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Indian Journal of Social Psychiatry, 2012, 28 (1-2), 43-52 Review Article
Shobit Garg, Ambrish S. Dharmadhikari, V.K. Sinha
Drug addiction constitutes a chronic central nervous system disorder and one of the most serious
public health problems globally. Most prominent feature of addictive behaviour is craving which can
be described as the psychic pain of addiction. It is an intractable obstacle confronted by subjects
with substance use disorders attempting to achieve abstinence. Craving is the key factor behind
compulsive drug-taking behaviour. Direct relationship between craving and relapse, though not
well established, appears to occur through intermediate factors. Incorporating craving
measurements into routine clinical practice can increase the patient's capacity to recognize and
monitor his internal states that are related to substance intake and this can be used in
recommending appropriate treatment. Craving seems to be a nonunitary phenomenon, and
different kinds of craving with different mechanisms have been proposed, so it is conceivable that
different drugs (including proposed immunotherapy) can be more or less effective in different kinds
of craving.
Key words: Addiction, craving, abstinence
have an earlier age at onset, have more days of abuse in The Webster's Dictionary (Neufeldt, 1990) has defined a given month and take less time to become addicted “crave” to ask for earnestly, to want greatly, and to yearn with greater severity. Cocaine-dependent women also for. Craving is an emotionally charged term and has demonstrate greater depressive symptomatology, irresistible, compulsive, appetitive and anticipatory longer abstinence, higher levels of drug craving and qualities. Craving is a poorly understood term used to seek more help after relapsing while men have more describe a variety of phenomenon related to subjective antisocial personality disorders (Weiss et al., 1997). Also and objective states that may lead to substance women exhibit less cocaine addiction–related pathology of the frontal cortex than do men (Chang et World Health Organization (WHO) Expert Committees on Mental Health and on Alcohol (1955) in 1954 THEORIES OF “CRAVING”
concluded that the term “Craving” was inappropriate because of its everyday connotations. Later craving 1. Conditioning based models: Four models based on
entered into ICD- 10 as one of the diagnostic criteria Ivan Pavlov's classical conditioning are: the withdrawal World Health organization (1992) but it does not model, the compensatory response model, the feature in DSM IV diagnostic criteria (DSM IV merely opponent process model, and the incentive states that craving is “likely to be experienced by most, if not all, individuals with substance dependence”) In withdrawal model individuals seek to consume drugs (American Psychiatric Association, 1994). Rankin et al.
in order to escape aversive state and to relieve (1979) referred to craving as a generic “predisposition withdrawal-related discomfort. Initially the lack of to drink”, comprising all levels of desire, but Kozlowski & drugs (an unconditioned stimulus) provokes a Wilkinson (1987) used craving only to describe urgent withdrawal syndrome (an unconditioned response).
desires. In spite of failure to reach a consensus in a Associated with the lack of drugs are drug paraphernalia meeting on craving by NIDA (US National Institute on that become conditioned stimuli to the withdrawal Drug Abuse) in 1991, craving is enjoying the renewed discomforts. During abstinence, these cues may interest in cue reactivity in relapse, neuroimaging and provoke a withdrawal response (a conditioned treatment modalities (MacKillop & Monti, 2007).
response) that is thought to create craving (Baker et al., GENDER DIFFERENCES IN THE CRAVING PROCESS
Whereas addiction is often attributed to men, women The opponent-process and compensatory response also are clearly affected. Cocaine-dependent women models state that the withdrawal response should be 2012 Indian Association for Social Psychiatry Indian Journal of Social Psychiatry, 2012, 28 (1-2), 43-52 opposite to the direct effects of the drug and be cerebral activity results in craving. In early withdrawal correlated to the level of tolerance Baker et al. (1986).
state, craving occurs to alleviate the imbalance. In later These also explain why craving appears in the abstinent recovery state, the altered brain functions returns to subjects long after the withdrawal symptoms have their original state but cravings may appear suddenly.
