After chronic and frequent cannabis use, the trajectory for developing CUD progresses. Addiction encompasses the adverse consequences of repeated drug misuse, which leads to neurobiological changes that further influence the neural circuitry involved in emotion, sensation, and higher order cognition [87]. Allostasis results from system neuroadaptations that change one’s homeostatic set-point in order to compensate for substance-induced changes in the brain. Neurotransmission and hormonal signalling adapt to accommodate the continual influence on reward circuitry by altering one’s set-point to maintain hedonic homeostasis. Consequentially, the cannabis user’s affective state, which is a combination of positive mood state processes and negative, anti-reward processes, becomes altered [87]. Dysfunctional reward neurotransmission (e.g. dopaminergic reward circuitry) results due to the consistent activations by, in this case, cannabis, as well as the anti-reward systems being developed and heightened [154]. This is due to the surge in reward activation followed by substance use, which then becomes downregulated to maintain allostasis, leading to chronic hypofunctioning of positive reinforcement circuitry and increased stress activation, such as hypothalamic-pituitary adrenal axis and corticotrophin releasing factor (CRF) stimulation [87]. Cannabis may blunt
