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Relapse

Relapse refers to the recurrence of signs and symptoms of a disease or condition after a period of apparent improvement or remission.^[1] In medical contexts, it commonly describes the re-emergence of illness following partial recovery, such as in cancer or chronic diseases, where treatment has temporarily controlled but not eradicated the underlying pathology.^[2] The term also encompasses a return to maladaptive behaviors, particularly in substance use disorders, where an individual resumes drug or alcohol consumption after a phase of abstinence or reduced use.^[3] In broader health and psychological frameworks, relapse is distinguished from a mere lapse—a brief, isolated slip—by its sustained nature, often indicating a setback that may require reevaluation of treatment strategies.^[4] For instance, in addiction recovery, relapse rates can be high, with studies showing that up to 40-60% of individuals experience at least one relapse within the first year of sobriety, influenced by factors like stress, environmental cues, and inadequate coping mechanisms.^[5] Prevention efforts typically involve cognitive-behavioral techniques, such as identifying high-risk situations and building relapse prevention plans, which emphasize long-term skill development over short-term abstinence alone.^[6] Relapse is not viewed as failure but as a common part of the recovery process in chronic conditions, underscoring the need for ongoing support and adaptive interventions.^[7] In diseases like multiple myeloma, specific criteria define relapse, including measurable increases in biomarkers or new symptoms, guiding clinical decisions on resuming therapy.^[8] Overall, understanding relapse informs holistic treatment approaches, promoting resilience and sustained health management across medical and behavioral domains.

Definition and Overview

Core Definition

In the context of addiction recovery, relapse refers to the resumption of substance use or addictive behaviors following a period of abstinence or significant reduction in such behaviors.^[9] This phenomenon is not merely an isolated incident but a multifaceted process involving cognitive, emotional, and behavioral elements that can lead to a return to pre-recovery patterns of use.^[10] Relapse is distinguished from a lapse, which involves a brief, isolated episode of use without progression to sustained patterns, whereas a full relapse entails a more prolonged and uncontrolled return to addictive behaviors.^[4] It also differs from withdrawal, which encompasses physiological symptoms occurring upon cessation of use, and from craving, which is an intense urge without actual consumption. The term's historical roots trace back to the 1970s, when researchers G. Alan Marlatt and Judith Gordon developed the relapse prevention model, framing relapse as a predictable response to high-risk situations rather than a moral failing.^[10] Epidemiological data indicate that relapse rates for substance use disorders range from 40% to 60% within the first year after treatment, comparable to recidivism rates in other chronic conditions like hypertension or asthma.^[9] This process often unfolds through identifiable stages, such as emotional, mental, and physical precursors leading to the act of use.^[11]

Stages of Relapse

The stages of relapse in addiction recovery represent a progressive, dynamic process that unfolds over time, often as part of the broader cycle of addiction where periods of abstinence alternate with returns to substance use. This model, originally detailed in an 11-phase framework and commonly distilled into three main stages—emotional, mental, and physical—emphasizes that relapse is not a sudden event but a gradual buildup of internal dysfunction that can be recognized before actual use occurs. The stages interconnect sequentially, with unresolved issues from earlier phases increasing vulnerability to later ones, though progression is not inevitable and depends on individual factors within the addiction cycle.^[12] Emotional relapse is the initial stage, characterized by emotional and behavioral changes that do not yet involve conscious thoughts of using but erode self-care and recovery foundations. Key indicators include bottling up feelings, social isolation, irregular attendance at support meetings, focusing excessively on others' problems rather than one's own, and neglecting basic needs such as balanced eating or adequate sleep—often summarized by the acronym HALT (hungry, angry, lonely, tired). Denial plays a central role, as individuals may dismiss these signs as unrelated to their recovery. This stage typically builds gradually over weeks or even months, setting the groundwork for further vulnerability without immediate awareness of the risk.^[12] Mental relapse follows as an internal tug-of-war emerges, where thoughts of using substances intensify and conflict with commitments to sobriety. Indicators encompass cravings for the substance, glamorizing or nostalgically recalling past use, minimizing the negative consequences of addiction, bargaining with oneself (e.g., rationalizing a "one-time" use), lying to cover growing urges, actively seeking opportunities to relapse, and planning the logistics of use. As resistance weakens, these thoughts become more frequent, often triggered by unresolved emotional distress from the prior stage. Unlike emotional relapse, this phase can develop over days to weeks, marking a critical transition point in the addiction cycle where cognitive distortions amplify the pull toward physical action.^[12] Physical relapse culminates in the actual resumption of substance use, often starting as a lapse—a single instance of use—that can rapidly escalate to full, uncontrolled relapse if not addressed. Key indicators include the behavioral act of obtaining and consuming the substance, frequently in secretive or high-risk settings to avoid detection. In this stage, neurobiological factors such as dopamine surges reinforce the behavior, contributing to immediate gratification and potential loss of control within the addiction cycle. The physical stage typically occurs abruptly, sometimes within hours of mental planning, contrasting the slower buildup of preceding phases and highlighting how earlier stages feed into acute breakdowns in recovery.^[12]

Neurobiological Basis

Dopamine Dysregulation

Dopamine dysregulation plays a pivotal role in relapse vulnerability within addiction, primarily through alterations in the mesolimbic reward pathway. This pathway, originating from dopamine neurons in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc) in the ventral striatum, is hyperactivated during craving states, leading to compulsive drug-seeking behaviors. Hyperactivity in the NAc, characterized by excessive dopamine release in response to drug cues, reinforces the motivational salience of substances and diminishes sensitivity to natural rewards, thereby increasing the propensity for relapse.^[13] A key biomarker of this dysregulation is the reduced availability of dopamine D2 receptors in the striatum, which is consistently observed across various substance use disorders and correlates with heightened relapse risk. Low D2 receptor availability, often approximately 20% lower than in non-addicted individuals, impairs the brain's ability to process rewards effectively, resulting in a hypofrontality that favors impulsive choices and reduced inhibition of drug-seeking. This reduction in D2 binding potential has been shown to predict poorer treatment outcomes and higher rates of relapse, as individuals with lower availability exhibit blunted dopamine responses to non-drug stimuli, perpetuating a cycle of vulnerability.^[14]^[15] Human positron emission tomography (PET) imaging studies further elucidate this process by demonstrating surges in striatal dopamine during exposure to relapse cues. For instance, in cocaine-dependent individuals, drug-related cues elicit significant increases in dopamine levels in the dorsal striatum, typically around 10-20%, which directly correlate with subjective craving intensity and predict subsequent drug preference. These phasic dopamine elevations in the NAc and surrounding striatal regions amplify the incentive value of cues, facilitating reinstatement of drug use even after prolonged abstinence.^[16]^[17] Genetic factors, particularly variants in the DRD2 gene, contribute substantially to this dysregulation by influencing D2 receptor density and function. The Taq1A polymorphism (rs1800497) in the DRD2 gene is associated with lower striatal D2 receptor availability, which heightens susceptibility to addiction and elevates relapse rates; for example, a pilot study found carriers of the A1 allele had an 89% relapse rate compared to 53% in non-carriers (odds ratio = 7.1) in alcohol dependence. These variants disrupt normal dopamine signaling, exacerbating reward deficits and cue reactivity, thus serving as heritable contributors to relapse proneness.^[18]^[19]

