Introduction
Cocaine use disorder (CUD) – the compulsive use of cocaine regardless of its medical, psychological, and behavioral penalties – is a extreme public health downside, affecting thousands and thousands of people globally. Within the United States (US) alone, roughly 2.2 million people use cocaine frequently (in contrast to 600,000 methamphetamine customers), 1.5 million of whom meet the Diagnostic and Statistical Guide for Psychological Problems (DSM-5) standards for CUD.1,2
Latest nationwide epidemiological information present that each cocaine use and cocaine-related issues, together with CUD, are rising in adults in addition to in adolescents.3–5 Within the US, the proportion of overdose deaths involving cocaine is rising, doubling in one yr alone between 2015 and 2016 – in 2017, among the many 70,237 drug overdose deaths in the US, about 20% concerned cocaine.6 Presently, the speed of cocaine overdose deaths is larger than opioid overdose deaths in Black males and girls.7 In 2011, cocaine use contributed to greater than 500,000 emergency room visits in the US8 due to overdose, medical disorders, accidents, and violence. As well as to contributing to medical emergencies, cocaine use causes many disabling and expensive health issues, together with coronary heart assault, stroke, neuropsychiatric problems, and will increase the chance of contracting HIV and hepatitis C.9,10 Cocaine use can also be related with frequent encounters with the legal justice system, together with crime, arrests, and imprisonment – and thus altered family buildings, which disproportionately affects minorities in half due to racial disparities in crack-cocaine sentencing.11–14 Multiple-third of homeless adults report lifetime cocaine use issues.15 The supply of effective and broadly accessible treatments for CUD stays an urgent problem.
The event of novel and efficacious treatments for CUD has been an space of intense analysis over the previous 3 a long time. The outcomes of these research have been the topic of a number of glorious systematic opinions and meta-analyses.16–19 On this evaluate article, we provide a clinically related overview of the present literature on CUD. We first summarize the clinical epidemiology of CUD and then comply with with an overview of the neurobehavioral penalties of short- and long-term cocaine use. We then summarize the present pharmacological and behavioral treatment approaches for CUD, and talk about rising treatment approaches.
Diagnostic Standards
The DSM-5 defines CUD as clinically important impairment or misery attributable to at least 2 of 11 standards in the previous 12 months.20 The 11 standards might be organized into the next 4 teams: 1) physiologic, together with craving, tolerance, and withdrawal, 2) loss of management of cocaine use, 3) cocaine use taking priority over different actions (together with obligations at residence, work, or school), and 4) different unfavorable penalties from cocaine use. In accordance to the DSM, the presence of two or three symptoms signifies gentle CUD, the presence of 4 or 5 symptoms signifies average CUD, and the presence of six or extra symptoms signifies extreme CUD.
The DSM-5 additionally provides definitions for totally different levels of remission. Early remission is outlined because the absence of symptoms, besides for cravings, for greater than 3 months and lower than 12 months, and sustained remission is outlined as 12 months with out symptoms, besides for cravings. CUD, like all substance use disorders, tends to be persistent and relapsing in nature, and, comparable to different persistent diseases, many patients require a number of episodes and modalities of treatment, which may collectively over time contribute to sustained recovery.21
The DSM-5 doesn’t provide a definition of recovery, and there isn’t a standardized definition of the time period. Whereas recovery has many meanings, most prolong past cessation of substance use, emphasizing improved health and broader adjustments in behavior and generally even identification.22
Medical Epidemiology
Overview
In accordance to the 2019 Nationwide Survey on Drug Use and Health, which included people aged 12 and older, 5.5 million people reported previous yr cocaine use.23 Amongst cocaine customers, about 20% will meet the factors for CUD at some level in their lifetime.24,25 Amongst people who report cocaine use (together with even simply as soon as), roughly 15% are estimated to progress to CUD inside the following 10 years26 – a charge of development larger than these discovered for hashish (8%) and alcohol (12–13%). Moreover, the velocity of development from first cocaine use to CUD is far quicker than the velocity of development from first use of alcohol to alcohol use disorder or from the primary use of hashish to hashish use disorder, with one in 16 to 20 cocaine customers changing into dependent inside the first yr of cocaine use.26 The Nationwide Epidemiological Survey of Alcohol and Associated Circumstances examine, using a large-scale community-based pattern, discovered that the likelihood estimate of transitioning from first substance use to dependence was 7.1% for people who use cocaine, in contrast to 2.0% for those that use nicotine, alcohol, or hashish.24 Though over time ongoing cocaine use continues to carry a excessive threat of progressing to CUD, on condition that the height threat for initiation of cocaine use happens at round age 20, a lot of the burden of CUD is carried by a youthful inhabitants who typically then battle to stop for a few years. For instance, Simpson et al discovered that one yr after completion of treatment (which in the examine ranged from outpatient to residential), 21% of people initially identified with CUD continued to use cocaine weekly, and the proportion of weekly cocaine customers rose to 25% at 5 years.11 Furthermore, 5 years after treatment, 18% reported having been arrested, emphasizing the excessive rates of the psychosocial influence, together with authorized stigma, of CUD.
Danger Elements
Many threat elements for CUD have been recognized, together with genetic, environmental, and different demographic and individual-level elements. Development from experimentation with cocaine to the event of addiction has a big genetic element.27 Whereas heritability estimates differ, CUD is believed to be one of essentially the most heritable mental health disorders28 – the chance for growing CUD is estimated to be up to 65% hereditary in girls and up to 79% heredity in males.29,30 Compared, the heritability for each alcohol and opioid use disorders is estimated to be 50% for each males and girls.31,32 Nonetheless, not like tobacco and alcohol use disorders, particular genes instantly linked to CUD stay to be recognized. Environmental elements enhance the chance of substance use disorders in normal; nonetheless, CUD, comparable to stimulant use disorders, is basically influenced by shared setting.33 Environmental elements can disproportionately have an effect on minority populations. For instance, black people have reported elevated use of cocaine in the extra addictive kind of crack,34 which, in one examine, was proven to be accounted for by elevated availability and shared social conditions in some communities.35 Black people additionally expertise longer gaps between problematic use and treatment entry.36 Different threat elements for growing CUD embrace impulsivity,37 childhood ADHD diagnosis,38 childhood antagonistic experiences,39 fewer years of education,40 decrease parental level of education,41 polysubstance abuse,42,43 and presence of co-occurring mental health disorders.24 Utilizing cocaine in extra addictive varieties comparable to crack-cocaine or by way of IV in contrast to intranasal routes,44 and utilizing cocaine extra ceaselessly and in larger quantities, all enhance the chance for CUD.25 Frequency of cocaine use appears to enhance the chance of CUD extra strongly than the quantity of use; nonetheless, frequency and quantity of use synergistically mix to enhance the chance of progressing to CUD.25
Co-Occurring Psychological Health Problems
Co-occurrence between CUD and different mental health disorders is ceaselessly noticed in each treatment samples and massive epidemiological research. Two research of treatment-seeking cocaine customers discovered comparable rates – 73.5% and 65% – of co-occurring lifetime mental health diagnoses, not together with a co-occurring substance use disorder.45,46 Amongst responders in the US Nationwide Epidemiologic Survey on Alcohol and Associated Circumstances (NESARC), 45% of cocaine customers reported a lifetime mood disorder, and 31% reported a lifetime anxiety disorder.47 In contrast to those that have by no means used cocaine, present cocaine use is related with an virtually tripled threat for depression (6% vs 16%) and a greater than doubled threat for anxiety disorders (11% vs 5%).48 A meta-analysis estimated an 11 to 28% lifetime prevalence of bipolar disorder amongst people with CUD, in contrast to 1 to 3% for these in the overall inhabitants.49
CUD is related with excessive rates of each polysubstance use and co-occurring substance use disorders. In a examine investigating mono vs polydrug use abuse, 77.8% of people who used cocaine reported polysubstance use (n = 21,970) – in phrases of utilizing substances concurrently, essentially the most common mixture reported was cocaine and alcohol.50 In a separate examine, in a pattern of 227 people with CUD, the prevalence of lifetime heroin, alcohol, and benzodiazepine dependence have been 46%, 29% and 25%, respectively.46 Concurrent use of cocaine and different drugs has a number of health dangers. For instance, co-use of cocaine and opioids contributes to cocaine overdose deaths,51 and co-use of alcohol and cocaine will increase blood cocaine levels by 30% and will increase cardiotoxicity by forming cocaethylene, a doubtlessly deadly byproduct.52 About 75–84% of cocaine customers additionally smoke cigarettes (the main trigger of preventable demise in the US),53,54 and the stop charge for smoking amongst cocaine customers is far decrease than for those that don’t use different illicit substances (13% vs 56%).54
Basically, co-occurring substance use disorders and different mental health disorders negatively influence the treatment final result of one another.55,56 That is true for CUD as effectively. The presence of mental health and substance use co-occurrence has a robust influence on the event and upkeep of CUD – contributing to the severity of CUD and to poorer treatment retention and outcomes.57–59 For instance, the presence of co-occurring depression is related with larger euphoria from cocaine use,60,61 extra intense cravings, and extra extreme withdrawal symptoms throughout early abstinence from cocaine.62,63 Co-occurring depression additionally predicts a better probability of relapse.64 Related to depression, cocaine use is a widely known threat issue for suicidal ideation and suicide try,65–67 emphasizing the dangers related with the co-occurrence of CUD and depression.
There are various theories as to why such excessive rates of co-occurrence exist between substance use disorders and different mental health disorders. Psychological health disorders and SUDs could have shared genetic vulnerabilities. In accordance to the self-medication speculation, people attempt to relieve symptoms of a psychiatric disorder (comparable to depression) or unwanted side effects of drugs (comparable to sedation).68,69 Options of anxiety and depression (comparable to unfavorable inner mood states, together with stress) could set off substance use.
One other in style concept to clarify excessive rates of co-occurrence is the shared vulnerability underlying substance use disorders and different mental health disorders (depression, bipolar disorder, and anxiety disorder). Genetic research that discovered overlapping shared vulnerability throughout substance use and different psychiatric disorders help this speculation. For instance, moderately than being solely pushed by genetic variations in underlying organic processes instantly linked to drug actions or drug metabolism, it’s seemingly that addiction is pushed by genetic variants that additionally mediate exercise in mind circuits and areas concerned in domains comparable to personality traits, reward, and mental health conditions.70
Clinically, it may possibly typically be troublesome to distinguish an unbiased (or primary) mood disorder from a mood disorder secondary to (or attributable to) a substance. This distinction typically depends on figuring out the temporal sequences of mood symptoms and substance use, which is aided by following a patient longitudinally. Major mood disorders are identified when symptoms precede substance use or exist during times of at least a number of weeks of abstinence. For people with lengthy histories of overlapping mood symptoms and substance use, making the excellence between an unbiased and secondary mood disorder might be difficult, significantly as mood and substance use disorders have a tendency to recur in nature, and patients with an SUD could have a troublesome time attaining lengthy durations of abstinence. For instance, for people with co-occurring CUD and depression, it might be troublesome to decide if depression is primary or attributable to cocaine withdrawal. Given the excessive rates of co-occurring mental health disorders seen in SUDs and the overlapping symptomatology throughout these disorders, new paradigms could also be wanted for how we expect about these conditions that we frequently attempt to diagnostically separate and deal with individually. Finally, each substance-induced and “primary” mood disorders want clinical consideration and treatment, even when making this distinction is difficult or not potential.
Intercourse Variations
CUD is related with important sex-based variations. Charges of lifetime CUD are larger amongst males – 3% for males vs 1.8% for girls.71 Girls, nonetheless, progress quicker than males from first cocaine use to addiction. This fast development is termed a “telescoped course”, and it might be associated to girls being extra seemingly to use crack cocaine, which is very addictive.72 The profile of co-occurring mental health disorders amongst males and girls with CUD additionally differ. Amongst people with CUD, males are extra seemingly to have co-occurring SUDs and ADHD, whereas girls are extra seemingly to have co-occurring anxiety disorders, eating disorders, and post-traumatic stress disorder.72–75 Amongst people who enter treatment for CUD, males and girls report equal rates of homelessness; nonetheless, girls are extra seemingly than males to report previous trauma and receive pharmacotherapies for psychiatric conditions, suggestive of a better level of complexity and a better illness burden.75,76 Girls who use cocaine additionally sometimes current to treatment reporting extra socioeconomic issues than males.74 They’re extra seemingly than males to be unemployed and receive public support,76 and they report larger interpersonal issues.74 They’re additionally extra seemingly than males to live with kids,76 and thus should steadiness treatment with childcare. Following treatment, girls are extra seemingly than males to return to cocaine use in the context of distressing emotional states and interpersonal battle.77 Collectively, these findings underscore the necessity for extra sex-specific and tailor-made treatment approaches, as mentioned beneath.
