4 ms·

Many people say the first time they use Prozac that it was so helpful they recommended to their friends but then after a while it wore off. How do you think ps

Many people say the first time they use Prozac that it was so helpful they recommended to their friends but then after a while it wore off. How do you think psychedelics work? They activate the serotonin 2a receptor. It’s nothing but a different drug that effects serotonin. Except it does it more intensely but like all these drugs that act on receptors they wear off because of something what’s called receptor density changes. For 70 years, we’ve been trying to manipulate receptors into making people feel good. It’s a losing proposition and it’s time to. We changed our thinking. For instance, if these people do have serotonin deficiencies, which is still possibly the case, what is it? That’s causing these deficiencies? Is it low, zinc, low B6, genetics, infection? There’s so many other things that we know that this could be, but we don’t try it.

foobiekr 1y ago
I think this is naive. A mushroom trip is fully metabolized and cleared in approximately 6-12 hours. Despite the similar levels of reduction in depressive symptoms for the subsequent weeks, the psilocin has been cleared on the day of, unlike prozac, and hasn't been stimulating 5HT2* at all for that afterglow and post-exposure period. Nobody other than crazy micro-dosers is taking mushrooms often enough to cause a change in receptor density and those people are putting themselves at risk of valvopathy due to 5HT2a restructuring of the heart valves (which, as an aside, is turning out to be a problem for people on prozac and other long-term SSRIs). A drug that is very occasional, point use, with no ongoing use, which has long term treatment results, is absolutely, utterly unlike prozac. That aside, let's say for the sake of argument that the mechanism is similar for prozac; I think that's wrong (one additional explanation may actually be: https://www.sciencedirect.com/science/article/abs/pii/S1567576924002716 https://www.sciencedirect.com/science/article/abs/pii/S15675... ) but whatever. If so, then psilocin is vastly superior to prozac because you are not required to have continuous exposure for the benefits, as the corresponding cost, withdrawal, sexual dysfunction, weight gain, heart issues, etc. are removed.
- FollowingTheDao 1y ago
  > Nobody other than crazy micro-dosers is taking mushrooms often enough to cause a change in receptor density This is so frustrating to me. Why not just google it before you think you know more about this than someone studying it for ten years? Two things can change receptor density: time and dose. A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain https://pubmed.ncbi.nlm.nih.gov/33467676/ https://pubmed.ncbi.nlm.nih.gov/33467676/ This is exactly why psychedelics last longer than prozac. It has less to do with half life and more to do with dose. How is the mechanism not at least comparative to prozac since it is well know they both effect serotonin? The risk with psilocin is exactly the dose, as many people find out. And you thing there are not cardiac side effects from psychedelics? A Case of Prolonged Mania, Psychosis, and Severe Depression After Psilocybin Use: Implications of Increased Psychedelic Drug Availability https://psychiatryonline.org/doi/full/10.1176/appi.ajp.22010073 https://psychiatryonline.org/doi/full/10.1176/appi.ajp.22010... Worsening suicidal ideation and prolonged adverse event following psilocybin administration in a clinical setting: case report and thematic analysis of one participant's experience https://pmc.ncbi.nlm.nih.gov/articles/PMC11698204/ https://pmc.ncbi.nlm.nih.gov/articles/PMC11698204/ Safety First: Potential Heart Health Risks of Microdosing https://petrieflom.law.harvard.edu/2022/04/13/safety-first-potential-heart-health-risks-of-microdosing/ https://petrieflom.law.harvard.edu/2022/04/13/safety-first-p...
  - foobiekr 1y ago
    You've studied it for ten years and didn't notice that the pig brain receptor changes were only measured at +7 days and are replying to a comment about long term effectiveness vs. prozac (which takes weeks to really show impact)? I have previously read that study. You should put it in context: for example, how quickly does the brain add A1 and A2 receptors for caffeine? (I already know the answer, but you might want to use it to contextualize that study). The study about the woman co-administering venlafaxine (Effexor) which is an SNRI might be worth considering as non-representative. Worsening suicidal ideation .. is not unique to _any_ antidepressant. Are you trying to suggest that this is somehow unique to psilocin? We were discussing prozac which is _well known to have this problem_. They got black box warnings for this reason. As for the heart study, I mentioned this myself elsewhere, and SSRIs are showing the same issue: https://columbiasurgery.org/news/columbia-surgery-researchers-find-link-between-serotonin-and-heart-valve-disease https://columbiasurgery.org/news/columbia-surgery-researcher... - much worse, however, because people take these drugs every day for decades.