Other Neurochemical Factors

Glutamate plays a critical role in cue-induced reinstatement of drug-seeking behavior, a key mechanism underlying relapse in addiction. Hyperactivity of NMDA receptors in regions such as the nucleus accumbens and prefrontal cortex facilitates synaptic plasticity changes, including long-term potentiation (LTP), which strengthens maladaptive associations between drug cues and reward.^[20] This glutamate-driven plasticity is evident in models of cocaine and nicotine addiction, where elevated extracellular glutamate levels during cue exposure promote reinstatement by enhancing excitatory transmission in cortico-striatal circuits.^[21] For instance, up-regulation of NMDA receptor subunits GluN2A and GluN2B in the accumbens has been shown to mediate rapid synaptic potentiation that sustains cue-induced relapse vulnerability.^[22] These processes interact briefly with dopamine-glutamate crosstalk in reward pathways, amplifying reinstatement signals.^[21] Serotonin and norepinephrine contribute to relapse through their roles in mood regulation and stress responses, with deficits heightening impulsivity and emotional dysregulation in addiction. Serotonin (5-HT) system dysfunction, particularly involving 5-HT2A and 5-HT2C receptors, impairs inhibitory control and increases cue reactivity, thereby elevating relapse risk in cocaine-dependent individuals.^[23] Low serotonin levels are associated with heightened impulsivity, a core predictor of compulsive drug-seeking and poor treatment outcomes.^[24] Similarly, norepinephrine dysregulation in the locus coeruleus and extended amygdala circuits exacerbates stress-induced negative affect, driving reinstatement via enhanced arousal and reduced prefrontal regulation during abstinence.^[25] Deficits in these monoamines collectively promote impulsive decision-making under stress, linking mood instability to sustained addiction vulnerability.^[26] The endocannabinoid system modulates relapse by influencing reward processing and cue reactivity, primarily through CB1 receptors in mesolimbic pathways. Endocannabinoids such as anandamide and 2-arachidonoylglycerol regulate inhibitory tone on dopamine release, and their dysregulation during withdrawal heightens vulnerability to environmental triggers.^[27] Antagonism of CB1 receptors, as demonstrated by rimonabant (SR141716), effectively attenuates cue-induced reinstatement of seeking behaviors for cocaine, nicotine, and alcohol by reducing glutamatergic excitation in the nucleus accumbens and prefrontal cortex.^[28] This intervention diminishes the motivational salience of drug cues, highlighting the system's therapeutic potential in curbing relapse propensity.^[29] Recent research as of 2025 has highlighted epigenetic mechanisms contributing to relapse vulnerability. For instance, the enzyme histone deacetylase 5 (HDAC5) plays a critical role in regulating gene expression in brain reward circuits, influencing susceptibility to drug-seeking reinstatement following stress or cues. Dysregulation of HDAC5 has been linked to persistent neuroadaptations that predict relapse in animal models of addiction.^[30] Interactions between these neurochemical systems and the hypothalamic-pituitary-adrenal (HPA) axis further exacerbate relapse, as cortisol elevations during stress disrupt balanced neurotransmission in reward and stress circuits. Acute stress activates the HPA axis, leading to glucocorticoid surges that enhance glutamate and norepinephrine release while suppressing serotonin signaling, thereby intensifying craving and impulsive responses.^[31] In abstinent individuals, dysregulated cortisol responses—often blunted or hyperreactive—correlate with increased reinstatement to drug cues or stressors, amplifying neurochemical imbalances that sustain addiction cycles.^[32] This HPA-mediated crosstalk underscores how stress hormones potentiate vulnerabilities in glutamate, monoamine, and endocannabinoid systems, promoting relapse in vulnerable populations.^[33]

Risk Factors

Biological Vulnerabilities

Biological vulnerabilities to relapse in substance use disorders stem primarily from genetic predispositions that influence susceptibility to addiction and its persistence. Twin and family studies have established that the heritability of substance use disorders, including vulnerability to relapse, ranges from 40% to 60%, indicating a substantial genetic contribution to the risk of returning to substance use after abstinence.^[34] This genetic liability is polygenic, involving multiple variants that heighten impulsivity and reward sensitivity, thereby increasing the likelihood of relapse under cue exposure or stress. For instance, variations in dopamine receptor genes, such as DRD2, have been linked to altered reward processing that may exacerbate relapse risk, though detailed neurochemical mechanisms are addressed elsewhere.^[35] Comorbid psychiatric conditions, particularly attention-deficit/hyperactivity disorder (ADHD) and other disorders like depression or anxiety, further amplify biological relapse vulnerability through shared genetic and neurodevelopmental pathways. Individuals with ADHD face a two- to four-fold increased risk of developing substance use disorders, with untreated symptoms leading to heightened impulsivity and poor executive function that predict higher relapse rates post-treatment.^[36] These comorbidities share overlapping genetic factors, accounting for 40-60% of the variance in substance use disorder risk, and involve dysregulated circuits in the prefrontal cortex and reward pathways that impair self-regulation and increase craving intensity.^[36] For example, adolescents with ADHD and co-occurring conduct disorder exhibit elevated odds of relapse due to these intertwined biological underpinnings.^[36] Physiological factors, such as age-related brain maturation, represent another key biological vulnerability, with adolescents showing heightened relapse risk owing to an immature prefrontal cortex. The prefrontal cortex, responsible for impulse control and decision-making, does not fully mature until the mid-20s, creating a developmental mismatch where the limbic reward system develops earlier and drives risk-taking behaviors.^[37] This immaturity contributes to relapse in adolescent substance use disorder treatment, as incomplete neural pruning and myelination reduce the ability to inhibit drug-seeking responses.^[38] Heavy substance exposure during this period can exacerbate prefrontal deficits, perpetuating a cycle of vulnerability.^[39] Endocrine influences, including elevated testosterone levels, correlate with increased impulsive behaviors that heighten relapse propensity in substance use disorders. Higher baseline testosterone has been associated with greater impulsivity and risk-taking, which in turn elevate the likelihood of relapse by impairing inhibitory control during abstinence.^[40] In males, this hormonal profile can intensify reward-driven responses to substance cues, contributing to poorer treatment outcomes and recurrent use.^[41] These effects underscore testosterone's role as a modulator of biological vulnerability, particularly in contexts of high-stress or cue-induced relapse scenarios.^[40]

Psychosocial Influences

Psychosocial influences play a significant role in the vulnerability to relapse among individuals recovering from substance use disorders, encompassing social, environmental, and psychological factors that exacerbate chronic stress and undermine recovery efforts. Lower socioeconomic status, often linked to social hierarchy disadvantages, correlates with elevated relapse risks through mechanisms of persistent psychosocial strain. For instance, individuals in lower social strata experience heightened chronic stress, which disrupts coping abilities and increases susceptibility to substance-seeking behaviors due to accumulated economic and social pressures.^[42]^[43] This chronic stress may interact with neurochemical pathways, such as heightened cortisol responses, briefly amplifying relapse propensity as noted in foundational stress-addiction models.^[31] Psychological factors, including low self-efficacy and unresolved trauma, further heighten relapse vulnerability by impairing an individual's confidence in maintaining abstinence and processing past adversities. Low self-efficacy—defined as diminished belief in one's ability to resist substance use—strongly predicts relapse episodes, with longitudinal studies showing that decreases in daily self-efficacy ratings precede full-blown returns to use in alcohol and drug recovery contexts.^[44] Similarly, unresolved trauma, such as from childhood adversity or interpersonal violence, fosters emotional dysregulation and co-occurring conditions like PTSD, which increase the odds of relapse by serving as an unaddressed emotional trigger that erodes resilience during recovery.^[45] These elements underscore the need for integrated psychological interventions to bolster self-perception and trauma resolution. Environmental influences in recovery settings, including ease of access to substances and peer pressure, create ongoing situational risks that propel relapse by normalizing or facilitating use. Proximity to substances in familiar environments reactivates learned associations, significantly reinstating seeking behaviors even after extinction training, as demonstrated in controlled studies where contextual cues alone increase relapse rates in animal models translated to human parallels.^[46] Peer pressure within social networks, particularly from non-recovering associates, exerts subtle or overt influences that challenge abstinence, with recovery-focused research highlighting how unsupportive peer dynamics contribute to reported relapse incidents in community-based programs.^[47] Cultural variations amplify these psychosocial risks through stigma, which varies across communities and intensifies stress in marginalized groups. In cultures with high stigma toward substance use disorders, affected individuals face social exclusion and shame, elevating psychosocial stress and reducing treatment engagement, thereby increasing relapse in stigmatized populations compared to low-stigma settings.^[48] For example, in certain ethnic or religious communities where addiction is viewed as moral failing, this stigma perpetuates isolation and chronic distress, hindering recovery networks and fostering a cycle of vulnerability.^[49]

