Comment · Thu, March 3, 2016 · Ceretropic & Nootropics Depot
Sensitization/upregulation of dopamine via microdosing stimulants - a viable strategy?
Original post in this thread
full_silver · 21 points
I don’t believe this has been discussed in r/Nootropics in depth, but is has been discussed in r/Drugs, r/Stims, r/(Ask)DrugNerds and Bluelight.
In a nutshell: microdosing stimulants (for example, 1.25-2.5mg dextroamphetamine, 5mg MPH, 2.5 adderall IR, etc) cause a phenomena known as sensitization (increased number of high sensitivity dopamine receptors in the brain), which results in the upregulation of dopamine. This is theorized to be a hormetic response (controversial in the scientific community). This leads to reverse tolerance of dopaminergic drugs in a way that makes subsequent dosing more powerful than a naïve user (or simple discontinuing use for then resuming after a few weeks). The consequences of dopamine sensitization are: (pros) increased motivation, confidence, focus, sense of well-being and (cons) inability to fall asleep or sleep for more than 6 hours/poor sleep quality, motor tics, irrational thinking and decision making, and extreme sensitivity to any dopaminergic stimulants (more pronounced side effects). There are also lots of anecdotes of people exploiting this method to enhance their MDMA and recreational adderall high.
Sensitization has been s…
What they were answering
full_silver · 1 points
/u/MisterYouAreSoDumb /u/gwern /u/Borax pls respond
u/MisterYouAreSoDumb · Ceretropic & Nootropics Depot
https://www.reddit.com/r/Stims/comments/3mbp3n/be_very_careful_with_low_doses_of_stimulants/
The results indicate that (1) a single injection of a low dose of AMPH enhances rotational behavior induced by a second injection of AMPH for up to 12 weeks; (2) multiple, weekly injections of AMPH produce a progressive enhancement in rotational behavior, over-and-above that produced by a single injection; (3) female rats show more robust sensitization than males following single or multiple injections of AMPH; (4) this sex difference may be due to the suppression of sensitization by an androgen, because removal of testicular hormones potentiates sensitization; (5) the long-lasting sensitization of rotational behavior produced by infrequent injections of AMPH is not due to drug-environment conditioning effects, but perhaps to a persistent AMPH-induced change(s) in brain catecholamine systems; and (6) a simple change in DA receptors is probably not involved, because the sensitization produced by infrequent injections of AMPH does not influence the rotation produced by a subsequent injection of apomorphine. The results illustrate an intriguing example of neuroplasticity that may have clinical relevance.
we favor the idea that the elevated extracellular concentrations of DA seen in sensitized animals are due to an increase in the ability of AMPH to induce DA release, because: (a) a sensitization-related enhancement in DA release has been reported in in vitro superfusion studies, in which the effects of reuptake are minimized; and (b) one would expect that a change in the reuptake carrier would result in higher extracellular concentrations of DA during the resting state, and there were none.
The data suggest that an enduring enhancement in DA neurotransmission, characterized by an increase in the releasability of DA, may be responsible for the enduring changes in behavior produced by past experience with AMPH. It is worth noting in this regard that activation of DA systems appears to be necessary for the development of behavioral sensitization, because concomitant treatment with a DA antagonist prevents sensitization to AMPH. The data presented here, however, do not allow us to ascertain the direction of putative cause-effect relations - - i.e. does the increase in DA release cause the enhanced behavioral response, or vice versa?