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1.
Hum Brain Mapp ; 45(11): e26787, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39023178

RESUMEN

Regular cannabis use is associated with cortex-wide changes in spontaneous and oscillatory activity, although the functional significance of such changes remains unclear. We hypothesized that regular cannabis use would suppress spontaneous gamma activity in regions serving cognitive control and scale with task performance. Participants (34 cannabis users, 33 nonusers) underwent an interview regarding their substance use history and completed the Eriksen flanker task during magnetoencephalography (MEG). MEG data were imaged in the time-frequency domain and virtual sensors were extracted from the peak voxels of the grand-averaged oscillatory interference maps to quantify spontaneous gamma activity during the pre-stimulus baseline period. We then assessed group-level differences in spontaneous and oscillatory gamma activity, and their relationship with task performance and cannabis use metrics. Both groups exhibited a significant behavioral flanker interference effect, with slower responses during incongruent relative to congruent trials. Mixed-model ANOVAs indicated significant gamma-frequency neural interference effects in the left frontal eye fields (FEF) and left temporoparietal junction (TPJ). Further, a group-by-condition interaction was detected in the left FEF, with nonusers exhibiting stronger gamma oscillations during incongruent relative to congruent trials and cannabis users showing no difference. In addition, spontaneous gamma activity was sharply suppressed in cannabis users relative to nonusers in the left FEF and TPJ. Finally, spontaneous gamma activity in the left FEF and TPJ was associated with task performance across all participants, and greater cannabis use was associated with weaker spontaneous gamma activity in the left TPJ of the cannabis users. Regular cannabis use was associated with weaker spontaneous gamma in the TPJ and FEF. Further, the degree of use may be proportionally related to the degree of suppression in spontaneous activity in the left TPJ.


Asunto(s)
Cognición , Ritmo Gamma , Magnetoencefalografía , Humanos , Masculino , Femenino , Adulto , Adulto Joven , Ritmo Gamma/fisiología , Cognición/fisiología , Mapeo Encefálico , Pruebas Neuropsicológicas , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Uso de la Marihuana
2.
Mol Cell Neurosci ; 125: 103852, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37061172

RESUMEN

Cannabis use disorder (CUD) is common and has in part a genetic basis. The risk factors underlying its development likely involve multiple genes that are polygenetic and interact with each other and the environment to ultimately lead to the disorder. Co-morbidity and genetic correlations have been identified between CUD and other disorders and traits in select populations primarily of European descent. If two or more traits, such as CUD and another disorder, are affected by the same genetic locus, they are said to be pleiotropic. The present study aimed to identify specific pleiotropic loci for the severity level of CUD in three high-risk population cohorts: American Indians (AI), Mexican Americans (MA), and European Americans (EA). Using a previously developed computational method based on a machine learning technique, we leveraged the entire GWAS catalog and identified 114, 119, and 165 potentially pleiotropic variants for CUD severity in AI, MA, and EA respectively. Ten pleiotropic loci were shared between the cohorts although the exact variants from each cohort differed. While majority of the pleiotropic genes were distinct in each cohort, they converged on numerous enriched biological pathways. The gene ontology terms associated with the pleiotropic genes were predominately related to synaptic functions and neurodevelopment. Notable pathways included Wnt/ß-catenin signaling, lipoprotein assembly, response to UV radiation, and components of the complement system. The pleiotropic genes were the most significantly differentially expressed in frontal cortex and coronary artery, up-regulated in adipose tissue, and down-regulated in testis, prostate, and ovary. They were significantly up-regulated in most brain tissues but were down-regulated in the cerebellum and hypothalamus. Our study is the first to attempt a large-scale pleiotropy detection scan for CUD severity. Our findings suggest that the different population cohorts may have distinct genetic factors for CUD, however they share pleiotropic genes from underlying pathways related to Alzheimer's disease, neuroplasticity, immune response, and reproductive endocrine systems.


