4 ms·

Drug processing in the body can sometimes be surprising. I learned recently about first pass effect which means the drug heads first to the liver and only what

Drug processing in the body can sometimes be surprising. I learned recently about first pass effect which means the drug heads first to the liver and only what passes through is available to the body. So if one ups the dose and the liver processing is saturated a double dose can deliver much more punch than two single ones. The body has many non-linear features and extrapolating several orders of magnitude is often not possible.

cwkoss 5y ago
Yep, this is why "boofing" (intrarectal) dosing has found rising popularity in the 'research chemical' scene over the past couple decades. The liver's effects on drugs is really fascinating. Grapefruit has a chemical that can inactive liver enzymes, so some drug addicts regularly drink grapefruit juice to 'get more bang for their buck'. Plain old black pepper (in large doses) inactivates a different enzyme IIRC. There are also some interesting anecdotal cases of people who claim to have found regimens of essential oils, which when consumed at the right schedule saturate liver enzymes to the extent that otherwise inert substances can produce recreationally psychoactive effects. Source: i have a morbid fascination with the 'frontier non-medical drug use' communities and follow their subreddits (/r/researchchemicals and /r/peptides being among the most interesting). There a lot of people who choose to make themselves guinea pigs quite recklessly and, thankfully for scientific advancement and future harm reduction, post in-depth reports of how these novel chemicals or preparations effected them. Recently, broad cheap availability of novel benzos have led many posters to deep addictions of such great magnitude that they struggle to convince doctors assisting with detox that they've actually been consuming equivalents of 1000x typical prescribed doses... until the doctor gives them massive doses of valium to detox and they still have severe seizures.
- whymauri 5y ago
  >There are also some interesting anecdotal cases of people who claim to have found regimens of essential oils, which when consumed at the right schedule saturate liver enzymes to the extent that otherwise inert substances can produce recreationally psychoactive effects. Are essential oils literally oils? Because I doubt they can have a metabolic effect due to their size and lipophilicity. My main concern is adsorption. But if they're small and greasy, then they may be promiscuous binders. Or do the essential oils carry other molecules along? Edit: I see now that individual oils carry many diverse constituents, including some small-to-medium sized lads. That's a pretty interesting shotgun strategy for controlling your metabolism, lol.
  - cwkoss 5y ago
    I'm not sure what "literally oils" means in a chemical sense, but all of the essential oils I've ever interacted with are hydrophobic and form a distinct layer on top of water. I'm not sure but that might be definitional to what an essential oil is. I've actually steam-distilled essential oils before: essentially you push a bunch of steam through plant material and condense it into a funnel that drains from the bottom, so water can flow out and be discarded while the oil remains in the funnel. (It's a pretty fun process IMO, and about as safe as boiling a pot of water). I don't think the human body can process most essential oils for caloric energy: molecularly they look much more like drugs - no long carbon chains.
- stordoff 5y ago
  > i have a morbid fascination with the 'frontier non-medical drug use' communities I share this interest. I've very little interest in using drugs recreationally myself, but find reading about it oddly fascinating, particularly the novel agents. Taking a chemical when you only have the vaguest idea of what it _may_ do crosses a line I would never want to, but I sympathise with the feeling of wanting to know the effects and being willing to take that risk. > broad cheap availability of novel benzos The RC benzos have always concerned me. I'm prescribed a benzodiazepine (20mg temazepam), and it usually induces a mild feeling of wanting more, even though there are no noticeable recreational effects at that dose (at least for me). None of the opiates I've ever been prescribed have done the same, for comparison. It felt obvious to me that using the novel benzos without medical oversight could easily lead to a rapidly escalating problem. A while ago I saw a poster seeking a synthesis for a benzo they claimed did not cause tolerance, and my first thought was this can only end poorly. I don't believe there was ever a follow-up post, but I sincerely hope they avoided any problems.
  - cwkoss 5y ago