Triggers and Precipitants

Internal Triggers

Internal triggers in relapse refer to self-generated psychological and physiological states that heighten vulnerability to substance use by prompting urges or justifications for resumption. Negative emotional states, such as anxiety, frustration, anger, and boredom, are among the most potent internal precipitants, often leading individuals to rationalize substance use as a means of emotional relief. For instance, clinical research has identified anger and frustration as reported relapse determinants in 29% of cases among men treated for alcohol addiction, while boredom and feelings of uselessness accounted for 10%. These emotions can distort decision-making, fostering thoughts that substance use will alleviate discomfort, thereby escalating risk during periods of low mood or idleness.^[50]^[51] Cognitive distortions further amplify internal triggers by warping perceptions of risk and self-control, facilitating rationalizations that undermine abstinence. Common distortions include all-or-nothing thinking, where individuals view a single lapse as total failure, and minimizing consequences, such as downplaying the harm of "just one use" despite known outcomes. In the relapse prevention model, these manifest as permission-giving beliefs or apparent efficacy cognitions, where distorted automatic thoughts about the benefits of use outweigh perceived costs, gradually eroding resolve. Studies emphasize that such distortions contribute to impaired control in addiction, not through overwhelming compulsions but via unreliable self-regulation over biased evaluations of substance effects.^[10]^[52] Physiological cues, including sleep deprivation, serve as internal amplifiers of urges by impairing emotional regulation and heightening sensitivity to cravings. Disrupted sleep, such as reduced slow-wave sleep, has been shown to predict relapse in alcohol use disorder, with early laboratory studies linking low sleep quality to increased drinking resumption. Clinical examples like the HALT framework—hungry, angry, lonely, tired—highlight how basic physiological imbalances, particularly tiredness from sleep deficits, interact with emotional states to elevate relapse risk, as noted in recovery protocols derived from cognitive-behavioral approaches. Internal triggers like these often intensify during the emotional stage of relapse, where unaddressed affective and somatic discomfort builds progressively.^[53]^[12]

External Triggers

External triggers for relapse in substance use disorders encompass situational and environmental factors that precipitate renewed use, often beyond the individual's immediate control. These precipitants activate conditioned responses through prior associations with substance use, potentially eliciting cravings that lead to relapse. Research indicates that such triggers contribute significantly to the high rates of relapse observed in recovery, with environmental and social elements playing key roles in disrupting abstinence. Social cues, particularly exposure to peers who use substances, serve as potent precipitants by reinforcing learned behaviors and normalizing use. For instance, interactions with individuals actively using drugs can facilitate drug-seeking behaviors, as demonstrated in animal models where social interaction with a relapsed partner increased cocaine self-administration and conditioned place preference in rats. Similarly, celebrations involving substances, such as holiday gatherings or social events where alcohol or drugs are central, heighten relapse risk due to their association with past use patterns; studies have noted increased substance-related admissions during holiday periods linked to these festive contexts. These social dynamics can evoke neurochemical responses similar to those in cue reactivity paradigms discussed in neurobiological research. Environmental contexts, including returning to high-risk locations after treatment, strongly influence relapse by reactivating contextual memories tied to prior substance use. Places where pharmacological effects of substances were previously experienced, such as former drinking venues, become potent triggers for renewed seeking in abstinent individuals, as evidenced by human laboratory studies showing amplified cue reactivity and drug-seeking in drug-associated settings. Post-treatment relocation to such environments has been linked to higher relapse rates, underscoring the importance of contextual avoidance in recovery planning. Acute stressors like job loss or relationship conflicts act as immediate precipitants by overwhelming coping resources and prompting substance use as a maladaptive response. Unemployment is associated with elevated substance use and relapse vulnerability, with meta-analyses revealing significantly higher rates of substance use disorders among the unemployed compared to employed individuals. Interpersonal conflicts, including relationship disputes, further exacerbate this risk through chronic stress mechanisms, where rejection sensitivity and interpersonal tension predict relapse in addicted populations. Media and advertising influences contribute to relapse by presenting substance cues that trigger cravings outside conscious awareness. Exposure to promotional content depicting substance use can elicit cue reactivity predictive of relapse, with systematic reviews confirming that drug cues in various formats, including marketing, play a significant role in subsequent use outcomes. In recent years, social media platforms have emerged as particularly potent triggers, where algorithm-driven content glamorizing substance use or featuring peer endorsements can rapidly evoke cravings and increase relapse risk, especially among younger individuals in recovery.^[54]

Prevention Strategies

Relapse Prevention Model

The Relapse Prevention (RP) model, developed by G. Alan Marlatt and Judith R. Gordon in 1985, is a cognitive-behavioral framework designed to help individuals with addictive behaviors anticipate, identify, and manage high-risk situations that may lead to relapse.^[10] The model conceptualizes relapse not as a singular event but as a dynamic process involving immediate determinants—such as exposure to high-risk situations and the availability of effective coping skills—and covert antecedents, including underlying lifestyle imbalances and cognitive distortions.^[10] Common high-risk situations, such as negative emotional states (accounting for over 50% of relapses when combined with conflicts) and social pressures (over 20%), include frustration or anxiety, interpersonal conflicts, social pressures to use substances, and exposure to cues associated with prior use.^[10] Effective coping responses, encompassing both behavioral strategies (e.g., avoiding triggers) and cognitive techniques (e.g., positive self-talk), are emphasized as key to building self-efficacy and averting lapses from escalating into full relapses.^[10] Core components of the model include self-monitoring, lifestyle balance, and balanced decision-making to foster long-term maintenance of abstinence or moderation.^[10] Self-monitoring involves tracking thoughts, emotions, and behaviors to recognize early warning signs of vulnerability, while lifestyle balance addresses broader imbalances such as inadequate stress management or overcommitment that may indirectly heighten relapse risk.^[10] Balanced decision-making encourages evaluating choices in light of their potential to lead to high-risk scenarios, promoting proactive adjustments. A critical element is the concept of apparently irrelevant decisions (AIDs), which are subtle, seemingly innocuous choices—such as altering one's route home to pass a bar or stocking alcohol "for guests"—that cumulatively steer individuals toward high-risk situations without conscious awareness.^[10] By inventorying these AIDs, individuals learn to interrupt the chain of events before reaching a crisis point. Empirical support for the RP model is robust, with meta-analyses demonstrating its effectiveness in reducing relapse frequency and severity across addictive behaviors, particularly alcohol use disorders.^[55] A seminal meta-analysis by Irvin et al. (1999) reviewed 26 studies involving over 9,500 participants and found an overall effect size of r = 0.14 for substance use reduction, with stronger effects for alcohol (r = 0.37), indicating moderate improvements in outcomes and relapse management compared to no treatment or alternative interventions.^[55] Adherence to the model has been associated with reduced relapse frequency and severity in follow-up studies, particularly when integrated into comprehensive treatment plans, though benefits often emerge more prominently in longer-term assessments (e.g., 12 months post-treatment).^[55] These findings underscore the model's utility in enhancing coping skills and self-regulation, contributing to sustained behavioral change. While primarily developed for addictive behaviors, the RP model has been adapted for managing relapse in other chronic conditions, such as diabetes, by emphasizing lifestyle balance.

