3 ms·

Excuse me, index. A dimensionless quantity. Nothing to do with potency. And you could hardly pick worse drugs to spread misinformation about.

civilitty 9y ago
I do not believe that you have the requisite knowledge of pharmacology to talk intelligently on these topics so you should stop correcting people who do, especially when your other comments suggest that your knowledge is based entirely on recreational drug databases. Anyone who has spent time working in the pharmaceutical industry knows that "therapeutic index" and "therapeutic ratio" are used interchangeably and that I never said anything even remotely related to either of those until you brought it up out of nowhere. The therapeutic index is the ratio of the therapeutic dose to the dose at which the drug starts becoming toxic in 50% of the sample. I repeat, for the third time, I was not talking about toxicity. We are discussing drug expiration dates and you will not experience toxicity from a drug that has been degraded over time to a dosage lower than the one you were prescribed, except in extremely rare circumstances. A drug's therapeutic index is entirely irrelevant to what I am talking about - I don't know how I can make that any more clear.
- sevenfive 9y ago
  But what you said was still totally wrong, regardless of whether you're talking about toxicity or anything else. LSD is not so finicky that a 25% change in the dose makes a noticeable difference -- most people would be hard pressed to tell the difference between a 100 ug tab and a 125 ug one. It also does not follow that because a drug is active in small amounts, i.e. micrograms instead of milligrams, that a small percent change in the dosage will be more important. Full stop illogical, and also not true in practice. So yes, I'm not a doctor and I don't know the jargon. And when I read your comment I forgot the article was about expiration dates, i.e. percent decrease. And yet you were still wrong on that particular point.
  - civilitty 9y ago
    LSD is an agonist for most classes of serotonin, dopamine, and adrenergic receptors - most of which have sensitive, nonlinear responses and all of which uptake the agonist at very different rates depending on individual biochemistry. We don't have the data to say for certain because of prohibition and the DEA's reluctance to allow researchers to study LSD but every other drug combination that operates on such a diverse set of receptors is extremely sensitive to dosage because all of those receptors have interdependent feedback loops - which makes them mostly useless for therapeutic uses. This is also why monoamine oxidase inhibitors (MAOIs) are so dangerous with such a wide array of drugs - the enzymes that break down monoamine neurotransmitters are regulated by serotonin+dopamine receptor interactions and even a tiny amount of MAO inhibitors can wreck havoc on that balance, causing some severe symptoms up to and including death. This happens because, even though MAOs are rather indiscriminate on which monoamines they target, their effect on each different neurotransmitter is variable and nonlinear. In my personal experience (a decade of Burning man), when you do have a known concentration of liquid LSD (measured with an LCMS) that you carefully handle, store, and dilute for dosages, 100 mcg and 125 mcg can mean the difference between a good trip and a bad one in at least a tenth of my sample size and can drastically change the intensity of hallucinations (going from zero to fractal visuals to aliens) in a good quarter - not to mention the effect on the body high and introspection. If you're buying tabs, the chances that you are even close to the original concentration falls rapidly the further removed you are from the original source. Most people can't tell the difference between a 100mcg and 125mcg tab because those dosages are exaggerated and many people feel stereotypical effects at lower dosages. You can easily test this by eating a significant fraction of a blotter: you are extremely unlikely to experience the effects described by the literature of 50 ng/mL blood concentrations even if you're lucky enough to get to 5 ng/mL effects with a few tabs.
    - sevenfive 9y ago
      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

I do not believe that you have the requisite knowledge of pharmacology to talk intelligently on these topics so you should stop correcting people who do, especially when your other comments suggest that your knowledge is based entirely on recreational drug databases. Anyone who has spent time working in the pharmaceutical industry knows that "therapeutic index" and "therapeutic ratio" are used interchangeably and that I never said anything even remotely related to either of those until you brought it up out of nowhere. The therapeutic index is the ratio of the therapeutic dose to the dose at which the drug starts becoming toxic in 50% of the sample. I repeat, for the third time, I was not talking about toxicity. We are discussing drug expiration dates and you will not experience toxicity from a drug that has been degraded over time to a dosage lower than the one you were prescribed, except in extremely rare circumstances. A drug's therapeutic index is entirely irrelevant to what I am talking about - I don't know how I can make that any more clear.

sevenfive 9y ago
But what you said was still totally wrong, regardless of whether you're talking about toxicity or anything else. LSD is not so finicky that a 25% change in the dose makes a noticeable difference -- most people would be hard pressed to tell the difference between a 100 ug tab and a 125 ug one. It also does not follow that because a drug is active in small amounts, i.e. micrograms instead of milligrams, that a small percent change in the dosage will be more important. Full stop illogical, and also not true in practice. So yes, I'm not a doctor and I don't know the jargon. And when I read your comment I forgot the article was about expiration dates, i.e. percent decrease. And yet you were still wrong on that particular point.
- civilitty 9y ago
  LSD is an agonist for most classes of serotonin, dopamine, and adrenergic receptors - most of which have sensitive, nonlinear responses and all of which uptake the agonist at very different rates depending on individual biochemistry. We don't have the data to say for certain because of prohibition and the DEA's reluctance to allow researchers to study LSD but every other drug combination that operates on such a diverse set of receptors is extremely sensitive to dosage because all of those receptors have interdependent feedback loops - which makes them mostly useless for therapeutic uses. This is also why monoamine oxidase inhibitors (MAOIs) are so dangerous with such a wide array of drugs - the enzymes that break down monoamine neurotransmitters are regulated by serotonin+dopamine receptor interactions and even a tiny amount of MAO inhibitors can wreck havoc on that balance, causing some severe symptoms up to and including death. This happens because, even though MAOs are rather indiscriminate on which monoamines they target, their effect on each different neurotransmitter is variable and nonlinear. In my personal experience (a decade of Burning man), when you do have a known concentration of liquid LSD (measured with an LCMS) that you carefully handle, store, and dilute for dosages, 100 mcg and 125 mcg can mean the difference between a good trip and a bad one in at least a tenth of my sample size and can drastically change the intensity of hallucinations (going from zero to fractal visuals to aliens) in a good quarter - not to mention the effect on the body high and introspection. If you're buying tabs, the chances that you are even close to the original concentration falls rapidly the further removed you are from the original source. Most people can't tell the difference between a 100mcg and 125mcg tab because those dosages are exaggerated and many people feel stereotypical effects at lower dosages. You can easily test this by eating a significant fraction of a blotter: you are extremely unlikely to experience the effects described by the literature of 50 ng/mL blood concentrations even if you're lucky enough to get to 5 ng/mL effects with a few tabs.
  - sevenfive 9y ago
    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.