National Institute On Drug Abuse Research Articles

HIV-Infection and Cocaine Use Regulate Semen Extracellular Vesicles Proteome and miRNAome in a Manner that Mediates Strategic Monocyte Haptotaxis Governed by mIR-128 Network

Background: Extracellular vesicles (EVs) are mediators of horizontal transfer of bioactive molecules between cells and regulators of cell-cell interaction. EV-mediated cell-cell interactions play roles in physiological and pathophysiological conditions. However, the effect of pathogens and cocaine use on EV composition and function are not fully understood. Methods: We obtained 64 seminal plasma specimens from HIV-1-uninfected (HIV—and HIV-1-infected (HIV+) participants who used cocaine (COC—) or did not use cocaine (COC+). The participants were divided into 4 clinical groups (16 per group) denoted as HIV–COC–, HIV–COC+, HIV+COC–, and HIV+COC+ were used. The seminal plasma was used to isolate EVs (SEVs) by differential centrifugation and PPLC-based size exclusion chromatography (SEC) as previously described. We used the SEV to study how HIV infection and cocaine regulate the repertoire and functions of EV-associated proteins, miRNA, and their interactome. After paired proteomics and small RNA-Sequencing (sRNA-Seq) analyses, we employed an in vitro two-dimensional-substrate single cell haptotaxis assay for quantitative assessment of the effect of different SEV on monocyte haptotaxis. Finally, we functionalized SEV with exogenous miR-128 to directly address the role of SEV-associated miR-128 on monocyte haptotaxis. Findings: Systems biology and multi-omics analysis showed that HIV infection (HIV+) and cocaine (COC) use (COC+) promote the release of SEV with dysregulated extracellular proteome (exProtein), miRNAome (exmiR), and exmiR networks. Integrating SEV proteome and miRNAome revealed a significant decrease in the enrichment of disease-associated, brain-enriched, and HIV-associated miR-128-3p (miR-128) in HIV+COC+ SEV along with a concomitant increase in miR-128 targets—PEAK1 and RND3/RhoE. Two-dimensional-substrate single cell haptotaxis showed that in the presence of HIV+COC+ SEVs, contact guidance provided by the extracellular matrix (ECM, collagen type 1) network facilitated far-ranging haptotactic cues that guided monocytes over longer distances. Functionalizing SEVs with miR-128 mimic revealed that the strategic changes in monocyte haptotaxis are in large part the result of SEV-associated miR-128. Interpretation: Compositionally and functionally distinct HIV+COC+ and HIV–COC– SEVs and their exmiR networks may provide cells relevant but divergent haptotactic guidance in the absence of chemotactic cues, under both physiological and pathophysiological conditions. Funding Statement: This work was supported by grants from the National Institute on Drug Abuse (NIDA), grants DA042348, DA050169 and DA053643 to C.M.O. Declaration of Interests: None to declare. Ethics Approval Statement: This study was conducted according to University regulations approved by Stony Brook University Institutional Review Boards (IRB # 201608703) using de-identified human specimens obtained through the Multicenter AIDS Cohort Study (MACS).

Teen marijuana and nicotine vaping remains high: MTF

The most recent Monitoring the Future (MTF) survey of teen substance use behaviors and attitudes, released last week by the National Institute on Drug Abuse (NIDA), found that nicotine and marijuana vaping levels remain markedly high but did not increase between 2019 and early 2020. From 2017 to 2019, the percentage of teenagers who said they vaped nicotine in the past 12 months roughly doubled for eighth graders from 7.5% to 16.5%, for 10th graders from 15.8% to 30.7% and for 12th graders from 18.8% to 35.3%. In 2020, the rates held steady at a respective 16.6%, 30.7% and 34.5%, according to the survey results released Dec. 15.

In Case You Haven't Heard…

The National Institute on Drug Abuse (NIDA) is looking at ways to increase access to methadone, which, for patients with opioid use disorder, is currently available only through opioid treatment programs (OTPs), ADAW has learned. NIDA wants to look at more than what would be allowed by regulation: primary care, pharmacies, mobile vans and more. This would be most likely done through NIDA's Clinical Trials Network. There are many treatment advocates who think less‐regulated systems would be valuable for long‐term stable patients, but not for new patients. It is expected that patients will play a role in whatever is developed — but this is not guaranteed, not by a long shot. Confidentiality is still a prized ingredient of going to an OTP.

