Deconstructing the neurobiology of cannabis use disorder

Abstract

There have been dramatic changes worldwide in the attitudes toward and consumption of recreational and medical cannabis. Cannabinoid receptors, which mediate the actions of cannabis, are abundantly expressed in brain regions known to mediate neural processes underlying reward, cognition, emotional regulation and stress responsivity relevant to addiction vulnerability. Despite debates regarding potential pathological consequences of cannabis use, cannabis use disorder is a clinical diagnosis with high prevalence in the general population and that often has its genesis in adolescence and in vulnerable individuals associated with psychiatric comorbidity, genetic and environmental factors. Integrated information from human and animal studies is beginning to expand insights regarding neurobiological systems associated with cannabis use disorder, which often share common neural characteristics with other substance use disorders, that could inform prevention and treatment strategies.

Fig. 1 |

Odds ratios of psychiatric conditions associated with CUD. Data based on the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) study. Figures: Debbie Maizels/Springer Nature.

Fig. 2 |

Overview of the dynamic patterns of the in vivo neurochemical-related alterations (based on PET, functional MRI, and H-MRS studies) associated with CUD. a, Line graphs indicate specific alterations during acute use as compared to neurobiological state in individuals with CUD, including during periods of abstinence. b, Dots indicate brain regions in which neurochemical marks reflective of CB1R, dopamine transporter (DAT) and dopamine (DA) synthesis have been detected in individuals with CUD. ACC, anterior cingulate cortex; DS, dorsal striatum; PCC, posterior cingulate cortex; VS, ventral striatum. Figures: Debbie Maizels/Springer Nature.

Fig. 3 |

Alterations of gray matter volume (based on MRI studies) detected in individuals with CUD. Colors denote decreased (red) and increased (blue) gray matter volume. Figures: Debbie Maizels/Springer Nature.

Fig. 4 |

Differences in functional activity (based on functional MRI and electroencephalogram studies) detected in the brain of abstinent individuals with CUD during exposure to specific tasks and stimuli. Increased activation in specific regions is indicated in the left panel in red, and reduced activation is depicted in the right panel in blue. The specific task- or stimulus-driven alteration in activity is indicated in each region and circuit. Amy, amygdala; hipp, hippocampus; MCN, mesocorticolimbic network; FC, frontal cortex; NAc, nucleus accumbens; Str, striatum; MB, midbrain. Figures: Debbie Maizels/Springer Nature.

Fig. 5 |

Synaptic perturbations based on animal models associated with chronic THC exposure (right) as compared to control condition (left) in glutamate and GABA synapses in the cortex. THC is known to have a greater effect on the interneuronal GABA microcircuit, most likely due to the greater (~20-fold) number of CB1R on cortical GABAergic interneuron axon terminals compared to glutamatergic terminals. AMDAR, AMDA receptor; GABAR, GABA receptor; NCAM, neural cell adhesion molecule; NMDAR, NMDA receptor. Figures: Debbie Maizels/Springer Nature.

Fig. 6 |

Factors contributing to CUD. Schematic summary of multiple factors that contribute to the neurobiological patterns documented in relation to cannabis use and eventual CUD, where the more pronounced neurobiological alterations are associated with greater severity of the disorder and behavioral consequences. FAAH, fatty acid amide hydrolase; Glut, glutamate; Vol, volume. Figures: Debbie Maizels/Springer Nature.