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in category addiction medicine

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1: Comparing rapid micro-induction and standard induction of buprenorphine/naloxone for treatment of opioid use disorder: Protocol for an open-label, parallel-group, superiority, randomized controlled trial
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Posted 26 May 2020

Comparing rapid micro-induction and standard induction of buprenorphine/naloxone for treatment of opioid use disorder: Protocol for an open-label, parallel-group, superiority, randomized controlled trial
4,349 downloads medRxiv addiction medicine

James S.H. Wong, Mohammadali Nikoo, Jean N. Westenberg, Janet G. Suen, Jennifer Wong, Reinhard M. Krausz, Christian G. Schutz, Marc Vogel, Jesse A. Sidhu, Jessica Moe, Shane Arishenkoff, Donald Griesdale, Nickie Mathew, Pouya Azar

Background: Buprenorphine/naloxone (Suboxone) is a current first-line treatment for opioid use disorder (OUD). The standard induction method of buprenorphine/naloxone requires patients to be abstinent from opioids and therefore experience withdrawal symptoms prior to induction, which can be a barrier in starting treatment. Rapid micro-induction (micro-dosing) involves the administration of small, frequent does of buprenorphine/naloxone and removes the need for a period of withdrawal prior to the start of treatment. This study aims to compare the effectiveness and safety of rapid micro-induction versus standard induction of buprenorphine/naloxone in patients with OUD. Methods: This is a randomized, open-label, two-arm, superiority, controlled trial comparing the safety and effectiveness of rapid micro-induction versus standard induction of buprenorphine/naloxone for the treatment of OUD. A total of 50 participants with OUD will be randomized at one Canadian hospital. The primary outcome is successful induction of buprenorphine/naloxone with low levels of withdrawal. Secondary outcomes are treatment retention, illicit drug use, self-reported drug use behaviour, craving, pain, physical health, safety, and client satisfaction. Discussion: This is the first randomized controlled trial to compare the effectiveness and safety of rapid micro-induction versus standard induction of buprenorphine/naloxone. This study will thereby generate evidence for a novel induction method which eliminates substantial barriers to the use of buprenorphine/naloxone in the midst of the ongoing opioid crisis.

2: A global survey on changes in the supply, price and use of illicit drugs and alcohol, and related complications during the 2020 COVID-19 pandemic
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Posted 21 Jul 2020

A global survey on changes in the supply, price and use of illicit drugs and alcohol, and related complications during the 2020 COVID-19 pandemic
1,856 downloads medRxiv addiction medicine

Ali Farhoudian, Seyed Ramin Radfar, Hossein Mohaddes Ardabili, Parnian Rafei, Mohsen Ebrahimi, Arash Khojasteh Zonoozi, Cornelis A J De Jong, Mehrnoosh Vahidi, Masud Yunesian, Christos Kouimtsidis, Shalini Arunogiri, Helena Hansen, Kathleen T Brady, Marc Potenza, ISAM-PPIG Global Survey Consortium, Alexander Mario Baldacchino, Hamed Ekhtiari

Background and aims: COVID-19 has infected more than 13 million people worldwide and impacted the lives of many more, with a particularly devastating impact on vulnerable populations, including people with substance use disorders (SUDs). Quarantines, travel bans, regulatory changes, social distancing and 'lockdown' measures have affected drug and alcohol supply chains and subsequently their availability, price and use patterns, with possible downstream effects on presentations of SUDs and demand for treatment. Given the lack of multicentric epidemiologic studies, we conducted a rapid global survey within the International Society of Addiction Medicine (ISAM) network in order to understand the status of substance-use patterns during the current pandemic. Design: Cross-sectional survey. Setting: Worldwide. Participants: Starting on April 4th, 2020 during a 5-week period, the survey received 185 responses from 77 countries. Measurements: To assess addiction medicine professionals' perceived changes in drug and alcohol supply, price, use pattern and related complications during the COVID-19 pandemic. Findings: Participants reported (among who answered ''decreased'' or ''increased'', percentage of those who were in majority is reported in the parenthesis) a decrease in drug supply (69.0%), and at the same time an increase in price (95.3%) globally. With respect to changes in use patterns, an increase in alcohol (71.7%), cannabis (63.0%), prescription opioids (70.9%), and sedative/hypnotics (84.6%) use was reported while the use of amphetamines (59.7%), cocaine (67.5%), and opiates (58.2%) was reported to decrease overall. Conclusions: The global report on changes in the availability, use patterns and complications of alcohol and drugs during the COVID-19 pandemic should be considered in making new policies and in developing mitigating measures and guidelines during the current pandemic (and probable future ones) in order to minimize risks to SUDs. Key words: COVID-19, pandemic, alcohol, drug, substance use disorder, supply, price.

