Chapter 23 — Quiz

Twenty-two questions. Answer before opening the key. Several questions have deliberately similar options; the distinctions they turn on are the ones the chapter is about.


1. The claim "this peptide is a nootropic," offered without further specification, receives ❌ in this chapter primarily because:

  • A. Animal data contradicts it
  • B. The compounds so described have failed randomized trials
  • C. It names no endpoint, no instrument, and no population, so nothing could confirm or refute it
  • D. Nootropics are not peptides

2. Semax is related to a fragment of which molecule?

  • A. Tuftsin
  • B. Adrenocorticotropic hormone (ACTH)
  • C. Angiotensin IV
  • D. Brain-derived neurotrophic factor

3. Selank is a synthetic analog related to:

  • A. An ACTH fragment
  • B. Ciliary neurotrophic factor
  • C. Tuftsin, an endogenous tetrapeptide from the heavy chain of immunoglobulin G
  • D. Vasopressin

4. Semax and Selank share a C-terminal Pro-Gly-Pro extension. Its principal purpose is to:

  • A. Increase receptor affinity
  • B. Resist rapid peptidase degradation and extend the molecule's useful life
  • C. Enable crossing of the blood-brain barrier from the bloodstream
  • D. Reduce immunogenicity

5. Which statement about the approval status of Semax and Selank is correct?

  • A. Both are approved in the E.U. but not the U.S.
  • B. Both are registered medicines in Russia and are not approved in the United States or the European Union
  • C. Both are approved in the U.S. for narrow neurological indications
  • D. Neither is approved anywhere; both are research chemicals

6. A compound is unapproved in the United States. In the large majority of such cases, the reason is:

  • A. The FDA reviewed a submitted dossier and rejected it on safety grounds
  • B. The FDA reviewed a submitted dossier and rejected it on efficacy grounds
  • C. No sponsor ever filed, usually for commercial reasons
  • D. An approval was granted and later withdrawn

7. "The accessibility of a finding to you is not a property of the finding." This sentence is directed against:

  • A. The credulous failure
  • B. The parochial failure
  • C. Rule 3
  • D. Publication bias

8. Which of the following is a documented problem of Western research literatures specifically named in §23.3?

  • A. Publication bias
  • B. Industry funding effects
  • C. Selective outcome reporting
  • D. All of the above

9. In the six-question grid of §23.3, an entry of "?" means:

  • A. The study failed that criterion
  • B. The study passed that criterion but did not report it
  • C. You could not determine the answer, and you are recording that fact rather than guessing
  • D. The criterion does not apply to that literature

10. Cerebrolysin is best described as:

  • A. A single synthetic peptide of defined sequence
  • B. A recombinant human neurotrophic protein
  • C. A preparation of low-molecular-weight peptides and free amino acids derived from porcine brain tissue
  • D. A mixture of amino acids only, with no peptide content

11. The chapter's rating for Cerebrolysin in stroke or dementia is ⚠️ because:

  • A. No human trials have been conducted
  • B. Randomized trials and meta-analyses exist and produce genuinely mixed results, with substantial heterogeneity and sustained methodological criticism
  • C. The evidence is uniformly positive but the product is unapproved in the U.S.
  • D. The evidence is entirely inaccessible in English

12. When a body of randomized evidence remains mixed after many trials and many years, the most common explanations include all of the following EXCEPT:

  • A. The true effect is small
  • B. The effect is conditional on population or timing
  • C. The effect is absent and positive results reflect ordinary bias
  • D. The effect is large but has been consistently overlooked

13. Dihexa is:

  • A. A tuftsin analog
  • B. A synthetic angiotensin IV analog reported to affect synaptogenesis in animal models
  • C. A porcine brain-derived mixture
  • D. A dipeptide ethyl ester

14. The ❌ assigned to Dihexa and P21 means:

  • A. The compounds have been shown not to work in humans
  • B. The compounds are unsafe
  • C. The confident human claims being made are unsupported, because no human trials have been completed
  • D. The preclinical work is unreliable

15. Noopept is discussed in this chapter mainly to make which point?

  • A. That dipeptides are more potent than longer peptides
  • B. That calling something a peptide borrows credibility the compound has not earned, and readers should notice when a category is doing rhetorical work
  • C. That small molecules are always safer than peptides
  • D. That oral administration is generally achievable for peptides

16. Which property of Noopept is inconsistent with it being a peptide drug in this book's sense?

  • A. It contains a proline residue
  • B. It is routinely administered orally and is roughly 320 daltons
  • C. It has been studied for cognitive endpoints
  • D. It is synthetic

17. An uncontrolled before-and-after cognitive study will typically show improvement even if the intervention is inert. The single largest reason is:

  • A. Regression to the mean
  • B. Practice effects
  • C. Measurement noise
  • D. Reporting bias

18. Baseline dependence implies which of the following?

  • A. A positive result in sleep-deprived participants supports a claim about rested participants
  • B. A null result in healthy young adults refutes a claim about impaired populations
  • C. A positive result in an impaired population does not support a claim about healthy adults
  • D. Effects are always larger in healthy populations