Acute and Power Neurobehavioral Results of Cocaine
Acute Results
There are a number of acute results of cocaine which will drive typical patterns of use. As a psychostimulant, cocaine prompts the sympathetic nervous system, inflicting elevated arousal, vigor, exercise, wakefulness, and elevated mood, in addition to diminished urge for food and sleep. Cocaine’s acute results final for roughly 20–half-hour; throughout this time customers report feeling an intense euphoria or “excessive.” Acutely, and like different drugs of abuse, cocaine will increase dopamine launch in the mind’s mesolimbic reward programs, and this effect is believed to underlie the euphoric and addictive potential of cocaine. At larger doses and with extra fast routes of administration (eg, smoked or intravenous vs intranasal), cocaine tends to induce extra strong euphoria, thereby rising the probability of growing addiction.78
In a examine of 36,309 adults in the US, 73% of cocaine customers reported utilizing an common of 0.8 grams on 0.4 days per week, in contrast to the remaining 27% who reported utilizing between 2.6 and 19 grams of cocaine every day, at least 3 or extra days per week.25 Throughout cocaine binges, cocaine is used in massive portions throughout a discrete interval till assets to achieve this have run out or the person is unable to proceed use. These durations are related with a better threat of taking part in legal behavior, contracting sexually transmitted diseases comparable to HIV, and participating in different impulsive behaviors with dire penalties for the individual and society.79,80
Neurobehavioral Options of People with Power Cocaine Use
Key neurobehavioral adjustments happen with continued common use of cocaine. These adjustments embrace the emergence of withdrawal following cessation of cocaine use and diminished euphoria from a given dose of cocaine (ie, tolerance), which may drive dose escalation. Signs of cocaine withdrawal embrace fatigue, psychomotor slowing, anxiety, depression, sleep disturbance, elevated urge for food, and intense craving for cocaine use. Though milder than withdrawal symptoms that accompany alcohol or opioid use, cocaine withdrawal symptoms can drive additional cocaine use due to bodily and psychological misery. Roughly 82–86% of cocaine customers expertise cocaine withdrawal – these estimates are based mostly on two current research, one of which included people utilizing cocaine at least twice every week for 6 months, and one of which included people who met standards for CUD.81,82 Those that expertise cocaine withdrawal are extra seemingly to use cocaine in bigger quantities, report stronger euphoria, and have extra extreme medical, psychiatric, and psychosocial issues.81
In accordance to the incentive-sensitization idea, addiction develops due to an elevated sensitivity to drug-related cues, even whereas the drug’s euphoric results are diminished. This phenomenon is pushed by discovered associations and neuroplastic mind adjustments, main to a drastic enhance of “wanting” or “needing” of the substance (eg, craving) which is usually decoupled from a corresponding “liking” of that substance.83 A technique to assess such hypersensitivity to drug-related cues is by measuring an computerized cognitive process referred to as attentional bias for that drug.84 As soon as an elevated attentional bias to cocaine develops, another rapidly notices cocaine-related cues and additionally has problem switching consideration to extra impartial stimuli.85,86 It has been advised that elevated attentional bias for cocaine cues could function a cognitive marker for CUD (reviewed in Sofuoglu et al 2014).87 The inducement-sensitization mannequin is especially related to CUD, as its core options are intense cravings (or “wanting” the substance), and excessive responsiveness to drug cues – as opposed to distinguished withdrawal symptoms, which have a tendency to accompany alcohol or opioid use.81
Power cocaine use is related with a number of persistent neurocognitive deficits. Individuals who chronically use cocaine show deficits in consideration (significantly sustained consideration), visible and working reminiscence, verbal fluency, sensory-perceptual features, response inhibition, and impulsivity (reviewed in Potvin).85,88,89 Notably, many of these deficits persist after a number of months of abstinence,85 indicating that they aren’t attributable to quick drug results or acute phases of withdrawal. In a meta-analysis of 15 research evaluating cocaine customers to wholesome controls, cocaine use brought on the best deficits in visible and working reminiscence and consideration.88 Moreover, neuro-imaging research, generally using practical magnetic resonance imaging (fMRI), performed on cocaine customers present decreases in activation or irregular blood circulation in mind areas that underlie govt and attentional operate, comparable to anterior cingulate,90 lateral prefrontal,90 prefrontal,91 and orbitofrontal cortices.92 It’s unclear if these cognitive deficits precede or comply with cocaine use. People with pre-existing cognitive deficits are extra seemingly to use substances and develop SUDs.93 Alternatively, persistent use of cocaine and different drugs (eg, alcohol, tobacco) could contribute to cognitive deficits in a dose-dependent method.94 Regardless of their trigger, cognitive deficits noticed in people with CUD have clinical relevance. For instance, amongst cocaine customers, treatment non-completers have a tendency to carry out worse in cognitive measures;95 constant with this, higher govt operate predicts longer retention in treatment.96 Deficits in govt functioning can lead to decreased “top-down” processes essential in recovery. For instance, govt features comparable to sustained consideration and response inhibition are seemingly wanted to help regulate drug use behavior,97,98 and it follows that breakdown in these processes enhances vulnerability to substance use and relapse. These types of cognitive deficits can also function a treatment goal for each pharmacologic and behavioral interventions, as we define beneath (see Remedies Focusing on Cognitive Deficits).
Lastly, neuroimaging research have revealed variations in underlying neural networks in people with CUD in contrast to wholesome controls who don’t use substances. As with different drugs of abuse, persistent publicity to cocaine causes neuroplastic adjustments that in the end dysregulate neural circuitry. Whereas totally different mind areas are affected by totally different phases of addiction, the mesocorticolimbic99 circuit is the core circuit affected. Whereas acute publicity to cocaine will increase synaptic dopamine launch in the mesolimbic circuit, persistent repeated publicity is related with diminished dopamine operate,100 underlying the anhedonia that accompanies substance use disorders. Trying to right imbalances in mind circuitry is the intention of rising treatments comparable to transcranial magnetic stimulation (see Non-Invasive Mind Stimulation Strategies, beneath).
Overview of Present Remedy Approaches
Pharmacotherapies
Over the previous few a long time, quite a few research have investigated pharmacologic treatments for CUD. Nonetheless, up to now, no medication has met the Meals and Drug Administration’s (FDA) standards for approval, which consists of treatment efficacy demonstrated in at least two adequately powered (sometimes n > 200) randomized, placebo-controlled trials (RCT). Whereas no drug class has confirmed to be effective,17 individual compounds with therapeutic promise have been used off-label. On this part, we talk about some of essentially the most related findings per drug class.
Antidepressants
Outcomes from a Cochrane evaluate,101 a scientific evaluate and meta-analysis,17 and an umbrella evaluate102 counsel that, as a category, antidepressants haven’t any constant effect on any clinically related measure of CUD studied up to now (together with cocaine use, sustained abstinence, retention, and hurt outcomes). As an alternative, antidepressants have been related with larger drop-out rates, presumably by inflicting antagonistic occasions – though the standard of the proof for this discovering has been deemed low.17,101
Among the many research which have discovered therapeutic results of antidepressants for CUD is a double-blind placebo-controlled trial administering citalopram, a selective serotonin reuptake inhibitor (SSRI) antidepressant. On this examine, citalopram was superior to placebo in lowering cocaine use, when mixed with a behavioral intervention (both cognitive-behavioral therapy or contingency management).103 Likewise, in a 12-week double-blind RCT, sertraline, one other SSRI, delayed time to returning to utilizing cocaine amongst 86 cocaine-dependent people with depressive symptoms who had already been abstinent for two weeks when the trial started.104 Lastly, in one other trial, bupropion, with a mechanism of motion that differs from SSRIs, enhanced the efficacy of contingency management in selling abstinence from cocaine.105,106
Psychostimulants
By mimicking some actions of cocaine by elevated dopaminergic exercise however with key variations in pharmacokinetic properties – comparable to slower onset of results and an extended half-life, and thus much less abuse threat – psychostimulants have been used off-label to promote abstinence from cocaine. Whereas a Cochrane evaluate that included 26 trials (N = 2366) discovered low energy proof that psychostimulants could promote abstinence in 14 trials (outlined by 3 weeks of non-use in 13 of the research and 2 weeks of non-use in 1 examine), no variations in cocaine use, examine retention, or hurt outcomes have been discovered.105 In one other examine, a high-dose (60 mg) however not low dose (30 mg) of sustained-release preparation of dextroamphetamine diminished cocaine use.107 Lastly, one other RCT administering 60 mg sustained-release dextroamphetamine in heroin- and cocaine-dependent people additionally being handled with methadone and diacetylmorphine discovered that dextroamphetamine was effectively tolerated and decreased days of cocaine use.108
Dopamine Agonists
A Cochrane evaluate of 17 research discovered no distinction between dopamine agonists (bromocriptine, amantadine, and pergolide) in any clinically related final result – together with optimistic urine samples for cocaine metabolites and examine retention.109 One other Cochrane evaluate of 24 trials discovered no distinction between dopamine agonists (together with bromocriptine, amantadine, and pramipexole) in contrast to placebo in treatment retention or abstinence from cocaine use amongst people with CUD.110 The authors additionally discovered no proof that combining a dopamine agonist with a psychosocial intervention improved treatment outcomes.110 A examine investigating amantadine to scale back cocaine use and cravings discovered it was no extra effective than placebo, in a gaggle of cocaine-dependent people who have been receiving methadone for co-occurring opioid use disorder.111 A separate examine inspecting amantadine’s efficacy in lowering cocaine withdrawal symptoms and bettering CUD outcomes discovered that amantadine decreased cocaine use, measured by urine samples and self-reports, in a gaggle of cocaine-dependent people who have been experiencing extreme withdrawal symptoms at the beginning of the examine.112 On this examine, amantadine didn’t promote abstinence in the people who skilled much less extreme cocaine withdrawal at the beginning of the examine, constant with the authors’ hypothesis that amantadine reduces cocaine withdrawal symptoms.
Modafinil is one other well-known cognitive enhancer with the potential to deal with CUD. Modafinil affects a number of neurotransmitter programs, and will increase dopamine by blocking dopamine transporters.113 In an inpatient setting, modafinil improved working reminiscence and sustained consideration in cocaine-dependent people (N= 16), in contrast to people randomized to escitalopram, escitalopram plus modafinil, or placebo.114 In a separate examine, modafinil treatment was related with extra days of abstinence from cocaine, when mixed with weekly one-hour psychotherapy classes.115 In one other examine, modafinil elevated the probability of unfavorable urine samples and probabilities of attaining cocaine abstinence for greater than 3 weeks after treatment.116 Nonetheless, in a follow-up examine, the authors have been unable to replicate this effect.117 A meta-analysis together with 11 research discovered that general, modafinil was not superior to placebo in bettering measures of CUD, but the authors famous that in a subgroup evaluation of 6 research performed in the US, modafinil elevated cocaine abstinence rates.118 The authors concluded that, based mostly on modafinil’s tolerability and good security profile, it deserves additional investigation.
Antipsychotics/Dopamine Blockers
A current Cochrane evaluate of 14 research (N = 719) investigating the efficacy of antipsychotic pharmacotherapy for the treatment of CUD (by way of actions on dopaminergic and serotonergic programs) discovered that antipsychotics diminished treatment drop-out rates however had no important effect on some other outcomes associated to CUD.119 Equally, a scientific evaluate and meta-analysis together with 8 RCTs investigating antipsychotics for the treatment of CUD concluded that antipsychotics could enhance treatment retention.17 Clozaril, nonetheless, has proven some promise in lowering substance use, together with cocaine use, in patients who’re receiving this medication for a co-occurring psychotic disorder.120,121
Anticonvulsants and Muscle Relaxants
Stimulation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) decreases activation of the dopamine reward circuitry. Thus, anticonvulsants, which enhance GABA exercise, could lower cocaine-induced dopamine launch and reinforcing results. A scientific evaluate of 20 RCTs (N = 2068) discovered no important distinction between anticonvulsants and placebo in cocaine use, craving, rates of anxiety and depression, and treatment retention.122 Research investigating topiramate, an anticonvulsant that stimulates GABA and inhibits glutamate, have discovered conflicting outcomes. A meta-analysis of 5 RCTs (N = 518) inspecting topiramate for CUD discovered that, in contrast to placebo, topiramate elevated abstinence (low energy of proof) however didn’t have an effect on examine retention (average energy of proof).17 A current RCT, accomplished after the above meta-analysis was revealed, discovered that, in contrast to placebo, topiramate decreased the quantity and frequency of cocaine use for the primary 4 weeks of the examine, however by week 12 there was no distinction between treatment with topiramate and placebo.123
Repurposing of Drugs Authorised to Deal with Different SUDs
With the exception of disulfiram – which has combined proof to deal with CUD – no important variations in outcomes have been discovered for drugs permitted to deal with different SUDs. Disulfiram inhibits the enzyme dopamine-beta-hydroxylase, which converts dopamine to norepinephrine, thus rising synaptic dopamine levels. Some clinical trials present that disulfiram could lower cocaine use in these with co-occurring opioid use disorder,124 and additionally in these with co-occurring alcohol use disorder with and with out co-administration of naltrexone.125 In a special examine, disulfiram diminished cocaine use in people with CUD who weren’t alcohol dependent or who didn’t drink alcohol throughout treatment, in contrast to those that have been utilizing alcohol or who have been alcohol dependent.126 A meta-analysis of 12 RCTs discovered low energy proof that disulfiram doesn’t enhance abstinence and as an alternative decreases retention; nonetheless, the authors famous that the proof was inadequate for drawing conclusions due to the heterogeneity of results measured.17
Ketamine
Lastly, ketamine has proven some promise as a novel treatment for SUDs together with CUD. NMDA receptors are believed to be the primary glutamate receptor concerned in discovered behavior, and ketamine, by NMDA receptor antagonism, modulates glutamate signaling. A current RCT discovered that one single subanesthetic ketamine infusion, in contrast to an infusion of midazolam, improved a number of treatment outcomes of CUD – together with decreasing the probability of utilizing cocaine and reducing cravings and relapse threat – in a gaggle of 55 cocaine-dependent people who additionally initiated mindfulness-based relapse prevention therapy (MBRPT) as half of the examine.127 MBRPT was mixed with ketamine as a result of the authors speculated that the 2 treatments would activate comparable mind networks and subsequently improve one another. Impressively, the group who acquired ketamine and therapy had larger rates of abstinence even at a 6-month follow-up. These promising findings warrant future research with bigger samples.
There are various the explanation why, regardless of quite a few research, no drugs have been permitted for CUD. These embrace methodological points, small pattern sizes main to underpowered research, excessive drop-out rates, and heterogeneity of each examine design and pattern inhabitants. Moreover, as noticed lately by Brandt et al, an amazing many pharmacological treatments for CUD have been explored; nonetheless, just a few research have been carried out for every individual medication.18 Thus, they argue that drugs which have demonstrated optimistic indicators in early research needs to be given additional investigation. Exploring mixture therapies is one other promising space.
