Over time, your brain adapts by down-regulating its own natural production and sensitivity to these chemicals, requiring you to consume more of the stimulant just to reach your normal baseline
The upregulation of calretinin may indicate its neuroprotective effect towards the cellular damage in the condition of inhibition of Ca 2+ influx to the cellular system by treatment with mitragynine
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[1] Deamidation proceeds much more quickly if the susceptible amino acid is followed by a small, flexible residue such as glycine whose low steric hindrance leaves the peptide group open for attack