Cognitive Behavioral Interventions

Cognitive behavioral interventions for relapse in substance use disorders emphasize practical strategies to disrupt the cycle of craving and use by targeting thoughts, behaviors, and environmental cues. These methods, rooted in evidence-based cognitive behavioral therapy (CBT), equip individuals with tools to recognize and manage high-risk situations effectively.^[56] Core techniques include urge surfing, a mindfulness-informed practice where individuals observe cravings as temporary waves that rise, peak, and subside, fostering tolerance without acting on the impulse; this approach reduces perceived urge intensity and promotes emotional regulation.^[10] Cognitive restructuring involves identifying maladaptive thoughts—such as minimizing risks or catastrophizing abstinence—and replacing them with balanced, realistic alternatives to prevent escalation toward relapse.^[56] Complementing these, stimulus control strategies modify the environment to limit exposure to triggers, such as removing drug paraphernalia or avoiding high-risk social settings, thereby decreasing automatic responses to cues.^[10] Skills training enhances these techniques through structured practice, including role-playing high-risk scenarios like social pressures or emotional distress to build refusal skills and alternative coping responses, increasing self-efficacy in real-world application.^[10] CBT interventions are delivered in both group and individual formats, with group sessions leveraging peer support for shared learning and accountability; meta-analyses show comparable efficacy across formats, with small to moderate effects on abstinence outcomes.^[57]^[58] Modern adaptations integrate mindfulness into traditional CBT, particularly in mindfulness-based relapse prevention (MBRP) programs tailored for addictions like alcohol and opioids, where techniques such as urge surfing are combined with meditation to improve awareness and reduce relapse rates by up to 30% compared to standard CBT alone.^[59] These tailored approaches address specific substance vulnerabilities, enhancing long-term recovery outcomes.^[60]

Treatment Approaches

Pharmacological Options

Naltrexone, an opioid receptor antagonist, is widely used to mitigate relapse in opioid and alcohol use disorders by competitively binding to mu-opioid receptors, thereby blocking the rewarding effects of these substances and reducing cravings.^[61] This mechanism attenuates the dopamine release associated with consumption, promoting abstinence in clinical settings.^[62] For instance, extended-release formulations have demonstrated efficacy in maintaining opioid abstinence, with studies showing reduced relapse rates over 24 weeks compared to placebo.^[63] Acamprosate, approved for alcohol dependence, functions as an NMDA receptor modulator that stabilizes glutamatergic neurotransmission, counteracting the hyperexcitability during protracted withdrawal and thereby lowering relapse risk.^[64] By normalizing glutamate levels in the brain, it helps sustain abstinence post-detoxification, with meta-analyses indicating a modest but significant increase in continuous abstinence rates over six months.^[65] Its amino acid-like structure contributes to minimal abuse potential, making it suitable for long-term use.^[66] Varenicline, a partial agonist at the α4β2 nicotinic acetylcholine receptors, aids in nicotine relapse prevention by partially stimulating these receptors to alleviate withdrawal symptoms while blocking full nicotine binding, which diminishes the satisfaction from smoking and curbs cravings.^[67] This dual action results in approximately half the dopamine release of nicotine, providing relief without reinforcement.^[68] Clinical trials have reported abstinence rates of up to 33% at one year, outperforming placebo and other aids.^[69] As of 2025, ibogaine derivatives represent promising emerging pharmacological options for broad-spectrum relapse prevention across substance use disorders, leveraging neuroplasticity promotion via GDNF and BDNF upregulation without ibogaine's hallucinogenic or cardiotoxic effects.^[70] For example, 18-methoxycoronaridine (18-MC), an analog targeting α3β4 nicotinic receptors, has shown in preclinical models a reduction in opioid and cocaine self-administration, with a completed Phase I trial in 2022 confirming safety and tolerability up to therapeutic doses.^[71] Similarly, tabernanthalog, a non-hallucinogenic ibogaine-inspired compound, attenuates alcohol and heroin-seeking behaviors in rodents by promoting neuroplasticity, though it remains in preclinical development as of November 2025, with a Phase 1 trial planned by Delix Therapeutics.^[72] Broader research momentum, including Texas's June 2025 $50 million funding for ibogaine clinical trials in opioid use disorder, PTSD, and traumatic brain injury, supports exploration of such derivatives.^[73] These derivatives aim to address multiple addiction pathways, with preclinical outcomes suggesting potential for single-dose interventions to extend abstinence periods.^[74]

Contingency Management Techniques

Contingency management (CM) techniques draw on the principles of operant conditioning, which posits that behaviors can be modified through systematic reinforcement of desired actions while withholding rewards for undesired ones. In addiction treatment, this translates to providing positive reinforcers—such as vouchers, cash equivalents, or prizes—for verified abstinence from substances, typically confirmed via urine toxicology screens or other objective tests. These rewards aim to increase the salience of abstinence over drug use by associating it with immediate, tangible benefits, thereby disrupting the cycle of relapse driven by habitual substance-seeking behaviors.^[75]^[76] Implementation protocols for CM emphasize structured, escalating reinforcement schedules to promote sustained abstinence. In voucher-based systems, participants receive monetary vouchers redeemable for goods and services, starting at low values (e.g., $2.50 for the first negative test) and increasing progressively (e.g., by $1.25 per consecutive clean test) up to a maximum, with a reset to the initial level following a positive test; this "shaping" procedure encourages longer abstinence periods by making prolonged success more rewarding. Prize-based alternatives, often used in resource-limited settings, involve participants drawing from a container ("fishbowl") filled with slips representing prizes of varying magnitudes (e.g., $1 to $100 retail items or gift cards), awarded only for negative tests, which introduces an element of chance while maintaining reinforcement frequency through thrice-weekly testing opportunities. These protocols are typically administered over 12–24 weeks in outpatient clinics, with safeguards like prize logs to ensure accountability.^[77]^[78] Efficacy evidence from randomized trials and meta-analyses supports CM's role in achieving short-term abstinence, particularly in cocaine use disorder. For instance, voucher-based CM has initiated abstinence in approximately 80% of participants and sustained treatment retention for six months or more in about 60%, outperforming non-contingent reward controls. Broader meta-analyses report moderate effect sizes (Cohen's d ≈ 0.54) for post-treatment abstinence across substances, with CM significantly reducing days of use compared to treatment as usual.^[79]^[80]^[81] Ethical considerations surrounding CM center on balancing its proven benefits against potential drawbacks in motivation and equity. While critics argue that external rewards may erode intrinsic drive for sobriety, longitudinal studies indicate no sustained loss of internal motivation post-treatment, with abstinence gains persisting for up to one year in many cases. Cost-effectiveness analyses highlight CM's value, estimating $300–$600 per client over 12 weeks, which offsets higher healthcare costs through reduced substance-related hospitalizations and improved retention; however, challenges include funding disparities that limit access for underserved populations and the risk of relapse rebound after rewards end, underscoring the need for tapered reinforcement or combined approaches.^[82]^[83]^[84]

Animal Models

Experimental Protocols

Experimental protocols in animal models of relapse primarily utilize rodents, such as rats and mice, and non-human primates in controlled addiction paradigms to investigate the mechanisms underlying drug-seeking behavior after abstinence. These models typically involve operant conditioning chambers where animals voluntarily self-administer drugs like cocaine, heroin, or alcohol, allowing researchers to manipulate variables such as drug dose, extinction periods, and reinstatement triggers in a standardized environment.^[85]^[86] Non-human primates, including rhesus monkeys, are employed for their closer neuroanatomical similarity to humans, particularly in studies requiring fine motor responses or long-term drug exposure effects.^[87] Adherence to ethical guidelines is paramount in these protocols, guided by the 3Rs principles—replacement, reduction, and refinement—updated through 2025 standards by organizations like the American Physiological Society and the British Psychological Society to minimize animal distress while maximizing scientific yield. Replacement strategies include computational modeling or in vitro assays where feasible, reduction limits animal numbers via power analysis for statistical robustness, and refinement incorporates analgesia, enriched housing, and non-invasive monitoring to alleviate suffering during self-administration or imaging procedures.^[88]^[89] All protocols require institutional animal care and use committee (IACUC) approval, ensuring compliance with international standards like those from the National Institutes of Health.^[90] The historical evolution of these protocols traces back to the 1960s, when intravenous self-administration paradigms were pioneered in rats (e.g., Weeks, 1962) to study drug reinforcement, marking a shift from passive administration to voluntary intake models that better mimic human addiction.^[91] By the 1980s and 1990s, these evolved to include extinction and reinstatement phases to probe relapse, with primate models gaining traction for pharmacokinetic accuracy. In the 2010s, optogenetics emerged as a transformative tool, enabling precise activation or inhibition of relapse-related neural circuits in rodents using light-sensitive proteins, thus bridging behavioral observations with causal neurobiology. In recent years, including as of 2025, genetic tools like CRISPR-Cas9 in mouse models have been increasingly used to dissect relapse circuitry, complementing traditional approaches.^[92]^[93]^[94] These animal protocols demonstrate substantial translational validity to human relapse, particularly in cue-reactivity paradigms, where conditioned stimuli elicit drug-seeking responses in both species with high concordance in neural activation patterns. For instance, rodent cue-induced reinstatement mirrors human functional MRI findings of ventral striatal engagement during craving.^[95] This alignment supports the use of animal models to inform human interventions, though limitations in cognitive complexity persist.