Psychosocial Remedies for Cocaine Use Disorder
Psychosocial treatments for CUD are restricted in selection however nonetheless are the present customary of observe for this disorder, representing the fruits of almost 4 a long time of clinical analysis.128–131 Right here, we talk about two approaches which have acquired the best diploma of empirical help: Contingency Administration (CM)130,132 and Cognitive-Behavioral Remedy for Substance Use Problems (CBT-SUD).133,134 We start by offering a short historical past of every treatment’s improvement earlier than describing its construction, utility, and empirical help. Lastly, we word treatment limitations and talk about ongoing efforts to refine these psychosocial interventions for CUD.
Contingency Administration
CM was first carried out in the US inside opioid treatment clinics, in which the likelihood of frequent goal drug-use monitoring (eg, by way of urine toxicology screens) and associated, salient pure rewards (eg, take-home methadone doses) allowed researchers to display the worth of optimistic contingencies in lowering substance use.131,135–137 CM was later utilized to CUD through the Nineteen Eighties, prompted in massive half by the shortage of effective pharmacotherapies for this situation.129,136,138 These preliminary efforts have been essential for establishing CM as a proper treatment and in the fruits of the treatment practiced at the moment.
Utility of CM attracts closely from operant conditioning rules, focusing on systematically adjusting reinforcers and punishers in a patient’s setting to enhance behavior in alignment with treatment targets.139 Abstinence, assessed by way of urine toxicology screens 2–3 occasions per week, is ceaselessly indicated as the primary treatment aim and reward for unfavorable (drug-free) toxicology screens function the primary reinforcer in CM. That’s, patients who provide unfavorable screens receive monetary-based vouchers130,140 or alternatives for prizes141,142 redeemable for retail items or companies. Voucher/prize-value is systematically elevated following consecutive unfavorable screens to incentivize sustained abstinence; conversely, optimistic screens or failure to submit urine screens at scheduled occasions outcomes in resetting of reward values to their preliminary levels. CM for CUD is usually supplied in an outpatient setting over 12-weeks132,143 and has been offered in each individual and group codecs.144
Inside this common framework, reinforcement is organized round a number of rules together with quickly and precisely detecting cocaine use, positively reinforcing abstinence close-in-time to detection, loss of optimistic reinforcement upon drug use, and incorporation of reinforcers to compete with drug use.129 Because the proof base supporting CM has grown, its refinements in its observe have equally developed, with, for instance, higher outcomes ensuing in extra quick provision of reinforcement following goal verification of abstinence or provision of higher-magnitude reinforcers.145,146 Moreover, people who display larger within-treatment abstinence have a tendency to present higher long-term outcomes after treatment ends.147
CM has routinely demonstrated a excessive level of efficacy in treating CUD, with a number of research and RCTs exhibiting effectiveness of CM over customary care and in patients who’ve co-occurring SUDs or mental health disorders.148–154 Research have additionally indicated that CM is effective throughout a number of totally different clinical teams, together with community155 and veteran populations.150 For instance, Bentzley et al performed a meta-analysis evaluating a number of totally different treatments for CUD together with psychotherapies, varied drugs (eg, antidepressants, psychostimulants, opioids), and placebo teams; collectively, outcomes advised solely CM was related with larger probability of unfavorable urine toxicology screens for cocaine.148
Regardless of CM’s in depth empirical help, a number of ongoing limitations impede its widespread adoption together with societal and provider stigma, issues about the sturdiness of treatment results, and pragmatic issues comparable to implementation costs and personnel availability.156 Moreover, there’s some concern with how CM might be carried out alongside different treatment approaches comparable to 12-step facilitation. Roughly two-thirds of substance use clinics report that the 12-step methodology is the predominant treatment approach.157,158 Clinic staff that use a 12-step approach could hesitate to implement CM due to philosophical or sensible issues.159 Nonetheless, CM is a remarkably effective intervention typically and in some meta-analyses has outperformed different lively treatments for CUD.148,149,160,161 Moreover, the emphasis on abstinence is constant with 12-step treatment views. Whereas reductions from peak treatment abstinence levels can happen, a number of research present lasting results of CM up to 1-year post-treatment completion.162–164 Lastly, whereas CM might be an costly treatment to implement (eg, patients in trials performed by Higgins et al might earn almost $1000)140, a big physique of analysis illustrates that CM might be carried out at costs as little as $240/per patient and performed in cost-effective codecs, comparable to in therapy teams. 155,165
Cognitive-Behavioral Remedy for Substance Use Problems (CBT-SUD)
CBT-SUD for CUD grew from broader efforts to apply cognitive-behavioral rules to the treatment of addictive behaviors. Drawing from applications of CBT in depression and anxiety, preliminary applications of CBT in addictive behaviors have been validated by Marlatt et al in patients searching for treatment for alcohol use.136,166,167 Following its preliminary validation, CBT-SUD was then utilized to deal with CUD, largely by the work of Carroll et al. These efforts culminated in the publication of Carroll’s seminal guide, A Cognitive-Behavioral Strategy: Treating Cocaine Dependancy.128,133,134 CBT-SUD has since turn out to be a broadly acquainted mannequin amongst practitioners with a robust proof base.
CBT-SUD focuses on serving to patients perceive their cocaine use and instructing them new skills to help handle it. A core side of this approach is the combination of “practical evaluation”, which aids patients in understanding the antecedents and penalties prompting/sustaining cocaine use. From this basis, patients receive skills coaching on how to perceive, acknowledge, and intervene throughout cravings/urges, determine and problem unhelpful cognitions associated to cocaine use, successfully problem-solve, implement assertive communication to refuse drug presents, scale back drug-related cues in their setting, and acknowledge and intervene on seemingly minor selections that may enhance threat of cocaine use.134 Inside this framework, classes are sometimes structured to guarantee time is allotted for psychoeducation, ability/residence observe evaluate, and introduction of novel skills. A number of “core” ability modules (eg, practical evaluation, coping with cravings, drug refusal skills)134 are integral parts of this manualized protocol, although later iterations have expanded these matters to embrace quite a few “adjunctive” modules (eg, mood management, listening skills, social and leisure counseling)168. In CBT-SUD, patients are requested to full common home-practice between every session that, as indicated above, is then reviewed by providers in subsequent conferences. CBT-SUD is usually performed in 1-hour weekly, individual classes occurring over 12 to 16 weeks; nonetheless, this treatment has generally been utilized in group codecs.169
There’s a massive physique of proof supporting the efficacy of CBT in treating CUD. A number of RCTs have proven CBT-SUD is effective in lowering cocaine use.126,170,171 Notably, some proof has indicated “sleeper results” of CBT-SUD for CUD, in which enhancements in cocaine use proceed after treatment completion.133 Rawson et al, for instance, performed an RCT in which methadone-maintained members with CUD have been randomly assigned to both CBT, CM, CBT+CM, or treatment as traditional (TAU).163 Their outcomes indicated reductions in cocaine use after the treatment interval (16 weeks) for each CM and CBT, although CM demonstrated barely bigger results instantly post-treatment; nonetheless, at 26- and 52-week follow-ups, CBT members continued demonstrating enhancements, ensuing in equal enhancements between CBT and CM at these timepoints. Thus, CBT-SUD is just not solely effective however its results could persist past the completion of treatment.
Regardless of CBT-SUD’s empirical help, a number of treatment issues and implementation limitations are essential to word. First, with respect to treatment issues, CBT-SUD’s efficacy is in half dependent on patient ability and generalization.172,173 That is exemplified in work by Decker et al that confirmed patients who accomplished lower than half of assigned residence observe demonstrated larger cocaine use than patients finishing greater than half of assigned residence observe; these results remained important even after statistically controlling for baseline cocaine use frequency and session attendance.174 Second, constancy has remained an ongoing problem to successfully implementing CBT-SUD,171,175 with analysis suggesting larger levels of didactic coaching and supervision are obligatory to preserve sufficient model-adherence in observe.176 Even amongst people who’ve been completely educated to use evidence-based treatments, like CBT-SUD, clinicians are usually not as adherent to treatment protocols despite the fact that they consider themselves to be competent.177 Collectively, these points current important sensible calls for from practitioners and administrations to guarantee sufficient supply of CBT-SUD for patients with CUD.
These limitations prompted variations in the supply of CBT-SUD, with essentially the most notable instance being a computer-assisted program often called “CBT4CBT”.178–181 CBT4CBT makes use of multimedia (eg, video, textual content, video games, cartoons) options to help coach patients by studying CBT-SUD coping skills. The platform provides a standardized methodology of delivering clinician-adjunctive companies to help deal with cocaine and different substance use disorders. Proof for CBT-SUD demonstrates comparable efficacy and effect period with its conventional modality typically for substance use disorders,178,182 in addition to particularly for CUD .183–185 In Carroll et al’s RCT of CBT4CBT, methadone-maintained patients with CUD who accomplished an 8-week course of the program reported excessive acceptability of CBT4CBT, alongside larger odds of acquiring ≥3 consecutive weeks of cocaine abstinence and unfavorable urine screens for all drugs; additional, these results have been retained at a 6-month follow-up.183 Lastly, cost-effectiveness analysis has advised stark superiority of CBT4CBT versus conventional implementations of CBT-SUD.186
Abstract of Psychosocial Remedies for CUD
In abstract, psychosocial treatments signify the present gold-standard for CUD treatment. Inside this broader class, CM and CBT-SUD at the moment have the best empirical help in optimistic treatment outcomes (eg, diminished cocaine use), collectively garnered over roughly 3 a long time of analysis and utility. Nonetheless, ongoing limitations stay together with implementation limitations comparable to stigma in direction of these practices, pragmatic limitations (eg, cost, staff availability), and mannequin adherence. Although ongoing analysis efforts are refining the extent and utility of these modalities (eg, computer-assisted strategies like CBT4CBT),179 there stays a necessity for larger dissemination and implementation of each CM and CBT-SUD for CUD.
Built-in Care and Mixed Remedies
Built-in treatment refers to when treatment of each the SUD and the co-occurring mental health disorder are delivered by the identical clinician or clinical group. This approach has been thought of the perfect treatment for people with co-occurring mental health disorders and SUDs at all levels of treatment (inpatient, outpatient, and so forth.).187–189 Though built-in treatment approaches are supported in the literature, a current Cochrane evaluate discovered low-quality proof of no distinction between built-in fashions of care and customary fashions of care for a number of outcomes together with substance use and international functioning.190 There are a number of causes that might clarify this discovering, together with the issue in standardizing built-in dual diagnosis treatment.191 Except for the difficulties in guaranteeing standardization of built-in treatment, there are different limitations to this type of care in each analysis and clinical observe. Most treatment centers are nonetheless not even designed to provide this type of care. For instance, a survey of 180 community addiction programs spanning residential treatment programs, outpatient programs, and intensive outpatient programs discovered that solely 20% supplied built-in or dual diagnosis companies,192 and a separate examine which sampled 256 programs throughout the US discovered that solely 18% of addiction treatment programs and 9% of mental health programs supplied built-in treatment approaches.193
Multimodal care sometimes consists of combining psychosocial interventions (comparable to CM or CBT) with drugs, and this approach typically has higher outcomes than treatment with a single intervention. For instance, in a examine investigating the efficacy of desipramine mixed with CM for the treatment of opioid and cocaine dependence, whereas each CM and desipramine have been individually effective in rising opioid and cocaine-negative urines, the mixed treatment was extra effective in bettering these outcomes than both treatment alone.194 Equally, people handled with 40mg fluoxetine and the environmental contingency of decreased clinic go to necessities for fewer cocaine-positive urine samples had fewer cocaine-positive urine samples than these handled with solely 20 mg fluoxetine or placebo.195 One other examine of 106 opioid-dependent cocaine customers discovered proof that combining CM with bupropion diminished cocaine use greater than bupropion alone, and for an extended interval than for CM alone.106 Taken collectively, these research underscore the potential synergism between behavioral and pharmacological treatments for CUD.
Rising Remedies
Remedies Focusing on Cognitive Deficits
As mentioned above, there are neurocognitive deficits related with common cocaine use. Many of these overlap with adjustments seen in the mental health disorders which might be generally co-occurring amongst people with CUD. As this overlap in symptomatology exists, cognitive domains maintain promise as treatment targets for each pharmacologic and behavioral interventions.196,197
Behavioral Remedies
Modifications in attentional bias, seen in each CUD and anxiety and depressive disorders, are a promising treatment goal (reviewed in).87 Attentional bias modification (ABM) is a comparatively new approach in which members learn the way to shift consideration away from drug cues and in direction of impartial cues.198 Authors of a current examine investigated ABM’s potential to scale back drug use behaviors in people with CUD – they discovered no variations between the group receiving ABM and the group receiving management therapy, though each teams report decreased use and cravings.199 One other examine discovered that depth of attentional bias could also be a predictor of imminent relapse to cocaine use, as measured and tracked by a hand-held moveable system.200 Constructing on these findings, moveable and user-friendly interventions could help people determine the necessity to regulate the depth and frequency of treatment or achieve a greater understanding of their very own distinctive triggers to use cocaine, in real-time.
Pharmacological Approaches
N-acetylcysteine, by balancing glutamate operate, could help scale back attentional bias to cocaine-related cues. This was supported by outcomes of a examine of 14 people who, throughout n-acetylcysteine treatment, had diminished attentional bias to cocaine cues.201 Additionally they had diminished cocaine decisions, as measured by the Drug Alternative Process in which members have been requested to select between cocaine and a financial reinforcer.
The cholinergic system performs a task in many cognitive processes together with consideration, reminiscence, mood, motivation, reward, and stress response. Findings from a number of strains of proof point out that the cholinergic system is one other promising potential goal for the treatment of CUD.202 Cholinesterase inhibitors, comparable to galantamine and rivastigmine, enhance synaptic acetylcholine levels and have been used to improve cognitive operate in neuropsychiatric disorders comparable to Alzheimer’s illness. Lately, amongst abstinent cocaine customers (N = 28), galantamine improved sustained consideration and working reminiscence features after solely 10 days.203 In one other examine performed amongst cocaine-dependent people (N = 41), rivastigmine improved efficiency on a measure of working reminiscence after 7 days of treatment.204 One other examine discovered a pattern for galantamine to lower cocaine use in methadone-maintained patients with opiate use disorder and CUD (N = 14);205 and in a bigger trial (N = 120) galantamine considerably diminished cocaine use in methadone-maintained patients.184 Notably, post-hoc analyses of information from this trial confirmed that galantamine additionally diminished opioid use.206 Conversely, a current randomized placebo-controlled trial of galantamine in patients with solely CUD confirmed no discount in cocaine use with galantamine treatment at both 8 mg/day (N = 31) or 16 mg/day (N = 30).207 Taken collectively, and mixed with galantamine’s security and tolerability, outcomes from these research point out that galantamine holds promise as a novel pharmacotherapy for CUD.
