To date, there has never been a reported case of congenital addiction . Whether or not the condition is heritable or latent may be debated until the end of time, but it is clear that an initial exposure initiates the process. While outliers of truly forcible exposure (not mere “peer pressure”) undoubtedly exist, for the most part this introduction to the substance follows a conscious decision, often facilitated by some perceived well-being deficit, whether pain, emotional distress, or simply boredom. Not everyone exposed, however, whether once or repetitively, goes on to develop dependence and addiction. Despite multiple substances with addictive potential, people furthermore generally seek out and develop a dependence upon a “drug of choice” or a limited combination thereof (e.g., alcohol and tobacco, or opioids and benzodiazepines).

In those in whom addiction develops, a well-documented progression from a “positive” reward-chasing cycle to one of “negative” pursuit of the habituated substance to avoid withdrawal phenomena exists. During the initial reward-mediated phase , powerful cravings for the substance generally develop that are inversely proportional to an inevitable experience of diminishing returns. This satisfaction-resistant drive supersedes/subjugates all others, and the pursuit of the substance becomes singular at the expense of all other goals and priorities. Ultimately (sometimes within a very short period) the switch to negative reinforcement occurs, mediated by powerful withdrawal symptoms both psychological and physical, and avoidance of this discomfort becomes the primary motivating factor. More often than not, the individual struggles with this increasing captivity and makes efforts to resist and desist to some degree. Relapse after varying periods of sobriety is common.

Questions to consider include:

There is no doubt that conditioning forms an essential part of the addictive process. There is much disagreement (as with most aspects of addiction) as to whether such learning/behavioral habituation represents compulsion or choice. While many regard conditioning as an ever-increasing state of helplessness, it clearly involves reinforcement of volitional behaviors and as such these models are considered under the rubric of addiction as choice in this survey.

Reinforcement of behavior is generally considered to occur as a result of direct pairing of a stimulus with a positive or negative response in the memory of the learner. This instrumental or operant conditioning is at the heart of habit formation and transcends the conscious/unconscious barrier, as evidenced by people lighting up a cigarette without even realizing it. Classical (Pavlovian) conditioning, whereby a secondary stimulus (e.g., Pavlov’s bell or a particular setting) becomes associated with the primary stimulus (e.g., meat or drug use), is well known to scientists, clinicians, and lay counselors alike to play a powerful role in addiction development and maintenance. These cues (e.g., “people, places, things” in the Alcoholics Anonymous lingo) often generally operate at the level of the subconscious and may well develop greater motivational power than the substance itself, especially as tolerance to the substance builds. The incentive sensitization theory formulated by Robinson and Berridge [15, 16] recognizes a distinction between wanting the substance vs. liking it, especially as time progresses and the reward diminishes, yet desire increases. This increasing “incentive salience” is postulated as underlying the overpowering cravings for the substance that develop despite waning positive reinforcement.

The well-known and consistent phenomenon of progression from a positive reinforcement-/reward-driven state to one of negative reinforcement avoidance involves “macro-level” psychobiological adaptations that presumably occur in concert with “micro-level” conditioning . Neurobiological correlates (and their ever-evolving nature) thought to be associated with this transition are discussed below; from a broader theoretical perspective, the opponent process theory of Solomon and Corbit [17] has been widely adapted to the field of addictionology. In general this theory proposes that highly pleasurable (or unpleasant) experiences generate an antagonistic or opponent response to restore emotional homeostasis; over time, desensitization to the initial stimulus occurs while the strength and duration of the opposing force appears to increase. In the context of addiction, tolerance and/or other mechanisms reduce the positive reinforcement; however, both physical and psychological withdrawal (opponent processes) gain increasing motivational power. Koob and Le Moal added to this general framework with their allostatic theory, postulating that a “chronic deviation of reward threshold” [18] occurs as a result of both decrease in reward sensitivity with repeated exposure and an augmented reactionary hormonal stress response. This altered hedonic threshold drives further drug-seeking not so much to achieve pleasure any longer but rather in an attempt to return to baseline.

