When an individual experiences withdrawal, there are two outcomes: a negative affective state common among many substances, described as the “rebound effect” or allostatic phenomenon, as well as drug-specific withdrawal symptoms. An allostasis deficit occurs due to physiological changes, including decreased dopamine, endogenous opioid peptides, serotonin and increased dynorphin, leading to symptoms, such as depression, dysphoria and pain, as well as decreased gamma-aminobutyric acid (GABA), neuropeptide-Y and increased corticotrophin releasing factor (CRF) leading to symptoms, such as anxiety, stress and panic attacks [87]. Koob has conceptualized addiction into a theory that involves a binge and intoxication stage, a withdrawal and negative affect stage, and a preoccupation and anticipation stage, all of which are fueled by negative reinforcement [154]. Negative reinforcement involves the removal of an aversive stimulus by cannabis use, therefore maintaining the behaviour. This can explain how cannabis may be used as a form of “self-medication” in maintaining addiction, in that individuals go through withdrawal in-between use and, to alleviate these symptoms, use cannabis. Negative reinforcement, or the reversal of withdrawal symptoms due to the deficit produced in the