Though the psychostimulant methylphenidate has proven promise in bettering response inhibition in cocaine-dependent people,208,209 clinical trials investigating methylphenidate’s capability to enhance symptoms of CUD have yielded combined outcomes.210 Methylphenidate, nonetheless, was proven to lower cocaine use in people with co-occurring ADHD and CUD, in comparison with controls,211 thereby supporting its use for patients with CUD and co-occurring ADHD.
Intercourse-Particular Remedies
Research investigating sex and gender variations in cravings, relapse, stress response, and different options of addiction (see Intercourse Variations) help the necessity for tailor-made treatment approaches to deal with sex and gender-specific wants. This consists of the likelihood of offering totally different drugs to males and girls. The feminine sex hormone progesterone, produced through the second half of the menstrual cycle, has been discovered to lower cravings and euphoria produced by substances of abuse together with cocaine, in addition to enhance cognitive operate.212–214 Progesterone can also scale back stress responses,215 that are extra distinguished in cocaine-dependent girls in contrast to males.216 A stronger stress response is a identified threat issue for substance use and relapse, significantly in girls drug customers. A story evaluate wanting at 16 research, 9 of which included patients with CUD, discovered cumulative proof supporting progesterone in its capability to lower cravings and subjective optimistic results of cocaine.215 Oxytocin can also play a task in modulating stress response. In a current examine of 112 adults with CUD, girls reported larger stress provoked by a social stress check than males, however had decreased cortisol response when the hormone oxytocin was administered intranasally 40 minutes prior to the check.217 A logical subsequent step could be to look at if intranasal oxytocin reduces cocaine use triggered by stress in girls.
Non-pharmacological interventions aimed at stress discount can also maintain promise to scale back cocaine use, significantly for girls. Authors of a examine investigating the connection of sex and cocaine dependence on cravings discovered that cocaine-dependent girl had elevated corticostriatal-limbic exercise – which correlated with craving – in response to stress, in contrast to cocaine-dependent males, who had activation of these areas in response to drug cues.218 The authors reported that these findings emphasize the significance of therapies focusing on stress discount, comparable to mindfulness skills,219 for girls. One other instance is providing companies that help with caretaker obligations.
Non-Invasive Mind Stimulation Strategies
In contrast to people who don’t use substances, people with CUD exhibit dysfunctional circuitry (see Neurobehavioral Options of People with Power Cocaine Use), which might be modulated by mind stimulation strategies. In transcranial magnetic stimulation (TMS), which is non-invasive and typically effectively tolerated, magnetic pulses are utilized to modulate exercise in particular cortical areas, thus assuaging sure symptoms by regulating underlying mind networks. TMS has been FDA permitted to deal with main depressive disorder and obsessive-compulsive disorder, and it’s being explored for a spread of different conditions together with substance use disorders. Most research goal the dorsolateral prefrontal cortex (DLPFC) with the intention of each rising prefrontal cortex functioning and strengthening the modulation by the DLPFC of the dopaminergic mesolimbic circuitry (reviewed by Diana et al, 2017).220 In transcranial direct present stimulation (tDCS), a weak electrical present is handed between two electrodes positioned on the scalp, which then modulates cortical excitability. tDCS additionally mostly targets the DLPFC, due to the reasoning talked about above. There have been a number of research inspecting these neurostimulation techniques as potential treatments for CUD (lately reviewed by Bolloni et al, 2018, Rachid, 2018, and Lupi et al, 2017).221–223 In abstract, a number of research discovered that TMS and tDCS have efficacy in lowering cravings224–228 or lowering dangerous behaviors229 discovered in CUD. Nonetheless, a number of methodological points deserve consideration. These embrace small pattern sizes, in some instances lack of a sham management group, variations in stimulation protocols used, and an unclear understanding of the mechanisms of the treatments. A number of authors emphasize the potential efficacy of these novel approaches in treating CUD and counsel methods to standardize these treatments, in addition to level to the energy of combining these techniques with neuroimaging to higher perceive and goal related neural circuits.220,223,230
Immunotherapies
For the reason that early 90s, researchers have tried to produce an anti-cocaine vaccine, which might block cocaine’s results (reviewed by Kinsey et al in).231 Whereas cocaine by itself doesn’t provoke an immune response, it may possibly stimulate the manufacturing of antibodies when certain to a bigger service protein. Consequently, in the presence of cocaine, these antibodies bind to cocaine, preventing it from reaching the mind and subsequently blocking its euphoric and reinforcing results. One cocaine vaccine – termed TA-CD – that was investigated by Part III trials was synthesized by linking succinylnorcocaine – a chemical spinoff of cocaine – to a service protein derived from the cholera B toxin (rCTB).232 In a double-blind, placebo-controlled randomized trial, cocaine-users who developed excessive antibody titers following vaccination diminished cocaine use; nonetheless, solely 38% of vaccinated people had ample antibody levels, and the antibodies remained elevated for solely 2 months.233 Notably, the favorable retention charge in this examine was attributed to the truth that the members have been in methadone upkeep treatment, which required frequent clinical visits. In a follow-up clinical trial with cocaine customers who weren’t on methadone, no important treatment variations have been discovered. Actually, those that had developed larger vaccine-induced antibody levels truly had extra positive-cocaine urines, indicating elevated cocaine use. The authors speculated that the people with larger antibody levels and extra positive-cocaine urines could have elevated cocaine use to overcome a blockade of euphoria attributable to the vaccine.234 Different cocaine vaccines are being explored in pre-clinical research.
Customized Remedies
Given the heterogeneity of the patient inhabitants concerned – every individual with CUD has various illness severity, private traits, backgrounds, and social help – personalised, multi-dimensional treatment approaches are wanted. Figuring out threat elements for SUDs, together with genetic,235 behavioral, and environmental, could help to predict treatment course and thus help in treatment choice. For instance, it has been advised that these with larger impulsivity could reply higher to behavioral interventions focusing on this symptom cluster,236 and, as talked about above, that feminine substance customers could particularly profit from a multidisciplinary group that may provide treatment for interpersonal stress comparable to mindfulness-based therapies.
Figuring out Remedies and Supporting Restoration
Solely 19% of people with CUD receive much-needed treatment.237 Referral to evidence-based substance use treatment and different wanted companies is important, and any time people with CUD interface with a health care group (in the emergency department, in primary care, and so forth.) is an essential alternative to hyperlink people to acceptable care. Treating CUD instantly is only one side of care that needs to be thought of. Actually, every individual can profit from a complete care plan that targets a number of domains (see Determine 1). After ruling out or managing mental health and medical emergencies – together with ones associated to intoxication, overdose, or withdrawal – it is vital to deal with a number of important domains of the patient’s expertise. These embrace addressing CUD and different co-occurring substance use disorders, mental health and emotional wants, medical and bodily wants, and social and environmental wants. Every individual’s motivational standing and targets must also be assessed. These domains needs to be constantly thought of to help guide an individual’s treatment plan, together with the suitable level of care (outpatient, inpatient, residential, and so forth.) which can be affected by the presence of co-occurring medical conditions or different important wants together with homelessness, or lack of sufficient social help. The American Society of Dependancy Drugs (ASAM) standards might be used to help make this type of evaluation and guide treatment.238
 |
Determine 1 CUD: A Complete Remedy Strategy: After ruling out the necessity for acute medical or psychiatric care, a dynamic complete treatment plan needs to be formulated for every patient based mostly on an ongoing evaluation of a number of important domains. This evaluation may help to decide the suitable level of care which can be decrease or larger, relying on a number of various factors (such because the presence or severity of co-occurring disorders or co-occurring substance use, presence of quick stressors, or totally different levels of social help). |
The Substance Abuse and Psychological Health Providers Administration (SAMHSA) presents a working definition of recovery as “a process of change by which people enhance their health and wellness, live a self-directed life, and try to attain their full potential”.239 This highlights recovery as a multi-step, evolving process that encompasses many domains.
In abstract, in this evaluate, we have now highlighted many challenges that exist in the sphere of CUD therapeutics, outlined evidence-based treatments, and underscored promising novel therapies. It’s our hope that we have now additionally highlighted the various present alternatives to help people with CUD in their recovery process. These alternatives have to be seized by professionals from a number of disciplines – from medicine to psychology and from social work to occupational therapy. Whereas it might take time for every individual with CUD to discover their very own distinctive mixture of treatments that can work greatest, it’s important to hold people engaged in care till their very own most effective path towards recovery might be found.
Funding
This analysis was supported by the New England Veterans Administration VISN 1 Psychological Sickness Analysis, Training and Medical Heart (MIRECC).
Disclosure
The authors report no conflicts of curiosity in this work.
References
1. Administration SAaMHS. Key Substance Use and Psychological Health Indicators in the United States: Outcomes from the 2017 Nationwide Survey on Drug Use and Health. HHS Publication No. SMA 18-5068, NSDUH Sequence H-53. Rockville, MD: Heart for Behavioral Health Statistics and High quality; 2018.
2. SAMHSA. Substance Abuse and Psychological Health Providers Administration. Outcomes from the 2013 Nationwide Survey on Drug Use and Health; Nationwide Findings. SAMHSA; 2014.
3. Simpson KJ, Moran MT, McCall KL, et al. Growing heroin, cocaine, and buprenorphine arrests reported to the Maine Diversion Alert Program. Forensic Sci Int. 2019;303:109924. doi:10.1016/j.forsciint.2019.109924
4. Schneider KE, Krawczyk N, Xuan Z, Johnson RM. Previous 15-year traits in lifetime cocaine use amongst US excessive school college students. Drug Alcohol Rely. 2018;183:69–72. doi:10.1016/j.drugalcdep.2017.10.028
5. John WS, Wu LT. Traits and correlates of cocaine use and cocaine use disorder in the United States from 2011 to 2015. Drug Alcohol Rely. 2017;180:376–384. doi:10.1016/j.drugalcdep.2017.08.031
6. Hedegaard H, Bastian BA, Trinidad JP, Spencer M, Warner M. Medication most ceaselessly concerned in drug overdose deaths: United States, 2011–2016. Natl Important Stat Rep. 2018;67(9):1–14.
7. Shiels MS, Freedman ND, Thomas D, Berrington de gonzalez A. Traits in U.S. drug overdose deaths in non-Hispanic black, Hispanic, and non-Hispanic white individuals, 2000–2015. Ann Intern Med. 2018;168(6):453–455. doi:10.7326/M17-1812
8. Crane EH. Highlights of the 2011 Medication Abuse Warning Network (DAWN) Findings on Drug-Associated Emergency Division Visits. Rockville, MD: Heart for Behavioral Health Statistics and High quality, Substance Abuse and Psychological Health Providers Administration; 2013.
9. Nnadi CU, Mimiko OA, McCurtis HL, Cadet JL. Neuropsychiatric results of cocaine use disorders. J Natl Med Assoc. 2005;97(11):1504–1515.
10. Khalsa JH, Elkashef A. Interventions for HIV and hepatitis C virus infections in leisure drug customers. Clin Infect Dis. 2010;50(11):1505–1511. doi:10.1086/652447
11. Simpson DD, Joe GW, Broome KM. A national 5-year follow-up of treatment outcomes for cocaine dependence. Arch Gen Psychiatry. 2002;59(6):538–544. doi:10.1001/archpsyc.59.6.538
12. Williams CT, Latkin CA. Neighborhood socioeconomic standing, private community attributes, and use of heroin and cocaine. Am J Prev Med. 2007;32(6 Suppl):S203–S210. doi:10.1016/j.amepre.2007.02.006
13. Palamar JJ, Davies S, Ompad DC, Cleland CM, Weitzman M. Powder cocaine and crack use in the United States: an examination of threat for arrest and socioeconomic disparities in use. Drug Alcohol Rely. 2015;149:108–116. doi:10.1016/j.drugalcdep.2015.01.029
14. Blumstein A. The infamous 100: 1 crack: powder disparity–the info inform us that it’s time to restore the steadiness. Federal Sentencing Reporter. 2003;16(1):87–92. doi:10.1525/fsr.2003.16.1.87
15. Childress S, Reitzel LR, Maria DS, Kendzor DE, Moisiuc A, Businelle MS. Psychological illness and substance use issues in relation to homelessness onset. Am J Health Behav. 2015;39(4):549–555. doi:10.5993/AJHB.39.4.11
16. Kampman KM. The treatment of cocaine use disorder. Sci Adv. 2019;5(10):eaax1532. doi:10.1126/sciadv.aax1532
17. Chan B, Kondo Okay, Freeman M, Ayers C, Montgomery J, Kansagara D. Pharmacotherapy for cocaine use disorder-a systematic evaluate and meta-analysis. J Gen Intern Med. 2019;34(12):2858–2873. doi:10.1007/s11606-019-05074-8
18. Brandt L, Chao T, Comer SD, Levin FR. Pharmacotherapeutic strategies for treating cocaine use disorder-what do we have now to provide? Dependancy. 2021;116(4):694–710. doi:10.1111/add.15242
19. Buchholz J, Saxon AJ. Drugs to deal with cocaine use disorders: present choices. Curr Opin Psychiatry. 2019;32(4):275–281. doi:10.1097/YCO.0000000000000518
20. American Psychiatric Affiliation. Diagnostic and Statistical Guide of Psychological Problems.
21. Dennis M, Scott CK. Managing addiction as a persistent situation. Addict Sci Clin Pract. 2007;4(1):45–55. doi:10.1151/ascp074145
22. Nelson J, Bundoc-Baronia R, Comiskey G, McGovern TF. Going through Dependancy in America: The Surgeon Common’s Report on Alcohol, Medication, and Health. Psychological Health Providers Administration (US); Workplace of the Surgeon Common (US); 2016.
