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Addiction is a chronic, relapsing condition, where an individual displays cravings, drug-seeking behaviors, and unpleasant withdrawal experiences when abstinent from their substance. Currently, there is a high rate of relapse for people with addiction disorders and there are no existing pharmacological treatments. Since 1997, scientists have been studying Ketamine as a treatment for alcoholism and substance abuse disorders, finding that it helps to decrease addictive behaviors (Ezquerra-Romano I et al., 2018).
Overconsumption disorders such as harmful drinking and substance use disorders are largely acquired behaviors. Neuroscientific models theorize that harmful behaviors such as these are encoded in the brain by maladaptive reward memories (MRMs), learned associations between defining traits of substances (ex. smell, taste, etc) and reward (Das et. al, 2019). When an individual with an abuse disorder encounters one of these stimuli, it acts as a trigger, provoking cravings and excessive consumption. These connections are stable when in long-term memory, but, during retrieval, memories are temporarily destabilized in order to update their contents. Once destabilized, memories use an N-Methyl D-Aspartate Receptor (NMDAR) mediated—MAPK/ERK—protein synthesis cascade to reconsolidate (Das et. al, 2019). Scientists believe that intervening during this process by blocking NMDA receptors may weaken MRMs, undermining an individual’s association between a substance and feelings of reward. This then makes it easier for a person with an overconsumption disorder to overcome their addiction. Therefore, scientists have turned to Ketamine for its ability to act as a safe, high-affinity non-competitive, NMDAR antagonist (Das et. al, 2019).
In one study, alcoholics were instructed to recall maladaptive reward memories of alcohol and were then given Ketamine intravenously. These individuals demonstrated a rapid decrease in the number of days per week in which they consumed alcohol as well as volume of alcohol consumed, whereas the control groups continued to consume alcohol at their usual frequency (Das et. al, 2019). Findings from this study indicate that interfering with NMDAR signaling diminishes MRMs and cravings for addictive substances. A similar study demonstrated that administration of Ketamine increased one-year abstinence rates in alcoholics by 66%, compared to 24% in the control group (Ezquerra-Romano I et al., 2018).
Other scientists theorize that when Ketamine antagonizes NMDA receptors, it impacts addictive behavior through processes other than by interfering with MRMS (Das et. al, 2019). Instead, interfering with NMDA receptors may succeed by enhancing neuroplasticity and neurogenesis, by disrupting relevant functional neural networks, by treating depressive symptoms, or by provoking mystical experiences and enhancing psychological therapy efficacy (Ezquerra-Romano I et al., 2018). Although the mechanism is unclear, Ketamine has been shown to help individuals with addiction and may be a promising treatment for substance abuse disorders.
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