Effect of tetrahydrocannabinol and melatonin combination on suicide ideation and behavior in dementia due to Alzheimer’s disease

Abstract

AbstractBackgroundSuicide 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).MethodTwelve 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.ResultIn 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.ConclusionTHC 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.