This reactivation can be triggered by stress which may The incentive model Stewart et al. (1984) posits that a activate the reward memory (Anton, 1999).The reward stimulus such as a bar becomes conditioned, thus memories may also reactivate neurochemical processes provoking similar physiological and psychological associated with past experiences of drug use and cause responses as actual drinking. If drinking does not take place, craving occurs to appreciate the positive aspects exposure causes allostasis, defined as ''a state of chronic 2. Cognitive
models The various cognitive models
deviation of the regulatory systems with establishment involving information-processing systems are as of a new set point''. An allostatic state involves a feed- forward mechanism rather than the negative feedback mechanism of homeostasis. Overactivation of the brain anticipatory effect of positive outcome expectancies reward system triggers the brain stress circuit or (beliefs) provoked by alcohol related cues. There is also antireward system, in order to limit the reward. Long motivational component i.e. intention to use, labeled term drug intake dysregulates the underlying ''urge'' and one may experience a craving and not an neurochemical functions (↓ Dopamine, ↓ Serotonin, ↑ urge – that is, be tempted but not intend to consume.
Corticotropin-releasing factor) resulting in an allostatic model Urges are modulated by positive and state. Antireward system and neurotransmitter changes negative affect urge network (Baker et al., 1986). The create powerful negative reinforcement. Craving arises positive affect urge network has information on the from the action of memory of the rewarding effects of direct pleasurable effects of the drug. Negative network drug use superimposed on a negative emotional state provokes urge based on the negative affect. Baker et al.
(1986) suggested that positive expectancies of Temporal-difference reinforcement learning model desirable drug effects are probably coded into the (TDRL)- In TDRL, actions are selected to maximize future negative affect network: the drug is more desirable rewards which are based on the strength of a value signal, defined as the expected future reward discounted by the expected time to the reward. This drinkers accustomed to no limits are prevented from value signal is carried by dopamine and produce drinking. For example, an individual decides to consume temporal-difference learning in the normal brain. TDRL a drink but if an obstacle prevents consumption, craving is based on assumptions about cocaine, which produce happens, considered to be a non-automatic, effortful a phasic increase in dopamine directly and push a response (Tiffany, 1999). Alcoholics exposed to alcohol person towards irrational behaviour (Redish, 2004).
cues had a slower reaction time on cognitively demanding tasks and perceive an ''extended now'' refers to the sensations that originate from the interior state, during periods of self-restraint resulting in relapse of the body. The interoceptive state is mediated by anterior insular cortex which has bidirectional 3. Psychobiological
models These models are directly
connections to the amygdala and the ventral striatum.
influenced by biological neural systems (neural circuitry, Alteration in interoceptive processing is due to an reward systems, and neuroanatomical) and are as altered ''prediction error'' which refers to the difference between the value of the anticipated sensation (i.e., the Neuroadaptive model- Craving is due to hyper- hoped for result) and the value of the current sensitization of the dopamine neural transmitter interoceptive state. Dysregulation of insular cortex system that in turn increases the incentive salience of (minimizes the body prediction error) causing non- drugs. ''Incentive salience'' makes stimuli more adaptive adjustment of the body prediction error attractive and turns ordinary wanting into excessive causes craving in addiction process (Paulus et al., 2009).
drug craving (Robinson & Berridge, 1993). Drugs causeneurobiological adaptations to maintain homeostasis 4. Motivational
models The motivational models of
and if drug consumption ceases, an imbalance in 2012 Indian Association for Social Psychiatry Indian Journal of Social Psychiatry, 2012, 28 (1-2), 43-52 Motivational model of alcohol use- Final common stereotypic thinking. The orbitofrontal is thought to pathway to alcohol use is motivational and the strength inhibit impulsive behaviour by sending evaluative of the motivation depends upon the emotional state information to the DLPC. Because the orbitofrontal one wish to achieve (Cox & Klinger, 1988). A person's cortex is connected through the DLPC to the basal desire to drink depends on the degree of incentive ganglia, its impairment may promote obsessive– motivation. The model also takes into account compulsive state. Individual memories interact with the personality, historical factors, direct chemical effects, judgment center of the orbitofrontal cortex in a highly past reinforcement from drinking, situational factors, specific way when an individual evaluates the level of risk or reward in a given situation.
