Years ago this idea was perpetuated on /r/Nootropics, /r/Stims and here on Longecity. I even made a thread about this here almost three years ago.
I found this post today on /r/DrugNerds today and it makes perfect sense so I wanted to share. That's all.
The 'sensitization from low doses of amphetamines' thing is actually a reddit myth perpetuated by a few people (such as /u/superagonist
, sorry for the callout but I have to tell it like it is) who have severely misinterpreted the studied. Almost every single claim made about it is completely false.First, not a single one of the studies linked by these people actually uses a "micro-dose". Most of them would be the equivalent to starter doses for ADHD. Here I'm unsure if super agonist does not understand the meaning of mg/kg, and that you have to multiply it by the overall weigh of the user. The study with the LOWEST dose of amphetamine he has linked is 0.4mg/kg. For me, a 68kg male, that would be over 25mg amph - actually higher than the therapeutic starting dose. There has never been a study on a 'micro-dose' on a stimulant, and why would there be? Scientists understand that it would just be the same effect except too small to study.Biologically it makes no sense for low doses of stimulants to have such a bad effect. The body has endogenous stimulants (such as phenylethylamine) active all the time, sometimes at low doses, sometimes at higher doses. Stimulants are only adding to the natural release of dopamine. Nothing we know about the mechanism of action of dexamph would suggest anything like what this story does, and no scientist studying this has ever posed this as a theory. Frankly, as a general rule, I'd imagine that it would be better to trust the scientists who dedicated their lives to studying the chemical before the reddit sleuths (no offense to the reddit sleuths here, myself included).Second, sensitization to the dopaminergic effects of amphetamines (and 'behavioral sensitization', which in animal model means enhancement of certain behavioral responses to stimulants, but not others) is indeed readily identified in animal models in the literature. There's just one problem as far as this theory is concerned: it is identified at many doses of stimulants in all kinds of stimulants. Here they identified dopamine sensitization from repeated high doses of cocaine. Here's one using a high dose of amph (and yes, 10mg/kg is a high dose, the equivalent of over 500 milligrams in a regular-sized human). And they've even found that sugar dependency and stress can induced a behavioral sensitization-like effect, which makes sense because the body releases those endogenous stimulants in response to stimulation. (However, it is not LOW amounts of stress but HIGH amounts of stress that is more likely to cause this).The studies suggest that the effect of dose on dopamine-induced sensitization is the opposite of what this nebulous theory claims: high (non-neurotoxic) doses are actually far more likely to cause behavioral sensitization than low doses. That Laviola study I linked showed sensitization occured far more readily from 10mg/kg than 2mg/kg. Further, like most drug-induced plasticity it appears to be dependent on the length of use, such that one use doesn't cause it.In other words, with stimulants as with almost anything else, the overwhelming body of evidence suggests that low doses of amphetamines are safer when it comes to the avoiding long-term effects. Color me shocked.Those who think high doses of dopaminergic drugs are supposed to cause downregulation and not upregulation might be confused by this result. (Perhaps this is where superagonist's confusion began too?) Basically, such a view is far too simplistic. This article lays out many of the theories for why behavioral sensitization occurs, from a downregulation of pre-synaptic neurons (which actually regulate the release of dopamine, such that a downregulation increases dopaminergic activity) to an increase in the readily-releasable pool of dopamine. Though that article is old, a peruse at a more recent but less comprehensive articles suggest they still don't really know 100%. What they do know now is the involvement of glutamate: the use of NMDA receptor antagonists blocked the development of behavioral sensitization. Further, it is associated with increased expression of AMPA receptors.Lastly, as for those testimonials, do some critical thinking: many are from extreme recreational drug users that were on many different chemicals at the time. Of course some of those chemicals could potentate the amphetamine, or synergize with it for nasty effects. Regular high-dose stimulant use (which many of the testimonial writers use) also makes the user more likely to have paranoia and delusions -- such as perhaps the delusion that they were permanently scarred by one dose of a drug based on an internet scare-story. Remember too that one can even more readily find testimonials about alien abduction.As for the safety of low-doses of benzedex: I'd suggest your best source for that would be long-term trials mandated by the FDA on drugs like that. Read the studies: was it generally well-tolerated? Did the users have to go off because of mounting side effects? What you will find is that despite some side effects fairly low doses of stimulants do not usually induce those "nasty effects" like persistent insomnia, etc. I would suggest that low doses would be fine occasionally (probably not all the time, though), and certainly safer than high doses.
