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|• addiction – a state characterized by compulsive engagement in rewarding behavior or compulsive drug use, despite adverse consequences|
|• reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them|
|• rewarding stimuli – stimuli that the brain interprets as intrinsically positive or as something to be approached.|
|• addictive drug – a drug that is both rewarding and reinforcing|
|• addictive behavior – a behavior that is both rewarding and reinforcing|
|• sensitization - an amplified response to a stimulus resulting from repeated exposure to it|
|• drug tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose|
|• drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose|
|• drug dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated drug intake|
|• physical dependence – dependence that involves physical–somatic withdrawal symptoms (e.g., fatigue)|
|• psychological dependence – dependence that involves emotional–motivational withdrawal symptoms (e.g., dysphoria and anhedonia)|
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Addiction is a state defined by compulsive engagement in naturally rewarding behavior or compulsive drug use, despite adverse consequences; it can be thought of as a disease or biological process leading to such behaviors.
According to many addiction specialists, potential non-drug addictions can include, but are not limited to, exercise addiction, food addiction, computer addiction and gambling. Currently, only substance addictions and gambling addiction are recognized by the DSM-5. ΔFosB, a gene transcription factor, is now known to be a critical component and common factor in the development of virtually all forms of behavioral and drug addictions. Classic hallmarks of addiction include impaired control over substances or behavior, preoccupation with substance or behavior, continued use despite consequences, and denial. Habits and patterns associated with addiction are typically characterized by immediate gratification (short-term reward), coupled with delayed deleterious effects (long-term costs).
Physiological dependence occurs when the body has to adjust to the substance by incorporating the substance into its "normal" functioning. This state creates the conditions of tolerance and withdrawal. Tolerance is the process by which the body continually adapts to the substance and requires increasingly larger amounts to achieve the original effects. Withdrawal refers to physical and psychological symptoms experienced when reducing or discontinuing a substance that the body has become dependent on. Symptoms of withdrawal generally include but are not limited to anxiety, irritability, intense cravings for the substance, nausea, hallucinations, headaches, cold sweats, and tremors.
Forms of dependence that are not mentioned in DSM-5 include:
Withdrawal is the body's reaction to abstaining from an addictive substance of which it has become dependant and tolerant. Without the substance, physiological functions that were dependent on the substance will react because of the body's tolerance and dependence of the substance. Chemical and hormonal imbalances may arise if the substance is not introduced. Physiological and psychological stress is to be expected if the substance is not re-introduced.
In addition to the traditional behavioral self-help groups and programs available for rehabilitation, there is a varied array of preventive and therapeutic approaches to combating addiction. For example, a common treatment option for opiate addiction is methadone maintenance. This process consists of administering the drug, a potent opiate with some potential for abuse, as a drink in a supervised clinical setting. In this way, the brain opiate levels increase slowly without producing the high but remain in the system long enough to deter addicts from injecting heroin.
Another form of drug therapy involves buprenorphine, a drug which seems to be even more promising than methadone. A partial agonist for certain opiate receptors, this treatment blocks the effects of opiates but produces only mild reactions itself. Moreover, this method of detoxification has little value in the drug market.
New research indicates that it may even be possible to develop antibodies which combat a particular drug's effect on the brain, rendering the pleasurable effects null. Recently, vaccines have been developed against cocaine, heroin, methamphetamine, and nicotine. These advances are already being tested in human clinical trials and show serious promise as a preventive and recovery measure for addicts or those prone to addiction.
Furthermore, another method of treatment for addiction that is being studied is deep brain stimulation. A serious procedure, DBS targets several brain regions including the nucleus accumbens, subthalamic nucleus, dorsal striatum, and medial prefrontal cortex among others. Other studies have concurred and demonstrated that stimulation of the nucleus accumbens, an area that is apparently one of the most promising regions, allowed a seventy-year-old man to stop smoking without issue and attain a normal weight.
The term addiction is also sometimes applied to compulsions that are not substance-related, such as compulsive shopping, sex addiction/compulsive sex, overeating, problem gambling, exercise/sport, compulsive or binge travel, and computer addiction. In these kinds of common usages, the term addiction is used to describe a recurring compulsion by an individual to engage in some rewarding activity, despite harmful consequences, as deemed by the user themselves to their individual health, mental state, or social life.
Current models of addiction from chronic addictive drug use involve alterations in gene expression in the mesocorticolimbic projection. The most important transcription factors that produce these alterations are ΔFosB, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and nuclear factor kappa B (NFκB). ΔFosB is the most significant gene transcription factor in addiction since its viral or genetic overexpression in the nucleus accumbens is necessary and sufficient for many of the neural adaptations seen in drug addiction; it has been implicated in addictions to alcohol, cannabinoids, cocaine, nicotine, phenylcyclidine, opiates, and substituted amphetamines. ΔJunD is the transcription factor which directly opposes ΔFosB. Increases in nucleus accumbens ΔJunD expression using viral vectors (a genetically engineered virus) can reduce or, with a large increase, even block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).