Multidimensional ambivalence model- This model TYPES OF CRAVING
consists of two parallel, motivational pathways, There are three types of craving based on three- approach (induces a craving) and avoidance (stops pathway psychobiological model as proposed by craving) and adds an ''evaluative space'' where these competing motives intersect. Also, it adds the key 1. Reward craving, involves those people who consume modulator ''access to alternative valued activities''. In because of a desire for the positive effects of alcohol.
the evaluative space, four subgroups can be found: The personality style is that of reward seekers, that is, a approach, avoidance, indifference, and ambivalence.
high sensitivity to positive reinforcement or rewarding Indifference consists of low approach and low events. They seek the neurotransmitter chemical avoidance, whereas ambivalence consists of high reward involving the opioidergic/ dopaminergic system approach and high avoidance (Breiner et al., 1999).
to compensate for a low level of cortical arousal.
5. Personality theories
2. Relief craving, involves those people who consume to Eysenck's theory of personality says that subjects with relieve tension or arousal. The personality style is stress high extraversion have difficulties in acquiring reactive. Relief craving is associated with aversive conditioned responses due to lower sedation motivational system or the behaviour inhibition system thresholds and high neuroticism is thought to enhance (BIS) (Gray, 1987). Relief craving is possibly due to a conditionability (Eysenck & Eysenck, 1985). Because dysregulation in the GABAergic/ glutamatergic systems craving can be regarded as a conditioned response to drug, lower extraversion and higher neuroticism, 3. Obsessive craving, involves those who are incapable of controlling their intrusive thoughts about drinking.
According to Gray (1987), Behavioural Approach System The personality style associated is characterized by low (BAS) regulates aversive motivation and the restraint or disinhibition, that is, ''the inability to Behavioural Inhibition System (BIS) regulates appetitive restrain impulses in the face of impending appetitive motivation. High BAS sensitivity is reflected in and aversive stimuli''. Obsessive craving may result from engagement in goal-directed efforts when the person is exposed to cues that predict reward.
Drummond (2000) also talked about ''cue-elicited NEUROANATOMY OF CRAVING
craving'' (conditioned response to a cue) and Anton (1999) proposed a neuroanatomical model ''withdrawal-related craving'' (during the withdrawal based on clinical experience, brain-imaging, and phase as an unconditioned response) with possibility of laboratory data. Various drugs increase dopamine levels in the nucleus accumbens. Three brain regions Koob & Moal (2008) also gave two types of craving. The are subsequently activated: the amygdala; the dorsal first, Type 1, was induced by memory of cues that had lateral prefrontal cortex (DLPC), the region where previously been paired with drug use. Type 2 craving reward memory are located, and the basal ganglia, a consist of a Type 1 craving situation superimposed onto region involved in repetitive thought and behaviour a change in emotional state characterized by dysphoria, patterns. The DLPC is also stimulated by sensory anxiety, or a residual negative emotion.
information from the frontal cortex in addition to affect ASSESSMENT OF DRUG CRAVING
from the amygdala and nucleus accumbens.
Both direct self-report questionnaires and indirect The DLPC in return sends information and sensitizes behavioural and physiological measures are used to nucleus accumbens to future drug cues. In addition, the assess the psychological experience of craving DLPC transmits the memory to the basal ganglia that may increase the craving reaction because of its role in Single-item ratings of subjective craving- Single-item 2012 Indian Association for Social Psychiatry Indian Journal of Social Psychiatry, 2012, 28 (1-2), 43-52 Likert-type rating or visual analogue scale (VAS) are There is now a range of medications available for each of used to indicate the degree of craving. Paper-and-pencil the major classes of addictive drugs: alcohol, cocaine, forms, control knob, dial or joysticks to a computer are used to record multiple repeated ratings of craving.
