Amphetamine

4-29-2021 links: Drugs reference: https://www.drugabuse.gov/news-events/nida-notes/2018/07/amphetamine-diverts-brains-path-to-maturity https://astralcodexten.substack.com/p/know-your-amphetamines

Amphetamine (Alpha-methyl-phenethylamine) #

• 
  • Levo is more physical/peripheral, dextro is mental.
• Amphetamine induces dopamine efflux through a dopamine transporter channel
• Regulation of Amphetamine-stimulated Dopamine Efflux by Protein Kinase Cβ
  • Increases surface expression of DAT and reverses their action to promote efflux of DA.
    • Amphetamines, unlike Methylphenidate or ritalin, also reverse the action of VMAT2, causing efflux/“open-to-out”.
    • A kinetic account for amphetamine-induced monoamine release
      • Amphetamine binds to DAT and is released in an inward conformation, and dopamine turns it right back around.
• Historically used for treating Depression. Makes sense; I mean think of Bupropion.
• Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain
  • Researchers have found that inhibiting the dopamine transporter (but not SLC18A2) will block the effects of amphetamine and cocaine; while, in another experiment, observing that disabling SLC18A2 (but not the dopamine transporter) prevents any notable action in test animals after amphetamine administration yet not cocaine administration. This suggests that amphetamine may be an atypical substrate with little to no ability to prevent dopamine reuptake via binding to the dopamine transporter but, instead, uses it to enter a neuron where it then interacts with SLC18A2 to induce efflux of dopamine from their vesicles into the cytoplasm whereupon dopamine transporters with amphetamine substrates attached move this recently liberated dopamine into the synaptic cleft
• Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine
  • Increased the number of dendritic branches and the density of dendritic spines on medium spiny neurons in the shell of the nucleus accumbens, and on apical dendrites of layer V pyramidal cells in the prefrontal cortex.
  • both drugs doubled the incidence of branched spines on medium spiny neurons
• Neurotoxic damage to dopamine axons/nerve endings recovers 100% after a few years. Serotonergic axons recover more slowly for unknown reasons.

Adderall #

• Composed of equal parts racemic amphetamine and dextroamphetamine, producing a 3:1 ratio between dextro and levo. CNS stimulant. Increases the activity of noradrenaline and dopamine in the brain Does not induce focus per se, but alertness.
• Sirsadalot: Low dose amphetamine is neurotoxic, causes severe downregulation
• https://old.reddit.com/r/Nootropics/comments/48nzl6/sensitizationupregulation_of_dopamine_via/
  • The dopamine-releasing effect of DRAs(/DRIs?) leads to the formation of synapses, providing a greater high in subsequent usage, for about a month. Then, physiological levels of dopamine won’t be able to reach these
  • JC says it desensitizes D2, but it’s D1 and D3 (may just be presynaptic) that get sensitized.
    • It does work. JC says 1.25-2.5 of dexamp (max 5mg, which is below the dose proven to be neurotoxic, but he never felt the need to go that high) works like 20 used to feel (after a few days of buildup). The supersensitivity does not last for months/years as per the rumors. Should be safe for up to a week straight. Then cycle off with bromantane (GDNF), PGC-1α activators. Most important thing is also protecting Complex I with pinealon, IPAM + NR, etc..
• Leo’s Biohacking Protocol To Make His Adderall Prescription More Effective
  • Leo and Longevity’s rationale for adderall is 5mg (never go above 10) of instant release with 2 days off a week minimum, ideally 3. And prefering high dextro. Used it for habituation, under the premise that the BDNF increase (there is a decrease at high(er) doses) from using will cause a positive reorganization of the brain, even after cessation.
  • Takes DHEA-S for Sigma Receptor upregulation to potentiate dopaminergic transmission. Also stacks with donepezil and Safinamide, a MAO-B inhibitor ans calcium channel inhibitor (to low E/I ratio).
  • Increase Neurogenesis while using amphetamines to protect from cell death.
• 2-FA is cleaner and has fewer side effects than dex. But the fluoridated analogues are just weak as hell. Most people on nootopics say the best functional RC stims would be 4f-Methylphenidate

Vyvanse #

Lisdexamphetamine, a dextroamphetamine prodrug.