Asunto(s)
Abuso de Marihuana , Masculino , Femenino , Humanos , Abuso de Marihuana/diagnóstico , Abuso de Marihuana/epidemiología , Factores de Riesgo , Fenotipo
3.
Cytotherapy ; 25(2): 210-219, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36443171

RESUMEN

BACKGROUND AIMS: Dendritic cell (DC)-based immunotherapy is a promising approach to treat cancer; however, there is no consensus on the manufacturing processes. Cell type heterogeneity in products manufactured by various methods is understudied and may elicit safety concerns from the regulatory perspective. METHODS: We characterized the cell type composition of a recently developed DC vaccine, CUD-002, consisting of DCs loaded with mRNA encoding personalized tumor neoantigens (NCT05270720). RESULTS: Using single-cell transcriptomic analysis as an unbiased approach, we found that >80% cells in the final product were DCs and the rest primarily comprised myelocytes and lymphocytes. Subsequent fluorescence-activated cell sorting analyses confirmed these cellular identities. These results indicate that unintended cells originate from leukapheresis, the first step of the manufacturing process, and thus likely safe. Consistently, no overt toxicity or tumorigenicity was observed in mice inoculated with CUD-002. CONCLUSIONS: Considering that leukapheresis is a widely used procedure for collecting diverse peripheral blood cell types to manufacture various cytotherapies, this study establishes a workflow to analyze and address regulatory considerations on cell type heterogeneity.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Vacunas , Animales , Ratones , Vacunas contra el Cáncer/genética , Células Dendríticas , Inmunoterapia/métodos , Neoplasias/terapia , Análisis de Secuencia de ARN , Vacunas/metabolismo , Estudios Clínicos como Asunto
4.
Pharmacol Res ; 191: 106746, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37001709

RESUMEN

Cannabis is among the most widely consumed psychoactive drugs around the world and cannabis use disorder (CUD) has no current approved pharmacological treatment. Nicotine and cannabis are commonly co-used which suggests there to be overlapping neurobiological actions supported primarily by the co-distribution of both receptor systems in the brain. There appears to be strong rationale to explore the role that nicotinic receptors play in cannabinoid dependence. Preclinical studies suggest that the ɑ7 nAChR subtype may play a role in modulating the reinforcing and discriminative stimulus effects of cannabinoids, while the ɑ4ß2 * nAChR subtype may be involved in modulating the motor and sedative effects of cannabinoids. Preclinical and human genetic studies point towards a potential role of the ɑ5, ɑ3, and ß4 nAChR subunits in CUD, while human GWAS studies strongly implicate the ɑ2 subunit as playing a role in CUD susceptibility. Clinical studies suggest that current smoking cessation agents, such as varenicline and bupropion, may also be beneficial in treating CUD, although more controlled studies are necessary. Additional behavioral, molecular, and mechanistic studies investigating the role of nAChR in the modulation of the pharmacological effects of cannabinoids are needed.


Asunto(s)
Cannabinoides , Receptores Nicotínicos , Humanos , Agonistas Nicotínicos , Cannabinoides/farmacología , Cannabinoides/uso terapéutico , Nicotina/farmacología , Vareniclina , Agonistas de Receptores de Cannabinoides
5.
J Neurochem ; 157(5): 1674-1696, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33891706

RESUMEN

Cannabis sativa is the most widely used illicit drug in the world. Its main psychoactive component is delta-9-tetrahydrocannabinol (THC), one of over 100 phytocannabinoid compounds produced by the cannabis plant. THC is the primary compound that drives cannabis abuse potential and is also used and prescribed medically for therapeutic qualities. Despite its therapeutic potential, a significant subpopulation of frequent cannabis or THC users will develop a drug use syndrome termed cannabis use disorder. Individuals suffering from cannabis use disorder exhibit many of the hallmarks of classical addictions including cravings, tolerance, and withdrawal symptoms. Currently, there are no efficacious treatments for cannabis use disorder or withdrawal symptoms. This makes both clinical and preclinical research on the neurobiological mechanisms of these syndromes ever more pertinent. Indeed, basic research using animal models has provided valuable evidence of the neural molecular and cellular actions of cannabis that mediate its behavioral effects. One of the main components being central action on the cannabinoid type-one receptor and downstream intracellular signaling related to the endogenous cannabinoid system. Back-translational studies have provided insight linking preclinical basic and behavioral biology research to better understand symptoms observed at the clinical level. This narrative review aims to summarize major research elucidating the molecular, cellular, and behavioral manifestations of cannabis/THC use that play a role in cannabis use disorder and withdrawal.


