Reduction of apathy and caregiver distress using a combination of tetrahydrocannabinol and melatonin in dementia due to Alzheimer’s disease
Bibliographic record
Abstract
Abstract Background Apathy is one of the most frequent and long‐lasting neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD). Up to 78% of AD patients exhibit apathy, which is related to caregiver distress, decreased quality of life, and increased morbidity. While many medications and behavioral interventions are used to treat apathy, the effects are often limited and lack in‐depth research to support these approaches. We present preliminary data for improvement in NPI‐apathy (NPI‐ap) scores and NPI Caregiver Distress (NPI‐D) scores using IGC‐AD1, a tetrahydrocannabinol (THC) and melatonin combination. 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. Solicited and non‐solicited adverse events (AEs) were monitored daily. In each Cohort, seven participants (5‐active, 2‐placebo) had apathy at baseline, as rated by the NPI‐ap. They were administered the NPI‐ap at EOT and the Wilcoxon matched pairs signed‐rank test (R‐Studio, dplyr) was used to compare the difference in NPI‐ap scores between baseline and EOT. A similar analysis was carried out for NPI‐D. Result In Cohort‐1 mean NPI‐ap at baseline and EOT was 5.4 and 3 respectively (mean difference = ‐2.4, v = 6, p = 0.091). In Cohort‐2 mean NPI‐ap at baseline and EOT was 5.2 and 2.4 respectively (mean difference = ‐2.8, v = 6, p = 0.087). In Cohort‐3 mean NPI‐ap at baseline and EOT was 5.2 and 2.6 respectively (mean difference = ‐2.6, v = 6, p = 0.087). Results for NPI‐D: (Cohort‐1:mean difference = ‐0.6, 37.5%, v = 6, p = 0.075; Cohort‐2:mean difference = ‐1.8, 69.2%, v = 15, p = 0.028; Cohort‐3:mean difference = ‐0.2, 12.5%, v = 2, p = 0.5). No serious AEs, no deaths, and no dropouts due to AEs were reported. No major changes in concomitant medications were observed. Conclusion As IGC‐AD1 contains THC, the results are intriguing because cannabis use has been associated with apathy but also increased empathy and sociality. In Cohort‐1, Cohort‐2, and Cohort‐3 NPI‐ap was reduced 44.44%, 53.85%, and 50% respectively. These results, while not statistically significant (p>0.05), appear clinically significant (reduction≥30%). A larger placebo‐controlled study is warranted.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| 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 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".