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 dopamine production and signalling with chronic use [127], which further supports the allostasis model. Hill describes this phenomenon in the context of anxiety as the “rebound effect” such that individuals will experience anxiety and proceed to use cannabis to temporarily alleviate these symptoms. Overtime, and once the acute effects of cannabis dissipate, however, one’s affective state becomes further exacerbated due to the long-term effects of the substance [71]. The question remains as to why the perception remains that cannabis has therapeutic effects towards mental illness when the relief may be only acute during the time of intoxication and, ultimately, lead to a reduction in affect through allostasis production (Figure 1).