Asunto(s)
Endocannabinoides , Abuso de Marihuana/fisiopatología , Fumar Marihuana/fisiopatología , Receptores de Cannabinoides , Síndrome de Abstinencia a Sustancias/fisiopatología , Animales , Dronabinol/farmacología , Tolerancia a Medicamentos , Humanos , Abuso de Marihuana/psicología , Fumar Marihuana/psicología , Síndrome de Abstinencia a Sustancias/psicología
6.
Subst Abus ; : 1-9, 2021 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-34283700

RESUMEN

BACKGROUND: Clinicians rely upon abstracts to provide them quick synopses of research findings that may apply to their practice. Spin can exist within these abstracts that distorts or misrepresents the findings. Our goal was to evaluate the level of spin within systematic reviews (SRs) focused on the treatment of cannabis use disorder (CUD). Methods: A systematic search was conducted in May 2020. To meet inclusion criteria, publications had to be either an SR or meta-analysis related to the treatment of cannabis use. Screening and data extraction was performed in a duplicate and masked fashion. Study quality was assessed using AMSTAR-2 Results: 16/24 SRs (66.7%) contained at least one form of spin in the abstract. The most common forms of spin identified were type 3-selective reporting of or overemphasis on efficacy outcomes or analysis favoring the beneficial effect of the experimental intervention (45.8%)-and type 8-the review's findings from a surrogate marker or a specific outcome to the global improvement of the disease (37.5%). No significant association between spin and intervention type, PRISMA requirements, or funding source was identified. Weak positive correlations were found between the presence of spin and abstract word count (r =.217) and between spin and AMSTAR-2 rating (r = 0.143). "Moderate" was the most common AMSTAR-2 rating (9/24, 37.5%), followed by "low" (7/24, 29.2%) and "critically low" (7/24, 29.2%). One systematic review received an AMSTAR-2 rating of "high" (1/24, 4.2%). Conclusions: Spin was common among abstracts from the SRs focused on the treatments for CUD. Higher quality studies may help reduce the overall rate as well as standardizing treatment outcomes. To facilitate this, we encourage all authors, peer-reviewers, and editors to be more aware of the various types of spin as they can help reduce the overall amount of spin seen within the literature.

7.
BMC Psychiatry ; 20(1): 153, 2020 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-32252720

RESUMEN

BACKGROUND: Sleep disturbance is a prominent and common complaint in people with cocaine use disorder (CUD), either during intake or withdrawal. Repetitive transcranial magnetic stimulation (rTMS) has shown promise as a treatment for CUD. Thus, we evaluated the relationship between self-perceived sleep quality and cocaine use pattern variables in outpatients with CUD undergoing an rTMS protocol targeted at the left dorsolateral prefrontal cortex. METHODS: This is a retrospective observational study including 87 patients diagnosed with CUD according to the DSM-5 criteria. Scores in Pittsburgh Sleep Quality Index (PSQI), Cocaine Craving Questionnaire (CCQ), Beck Depression Inventory-II (BDI-II), Self-rating Anxiety Scale (SAS), and Symptoms checklist 90-Revised (outcome used: Global Severity Index, GSI) were recorded at baseline, and after 5, 30, 60, and 90 days of rTMS treatment. Cocaine use was assessed by self-report and regular urine screens. RESULTS: Sleep disturbances (PSQI scores > 5) were common in patients at baseline (mean ± SD; PSQI score baseline: 9.24 ± 3.89; PSQI > 5 in 88.5% of patients). PSQI scores significantly improved after rTMS treatment (PSQI score Day 90: 6.12 ± 3.32). Significant and consistent improvements were also seen in craving and in negative-affect symptoms compared to baseline. Considering the lack of a control group, in order to help the conceptualization of the outcomes, we compared the results to a wait-list group (n = 10). No significant improvements were observed in the wait-list group in any of the outcome measures. CONCLUSIONS: The present findings support the therapeutic role of rTMS interventions for reducing cocaine use and accompanying symptoms such as sleep disturbance and negative-affect symptoms. TRIAL REGISTRATION: ClinicalTrials.gov.NCT03733821.