Spiritual/religious models for the most part fall under the (irrational) choice rubric as well. Inherently irrational deviation from an absolute (or even relative) standard of good/right behavior defines this perspective. It is an overly simplistic and ill-informed criticism of spiritual/religious models however to characterize them across the board as pure choice models prescribing improved willpower as the solution to overcoming addictive or other maladaptive behaviors. The widely acclaimed 12-step model introduced by Alcoholics Anonymous in the 1930s begins with the famous “I have a problem” confession (We admitted we were powerless over alcohol—that our lives had become unmanageable [19]) and is much more congruent (as is the quote from St. Paul gracing the Part heading) with an understanding of solidified behavior patterns that have escaped the control of the individual. “Voluntary slavery ” as described by Welch [20] describes a potency of compulsion at least equal to that of any biologic model and furthermore carries a more broad theoretical construct invoking the possibility of external control hearkening back to Martin Luther [21], St. Augustine [22], and holy writings centuries older than that.

The defining characteristic of spiritual/religious models is a deviation from right, not just choice. Many of these models recognize (and have helped draw attention to) the progressive loss of control. Key foci also include values and motivation (increasing in popularity both within addiction theory as well as therapeutic approaches). Addiction is often conceptualized in terms of a suboptimal attempt to meet valid needs/fill a void and in some paradigms even an aberrant form of worship [20, 23].

The current addictionology landscape is dominated by the viewpoint that addiction is a medical illness caused (or at least explainable) by perturbations of normal cerebral function. While not equivalent concepts, these terms “disease model” and “biologic model” are used jointly/interchangeably throughout this book to refer to the evolving concept that addiction is the result of functional or even structural abnormalities within the brain. Observations regarding the similarity of alcoholism to other known disease states began to find expression in the nineteenth century [26–28], but it was not until the American Medical Association’s House of Delegates in 1956 first declared alcoholism an “illness” [29] (subsequently labeling it a “disease” in 1966) that the door opened to a gradual and widespread reconceptualization of addiction among the medical and scientific communities. Supporters of this viewpoint drew attention to the fact that alcoholism exhibits a well-defined pattern of symptoms (and sequelae), with a generally chronic and progressive course, and may be treatable although shows significant vulnerability to relapse. The most notorious proponent of the alcoholism-as-disease theory was E.M. Jellinek, whose landmark treatise “The Disease Concept of Alcoholism” [30] in 1960 is still widely credited with bringing this theory into its current place of prominence. Jellinek’s work and even credentials however have fallen into disrepute lately as it appears that much of both were fabricated, and there are allegations that much of his published data were heavily biased and influenced by third party agendas [31–34].

Regardless of the veracity or reliability of Jellinek’s work and construct, the disease model’s ascension to prominence has facilitated considerable scientific and medical research, shedding light on neurobiologic substrates and genetic expressions that appear to be associated with increased addictive behaviors.

Some of the earliest evidence suggesting a biologic basis for addiction arose from observations that predisposition (and in extreme cases predetermination) to addiction is heritable. Clustering of behavior patterns within families and apparent preservation of the association despite early overhaul of the environment, e.g., adoption of the offspring by non-addicted parents, led to the hypothesis of a genetic vulnerability to addiction.

The explosive advances in DNA sequencing technology over the past three decades have facilitated the identification of numerous genes associated with substance use disorders and dependence/addiction including the well-studied DAT1 gene (encoding the dopamine transporter), polymorphisms of which have been linked to numerous pathologic states involving dopaminergism including conditions as diverse as alcoholism, Parkinson’s disease, and schizophrenia [35]. Several other allelic variants encoding various dopamine receptor and metabolic function including the ANKK1 gene TaqIA1 variant [LAWF1, MOY1], the DRD2 gene rs6277 variant [36], and the DBH gene rs1611115 variant [37] have all been associated with opioid and other substance use disorders.