Acute Cognitive Effects of the Dual Orexin Receptor Antagonist Lemborexant Compared With Suvorexant and Zolpidem in Recreational Sedative Users
Bibliographic record
Abstract
PURPOSE/BACKGROUND: As part of a human abuse potential (HAP) study of lemborexant (LEM), the effects of therapeutic (LEM 10 mg), and supratherapeutic doses of LEM 20 mg and LEM 30 mg on cognition and psychomotor performance were compared with placebo (PBO) and supratherapeutic doses of zolpidem (ZOL) 30 mg and suvorexant (SUV) 40 mg. Subjects (n = 32) were healthy, nondependent, recreational sedative users able to discriminate the effects of both SUV and ZOL from PBO on subjective drug measures. METHODS/PROCEDURES: The human abuse potential study was a single-dose, randomized, double-blind, PBO-controlled, 6-way crossover study. Eligible subjects admitted to the treatment phase completed the choice reaction test (CRT) and divided attention test. The CRT included measurements of recognition reaction time (RRT) and motor reaction time. FINDINGS/RESULTS: Recognition reaction time and mean maximum change from baseline (CFB max ) scores were significantly increased (slower performance) versus PBO for all LEM doses (all P < 0.001), ZOL ( P < 0.001), and SUV ( P = 0.004), and LEM (all doses) was not statistically different from ZOL or SUV. Motor reaction time and mean CFB max versus PBO were significantly increased for all LEM doses (all P < 0.001), and ZOL ( P < 0.001) and SUV ( P < 0.001). All LEM doses showed significantly decreased (better performance) mean CFB max versus ZOL (all P < 0.001), but not SUV. Notably, all cognitive effects in the CRT and divided attention test were limited to the main treatment phase (up to 8 hours postdose). IMPLICATIONS/CONCLUSIONS: All active doses of LEM, ZOL, and SUV generally increased reaction time and reduced divided attention capabilities versus PBO. However, at therapeutic/supratherapeutic doses, LEM led to significantly less cognitive impairment than supratherapeutic doses of ZOL in some measures.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".