Key Procedures and Techniques

In animal models of relapse, self-administration serves as a foundational procedure to establish voluntary drug intake, typically via intravenous or oral routes to replicate aspects of compulsive use in humans. Intravenous self-administration, first developed by implanting chronic jugular vein catheters in unrestrained rats, allows animals to press a lever or nose-poke to receive discrete infusions of drugs like cocaine or heroin, often paired with light or tone cues to condition seeking behavior. This method progressed from fixed-ratio schedules, where a set number of responses yields a reward, to progressive ratio schedules that exponentially increase the response requirement, culminating in a "breaking point" that quantifies motivation and reinforcement strength for the drug. Oral self-administration, commonly applied to ethanol or nicotine models, involves access to drug-laced solutions in bottles or lickometers, enabling study of intake patterns over extended periods.^[91]^[96] Extinction procedures follow acquisition of self-administration to model the reduction of drug-seeking during abstinence, consisting of daily sessions where animals are exposed to the operant chamber and drug-associated cues without reinforcement, leading to a progressive decline in responses such as lever presses. These sessions, often lasting 1-2 hours and spanning 10-21 days, target the inhibition of Pavlovian and instrumental associations, with response suppression reflecting context-dependent learning where the absence of drug delivery overrides prior contingencies. Metrics include the rate of response decay and spontaneous recovery tests to assess the durability of extinction, highlighting neural adaptations in regions like the infralimbic cortex and nucleus accumbens.^[97] Reinstatement protocols, conducted after stable extinction, probe relapse susceptibility by systematically reintroducing triggers to elicit robust renewal of extinguished responding without subsequent drug access. Cue-induced reinstatement presents discrete stimuli (e.g., lights or tones) previously paired with infusions, stress-induced variants apply intermittent footshock or yohimbine to mimic emotional precipitants, and drug-prime reinstatement involves a non-contingent low-dose injection to simulate exposure. Developed as a standardized assay in the late 20th century, this tripartite framework distinguishes relapse mechanisms, with each induction typically limited to short test sessions to avoid relearning. Cue- and prime-induced reinstatement often coincide with phasic dopamine surges in the nucleus accumbens shell.^[98] Neuroimaging integrates with these core procedures to visualize dynamic brain changes in real time, enhancing mechanistic insights into relapse circuitry. Functional magnetic resonance imaging (fMRI) in rodents, adapted for awake or lightly anesthetized states, measures blood-oxygen-level-dependent signals during cue exposure or early abstinence post-self-administration, revealing hypoactivation in the medial prefrontal cortex and ventral striatum in cocaine-experienced rats compared to controls. Complementarily, fast-scan cyclic voltammetry employs carbon-fiber microelectrodes implanted in the nucleus accumbens to detect sub-second dopamine release and reuptake kinetics during active self-administration sessions or reinstatement tests, calibrated against known standards for precise quantification of phasic transients.^[99]^[100]

Limitations and Sex Differences

Model Limitations

Animal models of relapse in addiction research, while valuable for elucidating neurobiological mechanisms, face significant limitations in replicating the cognitive complexity of human decision-making processes. Rodents and other commonly used species lack advanced metacognitive abilities, such as self-awareness and reflective evaluation of long-term consequences, which are central to human relapse scenarios involving internal conflict, moral reasoning, and anticipation of social repercussions.^[101] These models primarily capture instinctive cue-driven behaviors rather than the deliberate, self-regulatory choices observed in humans, leading to an oversimplification of relapse as a purely Pavlovian response.^[102] A key species-specific discrepancy arises in extinction learning, where rodents exhibit rapid attenuation of drug-seeking behaviors compared to the protracted, often lifelong vulnerability seen in humans. In rat models, extinction sessions typically achieve significant response suppression within days to weeks, whereas human relapse risk persists for months or years post-abstinence due to enduring memory traces and contextual triggers.^[103] This accelerated timeline in animals limits the models' ability to mimic the chronic intermittency of human relapse, where spontaneous recovery can occur long after initial extinction.^[104] Ethical constraints and translational gaps further undermine the applicability of these models, particularly the over-reliance on acute exposure paradigms that fail to replicate the chronic, escalating nature of human addiction. Animal studies often employ short-term drug administration to induce dependence, ignoring the cumulative neuroadaptations and comorbidities (e.g., psychiatric disorders) that characterize prolonged human use, which complicates direct extrapolation to clinical settings.^[105] Ethical guidelines restrict invasive manipulations in humans, justifying animal use, but this reliance perpetuates a cycle of low predictive validity, with models prioritizing mechanistic insights over holistic behavioral fidelity.^[106] Post-2020 critiques have intensified scrutiny on the ecological validity of these models, highlighting that many preclinical findings fail to replicate in human clinical trials, often due to discrepancies in environmental complexity and motivational contexts.^[107] Reviews emphasize that laboratory-controlled settings in animals strip away real-world variables like social dynamics and stress variability, reducing the models' relevance to naturalistic relapse triggers.^[108] These limitations underscore the need for complementary human-centric approaches to bridge the translational divide.

Sex-Specific Variations

Sex-specific variations in relapse patterns among individuals with substance use disorders reveal distinct biological and behavioral differences between males and females, influencing vulnerability and treatment responses. Biologically, females often exhibit a faster escalation to dependence compared to males, driven by hormonal influences such as estradiol, which enhances motivation for psychostimulants and amplifies the rewarding effects of drugs.^[109]^[110] This hormonal modulation, particularly through estrogen, contributes to higher rates of stress-induced relapse in females, where ovarian hormones increase reactivity to stressors and withdrawal experiences, making relapse more likely in response to emotional or environmental pressures.^[111]^[112] Behaviorally, these differences manifest in relapse triggers, with males showing greater proneness to cue-induced relapse—such as exposure to drug-associated stimuli—while females are more susceptible to relapse precipitated by emotional or stress-related factors.^[113] For instance, women experience heightened stress-induced cravings and anxiety in response to drug cues and stressors, leading to elevated relapse vulnerability during periods of hormonal flux.^[114] In the postpartum period, relapse rates among women with substance use histories are notably high, reaching up to 80% within two years after childbirth, often linked to stress and disrupted support systems, with particular risk in the first year.^[115] Clinical data further underscore these disparities through sex-disaggregated outcomes in treatment efficacy. For alcohol use disorder, pharmacotherapies like naltrexone demonstrate lower effectiveness in females compared to males, with aggregate analyses of clinical trials showing worse overall treatment outcomes for women, particularly attributable to reduced response to medications.^[116] This may stem from sex-specific neurobiological factors, including estrogen's interaction with reward pathways, which can diminish the impact of opioid antagonists in females.^[117] Despite these insights, significant gaps persist in research as of 2025, notably the underrepresentation of female subjects in animal models of addiction, which has historically limited understanding of sex-specific mechanisms and hindered the development of tailored interventions.^[118] Preclinical studies continue to predominantly feature male animals, overlooking estrous cycle variability and female-specific vulnerabilities, thereby perpetuating biases in translational research. Recent 2025 reviews have called for greater integration of sex differences in preclinical and clinical trials to enhance medication development for addiction.^[119]^[120] Addressing this underrepresentation is essential for advancing equitable and effective relapse prevention strategies.

