Comparison of Treatments for Cocaine Use Disorder Among Adults

Bentzley, Brandon S.; Han, Summer S.; Neuner, Sophie; Humphreys, Keith; Kampman, Kyle M.; Halpern, Casey H.

doi:10.1001/jamanetworkopen.2021.8049

Cited by 77 publications

(67 citation statements)

References 222 publications

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“…Accordingly, substance use disorder (SUD) diagnoses are common, with nearly 4% of the US population meeting diagnostic criteria in the past 12 months and 10% meeting criteria in their lifetime (Grant et al, 2016). At the same time, the effectiveness of existing treatments for SUDs is limited (Bentzley et al, 2021;Volkow, 2020;Witkiewitz et al, 2019). Although some people do recover without formal treatment, large numbers of individuals treated for an SUD drop out of treatment, do not respond to it, or return to harmful use.…”

Section: New Approaches To Deep Phenotyping In Addictionsmentioning

confidence: 99%

New approaches to deep phenotyping in addictions

Watts¹,

Latzman²,

Boness³

et al. 2022

Preprint

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Objective: The causes of substance use disorders (SUDs) are largely unknown and the effectiveness of their treatments is limited. One crucial impediment to research and treatment progress surrounds how SUDs are classified and diagnosed. Given the substantial heterogeneity among individuals diagnosed with a given SUD (e.g., alcohol use disorder), identifying novel research and treatment targets and developing new study designs is daunting. Method: In this paper, we review and integrate two recently developed frameworks, the NIDA Phenotyping Assessment Battery (NIDA PhAB) and the Hierarchical Taxonomy of Psychopathology (HiTOP), that hope to accelerate progress in understanding the causes and consequences of psychopathology by means of deep phenotyping, or finer-grained analysis of phenotypes. Results and Conclusions: NIDA PhAB focuses on addiction-related processes across multiple units of analysis, whereas HiTOP focuses on clinical phenotypes and covers a broader range of psychopathology. We highlight that NIDA PhAB and HiTOP together provide deep and broad characterizations of people diagnosed with SUDs and complement each other in their efforts to address widely known limitations of traditional classification systems and their diagnostic categories. Next, we show how NIDA PhAB and HiTOP can be integrated to facilitate optimal rich phenotyping of addiction-related phenomena. Finally, we argue that such deep phenotyping promises to advance our understanding of the neurobiology of SUD and addiction, which will guide the development of personalized medicine and interventions.

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Section: New Approaches To Deep Phenotyping In Addictionsmentioning

confidence: 99%

New approaches to deep phenotyping in addictions

Watts¹,

Latzman²,

Boness³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Recent data indicate that cocaine use, the prevalence of cocaine use disorder (CUD) and cocaine-related overdose deaths have been increasing in the United States (1)(2)(3)(4). Although cocaine use and abuse remain a significant public health concern, there are currently no FDA approved therapies for CUD.…”

Section: Introductionmentioning

confidence: 99%

Cocaine-Induced Locomotor Activation Differs Across Inbred Mouse Substrains

et al. 2022

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Cocaine use disorders (CUD) are devastating for affected individuals and impose a significant societal burden, but there are currently no FDA-approved therapies. The development of novel and effective treatments has been hindered by substantial gaps in our knowledge about the etiology of these disorders. The risk for developing a CUD is influenced by genetics, the environment and complex interactions between the two. Identifying specific genes and environmental risk factors that increase CUD risk would provide an avenue for the development of novel treatments. Rodent models of addiction-relevant behaviors have been a valuable tool for studying the genetics of behavioral responses to drugs of abuse. Traditional genetic mapping using genetically and phenotypically divergent inbred mice has been successful in identifying numerous chromosomal regions that influence addiction-relevant behaviors, but these strategies rarely result in identification of the causal gene or genetic variant. To overcome this challenge, reduced complexity crosses (RCC) between closely related inbred mouse strains have been proposed as a method for rapidly identifying and validating functional variants. The RCC approach is dependent on identifying phenotypic differences between substrains. To date, however, the study of addiction-relevant behaviors has been limited to very few sets of substrains, mostly comprising the C57BL/6 lineage. The present study expands upon the current literature to assess cocaine-induced locomotor activation in 20 inbred mouse substrains representing six inbred strain lineages (A/J, BALB/c, FVB/N, C3H/He, DBA/2 and NOD) that were either bred in-house or supplied directly by a commercial vendor. To our knowledge, we are the first to identify significant differences in cocaine-induced locomotor response in several of these inbred substrains. The identification of substrain differences allows for the initiation of RCC populations to more rapidly identify specific genetic variants associated with acute cocaine response. The observation of behavioral profiles that differ between mice generated in-house and those that are vendor-supplied also presents an opportunity to investigate the influence of environmental factors on cocaine-induced locomotor activity.

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“…However, the mesolimbic pathway is directly involved with the mechanisms of emotion control and reward. Thus, the alteration of dopaminergic neurotransmission in this area is related to the pathophysiology of several diseases, such as schizophrenia and drug addiction [ 7 , 8 , 9 , 10 , 11 , 12 ]. In addition, other pathophysiological processes are also involved in the alteration of dopaminergic neurotransmission, such as the establishment of arterial hypertension, bipolar disorder and major depression [ 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Pharmacological Evaluation of Novel Conformationally Restricted N-arylpiperazine Derivatives Characterized as D2/D3 Receptor Ligands, Candidates for the Treatment of Neurodegenerative Diseases

et al. 2022

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Most neurodegenerative diseases are multifactorial, and the discovery of several molecular mechanisms related to their pathogenesis is constantly advancing. Dopamine and dopaminergic receptor subtypes are involved in the pathophysiology of several neurological disorders, such as schizophrenia, depression and drug addiction. For this reason, the dopaminergic system and dopamine receptor ligands play a key role in the treatment of such disorders. In this context, a novel series of conformationally restricted N-arylpiperazine derivatives (5a–f) with a good affinity for D2/D3 dopamine receptors is reported herein. Compounds were designed as interphenylene analogs of the drugs aripiprazole (2) and cariprazine (3), presenting a 1,3-benzodioxolyl subunit as a ligand of the secondary binding site of these receptors. The six new N-arylpiperazine compounds were synthesized in good yields by using classical methodologies, and binding and guanosine triphosphate (GTP)-shift studies were performed. Affinity values below 1 μM for both target receptors and distinct profiles of intrinsic efficacy were found. Docking studies revealed that Compounds 5a–f present a different binding mode with dopamine D2 and D3 receptors, mainly as a consequence of the conformational restriction imposed on the flexible spacer groups of 2 and 3.

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Comparison of Treatments for Cocaine Use Disorder Among Adults

Abstract: This systematic review and meta-analysis uses data from clinical trials to compare treatments for cocaine use disorder and examines whether any treatment approaches are associated with reductions in cocaine use among adults who are actively using cocaine.

Cited by 77 publications

References 222 publications

New approaches to deep phenotyping in addictions

New approaches to deep phenotyping in addictions

Cocaine-Induced Locomotor Activation Differs Across Inbred Mouse Substrains

Design, Synthesis and Pharmacological Evaluation of Novel Conformationally Restricted N-arylpiperazine Derivatives Characterized as D2/D3 Receptor Ligands, Candidates for the Treatment of Neurodegenerative Diseases

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