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There are already tons of similar psychedelics available that are produced synthetically, including the extremely similar (if not identical, in terms of active

There are already tons of similar psychedelics available that are produced synthetically, including the extremely similar (if not identical, in terms of active metabolites and subjective experience) 4-AcO-DMT. Still, it's always good to see progress in this area, and for medical research I guess it's not acceptable to use analogues because "it should be similar!" isn't a medically sound reason to use an analog instead of the better researched psylocibin.

TheSpiceIsLife 9y ago
Aren't there a number of pharmaceutical drugs that are exactly "it should be similar"? The benzodiazepines spring to mind, as do many of the SSRI drugs. Amphetamine is chemically rated to that from which it is derived: ephedrine.
- tribby 9y ago
  no. drugs that act on GABAA, serotonin, norepinephrine, and dopamine receptors individually don't seem to affect the whole of the brain the way psychedelics do,[0] which we didn't really know about until 2016. from the available literature, which is scarce, it seems like psychedelics are more analogous to something like transcranial magnetic stimulation, which also "wakes up" and potentially even heals the prefrontal cortex. it's too bad it's so hard to study medical applications of these drugs. 0. http://www.pnas.org/content/113/17/4853.full http://www.pnas.org/content/113/17/4853.full
  - noir_lord 9y ago
    I take gabapentin for nerve damage, no euphoria but I do get a detached feeling of general wellness. Its not all good though, it also makes my head fuzzy, enough that it impacts work so I keep the doses to the minimum during the day and take some pain in return for clarity, it's a devils choice either way though.
  - TheSpiceIsLife 9y ago
    I'm confused as to what you are disagreeing with here. I was responding, in the general sense, to the claim that for medical research I guess it's not acceptable to use analogues because "it should be similar!" isn't a medically sound reason to use an analogue. This statement, evidently, doesn't map well to the field of pharmacology. The benzodiazepines comprise at least twenty different chemicals in five classes.[1] Structural analogues[2] are as common as horse shit in medicine and medical research. Structural analogues are also present in the SSRI class of drugs[3]. Psilocybin and dimethyltryptamine are structural analogues. It's unsurprising that their effects are broadly similar when ingested orally. With regards to your comment "... don't seem to affect the whole of the brain the way psychedelics do which we didn't really know about until 2016"... Surely that was evident to anyone who'd tried amphetamine at least once and mushrooms or LSD or DMT at least once. Amphetamine can be compared to caffeine, and even at high doses it doesn't really alter your way of perceiving the world. Where as the psychedelics, at sufficiently large doses, can be likened to being fucked open to God by Jesus, while riding a fluorescent unicorn and as you watch the universe unfold. 1. https://en.wikipedia.org/wiki/Benzodiazepine#Common_types https://en.wikipedia.org/wiki/Benzodiazepine#Common_types 2. https://en.wikipedia.org/wiki/Structural_analog https://en.wikipedia.org/wiki/Structural_analog 3. https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor#List_of_agents https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_i...
    - tribby 9y ago
      sorry, after re-reading the op I can see I misinterpreted your comment to mean SSRIs, benzodiazepines, and psilocybin had a similar effect on the brain. we don't disagree.
  - soundwave106 9y ago
    We actually do know that drugs that are considered "psychedelic" tend to have a dominant 5-HT2A agonist effect (serotonin targetting), actually. Chemical compounds are often not terribly specific, so other receptors get tickled as well... and there are other hallucinogen classifications that do not target serotonin receptors. But pretty much all of the "classic" psychedelics (ergolines and tryptamines) target 5-HT2A quite heavily; many phenethylamines also target 5-HT2A as well (although there is more receptor variety in that class of compounds). I believe you are right that much of the overall effect on the brain of these compounds is poorly understood.
scythe 9y ago
For synthesis, you don't need to know the exact pathway, but phosphorylation is very awkward synthetically, so you do need the enzyme for that (usually doesn't have to be the exact one, though). Synthetic psilocin is already a thing, it's just not sold because it's illegal and rapidly oxidized by air. Understanding the biosynthesis of stuff is more of a gateway to messing with it where it is or transplanting it into bacteria (which can be cheaper than synthesis).
drewmol 9y ago
>(if not identical, in terms of active metabolites and subjective experience) I suppose the limits of 'subjective experience' have way more fluctuation than the 'active metabolites' category they were able to test for.
byuu 9y ago
4-AcO-DMT is psilacetin, which is an acetylated form of 4-HO-DMT, or psilocin. Acetylization seems to result in an easier time crossing the blood-brain barrier, resulting in a quicker onset of effects, with a matched quicker comedown. You're still looking at a couple hours. Even without the psilocybin (or other alkaloids present), the experience appears mostly identical to P. cubensis mushrooms, but without the nausea, and seemingly a higher disposition toward producing negative experiences. It's incredibly easy to be overwhelmed by the euphoria being too intense, and dysphoria over negative effects such as akathisia. This can very easily spiral into mild panic attacks, knowing full well that things aren't going to wear off for a few more hours. The milder variants 4-AcO-MET and 4-AcO-DET seem to reduce negative experiences, but overall they're still far too unpredictable whether the experience will end up enjoyable or not. Whether natural or synthetic -- regrettably, the efficacy in treating depression and obsessive compulsive disorder appear to be overly optimistic.

