In the third part of this excellent review paper  (1) we look at the empirical evidence is presented suggesting that MBIs ameliorate addiction by enhancing cognitive regulation of a number of key processes.

Emotion Regulation

When individuals are unable to marshal effective problem-solving to resolve a stressor, lack of a favorable resolution may lead to deployment of emotion regulation efforts to manage the emotional distress elicited by the stressful circumstance. Neuroimaging research has provided evidence for a reciprocal, dual-system neural network model of emotion regulation comprised of a dorsal brain system (e.g., dlPFC, dACC, parietal cortex) subserving top-down cognitive control, and a ventral brain system (e.g., amygdala, striatum) subserving bottom-up emotional impulses (133–135). Top-down engagement of proactive cognitive control mechanisms regulates negative affect and attenuates the effects of emotional interference on cognition (135–138), and is associated with increased activation of PFC which in turn attenuates amygdala activation (139, 140). Research suggests that dysregulated emotional reactions occur when the reciprocal balance between the relative activation of bottom-up and top-down neural circuits becomes tipped in favor of bottom-up processes (141). A number of studies suggest that mindfulness training may counter this imbalance and augment emotion regulation [for reviews, see Ref. (78, 142)] by restructuring neural function in favor of context-dependent top-down control processes. For example, Goldin and Gross (143) demonstrated that individuals with elevated negative affect at baseline who later received mindfulness training exhibited increased emotion regulatory capacity coupled with greater recruitment of attentional control resources and reduced amygdala activation during exposure to negative, self-relevant stimuli. Thus, by enhancing top-down cognitive control over emotional responses in a context-dependent fashion, MBIs may reduce drug use precipitated by negative affective states.

Importantly, MBIs provide training in cultivating a state of mindful awareness and acceptance of the extant emotional response as a precondition for emotion regulation. While acceptance of aversive mental experience may itself result in reduced negative affect (144), mindfulness training may also exert downstream facilitative effects on cognitive regulation of emotion following the acute state of mindfulness. For instance, mindfulness training may promote cognitive reappraisal, the process by which the meaning of a stressful or adverse event is re-construed so as to reduce its negative emotional impact (125). One theoretical model posits a multi-stage process of mindful emotion regulation (1, 145). According to this model, during an adverse experience mindfulness practitioners first disengage from initial negative appraisals into the metacognitive state of mindfulness in which cognitions and emotions are viewed and accepted as transitory mental events without inherent veridicality. Subsequently, the scope of attention broadens to encompass a larger set of previously unattended information from which new situational appraisals may be generated. By accessing this enlarged set of contextual data, present circumstances may be reappraised in an adaptive fashion that promotes positive affect and behavioral activation. For instance, a newly abstinent alcohol dependent individual might reappraise an affront by a former “drinking buddy” as evidence of their need to build new, sober relationships. In support of this model, recent studies indicate that mindfulness during meditation predicts enhanced cognitive reappraisal (146), which in turn mediates the association of mindfulness and reduced substance craving (147). This context-dependent use of prefrontal regulatory strategy represents a “middle way” between hypo- and hyper-activation of cognitive control resources, thereby preventing resource depletion and untoward rebound effects.

Speculatively, this “mindful reappraisal” process may involve spreading activation in a number of brain networks. Generating the state of mindfulness in the midst of a negative affective state may activate the ACC and dlPFC (148, 149), which could facilitate metacognitive monitoring of emotional reactivity, foster attentional disengagement from negative appraisals, and regulate limbic activation. In so doing, the acute state of mindfulness may attenuate activation in brain areas that subserve self-referential, linguistic processing during emotional experience (e.g., mPFC) while promoting interoceptive recovery from negative appraisals by increasing activation in the insula (113). Metacognitive disengagement from the initial negative appraisal may result in non-elaborative attention to somatosensory information, thereby facilitating the set shifting process of cognitive reappraisal, as brain activations shift from posterior to anterior regions of cortex centered on the node of the OFC. During this process emotional interference is attenuated while alternate appraisals are retrieved from memory and evaluated for goodness-of-fit to situational parameters and demands (150).

