Altered effective connectivity within the default mode network in kratom (Mitragyna speciosa) users: A resting-state fMRI study

Kratom (Mitragyna speciosa) is a Southeast Asian plant with stimulant and opioid-like properties, traditionally used for its medicinal effects. However, its increasing popularity and potential for dependence raise concerns about its impact on brain function. This study investigated alterations in effective connectivity (EC) within the default mode network (DMN), a network associated with self-related processes, in kratom users compared to healthy controls. Ten regular kratom users (mean age: 27.30 ± 3.97) and seven healthy controls (mean age: 20.72 ± 1.88) underwent resting-state functional magnetic resonance imaging (rs-fMRI). The EC analyses were performed using spectral dynamic causal modelling to examine directional influences between DMN regions. A fully connected model best represented EC in both groups; however, the control group lacked a significant connection between the right inferior parietal cortex (RIPC) and the posterior cingulate cortex (PCC). Kratom users exhibited hyperconnectivity between the medial prefrontal cortex (MPFC) and the left inferior parietal lobule (LIPL) connection compared to controls. Additionally, negative correlations were identified between the duration of kratom use and connectivity from PCC to RIPC. In contrast, positive correlations were observed between the duration of use and connectivity from RIPC to PCC. These findings suggest that kratom consumption may alter EC within the DMN, particularly the MPFC→LIPL connection, potentially due to chronic intake. This preliminary study provides neuroimaging insights into the effects of kratom on the brain and contributes to ongoing discussions regarding its potential for dependence and therapeutic applications.