13 ms·

IME bad trips are mostly determined by how neurotic the tripper is. If you can accurately say that a 25% increase causes a 10% increase in bad trips, you must h

IME bad trips are mostly determined by how neurotic the tripper is. If you can accurately say that a 25% increase causes a 10% increase in bad trips, you must have quite a lot of experience. I at least know that if some people take one tab and others take two at the same time, the ones who took two don't go flying off the walls. Saying that a 25% change is more significant for more potent drugs is illogical on the face of it, because a % is a dimensionless quantity. If there is some subtle reason why this trend exists I'd love to hear it.

civilitty 9y ago
> Saying that a 25% change is more significant for more potent drugs is illogical on the face of it, because a % is a dimensionless quantity. If there is some subtle reason why this trend exists I'd love to hear it. Actually, the reverse is illogical because few biochemical systems have linear responses, especially when you're talking about something as complicated as the neurotransmitter systems that LSD effects. Potency depends on two factors: the affinity of the drug, or how well it binds to its target receptors, and efficacy, or the relationship between the concentration of the drug (and second order neurotransmitters) and the ability of the receptors to initiate a cellular response. Neither of those two factors are linear and they both change as the concentrations of the drug and its byproducts change. As neuron receptors are activated by LSD, they cause cells to release a flood of other neurotransmitters at varying concentrations (dependent on LSD concentration and individual brain chemistry) that start interacting in complex ways like preventing the LSD and other neurotransmitters from binding as effectively (lowering their affinity), potentiating the cellular response (increasing its strength aka increasing efficacy), or building tolerance (lowering efficacy due to exposure). Each receptor and neurotransmitter pair behaves differently. Neurotransmitters in general can't activate cellular responses before they are above a threshold potential that causes the neuron to react, after which the cellular response is never linear. A 2x increase in concentration will rarely achieve a 2x response unless it falls in a small range where the curve is mostly linear, and even then the complex interactions between all of the neurotransmitters will usually compound into a nonlinear response anyway. These interactions get so complicated, for example, that you get many cases were an opiate A, which is technically 10x more potent than an opiate B, can actually be less potent at treating mild pain because it has a steep response curve that doesn't ramp up until a certain dose. 10mcg/kg of opiate B might be 10x stronger than 10mcg/kg of opiate A (which could be too low to even feel the painkilling effects of opiate A) but once you hit 50mcg/kg concentrations, opiate A might be 10x more potent than opiate B, whose effects plateau with doses higher than 20mcg/kg. Potency is typically expressed as the [A]50 - the concentration of the drug at which you reach 50% of the maximum effect, which depends on the therapeutic effect you're looking for. So in this example, the [A]50 of opiate A in mild pain scenarios can be 25mcg/kg versus opiate B's 7 mcg/kg while with severe pain, the [A]50 of opiate B can be above its LD50 and opiate A's can be 30 mcg/kg because from 25 to 30 mcg/kg opiate A has an exponential response curve. Like I said, it's very complicated and when measuring potency, you're actually measuring the effects of concentration on "arbitrary units," which could be something concrete like a chemo drug's effectiveness at killing cancer cells or something subjective like pain relief. When it's the latter, especially, potency has a very specific meaning in pharmacology that is very different from how the word is used colloquially.
- sevenfive 9y ago
  This is just throwing around a lot of irrelevant details to obscure the fact that your original statement violates the dimensional analysis smell test -- I could make a shitty prodrug of LSD where the threshold dose is 1g instead of 50ug, but you wouldn't expect the 1g version to be less sensitive to a 25% change because it's "less potent." If you wanted to give examples of a drug where a 25% change is a big concern then warfarin or synthroid are much better examples than LSD. As it turns out, you know your shit, but it is still a sloppy statement.
  - civilitty 9y ago
    I tried explaining why you are wrong but I give up. You are incapable of accepting basic facts about biological systems and neuroscience that have been known for many decades, no matter how hard I try to explain it to you. Your "dimensional analysis smell test" is entirely idiotic in the face of those basic facts as accepted by the entire medical and biological research fields. Please don't talk about pharmacology. Period. You don't know what you are talking about and someone might make the mistake of believing otherwise and do something dangerous.
    - sevenfive 9y ago
      This is what you said: > There are a few compounds (like fentanyl or LSD) where the dosages are so small and the compound so potent that 10-25% makes a difference but for the majority, precision isn't that critical. As in, typical dosages for fent or LSD are on the order of micrograms, so we expect them to be sensitive to a 25% change, for other drugs where a typical dose is measured in mg or grams, 25% is less likely to be a big deal, etc. This is the only way to interpret what you wrote, and it doesn't make sense. No such trend exists. None of the "basic facts" which you "explained" above (which I already knew) go anywhere near supporting this assertion. Put another way, if you know the [A]50 you know one point on the dose-response curve, but in general that tells you nothing about the slope or shape of the curve near that point. Judging from your comment history, you are not an actual doctor or biomed researcher, just a programmer in that industry. Which makes your teeth-gnashing about what an authority you are a tad less persuasive.