19. A results section reads: "Significant improvements were observed in verbal fluency and processing speed, with a trend toward improvement in delayed recall." The most important missing piece of information is:

  • A. The participants' ages
  • B. The total number of comparisons performed, and which endpoint was pre-specified as primary
  • C. The manufacturer of the test battery
  • D. The time of day of testing

20. A "blinding integrity check" is:

  • A. Confirming that the placebo and active preparations look identical
  • B. Asking participants at the end of the study which arm they believe they were in, and reporting the result
  • C. Verifying that the randomization list was concealed from investigators
  • D. Testing the placebo for contamination

21. Why is the placebo arm of a cognitive enhancement trial not an inert condition?

  • A. Because placebos often contain active excipients
  • B. Because believing you have taken something that sharpens focus genuinely increases effort, arousal, and persistence, which genuinely improve task performance
  • C. Because participants in the placebo arm practice less
  • D. Because placebo response does not occur for objective endpoints

22. Which of the following is NOT part of the chapter's specification for a convincing trial?

  • A. Pre-registration of protocol, primary endpoint, and analysis plan
  • B. A single pre-specified primary endpoint on a validated instrument
  • C. Results reported regardless of outcome
  • D. Approval by the United States Food and Drug Administration before publication

Answer key **1 — C.** The rating attaches to a claim form, not a molecule (rule 1). An unspecified nootropic claim is not weakly supported; it is unevaluable, because no result could confirm or refute it. A is wrong because no molecule has been named for animal data to bear on. **2 — B.** Semax is a synthetic peptide related to a fragment of ACTH, built from the behaviorally active ACTH(4–10) region rather than the hormonal, cortisol-releasing function. **3 — C.** Tuftsin is an endogenous tetrapeptide from the heavy chain of immunoglobulin G, best known for immune-related activity — which is why it also appears in Chapter 18. **4 — B.** Proline resists peptidase attack; the tail is a half-life intervention of the kind Chapter 4 catalogs. Note what it does *not* do: it does not solve absorption, distribution, or blood-brain barrier penetration (option C is the common misreading). **5 — B.** Both were developed in Russia, both are registered medicines there, and neither is approved in the U.S. or E.U. **6 — C.** "The FDA has not approved it" and "the FDA looked and said no" are entirely different facts, and only the second is evidence about the compound. Filing means running new trials to a new agency's specification at considerable cost, often with an unclear patent position. **7 — B.** The parochial failure — dismissing work because it is unfamiliar or hard to reach. The sentence is the core rebuttal: a trial does not become less true because its report is in a language you do not read. **8 — D.** All three are named, along with the replication difficulties of the oxytocin literature (Chapter 21). The symmetry is the point: the standard is not "Western good, other bad." **9 — C.** "?" is a legitimate answer. It is not a zero and it is not a pass. Recording it honestly is the skill §23.3 teaches. **10 — C.** A mixture produced by enzymatic breakdown of biological tissue — which is why Field 1 of the dossier cannot be completed for it the way it can for a single-molecule drug. **11 — B.** This is the chapter's clearest ⚠️: real trials, accessible in English, and genuine disagreement. Contrast with the Semax/Selank ⚠️, which reflects limited *access* to evidence rather than conflict within it. **12 — D.** Large, reliable treatment effects are not shy; they show up in the first adequately powered trial and survive skeptical reanalysis. Twenty years of disagreement is itself a measurement, and what it measures is an upper bound on effect size. **13 — B.** An angiotensin IV analog, with hepatocyte growth factor and its receptor proposed as the mechanism. D describes Noopept. **14 — C.** Rule 2: ❌ describes the evidence, not the molecule's potential. Both compounds may yet turn out to do something in humans; the ❌ says only that today nobody knows. **15 — B.** The label matters because calling something a peptide borrows the credibility of insulin and semaglutide (§1.5). A category is not a finding. **16 — B.** Its size and oral activity are precisely the properties peptide drugs lack. Calling it a peptide attributes to it the constraints it escaped. **17 — B.** People improve on cognitive tests simply by repeating them, reliably and often for weeks or months. Regression to the mean and noise contribute, but practice effects are the dominant and most systematic term — which is why the control group is not a formality but the measurement. **18 — C.** Effects are frequently larger where there is more room to move. A, B, and D all invert or overreach the principle; note that B is the version skeptics commit. **19 — B.** Without the denominator, a list of positive findings is uninterpretable (§5.10). A pre-specified primary endpoint produces a different sentence entirely: *the primary endpoint was A; here is what happened to A.* **20 — B.** Cheap, rare, and highly informative. When you see it reported, the study has told you something about its authors independent of its result. **21 — B.** The placebo arm is a competing intervention working through motivation. This raises the bar for the active compound rather than lowering it — and it does not license "so the placebo is just as good," because the effect is a property of the belief, not of the molecule being sold. **22 — D.** Nothing in the chapter's specification is culturally or jurisdictionally specific. Every item is a countermeasure against a way humans fool themselves, and a trial run anywhere that meets it would move these ratings.