Asunto(s)
Trastornos Relacionados con Cocaína/terapia , Cocaína/efectos adversos , Sueño/fisiología , Estimulación Magnética Transcraneal/métodos , Adulto , Cocaína/administración & dosificación , Ansia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Prefrontal , Estudios Retrospectivos , Encuestas y Cuestionarios , Resultado del Tratamiento
8.
Psychol Med ; 48(9): 1540-1550, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29310741

RESUMEN

BACKGROUND: Exposure to child maltreatment has been shown to increase lifetime risk for substance use disorders (SUD). However, this has not been systematically examined among race/ethnic groups, for whom rates of exposure to assaultive violence and SUD differ. This study examined variation by race/ethnicity and gender in associations of alcohol (AUD), cannabis (CUD), and tobacco (TUD) use disorders with three types of childhood interpersonal violence (cIPV): physical abuse, sexual abuse, and witnessing parental violence. METHOD: Data from the National Epidemiologic Survey of Alcohol-Related Conditions-III (N: 36 309), a US nationally representative sample, was utilized to examine associations of DSM-5 AUD, CUD and TUD with cIPV among men and women of five racial/ethnic groups. Models were adjusted for additional risk factors (e.g. parental substance use problems, participant's co-occurring SUD). RESULTS: Independent contributions of childhood physical and sexual abuse to AUD, CUD, and TUD, and of witnessing parental violence to AUD and TUD were observed. Associations of cIPV and SUD were relatively similar across race/ethnicity and gender [Odds Ratios (ORs) ranged from 1.1 to 1.9], although associations of physical abuse with AUD and TUD were greater among males, associations of parental violence and AUD were greater among females, and associations of parental violence with AUD were greater among Hispanic women and American Indian men. CONCLUSIONS: Given the paucity of research in this area, and the potential identification of modifiable risk factors to reduce the impact of childhood interpersonal violence on SUDs, further research and consideration of tailoring prevention and intervention efforts to different populations are warranted.


Asunto(s)
Trastornos Relacionados con Alcohol/etnología , Maltrato a los Niños/etnología , Abuso de Marihuana/etnología , Tabaquismo/etnología , Violencia/etnología , Adulto , Niño , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Etnicidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos/epidemiología
9.
J Subst Use Addict Treat ; 167: 209486, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39151799

RESUMEN

INTRODUCTION: Recent expansion of cannabis legalization in multiple states calls for reexamination of the prevalence of cannabis use, cannabis use disorder (CUD), and the associations between CUD severity and substance use treatment. We used Andersen's behavioral model of healthcare use as the conceptual/analytic framework for examining treatment use. METHODS: We used data from the 2022 National Survey on Drug Use and Health (NSDUH; N = 47,100, age 18+) to describe the prevalence of past-year cannabis use, CUD and CUD severity, other substance use disorders, and substance use treatment. We compared sociodemographic, mental health, healthcare use, and cannabis and other substance use characteristics by CUD severity. Finally, we used logistic regression models to examine the associations between CUD severity and substance use treatment. RESULTS: Of the U.S. adult population, 23.0 % used cannabis in the past year; 7.0 % had a CUD (3.9 % mild, 1.9 % moderate, and 1.2 % severe CUD); and 4.7 % received substance use treatment. Of past-year cannabis users, 30.3 % had CUD (16.9 % mild, 8.4 % moderate, and 5.0 % severe CUD), and 9.6 % received substance use treatment. Cannabis users had 3-4 times higher rates of other substance use disorders than nonusers. Of those with CUD, 38.4 % had moderate/severe mental illness, 52.4 % had other substance use disorders, and 16.5 % received substance use treatment. Among all cannabis users, moderate (aOR [adjusted odds ratios] = 1.48, 95 % CI = 1.03-2.13) and severe (aOR = 2.57, 95 % CI = 1.60-4.11) CUDs were associated with greater odds of substance use treatment. Among cannabis users without nicotine dependence and alcohol, opioid, tranquilizer/sedative, and stimulant use disorders, only severe CUD (aOR = 6.03, 95 % CI = 3.37-10.78) was associated with greater odds of substance use treatment. CONCLUSIONS: This study shows increased prevalence of cannabis use and CUD among U.S. adults, and with or without other substance use disorders, CUD was associated with greater odds of substance use treatment. However, the overall low rate of treatment use among those with CUD is concerning. Healthcare providers need to provide education for both medical and recreational users on the development of tolerance and dependence. Harm reduction strategies to minimize the negative consequences of CUD are also needed.

10.
Brain Sci ; 14(3)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38539616

RESUMEN

Cannabis use disorder (CUD) is a growing public health concern, with rising prevalence and significant impact on individuals across age groups. This systematic review examines 24 studies investigating pharmacological and non-pharmacological interventions for CUD among adolescents (up to 17), young adults (18-24), and older adults (25-65). Database searches were conducted for randomized controlled trials of CUD interventions reporting outcomes such as cannabis use, abstinence, withdrawal symptoms, and treatment retention. For adolescents, interventions such as contingent rewards and family engagement have shown promise, while young adults benefit from technology-based platforms and peer support. In older adults, pharmacological adjuncts combined with counseling have shown promise in enhancing treatment outcomes. However, optimal treatment combinations remain uncertain, highlighting the need for further research. Addressing CUD requires tailored interventions that acknowledge developmental stages and challenges across the lifespan. Although promising interventions exist, further comparative effectiveness research is needed to delineate the most efficacious approaches.

