Assessing the Subjective and Physiological Effects of Intranasally Administered Crushed Extended‐Release Morphine Formulations with and without a Sequestered Naltrexone Core in Recreational Opioid Users
Bibliographic record
Abstract
OBJECTIVE: To evaluate the pharmacodynamic (PD) effects of morphine sulfate and naltrexone hydrochloride extended-release (MSN) capsules compared with controlled-release morphine sulfate (MS) and placebo when crushed and administered intranasally. METHODS: The present study was a randomized, double-blinded, placebo-controlled, single-dose (30 mg), three-way crossover study in healthy, nondependent recreational opioid users. PD measures included assessment of subjective drug effects using visual analogue scales (VAS) ranging from 0 to 100 and assessments of pupil diameter. Blood samples were collected for pharmacokinetic analyses. RESULTS: Both MS and MSN showed significantly higher PD values compared with placebo. MSN showed significantly lower scores for drug liking and high VAS scores on both mean peak effect (Emax) (69.6 and 55.2, respectively) and in area under the effect curve over 2 h (86.3 and 66.7, respectively) following dosing compared with MS (Emax 87.6 and 86.6, respectively; area under the curve over 2 h 120.6 and 132.9, respectively; P<0.001). MSN showed significantly lower Emax for all other positive subjective effects (good drug effects, overall drug liking, and take drug again VAS scores) compared with MS (P<0.001). Peak minimum pupil diameter was significantly larger for MSN than MS (P=0.002). Mean peak plasma concentration (Cmax) and median time to Cmax for morphine following administration of MSN and MS were similar (27.3 ng⁄mL and 0.57 h versus 27.7 ng⁄mL and 0.6 h, respectively). Naltrexone mean Cmax was 1497 pg⁄mL after MSN and median time to Cmax was 0.55 h. CONCLUSIONS: When crushed and administered intranasally, MSN was associated with significantly lower ratings of drug liking and other positive subjective effects compared with MS.
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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) | 0.000 | 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".