10 ms·

This is a very interesting piece of research. It needs to be put into context though - this isn't even a phase 1 trial, it's an observational study of veterans

by ajb 3y ago

This is a very interesting piece of research. It needs to be put into context though - this isn't even a phase 1 trial, it's an observational study of veterans who decided to go to Mexico to take ibogaine. There is no control group Other psychodelics, such as psilocybin, are further down the road to validated treatment. I'm not quite sure what stage they are at for PTSD but there are various groups doing RCTs for depression etc

red_admiral 3y ago
"small study finds" has happened before, in the context of mental health cures, for everything from LSD to yoga to going 48 hours without sleep. Many other things that can induce altered states of consciousness have probably been studied at small scale too (like you say, Psilocybin). For each one, there's always some subgroup that responds to it. "small study finds" is also how we landed ourselves with a replication crisis, so your comment about putting it into context is very appropriate.
sph 3y ago
Why Mexico when it is native to Central Africa?
- asveikau 3y ago
  I know nothing of this topic, but my guess is proximity to the United States and a different drug regulation scheme.
- namlem 3y ago
  Access to the American market.
Aurornis 3y ago
There was also no control group, which is a fatal flaw in any depression related study. If you're not aware: Depression studies have a very high placebo response rate. It's often hard to get new antidepressants to demonstrate improvements in studies not because the patients don't get better, but because the placebo group improves so much that the difference between the groups is small. This doesn't mean that antidepressants are placebo, it just means that if you take depressed people and tell them they're going to get better, then give them a lot of attention and activity from clinicians, they start to improve. This study definitely needs a control group, as the patients went all the way to Mexico on a small vacation to receive the drug. I guarantee that if you take a cohort of depressed patients, send them to Mexico for a short vacation and hand them a placebo pill that you tell them is an antidepressant, many of them will improve substantially on various measures upon return. This is why placebo control groups are critical for any depression study. I don't think it's a coincidence that so many of these psychedelics-for-depression studies omit control groups. Including a control group increases the cost, but it also is guaranteed to reduce the "wow factor" of a depression study. Therefore, they get omitted any time someone wants to make an antidepressant look effective. If this was a study for a new SSRI that didn't have a control group, people would be tearing it apart. For some reason people love stories about psychedelics doing magical things, though, so a lot of people are willing to overlook the most glaring fault of this study.
- BobaFloutist 3y ago
  PTSD is a dramatically different disorder to MDD though, no? It has pretty acute effects, and I don't know, but I would imagine it's less susceptible to placebo. Not to say this trial is any higher quality than it is, or that your sidebar on MDD wasn't interesting, but I'm not sure it's that effective of a comparison.
- worik 3y ago
  Yes. But psychedelic studies are impossible with double blind It is important to be rigorous in your study, but cannot expect too much Psychedelic therapies are not like antibiotic therapies, they interact in complex and confounding ways with set and setting
- elmomle 3y ago
  It is not the medicine by itself but the whole experience around it. Practitioners feel deeply that the medicine is an essential part of the experience. This raises the question, which I think is a very good one, of what a valid control would even look like.
danielvaughn 3y ago
What's frustrating is that Ibogaine has been known about for a long time. I remember reading, 20 years ago, about how Ibogaine had cured some people of alcoholism. It was all anecdotal at the time, but clearly there's something worth studying. I understand the hesitancy around drugs, but we've lost so much progress as a result of the bureaucratic red tape.
- sunshine_reggae 3y ago
  > What's frustrating is that Ibogaine has been known about for a long time. Not just Ibogaine - pretty much all of the "psychedelics". And it's just big pharma doing their evil deeds. Should have been obvious by now.
- jdietrich 3y ago
