[cubefox]

> But it’s a problem for researchers running double-blinded clinical trials, as participants can usually tell whether they have received ketamine or a placebo. [...] The scientists gave the volunteers ketamine or saline as placebo right after they were put under anesthesia, but before their surgery, essentially blinding them to any psychedelic or dissociative effects.

That's a genius way to avoid unblinding. All psychoactive treatment trials have this problem: placebo controlled studies rely on patients not being able to distinguish whether they are in the test group or the control group. I hope future studies (say, for psilocybin) can also use this study design.

[BobbyJo]

If I did drug trials for pain killers this way, would it give any useful data?

Depression and pain are subjective. Personally, I think removing the subjectivity from the trial voids the trial. It is a clever design, but it really just proves the benefit is in the experience and not the physical mechanism.

[cubefox]

Having amnesia (forgetting whether they had a trip and whether they were in the treatment group) would probably be better than anesthesia induced unconsciousness. Though I don't know whether short term amnesia can be easily induced.

[vorpalhex]

Pain has subjective parts but it is not merely subjective. You can measure how much effect ibuprofen or tylenol has, even with someone knocked out. You can see pain on an mri, even with someone knocked out.

[BobbyJo]

Never heard that before, source?

Also, anesthesia would ruin whatever you hoped to see on an MRI.

[vorpalhex]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019436/

https://pubmed.ncbi.nlm.nih.gov/17512757/

[operatingthetan]

Maybe I'm misunderstanding context, but my cat may need an MRI and I've learned it's standard in all veterinary medicine to use anesthesia for scans in order to keep the patients immobile.

[BobbyJo]

Yeah, but they aren't trying to watch the effect of a drug happening. Anesthesia is accomplished with drugs. You can't give a person 3 different drugs, then expect a brain scan to tell you how one works in isolation.

[andybak]

Am I missing something blindingly obvious here? I would have assumed that the therapeutic effects of a strong mind-altering substance relies on being conscious to, you know, experience the effects.

Saying "It didn't work while the subject was asleep so therefore must be placebo" is just a bizarre position to take.

Imagine if a study stated "Cognitive Behavioural Therapy found to be ineffective on unconscious patients".

[cubefox]

The trip is very short, but the effect as a useful antidepressant has to last a lot longer. It's not clear why the trip itself would have anything but short term effects on depression.

[andybak]

Well, it's a hell of a lot clearer than a trip you slept through having a lasting effect.