TheSpiceIsLife 9y ago

Aren't there a number of pharmaceutical drugs that are exactly "it should be similar"? The benzodiazepines spring to mind, as do many of the SSRI drugs. Amphetamine is chemically rated to that from which it is derived: ephedrine.

tribby 9y ago
no. drugs that act on GABAA, serotonin, norepinephrine, and dopamine receptors individually don't seem to affect the whole of the brain the way psychedelics do,[0] which we didn't really know about until 2016. from the available literature, which is scarce, it seems like psychedelics are more analogous to something like transcranial magnetic stimulation, which also "wakes up" and potentially even heals the prefrontal cortex. it's too bad it's so hard to study medical applications of these drugs. 0. http://www.pnas.org/content/113/17/4853.full http://www.pnas.org/content/113/17/4853.full
- noir_lord 9y ago
  I take gabapentin for nerve damage, no euphoria but I do get a detached feeling of general wellness. Its not all good though, it also makes my head fuzzy, enough that it impacts work so I keep the doses to the minimum during the day and take some pain in return for clarity, it's a devils choice either way though.
- TheSpiceIsLife 9y ago
  I'm confused as to what you are disagreeing with here. I was responding, in the general sense, to the claim that for medical research I guess it's not acceptable to use analogues because "it should be similar!" isn't a medically sound reason to use an analogue. This statement, evidently, doesn't map well to the field of pharmacology. The benzodiazepines comprise at least twenty different chemicals in five classes.[1] Structural analogues[2] are as common as horse shit in medicine and medical research. Structural analogues are also present in the SSRI class of drugs[3]. Psilocybin and dimethyltryptamine are structural analogues. It's unsurprising that their effects are broadly similar when ingested orally. With regards to your comment "... don't seem to affect the whole of the brain the way psychedelics do which we didn't really know about until 2016"... Surely that was evident to anyone who'd tried amphetamine at least once and mushrooms or LSD or DMT at least once. Amphetamine can be compared to caffeine, and even at high doses it doesn't really alter your way of perceiving the world. Where as the psychedelics, at sufficiently large doses, can be likened to being fucked open to God by Jesus, while riding a fluorescent unicorn and as you watch the universe unfold. 1. https://en.wikipedia.org/wiki/Benzodiazepine#Common_types https://en.wikipedia.org/wiki/Benzodiazepine#Common_types 2. https://en.wikipedia.org/wiki/Structural_analog https://en.wikipedia.org/wiki/Structural_analog 3. https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor#List_of_agents https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_i...
  - tribby 9y ago
    sorry, after re-reading the op I can see I misinterpreted your comment to mean SSRIs, benzodiazepines, and psilocybin had a similar effect on the brain. we don't disagree.
- soundwave106 9y ago
  We actually do know that drugs that are considered "psychedelic" tend to have a dominant 5-HT2A agonist effect (serotonin targetting), actually. Chemical compounds are often not terribly specific, so other receptors get tickled as well... and there are other hallucinogen classifications that do not target serotonin receptors. But pretty much all of the "classic" psychedelics (ergolines and tryptamines) target 5-HT2A quite heavily; many phenethylamines also target 5-HT2A as well (although there is more receptor variety in that class of compounds). I believe you are right that much of the overall effect on the brain of these compounds is poorly understood.

scythe 9y ago

For synthesis, you don't need to know the exact pathway, but phosphorylation is very awkward synthetically, so you do need the enzyme for that (usually doesn't have to be the exact one, though). Synthetic psilocin is already a thing, it's just not sold because it's illegal and rapidly oxidized by air. Understanding the biosynthesis of stuff is more of a gateway to messing with it where it is or transplanting it into bacteria (which can be cheaper than synthesis).

drewmol 9y ago

>(if not identical, in terms of active metabolites and subjective experience) I suppose the limits of 'subjective experience' have way more fluctuation than the 'active metabolites' category they were able to test for.

byuu 9y ago

4-AcO-DMT is psilacetin, which is an acetylated form of 4-HO-DMT, or psilocin. Acetylization seems to result in an easier time crossing the blood-brain barrier, resulting in a quicker onset of effects, with a matched quicker comedown. You're still looking at a couple hours. Even without the psilocybin (or other alkaloids present), the experience appears mostly identical to P. cubensis mushrooms, but without the nausea, and seemingly a higher disposition toward producing negative experiences. It's incredibly easy to be overwhelmed by the euphoria being too intense, and dysphoria over negative effects such as akathisia. This can very easily spiral into mild panic attacks, knowing full well that things aren't going to wear off for a few more hours. The milder variants 4-AcO-MET and 4-AcO-DET seem to reduce negative experiences, but overall they're still far too unpredictable whether the experience will end up enjoyable or not. Whether natural or synthetic -- regrettably, the efficacy in treating depression and obsessive compulsive disorder appear to be overly optimistic.