3: Take-Home Dosing Experiences among Persons Receiving Methadone Maintenance Treatment During COVID-19
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Posted 02 Sep 2020

Take-Home Dosing Experiences among Persons Receiving Methadone Maintenance Treatment During COVID-19
1,446 downloads medRxiv addiction medicine

Mary C. Figgatt, Zach Salazar, Elizabeth Day, Louise Vincent, Nabarun Dasgupta

PurposeMethadone maintenance treatment is a life-saving treatment for people with opioid use disorders (OUD). The coronavirus pandemic (COVID-19) introduces many concerns surrounding access to opioid treatment. In March 2020, the Substance Abuse and Mental Health Services Administration (SAMHSA) issued guidance allowing the expansion of take-home methadone doses. We sought to describe changes to treatment experiences from the perspective of persons receiving methadone at outpatient treatment facilities for OUD. MethodsWe conducted an in-person survey among 104 persons receiving methadone from three clinics in central North Carolina in June and July 2020. Surveys collected information on demographic characteristics, methadone treatment history, and experiences with take-home methadone doses in the context of COVID-19 (i.e., before and since March 2020). ResultsBefore COVID-19, the clinic-level percent of participants receiving any amount of days supply of take-home doses at each clinic ranged from 56% to 82%, while it ranged from 78% to 100% since COVID-19. The clinic-level percent of participants receiving a take-homes days supply of a week or longer (i.e., [≥]6 days) since COVID-19 ranged from 11% to 56%. Among 87 participants who received take-homes since COVID-19, only four reported selling their take-home doses. ConclusionsOur study found variation in experiences of take-home dosing by clinic and little diversion of take-home doses. While SAMSHA guidance should allow expanded access to take-home doses, adoption of these guidelines may vary at the clinic level. The adoption of these policies should be explored further, particularly in the context of benefits to patients seeking OUD treatment. HighlightsO_LIMethadone take-home dosing of survey participants varied by clinic. C_LIO_LIDiversion of take-home doses was rare. C_LIO_LIImplementation of COVID-19 opioid treatment guidelines should be examined further. C_LI

4: Ancestry May Confound Genetic Machine Learning: Candidate-Gene Prediction of Opioid Use Disorder as an Example
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Posted 14 Sep 2020

Ancestry May Confound Genetic Machine Learning: Candidate-Gene Prediction of Opioid Use Disorder as an Example
1,438 downloads medRxiv addiction medicine

Alexander S. Hatoum, Frank R Wendt, Marco Galimberti, Renato Polimanti, Benjamin M Neale, Henry Kranzler, Joel Gelernter, Howard Edenberg, Arpana Agrawal

Using genetics to predict the likelihood of future psychiatric disorders such as Opioid Use Disorder (OUD) poses scientific and ethical challenges. This report illustrates flaws in current machine learning (ML) approaches to such predictions using, as an example, a proposed genetic test for OUD derived from 16 candidate gene variants. In an independent sample of OUD cases and controls of European and African descent, results from five ML algorithms trained with purported "reward-system" candidate variants demonstrate that ML methods predict genomic ancestry rather than OUD. Further, sets of variants matched to the candidate SNPs by allele frequency produced similarly flawed predictions, questioning the plausibility of the selected candidate variants. We conclude that the genetic prediction of OUD (and by extension other highly polygenic psychiatric diseases) by ML has high potential to increase the likelihood of medical discrimination against population subgroups, with no benefit of accurate prediction for early intervention.