11.
Brain Sci ; 14(3)2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38539634

RESUMEN

Previous research has indicated that anticipating positive effects from cannabis use may be linked with increased frequency of cannabis consumption, yet these expectancies remain poorly understood in adults with social anxiety disorder (SAD). Thus, our study aimed to investigate the expectancies of the effects of cannabis use in 26 frequently using adults with SAD (age: 27.9 ± 7.3 years; 54% female) and 26 (age: 27.4 ± 6.7 years; 50% female) without. While no between-group differences were observed, both groups reported expecting tension reduction and relaxation (F = 0.001; p = 0.974), cravings, and physical effects (F = 1.10; p = 0.300), but denied global negative effects (F = 0.11; p = 0.744). The trajectory of cannabis use perceptions (further investigated in 12/26 participants/group) also showed no between-group differences. Before the initial use, positive perceptions may have led to initial and continuous cannabis consumption, while the symptoms of cannabis use disorder may have contributed to repeated use. Our data indicate that, regardless of psychiatric history, frequent cannabis-using adults are more likely to report positive expectancies, which are often associated with increased patterns of cannabis consumption. Psychoeducational programs and openly discussing the risks of cannabis may be beneficial in preventing and/or reducing cannabis use in people with SAD.

12.
Behav Res Ther ; 169: 104387, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37625353

RESUMEN

Trauma cue-elicited activation of automatic cannabis-related cognitive biases are theorized to contribute to comorbid posttraumatic stress disorder and cannabis use disorder. This phenomenon can be studied experimentally by combining the trauma cue reactivity paradigm (CRP) with cannabis-related cognitive processing tasks. In this study, we used a computerized cannabis approach-avoidance task (AAT) to assess automatic cannabis (vs. neutral) approach bias following personalized trauma (vs. neutral) CRP exposure. We hypothesized that selective cannabis (vs. neutral) approach biases on the AAT would be larger among participants with higher PTSD symptom severity, particularly following trauma (vs. neutral) cue exposure. We used a within-subjects experimental design with a continuous between-subjects moderator (PTSD symptom severity). Participants were exposed to both a trauma and neutral CRP in random order, completing a cannabis AAT (cannabis vs. neutral stimuli) following each cue exposure. Current cannabis users with histories of psychological trauma (n = 50; 34% male; mean age = 37.8 years) described their most traumatic lifetime event, and a similarly-detailed neutral event, according to an established interview protocol that served as the CRP. As hypothesized, an AAT stimulus type x PTSD symptom severity interaction emerged (p = .042) with approach bias greater to cannabis than neutral stimuli for participants with higher (p = .006), but not lower (p = .36), PTSD symptom severity. Contrasting expectations, the stimulus type x PTSD symptoms effect was not intensified by trauma cue exposure (p = .19). Selective cannabis approach bias may be chronically activated in cannabis users with higher PTSD symptom severity and may serve as an automatic cognitive mechanism to help explain PTSD-CUD co-morbidity.


Asunto(s)
Cannabis , Trauma Psicológico , Trastornos por Estrés Postraumático , Trastornos Relacionados con Sustancias , Humanos , Masculino , Adulto , Femenino , Trastornos por Estrés Postraumático/psicología , Señales (Psicología)
13.
J Psychoactive Drugs ; 55(4): 445-455, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36318094

RESUMEN

Using 2020 National Survey on Drug Use and Health data (N = 27,170, age 18+), we examined associations of psychological distress with: (1) cannabis use frequency among all adults, and (2) cannabis use disorder (CUD) among cannabis users. Of all adults, 18.2% reported past-year cannabis use, 12.9% reported mild-moderate psychological distress, and 12.9% reported serious psychological distress. Greater proportions of cannabis users, especially those under age 35, reported psychological distress. Of cannabis users, 28.1% met DSM-5 CUD criteria. Multinomial logistic regression results showed that serious, compared to no, psychological distress was significantly associated with cannabis use at all frequency levels. Both mild-moderate and serious levels of distress were associated with similar elevated CUD risk (RRR = 1.57, 95% CI = 1.15-2.15 for mild-moderate distress; RRR = 1.58, 95% CI = 1.19-2.09 for serious distress) and 2-4 times higher risks of having moderate or severe, compared to mild, CUD and higher odds of having alcohol use disorder. The prevalence of CUD and other substance use/use disorder among cannabis users is concerning as are the significant associations of psychological distress with greater cannabis use frequency, CUD, and other substance use/use disorder. Younger adults especially may benefit from increased behavioral health services given their high prevalence of psychological distress, cannabis use, and CUD.