References

[1]
Medical Definition of Relapse - RxList
Last updated on RxList: 3/29/2021 Relapse: The return of signs and symptoms of a disease after a remission.<|control11|><|separator|>
[2]
Definition of relapse - NCI Dictionary of Cancer Terms
The return of a disease or the signs and symptoms of a disease after a period of improvement. Relapse also refers to returning to the use of an addictive ...
[3]
Relapse (Return to Substance Use) - Cleveland Clinic
Apr 7, 2025 · A relapse is what happens when you return to using substances you want to avoid. It can mean a one-time slip-up or a return to regularly using drugs or alcohol.
[4]
Addiction Relapse: Risk Factors, Coping & Treatment Options
Jun 30, 2025 · A relapse is when a person returns to using drugs or alcohol after a period of sobriety. While a lapse is a brief “slip” where a person may drink or use, but ...
[5]
Relapse Prevention and the Five Rules of Recovery - PMC - NIH
Sep 3, 2015 · The main tools of relapse prevention are cognitive therapy and mind-body relaxation, which are used to develop healthy coping skills.
[6]
Fundamentals of Addiction: Preventing and managing relapse - CAMH
Lapses are often seen as part of recovery, whereas a true relapse suggests a need to take stock, reassess the situation and re-engage with some form of ...<|control11|><|separator|>
[7]
Relapse - Alcohol and Drug Foundation
A relapse happens when a person stops maintaining his or her goal of reducing or avoiding use of alcohol or other drugs and returns to previous levels of use.
[8]
What Is Multiple Myeloma Relapse?
Relapse is the reappearance of disease symptoms after a period of improvement. The IMWG response criteria specifically defines myeloma relapse criteria.
[9]
Treatment and Recovery | National Institute on Drug Abuse - NIDA
Jul 6, 2020 · This graph shows that relapse rates for substance use disorders is 40-60%,. JAMA, 284:1689-1695, 2000. Relapse rates for people treated for ...Missing: prevalence | Show results with:prevalence
[10]
Relapse Prevention: An Overview of Marlatt's Cognitive-Behavioral ...
Marlatt and Gordon (1980, 1985) have described a type of reaction by the drinker to a lapse called the abstinence violation effect, which may influence whether ...
[11]
Withdrawal: Expanding a Key Addiction Construct - PMC - NIH
Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse.Variability In Withdrawal... · Figure 3 · Underlying Causes Of...
[12]
Relapse prevention for addictive behaviors
Jul 19, 2011 · Marlatt's original RP model is depicted in Figure 1. A basic assumption is that relapse events are immediately preceded by a high-risk situation ...
[13]
Neurobiology of addiction: a neurocircuitry analysis - PubMed Central
Neurobiological mechanisms of the binge/intoxication stage. Drug reward. Drugs of abuse activate brain reward systems, and research on drug addiction has in ...
[14]
Imaging addiction: D2 receptors and dopamine signaling in the ...
Taken together, these studies in addiction suggest that low D2 receptor availability and dopamine release in the striatum are neurobiological markers of ...
[15]
Low Dopamine D2/D3 Receptor Availability is Associated with Steep ...
This finding fits with reports that low striatal D2/D3 receptor availability is associated with a higher risk of relapse among stimulant users, and may help to ...
[16]
Cocaine Cues and Dopamine in Dorsal Striatum
Jun 14, 2006 · Here we test whether dopamine increases occur to conditioned stimuli in human subjects addicted to cocaine and whether this is associated with drug craving.
[17]
Imaging dopamine's role in drug abuse and addiction - PMC
Here we describe PET imaging studies that investigate dopamine's involvement in drug abuse in the human brain.
[18]
Do Alcohol-dependent Individuals with DRD2 A1 Allele Have an ...
The present study is, to our knowledge, the first report of an association between the TaqI A1 allele and a substantially increased relapse rate.
[19]
Genomic factors associated with substance use disorder relapse
Oct 30, 2024 · Specific gene polymorphisms like DRD2, GABRA, COMT, and DAT may relate to SUD relapse. •. Epigenetics play a role in SUD, such as CpG ...
[20]
Glutamate and Reinstatement - PMC - NIH
In recent years, the involvement of glutamate in cue-, stress-, and drug-primed reinstatement has been further investigated in regards to relapse to cocaine as ...Missing: hyperactivity | Show results with:hyperactivity
[21]
Glutamate Transmission in Addiction - PMC - NIH
Cortico-striatal glutamate transmission has been implicated in both the initiation and expression of addiction related behaviors, such as locomotor ...Missing: hyperactivity | Show results with:hyperactivity
[22]
Reinstatement of nicotine seeking is mediated by glutamatergic ...
May 13, 2013 · These results indicate that up-regulated GluN2A, GluN2B, and rapid synaptic potentiation in the accumbens contribute to cue-induced relapse to nicotine use.Missing: hyperactivity | Show results with:hyperactivity
[23]
Contributions of Serotonin in Addiction Vulnerability - PMC
We examine the role of 5-HT receptors in impulsivity, a core behavior that contributes to the vulnerability to addiction and relapse.
[24]
Serotonin at the nexus of impulsivity and cue reactivity in cocaine ...
Maladaptive impulsivity and cue reactivity predict relapse in cocaine addiction. •. Relapse is associated with imbalanced 5-HT function in key neural circuits.
[25]
A Role for Brain Stress Systems in Addiction: Neuron - Cell Press
Activation of brain stress systems is hypothesized to be key to the negative emotional state produced by dependence that drives drug seeking through negative ...
[26]
Norepinephrine and Stimulant Addiction - PMC - PubMed Central
Stimulants increase synaptic levels of the monoamines dopamine (DA), serotonin (5-HT), and norepinephrine (NE). Stimulant reward is attributable mostly to ...
[27]
Endocannabinoid signaling in reward and addiction - PMC
Cannabinoid CB1 receptor antagonist AM251 inhibits cocaine-primed relapse in rats: role of glutamate in the nucleus accumbens. J Neurosci. 2006;26:8531–6 ...Neurobiology Of Reward · Addiction-Related Synaptic... · Cited References
[28]
THE CB1 ANTAGONIST RIMONABANT (SR141716) BLOCKS CUE ...
A wealth of evidence demonstrates that the cannabinoid CB1 receptor system is involved in both food and drug reward generally and cue reactivity specifically.
[29]
Cannabinoid CB1 receptors control conditioned drug seeking
Blockade of the CB1 receptor is particularly effective in reducing cue-induced reinstatement of drug seeking, an animal analogue of cue-induced relapse in human ...Missing: reactivity | Show results with:reactivity
[30]
Chronic Stress, Drug Use, and Vulnerability to Addiction - PMC
Stress is a well-known risk factor in the development of addiction and in addiction relapse vulnerability. A series of population-based and epidemiological ...
[31]
Stress and substance use disorders: risk, relapse, and treatment ...
Aug 15, 2024 · Psychological theories view drug misuse as a coping mechanism to reduce stress, anxiety, tension, withdrawal, and abstinence-related distress, ...
[32]
Drug-induced stress responses and addiction risk and relapse
This review mainly covers human research on the acute effects of different drugs of abuse (ie, nicotine, cannabis, psychostimulants, alcohol, and opioids)
[33]
Genetic studies of alcohol dependence in the context of the ...
The heritability of alcohol use disorders is estimated at approximately 50–60% of the total phenotypic variability. Vulnerability to alcohol use disorders can ...
[34]
The Genetic Basis of Addictive Disorders - PMC - PubMed Central
Heritability estimates are usually higher for addiction than for substance use; however, “no pathologic drug use” and “initiation of use” are also heritable, ...
[35]
Common Comorbidities with Substance Use Disorders Research ...
Numerous studies have documented an increased risk for substance use disorders in youth with untreated ADHD,, although some studies suggest that only those with ...
[36]
Adolescent Substance Use Disorders - PMC - NIH
May 24, 2022 · Adolescent substance use is associated with the leading causes of death in this age group: unintentional injury, suicide, and violence.
[37]
Adolescence: A high-risk time for substance use disorders
Aug 7, 2018 · The prefrontal cortex does not fully develop until the mid-20s, which makes teenagers' brains excellent at learning and absorbing new ...
[38]
[PDF] Principles of Adolescent Substance Use Disorder Treatment
The adolescent brain is often likened to a car with a fully functioning gas pedal (the reward system) but weak brakes (the prefrontal cortex). The brain ...<|separator|>
[39]
Hormones can influence drug addiction-A narrative review - PMC