civilitty 9y ago

> Saying that a 25% change is more significant for more potent drugs is illogical on the face of it, because a % is a dimensionless quantity. If there is some subtle reason why this trend exists I'd love to hear it. Actually, the reverse is illogical because few biochemical systems have linear responses, especially when you're talking about something as complicated as the neurotransmitter systems that LSD effects. Potency depends on two factors: the affinity of the drug, or how well it binds to its target receptors, and efficacy, or the relationship between the concentration of the drug (and second order neurotransmitters) and the ability of the receptors to initiate a cellular response. Neither of those two factors are linear and they both change as the concentrations of the drug and its byproducts change. As neuron receptors are activated by LSD, they cause cells to release a flood of other neurotransmitters at varying concentrations (dependent on LSD concentration and individual brain chemistry) that start interacting in complex ways like preventing the LSD and other neurotransmitters from binding as effectively (lowering their affinity), potentiating the cellular response (increasing its strength aka increasing efficacy), or building tolerance (lowering efficacy due to exposure). Each receptor and neurotransmitter pair behaves differently. Neurotransmitters in general can't activate cellular responses before they are above a threshold potential that causes the neuron to react, after which the cellular response is never linear. A 2x increase in concentration will rarely achieve a 2x response unless it falls in a small range where the curve is mostly linear, and even then the complex interactions between all of the neurotransmitters will usually compound into a nonlinear response anyway. These interactions get so complicated, for example, that you get many cases were an opiate A, which is technically 10x more potent than an opiate B, can actually be less potent at treating mild pain because it has a steep response curve that doesn't ramp up until a certain dose. 10mcg/kg of opiate B might be 10x stronger than 10mcg/kg of opiate A (which could be too low to even feel the painkilling effects of opiate A) but once you hit 50mcg/kg concentrations, opiate A might be 10x more potent than opiate B, whose effects plateau with doses higher than 20mcg/kg. Potency is typically expressed as the [A]50 - the concentration of the drug at which you reach 50% of the maximum effect, which depends on the therapeutic effect you're looking for. So in this example, the [A]50 of opiate A in mild pain scenarios can be 25mcg/kg versus opiate B's 7 mcg/kg while with severe pain, the [A]50 of opiate B can be above its LD50 and opiate A's can be 30 mcg/kg because from 25 to 30 mcg/kg opiate A has an exponential response curve. Like I said, it's very complicated and when measuring potency, you're actually measuring the effects of concentration on "arbitrary units," which could be something concrete like a chemo drug's effectiveness at killing cancer cells or something subjective like pain relief. When it's the latter, especially, potency has a very specific meaning in pharmacology that is very different from how the word is used colloquially.

sevenfive 9y ago
This is just throwing around a lot of irrelevant details to obscure the fact that your original statement violates the dimensional analysis smell test -- I could make a shitty prodrug of LSD where the threshold dose is 1g instead of 50ug, but you wouldn't expect the 1g version to be less sensitive to a 25% change because it's "less potent." If you wanted to give examples of a drug where a 25% change is a big concern then warfarin or synthroid are much better examples than LSD. As it turns out, you know your shit, but it is still a sloppy statement.
- civilitty 9y ago
  I tried explaining why you are wrong but I give up. You are incapable of accepting basic facts about biological systems and neuroscience that have been known for many decades, no matter how hard I try to explain it to you. Your "dimensional analysis smell test" is entirely idiotic in the face of those basic facts as accepted by the entire medical and biological research fields. Please don't talk about pharmacology. Period. You don't know what you are talking about and someone might make the mistake of believing otherwise and do something dangerous.
  - sevenfive 9y ago
    This is what you said: > There are a few compounds (like fentanyl or LSD) where the dosages are so small and the compound so potent that 10-25% makes a difference but for the majority, precision isn't that critical. As in, typical dosages for fent or LSD are on the order of micrograms, so we expect them to be sensitive to a 25% change, for other drugs where a typical dose is measured in mg or grams, 25% is less likely to be a big deal, etc. This is the only way to interpret what you wrote, and it doesn't make sense. No such trend exists. None of the "basic facts" which you "explained" above (which I already knew) go anywhere near supporting this assertion. Put another way, if you know the [A]50 you know one point on the dose-response curve, but in general that tells you nothing about the slope or shape of the curve near that point. Judging from your comment history, you are not an actual doctor or biomed researcher, just a programmer in that industry. Which makes your teeth-gnashing about what an authority you are a tad less persuasive.