  Research has long been held up by legal obstacles, but articles like this are promoting an entirely false optimism about psychedelics. I live with a treatment-resistant mental illness, I have participated in clinical trials for psychedelics and I follow the field closely. Sadly, what we are seeing is almost certainly a hype bubble rather than a genuine breakthrough. We now have a useful body of research on psychedelics as a treatment for psychiatric disorders. We can be reasonably confident that they do indeed work, but the effect size in depression and anxiety appears to be very similar to SSRI antidepressants or cognitive behavioural therapy. Research into addiction is more limited, but plausible effect sizes are again comparable to existing treatments. We're much less confident about the risk profile (especially in real-world clinical settings), so any marginal benefits in efficacy might be outweighed by safety risks. Psychedelics might still prove useful as a second- or third-line treatment for a minority of patients, which I don't want to underplay - severe mental illness is truly awful and each additional patient in remission is a person given a second chance at life. They might provide insights that guide us towards better treatments in the future, but in this respect the NMDAR-agonists (ketamine etc) look far more promising. Unfortunately, the promise of psychedelics as a revolution in psychiatry is a busted flush. I wish I wasn't saying this, but the data doesn't care what my wishes are. We have reached the point in the curve where decent, well-meaning researchers are tinkering with the analysis post-hoc to try and make psychedelics look marginally more effective than existing treatments. A lot of money has been committed to research, the results are deeply disappointing, serious researchers are trying to salvage something useful, but all the while there's a steady drumbeat of deluded quacks and uninformed journalists continuing to peddle a narrative that has been thoroughly demolished. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399008/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399008/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278160/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278160/
goles 3y ago
It’s also worth noting the study size was only 30 veterans. All of them special forces apparently, which probably introduces a lot of other factors. Plus several participants failed to complete baseline or follow up work. Regardless, hopefully studied further in the future (legally)!
fragmede 3y ago
You don't need a control group at this stage to see there's something there that's worth further investigation. What's the control look like here? Do some elaborate ceremony, sit around in a circle, pretend to get high and see if the PTSD goes away? In the name of science, sure let's do that.
- cpncrunch 3y ago
  >You don't need a control group at this stage to see there's something there that's worth further investigation Actually, you do, as the placebo effect is very strong for depression. >What's the control look like here? You can give the drug during anaesthesia, like in the recent Ketamine trial. https://news.ycombinator.com/item?id=37948938 https://news.ycombinator.com/item?id=37948938
  - deleted 3y ago
    [deleted]
  - travisjungroth 3y ago
    > Actually, you do, as the placebo effect is very strong for depression. Is it an 80% reduction in symptoms? The trip may very well be an essential part of the experience. Giving it during anesthesia would be very different. Psychedelics just aren’t amenable to placebo controls. That doesn’t mean throw the whole science out, you just need to… control for that. You could have a non-placebo control of similar effort (talk therapy?) to control for drop outs. You could have alternative therapy as baseline.
    - cpncrunch 3y ago
      It was 50% reduction. Presumably a trip and not being anaethsetised would result in an even greater placebo effect. >You could have a non-placebo control of similar effort (talk therapy?) to control for drop outs. You could have alternative therapy as baseline. But that would have a much smaller placebo effect, and there would be no blinding to treatment. Comparing the two treatments wouldn't tell us anything. >The trip may very well be an essential part of the experience. Yes, I think it is, even if it is a very effective placebo. My point is that you don't need a psychedelic to cure depression of PTSD.
loceng 3y ago
MDMA is the furthest down the road to being clinically available.
- namlem 3y ago
  Yeah, phase 3 trials are concluded, it's now awaiting FDA review. Likely to be approved by the end of this year.
- d1str0 3y ago
  Ketamine in the form of Spravato is currently clinically available.
  - loceng 3y ago
    Good point. It's also covered, ketamine via IV, for pain management in some Canadian provinces.
  - NoZebra120vClip 3y ago
    [flagged]
    - loceng 3y ago
      The whole Matthew Perry situation has a lot of odd behaviour to it, and I'd make a bet and put odds on ketamine being a cover story to detract from the likely culprit.
    - asveikau 3y ago
      So maybe don't use it unsupervised in a hot tub?
    - ThePowerOfFuet 3y ago
      Propofol is a useful, well-tested anesthetic. Michael Jackson abused it and discovered the consequences, but that doesn't make it any less legitimate of a drug.
      - 3y ago
6stringmerc 3y ago
[dead]

