“Addiction”, is widely viewed as a chronic, relapsing, neurobiological disorder, characterized by compulsive use of alcohol or substances, despite serious negative consequences. It involves both physiological and psychological dependence and leads to the emergence of a negative emotional state.  The Diagnostic and Statistical Manual of Mental Disorders, DSM-5, combines DSM-IV categories of substance abuse and dependence into a single disorder, on a continuum from mild to severe (1). This continuum is conceptually important to both ‘conditioning’ models, or positive or negative reinforcement models (2-5), as they consider the transition from initial substance use to abuse to addiction.

The definition of addiction by the American Society of Addiction Medicine (ASAM) includes the terms, craving, persistent risk, and emphasises risk of relapse after periods of abstinence triggered by exposure to substance-related cues and emotional stressors (6). This conceptualisation points to the role of substance-related cues, e.g., environmental stimuli that are strongly associated with the effects of the administration of substances and acquire incentive salience through Pavlovian conditioning, as well as stress (an internal cue), as major determinants of relapse.

According to one prominent positive reinforcement model, the Incentive Sensitisation (IS) Model (1), addiction is the result of neural sensitisation of reward circuits (centred in the  brain “reward” region of the ventral striatum (VS)) by the neurotransmitter dopamine. Positive reinforcement mechanisms lead to a non-associative learning process, referred to as sensitization, in which repeated confrontation with a substance-related cue (which acts as a reinforcer) results in the progressive amplification of a response (substance seeking). This ‘sensitisation’ or hypersensitivity may be independent of negative withdrawal symptoms or an individual’s general negative emotional state and leads to compulsive substance-seeking and substance-taking. These mechanisms of positive reinforcement leave addicts vulnerable to relapse when confronted by substance-related cues which trigger a pathological “wanting”, as progressively distinct from initial reward-linked “liking”.

In short, IS produces a bias of attentional processing towards substance-associated stimuli and a pathological wanting of alcohol or substances. Sensitisation and attentional bias has been demonstrated in various studies (8,9). Later extensions of IS theory (3) pose that this pathological wanting is accompanied by increasingly impaired executive control over behaviour. This arises due to the chronic effects of substance abuse on the prefrontal cortex, with deleterious consequences for cognitive control of pathological wanting.

Basic negative reinforcement models pose that addictive behaviour is the consequence of persistent negative affect (NA). This NA is associated with neuroadaptive changes in brain stress and reward circuits, which leave addicts vulnerable to cue-associated stimuli prompting a desire to relieve their negative emotional states (4,5).

During the progression of use to abuse to addiction stress chemicals progressively attempt to overcome the chronic presence of the perturbing substance and to restore normal function of the brain by opposing the substance rewarding (dopaminergic) effects.  Persistence of these ‘opposing effects’ after substance discontinuation produces an adaptation in stress systems leading to allostasis, a chronic deviation from homeostasis, with resultant heightened stress response and lower dopamine during the addiction cycle.

Evidence for the involvement of both systems comes from imaging studies of addicted individuals during withdrawal or protracted abstinence, which have shown decreases in dopamine D2 receptor density (hypothesized to reflect hypodopaminergic function) (10,11) as well as alteration in brain stress systems, such as increase in glucocorticoids (5).

These changes continue to persist even when an addicted individual experiences a state of protracted abstinence. “Cues” that normally elicit substance-seeking behaviour are conceived as having greater impact during such periods of protracted abstinence. Persistent NA increases their incentive salience and desire to use substances in an attempt to relieve this NA

These are both primarily neurobiological account of  addiction.  They are both limited in their definition of the cognitive and affective factors that mediate these neurobiological impairments. By this we mean that there is no mention of how the well documented cognitive distortions, executive dysfunction and emotional dysregulation drive this addiction cycle forward. Viewing this defintion it is difficult not to view the addicted individual as resembling a automat, or robotic individual rather than as a thinking, feeling, acting entity. This is what diagnosis of addiction needs to more fully consider.

What is it like to be an addict or alcoholic especially a sober or clean one, and in “recovery”. Then the phenomenological realities of everyday recovery could be weighed against this neurobiological evidence. For example in terms of the reasons for relapse implicated in the above definition, we have rarely heard of a committed abstinent addict in recovery who relapsed simply because he was lured siren like to some cue associated stimuli; we are talking about recovery here too. That is not to say cue reactivity is not a valid construct, it is obviously. Recovering alcoholics  exhibit an automatic, that is involuntary,  attentional bias towards drug and alcohol-related “cues”. This is a torturous aspect of early recovery thus most therapeutic regimes advise those in early abstinence and recovery to avoid “people, places and things” that act as  cue-associated stimuli. In fact, some in early recovery do challenge this only to learn painfully as the result by thinking they can spend time, like before, in drinking establishments,  only to find that it is “like sitting in a hairdressors  all day and not expecting to eventually get a haircut!” These individuals in recovery are also prone to “cues” just as they were in early recovery but perhaps less so, as this early recovery period is a period of great distress and heightened neuro-endocrinological activity which we believe, and will explain more fully at a later juncture, heightens motivational salience of cues.

