Smoking meth is described by some as more fiendish than than injecting it - the onset is slightly quicker, and the comedown possibly harsher. It's also much easier to redose by smoking than injecting, so chances are it'll happen more often. Furthermore, the injection drug users may be more aware of the exact doses they're taking than the smokers.
No. Rectal, intranasal, and inhaled methamphetamine all bypass first-pass metabolism. Your liver still gets to metabolize it in the end, just not before it reaches your brain - all except orally.
As far as I know, methamphetamine is mostly neurotoxic, due to massive cascading dopamine release, which in excess is damaging to dopaminergic neurons. I've read a study where intravenous use of amphetamines has led to liver damage and failure, but mostly due to intravenous use (of MDMA, still an amphetamine) - hepatoxicity isn't the biggest concern, though.
Injecting it has all the familiar risks, but assuming you're doing it the Harm Reduction way with fresh, clean needles, sterile equipment, you still have to worry about impurities in the meth, pulmonary embolisms, and the damage of injecting a very caustic substance into your arteries. Also you can't undo your last dose if you realized you shot too much. You can puke out what you've eaten.
Smoking is pretty bad too, but that's mostly due to the intensity and addictiveness of the drug when taken by that ROA.
Eating and insufflating can have bad effects in the long term - again, it's caustic, so it's not gonna go your innads much good.
http://en.wikipedia.org/wiki/Drug_injection
All that said, a few of my friends that aren't complete junkies always inject their stimulants and knowing their sources are good, their harm reduction standards impeccable and their technique better than any nurse I've seen, I trust them to control their amphetamine use more than any others I know. But they know their dose and weigh out every single shot carefully. And to be fair, with the increased BA of and IV shot, to take a comparable amount intranasally would be absolute hell on your nasal cavities, probably worse if done on a weekly basis.
We're operating under a hypothetical assumption/control that everything is done "properly" in a completely healthy 5"10 individual.
The lungs are a bit of a wildcard and unique in this FPM pathway. The lungs are the 3rd major detoxing organ besides the liver and kidneys. Rectal administration is only capable of partially bypassing FPM.
If you have
ANY digestive disorder/issues, skin disorder/issues, you have liver damage and the liver is congested from "toxins" coming from the environment and the body itself. You're taking in too many things from the environment and food that the liver is unable to process properly. Adding in drugs which take detoxification priority in the body such as alcohol, ketones (not exactly a poison, but the liver treats ketones uniquely) or all synthetic medications is adding stress to an already overloaded liver. Thus, liver damage accumulates.
Realistically speaking, MOST people nowadays have varying degrees of liver damage. That includes seemingly healthy teenagers who consume junk food on a regular basis. Any ROA which stresses the liver is the MOST DANGEROUS and taxing on the human body.
If you have a bum liver (it's just safe to assume at this point that we all have a bum liver) your body is also not degrading byproducts of its own metabolism properly either - namely neurotransmitters. When we take something dopaminergic, that's adding even more fuel to the fire. I can't imagine science has gotten this far yet as to study the autophagic behavior of less-than-greatly-functioning organs on its own metabolic byproducts. We just know that stuff gets recycled or it doesn't. And when it doesn't, well, we haven't quite reached that point yet.
Why does
any of this FPM/in vivo detoxification matter? If the liver is unable to deal with any of the above, the lungs take on the responsibility of what the liver was unable to detoxify. The issue with this is simple: the lungs aren't meant to take on such a role and thus lung damage inevitably occurs unless the person fixes the underlying issues leading to acute or severe liver damage (remember: you can have
varying degrees of NAFLD or cirrhosis.)
What factors into the liver's ability to detoxify? Well, a shitload of stuff ranging from intestinal bacteria to hepatic circulation, to low Vitamin K2 levels to incomplete demethylation. I can't in all good consciousness recommend that if people take substances, to take them in the most volatile way possible.
FPM is a mechanism that's supposed to mitigate the damage from whatever "toxins" we intake. And if that mechanism is broken completely (moderate cirrhosis/moderate NAFLD) or even just functioning slightly below average, you've just opened the door to an array of different metabolic/drug byproducts flooding your body. You can't rely on FPM because if you live in the modern world, you have a bum liver and thus FPM is just wishful thinking.
How do you figure drugs which completely bypass FPM through IV end up back in the liver and undergo the same process as FPM? They don't. They (or their byproducts) enter the liver again because of our closed circulatory system, but the blood doesn't enter the liver through the GI tract, which it would in the case of FPM. Depending on certain factors, I imagine mostly related to diffusion, solubility, and general metabolism, some of these drugs and their byproducts would be present in the arterial portal/arterial blood. This is not how the liver would be traditionally introduced to a drug. IV injection doesn't exactly do the process completely in reverse, but it's
somewhat reversed. The process that initiates FPM is the circulation of [insert whatever] into the liver from the GI tract and the venous blood of a few other miscellaneous organs.
I do, however, agree with you that IV drugs and not just meth, tend to have more neurotoxic potential (also worthwhile to note that the BBB is not this impregnable fortress it's made out to be. It's more like a coffee filter and undoubtedly certain compounds can damage the BBB and let in "stuff" that would otherwise be unable to get through in our Uberhealthy test subject.)
In addition, once the drug is in your bloodstream, the kidneys can take on their many functions. One of which is regulating acid-alkaline balance in the body. This, among with other detox pathways in the body, would certainly mitigate
some of Methamphetamine HCl caustic effects before it had the chance to become neurotoxic or hepatotoxic.
I am of the persuasion that "proper" IV methamphetamine use will cause less damage in the long-term than smoked methamphetamine. Having read anecdotal evidence, trip reports and through personal contact with my disturbingly-functional-in-everyday-life-but-addicted-to-meth buddies, we've reached some agreement that smoking meth, for one reason or another, just makes people feel "weird" after a while and the pleasure of the drug is diminished, along with the side effects becoming more profound. This unpleasant "weird" can be avoided almost entirely if the ROA goes from smoking -> slamming. After the initial rush of an IV injection and your heart rate drops, it seems to be a much smoother ride from there and a more even comedown.
Just my $0.02. Feel free to poke holes where necessary, just offering a perspective and basic facts about human physiology which are often overlooked completely. Thanks for the input.