    Well, to share some of my favorite morbid findings: --- Melanotan is a peptide that increases skin pigmentation. Some people have tested it to the extreme, and the pictures are some combination of funny, terrifying and "at what point is this racially offensive blackface?". Also supposedly causes erections similarly to sildenafil . https://www.reddit.com/r/WTF/comments/3gxjem/before_and_after_photos_of_a_man_injecting/ https://www.reddit.com/r/WTF/comments/3gxjem/before_and_afte... --- The etizolam not wokrign meme https://www.google.com/search?q=etizolam+not+working+reddit https://www.google.com/search?q=etizolam+not+working+reddit Unfortunately can't find the original post, but when this benzo was easy to buy, there were frequent threads for a while from different users who were complaining that they weren't feeling the effects... often with many spelling errors that led many commenters to be pretty sure that it was working just fine and the posters are just not aware of how intoxicated they are. Became a bit of a meme. Kind of like the 'roofie circle' Gob story arc from arrested development, it seems very common that people will take some, forget they took it once it kicks in, take more, forget, and so on. When you can order 1000 doses for the price of a paycheck, it leads to very bad outcomes. Often these stories end up with people blacking out for weeks or months at a time, destroying personal relationships, property and their careers, and only regain awareness after weeks in jail or a hospital. Pretty scary stuff. Also, several stories from people buying time locked safes so they don't redose, blacking out, and finding their timelocked safe destroyed and empty. --- Cops arrest guy with RCs, etizolam and a mescaline derivative. Cop "accidentally" gets some on his lips (probably thought it was heroin and had a dip?) and gets sent to the infirmary tripping. Suspect is released when the substances turn out to be legal (but not for long - possibly in part because of this incident) https://www.reddit.com/r/researchchemicals/comments/fpery3/caught_with_etizolam/ https://www.reddit.com/r/researchchemicals/comments/fpery3/c... --- The stories about "bath salts" pyrovalerones like aPVP and MDPV are quite insane. Extremely potent and addictive. These are like the fentanyls of the stimulant class and propel users into psychosis with relative ease. Like, compressing the effects of a 2-week meth binge into a single weekend, with all of the negatives that come along with that. I believe the report of the florida man who ate someone's face off was under the influence of one of these. https://erowid.org/experiences/exp.php?ID=101129 https://erowid.org/experiences/exp.php?ID=101129 http://www.orangejuiceblog.com/2011/05/man-high-on-bath-salts-found-wearing-lingerie-next-to-dead-goat/ http://www.orangejuiceblog.com/2011/05/man-high-on-bath-salt... https://en.wikipedia.org/wiki/Miami_cannibal_attack https://en.wikipedia.org/wiki/Miami_cannibal_attack
- Nursie 5y ago
  I used to take a more active interest in that scene, some years ago. I had dabbled with well known substances over the years but had always been fascinated by the reports of novel or unusual substances on erowid, and resources like Tihkal and Pihkal. So to me the sudden easy availability of (say) variations on the MDMA molecule to skirt past the UK misuse of drugs act (at the time) that resulted in the aminopropylbenzofuran family were an amazing thing, a little because of the legal status but mainly because it was appealing in itself. I wouldn't know where to find MDA, or MDEA or such things, but suddenly APB, MAPB, EAPB and other variants were there. I was able to try some of the novel tryptamines that came out of that without having the in-depth illicit-chemist hookups usually needed to source these things, even a novel lysergamide or two. You're right to be concerned about the novel benzos, and also the novel cannabinoids, IMHO.
- astrange 5y ago
  > Plain old black pepper (in large doses) inactivates a different enzyme IIRC. It's actually surprisingly effective as long as you don't mind just eating peppercorns. It definitely reduces the high from THC in edibles (and it's the only thing I know of that does besides CBD), and it promotes the health effects of turmeric.
astrange 5y ago
> So if one ups the dose and the liver processing is saturated a double dose can deliver much more punch than two single ones. The body has many non-linear features and extrapolating several orders of magnitude is often not possible. Since we're talking about amphetamine here, this is actually the way Vyvanse works (it's bound to L-lysine and the liver splits it apart) and those nonlinearities are the reason it has such a longer effect life than Dexedrine/Adderall IR. As an unfortunate side effect, you have to watch the pH of the meal you take it with, eg taking it with orange juice completely inactivates it.

