Intrinsic Frontolimbic Connectivity and Mood Symptoms in Young Adult Cannabis Users

Abstract

Objective: The endocannbinoid system and cannabis exposure has been implicated in emotional processing. The current study examined whether regular cannabis users demonstrated abnormal intrinsic (a.k.a. resting state) frontolimbic connectivity compared to non-users. A secondary aim examined the relationship between cannabis group connectivity differences and self-reported mood and affect symptoms.Method: Participants included 79 cannabis-using and 80 non-using control emerging adults (ages of 18–30), balanced for gender, reading ability, and age. Standard multiple regressions were used to predict if cannabis group status was associated with frontolimbic connectivity after controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis.Results: After controlling for research site, past month alcohol and nicotine use, and days of abstinence from cannabis, cannabis users demonstrated significantly greater connectivity between left rACC and the following: right rACC (p = 0.001; corrected p = 0.05; f2 = 0.55), left amygdala (p = 0.03; corrected p = 0.47; f 2 = 0.17), and left insula (p = 0.03; corrected p = 0.47; f 2 = 0.16). Among cannabis users, greater bilateral rACC connectivity was significantly associated with greater subthreshold depressive symptoms (p = 0.02).Conclusions: Cannabis using young adults demonstrated greater connectivity within frontolimbic regions compared to controls. In cannabis users, greater bilateral rACC intrinsic connectivity was associated with greater levels of subthreshold depression symptoms. Current findings suggest that regular cannabis use during adolescence is associated with abnormal frontolimbic connectivity, especially in cognitive control and emotion regulation regions.

Down and High: Reflections Regarding Depression and Cannabis

“…Cannabis is one of the most used substances worldwide (8). After alcohol and tobacco, cannabis ranks first for used substances in the United States (US) (9,10) and Canada (11).…”

“…The endogenous cannabinoid (or endocannabinoids) system (ECS) ( 29) is involved in regulating functions such as mood, cognition, feeding behavior, pain perception, inflammation, and stress responses (8,30). Furthermore, there is evidence that a hypoactive ECS may contribute to depression in humans (6).…”

“…The CB1 receptor is widely expressed in regions which are involved in reward and cognitive functions (30). The CB1 receptor modulates the GABAergic, glutamatergic, serotoninergic and noradrenergic systems (5,6,8) and promotes myelination (32).…”

“…At the neurobiological level, CB1 receptor density in the frontolimbic system has been shown to be lower in people consuming cannabis regularly. Those alterations with daily CU are reversed following a month of abstinence (8,95). This implies that it is necessary to maintain cannabis cessation for at least a month before evaluating its impact on clinical symptoms.…”

Altered amygdala-cortical connectivity in individuals with Cannabis use disorder

“…Furthermore, resting-state functional connectivity (rsFC) analyses can enhance understanding of specific brain networks and organization, particularly relating to the amygdala. A small number of studies have examined rsFC in CUD (Pujol et al, 2014; Shollenbarger et al, 2019; Whitfield-Gabrieli et al, 2018), but two of the three studies focused on the default-mode network (DMN) (Pujol et al, 2014; Whitfield-Gabrieli et al, 2018). One of these studies showed that long-term cannabis users have increased DMN connectivity with certain subregions of the PCC, along with decreased connectivity with other subregions compared to controls (Pujol et al, 2014).…”