HJNO May/Jun 2022

DRUG ADDICTION compulsivity in addiction altogether [5–7, 89], typically using a literal interpretation, i.e., that a person who uses alcohol or drugs simply cannot do otherwise. Were that the intended meaning in theories of addiction— which it is not—it would clearly be invali- dated by observations of preserved sensitiv- ity of behavior to contingencies in addiction. Indeed, substance use is influenced both by the availability of alternative reinforcers, and the state of the organism. The roots of this insight date back to 1940, when Spragg found that chimpanzees would normally choose a banana over morphine. However, when physically dependent and in a state of withdrawal, their choice preference would reverse [102]. The critical role of alterna- tive reinforcers was elegantly brought into modern neuroscience byAhmed et al., who showed that rats extensively trained to self- administer cocaine would readily forego the drug if offered a sweet solution as an alter- native [103]. This was later also found to be the case for heroin [103], methamphetamine [104] and alcohol [105]. Early residential laboratory studies on alcohol use disorder indeed revealed orderly operant control over alcohol consumption [106]. Further- more, efficacy of treatment approaches such as contingency management, which pro- vides systematic incentives for abstinence [107], supports the notion that behavioral choices in patients with addictions remain sensitive to reward contingencies. Evidence that a capacity for choosing advantageously is preserved in addiction provides a valid argument against a narrow concept of “compulsivity” as rigid, immu- table behavior that applies to all patients. It does not, however, provide an argument against addiction as a brain disease. If not from the brain, from where do the healthy and unhealthy choices people make origi- nate?The critical question is whether addic- tive behaviors—for the most part—result from healthy brains responding normally to externally determined contingencies; or rather from a pathology of brain circuits that, through probabilistic shifts, promotes the likelihood of maladaptive choices even when reward contingencies are within a normal range. To resolve this question, it is critical to understand that the ability to choose advantageously is not an all-or- nothing phenomenon, but rather is about probabilities and their shifts, multiple fac- ulties within human cognition, and their interaction. Yes, it is clear that most people whom we would consider to suffer from addiction remain able to choose advanta- geously much, if not most, of the time. How- ever, it is also clear that the probability of them choosing to their own disadvantage, even when more salutary options are avail- able and sometimes at the expense of losing their life, is systematically and quantifiably increased. There is a freedom of choice, yet there is a shift of prevailing choices that nevertheless can kill. Synthesized, the notion of addiction as a disease of choice and addiction as a brain disease can be understood as two sides of the same coin. Both of these perspectives are informative, and they are complemen- tary. Viewed this way, addiction is a brain disease in which a person’s choice facul- ties become profoundly compromised. To articulate it more specifically, embedded in and principally executed by the central ner- vous system, addiction can be understood as a disorder of choice preferences, prefer- ences that overvalue immediate reinforce- ment (both positive and negative), prefer- ences for drug-reinforcement in spite of costs, and preferences that are unstable (“I’ll never drink like that again;” “this will be my last cigarette”), prone to reversals in the form of lapses and relapse. From a contemporary neuroscience perspective, pre-existing vulnerabilities and persistent drug use lead to a vicious circle of substan- tive disruptions in the brain that impair and undermine choice capacities for adaptive behavior, but do not annihilate them. Evi- dence of generally intact decision making does not fundamentally contradict addic- tion as a brain disease. CONCLUSIONS The present paper is a response to the increasing number of criticisms of the view that addiction is a chronic relapsing brain disease. In many cases, we show that those criticisms target tenets that are neither “SYNTHESIZED, THE NOTION OF ADDICTION AS A DISEASE OF CHOICE AND ADDICTION AS A BRAIN DISEASE CAN BE UNDERSTOOD AS TWO SIDES OF THE SAME COIN. ... TO ARTICULATE IT MORE SPECIFICALLY, EMBEDDED IN AND PRINCIPALLY EXECUTED BY THE CENTRAL NERVOUS SYSTEM, ADDICTION CAN BE UNDERSTOOD AS A DISORDER OF CHOICE PREFERENCES.”