foobiekr 1y ago

I think this is naive. A mushroom trip is fully metabolized and cleared in approximately 6-12 hours. Despite the similar levels of reduction in depressive symptoms for the subsequent weeks, the psilocin has been cleared on the day of, unlike prozac, and hasn't been stimulating 5HT2* at all for that afterglow and post-exposure period. Nobody other than crazy micro-dosers is taking mushrooms often enough to cause a change in receptor density and those people are putting themselves at risk of valvopathy due to 5HT2a restructuring of the heart valves (which, as an aside, is turning out to be a problem for people on prozac and other long-term SSRIs). A drug that is very occasional, point use, with no ongoing use, which has long term treatment results, is absolutely, utterly unlike prozac. That aside, let's say for the sake of argument that the mechanism is similar for prozac; I think that's wrong (one additional explanation may actually be: https://www.sciencedirect.com/science/article/abs/pii/S1567576924002716 https://www.sciencedirect.com/science/article/abs/pii/S15675... ) but whatever. If so, then psilocin is vastly superior to prozac because you are not required to have continuous exposure for the benefits, as the corresponding cost, withdrawal, sexual dysfunction, weight gain, heart issues, etc. are removed.

FollowingTheDao 1y ago
> Nobody other than crazy micro-dosers is taking mushrooms often enough to cause a change in receptor density This is so frustrating to me. Why not just google it before you think you know more about this than someone studying it for ten years? Two things can change receptor density: time and dose. A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain https://pubmed.ncbi.nlm.nih.gov/33467676/ https://pubmed.ncbi.nlm.nih.gov/33467676/ This is exactly why psychedelics last longer than prozac. It has less to do with half life and more to do with dose. How is the mechanism not at least comparative to prozac since it is well know they both effect serotonin? The risk with psilocin is exactly the dose, as many people find out. And you thing there are not cardiac side effects from psychedelics? A Case of Prolonged Mania, Psychosis, and Severe Depression After Psilocybin Use: Implications of Increased Psychedelic Drug Availability https://psychiatryonline.org/doi/full/10.1176/appi.ajp.22010073 https://psychiatryonline.org/doi/full/10.1176/appi.ajp.22010... Worsening suicidal ideation and prolonged adverse event following psilocybin administration in a clinical setting: case report and thematic analysis of one participant's experience https://pmc.ncbi.nlm.nih.gov/articles/PMC11698204/ https://pmc.ncbi.nlm.nih.gov/articles/PMC11698204/ Safety First: Potential Heart Health Risks of Microdosing https://petrieflom.law.harvard.edu/2022/04/13/safety-first-potential-heart-health-risks-of-microdosing/ https://petrieflom.law.harvard.edu/2022/04/13/safety-first-p...
- foobiekr 1y ago
  You've studied it for ten years and didn't notice that the pig brain receptor changes were only measured at +7 days and are replying to a comment about long term effectiveness vs. prozac (which takes weeks to really show impact)? I have previously read that study. You should put it in context: for example, how quickly does the brain add A1 and A2 receptors for caffeine? (I already know the answer, but you might want to use it to contextualize that study). The study about the woman co-administering venlafaxine (Effexor) which is an SNRI might be worth considering as non-representative. Worsening suicidal ideation .. is not unique to _any_ antidepressant. Are you trying to suggest that this is somehow unique to psilocin? We were discussing prozac which is _well known to have this problem_. They got black box warnings for this reason. As for the heart study, I mentioned this myself elsewhere, and SSRIs are showing the same issue: https://columbiasurgery.org/news/columbia-surgery-researchers-find-link-between-serotonin-and-heart-valve-disease https://columbiasurgery.org/news/columbia-surgery-researcher... - much worse, however, because people take these drugs every day for decades.