The effects of mindfulness-centered regulation of negative emotion might be measured with a standard emotion regulation paradigm [c.f. (137)], in which participants are instructed to use reappraisal to reduce negative affect in response to exposure to aversive visual stimuli [e.g., images from the International Affective Picture System; (151)]. In this task paradigm, mindfulness practitioners may exhibit enhanced reappraisal efficacy, as evidenced by reduced self-reported and psychophysiological responses to aversive stimuli on reappraise relative to attend trials. In that regard, a study employing ERP analysis found that when compared to controls, meditators exhibited significantly greater reappraisal efficacy as evidenced by significantly larger attenuation of brain activity during reappraisal of stressful stimuli in centro-parietal regions subserving attentional and emotional processing (152).

Stress Reactivity

In addition to pro-regulatory effects on emotion, mindfulness training may facilitate neurocognitive regulation of the effects of stress on the autonomic nervous system. As addicts in treatment develop dispositional mindfulness through mindfulness training, they may be more able to engage prefrontal cortical modulation of the sympathetic “fight-or-flight” response via parasympathetic nervous system activation of the “vagal brake,” resulting in increased HRV and heart-rate deceleration in the face of stress or addictive cues (153, 154). Thus, increasing dispositional mindfulness may be reflective of greater neurovisceral integration and flexibility in the central autonomic network (67). This network is comprised of neuroanatomic and functional linkages between central (e.g., PFC and ACC) and autonomic (e.g., vagus nerve) nervous system structures which coordinate the self-regulation of attention, cognition, and emotion while exerting regulatory influences over perturbations to visceral homeostasis (155), such as those that might be evoked in abstinent substance dependent individuals exposed to stressful and/or substance-related stimuli. Mindful individuals may have greater capacity for contextually appropriate engagement and subsequent disengagement of neurocognitive resources in response to the presence and absence of stress and drug-cues. Such autonomic flexibility (156) engendered through mindfulness training may help persons in recovery from addiction adapt to situational demands without succumbing to a stress-precipitated relapse.

This hypothesis is consistent with evidence of the effects of mindfulness on neural function in dlPFC and ACC (149, 157), key structures involved in central autonomic regulation of HRV via downstream influences on the amygdala and hypothalamus (158, 159). Congruent with such findings, MBIs increase parasympathetically mediated HRV to an even greater extent than relaxation therapy (160,161), and decreases sympathetically mediated indices of stress (8), including blood pressure (162), heart rate (163), skin conductance responses (161), and muscle tension (164). These effects of mindfulness-centered regulation on autonomic function may result in improved ability to manage substance cue-reactivity. In support of this hypothesis, a Mindfulness-Oriented Recovery Enhancement intervention for alcohol dependence increased HRV recovery from stress and alcohol cue-reactivity (7). Congruent with this finding, relative to their less mindful counterparts, alcohol dependent individuals with higher levels of dispositional mindfulness exhibited greater attentional disengagement from alcohol cues which predicted the extent to which their HRV recovered from alcohol cue-exposure levels (67). Lastly, persons participating a mindfulness-based smoking cessation intervention who exhibited increased HRV during mindfulness meditation smoked fewer cigarettes following treatment than those who exhibited decreased HRV (165). Thus, addicts who develop dispositional mindfulness through participation in MBIs may become better able to regulate appetitive responses by virtue of enhanced neurocognitive control over autonomic reactivity to stress and substance cues.

The effects of MBIs on cognitive regulation of autonomic cue-reactivity might be measured with a stress-primed cue-reactivity paradigm, in which participants are first exposed to a laboratory stress induction [e.g., aversive IAPS images, c.f. (7); or the TSST, c.f. (132)], then exposed to substance-related cues (either in vivo, imaginally, or images of alcohol or drugs), and finally asked to use mindfulness skills to downregulate the resultant state of autonomic arousal.

