or] 5mg Desoxyn (methamphetamine) no more than 5 days per week
Diet: Mostly fresh and raw foods, along with lots of good monounsaturated fats to ensure a good balance of Omega-3/6/9s; I try to get most of my essential nutrients and vitamins from food as this is wholly more effective than supplements whenever possible (Avocados, blueberries, mangoes, eggs, white fish, salmon, grass-fed beef, onions, & spinach, pecans, brazil nuts, flax seed, etc.)
Supplements:
- Magnesium Glycinate (800mg/day) - A bio-available form of magnesium which acts as an NMDA antagonist and (I believe--can't find the source now) regulates the Ca+ channels to prevent dopamine auto-oxidation and excitotoxicity in the pre-synaptic neuron.
- PQQ (20mg/day) - A quinone that supposedly increases the rate of mitochondrial biogenesis and function.
- Methylphenidate [Ritalin] (10mg/day) - A DA D2 antagonist which has proven to reduce the negative effects of VMAT-2 redistribution by preventing the amphetamine-induced decreases in vesicular DA uptake.
- Cerebrolysin (5ml x 20 days every 2 months) - A powerful amino-based compound extracted from the pig brain which seems to have universally neuroprotective and restorative effects, as well as significant (though temporary) increases in NGF & BDNF expression.
- MK801 (NMDA Antagonist) - A powerful NMDA antagonist that appears to prevent glutamate-induced hyperthermia (http://www.sciencedi...02839089290104W). Perhaps by preventing the glutamate-induced activation of the AMPA & NMDA receptors, the Ca2+ influx to the DAergic neuron can be mitigated and thus prevent mitochondrial damage and excitotoxicity. (http://www.ncbi.nlm....5?dopt=Abstract)
- SCH23390 (D1 Receptor Antagonist) - A D1 receptor antagonist that appears to prevent the DAergic deficits caused by repeated amphetamine administration... This seems both intriguing, as well as strange given that D1 receptors are localized to the post-synaptic neurons of the striatum (http://www.ncbi.nlm....7?dopt=Abstract), (http://www.ncbi.nlm....1?dopt=Abstract)
- nNOS Inhibitors - Pretreatment of mice with nNOS inhibitors has shown to prevent persistent DA deficits caused by amphetamine administration. (http://www.ncbi.nlm....7?dopt=Abstract), (http://www.ncbi.nlm....5?dopt=Abstract)
- Eticlopride (D2 Receptor Antagonist) - Seems to counteract amphetamine-induced hyperthermia which is an important component of DAergic neurotoxicity (http://www.ncbi.nlm....3?dopt=Abstract)
Questions for the Board:
Unfortunately, while I have done copious amounts of research, my medical knowledge is still rather myopic and limited. I'm hoping some of the more knowledgeable members on the board will be able to answer and address the following questions
- Of the experimental compounds above (that I have yet to try), are there any contraindications or dangerous interactions that I may have overlooked?
- Are the doses of the supplements I am currently taking sufficient, and in proper balance? (specifically in regards to the methylphenidate:amphetamine ratio)
- Of the supplements I am currently taking, which would be classified as preventative & useful in pretreatment (prior to administration of amphetamines), and which are primarily reparative (to restore neuronal function and reverse deficits after administration)
- MK801 appears to be a non-competitive NMDA antagonist while LY274614 is a competitive agonist; Both seem to be effective in preventing DA depletion when administered shortly before & after amphetamines, however can someone illuminate the differences between competitive/non-competitive NMDA antagonists, and what implications these have in practical terms?
Edited by lmlj, 19 February 2012 - 08:58 PM.
