[kortex]

> But normal. The cloud of thoughts gone, I am able to make myself do anything with one thought, I have energy, the aches are gone, the tinnitus is gone, I don't second guess, I don't overthink. I just am and I do. It's amazing.

Have you been evaluated for ADHD? This is one of the classic tells. Methylphenidate is structurally and chemically very similar to cocaine.

Vyvanse is definitely the best when it comes to duration and classical stimulants. Modafinil has even longer duration, but it isn't always as effective at targeting ADHD symptoms. Vyvanse is kind of stupid expensive, but you can get a savings card. It would be $330 for me even with a good Rx plan, and the card knocks it down to $45/month. Sounds like you would also respond well to Concerta (extended release methylphenidate). I don't like it because I apparently have the metabolism of a honeybadger and get like 4-6h of otherwise "all day" meds like concerta. I have to split my vyvanse and take it in two doses to get a full day.

> This is what people like Bezos and Musk must be like

My headcannon is both these guys are ADHD and/or on the spectrum, have a doctor's script for vyvanse, adderall, modafinil, and/or whatever else, and have figured out how to ride the tolerance curve properly to maximize productivity.

[inter_netuser]

I have no idea why people like Vyvanse so much. It’s just time release with a fancy mechanism and paranoia around abuse potential of instant release formulations, which work just as well in most, if not all.

However, Ritalin is less neurotoxic than amphetamines that can indeed hike your risks of Parkinson’s (and probably few other things)

[kortex]

Because it's been life-changing for me, and countless others? It's not just time release; that's the old school drugs like Concerta.

The chief problem I have with all stimulants is too fast of an impulse response. It comes on too fast, crashes too fast. For me, for instant release drugs, I experience the following half-lives:

- methylphenidate: 60-90m

- amphetamine salts/dexedrine: 3-4h

- caffeine: 3h

- modafinil: 6-8h

Once a drug reaches about 1.5 HLs (about one Tau/time constant, conveniently), I start fading hard. There is a hysteresis effect: peaking/crashing/re-dosing is not the same as plateauing at some in-between value. Once my brain checks out, that's kind of it for the day.

So what Concerta, Adderall XR, and similar do for me, is give me what feels like two randomly spaced doses of instant release over a 4-6h window. This is unpredictable and thrashes my mental state. It peaks too high and crashes too low. The companies market these drugs based on averaging the plasma profiles of individuals to show a nice smooth curve, but I dug into the literature and this is NOT what you see on an individual level, at all. Concerta just doesn't do it for me.

Vyvanse is way smoother. The plasma peak is already low-pass filtered by the pharmacokinetics of hydrolysis of the lysdexamphetamine. As a result, my subjective experience is basically a 6h plateau. I split my dose to basically get a nice, actually smooth profile over 8-12h with a gentle taper instead of a crash. That also means lower peak plasma conc, and peak plasma is the greatest risk factor in neurotoxicity.

If you actually dig into the literature on neurotoxicity of amphetamines, you basically don't see any until you start getting to the equivalent of 50-100mg IR, and even then it's basically within the noise floor until you get to hundreds of mg per day.

[0des]

Ritalin does damage to DNA, if that counts for anything.

[inter_netuser]

To DNA? as in cancers?

Pls send some studies, very interesting.

[0des]

Sure. The early history of ritalin was the first sign to me that pharmatech industry owns their regulators. Check out the follow up research on 8-hydroxyguanine glycosylase as an indicator of oxidative DNA damage in response to the 2005 nih publications asserting no increased biomarkers, its somewhat surprising on both sides for Ritalin and the popular amphetamine alternative as well.

https://link.springer.com/article/10.1007/s00702-010-0408-5

[kortex]

> The aim of the present study was to examine the effects of drugs (amphetamine, methylphenidate and atomoxetine)

> We observed decreased expression of this enzyme for all applied substances.

Yeah no I'm not buying it. Amphetamine, perhaps, but atomoxetine causing DNA damage? That sets off my "spurious results" detector, hard.

I'll look into it more but I've done deep research into all things psychostimulants and I have not seen any indication of genotoxicity of methylphenidate or atomoxetine. Amphetamine has a slight risk of increased oxidative stress due to making dopamine leak places where it shouldn't, and DA's electronic structure makes it prone to generating singlet oxygen and ROS, but it's typically only observed in really high doses, like the equivalent of hundreds of mgs per dose.

Like, maybe there's some increased ROS due to any drug that boosts DA/NA (oxidizing catecholamines produces ROS in general), but like, "ritalin causes DNA damage" is the wrong conclusion to draw from that.