Natural Reward Processing

With repeated drug-use, neural sensitization may occur whereby the drug elicits a potent response in striatal-dopamine neurons coupled with a strong degree of positive reinforcement. At the same time, long-term exposure to drugs significantly attenuates neural responses to intrinsically rewarding stimuli in the environment (e.g., a beautiful landscape, the smile of a baby, a delicious meal). In other words, through neuroadaptation the addicted individual learns to experience reward via self-administration of drugs rather than by enjoying the subtle beauty of the natural environment or the affiliative or health-promoting objects found therein. This re-wiring of reward learning entrenches the drug user in a cycle of drug-taking that serves to maintain the ongoing use of drugs. Indeed, vulnerability to relapse has been attributed to increased incentive salience of drug-cues and decreased salience of intrinsically rewarding stimuli (166, 167). Though pharmacotherapies may provide acute relief to drug addiction-related anhedonia, their effectiveness in facilitating restoration of normal, healthy reward learning remain unknown. Thus, therapies that target reward processes over the long-term, either in the absence of, in adjunct to, or after pharmacotherapies have been discontinued, are very much needed.

By teaching participants to mindfully attend to pleasurable objects, events, and experiences, MBIs may amplify hedonic processing of natural rewards and thereby counter the allostatic effects of addiction on reward neurocircuitry. This form of selective attention to positive experience, known as savoring, is one of the most robust positive emotion regulation strategies (168). During savoring, one not only attends to a broadened diversity and range of sensations and perceptions, but also to the positive emotions elicited by the sensory-perceptual experience. As such, attending to present-moment experience prospectively predicts positive emotion (169). Thus, learning to mindfully savor pleasant events may offset negative affective states that often trigger addictive responses, and restore the salience of naturally occurring and intrinsically rewarding objects and events (e.g., social affiliation, healthy diet and exercise behaviors, engagement with novel and stimulus-rich environments, etc.). Through mindful savoring, MBIs may provide a means of reward replenishment and ultimately reverse the reward deficiency syndrome inherent in addiction – a therapeutic process plausibly important for allaying craving and deterring relapse.

Research suggests that mindfulness training can increase reward experience and positive emotion in both healthy and clinical populations (7). In studies of healthy individuals, mindfully savoring food items increased pleasure from eating (170), and mindfulness training amplified positive stimulus evaluations (171) and increased positive emotional information processing (172). In clinical populations with low positive and high negative affect, MBIs have been shown to be effective means of enhancing positive emotion. Studies demonstrate facilitative effects of mindfulness training on positive affect on patients with major depressive disorder (173), bipolar disorder (174), and HIV (175). Importantly, Geschwind et al. (173) found that Mindfulness-Based Cognitive Therapy increased reward experiences from pleasant daily events among persons in partial remission from major depressive disorder. Insofar as intentional up-regulation of positive emotion is believed to involve increased activation in a predominantly left lateralized prefrontal network that potentiates striatal activation (135, 176), mindfulness-induced positive affectivity may remediate impaired dopaminergic responses in the striatum to hedonic stimuli. Plausibly, MBIs, which also increase left lateralized PFC activity (177), may restore natural reward processes among drug addicted individuals seeking abstinence. The most direct support of this hypothesis stems from recent findings from a RCT of Mindfulness-Oriented Recovery Enhancement for prescription-opioid-misusing chronic pain patients. Participation in 8 weeks of this particular MBI (which specifically focuses on mindful savoring as a key therapeutic process) resulted in significantly enhanced reward responsiveness as indicated by cardiac autonomic responses to positive emotional stimuli presented during a dot probe task. Crucially, the opioid craving-reductive effects of the intervention were statistically mediated by enhancements in reward responsiveness (Garland et al., submitted for publication).