cwkoss 5y ago

Yep, this is why "boofing" (intrarectal) dosing has found rising popularity in the 'research chemical' scene over the past couple decades. The liver's effects on drugs is really fascinating. Grapefruit has a chemical that can inactive liver enzymes, so some drug addicts regularly drink grapefruit juice to 'get more bang for their buck'. Plain old black pepper (in large doses) inactivates a different enzyme IIRC. There are also some interesting anecdotal cases of people who claim to have found regimens of essential oils, which when consumed at the right schedule saturate liver enzymes to the extent that otherwise inert substances can produce recreationally psychoactive effects. Source: i have a morbid fascination with the 'frontier non-medical drug use' communities and follow their subreddits (/r/researchchemicals and /r/peptides being among the most interesting). There a lot of people who choose to make themselves guinea pigs quite recklessly and, thankfully for scientific advancement and future harm reduction, post in-depth reports of how these novel chemicals or preparations effected them. Recently, broad cheap availability of novel benzos have led many posters to deep addictions of such great magnitude that they struggle to convince doctors assisting with detox that they've actually been consuming equivalents of 1000x typical prescribed doses... until the doctor gives them massive doses of valium to detox and they still have severe seizures.

whymauri 5y ago
>There are also some interesting anecdotal cases of people who claim to have found regimens of essential oils, which when consumed at the right schedule saturate liver enzymes to the extent that otherwise inert substances can produce recreationally psychoactive effects. Are essential oils literally oils? Because I doubt they can have a metabolic effect due to their size and lipophilicity. My main concern is adsorption. But if they're small and greasy, then they may be promiscuous binders. Or do the essential oils carry other molecules along? Edit: I see now that individual oils carry many diverse constituents, including some small-to-medium sized lads. That's a pretty interesting shotgun strategy for controlling your metabolism, lol.
- cwkoss 5y ago
  I'm not sure what "literally oils" means in a chemical sense, but all of the essential oils I've ever interacted with are hydrophobic and form a distinct layer on top of water. I'm not sure but that might be definitional to what an essential oil is. I've actually steam-distilled essential oils before: essentially you push a bunch of steam through plant material and condense it into a funnel that drains from the bottom, so water can flow out and be discarded while the oil remains in the funnel. (It's a pretty fun process IMO, and about as safe as boiling a pot of water). I don't think the human body can process most essential oils for caloric energy: molecularly they look much more like drugs - no long carbon chains.
stordoff 5y ago
> i have a morbid fascination with the 'frontier non-medical drug use' communities I share this interest. I've very little interest in using drugs recreationally myself, but find reading about it oddly fascinating, particularly the novel agents. Taking a chemical when you only have the vaguest idea of what it _may_ do crosses a line I would never want to, but I sympathise with the feeling of wanting to know the effects and being willing to take that risk. > broad cheap availability of novel benzos The RC benzos have always concerned me. I'm prescribed a benzodiazepine (20mg temazepam), and it usually induces a mild feeling of wanting more, even though there are no noticeable recreational effects at that dose (at least for me). None of the opiates I've ever been prescribed have done the same, for comparison. It felt obvious to me that using the novel benzos without medical oversight could easily lead to a rapidly escalating problem. A while ago I saw a poster seeking a synthesis for a benzo they claimed did not cause tolerance, and my first thought was this can only end poorly. I don't believe there was ever a follow-up post, but I sincerely hope they avoided any problems.
- cwkoss 5y ago