There is an excellent paper (12) which highlights how stress heightens cue based craving by activating certain brain regions such as the ventral medial prefrontal cortex and ventral striatum, which are always hyperactive, we believe in recovering individuals, and how greater stress hypoactivates these areas so that more automatic, compulsive processes are activated and regions like the dorsal striatum are  more implicated. Stress at a heightened level makes behaviour more automatic, without explicit knowledge of future consequence.

However, we know of hundreds and hundreds of recovering alcoholics who regularly attend family or social functions in which alcohol is widely served and consumed. They seem to have little difficulties with this as “long as they are in a spiritual fit place” which we interpret as them saying they are free from stress and emotional distress and so are not responding to cues in the manner most studies suggest they should be! We thus forward the idea that cue reactivity is also a function of stress response.

We have also heard of recovering alcoholics who have a distress response while in these situations and have had to suddenly leave which is the effect of stress heightening the salience of these “cues”.  Alcohol is described as “cunning, powerful, baffling” in the Big Book of Alcoholics Anonymous “without help it is too much for us” and be believe it becomes too much for us when we start becoming distressed.

On the other hand, we have witnessed and heard of dozens of people relapsing because they have found it difficult coping with chronic stress and emotional distress. It’s this “to hell with it!” response which often precedes relapse. It is this affective dysregulation and inability to cope with negative emotions. It is not simply due to levels of stress/distress. It is due to, we suggest, an emotional distress habit bias in which habitual, automatic response is triggered by distress which is beyond the “must do!” compulsion posited by Everitt and Robbins and is an emotionally distressed “to hell with it!”” or “I can’t cope with this!”  response.

The ventral medial prefrontal cortex is also involved in the top-down control/regulation of emotions. If it is hyperactive, it is due to persistent emotional regulation difficulties. The brain of recovering alcoholics, especially in early recovery, rarely “shuts off” and is primed to become compulsive due to this severely restricted conscious, top-down cognitive control. This  study ( )  is also showing these difficulties in relation to cue-associated stimuli – the response here is not simply appetitive craving but  also aversive.  It may be causing a threat based emotional dysregulation which under higher levels of stress induction because a compulsive response to this emotional distress, like a “fight of flight response”,  it is a “get me outta here!”, “I can’t cope with this!” response which in time can become a “to hell with it!” response.

It underlies why it is emotional dysregulation, heightened in the addiction cycle, by a state of allostasis, i.e. impaired, maladaptive  and hyperactive stress responding (although we feel there also may be a case for a premorbid allostasis in certain individuals due to early life abuse of one sort or the other which alters stress systems and creates a persistent and maladaptive stress response) that drives the addiction cycle on.

Most alcoholics  have difficulties with emotional and stress regulation. The above neural substrates implicated in neurobiological accounts of addiction also overlap with those involved in emotional regulation. In fact may be at the roots of their disease, this stress and emotional dysregulation. Considering that many alcoholics state that they have always had these difficulties is it not unreasonable to ask whether these dysregulation issues are not at the heart of this condition and may even be a premorbid vulnerability which feeds the whole subsequent addiction cycle?

There is not divorce from the internal and the external environment, one interacts and impacts on the other. Is it not time for neuro-scientific inquiry to marry the experimental evidence with theoretical frameworks which also include an appreciation of the very real emotional, perceptual, cognitive, executive and memory difficulties which seem to beset most alcoholics and addicts in recovery? Otherwise, science will not be able to predict why these individuals relapse or effectively suggest effective treatment of these conditions.

Is it not time to start marrying the experimental with the ancedotal?

References

1.  American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. pp. 5–25.

2. Robinson, T.E., & Berridge, K.C. (1993). The neural basis of drug craving: An incentive-sensitization theory of addiction. Brain Research, 18, 247-291

3. Robinson, T. E., & Berridge, K. C. (2008). The incentive sensitization theory of addiction: some current issues. Philosophical Transactions of the Royal Society B: Biological Sciences, 363(1507), 3137-3146

4.  Koob GF, Le Moal M. Drug abuse: hedonic homeostatic dysregulation. Science. 1997; 278:52–58

5. Koob, G. F., & LeMoal, M. (2001). Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology, 24, 97–129.

6.  Morse RM, Flavin DK (1992). “The definition of alcoholism. The Joint Committee of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism“. JAMA 268 (8): 1012–4

7. Everitt, B. J., & Robbins, T. W. (2005). Neural systems of reinforcement for drug addiction: From actions to habits to compulsion. Nature Neuroscience, 8, 1481–1489

8. Leyton M. Conditioned and sensitized responses to stimulant drugs in humans. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2007;31:1601–1613.

9.  Franken, I. H. (2003). Drug craving and addiction: integrating psychological and neuropsychopharmacological approaches. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 27(4), 563-579

10. Volkow ND, Wang GJ, Fowler JS, et al. Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature. 1997;386:830–3.

11. Volkow, N. D., Fowler, J. S., & Wang, G. J. (2002). Role of dopamine in drug reinforcement and addiction in humans: results from imaging studies. Behavioural pharmacology, 13(5-6), 355-366.

12. Seo, D., Lacadie, C. M., Tuit, K., Hong, K. I., Constable, R. T., & Sinha, R. (2013). Disrupted ventromedial prefrontal function, alcohol craving, and subsequent relapse risk. JAMA psychiatry, 70(7), 727-739.