# Metabolic Profile of Male Cannabis Users and Estimation of Candidate Biomarkers

## TL;DR

This study identifies potential biomarkers and metabolic pathways affected by cannabis use in males, using urine metabolomic analysis.

## Contribution

The study presents novel candidate biomarkers and metabolic insights specific to male cannabis users.

## Key findings

- 92 metabolites showed significant differences between cannabis users and nonusers.
- Amino acid and vitamin metabolism pathways were prominently affected.
- Four metabolites (salsoline, 6-thiourate, procollagen 5-hydroxy-lysine, and biotin) showed high AUC values as potential biomarkers.

## Abstract

Tetrahydrocannabinol
(THC), the primary psychoactive compound of
cannabis, is the most widely abused substance worldwide, with an annual
prevalence of 4.3% of adults and 5.3% of the 15–16 year-old
population estimated as of 2022. THC has both acute and chronic effects
through the dopaminergic and endocannabinoid systems. This study was
conducted to better understand the metabolites and metabolic pathways
in biological systems affected by cannabis, which may help find practical
diagnostic and treatment approaches for people with cannabis dependence
in the future. Metabolomic analysis of urine samples was performed
using gas chromatography–mass spectrometry (GC–MS).
MetaboAnalyst software was used to determine sample metabolite profiles,
which were then subjected to multivariate statistical analysis. From
data of over 200 metabolites in each sample of cannabis users, 92
metabolites with a p-value of less than 0.05 were
selected for further analyses, of which 38 showed a decrease and 54
showed an increase compared to the nonuser group. Based on 43 metabolites
(VIP > 1), subjected to MetaboAnalyst and CPDB, amino acid metabolism
(especially arginine, methionine, and cysteine), vitamin metabolism
(particularly biotin), and the urea cycle were the primarily affected
metabolic pathways. The AUC values of the four metabolites (salsoline,
6-thiourate, procollagen 5-hydroxy-
l
-lysine,
and biotin) with the highest VIP scores were between 0.93 and 0.98,
with no significant difference. Metabolites with high VIP scores hold
promise as biomarker candidates for identifying cannabis users, and
the prominent pathways provide new insights into the understanding
of the metabolic effects of cannabis.