23. High quality CfBHSa. Outcomes from the 2019 Nationwide Survey on Drug Use and Health: Detailed Tables. Rockville, MD: Substance Abuse and Psychological Health Providers Administration; Division of Health and Human Providers; 2020.
24. Lopez-Quintero C, Cobos JP, Hasin DS. Likelihood and predictors of transition from first use to dependence on nicotine, alcohol, hashish, and cocaine: outcomes of the Nationwide Epidemiologic Survey on Alcohol and Associated Circumstances (NESARC). Drug Alcohol Rely. 2011;115(1–2):120–130. doi:10.1016/j.drugalcdep.2010.11.004
25. Liu Y, Cheong J, Vaddiparti Okay, Cottler LB. The affiliation between amount, frequency and period of cocaine use through the heaviest use interval and DSM-5 cocaine use disorder. Drug Alcohol Rely. 2020;213:108114. doi:10.1016/j.drugalcdep.2020.108114
26. Wagner FA, Anthony JC. From first drug use to drug dependence; developmental durations of threat for dependence upon marijuana, cocaine, and alcohol. Neuropsychopharmacology. 2002;26(4):479–488. doi:10.1016/S0893-133X(01)00367-0
27. Pierce RC, Fant B, Swinford-Jackson SE, Heller EA, Berrettini WH, Wimmer ME. Environmental, genetic and epigenetic contributions to cocaine addiction. Neuropsychopharmacology. 2018;43(7):1471–1480. doi:10.1038/s41386-018-0008-x
28. Goldman D, Oroszi G, Ducci F. The genetics of addictions: uncovering the genes. Nat Rev Genet. 2005;6(7):521–532. doi:10.1038/nrg1635
29. Kendler KS, Karkowski LM, Neale MC, Prescott CA. Illicit psychoactive substance use, heavy use, abuse, and dependence in a US population-based pattern of male twins. Arch Gen Psychiatry. 2000;57(3):261–269. doi:10.1001/archpsyc.57.3.261
30. Kendler KS, Prescott CA. Cocaine use, abuse and dependence in a population-based pattern of feminine twins. Br J Psychiatry. 1998;173:345–350. doi:10.1192/bjp.173.4.345
31. Deak JD, Miller AP, Gizer IR. Genetics of alcohol use disorder: a evaluate. Curr Opin Psychol. 2019;27:56–61. doi:10.1016/j.copsyc.2018.07.012
32. Tsuang MT, Lyons MJ, Harley RM, et al. Genetic and environmental influences on transitions in drug use. Behav Genet. 1999;29(6):473–479. doi:10.1023/A:1021635223370
33. Ystrom E, Reichborn-Kjennerud T, Neale MC, Kendler KS. Genetic and environmental threat elements for illicit substance use and use disorders: joint evaluation of self and co-twin rankings. Behav Genet. 2014;44(1):1–13. doi:10.1007/s10519-013-9626-6
34. Chen Okay, Kandel D. Relationship between extent of cocaine use and dependence amongst adolescents and adults in the United States. Drug Alcohol Rely. 2002;68(1):65–85. doi:10.1016/S0376-8716(02)00086-8
35. Lillie-Blanton M, Anthony JC, Schuster CR. Probing the that means of racial/ethnic group comparisons in crack cocaine smoking. JAMA. 1993;269(8):993–997. doi:10.1001/jama.1993.03500080041029
36. Lewis B, Hoffman L, Garcia CC, Nixon SJ. Race and socioeconomic standing in substance use development and treatment entry. J Ethn Subst Abuse. 2018;17(2):150–166. doi:10.1080/15332640.2017.1336959
37. Moeller FG, Dougherty DM, Barratt ES, Schmitz JM, Swann AC, Grabowski J. The influence of impulsivity on cocaine use and retention in treatment. J Subst Abuse Deal with. 2001;21(4):193–198. doi:10.1016/S0740-5472(01)00202-1
38. Lee SS, Humphreys KL, Flory Okay, Liu R, Glass Okay. Potential affiliation of childhood attention-deficit/hyperactivity disorder (ADHD) and substance use and abuse/dependence: a meta-analytic evaluate. Clin Psychol Rev. 2011;31(3):328–341. doi:10.1016/j.cpr.2011.01.006
39. Tang S, Jones CM, Knowledge A, Lin HC, Bacon S, Houry D. Opposed childhood experiences and stimulant use disorders amongst adults in the United States. Psychiatry Res. 2021;299:113870. doi:10.1016/j.psychres.2021.113870
40. Dokkedal-Silva V, Fernandes GL, Morelhao PK, et al. Sleep, psychiatric and socioeconomic elements related with substance use in a big inhabitants pattern: a cross-sectional examine. Pharmacol Biochem Behav. 2021;210:173274. doi:10.1016/j.pbb.2021.173274
41. Palamar JJ, Ompad DC. Demographic and socioeconomic correlates of powder cocaine and crack use amongst excessive school seniors in the United States. Am J Drug Alcohol Abuse. 2014;40(1):37–43. doi:10.3109/00952990.2013.838961
42. Liu Y, Elliott AL, Serdarevic M, Leeman RF, Cottler LB. A latent class evaluation of the past-30-day substance use patterns amongst lifetime cocaine customers: findings from a community pattern in North Central Florida. Addict Behav Rep. 2019;9:100170. doi:10.1016/j.abrep.2019.100170
43. Florez-Salamanca L, Secades-Villa R, Hasin DS, et al. Likelihood and predictors of transition from abuse to dependence on alcohol, hashish, and cocaine: outcomes from the Nationwide Epidemiologic Survey on Alcohol and Associated Circumstances. Am J Drug Alcohol Abuse. 2013;39(3):168–179. doi:10.3109/00952990.2013.772618
44. Gossop M, Griffiths P, Powis B, Strang J. Cocaine: patterns of use, route of administration, and severity of dependence. Br J Psychiatry. 1994;164(5):660–664. doi:10.1192/bjp.164.5.660
45. Rounsaville BJ, Anton SF, Carroll Okay, Budde D, Prusoff BA, Gawin F. Psychiatric diagnoses of treatment-seeking cocaine abusers. Arch Gen Psychiatry. 1991;48(1):43–51. doi:10.1001/archpsyc.1991.01810250045005
46. Vergara-Moragues E, Gonzalez-Saiz F, Lozano OM, et al. Psychiatric comorbidity in cocaine customers handled in therapeutic community: substance-induced versus unbiased disorders. Psychiatry Res. 2012;200(2–3):734–741. doi:10.1016/j.psychres.2012.07.043
47. Conway KP, Compton W, Stinson FS, Grant BF. Lifetime comorbidity of DSM-IV mood and anxiety disorders and particular drug use disorders: outcomes from the Nationwide Epidemiologic Survey on Alcohol and Associated Circumstances. J Clin Psychiatry. 2006;67(2):247–257. doi:10.4088/jcp.v67n0211
48. Kandel DB, Huang FY, Davies M. Comorbidity between patterns of substance use dependence and psychiatric syndromes. Drug Alcohol Rely. 2001;64(2):233–241. doi:10.1016/S0376-8716(01)00126-0
49. Hunt GE, Malhi GS, Cleary M, Lai HM, Sitharthan T. Comorbidity of bipolar and substance use disorders in national surveys of normal populations, 1990–2015: systematic evaluate and meta-analysis. J Have an effect on Disord. 2016;206:321–330. doi:10.1016/j.jad.2016.06.051
50. Kedia S, Promote MA, Relyea G. Mono- versus polydrug abuse patterns amongst publicly funded shoppers. Subst Abuse Deal with Prev Coverage. 2007;2:33. doi:10.1186/1747-597X-2-33
51. Kariisa M, Scholl L, Wilson N, Seth P, Hoots B. Drug overdose deaths involving cocaine and psychostimulants with abuse potential – United States, 2003–2017. MMWR Morb Mortal Wkly Rep. 2019;68(17):388–395. doi:10.15585/mmwr.mm6817a3
52. Pennings EJ, Leccese AP, Wolff FA. Results of concurrent use of alcohol and cocaine. Dependancy. 2002;97(7):773–783. doi:10.1046/j.1360-0443.2002.00158.x
53. Budney AJ, Higgins ST, Hughes JR, Bickel WK. Nicotine and caffeine use in cocaine-dependent people. J Subst Abuse. 1993;5(2):117–130. doi:10.1016/0899-3289(93)90056-H
54. Richter KP, Ahluwalia HK, Mosier MC, Nazir N, Ahluwalia JS. A population-based examine of cigarette smoking amongst illicit drug customers in the United States. Dependancy. 2002;97(7):861–869. doi:10.1046/j.1360-0443.2002.00162.x
55. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and different drug abuse. Outcomes from the Epidemiologic Catchment Space (ECA) examine. JAMA. 1990;264(19):2511–2518. doi:10.1001/jama.1990.03450190043026
56. Rounsaville BJ. Remedy of cocaine dependence and depression. Biol Psychiatry. 2004;56(10):803–809. doi:10.1016/j.biopsych.2004.05.009
57. Poling J, Kosten TR, Sofuoglu M. Remedy final result predictors for cocaine dependence. Am J Drug Alcohol Abuse. 2007;33(2):191–206. doi:10.1080/00952990701199416
58. Carroll KM, Energy ME, Bryant Okay, Rounsaville BJ. One-year follow-up standing of treatment-seeking cocaine abusers. Psychopathology and dependence severity as predictors of final result. J Nerv Ment Dis. 1993;181(2):71–79. doi:10.1097/00005053-199302000-00001
59. Merikangas KR, Kalaydjian A. Magnitude and influence of comorbidity of mental disorders from epidemiologic surveys. Curr Opin Psychiatry. 2007;20(4):353–358. doi:10.1097/YCO.0b013e3281c61dc5
60. Newton TF, Kalechstein AD, Tervo KE, Ling W. Irritability following abstinence from cocaine predicts euphoric results of cocaine administration. Addict Behav. 2003;28(4):817–821. doi:10.1016/S0306-4603(01)00273-8
61. Uslaner J, Kalechstein A, Richter T, Ling W, Newton T. Affiliation of depressive symptoms throughout abstinence with the subjective excessive produced by cocaine. Am J Psychiatry. 1999;156(9):1444–1446. doi:10.1176/ajp.156.9.1444
62. Elman I, Karlsgodt KH, Gastfriend DR, Chabris CF, Breiter HC. Cocaine-primed craving and its relationship to depressive symptomatology in people with cocaine dependence. J Psychopharmacol. 2002;16(2):163–167. doi:10.1177/026988110201600207
63. Helmus TC, Downey KK, Wang LM, Rhodes GL, Schuster CR. The connection between self-reported cocaine withdrawal symptoms and historical past of depression. Addict Behav. 2001;26(3):461–467. doi:10.1016/S0306-4603(00)00105-2
64. McKay JR, Pettinati HM, Morrison R, Feeley M, Mulvaney FD, Gallop R. Relation of depression diagnoses to 2-year outcomes in cocaine-dependent patients in a randomized continuing care examine. Psychol Addict Behav. 2002;16(3):225–235. doi:10.1037/0893-164X.16.3.225
65. Abdalla RR, Miguel AC, Brietzke E, Caetano R, Laranjeira R, Madruga CS. Suicidal behavior amongst substance customers: information from the Second Brazilian Nationwide Alcohol and Drug Survey (II BNADS). Braz J Psychiatry. 2019;41(5):437–440. doi:10.1590/1516-4446-2018-0054
66. Bohnert KM, Ilgen MA, Louzon S, McCarthy JF, Katz IR. Substance use disorders and the chance of suicide mortality amongst males and girls in the US Veterans Health Administration. Dependancy. 2017;112(7):1193–1201. doi:10.1111/add.13774
67. Pavarin RM, Fioritti A. Mortality traits amongst cocaine customers handled between 1989 and 2013 in Northern Italy: outcomes of a longitudinal examine. J Psychoactive Medication. 2018;50(1):72–80. doi:10.1080/02791072.2017.1365976
68. Khantzian EJ. The self-medication speculation of addictive disorders: focus on heroin and cocaine dependence. Am J Psychiatry. 1985;142(11):1259–1264.
69. Khantzian EJ. Self-regulation and self-medication elements in alcoholism and the addictions. Similarities and variations. Latest Dev Alcohol. 1990;8:255–271.