The effects of mindfulness-centered regulation of reward processing might be measured with a positive emotion regulation neuroimaging paradigm, in which participants are instructed to up-regulate positive affective response to intrinsically rewarding stimuli. If mindfulness training fosters reward processing, individuals in recovery from addiction might exhibit enhanced dopaminergic striatal responses to naturally rewarding stimuli coupled with enhanced ratings of stimulus valence. Alternatively, the Effort Expenditure for Rewards Task [EEfRT, (178)] is a task probe of a subject’s willingness to expend effort to receive reward, and theoretically an indirect probe of dopamine-mediated reward processes. In brief, during this task, subjects are provided with a choice period in which they may choose to perform either an easy task for a smaller reward or a hard task for a larger reward. The probability of winning is manipulated and stated to the subject during the choice period. Following the choice period, subjects perform the task and receive feedback about their wins. MBI-related enhancement of reward responsiveness might be indexed by increasing hard task engagement and modifying reaction times on the task.

Exposure and Extinction

Individuals in early recovery from addiction often attempt to suppress craving for drugs and alcohol as a means of maintaining abstinence. However, these suppression attempts often backfire, resulting in depletion of self-control resources (1, 179) and a consequent rebound of substance-related thoughts (50, 51). Critically, attempted avoidance of substance cue-reactivity may prevent extinction learning from occurring, which requires inhibition of conditioned responses in the presence of conditioned stimuli. In contrast, mindfulness training provides an effective alternative to suppressing unwanted substance-related thoughts, emotions, and urges by promoting acceptance of and exposure to these mental experiences. By learning to tolerate aversive psychological events through acceptance rather than avoidance, mindful exposure to substance-related thoughts and cues may prevent the post-suppression rebound effect and facilitate desensitization to conditioned stimuli (78). When engaged over time, this practice might result in extinction learning of previously conditioned associations between substance cue-reactivity and addictive behaviors.

In support of this hypothesis, changes in thought suppression have been shown to partially mediate effects of mindfulness training on alcohol use and drinking consequences (180). Furthermore, Mindfulness-Oriented Recovery Enhancement treatment led to significant reductions in thought suppression which were associated with improved capacity to inhibit drinking urges, decreased alcohol attentional bias, and increased HRV recovery from stress and alcohol cues (7). Relatedly, among a sample of persons in long-term treatment for co-occurring psychiatric and substance use disorders, individuals with higher levels of dispositional mindfulness exhibited less craving for substances and were less likely to develop post-traumatic stress symptoms in response to trauma (66). Thus, MBIs may reduce the tendency to suppress aversive psychological experiences, thereby allowing urges that had been previously suppressed to become accessible to explicit cognitive control. As suppression decreases, controlled cognitive processing can be more effectively deployed to inhibit and counter addictive responses.

The effects of MBIs on cognitive regulation of extinction learning might be measured by combining neuroimaging, self-reported craving, and self-reported emotion regulatory strategy during a drug cue-reactivity paradigm. Pre- and post-mindfulness training, addicts could participate in cue-exposure sessions (e.g., a smoker might be asked to handle cigarettes, ashtrays, and lighters without smoking for a limited period of time, followed by an ad libitum smoking session) in which skin conductance, heart rate, and craving responses could be measured throughout. If mindfulness enhances cognitive regulation of extinction learning, cue-elicited skin conductance, heart rate, and self-reported craving would be reduced following mindfulness training relative to an active control intervention, as would drug-use following the cue-exposure session.

Although we have described the aforementioned therapeutic mechanisms of mindfulness-centered regulation as discrete processes linked in a sequential, linear fashion, in actuality they often run in parallel and may be linked in a recursive, self-reinforcing system of positive feedback loops. Figure 2depicts the hypothesized interactions between these processes and therapeutic targets of MBIs.