5: Problem drinking before and during the COVID-19 crisis in US and UK adults: Evidence from two population-based longitudinal studies
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Posted 28 Jun 2020

Problem drinking before and during the COVID-19 crisis in US and UK adults: Evidence from two population-based longitudinal studies
1,384 downloads medRxiv addiction medicine

Michael Daly, Eric Robinson

Background The impact of the COVID-19 crisis on potentially harmful alcohol consumption is unclear. Aims To test whether the prevalence of problem drinking has changed from before to during the COVID-19 crisis in the US and UK. Design/Setting We examined nationally representative longitudinal data on how problem drinking has changed from pre-pandemic levels among adults in the US (N=7,327; Understanding America Study) and UK (N=12,594; UK Household Longitudinal Study). Methods In the US, we examined rates of consuming alcohol [&ge;] 4 times in the past week at baseline (March, 2020) and across four waves of follow-up (April-May, 2020). In the UK we assessed the prevalence of consuming alcohol [&ge;] 4 times per week and weekly heavy episodic drinking using the AUDIT-C at baseline (2017-2019) and during the COVID-19 lockdown (April, 2020). We also tested whether there were specific groups at greater risk of increased problem drinking during the pandemic. Results Among US adults, there was a statistically significant increase in the percentage of participants reporting drinking alcohol [&ge;] 4 times a week which rose significantly from 11.7% to 17.9% (53% increase, p < .001) as the COVID-19 crisis developed in the US. Among UK adults, the percentage of participants reporting drinking [&ge;] 4 times a week increased significantly from 14.2% to 23% (62% increase, p < .001) and heavy episodic drinking at least weekly increased significantly from 9.7% to 16.6% (71% increase, p < .001) when compared to pre-COVID-19 lockdown levels. Trends were similar across population demographics, although those aged under 50 years and higher income groups displayed the largest increases. Conclusions The COVID-19 crisis has been associated with substantial increases in problematic drinking in both US and UK adults.

6: A Randomized Controlled Trial of a Digital Therapeutic Intervention for Smoking Cessation.
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Posted 26 Jun 2020

A Randomized Controlled Trial of a Digital Therapeutic Intervention for Smoking Cessation.
1,368 downloads medRxiv addiction medicine

Jamie Webb, Sarrah Peerbux, Peter Smittenaar, Sarim Siddiqui, Yusuf Sherwani, Maroof Ahmed, Hannah MacRae, Hannah Puri, Sangita Bhalla, Azeem Majeed

Background and Aims: Tobacco smoking remains the leading cause of preventable death and disease worldwide. Digital interventions delivered through smartphones offer a promising alternative to traditional methods, but little is known about their effectiveness. Our aim was to determine the effectiveness of Quit Genius, a novel digital therapeutic intervention for smoking cessation. Design: Two-arm, single-blinded, parallel-group randomized controlled trial Setting: Referrals from primary care practices Participants: 556 Adult smokers (aged [&ge;]18 years), smoking at least five cigarettes a day for the past year. 530 were included for the final analysis. Intervention and comparator: Digital therapeutic intervention for smoking cessation consisting of a smartphone application delivering cognitive behavioral therapy content, one-to-one coaching, craving tools and tracking capabilities. The control intervention was Very Brief Advice along the Ask, Advise, Act model. All participants were offered nicotine replacement therapy for three months. A random half of each arm was assigned a carbon monoxide (CO) device for biochemical verification. Measurements: The primary outcome was self-reported seven-day point prevalence abstinence at four-weeks post quit date. Findings: 556 participants were randomized (treatment n=277, control n=279). The intention-to-treat analysis included 530 participants (n=265 in each arm; 11 excluded for randomization before trial registration, and 15 for protocol violations at baseline visit). At four weeks post-quit date, 45% of participants in the treatment arm had not smoked in the preceding seven days, compared to 29% in control (risk ratio 1.55 [1.23, 1.96], p = 0.0002; intention-to-treat, n=530). Self-reported seven-day abstinence agreed with CO measurement (CO <10 ppm) in 96% of cases (80/83) where CO readings were available. No harmful effects of the intervention were observed. Conclusions: The Quit Genius digital therapeutic intervention is a superior treatment in achieving smoking cessation four weeks post quit date compared to very brief advice.

