A Computational Hypothesis for Allostasis: Delineation of Substance Dependence, Conventional Therapies, and Alternative Treatments

Abstract

The allostatic theory of drug abuse describes the brain’s reward system alterations as substance misuse progresses. Neural adaptations arising from the reward system itself and from the antireward system provide the subject with functional stability, while affecting the person’s mood. We propose a computational hypothesis describing how a virtual subject’s drug consumption, cognitive substrate, and mood interface with reward and antireward systems. Reward system adaptations are assumed interrelated with the ongoing neural activity defining behavior toward drug intake, including activity in the nucleus accumbens, ventral tegmental area, and prefrontal cortex (PFC). Antireward system adaptations are assumed to mutually connect with higher-order cognitive processes occurring within PFC, orbitofrontal cortex, and anterior cingulate cortex. The subject’s mood estimation is a provisional function of reward components. The presented knowledge repository model incorporates pharmacokinetic, pharmacodynamic, neuropsychological, cognitive, and behavioral components. Patterns of tobacco smoking exemplify the framework’s predictive properties: escalation of cigarette consumption, conventional treatments similar to nicotine patches, and alternative medical practices comparable to meditation. The primary outcomes include an estimate of the virtual subject’s mood and the daily account of drug intakes. The main limitation of this study resides in the 21 time-dependent processes which partially describe the complex phenomena of drug addiction and involve a large number of parameters which may underconstrain the framework. Our model predicts that reward system adaptations account for mood stabilization, whereas antireward system adaptations delineate mood improvement and reduction in drug consumption. This investigation provides formal arguments encouraging current rehabilitation therapies to include meditation-like practices along with pharmaceutical drugs and behavioral counseling.

A Control Theory Model of Smoking

“…Other assumptions simplify parameter variation, an impact of environmental stressors, and ignore potential drug-seeking behaviors during withdrawal and craving. Although several complex models (Lamy, 2011; Levy, 2013) simultaneously include many aspects of measurable and unmeasurable human behavior, we started with a relatively simple model that was recently validated on data from animal experiments (Bobashev et al, 2015) and developed a representation of a specific substance use theory.…”

“…Comprehending a cascade of feedback loops between a variety of biologic, neurocognitive, behavioral, social, and environmental factors is one of the main challenges in substance use research. A few models exist that describe various feedback loops (Lamy et al, 2011; Levy et al, 2013; O’Reilly & Munakata, 2000). However, most of these models are quite complex, and their practical utility for prevention and treatment is low.…”

Behavioral Posology: A Novel Paradigm for Modeling the Healthy Limits of Behaviors

“…By changing the ratio of a-and b-process magnitudes, one can easily adjust the rate of development of allostasis and apparent tolerance. If more sophisticated modification is required, one could add a parallel tolerance compartment to create a feedback loop, similar to those in control system models of addiction in the literature (e.g., Ahmed & Koob, 2005;Amigó et al, 2008;Bobashev et al, 2017;Chou & D'Orsogna, 2022;Dumas & Pollack, 2008;Gårdmark et al, 1999;Levy et al, 2013;Newlin et al, 2012;Peper, 2009b;Porchet et al, 1988;Upton & Mould, 2014;Zou et al, 2020). Several types of functional tolerance, both competitive and non-competitive, could be added, including both pharmacokinetic tolerance (such as changes in metabolite production or transporter function) and pharmacodynamic tolerance (such as modifications to receptor functionality or changes to signal pathways) (Dumas & Pollack, 2008).…”

Allostasis as a Conceptual Framework Linking Bipolar Disorder and Addiction

“…Converging data from addiction and BD studies suggest that these disorders involve similar allostatic processes, and allostasis can contribute to unify these disorders under a unitary perspective. In this context, the concepts of allostasis and AL provide both a pathophysiological model for the understanding of BD-addiction comorbidity and a new perspective for the development of novel therapeutic strategies for the treatment of comorbid patients ( 100 , 101 ).…”