However, about the application of testosterone in individuals with substance use disorder ... These cognitive and mood abnormalities increase the risk of relapse ...
[40]
Chronic Testosterone Increases Impulsivity and Influences the ...
Several studies have shown that testosterone can cause impulsivity in humans, which in turn, is linked with mood-related psychiatric disorders and higher risk ...
[41]
[PDF] Factors Associated with Relapses in Alcohol and Substance Use ...
Conversely, factors such as positive family functioning, strong social support, treatment motivation and regular medication appear to decrease relapse rates.Missing: hierarchy | Show results with:hierarchy
[42]
Social vulnerabilities for substance use: Stressors, socially toxic ...
May 1, 2021 · Hierarchical status predicts behavioral vulnerability and nucleus accumbens metabolic profile following chronic social defeat stress. Curr ...
[43]
The Role of Self-Efficacy in the Treatment of Substance Use Disorders
They found that self-efficacy increased as abstinence was maintained. They also found that decreases in daily self-efficacy predicted relapse back to smoking.
[44]
Trauma and Stress | National Institute on Drug Abuse - NIDA
Feb 6, 2024 · Many people who have been diagnosed with post-traumatic stress disorder (PTSD) also have a substance use disorder. There are effective ...
[45]
The Potent Effect of Environmental Context on Relapse to Alcohol ...
Environments in which the pharmacological effects of alcohol have been experienced become potent triggers for relapse in abstinent humans.
[46]
Youth Perceptions About Substance Use Relapse - PMC - NIH
To qualitatively explore how treatment-involved youth retrospectively contextualize relapse from substance use. Fourteen focus groups were conducted with ...
[47]
Stigma toward substance use disorders: a multinational perspective ...
The stigma surrounding persons living with substance use disorders (SUDs) is a ubiquitous phenomenon that has had detrimental effects on affected individuals.
[48]
The stigma that undermines care
Jun 1, 2019 · Psychologists are working to tear down the stereotypes and biased language that foster discrimination against those with opioid and other substance use ...
[49]
Relapse determinants reported by men treated for alcohol addiction
Among the relapse determinants reported were anger and frustration (29%), social pressure (23%), intrapersonal temptation (21%), boredom and uselessness (10%), ...
[50]
Preventing relapse - American Psychological Association
Jun 1, 2001 · Depression, anger, anxiety, frustration or boredom seemed to catapult the abstinent person back into drinking. The researchers thought that ...
[51]
Impaired control in addiction involves cognitive distortions and ...
Feb 10, 2022 · Impaired control in addiction involves cognitive distortions and unreliable self-control, not compulsive desires and overwhelmed self-control.
[52]
Sleep Disturbance in Substance Use Disorders - PMC
Early laboratory studies suggested that low levels of slow wave sleep are predictive of alcohol drinking relapse (22). Other more recent studies have identified ...Missing: cues | Show results with:cues
[53]
Efficacy of relapse prevention: a meta-analytic review - PubMed
A meta-analysis was performed to evaluate the overall effectiveness of RP and the extent to which certain variables may relate to treatment outcome. Twenty-six ...Missing: effect size reduction
[54]
Cognitive-Behavioral Therapy for Substance Use Disorders - NIH
Cognitive behavioral therapy (CBT) for substance use disorders has demonstrated efficacy as both a monotherapy and as part of combination treatment strategies.
[55]
An Evaluation of Cognitive Behavioral Therapy for Substance Use ...
CBT produced small to moderate effects on substance use when compared to inactive treatment and was most effective at early follow-up (1–6 months post-treatment) ...
[56]
Group treatment for substance use disorder in adults: A systematic ...
It was found that group therapy can be effective when added to treatment-as-usual or compared to a wait-list control condition, but very few differences were ...
[57]
Mindfulness-based treatment of addiction: current state of the field ...
Apr 18, 2018 · This article reviews current research evaluating MBIs as a treatment for addiction, with a focus on findings pertaining to clinical outcomes and biobehavioral ...
[58]
Mindfulness-based programs for substance use disorders
Jul 29, 2020 · Findings from this review indicated that MBIs were more effective than control conditions (e.g., treatment as usual (TAU), relapse prevention ...
[59]
Naltrexone - StatPearls - NCBI Bookshelf
May 30, 2023 · Mechanism of Action Naltrexone blocks the effect of opioids and prevents opioid intoxication and physiologic dependence on opioid users. ...
[60]
Naltrexone for the Management of Alcohol Dependence - PMC
Naltrexone is an agent that blocks opioid receptors, particularly the μ-opioid receptor. Use of this agent in animal models leads to a reduction of dopamine ...
[61]
Naltrexone Depot Formulations for Opioid and Alcohol Dependence
Naltrexone is an opioid receptor antagonist that blocks the reinforcing effects of opioids and reduces alcohol consumption and craving.
[62]
The clinical pharmacology of acamprosate - PMC - PubMed Central
Acamprosate is one of the few medications licensed for prevention of relapse in alcohol dependence, and over time it has proved to be significantly, if ...
[63]
Meta-analysis of naltrexone and acamprosate for treating alcohol ...
Conclusions. In treatment for alcohol use disorders, acamprosate has been found to be slightly more efficacious in promoting abstinence and naltrexone slightly ...
[64]
Acamprosate for treatment of alcohol dependence - PubMed Central
Feb 1, 2012 · Acamprosate, or N-acetyl homotaurine, is an N-methyl-D-aspartate receptor modulator approved by the Food and Drug Administration (FDA) as a ...
[65]
Varenicline - StatPearls - NCBI Bookshelf - NIH
... partial agonist activity while preventing nicotine binding to these receptors. This precludes the ability of nicotine to activate α4β2 receptors and ...Continuing Education Activity · Indications · Mechanism of Action · Administration
[66]
Varenicline for smoking cessation: a narrative review of efficacy ...
Binding of the partial agonist varenicline to the α4β2 receptor results in a dopamine release that is half of that released by the pure agonist nicotine.
[67]
Nicotine receptor partial agonists for smoking cessation - PMC
Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms ...
[68]
Old Dog, New Tricks: Ibogaine and Its Analogs as Potential ...
Sep 25, 2025 · (2−4) Recent reports suggest that a single dose of magnesium-ibogaine treatment improves the post-traumatic stress disorder (PTSD), depression, ...
[69]
18-Methoxycoronaridine blocks context-induced reinstatement ...
Numerous studies utilizing drug self-administration have shown the importance of conditioned cues in maintaining and reinstating addictive behaviors.Missing: clinical trials
[70]
Effects of psychedelics on opioid use disorder: a scoping review of ...
Jan 21, 2025 · In another experiment, ibogaine administration significantly reduced naloxone-induced place aversion. These results indicate potential for ...
[71]
A review of contingency management for the treatment of substance ...
Aug 13, 2018 · A review of contingency management for the treatment of substance-use disorders: adaptation for underserved populations, use of experimental technologies,
[72]
Contingency Management - an overview | ScienceDirect Topics
Contingency management is a widely used behavioral therapy for treating substance use disorders and is regarded as effective in clinical application.
[73]
WHAT IS CONTINGENCY MANAGEMENT? - NCBI - NIH
In abstinence-based CM protocols, people do not receive an incentive unless they test negative for the target substance. In CM protocols that reinforce ...
[74]
[PDF] contingency-management-advisory-pep24-06-001.pdf
SAMHSA grant programs that authorize a CM intervention support the implementation of either escalating voucher CM or prize-based CM in an evidence-based manner.
[75]
Contingency management for cocaine treatment: Cash vs. vouchers
In a recent meta-analysis, CM interventions significantly outperformed other behavioral interventions and treatment as usual (Lussier, Heil, Mongeon, Badger, & ...
[76]
Long-Term Efficacy of Contingency Management Treatment Based ...
This meta-analysis focused on objective indices of drug use (ie, urine toxicology) to examine the effects of CM on illicit substance use up to 1 year following ...
[77]
Contingency management for drug use disorders: Meta-analysis ...
Mar 23, 2022 · Considering only the moderate quality meta-analyses, the effect of CM versus control on posttreatment abstinence was d = 0.54 [0.43, 0.64] and ...<|separator|>