7: Associations between inhibitory control, stress, and alcohol (mis)use during the first wave of the COVID-19 pandemic in the UK: a national cross-sectional study utilising data from four birth cohorts
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Posted 25 Sep 2020

Associations between inhibitory control, stress, and alcohol (mis)use during the first wave of the COVID-19 pandemic in the UK: a national cross-sectional study utilising data from four birth cohorts
1,155 downloads medRxiv addiction medicine

James M Clay, Lorenzo D Stafford, Matthew O Parker

Aims. To investigate: (1) alcohol use during the pandemic in the UK; and (2) the extent to which poor inhibitory control and/or stress were associated with any change in alcohol use or hazardous drinking. Design. Cross-sectional online survey administered between 2 and 31 May 2020. Setting. UK. Participants. 13,453 respondents aged 19 - 62 years comprising participants of four nationally representative birth cohorts (19, 30, 50 and 62-years old). Measurements. Change in alcohol use and risk of alcohol-related harm due to hazardous drinking and change in stress since the start of the Coronavirus outbreak; inhibitory control (impatience and risk-taking); and sociodemographic characteristics, including diagnosed or suspected COVID-19, and key worker status. Findings. Most respondents reported consuming/feeling the same amount or less alcohol/stress. However, a significant minority, particularly among thirty- (29.08%) and fifty-year-olds (26.67%), reported drinking more, and between 32.23% and 45.02% of respondents reported feeling more stressed depending on cohort. Being female was associated with an increased likelihood of reporting heightened stress (OR19 = 1.54, 95% CI 1.08 to 2.20; OR30 = 1.93, 95% CI 1.39 to 2.70; OR50 = 1.62, 95% CI 1.37 to 1.92; OR62 = 2.03, 95% CI 1.66 to 2.48). Stress was associated with hazardous drinking among 30-year-olds (OR = 3.77, 95% CI 1.15 to 12.28). Impatience was associated with both increased alcohol use (1.14, 95% CI 1.06, 1.24) and hazardous drinking (1.20, 95% CI 1.05, 1.38) among 19-year-olds. Risk-taking was associated with hazardous drinking for 30-year-olds (OR = 1.18, 95% CI 1.05, 1.32). Conclusions. These data highlight concerns about the UK government's stance on the "essential" nature of off-premises alcohol sales during the lockdown, particularly from a public health perspective, when considering those at risk of alcohol misuse and alcohol-related harm.

8: Moderators of changes in smoking, drinking, and quitting behaviour associated with the first Covid-19 lockdown in England
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Posted 17 Feb 2021

Moderators of changes in smoking, drinking, and quitting behaviour associated with the first Covid-19 lockdown in England
1,120 downloads medRxiv addiction medicine