by ajb 3y ago

red_admiral 3y ago

"small study finds" has happened before, in the context of mental health cures, for everything from LSD to yoga to going 48 hours without sleep. Many other things that can induce altered states of consciousness have probably been studied at small scale too (like you say, Psilocybin). For each one, there's always some subgroup that responds to it. "small study finds" is also how we landed ourselves with a replication crisis, so your comment about putting it into context is very appropriate.

sph 3y ago

Why Mexico when it is native to Central Africa?

asveikau 3y ago
I know nothing of this topic, but my guess is proximity to the United States and a different drug regulation scheme.
namlem 3y ago
Access to the American market.

Aurornis 3y ago

There was also no control group, which is a fatal flaw in any depression related study. If you're not aware: Depression studies have a very high placebo response rate. It's often hard to get new antidepressants to demonstrate improvements in studies not because the patients don't get better, but because the placebo group improves so much that the difference between the groups is small. This doesn't mean that antidepressants are placebo, it just means that if you take depressed people and tell them they're going to get better, then give them a lot of attention and activity from clinicians, they start to improve. This study definitely needs a control group, as the patients went all the way to Mexico on a small vacation to receive the drug. I guarantee that if you take a cohort of depressed patients, send them to Mexico for a short vacation and hand them a placebo pill that you tell them is an antidepressant, many of them will improve substantially on various measures upon return. This is why placebo control groups are critical for any depression study. I don't think it's a coincidence that so many of these psychedelics-for-depression studies omit control groups. Including a control group increases the cost, but it also is guaranteed to reduce the "wow factor" of a depression study. Therefore, they get omitted any time someone wants to make an antidepressant look effective. If this was a study for a new SSRI that didn't have a control group, people would be tearing it apart. For some reason people love stories about psychedelics doing magical things, though, so a lot of people are willing to overlook the most glaring fault of this study.

BobaFloutist 3y ago
PTSD is a dramatically different disorder to MDD though, no? It has pretty acute effects, and I don't know, but I would imagine it's less susceptible to placebo. Not to say this trial is any higher quality than it is, or that your sidebar on MDD wasn't interesting, but I'm not sure it's that effective of a comparison.
worik 3y ago
Yes. But psychedelic studies are impossible with double blind It is important to be rigorous in your study, but cannot expect too much Psychedelic therapies are not like antibiotic therapies, they interact in complex and confounding ways with set and setting
elmomle 3y ago
It is not the medicine by itself but the whole experience around it. Practitioners feel deeply that the medicine is an essential part of the experience. This raises the question, which I think is a very good one, of what a valid control would even look like.

danielvaughn 3y ago

What's frustrating is that Ibogaine has been known about for a long time. I remember reading, 20 years ago, about how Ibogaine had cured some people of alcoholism. It was all anecdotal at the time, but clearly there's something worth studying. I understand the hesitancy around drugs, but we've lost so much progress as a result of the bureaucratic red tape.