Conclusion

In contrast to mindfulness, which leads to cognitive and behavioral flexibility, addiction may be characterized by mindlessness, i.e., habitual or scripted responses that are often deployed automatically without conscious volition or regard for goodness-of-fit with present goals or the socioenvironmental context. Although procurement of many psychoactive substances requires significant planning and intentionality, the appetitive drive that motivates drug seeking may emerge in a context of mindlessness, manifested as obsessional thoughts of using and compulsive urges that seem to arise in an unbidden and intrusive fashion in direct contradiction to rational decision making. Moreover, the behavioral routines involved in the ritual of drug administration can become automated and executed mindlessly in much the same was as other complex repertoires can be engaged without conscious volition by conditioned contextual cues (26). Hence, individuals treated for substance dependence with higher levels of mindlessness tend to experience higher levels of craving (66) and consume larger quantities of addictive substances than their more mindful counterparts (1). These findings suggest that habitual, reflexive responding can confer vulnerability to individuals in recovery. Conversely, greater attention to and awareness of one’s reactions to substance-related cues predicts less substance use among persons in recovery from addiction (111). In light of Tiffany’s (20) proposal that automaticity drives appetitive addictive responses, mindfulness of one’s automatized reactions would presumably allow for greater self-regulation of mindless reactions elicited by drug-cues, and increase proactive cognitive control over substance use.

Addiction involves deleterious neuroplastic changes in frontal-striatal-limbic circuitry that results from chronic drug-use. We hypothesize that this drug-induced neuroplasticity may be remediated through participation in MBIs. Specific knowledge of the neuroplastic alterations underpinning dysregulated circuit-function in addiction may inform treatment development efforts to drive the next generation of MBIs. For example, in light of evidence that dopaminergic salience networks involved in normal human learning and reward become usurped during the addictive process and biased in favor of drug-relevant stimuli, MBIs should be explicitly tailored to address reward processing deficits by emphasizing skills that enhance savoring of natural, non-drug related rewards. Though most current MBIs have underemphasized this potential treatment target, one novel MBI, Mindfulness-Oriented Recovery Enhancement (6–8) places a special emphasis on providing training in mindful savoring as an approach to restoring natural reward responsiveness. Concomitantly, a growing recognition of the role of attentional bias in addiction points to the potential clinical utility of focused attention forms of mindfulness practice as means of strengthening lateral frontal (dlPFC)-parietal networks involved in attentional (re)orienting from drug-cues; in that regard, recent ERP analyses of EEG data suggest that regular, brief mindfulness practice of focused attention on respiratory sensations strengthens electrophysiological indices of enhanced attentional control (181). Conversely, open monitoring forms of mindfulness meditation that target medial frontal (ACC)-parietal-thalamic regulation of striatal circuits might be most useful for generating awareness of cue-elicited activation of drug-use action schemas and could enable the practitioner to regain conscious cognitive control of automatized addictive behavioral routines. Thus, translating findings from the leading edge of neuroscience into the treatment development process may result in ever more specialized and efficacious MBIs targeted to meet the unique challenges of addictions treatment.