ΔFosB also plays an important role in regulating behavioral responses to natural (non-drug) rewards, such as palatable food, sex, and exercise. Natural rewards, like drugs of abuse, induce gene expression of ΔFosB in the nucleus accumbens, and chronic acquisition of these rewards can result in a similar pathological addictive state through ΔFosB overexpression. Consequently, ΔFosB is the key transcription factor involved in addictions to natural rewards (i.e., behavioral addictions) as well; in particular, ΔFosB in the nucleus accumbens is critical for the reinforcing effects of sexual reward. Research on the interaction between natural and drug rewards suggests that dopaminergic psychostimulants (e.g., amphetamine) and sexual behavior act on similar biomolecular mechanisms to induce ΔFosB in the nucleus accumbens and possess bidirectional cross-sensitization effects that are mediated through ΔFosB. This phenomenon is notable since, in humans, a dopamine dysregulation syndrome, characterized by drug-induced compulsive engagement in natural rewards (specifically, sexual activity, shopping, and gambling), has also been observed in some individuals taking dopaminergic medications.
The release of dopamine in the nucleus accumbens plays a role in the reinforcing qualities of many forms of stimuli, including naturally reinforcing stimuli like palatable food and sex. Altered dopamine neurotransmission is frequently observed following the development of an addictive state. In humans and lab animals that have developed an addiction, alterations in dopamine or opiate neurotransmission in the nucleus accumbens and other parts of the striatum are evident. Studies have found that use of certain drugs (e.g., nicotine) affect cholinergic neurons that innervate the reward system, in turn affecting dopamine signaling in this region.
|Form of neural or behavioral plasticity||Type of reinforcer||Sources|
|Opiates||Psychostimulants||High fat or sugar food||Sexual reward||Exercise||Environmental enrichment|
in the nucleus accumbens
|Escalation of intake||Yes||Yes||Yes|||
conditioned place preference
|Reinstatement of drug-seeking behavior||↑||↑||↓||↓|||
in the nucleus accumbens
|Sensitized dopamine response|
in the nucleus accumbens
|Altered striatal dopamine signaling||↓DRD2, ↑DRD3||↑DRD1, ↓DRD2, ↑DRD3||↑DRD1, ↓DRD2, ↑DRD3||↑DRD2||↑DRD2|||
|Altered striatal opioid signaling||↑μ-opioid receptors||↑μ-opioid receptors|
|↑μ-opioid receptors||↑μ-opioid receptors||No change||No change|||
|Changes in striatal opioid peptides||↑dynorphin||↑dynorphin||↓enkephalin||↑dynorphin||↑dynorphin|||
|Mesocorticolimbic Synaptic Plasticity|
|Number of dendrites in the nucleus accumbens||↓||↑||↑|||
|Dendritic spine density in|
the nucleus accumbens
Research has consistently shown strong associations between affective disorders and substance use disorders. Specifically, people with mood disorders are at increased risk of substance use disorders. Affect and addiction can be related in a variety of ways as they play a crucial role in influencing motivated behaviours. For instance, affect facilitates action, directs attention, prepares the individual for a physical response, and guides behaviour to meet particular needs. Moreover, affect is implicated in a range of concepts relevant to addiction: negative reinforcement and positive reinforcement, behaviour motivation, regulation of cognition and mood, and reasoning and decision making. Emotion-motivated reasoning has been shown to influence addictive behaviours via selecting outcomes that minimize negative affective states while maximizing positive affective states.
The relationship between negative affect and substance use disorders has been the most widely studied model of addiction. It proposes that individuals who experience the greatest levels of negative affect are at the greatest risk of using substances or behaviours as a coping (psychology) mechanism. Here, substances and behaviours are used to improve mood and distract from unpleasant feelings. Once physical dependence has been established, substance abuse is primarily motivated by a desire to avoid negative affective states associated with withdrawal. Individuals high in affective mood disorders (anxiety) most commonly report high levels of negative affect associated with cravings. The relationship between negative affect and addiction is not unidirectional. That is, while positive affect increases the likelihood of initiation of substance use, the negative affective states produced by withdrawal are the most commonly reported factors for continued use.
Key to this concept is the Hedonic Hypothesis, which states that individuals initiate use of the substance or behaviour for their pleasurable effects, but then take it compulsively to avoid withdrawal symptoms, resulting in dependence. Based on this hypothesis, some researchers believe that individuals engaging in risky use of substances or behaviours may be over-responsing to negative stimuli, which leads to addiction.