14.
Int J Neonatal Screen ; 9(1)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36810318

RESUMEN

Primary Carnitine Deficiency (PCD) is a fatty acid oxidation disorder that will be included in the expansion of the French newborn screening (NBS) program at the beginning of 2023. This disease is of high complexity to screen, due to its pathophysiology and wide clinical spectrum. To date, few countries screen newborns for PCD and struggle with high false positive rates. Some have even removed PCD from their screening programs. To understand the risks and pitfalls of implementing PCD to the newborn screening program, we reviewed and analyzed the literature to identify hurdles and benefits from the experiences of countries already screening this inborn error of metabolism. In this study, we therefore, present the main pitfalls encountered and a worldwide overview of current practices in PCD newborn screening. In addition, we address the optimized screening algorithm that has been determined in France for the implementation of this new condition.

15.
Neuropsychologia ; 185: 108581, 2023 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-37156411

RESUMEN

A simple reaction time (SRT) difference between responses to visual stimuli presented ipsilaterally and contralaterally to the responding hand, known as the Poffenberger effect or the crossed-uncrossed difference (CUD), has been commonly interpreted as a measure of interhemispheric transfer time (IHTT). However, the validity of this interpretation and the measure's reliability have been debated. The present study aimed at obtaining reliable evidence of the influence of spatial attention on the CUD, which would provide an argument against the classical interpretation of CUD. To meet the high statistical power requirements, over 100 thousand SRTs in total were collected from 12 participants. The task had three stimulus presentation conditions differing in the degree of stimulus location uncertainty: blocked (no uncertainty), randomized (full uncertainty), and mixed (25% uncertainty). The results showed robust effects of location uncertainty, proving spatial attention's contribution to the CUD. Further, we observed a strong visual-field asymmetry reflecting the right hemisphere specialization in target detection and spatial reorienting. Lastly, despite exceptional reliability of the component SRT measures, the CUD reliability was still too low to justify using this measure as an index of individual differences.


Asunto(s)
Atención , Lateralidad Funcional , Humanos , Lateralidad Funcional/fisiología , Reproducibilidad de los Resultados , Atención/fisiología , Tiempo de Reacción/fisiología , Campos Visuales
16.
bioRxiv ; 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-38045392

RESUMEN

Background: The biological mechanisms that contribute to cocaine and other substance use disorders involve an array of cortical and subcortical systems. Prior work on the development and maintenance of substance use has largely focused on cortico-striatal circuits, with relatively less attention on alterations within and across large-scale functional brain networks, and associated aspects of the dopamine system. The brain-wide pattern of temporal co-activation between distinct brain regions, referred to as the functional connectome, underpins individual differences in behavior. Critically, the functional connectome correlates of substance use and their specificity to dopamine receptor densities relative to other metabotropic receptors classes remains to be established. Methods: We comprehensively characterized brain-wide differences in functional connectivity across multiple scales, including individual connections, regions, and networks in participants with cocaine use disorder (CUD; n=69) and healthy matched controls (n=62), Further, we studied the relationship between the observed functional connectivity signatures of CUD and the spatial distribution of a broad range of normative neurotransmitter receptor and transporter bindings as assessed through 18 different normative positron emission tomography (PET) maps. Results: Our analyses identified a widespread profile of functional connectivity differences between individuals with CUD and matched healthy comparison participants (8.8% of total edges; 8,185 edges; pFWE=0.025). We largely find lower connectivity preferentially linking default network and subcortical regions, and higher within-network connectivity in the default network in participants with CUD. Furthermore, we find consistent and replicable associations between signatures of CUD and normative spatial density of dopamine D2/3 receptors. Conclusions: Our analyses revealed a widespread profile of altered connectivity in individuals with CUD that extends across the functional connectome and implicates multiple circuits. This profile is robustly coupled with normative dopamine D2/3 receptors densities. Underscoring the translational potential of connectomic approaches for the study of in vivo brain functions, CUD-linked aspects of brain function were spatially coupled to disorder relevant neurotransmitter systems.