70. Kendler KS, Jacobson KC, Prescott CA, Neale MC. Specificity of genetic and environmental threat elements for use and abuse/dependence of hashish, cocaine, hallucinogens, sedatives, stimulants, and opiates in male twins. Am J Psychiatry. 2003;160(4):687–695. doi:10.1176/appi.ajp.160.4.687
71. Grant BF, Saha TD, Ruan WJ, et al. Epidemiology of DSM-5 drug use disorder: outcomes from the national epidemiologic survey on alcohol and associated conditions-III. JAMA Psychiatry. 2016;73(1):39–47. doi:10.1001/jamapsychiatry.2015.2132
72. McCance-Katz EF, Carroll KM, Rounsaville BJ. Gender variations in treatment-seeking cocaine abusers–implications for treatment and prognosis. Am J Addict. 1999;8(4):300–311. doi:10.1080/105504999305703
73. Pedraz M, Araos P, Garcia-Marchena N, et al. Intercourse variations in psychiatric comorbidity and plasma biomarkers for cocaine addiction in abstinent cocaine-addicted topics in outpatient settings. Entrance Psychiatry. 2015;6:17. doi:10.3389/fpsyt.2015.00017
74. Najavits LM, Lester KM. Gender variations in cocaine dependence. Drug Alcohol Rely. 2008;97(1–2):190–194. doi:10.1016/j.drugalcdep.2008.04.012
75. Requena-Ocana N, Flores-Lopez M, Martin AS, et al. Affect of gender and education on cocaine customers in an outpatient cohort in Spain. Sci Rep. 2021;11(1):20928. doi:10.1038/s41598-021-00472-7
76. Wong CJ, Badger GJ, Sigmon SC, Higgins ST. Inspecting potential gender variations amongst cocaine-dependent outpatients. Exp Clin Psychopharmacol. 2002;10(3):316–323. doi:10.1037/1064-1297.10.3.316
77. Terry-McElrath YM, O’Malley PM, Johnston LD. Causes for drug use amongst American youth by consumption level, gender, and race/ethnicity: 1976–2005. J Drug Points. 2009;39(3):677–714. doi:10.1177/002204260903900310
78. Boutrel B, Koob GF. What retains us awake: the neuropharmacology of stimulants and wakefulness-promoting drugs. Sleep. 2004;27(6):1181–1194. doi:10.1093/sleep/27.6.1181
79. Harzke AJ, Williams ML, Bowen AM. Binge use of crack cocaine and sexual threat behaviors amongst African-American, HIV-positive customers. AIDS Behav. 2009;13(6):1106–1118. doi:10.1007/s10461-008-9450-9
80. Roy E, Arruda N, Jutras-Aswad D, et al. Inspecting the hyperlink between cocaine binging and individual, social and behavioral elements amongst street-based cocaine customers. Addict Behav. 2017;68:66–72. doi:10.1016/j.addbeh.2017.01.012
81. Sofuoglu M, Dudish-Poulsen S, Brown SB, Hatsukami DK. Affiliation of cocaine withdrawal symptoms with extra extreme dependence and enhanced subjective response to cocaine. Drug Alcohol Rely. 2003;69(3):273–282. doi:10.1016/S0376-8716(02)00328-9
82. Schuckit MA, Daeppen JB, Danko GP, et al. Medical implications for 4 drugs of the DSM-IV distinction between substance dependence with and and not using a physiological element. Am J Psychiatry. 1999;156(1):41–49. doi:10.1176/ajp.156.1.41
83. Berridge KC, Robinson TE. Liking, wanting, and the incentive-sensitization idea of addiction. Am Psychol. 2016;71(8):670–679. doi:10.1037/amp0000059
84. Cox WM, Fadardi JS, Intriligator JM, Klinger E. Attentional bias modification for addictive behaviors: clinical implications. CNS Spectr. 2014;19(3):215–224. doi:10.1017/S1092852914000091
85. Potvin S, Stavro Okay, Rizkallah E, Pelletier J. Cocaine and cognition: a scientific quantitative evaluate. J Addict Med. 2014;8(5):368–376. doi:10.1097/ADM.0000000000000066
86. Liu S, Lane SD, Schmitz JM, Waters AJ, Cunningham KA, Moeller FG. Relationship between attentional bias to cocaine-related stimuli and impulsivity in cocaine-dependent topics. Am J Drug Alcohol Abuse. 2011;37(2):117–122. doi:10.3109/00952990.2010.543204
87. Leeman RF, Robinson CD, Waters AJ, Sofuoglu M. A important evaluate of the literature on attentional bias in cocaine use disorder and options for future analysis. Exp Clin Psychopharmacol. 2014;22(6):469–483. doi:10.1037/a0037806
88. Jovanovski D, Erb S, Zakzanis KK. Neurocognitive deficits in cocaine customers: a quantitative evaluate of the proof. J Clin Exp Neuropsychol. 2005;27(2):189–204. doi:10.1080/13803390490515694
89. Goldstein RZ, Leskovjan AC, Hoff AL, et al. Severity of neuropsychological impairment in cocaine and alcohol addiction: affiliation with metabolism in the prefrontal cortex. Neuropsychologia. 2004;42(11):1447–1458. doi:10.1016/j.neuropsychologia.2004.04.002
90. Bolla Okay, Ernst M, Kiehl Okay, et al. Prefrontal cortical dysfunction in abstinent cocaine abusers. J Neuropsychiatry Clin Neurosci. 2004;16(4):456–464. doi:10.1176/jnp.16.4.456
91. Volkow ND, Mullani N, Gould KL, Adler S, Krajewski Okay. Cerebral blood circulation in persistent cocaine customers: a examine with positron emission tomography. Br J Psychiatry. 1988;152:641–648. doi:10.1192/bjp.152.5.641
92. Volkow ND, Fowler JS, Wolf AP, et al. Modifications in mind glucose metabolism in cocaine dependence and withdrawal. Am J Psychiatry. 1991;148(5):621–626.
93. Wagner M, Schulze-Rauschenbach S, Petrovsky N, et al. Neurocognitive impairments in non-deprived people who smoke–outcomes from a population-based multi-center examine on smoking-related behavior. Addict Biol. 2013;18(4):752–761. doi:10.1111/j.1369-1600.2011.00429.x
94. Bolla KI, Rothman R, Cadet JL. Dose-related neurobehavioral results of persistent cocaine use. J Neuropsychiatry Clin Neurosci. 1999;11(3):361–369. doi:10.1176/jnp.11.3.361
95. Aharonovich E, Nunes E, Hasin D. Cognitive impairment, retention and abstinence amongst cocaine abusers in cognitive-behavioral treatment. Drug Alcohol Rely. 2003;71(2):207–211. doi:10.1016/S0376-8716(03)00092-9
96. Verdejo-Garcia A, Betanzos-Espinosa P, Lozano OM, et al. Self-regulation and treatment retention in cocaine dependent people: a longitudinal examine. Drug Alcohol Rely. 2012;122(1–2):142–148. doi:10.1016/j.drugalcdep.2011.09.025
97. Chambers CD, Garavan H, Bellgrove MA. Insights into the neural foundation of response inhibition from cognitive and clinical neuroscience. Neurosci Biobehav Rev. 2009;33(5):631–646. doi:10.1016/j.neubiorev.2008.08.016
98. Posner MI, Rothbart MK. Analysis on consideration networks as a mannequin for the combination of psychological science. Annu Rev Psychol. 2007;58:1–23. doi:10.1146/annurev.psych.58.110405.085516
99. Volkow ND, Morales M. The mind on drugs: from reward to addiction. Cell. 2015;162(4):712–725. doi:10.1016/j.cell.2015.07.046
100. Volkow ND, Wang GJ, Fowler JS. Imaging research of cocaine in the human mind and research of the cocaine addict. Ann N Y Acad Sci. 1997;820:
101. Pani PP, Trogu E, Vecchi S, Amato L, Antidepressants for cocaine dependence and problematic cocaine use. Cochrane Database Syst Rev. 2011;(12):CD002950. doi:10.1002/14651858.CD002950.pub3
102. Ronsley C, Nolan S, Knight R, et al. Remedy of stimulant use disorder: a scientific evaluate of opinions. PLoS One. 2020;15(6):e0234809. doi:10.1371/journal.pone.0234809
103. Moeller FG, Schmitz JM, Steinberg JL, et al. Citalopram mixed with behavioral therapy reduces cocaine use: a double-blind, placebo-controlled trial. Am J Drug Alcohol Abuse. 2007;33(3):367–378. doi:10.1080/00952990701313686
104. Oliveto A, Poling J, Mancino MJ, et al. Sertraline delays relapse in lately abstinent cocaine-dependent patients with depressive symptoms. Dependancy. 2012;107(1):131–141. doi:10.1111/j.1360-0443.2011.03552.x
105. Castells X, Cunill R, Perez-Mana C, Vidal X, Capella D. Psychostimulant drugs for cocaine dependence. Cochrane Database Syst Rev. 2016;9:CD007380. doi:10.1002/14651858.CD007380.pub4
106. Poling J, Oliveto A, Petry N, et al. Six-month trial of bupropion with contingency management for cocaine dependence in a methadone-maintained inhabitants. Arch Gen Psychiatry. 2006;63(2):219–228. doi:10.1001/archpsyc.63.2.219
107. Grabowski J, Rhoades H, Stotts A, et al. Agonist-like or antagonist-like treatment for cocaine dependence with methadone for heroin dependence: two double-blind randomized clinical trials. Neuropsychopharmacology. 2004;29(5):969–981. doi:10.1038/sj.npp.1300392
108. Nuijten M, Blanken P, van de Wetering B, Nuijen B, van den Brink W, Hendriks VM. Sustained-release dexamfetamine in the treatment of persistent cocaine-dependent patients on heroin-assisted treatment: a randomised, double-blind, placebo-controlled trial. Lancet. 2016;387(10034):2226–2234. doi:10.1016/S0140-6736(16)00205-1
109. Soares BG, Lima MS, Reisser AA, Farrell M, Dopamine agonists for cocaine dependence. Cochrane Database Syst Rev. 2003;(2):CD003352. doi:10.1002/14651858.CD003352
110. Minozzi S, Amato L, Pani PP, et al. Dopamine agonists for the treatment of cocaine dependence. Cochrane Database Syst Rev. 2015;(5):CD003352. doi:10.1002/14651858.CD003352.pub4
111. Handelsman L, Limpitlaw L, Williams D, Schmeidler J, Paris P, Stimmel B. Amantadine doesn’t scale back cocaine use or craving in cocaine-dependent methadone upkeep patients. Drug Alcohol Rely. 1995;39(3):173–180. doi:10.1016/0376-8716(95)01154-9
112. Kampman KM, Volpicelli JR, Alterman AI, Cornish J, O’Brien CP. Amantadine in the treatment of cocaine-dependent patients with extreme withdrawal symptoms. Am J Psychiatry. 2000;157(12):2052–2054. doi:10.1176/appi.ajp.157.12.2052
113. Volkow ND, Fowler JS, Logan J, et al. Results of modafinil on dopamine and dopamine transporters in the male human mind: clinical implications. JAMA. 2009;301(11):1148–1154. doi:10.1001/jama.2009.351
114. Kalechstein AD, Mahoney JJ, Yoon JH, Bennett R, De la Garza R. Modafinil, however not escitalopram, improves working reminiscence and sustained consideration in long-term, high-dose cocaine customers. Neuropharmacology. 2013;64:472–478. doi:10.1016/j.neuropharm.2012.06.064
115. Anderson AL, Reid MS, Li SH, et al. Modafinil for the treatment of cocaine dependence. Drug Alcohol Rely. 2009;104(1–2):133–139. doi:10.1016/j.drugalcdep.2009.04.015
116. Dackis CA, Kampman KM, Lynch KG, Pettinati HM, O’Brien CP. A double-blind, placebo-controlled trial of modafinil for cocaine dependence. Neuropsychopharmacology. 2005;30(1):205–211. doi:10.1038/sj.npp.1300600
117. Dackis CA, Kampman KM, Lynch KG, et al. A double-blind, placebo-controlled trial of modafinil for cocaine dependence. J Subst Abuse Deal with. 2012;43(3):303–312. doi:10.1016/j.jsat.2011.12.014
118. Sangroula D, Motiwala F, Wagle B, Shah VC, Hagi Okay, Lippmann S. Modafinil treatment of cocaine dependence: a scientific evaluate and meta-analysis. Subst Use Misuse. 2017;52(10):1292–1306. doi:10.1080/10826084.2016.1276597
119. Indave BI, Minozzi S, Pani PP, Amato L. Antipsychotic drugs for cocaine dependence. Cochrane Database Syst Rev. 2016;3:CD006306. doi:10.1002/14651858.CD006306.pub3
120. Drake RE, Xie H, McHugo GJ, Inexperienced AI. The consequences of clozapine on alcohol and drug use disorders amongst patients with schizophrenia. Schizophr Bull. 2000;26(2):441–449. doi:10.1093/oxfordjournals.schbul.a033464
121. Zimmet SV, Strous RD, Burgess ES, Kohnstamm S, Inexperienced AI. Results of clozapine on substance use in patients with schizophrenia and schizoaffective disorder: a retrospective survey. J Clin Psychopharmacol. 2000;20(1):94–98. doi:10.1097/00004714-200002000-00016
122. Minozzi S, Cinquini M, Amato L, et al. Anticonvulsants for cocaine dependence. Cochrane Database Syst Rev. 2015;2015(4):CD006754.
123. Baldacara L, Cogo-Moreira H, Parreira BL, et al. Efficacy of topiramate in the treatment of crack cocaine dependence: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry. 2016;77(3):398–406. doi:10.4088/JCP.14m09377
124. Petrakis IL, Carroll KM, Nich C, et al. Disulfiram treatment for cocaine dependence in methadone-maintained opioid addicts. Dependancy. 2000;95(2):219–228. doi:10.1046/j.1360-0443.2000.9522198.x
125. Pettinati HM, Kampman KM, Lynch KG, et al. A double blind, placebo-controlled trial that mixes disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence. Addict Behav. 2008;33(5):651–667. doi:10.1016/j.addbeh.2007.11.011
126. Carroll KM, Fenton LR, Ball SA, et al. Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients: a randomized placebo-controlled trial. Arch Gen Psychiatry. 2004;61(3):264–272. doi:10.1001/archpsyc.61.3.264
127. Dakwar E, Nunes EV, Hart CL, et al. A single ketamine infusion mixed with mindfulness-based behavioral modification to deal with cocaine dependence: a randomized clinical trial. Am J Psychiatry. 2019;176(11):923–930. doi:10.1176/appi.ajp.2019.18101123
128. Carroll KM. Remedy Manuals for Drug Dependancy, Guide 1: A Cognitive-Behavioral Strategy: Treating Cocaine Dependancy. Nationwide Institute on Drug Abuse; 1998:55–65.
129. Higgins ST, Delaney DD, Budney AJ, et al. A behavioral approach to attaining preliminary cocaine abstinence. Am J Psychiatry. 1991;148(9):1218–1224.