1. Anticraving drugs for Alcohol
Multi-item self-report questionnaires- Various Three US FDA approved medications for the relapse questionnaires like Obsessive–Compulsive Drinking prevention of alcohol are Naltrexone, Acamprosate and Scale (OCDS) Anton et al. (1995); Obsessive– Compulsive Drug Use Scale (OCDUS) Franken (2002) one Naltrexone is approved by the US FDA in and Temptation and Restraint Inventory (TRI) Collins & 1994 that diminishes the rewarding effects by reducing Lapp (1992) are used to assess craving Rosenberg dopamine in VTA (Ventral Tegmental Area) and nucleus accumbens and release of endogenous opioids like edures The instructions are similar to the free association in psychoanalytic therapy, in that It reduces craving for both dependent patients and participants are asked to speak their thoughts aloud social drinkers. There are reviews and meta-analyses, without any judgment, except that they do so during along with 29 published randomized placebo controlled cue exposure or after imagining themselves in a drug trials, some supportive and some not (Kranzler, 2000; related situation (Shadel et al., 2004).
Richardson et al., 2008). Naltrexone significantly Indirect or proxy measures of cra
ving Various indirect
reduces craving and rates in heavy drinkers by 30-60%, ways of assessing craving are as follows: though abstinence is seen usually in 25-35% cases dreams Substance-related dreams are the Pettinati et al. (2006).The dose is 50-100 mg per day.
expression of unconscious wishes to resume drug use.
Potential barriers are non-adherence (at least 80% The frequency and prevalence of substance-related compliance with daily administration of the drug is likely dreams are associated significantly, if only moderately, A long acting injectable formulation of Naltrexone 2. Behavioural indications of craving- Proposed (encapsulated naltrexone 380 mg in bio-degradable behavioural indicators of craving in people include microspheres) was approved by the US FDA in 2006.
latency to consume one's drug of choice, amount or Therapeutic levels are maintained for a month. It also speed of consumption, interpuff or inter-sip interval, has reduced side effects and less chance of hepatic and willingness to “work” for access to one's drug.
3. Psychophysiological measures of e It was approved in 2004 in US for clinical salivation (measured by dental rolls placed in the use. It affects calcium channels and decrease in CNS subject's mouth) predicts relapse following treatment, excitatory system by reducing glutamate Dahchour & though moderately. Greater self-reported craving and DeWitte (2003). It has no abuse potential and has eye blinks are found when smokers recalled smoking- favourable side effect profile. Double-blind clinical trials related sentences. Exposure to drug related stimuli (1.3–3 g/day, orally administered) and meta-analysis resulted in significant increase in heart rate in smokers, have shown the efficacy of acamprosate in decreasing problem drinkers and cocaine abusers (but not heroin craving and maintaining abstinence (Mann, 2004).
addicts), and significant increase in sweat gland activity Comparison between acamprosate and naltrexone and in all four groups (Rosenberg, 2009).
other drugs: Overall acamprosate showed increase in 4. Attentional bias- Performance on attention-related the cumulative abstinence period, decrease the tasks such as the addiction-stroop and dot-probe likelihood of return to drinking, and better compliance procedure may serve as proxy measures of subjective (effect better with higher doses) compared to craving. Longer reaction times on addiction-related naltrexone. More recent studies of naltrexone have words from contrast words, distinguish substance found less favourable outcomes. Overall evidence abusers from non-abusers, and predict relapse favour acamprosate because of more number of studies following a period of abstinence (Cox et al., 2006). Also have been conducted with it, with longer duration, and attentional bias is inferred by faster reaction time when better acceptability in patient groups due to lesser the probe replaces a drug-related stimulus than when it adverse effects as compared to naltrexone. One replaces the neutral stimulus (Rosenberg, 2009).
potential advantage of naltrexone (though not studied ANTICRAVING MEDICATIONS
well) is its convenience of administration. Taking two 2012 Indian Association for Social Psychiatry Indian Journal of Social Psychiatry, 2012, 28 (1-2), 43-52 tablets of acamprosate thrice a day may be Tiapride It has shown to promote abstinence, seems to cumbersome for some patients and may affect be well tolerated, although 4 cases of late dyskinesia compliance as compared to the relatively simpler have been reported (Shaw et al., 1994).
