HJAR May/Jun 2022

HEALTHCARE JOURNAL OF ARKANSAS I  MAY / JUN 2022 29 vulnerability. Those findings in turn pro- vided translation of data from nonhuman primates, which showed that D2 recep- tor availability can be altered by changes in social hierarchy, and that these changes are associated with the motivation to obtain cocaine [74]. Epidemiologically, it is well established that social determinants of health, includ- ing major racial and ethnic disparities, play a significant role in the risk for addiction [75, 76]. Contemporary neuroscience is illumi- nating how those factors penetrate the brain [77] and, in some cases, reveals pathways of resilience [78] and how evidence-based prevention can interrupt those adverse con- sequences [79, 80]. In other words, from our perspective, viewing addiction as a brain disease in no way negates the importance of social determinants of health or societal inequalities as critical influences. In fact, as shown by the studies correlating dopamine receptors with social experience, imag- ing is capable of capturing the impact of the social environment on brain function. This provides a platform for understand- ing how those influences become embed- ded in the biology of the brain, which pro- vides a biological roadmap for prevention and intervention. We therefore argue that a contemporary view of addiction as a brain disease does not deny the influence of social, environ- mental, developmental, or socioeconomic processes, but rather proposes that the brain is the underlying material substrate upon which those factors impinge and from which the responses originate. Because of this, neurobiology is a critical level of anal- ysis for understanding addiction, although certainly not the only one. It is recognized throughout modern medicine that a host of biological and non-biological factors give rise to disease; understanding the biological pathophysiology is critical for understand- ing etiology and informing treatment. Is a view of addiction as a brain disease deterministic? A common criticism of the notion that addiction is a brain disease is that it is reductionist and in the end therefore deter- ministic [81, 82]. This is a fundamental mis- representation. As indicated above, viewing addiction as a brain disease simply states that neurobiology is an undeniable compo- nent of addiction. A reason for determin- istic interpretations may be that modern neuroscience emphasizes an understand- ing of proximal causality within research designs (e.g., whether an observed link between biological processes is mediated by a specific mechanism). That does not in any way reflect a superordinate assump- tion that neuroscience will achieve global causality. On the contrary, since we realize that addiction involves interactions between biology, environment and society, ultimate (complete) prediction of behavior based on an understanding of neural processes alone is neither expected, nor a goal. A fairer representation of a contempo- rary neuroscience view is that it believes insights from neurobiology allow useful probabilistic models to be developed of the inherently stochastic processes involved in behavior [see [83] for an elegant recent example]. Changes in brain function and structure in addiction exert a power- ful probabilistic influence over a person’s behavior, but one that is highly multifac- torial, variable, and thus stochastic. Philo- sophically, this is best understood as being aligned with indeterminism, a perspective that has a deep history in philosophy and psychology [84]. In modern neuroscience, it refers to the position that the dynamic com- plexity of the brain, given the probabilistic threshold-gated nature of its biology (e.g., action potential depolarization, ion chan- nel gating), means that behavior cannot be definitively predicted in any individual instance [85, 86]. Driven by compulsion, or free to choose? A major criticism of the brain disease view of addiction, and one that is related to the issue of determinism vs indetermin- ism, centers around the term “compulsivity” [6, 87–90] and the different meanings it is given. Prominent addiction theories state that addiction is characterized by a transi- tion from controlled to “compulsive” drug seeking and taking [91–95], but allocate somewhat different meanings to “compul- sivity”. By some accounts, compulsive sub- stance use is habitual and insensitive to its outcomes [92, 94, 96]. Others refer to com- pulsive use as a result of increasing incen- tive value of drug associated cues [97], while others view it as driven by a recruitment of systems that encode negative affective states [95, 98]. The prototype for compulsive behavior is provided by obsessive-compulsive dis- order (OCD), where compulsion refers to repeatedly and stereotypically carrying out actions that in themselves may be mean- ingful, but lose their purpose and become harmful when performed in excess, such as persistent handwashing until skin injuries result. Crucially, this happens despite a con- scious desire to do otherwise. Attempts to resist these compulsions result in increas- ing and ultimately intractable anxiety [99]. This is in important ways different from the meaning of compulsivity as commonly used in addiction theories. In the addiction field, compulsive drug use typically refers to inflexible, drug-centered behavior in which substance use is insensitive to adverse con- sequences [100]. Although this phenom- enon is not necessarily present in every patient, it reflects important symptoms of clinical addiction, and is captured by sev- eral DSM-5 criteria for SUD [101]. Examples are needle-sharing despite knowledge of a risk to contract HIV or Hepatitis C, drinking despite a knowledge of having liver cirrho- sis, but also the neglect of social and profes- sional activities that previously were more important than substance use. While these behaviors do show similarities with the compulsions of OCD, there are also impor- tant differences. For example, “compulsive” substance use is not necessarily accompa- nied by a conscious desire to withhold the behavior, nor is addictive behavior consis- tently impervious to change. Critics question the existence of