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I'm reading about the toxicology of LSD, and the acute and subacute adverse effects (hypertension, hyperthermia, tachycardia) have been described as moderate in this article, modest in this article (page 2) and significant in this article (page 10). The second article cites the first and third articles when stating the modesty of the aforementioned effects.

By what standards are they designating these acute and subacute adverse effects moderate? Is there a scale one can look at to give the different safety levels of the intensity adverse reactions to pharmacological agents relative to their duration? According to this article, if one were to have these blood pressures chronically, then it'd be a problem. However, these effects are only acute, which probably increases the safety levels. According to the the first and third articles, there was little to no increase in adverse reaction between the LSD-ingesting and placebo-control groups.

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"Moderate" and "modest" are just descriptive adjectives. They don't have any quantitative meaning, and I'm not aware of any effort to standardize their meaning for these sorts of measures (blood pressure, heart rate, temperature), nor do the authors reference any such effort in using those terms. I think it would be fair to characterize these adjectives as referring to effects that are measurable but not of immediate clinical concern according to the authors. However, experts could of course vary on what sizes of effects they consider clinically concerning. One might compare to other types of "normal" baselines besides rest, like parameters one would observe during moderate exercise, but these authors haven't done that directly.

"Significant" is refering to statistical hypothesis testing, where "significant" refers to an effect that passes some predetermined threshold for deciding an effect is unlikely to have resulted purely by chance. Statistical significance says very little to nothing about the size of an effect, besides saying that it is probably different from zero. If you had a sufficiently sensitive scale (and/or a large enough sample size), you could weigh people before and after eating a cough drop and state that cough drops cause significant weight gain. After all, someone's weight after eating a ~3 gram cough drop will be approximately equal to their prior weight plus the 3 gram weight of a cough drop. There is a push in medical statistics these days to emphasize measures of effect size instead of or in addition to measures of statistical significance to avoid overstating the importance of effects that are statistically, but not clinically, significant.

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  • .Aha I see, I was wondering about the discrepancy between the two articles saying modest and the one article saying significant. So, pretty much, the authors saying the effects to be modest/moderate doesn't really mean anything more than that the authors deem the effects modest/moderate? Is there any place to view what values for blood pressure, body temp. and heart rate in proportion to duration pass the threshold for clinical concern? That would give me a more objective way to quantify the severity of these adverse effects.
    – A. Kvåle
    Jun 19, 2021 at 1:45
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    @A.Kvåle I don't think they're calling them adverse events, just physiological changes (though on mobile and not opening the papers now to check their language). The exact parameter changes that matter would depend somewhat on the individual so it's hard to give any precise number. A hypertensive crisis is typically 180 systolic or 120 diastolic. Resting heart rates over 100 are concerning but not necessarily a problem over short intervals (exercise for example).
    – Bryan Krause is on strike ♦
    Jun 19, 2021 at 3:05
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    @A.Kvåle Adverse effects are separate from the physiological parameters. They're in table S2 of one paper and S3 of the other. Difficulty concentrating, headache, exhaustion, dizziness, lack of appetite, dry mouth, imbalance, nausea, fatigue.
    – Bryan Krause is on strike ♦
    Jun 19, 2021 at 20:20
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    @A.Kvåle I don't think there's any way to make a generalizable benchmark for that.
    – Bryan Krause is on strike ♦
    Jun 19, 2021 at 21:03
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    sciencedirect.com/science/article/pii/S0006322314009093 is the primary URL for the article. Rather than vague assessments from the physiological parameters, you're probably better off judging LSD by the rate at which people suffer consequences from using it...which is vanishingly low when used in a supportive environment (though there is concern about psychological effects, which are particularly hard to study...). That is, people can get hurt by their own actions but don't typically get hurt by the drug.
    – Bryan Krause is on strike ♦
    Jun 19, 2021 at 23:08

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