regimen of naltrexone one tablet per day (Dhawan & ol It reduces alcohol intake in a rat model, but the anti-alcohol effect is weakly selective and Effect is synergistic when acamprosate is combined with nonspecific. Pilot studies suggest its role in treatment of disulfiram (Besson et al., 1998). Acamprosate is said to substance abuse in psychiatric patients (Wiesbeck et al., be a cost effective treatment. However, in India, Disulfiram is cheaper than either Naltrexone or Methadone- Short-term methadone administration Acamprosate (Dhawan & Jhanjee, 2007).
has shown to reduce alcohol consumption in heroin Disulfiram It reduces the daily struggle against urges addicted patients (Caputo et al., 2002).
toward alcohol. It is reserved for patients who have Glutamatergic compounds- Memantine and previously failed one or more courses of treatment or lamotrigine have shown to reduce craving but in animal who are motivated to achieve complete abstinence models and further clinical studies are needed (Brewer, 2005). Disulfiram use is now a second line treatment after Naltrexone and Acamprosate. Several 2. Aniticraving agents for Cocaine
reviews support the efficacy (Suh et al., 2006) but lack of Many agents have been tested and demonstrated to be double blind controlled and randomized controlled ineffective as treatment for cocaine dependence (Levy, trials are hindrance. A long acting depot preparation in the form of an implant has similar pharmacological Various drugs such as dopamine antagonists profile like oral Disulfiram (Johnsen & Marland, 1992).
(haloperidol, flupenthixol), dopamine-enhancing No current research evidence is available on this agent's (disulfiram and modafinil), dopamine agonists (bromocriptine, amantadine, pergolide and levodopa), en It (15 mg/day for the first three days and 30 topirimate, propranolol, vigabatrin, methylphenidate mg/day subsequently) is effective in reducing intake, inducing and maintaining abstinence. Also it has good Disorder), buprenorphine, imipramine (in comorbid tolerability and low side effects, without any risk of depression), nifedipine and nimodipine have shown abuse and also relieves symptoms of alcohol some efficacy in reducing the reinforcing effects of cocaine but further studies are needed (Grabowski et al., 1994; Nunes et al., 1995; Compton et al., 1995; e It (25–300 mg/day for 12 weeks) promotes Handelsman et al., 1995; Kuzmin et al., 1996; Kampman abstinence and reduces intake and craving. Recent et al., 2002; Kampman et al., 2003; Carroll et al., 2004; studies have shown to reduce addiction severity and in Kampman et al., 2004; Hart et al., 2006; Levy, 2009; ).
increasing the patient's quality of life (Johnson et al., O t h e r d r u g s i n c l u d e m a z i n d o l , f l u oxe t i n e , carbamazepine, lithium, naltrexone and 4-iodococaine.
Serotonin Reuptake Inhibitors and Ondansetron- All have been postulated to alter reinforcing effects of Fluoxetine (20 mg/day for the first 2 weeks then 40 cocaine. Comparative studies are still pending (Levy, mg/day) has proved to be effective in reducing depressive symptoms and alcohol consumption 3. Anticraving agents for Nicotine
together (Cornelius et al., 1997). Agabio et al. (2001) Non-nicotine medications can be used in combination showed that SSRIs might be useful in patients with late- with nicotine replacement for nicotine cessation.
onset alcohol dependence, while ondansetron (0.5–4 Bupropion was approved by the FDA for smoking mg for 6 weeks) could be effective in patients with early- cessation. It reduces craving by action on dopamine.
Bupropion, alone (30.3%) or in combination with the nicotine patch (35.5%), had superior abstinent rates to detoxification of anxious subjects. A recent study, the nicotine patch or placebo alone (Jorenby et al.
however, has not confirmed the efficacy of buspirone versus placebo in decreasing alcohol consumption Varenicline (approved in 2006 by the FDA as an aid to smoking cessation) is a 4, 2 nicotinic acetylcholine receptor partial agonist. Varenicline had significantly 2012 Indian Association for Social Psychiatry Indian Journal of Social Psychiatry, 2012, 28 (1-2), 43-52 greater abstinence rates at 12 and 52 weeks than Table 1: Current status of vaccines in clinical trials
placebo or bupropion (Jorenby et al., 2006).