Importantly, although various drugs of abuse do share some common neurobiological underpinnings, there is also variability in the circuit-level function associated with different psychoactive agents. Similarly, while addiction to drugs may share overarching neural substrates with some behavioral addictions [e.g., food addiction, (182)], there may be important differences in the functional connectivity or node strength of neural networks involved in these various forms of addiction. Despite these differences, given our assertion that MBIs strengthen domain-general neurocognitive resources that can be used to target common transdiagnostic processes (i.e., automaticity, attentional bias, appraisal, emotion regulation, cue-elicited craving, stress reactivity, and extinction learning) we hypothesize that MBIs would have similar efficacy across a wide range of addictions. In contrast, the efficacy of MBIs may be moderated by key individual differences – an, important understudied area of research crucial to understanding the path from drug initiation to dependence to recovery. For instance, we hypothesize that extant MBIs may be less effective for individuals lacking motivation or readiness to change, because current programs do not integrate motivational components with mindfulness training, and evidence suggests that mindfulness alone may not facilitate readiness to change (Garland et al., submitted for publication). Similarly, MBIs may be more effective for individuals in early to late abstinence as opposed to individuals in active addiction; exposure to ubiquitous drug-related cues and an environment that affords ready access to drugs may promote a more automatized form of drug-use (20) that does not allow a novitiate of mindfulness (whose prefrontally mediated executive functions have atrophied due to years of drug-use) to marshal proactive cognitive control via mindfulness practice. In contrast, inpatient treatment settings may provide respite from cue-elicited craving and contextual triggers of striatally mediated habit responses, and therefore allow a fledgling mindfulness practitioner the opportunity to exercise PFC functionality in a safe environment until it has reached sufficient strength to allow the person to navigate a socio-cultural context beset by stressors and conditioned appetitive stimuli. Thus, mindfulness training may have heterogeneous effects across individuals depending on the natural history and trajectory of their addiction and treatment process.

The conceptual framework we have outlined in this paper may also have utility in developing temporally sequenced descriptions of neurocognitive processes targeted by MBIs. We offer the following speculative, hypothetical account based on our clinical and research experience using MBIs to treat persons diagnosed with substance use disorders. When a recovering addict with a history of using drugs to cope with negative emotions encounters a cue associated with past drug-use episodes while in the context of a stressful environment (e.g., walking past a bar after getting in an argument with a work supervisor), this encounter may activate cortico-limbic-striatal circuits subserving drug-use action schemas. After completing a course in mindfulness training, the addict may become more aware of the automatic addictive habit as it is activated, allowing for top-down regulation of the precipitating negative emotional state and the bottom-up appetitive urge. Specifically, the individual may engage in mindful breathing to first disengage from and then restructure negative cognitive appraisals, thereby reducing limbic (e.g., amygdala) activity, autonomic reactivity, and dysphoric emotions related to the stressor. Concurrently, the individual may become aware of when his attention has been automatically captured by the sight of people drinking in the window of the bar, and, through formal mindfulness practice, activate fronto-parietal mediated attentional networks to disengage and shift focus onto the neutral sensation of respiration. During this process, as sensations of craving arise, the individual may engage in metacognitive monitoring of these sensations, and in so doing, facilitate prefrontal down-regulation of limbic-striatal activation. As mindfulness of craving is sustained over time without drug-use, the sensations of craving may abate, promoting extinction learning to weaken associative linkages between conditioned addiction-related stimuli and the attendant conditioned appetitive response. Once working memory has been cleared of active representations of substance use, the individual may shift attention to savor non-drug related rewards, such as the sense of accomplishment that may arise from successfully resisting the temptation to drink (i.e., self-efficacy), appreciating the beauty of the sunset on the walk home without being clouded by inebriation, or the comforting touch of a loved one upon returning home safe and sober. Through repeated practice of regulating addictive responses and extracting pleasure from life in the absence of substance use, the individual may re-establish healthy dopaminergic tone and foster neuroplasticity in brain areas subserving increased dispositional mindfulness.

Ultimately, mindfulness may facilitate a novel, adaptive response to the canonical “people, places, and things” that tend to elicit addictive behavior as a scripted, habitual reaction. In so doing, the practice of mindfulness may attenuate stress reactivity and suppression while disrupting addictive automaticity, resulting in an increased ability to regulate and recover from addictive urges. The neurocognitive framework we have presented is intended to stimulate future research and facilitate the optimization of MBIs for the treatment of addiction. The tools of modern science have only begun to elucidate the many ways in which mindfulness training targets the risk chain of addiction at the attention-appraisal-emotion interface.”

I will critique this very interesting model in due course.

References

1. Garland, E. L., Froeliger, B., & Howard, M. O. (2013). Mindfulness  training targets neurocognitive mechanisms of addiction at the attention-appraisal-emotion interface. Frontiers in psychiatry, 4.