130. Higgins ST, Kurti AN, Davis DR. Voucher-based contingency management is efficacious however underutilized in treating addictions. Perspect Behav Sci. 2019;42(3):501–524. doi:10.1007/s40614-019-00216-z
131. Stitzer M, Bigelow G. Contingency management in a methadone upkeep program: availability of reinforcers. Int J Addictions. 1978;13(5):737–746. doi:10.3109/10826087809039299
132. Petry NM, Alessi SM, Ledgerwood DM. Contingency management delivered by community therapists in outpatient settings. Drug Alcohol Rely. 2012;122(1–2):86–92. doi:10.1016/j.drugalcdep.2011.09.015
133. Carroll KM, Rounsaville BJ, Nich C, Gordon LT, Wirtz PW, Gawin F. One-year follow-up of psychotherapy and pharmacotherapy for cocaine dependence. Delayed emergence of psychotherapy results. Arch Gen Psychiatry. 1994;51(12):989–997. doi:10.1001/archpsyc.1994.03950120061010
134. Carroll KM, Nich C, Ball SA, McCance E, Rounsavile BJ. Remedy of cocaine and alcohol dependence with psychotherapy and disulfiram. Dependancy. 1998;93(5):713–727. doi:10.1046/j.1360-0443.1998.9357137.x
135. Stitzer ML, Bickel WK, Bigelow GE, Liebson IA. Impact of methadone dose contingencies on urinalysis check outcomes of polydrug-abusing methadone-maintenance patients. Drug Alcohol Rely. 1986;18(4):341–348. doi:10.1016/0376-8716(86)90097-9
136. Carroll KM. Misplaced in translation? Transferring contingency management and cognitive behavioral therapy into clinical observe. Ann N Y Acad Sci. 2014;1327(1):94. doi:10.1111/nyas.12501
137. Stitzer ML, Grabowski J, Henningfield JE. Behavioral intervention techniques in drug abuse treatment: abstract of dialogue. NIDA analysis monograph. 1984.
138. Budney AJ, Higgins ST. Remedy Guide for Drug Dependancy Guide 2: A Neighborhood Reinforcement Plus Vouchers Strategy: Treating Cocaine Dependancy. Rockville, MD: Nationwide Institute on Drug Abuse; 1998.
139. Heil SH, Davis DR, Arger CA, Higgins ST. Contingency management and the community reinforcement approach. In: Miller SC, Fiellin DA, Rosenthal RN, Saitz R, editors. The ASAM Ideas of Dependancy Drugs.
140. Higgins ST, Budney AJ, Bickel WK, Foerg FE, Donham R, Badger GJ. Incentives enhance final result in outpatient behavioral treatment of cocaine dependence. Arch Gen Psychiatry. 1994;51(7):568–576. doi:10.1001/archpsyc.1994.03950070060011
141. Petry NM. Contingency Administration for Substance Abuse Remedy: A Information to Implementing This Proof-Based mostly Observe. Routledge; 2013.
142. Petry NM, Martin B, Cooney JL, Kranzler HR. Give them prizes and they are going to come: contingency management for treatment of alcohol dependence. J Seek the advice of Clin Psychol. 2000;68(2):250. doi:10.1037/0022-006X.68.2.250
143. Petry NM, Barry D, Alessi SM, Rounsaville BJ, Carroll KM. A randomized trial adapting contingency management targets based mostly on preliminary abstinence standing of cocaine-dependent patients. J Seek the advice of Clin Psychol. 2012;80(2):276. doi:10.1037/a0026883
144. Petry NM, Weinstock J, Alessi SM. A randomized trial of contingency management delivered in the context of group counseling. J Seek the advice of Clin Psychol. 2011;79(5):686. doi:10.1037/a0024813
145. Lussier JP, Heil SH, Mongeon JA, Badger GJ, Higgins ST. A meta‐evaluation of voucher‐based mostly reinforcement therapy for substance use disorders. Dependancy. 2006;101(2):192–203. doi:10.1111/j.1360-0443.2006.01311.x
146. Higgins ST, Heil SH, Dantona R, Donham R, Matthews M, Badger GJ. Results of various the financial worth of voucher‐based mostly incentives on abstinence achieved throughout and following treatment amongst cocaine‐dependent outpatients. Dependancy. 2007;102(2):271–281. doi:10.1111/j.1360-0443.2006.01664.x
147. Higgins ST, Wong CJ, Badger GJ, Ogden DEH, Dantona RL. Contingent reinforcement will increase cocaine abstinence throughout outpatient treatment and 1 yr of follow-up. J Seek the advice of Clin Psychol. 2000;68(1):64. doi:10.1037/0022-006X.68.1.64
148. Bentzley BS, Han SS, Neuner S, Humphreys Okay, Kampman KM, Halpern CH. Comparability of treatments for cocaine use disorder amongst adults: a scientific evaluate and meta-analysis. JAMA Network Open. 2021;4(5):e218049–e218049. doi:10.1001/jamanetworkopen.2021.8049
149. De Crescenzo F, Ciabattini M, D’Alò GL, et al. Comparative efficacy and acceptability of psychosocial interventions for people with cocaine and amphetamine addiction: a scientific evaluate and community meta-analysis. PLoS Med. 2018;15(12):e1002715. doi:10.1371/journal.pmed.1002715
150. DePhilippis D, Petry NM, Bonn-Miller MO, Rosenbach SB, McKay JR. The national implementation of Contingency Administration (CM) in the department of veterans affairs: attendance at CM classes and substance use outcomes. Drug Alcohol Rely. 2018;185:367–373. doi:10.1016/j.drugalcdep.2017.12.020
151. Farronato NS, Dürsteler-MacFarland KM, Wiesbeck GA, Petitjean SA. A scientific evaluate evaluating cognitive-behavioral therapy and contingency management for cocaine dependence. J Addict Dis. 2013;32(3):274–287. doi:10.1080/10550887.2013.824328
152. Petry NM, Alessi SM, Hanson T, Sierra S. Randomized trial of contingent prizes versus vouchers in cocaine-using methadone patients. J Seek the advice of Clin Psychol. 2007;75(6):983. doi:10.1037/0022-006X.75.6.983
153. Rash CJ, Alessi SM, Petry NM. Cocaine abusers with and with out alcohol dependence reply equally effectively to contingency management treatments. Exp Clin Psychopharmacol. 2008;16(4):275. doi:10.1037/a0012787
154. Weiss LM, Petry NM. Interplay results of age and contingency management treatments in cocaine-dependent outpatients. Exp Clin Psychopharmacol. 2011;19(2):173. doi:10.1037/a0023031
155. Petry NM, Peirce JM, Stitzer ML, et al. Impact of prize-based incentives on outcomes in stimulant abusers in outpatient psychosocial treatment programs: a national drug abuse treatment clinical trials community examine. Arch Gen Psychiatry. 2005;62(10):1148–1156. doi:10.1001/archpsyc.62.10.1148
156. Petry NM. Contingency management treatments: controversies and challenges. 2010.
157. Roman P, Blum T. Nationwide Remedy Heart Examine: Abstract Report. Institute for Behavioral Analysis, College of Georgia; 1997.
158. Roman PM, Johnson J. Nationwide Remedy Heart Examine Abstract Report: Non-public Remedy Facilities. Athens, GA: Institute for Behavioral Analysis, College of Georgia; 2004.
159. Rash CJ, Petry NM, Kirby KC, Martino S, Roll J, Stitzer ML. Figuring out provider beliefs associated to contingency management adoption utilizing the contingency management beliefs questionnaire. Drug Alcohol Rely. 2012;121(3):205–212. doi:10.1016/j.drugalcdep.2011.08.027
160. Dutra L, Stathopoulou G, Basden SL, Leyro TM, Powers MB, Otto MW. A meta-analytic evaluate of psychosocial interventions for substance use disorders. Am J Psychiatry. 2008;165(2):179–187. doi:10.1176/appi.ajp.2007.06111851
161. Prendergast M, Podus D, Finney J, Greenwell L, Roll J. Contingency management for treatment of substance use disorders: a meta-analysis. Dependancy. 2006;101(11):1546–1560. doi:10.1111/j.1360-0443.2006.01581.x
162. Higgins ST, Wong CJ, Badger GJ, Ogden DE, Dantona RL. Contingent reinforcement will increase cocaine abstinence throughout outpatient treatment and 1 yr of follow-up. J Seek the advice of Clin Psychol. 2000;68(1):64–72.
163. Rawson RA, Huber A, McCann M, et al. A comparability of contingency management and cognitive-behavioral approaches throughout methadone upkeep treatment for cocaine dependence. Arch Gen Psychiatry. 2002;59(9):817–824. doi:10.1001/archpsyc.59.9.817
164. Rawson RA, McCann MJ, Flammino F, et al. A comparability of contingency management and cognitive‐behavioral approaches for stimulant‐dependent people. Dependancy. 2006;101(2):267–274. doi:10.1111/j.1360-0443.2006.01312.x
165. Petry NM, Tedford J, Austin M, Nich C, Carroll KM, Rounsaville BJ. Prize reinforcement contingency management for treating cocaine customers: how low can we go, and with whom? Dependancy. 2004;99(3):349–360. doi:10.1111/j.1360-0443.2003.00642.x
166. Chaney EF, O’Leary MR, Marlatt GA. Talent coaching with alcoholics. J Seek the advice of Clin Psychol. 1978;46(5):1092. doi:10.1037/0022-006X.46.5.1092
167. Marlatt GA, Donovan DM. Relapse Prevention: Upkeep Methods in the Remedy of Addictive Behaviors. Guilford Press; 2005.
168. DeMarce J, Gnys M, Raffa S, Karlin B. Cognitive Behavioral Remedy for Substance Use Problems Amongst Veterans: Therapist Guide. Washington, DC: US Division of Veterans Affairs; 2014.
169. McHugh RK, Kim J, Perrins SP, Weiss RD. Group therapy for substance use disorders. In: Textbook of Dependancy Remedy. Springer; 2021:433–446.
170. Petitjean SA, Dürsteler-MacFarland KM, Krokar MC, et al. A randomized, controlled trial of mixed cognitive-behavioral therapy plus prize-based contingency management for cocaine dependence. Drug Alcohol Rely. 2014;145:94–100. doi:10.1016/j.drugalcdep.2014.09.785
171. Carroll Okay, Nich C, Rounsaville B. Use of observer and therapist rankings to monitor supply of coping skills treatment for cocaine abusers: utility of therapist session checklists. Psychother Res. 1998;8:307–320. doi:10.1093/ptr/8.3.307
172. Gonzalez VM, Schmitz JM, DeLaune KA. The position of homework in cognitive-behavioral therapy for cocaine dependence. J Seek the advice of Clin Psychol. 2006;74(3):633. doi:10.1037/0022-006X.74.3.633
173. Carroll KM, Nich C, Ball SA. Observe makes progress? Homework assignments and final result in treatment of cocaine dependence. J Seek the advice of Clin Psychol. 2005;73(4):749. doi:10.1037/0022-006X.73.4.749
174. Decker SE, Kiluk BD, Frankforter T, Babuscio T, Nich C, Carroll KM. Simply exhibiting up is just not sufficient: homework adherence and final result in cognitive–behavioral therapy for cocaine dependence. J Seek the advice of Clin Psychol. 2016;84(10):907. doi:10.1037/ccp0000126
175. Carroll KM, Nich C, Sifry RL, et al. A normal system for evaluating therapist adherence and competence in psychotherapy analysis in the addictions. Drug Alcohol Rely. 2000;57(3):225–238. doi:10.1016/S0376-8716(99)00049-6
176. Sholomskas DE, Syracuse-Siewert G, Rounsaville BJ, Ball SA, Nuro KF, Carroll KM. We don’t prepare in useless: a dissemination trial of three strategies of coaching clinicians in cognitive-behavioral therapy. J Seek the advice of Clin Psychol. 2005;73(1):106. doi:10.1037/0022-006X.73.1.106
177. Santa Ana EJ, Martino S, Ball SA, Nich C, Frankforter TL, Carroll KM. What is common about “treatment-as-usual”? Knowledge from two multisite effectiveness trials. J Subst Abuse Deal with. 2008;35(4):369–379. doi:10.1016/j.jsat.2008.01.003
178. Carroll KM, Ball SA, Martino S, et al. Laptop-assisted supply of cognitive-behavioral therapy for addiction: a randomized trial of CBT4CBT. Am J Psychiatry. 2008;165(7):881–888. doi:10.1176/appi.ajp.2008.07111835
179. Carroll KM. CBT4CBT, LLC: builders of pc based mostly coaching for cognitive behavioral therapy; 2019. Out there from: https://cbt4cbt.com/.