Negative affect has also been a powerful predictor in terms of vulnerability to addiction in adolescents. High-risk adolescents have been found to be highly reactive to negative stimuli, which increases their motivation to engage in substance use following a negative emotion-arousing situation. Moreover, it has been established that adolescents high in negative affect are at increased risk for moving from recreational use to problematic use despite a family history of addiction.
Furthermore, the trait negative urgency, the propensity to engage in risky behaviour in response to distress, is highly predictive of certain aspects of substance abuse in adolescents. Early individual differences in emotional differences in reactivity and regulation underlie the later emergence of the trait 'negative urgency'.
Unlike negative affect, positive affect is related to addiction in both high and low forms. For example, individuals high in positive affect are more likely to engage in risky behaviour, such as drug use. Individuals with high positive affect in response to use are more likely to seek out substances for hedonic reasons. Conversely, low positive affect may prompt initial use due to lack of responsiveness to natural rewards.
Extensive personality research has been done that links positive emotional states to individual differences in risky behaviour. The trait positive urgency, defined as the tendency to engage in risky behaviour under conditions of extreme positive affect, is predictive of substance or behavioural problems that lead to addiction. This trait represents an underlying dysregulation in response to extreme affective states and has a direct impact on behaviour. The trait 'positive urgency' has been shown to have a predictive relationship with increases in drinking quantity and alcohol-related problems in college, as well as drug use in college. Furthermore, this trait provides important information on how positive affect can increase the likelihood of engaging in substance abuse.
Another important factor to consider is the individual differences in the experience of pleasurable effects brought on by the substance or behaviour. It is reasoned that certain individuals may be more sensitive to the pleasurable effects and thus experience them with greater intensity, resulting in addiction. For example, over-responsiveness to substance affects has been found in cocaine addicts - an increased response to methylphenidate in the brain regions associated with emotional reactivity and mood. Thus, strong emotional responses that addicted individuals show in response to substances or behaviours might be results of enhanced sensitivity to their effects.
Individuals differ in the way by which they metabolize substances, such as alcohol; these positive reinforcing effects are partly predetermined. Individual reactivity to the effects of substances may affect motivation to use. For example, if a person experiences strong positive (and weak negative) effects from a substance, due to their biochemical profile, their expectations of the positive effects from the substance will be heightened, therefore increasing their desire for continued use, resulting in dependence. According to this model, the experience of the positive mood enhances implicit attention to substance cues and implicit associations between reward and substance use.
Interestingly, many addicts report symptoms of anhedonia (i.e., the inability to experience pleasure). Results of chronic deviation of the brain's reward set point, which follow a prolonged intoxication, diminish responsiveness to natural positive stimuli. This may result in an over-responsiveness to substance-related cues, coupled with an impaired capacity to initiate behaviours in response to natural rewards. Thus, low positive affect inhibits the individual's ability to replace drug-taking with other rewarding activities. It has also been proposed that during substance dependence the somatic states that guide decision-making are weakened in relation to natural rewards, while at the same time they enhance the emotional response to drug-related stimuli.
Compulsive behaviours characterized by addiction are underpinned by two interacting systems: (a) impulsivity, and (b) reflection. Impulsivity is responsible for the rapid signalling of the affective importance of a stimuli. Reflection cognitively evaluates the signal before altering the behavioural response. Dysfunction in impulsivity exaggerates the emotional impact of the drug-related stimuli and attenuates the impact of natural reinforcement. Dysregulation in reflection results in the inability to override impulsivity, thus resulting in addiction. Under-responsiveness to naturally occurring positive stimuli is a crucial element that biases the individual towards the use of substances or behaviours and away from non-drug alternatives.
Temperamental effortful control is defined as the ability to suppress a dominant response in order to perform a subdominant response. In other words, it is the degree of control the individual has over impulses and emotions, which includes the ability to focus or shift attention. Temperamental effortful control can influence addiction in a number of ways.
Low levels of effortful control can render the individual less able to distract themselves from unpleasant feelings or overcome strong affective impulses, resulting in maladaptive responses to distress - such as continued substance use. Low effortful control may also interact with negative and positive affect, predisposing individuals to substance or behavioural use, and impair their ability to control use.
A general inability to control affective states may impair the conditioning of behaviour associated with rewards and punishment, may increase susceptibility to biasing by substance-related cues, and could tax self-regulatory capacity. Such conditions may render individuals unable to interrupt automatic drug-seeking behaviours. Abnormal levels of positive and negative affect can be increased by low effortful control. For example, high positive affect may interact with low effortful control in increasing risk of addiction amongst vulnerable populations.