[78]
What are the ethical implications of using prize-based contingency ...
Aug 4, 2021 · This scoping review offers important insights into the ethics on PB-CM and its implications for research ethics, clinical ethics, and public health ethics.
[79]
None
Summary of each segment:
[80]
[PDF] AN ETHICAL ARGUMENT FOR THE USE OF CONTINGENCY ...
CM should be widely implemented as a more clinically efficacious and cost-efficient strategy for addressing the drug use crisis compared to current approaches.
[81]
Animal Models of Substance Abuse and Addiction - PubMed Central
To extend the use of an animal (both rodents and primates), investigators ... Controlling caloric consumption: protocols for rodents and rhesus monkeys.Relapse To Drug Use · Conditioned Place Preference · Preclinical Abuse Liability...
[82]
Animal Models of (or for) Aggression Reward, Addiction, and Relapse
May 22, 2019 · We and others have selected outbred male mice as experimental ... rodents and primates (Miczek et al., 1984, 1993). Similarly, Fish et ...
[83]
Nonhuman Primate Models of Addiction and PET Imaging
1.2 Nonhuman Primates as Research Subjects. The development of new imaging modalities has made in vivo small animal imaging using rodents an exciting line of ...
[84]
Ethical Animal Research - The 3Rs as Guiding Principles
The APS advances ethical animal research through the 3Rs: Reduction, Refinement, and Replacement.
[85]
Animal testing and the 3Rs: An introduction
Nov 6, 2024 · To conclude, the principles of the 3Rs—Replacement, Reduction, and Refinement—represent a vital framework for ethical animal research, balancing ...
[86]
Guidelines for Ethical Conduct in the Care and Use of Animals
The following guidelines were developed by the American Psychological Association (APA) for use by psychologists working with nonhuman animals.
[87]
Nicotine self-administration research: the legacy of Steven R ...
By the 1970s, animal drug self-administration testing was increasingly recognized as a key preclinical method for abuse potential assessment (Brady and Lukas ...
[88]
Optogenetic inhibition of cocaine seeking in rats - Wiley Online Library
Jul 24, 2012 · Inhibitory optogenetics was used to examine the roles of the prelimbic cortex (PL), the nucleus accumbens core (NAcore) and the PL ...<|control11|><|separator|>
[89]
Optogenetics: potentials for addiction research - PMC
First, optogenetics allows scientist to turn neurons on and off safely in intact invertebrate and vertebrate brains and in freely moving animals, avoiding any ...
[90]
A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine ...
Jun 18, 2018 · The cue reactivity test is a surrogate measure for cocaine relapse vulnerability in humans. Protocol. All animal manipulations are carried out ...
[91]
Method for Automatic Intravenous Injections in Unrestrained Rats
The study used a self-injection technique for intravenous morphine injections in unrestrained rats. The rate of self-injection varied inversely with the dose.
[92]
Full article: Animal models of addiction - Taylor & Francis Online
Apr 1, 2022 · Animal models of drug consumption and addiction provide predictive validity. This predictive power is best illustrated in alcohol research.
[93]
Review Extinction of drug seeking - ScienceDirect.com
There is evidence that extinction can ameliorate or reverse the neuroadaptations produced by chronic drug self-administration and/or by spontaneous abstinence ...
[94]
Page Unavailable | SpringerLink
Insufficient relevant content. The provided URL (https://link.springer.com/article/10.1007/s00213-002-1221-x) leads to a "Page Not Found" error, and no substantive information about the reinstatement model, self-administration, extinction, or types of reinstatement (cue, stress, drug-prime) is available. The page only contains a privacy policy notice and a broken link.
[95]
Cocaine addicted rats show reduced neural activity as ... - Nature
Nov 9, 2020 · We show that addict-like rats exhibit reduced neuronal activity compared to cocaine-naïve controls during the first week of abstinence.
[96]
Measurement of Dopamine Using Fast Scan Cyclic Voltammetry in ...
Oct 5, 2018 · This protocol will focus on the use of ex vivo FSCV for the detection of dopamine within the nucleus accumbens in slices obtained from rodents.
[97]
Understanding Addiction Using Animal Models - Frontiers
We will review the most common preclinical models of addictive behavior and discuss the advantages and disadvantages of each.
[98]
Animal models of addiction - PMC - PubMed Central - NIH
Humans and laboratory animals, such as monkeys, rats, and mice, voluntarily take drugs by different routes of administration, be it orally or intravenously. If ...Missing: concordance | Show results with:concordance
[99]
Extinction vs. Abstinence: A Review of the Molecular and Circuit ...
The rodent model most commonly used to study relapse is the intravenous self-administration (IVSA) model. Rodents are trained to self-administer cocaine in an ...
[100]
Context and extinction: Mechanisms of relapse in drug self ...
Like many pathological behaviours, substance abuse is learned. Drug taking is an operant behaviour that is reinforced by its consequences (the effects of ...Missing: species | Show results with:species
[101]
Inappropriate modeling of chronic and complex disorders - NIH
Jul 31, 2019 · Preclinical investigations such as animal modeling make the basis of clinical investigations and subsequently patient care.
[102]
Animal models of psychoactive drug use and addiction
Oct 15, 2018 · This opinion review attempts a critical analysis of some aspects of current addiction neuroscience using animal models.
[103]
Examining Replicability in Addictions Research: How to Assess ...
Rate of replication ranged from 39% (subjective agreement on replication) to 47% (based on overlapping confidence intervals) depending on the method used, but ...
[104]
Translational opportunities in animal and human models to study ...
Sep 29, 2021 · Breakpoints are higher when assessed in alcohol withdrawal [62] and in female rats [63]. In addition, rodent and non-human primate studies ...Conditioned Place Preference · Reversal Learning · Behavioral Economics And...
[105]
Sex differences in vulnerability to addiction - ScienceDirect
Apr 1, 2021 · Estradiol increases females' motivation to attain psychostimulants and enhances the value of drug related cues, which ultimately increases their ...
[106]
Sex and estrogen influence drug abuse - Cell Press
In all phases of drug abuse, females seem to be more sensitive to the rewarding effects of drugs than males, and estrogen is a major factor that underlies these ...<|separator|>
[107]
Ovarian hormones and propensity to drug relapse: A review
In general, women show greater propensity to drug relapse than men, owing perhaps to divergent withdrawal experiences and increased reactivity.
[108]
SEX DIFFERENCES, GENDER AND ADDICTION - PMC
Among the vulnerable populations, females escalate drug use more rapidly than males and relapse is more likely to be triggered by stressful events or drug- ...
[109]
Sex, Stress, and Drug Cues in Addiction - Psychiatry Online
Apr 1, 2012 · There is a growing body of evidence that the effects of stress and cue reactivity on drug addiction may differ by gender. Although drug use ...<|separator|>
[110]
Sex differences in the neuroadaptations associated with incubated ...
Women with a cocaine use disorder also experience more drug-related medical and psychological complications, report greater stress-induced cravings, and longer ...
[111]
Perinatal substance use: A prospective evaluation of abstinence and ...
May 1, 2015 · Postpartum, 80% of women abstinent in the last month of pregnancy relapsed to at least one substance. The mean days to relapse was 109.67 (26.34) ...
[112]
Consideration of sex and gender differences in addiction medication ...
Jun 27, 2022 · An aggregate analysis of five trials (n = 434) found that women had worse treatment outcomes than men, which was primarily accounted for by ...
[113]
Sex Differences and the Role of Estradiol in Mesolimbic Reward ...
This review demonstrates the link between sex differences in cocaine and opiate addiction and the role of E2 as a major driver of these sex differences.
[114]
Inclusion of females does not increase variability in rodent research ...
The underrepresentation of female subjects in animal research has gained attention in recent years, and new NIH guidelines aim to address this problem early, at ...
[115]
An analysis of neuroscience and psychiatry papers published from ...
Apr 19, 2022 · Many health disparities in treatment and diagnosis have been attributed to the lack of research in females in both animal models and in ...