0612 Evaluation of Abuse Potential of the Narcolepsy Medication Pitolisant
Bibliographic record
Abstract
All medications currently approved by the US FDA for the treatment of narcolepsy are controlled substances. Pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, is approved in Europe for the treatment of narcolepsy with or without cataplexy in adults. This randomized, double-blind, active- and placebo-controlled, single-dummy, 4-sequence 4-way crossover study evaluated the abuse potential of single-dose pitolisant (35.6 mg [therapeutic dose] and 213.6 mg [supratherapeutic dose]) compared with the stimulant phentermine HCl (60 mg; a Schedule IV controlled substance) and placebo in nondependent recreational stimulant users. The primary endpoint was peak effect (Emax) for Drug Liking “at this moment” on a bipolar visual analogue scale (0=strong disliking, 100=strong liking). Key secondary endpoints included Overall Drug Liking and willingness to Take Drug Again. Between-treatment comparisons were analyzed using a mixed-effect model for a crossover study. After confirming their ability to discriminate phentermine (active control) from placebo, 43 participants were randomly assigned to 1 of 4 treatment sequences. For 38 participants who completed the study (73.7% male; 65.8% white; mean age, 33.3 years), mean (SE) Drug Liking Emax was 78.7 (2.8), 59.0 (2.1), 57.3 (2.1), and 56.1 (2.1), respectively, for phentermine, pitolisant 213.6 mg, pitolisant 35.6 mg, and placebo. Mean Drug Liking Emax was significantly greater for phentermine compared with placebo (P<0.0001), confirming study validity. For both doses of pitolisant, mean Drug Liking Emax was significantly lower compared with phentermine (P<0.0001) and similar to placebo. Additionally, for Overall Drug Liking and Take Drug Again, mean Emax scores were significantly lower for pitolisant (both doses) relative to phentermine (P<0.0001) and similar for pitolisant (both doses) compared with placebo. The most common adverse event with pitolisant was headache (pitolisant 35.6 mg, 15.0%; pitolisant 213.6 mg, 25.0%; placebo, 12.2%; phentermine, 10.3%). Pitolisant demonstrated significantly lower Drug Liking and willingness to Take Drug Again compared with phentermine and a profile similar to placebo; together with the lack of any abuse signal in preclinical studies, these findings suggest that pitolisant has minimal risk of abuse. Bioprojet Pharma and Harmony Biosciences, LLC.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".