Prediction of suicidal thoughts and behaviors based on the diurnal cortisol pattern and THC dosage in continued cannabis users, a 5 year population-based matched cohort study

Abstract

It appears that the THC dosage is the link between dysregulation of the hypothalamic pituitary adrenal (HPA) axis and suicidal thoughts and behaviors (STB). We proposed a new model to understand the underlying pathophysiological mechanism of STB based on the interaction of cortisol and THC dosage.From September 1, 2019, to January 1, 2024, we conducted a population-based, matched-pair, nested case-control study resulting from a three-wave complete longitudinal, multicenter cohort study on a sample of congress 60 clients. A total of 368 male continued cannabis users (CCu) were allocated to four categories, including low, moderate and high THC dosages and relapse, using optimal matching. Several HPA axis measures were analyzed in the saliva using liquid chromatography with tandem mass spectrometry (LC-MS-MS), and carboxylic acids levels in the urine were assessed via gas chromatography/mass spectrometry (GC–MS). We used structural equation modeling (SEM) to examine the relationship between the variables of interest and the model fit test, and used the Akaike information criterion (AIC) to compare the model fit and select the best-fitting model. Population attributable fractions (PAFs) and cumulative risk score were also calculated for the best-fitting pattern.The analysis showed that the likelihood of STB in individuals with a cortisol awakening response (CAR) and a blunted diurnal cortisol slope (DCS) and higher area under the curve (AUC) who reported heavy cannabis use was more than three times higher than the control group (OR 3.2, 95 % CI 2.4–4.1).These findings indicate the importance of the specific cortisol secretion pattern in the increased clinical expression of STB and may be an important factor for guiding preventive efforts in this area.