  Well, to share some of my favorite morbid findings: --- Melanotan is a peptide that increases skin pigmentation. Some people have tested it to the extreme, and the pictures are some combination of funny, terrifying and "at what point is this racially offensive blackface?". Also supposedly causes erections similarly to sildenafil . https://www.reddit.com/r/WTF/comments/3gxjem/before_and_after_photos_of_a_man_injecting/ https://www.reddit.com/r/WTF/comments/3gxjem/before_and_afte... --- The etizolam not wokrign meme https://www.google.com/search?q=etizolam+not+working+reddit https://www.google.com/search?q=etizolam+not+working+reddit Unfortunately can't find the original post, but when this benzo was easy to buy, there were frequent threads for a while from different users who were complaining that they weren't feeling the effects... often with many spelling errors that led many commenters to be pretty sure that it was working just fine and the posters are just not aware of how intoxicated they are. Became a bit of a meme. Kind of like the 'roofie circle' Gob story arc from arrested development, it seems very common that people will take some, forget they took it once it kicks in, take more, forget, and so on. When you can order 1000 doses for the price of a paycheck, it leads to very bad outcomes. Often these stories end up with people blacking out for weeks or months at a time, destroying personal relationships, property and their careers, and only regain awareness after weeks in jail or a hospital. Pretty scary stuff. Also, several stories from people buying time locked safes so they don't redose, blacking out, and finding their timelocked safe destroyed and empty. --- Cops arrest guy with RCs, etizolam and a mescaline derivative. Cop "accidentally" gets some on his lips (probably thought it was heroin and had a dip?) and gets sent to the infirmary tripping. Suspect is released when the substances turn out to be legal (but not for long - possibly in part because of this incident) https://www.reddit.com/r/researchchemicals/comments/fpery3/caught_with_etizolam/ https://www.reddit.com/r/researchchemicals/comments/fpery3/c... --- The stories about "bath salts" pyrovalerones like aPVP and MDPV are quite insane. Extremely potent and addictive. These are like the fentanyls of the stimulant class and propel users into psychosis with relative ease. Like, compressing the effects of a 2-week meth binge into a single weekend, with all of the negatives that come along with that. I believe the report of the florida man who ate someone's face off was under the influence of one of these. https://erowid.org/experiences/exp.php?ID=101129 https://erowid.org/experiences/exp.php?ID=101129 http://www.orangejuiceblog.com/2011/05/man-high-on-bath-salts-found-wearing-lingerie-next-to-dead-goat/ http://www.orangejuiceblog.com/2011/05/man-high-on-bath-salt... https://en.wikipedia.org/wiki/Miami_cannibal_attack https://en.wikipedia.org/wiki/Miami_cannibal_attack
Nursie 5y ago
I used to take a more active interest in that scene, some years ago. I had dabbled with well known substances over the years but had always been fascinated by the reports of novel or unusual substances on erowid, and resources like Tihkal and Pihkal. So to me the sudden easy availability of (say) variations on the MDMA molecule to skirt past the UK misuse of drugs act (at the time) that resulted in the aminopropylbenzofuran family were an amazing thing, a little because of the legal status but mainly because it was appealing in itself. I wouldn't know where to find MDA, or MDEA or such things, but suddenly APB, MAPB, EAPB and other variants were there. I was able to try some of the novel tryptamines that came out of that without having the in-depth illicit-chemist hookups usually needed to source these things, even a novel lysergamide or two. You're right to be concerned about the novel benzos, and also the novel cannabinoids, IMHO.
astrange 5y ago
> Plain old black pepper (in large doses) inactivates a different enzyme IIRC. It's actually surprisingly effective as long as you don't mind just eating peppercorns. It definitely reduces the high from THC in edibles (and it's the only thing I know of that does besides CBD), and it promotes the health effects of turmeric.

astrange 5y ago

> So if one ups the dose and the liver processing is saturated a double dose can deliver much more punch than two single ones. The body has many non-linear features and extrapolating several orders of magnitude is often not possible. Since we're talking about amphetamine here, this is actually the way Vyvanse works (it's bound to L-lysine and the liver splits it apart) and those nonlinearities are the reason it has such a longer effect life than Dexedrine/Adderall IR. As an unfortunate side effect, you have to watch the pH of the meal you take it with, eg taking it with orange juice completely inactivates it.