Rimonabant is a specific antagonist to cannabinoid Drug-Carrier
Human Studies
receptor 1 (CB-1). Randomized controlled trials show that rimonabant is effective for patients wishing to lose weight and stop smoking. This drug is advancing through the FDA approval process (O'Brien, 2005).
Nortriptyline and clonidine both appear effective, but are considered second-line treatments (due to potential side effects and lack of FDA sanction as smoking cessation aids) (Marlatt & Witkiewitz, 2005).
4. Anticraving agents for Opiate Addiction
Strategy to maintain the patient with a medication in the same pharmacological category (methadone orbuprenorphine) as the prior drug of dependence PSYCHOLOGICAL MANAGEMENT OF CRAVING
enables a subject with opiate addiciton to function Psychological treatment for reducing craving can be normally with little or no drug craving. Naltrexone can aid in the maintenance of the opiate-free state. If a 1. Procedures that are designed to decrease the former addict “slips” and takes a dose of heroin while likelihood of the onset of craving that include stimulus taking maintenance naltrexone, the effects will be control, cue exposure, aversion therapy, coping imagery neutralized. Many report no craving possibly because they learn that opiates are unavailable because of the 2. Procedures that are designed to decrease the intensity and duration of craving include cognitive and 5. Anticraving agents for Inhalant abuse
S h a r p & R o s e n b e r g ( 1 9 9 7 ) r e p o r t e d t h a t trol Externally triggered craving can be pharmacotherapy is not usually useful in inhalant abuse.
reduced by minimizing exposure to the cues. Simple Once detoxified, antidepressants, anxiolytics, or avoidance of the situation is the best strategy especially neuroleptics can be used as an adjunct to counseling, in those filled with multiple cues for indulgence, before depending on the problems that initially contributed to coping responses are strong Marlatt & Witkiewitz IMMUNOTHERAPY FOR THE TREATMENT OF DRUG
Cue Exposure- Cue exposure involves repetitive exposure to cues, producing extinction of craving Antibody therapy prevents drugs of abuse from entering responses. It is most effective when exposure to drug the CNS and reduce rush, euphoria. This is accomplished cues is paired with strategies designed to combat through a pharmacokinetic antagonism which reduces everyday temptations. Efficacy in reducing relapse to the amount of drug in the brain, the rate of clearance alcohol, nicotine, opiates, and cocaine is seen.
across the blood–brain barrier and the volume of drug Aversion therapy- Aversion therapy involves pairing distribution. Active immunization with drug–protein of alcohol cues with an aversive stimulus, a procedure conjugate vaccines has been tested for cocaine, heroin, by which alcohol cues come to elicit an aversive reaction methamphetamine, and nicotine in animal and passive rather than craving. In contrast to cue-exposure, the immunization with high affinity monoclonal antibodies goal of aversion therapy is to increase reactivity to has been tested for cocaine, methamphetamine, alcohol cues, because such cue reactivity is assumed to nicotine, and phencyclidine in preclinical animal reflect conditioned nausea. Increased bodily reaction models. The specificity of the therapies (table 1), the following aversive reaction should be associated with lack of addiction liability, minimal side effects (itching successful outcome (Baker et al., 1987).
and redness at injection site) and long-lasting protection Coping Imagery- “Urge Surfing” technique can be offer major therapeutic benefits Kosten & Owens used to gain control by the patients. Client first labels the internal sensations and cognitive preoccupations asan urge or craving and then fosters an attitude of 2012 Indian Association for Social Psychiatry Indian Journal of Social Psychiatry, 2012, 28 (1-2), 43-52 detachment and disidentification regarding the wave of and alcoholism.Expert opinion on therapeutic targets, desire. Clients are initially taught the urge surfing technique through guided imagery and then to try it on American Psychiatric Association. (1994) Diagnostic and their own whenever they are exposed to substance statistical manual of mental disorders, Washington, DC.
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Shobit Garg, D.P.M., Junior Resident, Central
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Ambrish S. Dharmadhik
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Vinod K. Sinha, M.D., D.P.M., (Corresponding
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2012 Indian Association for Social Psychiatry


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