sunshine_reggae 3y ago
> What's frustrating is that Ibogaine has been known about for a long time. Not just Ibogaine - pretty much all of the "psychedelics". And it's just big pharma doing their evil deeds. Should have been obvious by now.
jdietrich 3y ago
Research has long been held up by legal obstacles, but articles like this are promoting an entirely false optimism about psychedelics. I live with a treatment-resistant mental illness, I have participated in clinical trials for psychedelics and I follow the field closely. Sadly, what we are seeing is almost certainly a hype bubble rather than a genuine breakthrough. We now have a useful body of research on psychedelics as a treatment for psychiatric disorders. We can be reasonably confident that they do indeed work, but the effect size in depression and anxiety appears to be very similar to SSRI antidepressants or cognitive behavioural therapy. Research into addiction is more limited, but plausible effect sizes are again comparable to existing treatments. We're much less confident about the risk profile (especially in real-world clinical settings), so any marginal benefits in efficacy might be outweighed by safety risks. Psychedelics might still prove useful as a second- or third-line treatment for a minority of patients, which I don't want to underplay - severe mental illness is truly awful and each additional patient in remission is a person given a second chance at life. They might provide insights that guide us towards better treatments in the future, but in this respect the NMDAR-agonists (ketamine etc) look far more promising. Unfortunately, the promise of psychedelics as a revolution in psychiatry is a busted flush. I wish I wasn't saying this, but the data doesn't care what my wishes are. We have reached the point in the curve where decent, well-meaning researchers are tinkering with the analysis post-hoc to try and make psychedelics look marginally more effective than existing treatments. A lot of money has been committed to research, the results are deeply disappointing, serious researchers are trying to salvage something useful, but all the while there's a steady drumbeat of deluded quacks and uninformed journalists continuing to peddle a narrative that has been thoroughly demolished. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399008/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399008/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278160/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278160/

goles 3y ago

It’s also worth noting the study size was only 30 veterans. All of them special forces apparently, which probably introduces a lot of other factors. Plus several participants failed to complete baseline or follow up work. Regardless, hopefully studied further in the future (legally)!

fragmede 3y ago

You don't need a control group at this stage to see there's something there that's worth further investigation. What's the control look like here? Do some elaborate ceremony, sit around in a circle, pretend to get high and see if the PTSD goes away? In the name of science, sure let's do that.

cpncrunch 3y ago
>You don't need a control group at this stage to see there's something there that's worth further investigation Actually, you do, as the placebo effect is very strong for depression. >What's the control look like here? You can give the drug during anaesthesia, like in the recent Ketamine trial. https://news.ycombinator.com/item?id=37948938 https://news.ycombinator.com/item?id=37948938
- deleted 3y ago
  [deleted]
- travisjungroth 3y ago
  > Actually, you do, as the placebo effect is very strong for depression. Is it an 80% reduction in symptoms? The trip may very well be an essential part of the experience. Giving it during anesthesia would be very different. Psychedelics just aren’t amenable to placebo controls. That doesn’t mean throw the whole science out, you just need to… control for that. You could have a non-placebo control of similar effort (talk therapy?) to control for drop outs. You could have alternative therapy as baseline.
  - cpncrunch 3y ago
    It was 50% reduction. Presumably a trip and not being anaethsetised would result in an even greater placebo effect. >You could have a non-placebo control of similar effort (talk therapy?) to control for drop outs. You could have alternative therapy as baseline. But that would have a much smaller placebo effect, and there would be no blinding to treatment. Comparing the two treatments wouldn't tell us anything. >The trip may very well be an essential part of the experience. Yes, I think it is, even if it is a very effective placebo. My point is that you don't need a psychedelic to cure depression of PTSD.

loceng 3y ago

MDMA is the furthest down the road to being clinically available.

namlem 3y ago
Yeah, phase 3 trials are concluded, it's now awaiting FDA review. Likely to be approved by the end of this year.
d1str0 3y ago
Ketamine in the form of Spravato is currently clinically available.
- loceng 3y ago
  Good point. It's also covered, ketamine via IV, for pain management in some Canadian provinces.
- NoZebra120vClip 3y ago
  [flagged]
  - loceng 3y ago
    The whole Matthew Perry situation has a lot of odd behaviour to it, and I'd make a bet and put odds on ketamine being a cover story to detract from the likely culprit.
  - asveikau 3y ago
    So maybe don't use it unsupervised in a hot tub?
  - ThePowerOfFuet 3y ago
    Propofol is a useful, well-tested anesthetic. Michael Jackson abused it and discovered the consequences, but that doesn't make it any less legitimate of a drug.
    - 3y ago

6stringmerc 3y ago

[dead]