Chapter 23 — Exercises

Thirty-four items. Work them in any order. Items marked † are the hard ones — they require you to hold two positions at once, or to reason to a conclusion the chapter does not hand you. No answers are provided here; several of these have no single correct answer, and the ones that do are checkable against §23.1–§23.9.

A few ground rules carried over from Chapter 5. Every rating you write must attach to a claim with a population and an endpoint. Every rating must state what would change it. And no exercise in this set asks you to decide whether anyone should take anything — that question is not in this book's scope, and any answer you write that reads like advice has answered a different question.

Part A — Taking claims apart

A. Rewrite each of the following as an evaluable claim with a population, an endpoint, and a timeframe. If a statement cannot be rewritten without inventing content, say so and explain what is missing. 1. "Supports cognitive function." 2. "Neuroprotective." 3. "Enhances mental clarity and focus." 4. "Improves brain health."

B. The §23.1 table lists seven things "nootropic" might mean. For each of the seven, name one population in which that endpoint would be easy to move and one in which it would be hard, and say why.

C. Chapter 10 examined "anti-inflammatory" and Chapter 18 examined "immune modulation." State the structural flaw all three terms share in a single sentence that uses none of the three phrases. Then name a fourth term, from anywhere in medicine or nutrition, that has the same flaw.

D. † A vendor's page says a compound is "clinically studied for neuroprotection." Write down every distinct thing that sentence could be true of — including the readings under which it is true and tells you nothing useful. Then write the single question you would ask to collapse the ambiguity.

E. "Improves attention in sleep-deprived adults" promises less than "improves cognition." Explain in three sentences why the smaller claim is the more valuable one, using the word falsifiable once.

Part B — Semax, Selank, and the design idea

F. Draw the shared architecture of Semax and Selank from memory: the active fragment each derives from, and the shared tail. Label which part supplies the proposed activity and which part addresses a pharmacokinetic problem.

G. Explain, using §1.2, why proline is a sensible residue to put at the end of a short peptide you want to survive in the bloodstream. Then explain what glycine is doing between the two prolines.

H. A stabilizing tail solves one of the four problems Chapter 4 catalogs. Name the other three, and state for each whether Pro-Gly-Pro addresses it.

I. Both compounds are typically given intranasally. List every distinct uncertainty Chapter 22 attaches to that route, and for each one say whether it would tend to produce a false positive, a false negative, or unpredictable noise in a trial.

J. † A source states that Semax has a "prolonged duration of action." Write two different claims this sentence could be making, name the different evidence each would require, and explain how a trophic mechanism makes it possible for both to be true simultaneously without either supporting the other.

K. Someone tells you the BDNF mechanism "explains why Semax works." Identify the rule this violates and rewrite their sentence so that it says only what mechanism evidence can support.

L. Distinguish, in your own words, these three statements about a compound: (i) the FDA has not approved it; (ii) the FDA reviewed it and declined to approve it; (iii) no sponsor has ever filed for it. Which of the three is evidence about the compound?

Part C — Evidence from another regulatory culture

M. Write out the six trial-quality questions from Chapters 5 and 6 from memory. Beside each, write what you would need in order to answer it, and mark which of those you could obtain for a paper you cannot read.

N. State the parochial failure and the credulous failure in one sentence each, then write one sentence identifying what they have in common.

O. † Rule 4 says never downgrade with distaste. Write down an honest example, from your own thinking, of a time you found a source less credible for a reason that turned out to be about the source's origin, presentation, or associations rather than its content. Then write the specific study-quality question you should have asked instead.

P. For each item below, decide whether it is a fact about the evidence or a fact about your access to the evidence, and say why the distinction matters: 1. The trials were small. 2. The full texts are in a language you do not read. 3. The primary endpoint was not pre-specified. 4. The journal is not indexed in the database you searched. 5. Blinding was not reported. 6. No systematic review in your language has assessed the studies.

Q. Chapter 21 described replication difficulties in the intranasal oxytocin literature. Write a paragraph explaining why that literature is a useful comparison here — and be specific about what it does and does not license you to conclude about any other literature.

R. † Construct the strongest possible version of the argument that a long-registered foreign medicine deserves more credence than this chapter gives it. Make it genuinely strong: use real principles, not straw. Then write the strongest reply. Then state which parts of the original argument survive the reply.

S. "An absence of trials is often a fact about money rather than a fact about biology" (§23.3). Give two examples from elsewhere in this book where that is true, and one situation where the absence of trials genuinely is informative about the compound.