180. Kiluk BD, DeVito EE, Buck MB, Hunkele Okay, Nich C, Carroll KM. Impact of computerized cognitive behavioral therapy on acquisition of coping skills amongst cocaine-dependent people enrolled in methadone upkeep. J Subst Abuse Deal with. 2017;82:87–92. doi:10.1016/j.jsat.2017.09.011
181. Kiluk BD, Nich C, Buck MB, et al. Randomized clinical trial of computerized and clinician-delivered CBT in comparability with customary outpatient treatment for substance use disorders: primary within-treatment and follow-up outcomes. Am J Psychiatry. 2018;175(9):853–863. doi:10.1176/appi.ajp.2018.17090978
182. Carroll KM, Ball SA, Martino S, Nich C, Babuscio TA, Rounsaville BJ. Enduring results of a computer-assisted coaching program for cognitive behavioral therapy: a 6-month follow-up of CBT4CBT. Drug Alcohol Rely. 2009;100(1–2):178–181. doi:10.1016/j.drugalcdep.2008.09.015
183. Carroll KM, Kiluk BD, Nich C, et al. Laptop-assisted supply of cognitive-behavioral therapy: efficacy and sturdiness of CBT4CBT amongst cocaine-dependent people maintained on methadone. Am J Psychiatry. 2014;171(4):436–444. doi:10.1176/appi.ajp.2013.13070987
184. Carroll KM, Nich C, DeVito EE, Shi JM, Sofuoglu M. Galantamine and computerized cognitive behavioral therapy for cocaine dependence: a randomized clinical trial. J Clin Psychiatry. 2018;79(1):17m11669. doi:10.4088/JCP.17m11669
185. DeVito EE, Kiluk BD, Nich C, Mouratidis M, Carroll KM. Drug stroop: mechanisms of response to computerized cognitive behavioral therapy for cocaine dependence in a randomized clinical trial. Drug Alcohol Rely. 2018;183:162–168. doi:10.1016/j.drugalcdep.2017.10.022
186. Olmstead TA, Ostrow CD, Carroll KM. Price-effectiveness of computer-assisted coaching in cognitive-behavioral therapy as an adjunct to customary care for addiction. Drug Alcohol Rely. 2010;110(3):200–207. doi:10.1016/j.drugalcdep.2010.02.022
187. Horsfall J, Cleary M, Hunt GE, Walter G. Psychosocial treatments for people with co-occurring extreme mental sicknesses and substance use disorders (dual diagnosis): a evaluate of empirical proof. Harv Rev Psychiatry. 2009;17(1):24–34. doi:10.1080/10673220902724599
188. Drake RE, Essock SM, Shaner A, et al. Implementing dual diagnosis companies for shoppers with extreme mental illness. Psychiatr Serv. 2001;52(4):469–476. doi:10.1176/appi.ps.52.4.469
189. Mangrum LF, Spence RT, Lopez M. Built-in versus parallel treatment of co-occurring psychiatric and substance use disorders. J Subst Abuse Deal with. 2006;30(1):79–84. doi:10.1016/j.jsat.2005.10.004
190. Hunt GE, Siegfried N, Morley Okay, Brooke-Sumner C, Cleary M. Psychosocial interventions for people with each extreme mental illness and substance misuse. Cochrane Database Syst Rev. 2019;12:CD001088. doi:10.1002/14651858.CD001088.pub4
191. Mueser KT, Torrey WC, Lynde D, Singer P, Drake RE. Implementing evidence-based practices for people with extreme mental illness. Behav Modif. 2003;27(3):387–411. doi:10.1177/0145445503027003007
192. Lambert-Harris C, Saunders EC, McGovern MP, Xie H. Organizational capability to deal with co-occurring substance use and psychiatric disorders: assessing variation by level of care. J Addict Med. 2013;7(1):25–32. doi:10.1097/ADM.0b013e318276e7a4
193. McGovern MP, Lambert-Harris C, Gotham HJ, Claus RE, Xie H. Twin diagnosis functionality in mental health and addiction treatment companies: an evaluation of programs throughout a number of state programs. Adm Coverage Ment Health. 2014;41(2):205–214. doi:10.1007/s10488-012-0449-1
194. Kosten T, Oliveto A, Feingold A, et al. Desipramine and contingency management for cocaine and opiate dependence in buprenorphine maintained patients. Drug Alcohol Rely. 2003;70(3):315–325. doi:10.1016/S0376-8716(03)00032-2
195. Schmitz JM, Rhoades HM, Elk R, Creson D, Hussein I, Grabowski J. Medicine take-home doses and contingency management. Exp Clin Psychopharmacol. 1998;6(2):162–168. doi:10.1037/1064-1297.6.2.162
196. Sofuoglu M, DeVito EE, Waters AJ, Carroll KM. Cognitive operate as a transdiagnostic treatment goal in stimulant use disorders. J Twin Diagn. 2016;12(1):90–106. doi:10.1080/15504263.2016.1146383
197. Schumann G, Binder EB, Holte A, et al. Stratified medicine for mental disorders. Eur Neuropsychopharmacol. 2014;24(1):5–50. doi:10.1016/j.euroneuro.2013.09.010
198. Wiers RW, Gladwin TE, Hofmann W, Salemink E, Ridderinkhof KR. Cognitive bias modification and cognitive management coaching in addiction and associated psychopathology: mechanisms, clinical views, and methods ahead. Clin Psychol Sci. 2013;1:912–212. doi:10.1177/2167702612466547
199. Mayer AR, Wilcox CE, Dodd AB, et al. The efficacy of consideration bias modification therapy in cocaine use disorders. Am J Drug Alcohol Abuse. 2016;42(4):459–468. doi:10.3109/00952990.2016.1151523
200. Marhe R, Waters AJ, van de Wetering BJ, Franken IH. Implicit and specific drug-related cognitions throughout cleansing treatment are related with drug relapse: an ecological momentary evaluation examine. J Seek the advice of Clin Psychol. 2013;81(1):1–12. doi:10.1037/a0030754
201. Levi Bolin B, Alcorn JL, Lile JA, et al. N-Acetylcysteine reduces cocaine-cue attentional bias and differentially alters cocaine self-administration based mostly on dosing order. Drug Alcohol Rely. 2017;178:452–460. doi:10.1016/j.drugalcdep.2017.05.039
202. Sofuoglu M, Mooney M. Cholinergic functioning in stimulant addiction: implications for drugs improvement. CNS Medication. 2009;23(11):939–952. doi:10.2165/11310920-000000000-00000
203. Sofuoglu M, Waters AJ, Poling J, Carroll KM. Galantamine improves sustained consideration in persistent cocaine customers. Exp Clin Psychopharmacol. 2011;19(1):11–19. doi:10.1037/a0022213
204. Mahoney JJ, Kalechstein AD, Verrico CD, Arnoudse NM, Shapiro BA, De La Garza R. Preliminary findings of the consequences of rivastigmine, an acetylcholinesterase inhibitor, on working reminiscence in cocaine-dependent volunteers. Prog Neuropsychopharmacol Biol Psychiatry. 2014;50:137–142. doi:10.1016/j.pnpbp.2013.11.001
205. Sofuoglu M, Carroll KM. Results of galantamine on cocaine use in persistent cocaine customers. Am J Addict. 2011;20(3):302–303. doi:10.1111/j.1521-0391.2011.00130.x
206. Carroll KM, DeVito EE, Yip SW, Nich C, Sofuoglu M. Double-blind placebo-controlled trial of galantamine for methadone-maintained people with cocaine use disorder: secondary evaluation of results on illicit opioid use. Am J Addict. 2019;28(4):238–245. doi:10.1111/ajad.12904
207. DeVito EE, Carroll KM, Babuscio T, Nich C, Sofuoglu M. Randomized placebo-controlled trial of galantamine in people with cocaine use disorder. J Subst Abuse Deal with. 2019;107:29–37. doi:10.1016/j.jsat.2019.08.009
208. Goldstein RZ, Woicik PA, Maloney T, et al. Oral methylphenidate normalizes cingulate exercise in cocaine addiction throughout a salient cognitive process. Proc Natl Acad Sci U S A. 2010;107(38):16667–16672. doi:10.1073/pnas.1011455107
209. Li CS, Morgan PT, Matuskey D, et al. Organic markers of the consequences of intravenous methylphenidate on bettering inhibitory management in cocaine-dependent patients. Proc Natl Acad Sci U S A. 2010;107(32):14455–14459. doi:10.1073/pnas.1002467107
210. Dursteler KM, Berger EM, Strasser J, et al. Medical potential of methylphenidate in the treatment of cocaine addiction: a evaluate of the present proof. Subst Abuse Rehabil. 2015;6:61–74. doi:10.2147/SAR.S50807
211. Levin FR, Evans SM, Brooks DJ, Garawi F. Remedy of cocaine dependent treatment seekers with adult ADHD: double-blind comparability of methylphenidate and placebo. Drug Alcohol Rely. 2007;87(1):20–29. doi:10.1016/j.drugalcdep.2006.07.004
212. Evans SM, Haney M, Foltin RW. The consequences of smoked cocaine through the follicular and luteal phases of the menstrual cycle in girls. Psychopharmacology. 2002;159(4):397–406. doi:10.1007/s00213-001-0944-7
213. Sofuoglu M, Mouratidis M, Mooney M. Progesterone improves cognitive efficiency and attenuates smoking urges in abstinent people who smoke. Psychoneuroendocrinology. 2011;36(1):123–132. doi:10.1016/j.psyneuen.2010.07.005
214. Sofuoglu M, Dudish-Poulsen S, Nelson D, Pentel PR, Hatsukami DK. Intercourse and menstrual cycle variations in the subjective results from smoked cocaine in people. Exp Clin Psychopharmacol. 1999;7(3):274–283. doi:10.1037/1064-1297.7.3.274
215. Peltier MR, Sofuoglu M. Function of exogenous progesterone in the treatment of males and girls with substance use disorders: a story evaluate. CNS Medication. 2018;32(5):421–435. doi:10.1007/s40263-018-0525-5
216. Again SE, Brady KT, Jackson JL, Salstrom S, Zinzow H. Gender variations in stress reactivity amongst cocaine-dependent people. Psychopharmacology. 2005;180(1):169–176. doi:10.1007/s00213-004-2129-7
217. Sherman BJ, Baker NL, Brady KT, Joseph JE, Nunn LM, McRae-Clark A. The effect of oxytocin, gender, and ovarian hormones on stress reactivity in people with cocaine use disorder. Psychopharmacology. 2020;237(7):2031–2042. doi:10.1007/s00213-020-05516-w
218. Potenza MN, Hong KI, Lacadie CM, Fulbright RK, Tuit KL, Sinha R. Neural correlates of stress-induced and cue-induced drug craving: influences of sex and cocaine dependence. Am J Psychiatry. 2012;169(4):406–414. doi:10.1176/appi.ajp.2011.11020289
219. Brewer JA, Sinha R, Chen JA, et al. Mindfulness coaching and stress reactivity in substance abuse: outcomes from a randomized, controlled stage I pilot examine. Substance Abuse. 2009;30(4):306–317. doi:10.1080/08897070903250241
220. Diana M, Raij T, Melis M, Nummenmaa A, Leggio L, Bonci A. Rehabilitating the addicted mind with transcranial magnetic stimulation. Nat Rev Neurosci. 2017;18(11):685–693. doi:10.1038/nrn.2017.113
221. Bolloni C, Badas P, Corona G, Diana M. Transcranial magnetic stimulation for the treatment of cocaine addiction: proof to date. Subst Abuse Rehabil. 2018;9:11–21. doi:10.2147/SAR.S161206
222. Rachid F. Neurostimulation techniques in the treatment of cocaine dependence: a evaluate of the literature. Addict Behav. 2018;76:145–155. doi:10.1016/j.addbeh.2017.08.004
223. Lupi M, Martinotti G, Santacroce R, et al. Transcranial direct present stimulation in substance use disorders: a scientific evaluate of scientific literature. J ECT. 2017;33(3):203–209. doi:10.1097/YCT.0000000000000401
224. Terraneo A, Leggio L, Saladini M, Ermani M, Bonci A, Gallimberti L. Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: a pilot examine. Eur Neuropsychopharmacol. 2016;26(1):37–44. doi:10.1016/j.euroneuro.2015.11.011
225. Rapinesi C, Kotzalidis GD, Ferracuti S, et al. Add-on excessive frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex in depressive episodes of patients with main depressive disorder, bipolar disorder I, and main depressive with alcohol use disorders. Neurosci Lett. 2018;671:128–132. doi:10.1016/j.neulet.2018.02.029
226. Politi E, Fauci E, Santoro A, Smeraldi E. Day by day classes of transcranial magnetic stimulation to the left prefrontal cortex regularly scale back cocaine craving. Am J Addict. 2008;17(4):345–346. doi:10.1080/10550490802139283
227. Camprodon JA, Martinez-Raga J, Alonso-Alonso M, Shih MC, Pascual-Leone A. One session of excessive frequency repetitive transcranial magnetic stimulation (rTMS) to the proper prefrontal cortex transiently reduces cocaine craving. Drug Alcohol Rely. 2007;86(1):91–94. doi:10.1016/j.drugalcdep.2006.06.002
228. Batista EK, Klauss J, Fregni F, Nitsche MA, Nakamura-Palacios EM. A randomized placebo-controlled trial of focused prefrontal cortex modulation with bilateral tDCS in patients with crack-cocaine dependence. Int J Neuropsychopharmacol. 2015;18(12):pyv066. doi:10.1093/ijnp/pyv066
229. Gorini A, Lucchiari C, Russell-Edu W, Pravettoni G. Modulation of dangerous decisions in lately abstinent dependent cocaine customers: a transcranial direct-current stimulation examine. Entrance Hum Neurosci. 2014;8:661. doi:10.3389/fnhum.2014.00661
230. Shen Y, Ward HB. Transcranial magnetic stimulation and neuroimaging for cocaine use disorder: evaluate and future instructions. Am J Drug Alcohol Abuse. 2021;47(2):144–153. doi:10.1080/00952990.2020.1841784
231. Kinsey BM, Kosten TR, Orson FM. Anti-cocaine vaccine improvement. Knowledgeable Rev Vaccines. 2010;9(9):1109–1114. doi:10.1586/erv.10.102
232. Shen XY, Orson FM, Kosten TR. Vaccines in opposition to drug abuse. Clin Pharmacol Ther. 2012;91(1):60–70. doi:10.1038/clpt.2011.281
233. Martell BA, Orson FM, Poling J, et al. Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial. Arch Gen Psychiatry. 2009;66(10):1116–1123. doi:10.1001/archgenpsychiatry.2009.128
234. Kosten TR, Domingo CB, Shorter D, et al. Vaccine for cocaine dependence: a randomized double-blind placebo-controlled efficacy trial. Drug Alcohol Rely. 2014;140:42–47. doi:10.1016/j.drugalcdep.2014.04.003
235. Jones JD, Comer SD. A evaluate of pharmacogenetic research of substance-related disorders. Drug Alcohol Rely. 2015;152:1–14. doi:10.1016/j.drugalcdep.2015.03.003
236. Schmitz JM, Mooney ME, Inexperienced CE, et al. Baseline neurocognitive profiles differentiate abstainers and non-abstainers in a cocaine clinical trial. J Addict Dis. 2009;28(3):250–257. doi:10.1080/10550880903028502
237. (SAHMSA) SAaMHSA. Key Substance Use and Psychological Health Indicators in the United States: Outcomes from the 2018 Nationwide Survey on Drug Use and Health. SAaMHSA; 2019.
238. Mee-Lee D, Shulman G, Fishman M. The ASAM standards. In: Remedy Standards for Addictive, Substance-Associated, and Co-Occurring Circumstances.
239. (SAMHSA) SAaMHSA. SAMHSA working definition of recovery: 10 guiding rules of recovery. In: Providers DoHaH. Rockville: SAaMHSA; 2012.