Effect of tetrahydrocannabinol and melatonin combination on suicide ideation and behavior in dementia due to Alzheimer’s disease
Bibliographic record
Abstract
Abstract Background Suicide ideation in young adults increases with regular use of marijuana. Separately, prevalence of suicide and dementia also increases with age, and Alzheimer’s disease (AD) is associated with a moderate risk of suicide. The Columbia‐Suicide Severity Scale (C‐SSRS) has been used since the FDA guidance in 2012, however, it has not been validated. Studies show its effectiveness in mild to moderate dementia, but not in severe dementia. Here, we present preliminary data on the application of C‐SSRS in a Phase 1 trial on AD patients using IGC‐AD1, a combination of tetrahydrocannabinol (THC) and melatonin (IGC‐AD1). Method Twelve patients with mild (15.38%) to moderate (84.6%) AD (NIA‐criteria, 10‐active, 2‐placebo, 81.5 ± 5.5yrs, 69.2% women) participated in a three Cohort Phase‐1, MAD, safety, and tolerability trial (IND146069, NCT04749563). In Cohort‐1, IGC‐AD1 was administered QD at 1ml for 14‐days (EOT). In Cohorts 2 and 3, one ml BID and TID were administered respectively with a minimum of 4‐days washout between Cohorts. Daily, solicited, and non‐solicited adverse events (AEs) were monitored along with vital signs. For all three Cohorts the C‐SSRS was administered at baseline and again on days 5,10, EOT and EOT+2 by a neuropsychologist. In addition, suicidal ideation was included as a solicited adverse event (AE) that was reported daily. Result In 420 man‐days (10 patients on active * 14 days * 3‐Cohorts) of dosing there was one day on which a participant on active medication self‐reported suicidal ideation as part of the solicited AEs. It self‐resolved the next day. All 150 administrations of C‐SSRS to the participants on active medication, across all three Cohorts, showed no suicide ideation or behavior. Likewise, across 30 administrations in the placebo group there were no suicide ideations or behaviors. No serious AEs, no deaths, and no dropouts due to AEs were reported. No major changes in concomitant medications were reported. Conclusion THC and melatonin in IGC‐AD1 did not increase the risk of developing suicidal ideation or behavior as assessed by the C‐SSRS in the mild to moderate AD trial population. The preliminary results also show that IGC‐AD1 was well tolerated and safe.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".