T. † Design a five-step procedure that a reader with no relevant language skills could follow to form a defensible position on an inaccessible literature. Your procedure must produce a written output, must specify at least one thing the reader should refuse to conclude, and must include a condition under which the reader revisits it.

Part D — Cerebrolysin and mixed evidence

U. Cerebrolysin is a mixture rather than a single molecule. List three consequences of that for how its trial literature should be read.

V. Try to fill in Field 1 of the dossier (Chapter 1) for Cerebrolysin. Where you cannot complete a line, write what you would need in order to complete it. What does the shape of the resulting entry tell you?

W. §23.4 lists four things "mixed results" usually mean. Rank them by how often you would expect each to be the answer for a treatment tested repeatedly over twenty years, and defend your ranking in three sentences.

X. † A reader concludes: "The evidence is mixed, so the honest position is that we do not know whether it works, which means it might work very well." Identify the error in the second half of that sentence, and state precisely what mixed evidence after many trials does tell you about the likely size of an effect.

Y. Both Semax/Selank and Cerebrolysin receive ⚠️. Write the two ratings out in the four-line format and then write one paragraph explaining, to someone who has only seen the symbols, why they are not the same rating.

Part E — Preclinical-only compounds and the label question

Z. Write the ❌ rating for Dihexa and P21 in the four-line format without looking at §23.5. Then compare yours to the book's and note any difference in the "what would change it" line.

AA. Chapter 17 established a posture toward preclinical-only compounds. State it in two sentences, then apply it to a compound not discussed in this chapter.

AB. † "Interesting animal data and no human evidence are both true, and neither cancels the other." Explain why people find this position so hard to hold, and describe the rhetorical pressure that pushes readers toward one side or the other. Then write the sentence you would use to state the position to a skeptical friend in one breath.

AC. Explain why "no human trials" is not the same claim as "known to be unsafe," and why the difference does not make the situation more reassuring.

AD. Noopept is roughly 320 daltons. Place it on the §1.6 size spectrum and list every practical property that follows from its position there. Then explain what calling it a peptide obscures.

AE. Find three products or articles that use the word peptide in a place where it is doing rhetorical rather than descriptive work. For each, write the sentence with the word removed and note what is lost — and whether anything true was lost.

Part F — Cognitive endpoints and placebo

AF. Reproduce the six-term diagram from §23.7 from memory. Then, for each of the five non-drug terms, name one design feature that controls it.

AG. † An investigator proposes a study: forty healthy adults, a validated cognitive battery at baseline and at eight weeks, self-reported focus ratings weekly, no control group, because "each participant serves as their own control." Write a one-page critique. Identify what the design can legitimately establish, what it cannot, and what the single most consequential change would be. Then estimate — with reasoning, not a number pulled from air — the direction and rough size of the change you would expect to see even if the compound were entirely inert.

AH. For each of the five failure modes in §23.7, write one sentence describing how it would show up in a personal self-experiment rather than in a formal trial.

AI. Design an active comparator for a hypothetical intranasal cognitive peptide. State what sensations it must reproduce, what it must not do, and how you would verify that it worked as a comparator.

AJ. † A trial reports a statistically significant improvement on its pre-specified primary endpoint, and also reports that 78% of participants correctly identified their allocation. Write down what you now believe about the result, what you would need in order to move from that belief to a firmer one, and whether the honest reading changes if the compound's side-effect profile is described as "mild and comparable between arms."

AK. Explain why the placebo arm in an enhancement trial is not an inert condition. Then explain why that observation does not license the conclusion "so the placebo is just as good."

AL. † Write the trial protocol summary — one page, no numbers you cannot justify — for a study that would move the Semax rating from ⚠️ to either ✅ or ❌. Include the population, the single primary endpoint and its instrument, the comparator, the duration, the pre-registration commitment, and the publication commitment. Then write the one sentence you would add explaining why the trial is worth running given everything in §23.3.

Part G — Dossier work

AM. Complete Field 5 for one compound in your own dossier using the §23.3 six-question grid, with "?" entered honestly wherever it belongs. Count your question marks. If there are none, check whether you have actually read the primary sources or only summaries of them.

AN. † Go back through your dossier and identify any entry where your rating has moved since you first wrote it. For each, state whether it moved because new evidence arrived, because you read something you had previously only skimmed, or because your feelings about the compound changed. Be honest about the third category. Then write one sentence about what the pattern suggests about your own bias — the same question Chapter 40 will ask you formally.