Behavioral and Enhanced Perinatal Intervention (B-EPIC): A randomized trial targeting tobacco use among opioid dependent pregnant women

BackgroundOpioid use during pregnancy is a significant public health issue. The standard of care for treating opioid use disorder during pregnancy includes medications for opioid disorder (MOUD). However, tobacco use often goes unaddressed among pregnant women on MOUD. In 2018, our team received a National Institute on Drug Abuse (NIDA) funded R34 to conduct a three year-randomized trial to test the feasibility of a novel tobacco intervention for pregnant women receiving MOUD. AimsThe aims of this study are: (1) to determine the impact of the B-EPIC intervention on maternal tobacco use and stage of change; (2) to determine the impact of B-EPIC on tobacco-related maternal and infant health outcomes including gestational age at birth, birthweight, NAS diagnosis and severity, and number of ear and respiratory infections during the first six months; (3) to compare healthcare utilization and costs incurred by pregnant patients that receive the B-EPIC intervention versus TAU. MethodsWe plan to enroll 100 pregnant women on MOUD for this randomized controlled trial (B-EPIC intervention n = 50 and treatment as usual n = 50). A major strength of this study is its wide range of health and economic outcomes assessed on mother, neonate and the infant. ConclusionsDespite the very high rates of smoking among pregnant women with OUD, there are few tobacco treatment interventions that have been tailored for this high - risk population. The overall goal of this study is to move towards a tobacco treatment standard for pregnant women receiving treatment for OUD.

Epistatic evidence for gender-dependant slow neurotransmission signalling in substance use disorders: PPP1R12B versus PPP1R1B.

BackgroundSlow neurotransmission including DARPP-32 signalling is implicated in substance use disorders (SUDs) by experimental systems but not yet in the human aetiology. PPP1R12B, encoding another protein in the DARPP-32 family, hasn't been studied in the brain.MethodsBrain-regional gene activity was assessed in three different animal models of SUDs for mRNA level alterations. Genetic associations were assessed by meta-analysis of pre-existing dbGaP GWAS datasets for main effects and epistasis with known genetic risks, followed by cell type-specific pathway delineation. Parkinson's disease (PD) was included as a dopamine-related disease control for SUDs.FindingsIn animal models of SUDs, environmentally-altered PPP1R12B expression sex-dependently involves motivation-related brain regions. In humans with polysubstance abuse, meta-analysis of pre-existing datasets revealed that PPP1R12B and PPP1R1B, although expressed in dopamine vs. dopamine-recipient neurons, exerted similar interactions with known genetic risks such as ACTR1B and DRD2 in men but with ADH1B, HGFAC and DRD3 in women. These interactions reached genome-wide significances (Pmeta<10−20) for SUDs but not for PD (disease selectivity: P = 4.8 × 10−142, OR = 6.7 for PPP1R12B; P = 8.0 × 10−8, OR = 2.1 for PPP1R1B). CADM2 was the common risk in the molecular signalling regardless of gender and cell type.InterpretationGender-dependant slow neurotransmission may convey both genetic and environmental vulnerabilities selectively to SUDs.FundingGrants from National Institute on Drug Abuse (NIDA) and National Institute on Alcohol Abuse and Alcoholism (NIAAA) of U.S.A. and National Natural Science Foundation of China (NSFC).

The opioid-impaired provider: A call for national guidance to maximize rehabilitation while protecting patient safety.

The opioid-impaired provider: A call for national guidance to maximize rehabilitation while protecting patient safety.

Vaping nicotine and marijuana more than doubles among college‐age students

The annual Monitoring the Future (MTF) report from the National Institute on Drug Abuse (NIDA) on 19–22‐year‐olds revealed dramatic increases in vaping of marijuana and nicotine among college students and young adults. The study shows that marijuana use is almost at its highest level in the past 4 decades.

Vaping nicotine and marijuana more than doubled

Last week, the annual Monitoring the Future (MTF) report from the National Institute on Drug Abuse (NIDA) revealed dramatic increases in vaping of marijuana and nicotine among college students and young adults. The study shows that marijuana use is almost at its highest level in the past four decades.

Erectile Dysfunction in a Sample of Sexually Active Young Adult Men from a U.S. Cohort: Demographic, Metabolic and Mental Health Correlates.