Gray's Reinforcement sensitivity theory (RST) consists of two motivational systems: the Behaviour Inhibition System (BIS) and the Behaviour Activation System (BAS). The BIS is responsible for organizing behaviour in response to adverse stimuli. In other words, stimuli associated with punishment or the omission/termination of reward, are believed to underlie anxiety. The purpose of the BIS is to initiate behaviour inhibition, or interrupt ongoing behaviour, while the BAS is sensitive to stimuli that signal reward and/or relief from punishment (impusivity). In accordance with the RST, an association was found between people with extreme scores in BIS/BAS and adjustment problems. BIS and BAS reactivity correspond with individual trait differences in positive affect and negative affect - The BAS is associated with trait impulsivity and positive affect, while the BIS is associated with trait negative affect. For instance, it has been postulated that high BIS is related to anxiety, while high BAS is related to conduct disorders or impulsivity.
According to this model substance abuse problems may arise under two different personality traits: low BIS and high BAS. Since the BAS promotes the individual to pursue actions that may result in reward, BAS sensitivity is involved in the initiation of addiction. Significant associations have been found between high BAS such as alcohol misuse in school girls, hazardous drinking in men, illicit drug abuse, and tobacco use. BAS sensitivity is a significant predictor of reactivity to substance cues, or cravings. Conversely, BIS sensitivity is involved in avoiding negative situations or affect (such as withdrawal). Low BIS has been positively associated with continuing the addiction to relieve feelings of withdrawal, or for continued use to alleviate negative affect.
The model of impulsivity states that individuals high in impulsivity are at greater risk of addictive behaviours. The model proposes a two dimensional trait characteristic for the initiation and continuation of substance/behavioural abuse:
Both high RD and RI individuals are found to have difficulty in making decisions that have future consequences. Individuals high in RD experience greater reinforcement when initially engaging in the addictive behaviour, and experience stronger conditioned associations with continued use. Individuals high in RI experience greater difficulty resisting cravings even in the face of negative consequences. Some moderators of RD and RI on the severity of addiction are stress and negative affect (such as feeling depressed). That is, individuals high in RD/RI who also experience high levels of negative affect or stress, present more severe addictive behaviours. For example, if an individual is experiencing emotional distress, the distress experienced may lessen impulse control if they believe that engaging in addictive behaviour will decrease negative affect. According to this model, adolescents who are high in RI are at greater risk for developing addictions. Interestingly, low RI has been shown to moderate some of the risk of addiction due to family history. High RI for individual without a family history of addiction has been related to poor decision-making.
Cloninger's Tri-Dimensional Personality Theory states that personality comprises three genetically independent dimensions:
Each personality dimension lies on a spectrum ranging from low to high. For example, individuals high in NS are impulsive, while individual's low in NS are reflective. Interactions between each of these three personality dimensions lead to different responses to novelty, punishment and rewards.
This model was extended to alcohol use disorders proposing that individuals with alcohol use disorders have extreme temperaments (i.e. are very high or very low in NS, HA, and RD). This model proposes that alcoholics can be classified in two groups based on the combinations of their three personality dimensions:
Type I alcoholics have a late onset of alcohol-related problems, experience guilt and fear associated with consumption, lose control once drinking is initiated, engage in alcohol-related antisocial conduct, and rarely exhibit spontaneous alcohol-seeking behaviour. Type I alcoholics are thought to be low in NS and high in HA and RD, exhibiting behaviors that are motionally dependent, rigid, perfectionistic, anxious, quiet, patient, and introverted.
Type II alcoholics have an earlier onset of alcohol-related problems, less ability to abstain from alcohol, more frequent alcohol-related antisocial behaviour, less loss of control once drinking commenced, and less guilt or fear associated with drinking. These individuals are high in NS, and low in HA and RD, which means they may be typically aggressive, impulsive, active, talkative, and impatient.
In the mid-20th century critics of the addiction model, notably Thomas Szasz, claimed that the concept of addiction was not normatively neutral, but inherently included a normative component that was arguably out of place in scientific discourse. Szasz cited, for example, Goodman and Gilman's The Pharmacological Basis of Therapeutics, which defined "drug abuse" as "the use, usually by self-administration, of any drug in a manner that deviates from the approved medical or social patterns within a given culture." In investigating the history of the word "addiction," Szasz found that until the 20th century, the term meant "simply a strong inclination toward certain kinds of conduct, with little or no pejorative meaning attached to it." The Oxford English Dictionary included examples of addiction "to civil affairs" and "to useful reading." Szasz observed that the term transformed over time into a "stigmatizing label" with "pejorative meaning." Szasz drew an analogy between this stigmatization of minority psychopharmacological habits and the stigmatization of minority sexual habits
Just as socially disapproved pharmacological behavior constitutes "drug abuse," and is officially recognized as an illness by a medical profession that is a licensed agency of the state, so socially disapproved sexual behavior constitutes a "perversion" and is also officially recognized as an illness; and so, more generally, socially disapproved personal behavior of any kind constitutes "mental illnesses."
Szasz's views were criticized for failing to account for the effect of physiological dependence.
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