3 ms·

Correct me if I'm wrong, because I don't have a great grasp of drugs or biological pathways. The following is my extremely lay understanding: * The reason peop

Correct me if I'm wrong, because I don't have a great grasp of drugs or biological pathways. The following is my extremely lay understanding: * The reason people started taking MDMA was that it caused their brains to release large bursts of seratonin, which felt good. * Receptors to seratonin tended to be overwhelmed, which caused people in the short term to be unable to achieve the same levels of ecstasy, and in the long term caused them to (grow new receptors? or at least...) have a perceived deficit of seratonin; causing short and long term depression in MDMA users. Surely, injecting yourself with the chemical that causes your brain to be happy can't just work forever...right?

simiones 3y ago
Serotonin doesn't cause you to be happy. Its effects are more basic in some ways, but also more complex in others. It is a chemical which serves a purpose in at least all forms of multi-cellular life, from plants to animals - so you can imagine how old and fundamental its role is. Also, depression is not caused by low serotonin levels: https://www.nature.com/articles/s41380-022-01661-0 https://www.nature.com/articles/s41380-022-01661-0 > The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.
- svnt 3y ago
  >> provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations I did not read your paper, but believe parent is making a different claim: it is not lowered serotonin levels or reduced activity, but an increase in receptors (perhaps a proxy for expected serotonin levels) that is causing the problem. If this paper is specifically addressing serotonin levels or movement I can’t see how it could address receptor density.
  - simiones 3y ago
    The paper is specifically claiming there is just no association between serotonin activity and depression. By my understanding, that should include increased/decreased receptors, reuptake, breakdown etc.
    - svnt 3y ago
      Ok, I read the paper. Here is the most pertinent part on receptors: > Fourteen different serotonin receptors have been identified, with most research on depression focusing on the 5-HT1A receptor [11, 34]. Since the functions of other 5-HT receptors and their relationship to depression have not been well characterised, we restricted our analysis to data on 5-HT1A receptors [11, 34]. So they reviewed two 2016 meta analyses of one out of fourteen known receptors involved in the process. > Both meta-analyses were based on studies that predominantly involved patients who were taking or had recently taken (within 1–3 weeks of scanning) antidepressants or other types of psychiatric medication, and both sets of authors commented on the possible influence of prior or current medication on findings. So both meta analyses were very sensitive to temporally proximate relevant medication use. Of the two receptor analyses: > one analysis was of very low quality [37], … and one was strongly influenced by three studies and publication bias was present [38]. This is about as little (and sadly as much) as one could do to address receptors, and about as far from a dismissal of association of receptor count and depression as it is possible to get.
dmbche 3y ago
If anything it's probably the other way around - I'd posit that the portion of the population the does mdma, speed and the like is on aberage more depressed than someone "sober". Chicken and egg

simiones 3y ago

Serotonin doesn't cause you to be happy. Its effects are more basic in some ways, but also more complex in others. It is a chemical which serves a purpose in at least all forms of multi-cellular life, from plants to animals - so you can imagine how old and fundamental its role is. Also, depression is not caused by low serotonin levels: https://www.nature.com/articles/s41380-022-01661-0 https://www.nature.com/articles/s41380-022-01661-0 > The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.

svnt 3y ago
>> provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations I did not read your paper, but believe parent is making a different claim: it is not lowered serotonin levels or reduced activity, but an increase in receptors (perhaps a proxy for expected serotonin levels) that is causing the problem. If this paper is specifically addressing serotonin levels or movement I can’t see how it could address receptor density.
- simiones 3y ago
  The paper is specifically claiming there is just no association between serotonin activity and depression. By my understanding, that should include increased/decreased receptors, reuptake, breakdown etc.
  - svnt 3y ago
    Ok, I read the paper. Here is the most pertinent part on receptors: > Fourteen different serotonin receptors have been identified, with most research on depression focusing on the 5-HT1A receptor [11, 34]. Since the functions of other 5-HT receptors and their relationship to depression have not been well characterised, we restricted our analysis to data on 5-HT1A receptors [11, 34]. So they reviewed two 2016 meta analyses of one out of fourteen known receptors involved in the process. > Both meta-analyses were based on studies that predominantly involved patients who were taking or had recently taken (within 1–3 weeks of scanning) antidepressants or other types of psychiatric medication, and both sets of authors commented on the possible influence of prior or current medication on findings. So both meta analyses were very sensitive to temporally proximate relevant medication use. Of the two receptor analyses: > one analysis was of very low quality [37], … and one was strongly influenced by three studies and publication bias was present [38]. This is about as little (and sadly as much) as one could do to address receptors, and about as far from a dismissal of association of receptor count and depression as it is possible to get.

dmbche 3y ago

If anything it's probably the other way around - I'd posit that the portion of the population the does mdma, speed and the like is on aberage more depressed than someone "sober". Chicken and egg