Little is understood about physiological and psychological correlates of erectile dysfunction among younger men. We examined prevalence and correlates of erectile dysfunction in a large U.S. sample of 18 to 31-year-old men. Erectile dysfunction prevalence and severity (defined using the International Index of Erectile Function-5 scale) were examined in cross-sectional survey data from 2,660 sexually active men, age 18 to 31 years, from the 2013 Growing Up Today Study. Erectile dysfunction medication and supplement use were self-reported. Multivariable models estimated associations of moderate-to-severe erectile dysfunction with demographic (age, marital status), metabolic (body mass index, waist circumference, history of diabetes, hypertension, hypercholesterolemia) and mental health (depression, anxiety, antidepressant use, tranquilizer use) variables. Among sexually active men 11.3% reported mild erectile dysfunction and 2.9% reported moderate-to-severe erectile dysfunction. Married/partnered men had 65% lower odds of erectile dysfunction compared to single men. Adjusting for history of depression, antidepressant use was associated with more than 3 times the odds of moderate-to-severe erectile dysfunction. Anxiety was associated with greater odds of moderate-to-severe erectile dysfunction, as was tranquilizer use. Few men (2%) reported using erectile dysfunction medication or supplements. However, among them, 29.7% misused prescription erectile dysfunction medication. Limitations include reliance upon cross-sectional data and the sample's limited racial/ethnic and socioeconomic diversity. Erectile dysfunction was common in a large sample of sexually active young adult men from a U.S. cohort and was associated with relationship status and mental health. Health providers should screen for erectile dysfunction in young men, and monitor use of prescription erectile dysfunction medications and supplements for sexual functioning.

NASADAD to NIDA: Connect research to practice

When the National Institute on Drug Abuse (NIDA) sought input on its five‐year plan, the people responsible for publicly funded prevention, treatment and recovery — state directors — called for returning to the days of communication between federal agencies like the Substance Abuse and Mental Health Services Administration (SAMHSA) and between NIDA researchers and the service delivery system. In an Aug. 7 letter to NIDA's strategic planning team, Robert I.L. Morrison, executive director of the National Association of State Alcohol and Drug Abuse Directors (NASADAD), noted that each state alcohol and drug agency has a critical role to play in NIDA initiatives. This role includes.

Characteristics of school-based drug prevention programs in Brazil.

The aim of this study was to identify the main characteristics of school-based drug prevention programs in Brazil and verify whether these interventions apply the prevention principles suggested by the National Institute on Drug Abuse (NIDA). A cross-sectional study was conducted using a random national sample of 1,151 public and private school managers. The data were collected using an online questionnaire. Poisson regression was used to identify factors associated with the application of a greater number of prevention principles in the programs. The findings showed that programs were generally sporadic, had an average duration of one semester, incorporated different program models, and primarily directed at students. The most active organization in the delivery of programs was the Military Police. Private schools were shown to be 14% more likely to apply more good practice principles than public schools. Furthermore, programs delivered by school staff, health institutions, or departments of education were more likely to apply more prevention principles. Efforts are needed to improve drug prevention practice in Brazilian schools. Our findings show that, overall, school-based drug prevention programs do not apply the NIDA prevention principles.

Measuring the Effectiveness of Benzodiazepine Prescriptions Control in Community Setting Using Prescription Drug Monitoring Program (PDMP).

