3 ms·

Shulgin really makes a good case for testing psychedelics on humans. Ultimately it is the only test if a drug is "good" for therapy or not.

sterlind 5y ago
Shulgin hailed from a time before we had all these fancy tests. Binding affinity, mRNA and protein production, physiological changes can all be measured easily in the lab. There's a section in PiHKAL where Shulgin talks about a researcher measuring properties of psychedelics using the twitches of a sheep's stomach. That's because it contains serotonin receptors, and psychedelics induce muscle contraction. This is a common way to measure binding affinity to 5-HT receptors today, but it was quite exotic back then. I think Shulgin was most opposed to animal testing because there wasn't as much to learn from them. Now there is, though admittedly I think we could do with a bit more taste-testing today.
- pmoriarty 5y ago
  "There's a section in PiHKAL where Shulgin talks about a researcher measuring properties of psychedelics using the twitches of a sheep's stomach. That's because it contains serotonin receptors, and psychedelics induce muscle contraction. This is a common way to measure binding affinity to 5-HT receptors today, but it was quite exotic back then." Not all psychedelics affect serotonin receptors. For example, muscimol[1], the psychedelic constituent of amanita muscaria mushrooms affects GABA receptors, not serotonin receptors. So the absence of muscle contractions caused by serotonin activation in sheep stomachs would miss the psychedelic activity of muscimol and other psychedelics which don't affect serotonin receptors. [1] - https://en.wikipedia.org/wiki/Muscimol https://en.wikipedia.org/wiki/Muscimol
  - sterlind 5y ago
    I'd argue that muscimol, salvia, ketamine etc. are hallucinogens, and reserve the label of psychedelic for serotonin agonists. But others argue they deserve the label, so perhaps we could compromise on "classical psychedelic."
    - pmoriarty 5y ago
      The original meaning of psychedelic is "mind manifesting", which has nothing to do with serotonin. The term "hallucinogen" is a misnomer, because the effects of psychedelic substances (including muscimol, salvia, ketamine, etc..) don't always involve hallucinations. For example, if you forgive yourself or your parents under their influence (not an uncommon effect), that's not a hallucination. If you're able to face some traumatic event in your past while under their effects, and are no longer frightened of this traumatic event, that's not a hallucination. If a suicidal person no longer wants to kill themselves after taking a psychedelic, or a terminally ill person is finally able to achieve peace with the fact that they're going to die, that's not a hallucination. That's not to mention the quite common feeling while under the effect of psychedelics that what one experiences is "more real" than what one experiences under normal, waking consciousness, etc. I don't view the term "psychedelic" as perfect, but it's much better than "hallucinogen".
- Synaesthesia 5y ago
  Yes you can learn all about the binding affinity for different receptors, which is great and valuable, it can help you find promising candidates. However you will never know what a drug does and what it's like until human trials.
quantified 5y ago
It’s not like humans haven’t been using ibogaine, and for this very purpose too. If you’re addicted to heroin, the side effects of ibogaine can be worth it.

sterlind 5y ago

Shulgin hailed from a time before we had all these fancy tests. Binding affinity, mRNA and protein production, physiological changes can all be measured easily in the lab. There's a section in PiHKAL where Shulgin talks about a researcher measuring properties of psychedelics using the twitches of a sheep's stomach. That's because it contains serotonin receptors, and psychedelics induce muscle contraction. This is a common way to measure binding affinity to 5-HT receptors today, but it was quite exotic back then. I think Shulgin was most opposed to animal testing because there wasn't as much to learn from them. Now there is, though admittedly I think we could do with a bit more taste-testing today.

pmoriarty 5y ago
"There's a section in PiHKAL where Shulgin talks about a researcher measuring properties of psychedelics using the twitches of a sheep's stomach. That's because it contains serotonin receptors, and psychedelics induce muscle contraction. This is a common way to measure binding affinity to 5-HT receptors today, but it was quite exotic back then." Not all psychedelics affect serotonin receptors. For example, muscimol[1], the psychedelic constituent of amanita muscaria mushrooms affects GABA receptors, not serotonin receptors. So the absence of muscle contractions caused by serotonin activation in sheep stomachs would miss the psychedelic activity of muscimol and other psychedelics which don't affect serotonin receptors. [1] - https://en.wikipedia.org/wiki/Muscimol https://en.wikipedia.org/wiki/Muscimol
- sterlind 5y ago
  I'd argue that muscimol, salvia, ketamine etc. are hallucinogens, and reserve the label of psychedelic for serotonin agonists. But others argue they deserve the label, so perhaps we could compromise on "classical psychedelic."
  - pmoriarty 5y ago
    The original meaning of psychedelic is "mind manifesting", which has nothing to do with serotonin. The term "hallucinogen" is a misnomer, because the effects of psychedelic substances (including muscimol, salvia, ketamine, etc..) don't always involve hallucinations. For example, if you forgive yourself or your parents under their influence (not an uncommon effect), that's not a hallucination. If you're able to face some traumatic event in your past while under their effects, and are no longer frightened of this traumatic event, that's not a hallucination. If a suicidal person no longer wants to kill themselves after taking a psychedelic, or a terminally ill person is finally able to achieve peace with the fact that they're going to die, that's not a hallucination. That's not to mention the quite common feeling while under the effect of psychedelics that what one experiences is "more real" than what one experiences under normal, waking consciousness, etc. I don't view the term "psychedelic" as perfect, but it's much better than "hallucinogen".
Synaesthesia 5y ago
Yes you can learn all about the binding affinity for different receptors, which is great and valuable, it can help you find promising candidates. However you will never know what a drug does and what it's like until human trials.

quantified 5y ago

It’s not like humans haven’t been using ibogaine, and for this very purpose too. If you’re addicted to heroin, the side effects of ibogaine can be worth it.