nothinghere @offlabelhuman

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George Ferman @Helios_Movement

2 weeks ago

Having ADHD (or general anhedonia) and not trying even 10-15mg of zinc in the morning is mind-blowing. Besides the fact that a lot of people with ADHD (and anhedonia) are deficient, zinc acts as a non-competitive blocker of the human dopamine transporter (DAT). Normally, after dopamine is released into the synaptic cleft, it binds to dopamine receptors on the postsynaptic neuron to exert its effects. The DAT then clears the dopamine from the synapse and recycles it back into the presynaptic neuron. So it helps to terminate the action of dopamine by transporting it back into the presynaptic neuron. So when we inhibit it, we slow down the cleanup of dopamine and leave more of the chemical active in the synapses. Ritalin for example is a highly effective DAT inhibitor. Its structural mechanism differs completely from zinc obviously. While zinc acts as a non-competitive, allosteric clamp that locks the transporter from a side-pocket, methylphenidate operates primarily as an orthosteric blocker. It targets the S1 central binding site of the dopamine transporter. This is the exact same internal structural pocket where the dopamine molecule itself lands to be moved across the membrane. By sitting directly inside the central channel core, it acts like a physical plug and thus dopamine cannot bind to the transporter at all. Now unlike competitive inhibitors (such as cocaine or Ritalin), which bind directly to the central S1 substrate site halfway across the cell membrane, zinc acts at an entirely independent allosteric site on the outer surface of the transporter. By anchoring itself to this distinct outer pocket, zinc physically restrains the movement of the transporter. It acts as a rigid macromolecular bridge that locks the DAT machinery in an "outward-open" conformation. While the central channel remains open, the transporter is effectively paralyzed, it can no longer undergo the conformational rotation required to pull dopamine out of the synapse and back into the cell. For someone struggling with ADHD or anhedonia, this highly efficient, non-competitive blocking action provides a unique therapeutic advantage. Because zinc does not compete for the central keyhole, its ability to stop the cellular "vacuum cleaner" cannot be overridden by fluctuating concentrations of natural dopamine. It forces a baseline level of dopamine to pool within the synaptic cleft. This is why DAT inhibitors usually increase the effectiveness of stimulants. In the context of ADHD, this prolonged synaptic activity helps satisfy under-stimulated reward pathways. In the case of anhedonia this steady accumulation of active dopamine lowers the activation threshold required to feel pleasure, motivation and goal-directed drive. Other natural DAT inhibitors that you might be aware of are ginkgo and saffron. P.S: In general, if you have difficulty initiating and maintaining actions that require a fair amount of effort, you can try pairing: -A releaser or release-enhancing agent that raises the amount of dopamine available extracellularly. -A DAT inhibitor that blocks reuptake, prolonging and amplifying that signal -A NET inhibitor that supports prefrontal functions needed to stick with an action. A classic combination would be thiamine or L tyrosine + zinc or ginkgo+ P5P + saffron. Is this for everyone? No. For some people, it won't be enough. For others, it will cause borderline hypomania. For others, it will cause profound diarrhea. If you fit one of these categories you can find alternatives here: fitandball.gumroad.com/l/brain20/v30

nothinghere @offlabelhuman

George Ferman @Helios_Movement

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nothinghere @offlabelhuman

nothinghere @offlabelhuman

nothinghere @offlabelhuman

nothinghere @offlabelhuman

nothinghere @offlabelhuman

nothinghere @offlabelhuman

nothinghere @offlabelhuman

nothinghere @offlabelhuman

nothinghere @offlabelhuman

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nothinghere @offlabelhuman

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