Benzodiazepines have been widely prescribed for several years for the treatment of anxiety, insomnia, and post-traumatic stress disorder (PTSD). Benzodiazepines were meant to be for short term use but in clinical settings long term use has been the "norm" for the treatment. Benzodiazepines are known for addiction potential and have been involved in accidental overdose deaths. According to the National Institute on Drug Abuse (NIDA), there has been a tenfold increase in the number of deaths due to overdose from 1999 to 2017. Benzodiazepines contributed to staggering high figures of 11,537 deaths in 2017 alone. Kentucky was ranked 4th in overdose related deaths in 2015 by CDC. Seeing this rise in overdose deaths, our community mental health clinics (CMHC) took the initiative to protect the community by removing benzodiazepines from the approved formulary in all adult outpatient community mental health clinics (total six clinics) in 2016. This project was initiated to protect the community from overdose deaths. In order to see the decrease in the benzodiazepine prescriptions, we did a quarterly Kentucky All Schedule Prescription Electronic Reporting (KASPER) prescriber's reports to see the trend. The goal of this project was to monitor the trend of benzodiazepine prescription control in CMHC. Our hypothesis was implementation of CMHC "No Benzodiazepine" policy would decrease in the number of prescriptions. To implement this change, we made a committee to educate staff including physicians, APRN's and therapists. Patients were also educated and informed regarding benzodiazepine free policy. Education materials were posted in the clinics and handed over to patients. Patients were offered individual and group therapy sessions to learn coping skills to cope with their anxiety. Patients had the option of inpatient detoxification, if clinically indicated. No new patients were started on benzodiazepines and patients who were already on benzodiazepines were slowly titrated off. Slow titration over the course of a few months was done as needed and tolerated. Quarterly, prescriber's prescription reports were generated with the help of KASPER (KASPER is PDMP in the state of Kentucky). After analyzing quarterly reports over the span of 2years, we concluded that there was a total of 89% decrease in benzodiazepine prescriptions. We are hoping to reach close to 100% in the next few years. We conduct a Mental Health Statistics Improvement Program (MHSIP) which is a general patient satisfaction survey done annually. We used this data to monitor the change with this new policy. Open patients report was run to monitor any change in case load before and after the implementation of the policy. After compilation of the KASPER/ PDMP data of all the prescribers- MD's and APRN's, we found an 89% decrease in the number of benzodiazepines prescriptions over the span of 2years. We did the open patients report and did not find any decrease in case load. In 2016, there were 10,359 open patients and in 2018 there were 12,266 open patients. We reviewed the MHSIP general patient satisfaction survey that is done annually, and we did not find any major difference in overall satisfaction as compared to previous years. These practice- based interventions implementing harm reduction strategies suggest that, although it was a difficult task, with strict adherence to no benzodiazepine policy, we were able to achieve a stark drop in the number of benzodiazepine prescriptions, in the span of 2years, and have been able to continue to maintain the low numbers of benzodiazepine prescriptions.

Cannabis research stalled by federal inaction

Researchers in the US who want to investigate the medical benefits and risks of cannabis are frustrated. They would like to evaluate the wide array of cannabis products sold in states where cannabis is legal, but federal law prohibits them from doing so because cannabis is still illegal at the federal level. Most studies on the therapeutic effects of cannabis have relied on synthetic formulations of specific chemicals made by cannabis plants, such as the cannabinoids tetrahydrocannabinol (THC)—the psychoactive component of cannabis—and cannabidiol (CBD). A few researchers have looked at the efficacy of whole cannabis plants to treat chronic pain, but no clinical studies have been conducted on cannabis products purchased from state-authorized dispensaries. US researchers can only study the effects of cannabis using plant material grown by the University of Mississippi under contract with the National Institute on Drug Abuse (NIDA). In March, the US Drug Enforcement Administration released

NIDA: Plethora of treatments for SUDs, regardless of substance

When people refer to “evidence‐based” treatment, they mean treatment that has been proven to be effective and has been incorporated into strict protocols via manuals, so they can be replicated. The National Institute on Drug Abuse (NIDA) has been tracking the many treatment models for general substance use disorders, as well as for specific substances. Motivational interviewing (MI), medication‐assisted treatment (MAT), contingency management (CM) and cognitive behavioral therapy (CBT) are all evidence‐based modalities, explained Ruben Baler, Ph.D., NIDA health scientist, in an email to ADAW.

Recidivism Among Justice-Involved Youth: Findings From JJ-TRIALS.

Recidivism, and the factors related to it, remains a highly significant concern among juvenile justice researchers, practitioners, and policy makers. Recent studies highlight the need to examine multiple measures of recidivism as well as conduct multilevel analyses of this phenomenon. Using data collected in a National Institute on Drug Abuse (NIDA)-funded Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS) cooperative agreement, we examined individual- and site-level factors related to 1-year recidivism among probation youth in 20 sites in five states to answer research questions related to how recidivism rates differ across sites and the relationships between individual-level variables and a county-level concentrated disadvantage measure and recidivism. Our findings of large site differences in recidivism rates, and complex relationships between individual and county-level predictors of recidivism, highlight the need for more nuanced, contextually informed, multilevel approaches in studying recidivism among juveniles.