17.
Gene ; 851: 147048, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36379386

RESUMEN

Cannabis is one of the most commonly used psychoactive substances, which could induce moderate-severe cannabis use disorders (CUD). Here, a tissue-specific transcriptome-wide association study (TWAS) of CUD was performed by FUSION and S-PrediXcan, utilizing a genome-wide association study (GWAS) dataset of CUD (including 43,380 cases and 141,385 controls of European ancestry) and gene expression reference data from 17 different brain-related and non-brain related tissues, with totally 26 TWAS-associated genes were identified, including CADM2 (P = 2.13 × 10-17), SRR (P = 8.09 × 10-9) and TUFM (P = 1.24 × 10-8). Fine-mapping of causal gene sets (FOCUS) was used to prioritize genes with strong evidence for causality, and SRR, CADM2-AS1, and SH2B1 were prioritized with a posterior probability of 0.973, 0.951, and 0.788, respectively. Furthermore, gene ontology (GO) and pathway enrichment analysis on CUD-associated genes were performed, including cytosol, protein binding, nucleoplasm, metabolic pathways, and herpes simplex virus 1 infection. These findings could provide new insights for understanding the mechanism of CUD.


Asunto(s)
Abuso de Marihuana , Transcriptoma , Humanos , Estudio de Asociación del Genoma Completo , Perfilación de la Expresión Génica , Predisposición Genética a la Enfermedad , Abuso de Marihuana/genética , ARN Mensajero/genética , Polimorfismo de Nucleótido Simple , Proteínas Adaptadoras Transductoras de Señales/genética
18.
Brain Sci ; 13(12)2023 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-38137146

RESUMEN

Social anxiety disorder (SAD) is a debilitating psychiatric condition. Consequently, it is common for those affected to resort to cannabis to cope with their symptoms. The primary objective of this study was to understand the differences between motivations for cannabis use in adults with and without SAD. We employed convergent, mixed methods to collect the data. Twenty-six individuals (age: 27.9 ± 7.3 years; 54% female) with and twenty-six (age: 27.4 ± 6.7 years; 50% female) without SAD were administered Marijuana Motives Measure (MMM). Motivations to initiate, continue, and maintain cannabis use were assessed in 12/26 participants in both groups using in-depth interviews. Cannabis weekly consumption was 3.8-fold and frequency 1.3-fold higher in the SAD group. Coping (F = 10.02; p <0.001; η2 = 0.46) and social (F = 2.81; p = 0.036; η2 = 0.19) motivations were also higher in the SAD group, after controlling for age, sex, and current CUD. The need to cope with symptoms of SAD may have been the driving force for repeated cannabis consumption. Psychoeducational programs educating children about the risk of using cannabis to cope with SAD should be implemented in vocational settings early on.

20.
Front Psychiatry ; 13: 1035345, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36339845

RESUMEN

Cannabis use and Cannabis Use Disorder (CUD) have been increasing. There are no FDA approved medications and evidence-based psychotherapy is limited by insufficient providers, serving very few patients effectively. The lack of resources for prevention and treatment of CUD has resulted in a significant gap between the need for services and access to treatment. The creation of a scalable system to prevent, screen, refer and provide treatment for a chronic, relapsing diagnosis like CUD could be achieved through the application of technology. Many studies have utilized ecological momentary assessments (EMA) in treatment seeking and non-treatment seeking cannabis users. EMA allows for repeated, intensive, longitudinal data collection in vivo. EMA has been studied in cannabis use and its association with affect, craving, withdrawal, other substances, impulsivity, and interpersonal behaviors. EMA has the potential to serve as a valuable monitoring tool in prevention, screening, and treatment for CUD. Research has also focused on the development of internet and application-based treatments for CUD, including a currently available prescription digital therapeutic. Treatment options have expanded to more broadly incorporate telehealth as an option for CUD treatment with broad acceptance and change in regulation following the COVID-19 pandemic. While technology has limitations, including cost, privacy concerns, and issues with engagement, it will be a necessary medium to meet societal health needs as a consequence of an ever-changing cannabis regulatory landscape. Future work should focus on improving existing platforms while ethically incorporating other functions (e.g., sensors) to optimize a public and clinical health approach to CUD.

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