In Case You Haven't Heard…

If you read the recent interview Nora Volkow, M.D., director of the National Institute on Drug Abuse (NIDA), did with Kaiser Health News (https://www.healthleadersmedia.com/clinical‐care/vaping‐opioid‐addiction‐accelerate‐coronavirus‐risks‐says‐nida‐director), you may have been surprised to see that she said, “Methadone clinics are closing. If they're not closing, they're unable to process the same number of patients — because the staff is getting sick.…” We contacted the NIDA press office to find out where she got this information. The “senior media manager (contractor)” sent this response: “We wish that we had more concrete information to share. As you might expect, data and aggregated, hard numbers on what is happening in communities is difficult to come by these days. We are hearing anecdotal reports, which Nora has mentioned in recent interviews. A good source to contact might be the American Association for the Treatment of Opioid Dependence — they may have a better sense of how things are playing out, or be able to speak to that more directly.” Mark Parrino, president of AATOD, did not have more information, however. “I have not heard about program closings, with the exception of those two programs in Virginia about four weeks ago. They reopened after 14 days. There may be other programs that have closed due to COVID‐19, but I have not heard about them. I do not know what Dr. Volkow is referencing. Is she talking about programs that are temporarily closing due to COVID‐19 infection? In reading through the article, this would appear to be the case. Or is she referencing program closing as a trend? When Nora says things like this, I generally check with Jack Stein, who is the chief of staff at NIDA. He is quite sharp and may be able to provide some background.” We subsequently emailed Stein to follow up, but he did not respond.

ABCD study funding extended

The Adolescent Brain Cognitive Development (ABCD) study supported by the National Institutes of Health has received almost $290 million in new funding for 7 years, the National Institute on Drug Abuse (NIDA) announced last week. The study, launched in 2015, is following almost 12,000 children for at least 10 years, beginning at the age of 9 or 10. The new funding will go to the University of California, San Diego, for a coordinating center and data informatics center, as well as to the project sites where children are assessed.

ABCD study funded for at least seven more years

The Adolescent Brain Cognitive Development (ABCD) study supported by the National Institutes of Health has received almost $290 million in new funding for seven years, the National Institute on Drug Abuse (NIDA) announced last week. The study, launched in 2015 (see “First 13 grants awarded in NIDA‐NIAAA teen study,” ADAW Oct. 5, 2015; https://onlinelibrary.wiley.com/doi/epdf/10.1002/adaw.30343), is following almost 12,000 children for at least 10 years, beginning at the age of 9 or 10. The new funding will go to the University of California, San Diego, for a coordinating center and data informatics center, as well as to the project sites where children are assessed.

Discriminant Function Analyses: Classifying Drugs/Violence Victimization Typologies Among Incarcerated Rural Women.

This study examined the relationship between drug use and violence victimization among incarcerated women in Appalachian Kentucky. The purpose of this study was to test the utility of Goldstein's tripartite conceptual framework among rural incarcerated women, by examining whether distinct drugs/violence nexus groups could be classified based on psychopharmacological, economic-compulsive, and systemic factors. This study used secondary data from a National Institute on Drug Abuse (NIDA)-funded grant focused on risk reduction among high-risk incarcerated women in Appalachia (N = 400). Predicted drugs/violence groups were developed using a series of discriminant function analyses. The data yielded three statistically significant discriminant models. Findings of the classified groupings indicated support for three distinct drugs/violence victimization subgroups. The psychopharmacological group showed the greatest prevalence (n = 181; Wilks's λ = .389, F = 3.94, p < .001), followed by the economic-compulsive group (n = 77; Wilks's λ = .584, F = 11.86, p < .001) and systemic group (n = 55) significant (Wilks's λ = .994, F = 2.247, p < .035). To date, this is the first study to report a relationship between systemic violence victimization among rural communities. These findings could offer novel considerations for theory development and implications for clinical practice regarding the drug-related risks for violence victimization among rural incarcerated women.

Trauma, substance use, and mental health symptoms in transitional age youth experiencing homelessness.

This descriptive study examined the prevalence and correlates of trauma, substance use, and mental health symptoms in homeless transitional age youth (TAY) in San Francisco. One hundred homeless TAY were recruited from a community-based organization to complete a survey on trauma, mental health symptoms, and substance use. We used these measures: National Institute on Drug Abuse (NIDA)-Modified Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) for frequency and risk level of substance use; the 10-item Adverse Childhood Experiences (ACEs) for prevalence of trauma; the Post-traumatic Stress Disorder Checklist for DSM-5 for post-traumatic stress disorder (PTSD) symptoms; Center for Epidemiologic Studies Depression Scale for depression symptoms; and Generalized Anxiety Disorder 7-item for anxiety symptoms. Almost all (n=98) participants experienced at least one ACE during childhood, and 77% experienced four or more. Most participants (80%) reached the diagnostic threshold for PTSD, 74% for depression, and 51% for moderate anxiety. Symptoms of PTSD, anxiety, and depression were all significantly correlated with use of opioids and stimulants. Trauma, and co-occurring substance use and mental health problems are prevalent among homeless TAY. Individual- and community-level interventions are needed to address and improve the health of this population.