Sarah E Jackson, Emma Beard, Colin Angus, Matt Field, Jamie Brown

Aim: To estimate changes in smoking, drinking, and quitting behaviour from before to during the first Covid-19 lockdown in England, and whether changes differed by age, sex, or social grade. Design: Representative cross-sectional surveys of adults, collected monthly between August 2018 and July 2020. Setting: England. Participants: 36,980 adults ([&ge;]18y). Measurements: Independent variables were survey month (pre-lockdown: August-February vs. lockdown months: April-July) and year (pandemic: 2019/20 vs. comparator: 2018/19). Smoking outcomes were smoking prevalence, cessation, quit attempts, quit success, and use of evidence-based or remote cessation support. Drinking outcomes were high-risk drinking prevalence, alcohol reduction attempts, and use of evidence-based or remote support. Moderators were age, sex, and occupational social grade (ABC1=more advantaged/C2DE=less advantaged). Findings: Relative to changes over the same time period in 2018/19, lockdown was associated with significant increases in smoking prevalence (+24.7% in 2019/20 vs. 0.0% in 2018/19, ORadj=1.35[95%CI=1.12-1.63]) and quit attempts (+39.9% vs. -22.2%, ORadj=2.48[1.76-3.50]) among 18-34 year-olds, but not older groups. Increases in cessation (+156.4% vs. -12.5%, ORadj=3.08[1.86-5.09]) and the success rate of quit attempts (+99.2% vs. +0.8%, ORadj=2.29[1.31-3.98]) were also observed, and did not differ significantly by age, sex, or social grade. Lockdown was associated with a significant increase in high-risk drinking prevalence across all sociodemographic groups (+39.5% vs. -7.8%, ORadj=1.80[1.64-1.98]), with particularly high increases among women (ORadj=2.17[1.87-2.53]) and social grades C2DE (ORadj=2.34[2.00-2.74]). Alcohol reduction attempts increased significantly among high-risk drinkers from social grades ABC1 (ORadj=2.31[1.78-3.00]) but not C2DE (ORadj=1.25[0.83-1.88]), with larger increases among those aged 18-34 (ORadj=2.56[1.72-3.81]) and [&ge;]60 (ORadj=1.43[1.05-1.95]) than 35-59 (ORadj=2.51[1.51-4.18]). There were few significant changes in use of support for smoking cessation or alcohol reduction, although samples were small. Conclusions: In England, the first Covid-19 lockdown was associated with increased smoking prevalence among younger adults, and increased high-risk drinking prevalence among all adults. Smoking cessation activity also increased: more younger smokers made quit attempts during lockdown and more smokers quit successfully. Socioeconomic disparities in drinking behaviour were evident: high-risk drinking increased by more among women and those from less advantaged social grades (C2DE) but the rate of reduction attempts increased only among the more advantaged social grades (ABC1).

9: Reorganization of Substance Use Treatment and Harm Reduction Services during the COVID-19 Pandemic: A Global Survey
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Posted 22 Sep 2020

Reorganization of Substance Use Treatment and Harm Reduction Services during the COVID-19 Pandemic: A Global Survey
1,070 downloads medRxiv addiction medicine

Seyed Ramin Radfar, Cornelis A J De Jong, Ali Farhoudian, Mohsen Ebrahimi, Parnian Rafei, Mehrnoosh Vahidi, Masud Yunesian, Christos Kouimtsidis, Shalini Arunogiri, Omid Massah, Abbas Deylamizadeh, Kathleen T Brady, Anja Busse, ISAM-PPIG Global Survey Consortium, Marc Potenza, Hamed Ekhtiari, Alexander Mario Baldacchino

Background: The COVID-19 pandemic has impacted people with substance use disorders (SUDs) worldwide, and healthcare systems have reorganized their services in response to the pandemic. Methods: One week after the announcement of the COVID-19 as a pandemic, in a global survey, 177 addiction medicine professionals described COVID-19-related health responses in their own 77 countries in terms of SUD treatment and harm reduction services. The health response is categorized around (1) managerial measures and systems, (2) logistics, (3) service providers, and (4) vulnerable groups. Results: Respondents from over 88% of countries reported that core medical and psychiatric care for SUDs had continued; however, only 56% of countries reported having had any business continuity plan, and 37.5% of countries reported shortages of methadone or buprenorphine supplies. Participants of 41% of countries reported partial discontinuation of harm-reduction services such as needle and syringe programs and condom distribution. 57% of overdose prevention interventions and 81% of outreach services also having been negatively impacted. Conclusions: Participants reported that SUD treatment and harm reduction services had been significantly impacted globally early during the COVID-19 pandemic. Based on our findings, we provide a series of recommendations to support countries to be prepared more efficiently for future waves or similar pandemics to 1) help policymakers generate business continuity plans, 2) maintain the use of evidence-based interventions for people with SUDs, 3) be prepared for adequate medication supplies, 4) integrate harm reduction programs with other treatment modalities and 5) have specific considerations for vulnerable groups such as immigrants and refugees.

10: Genetic Liability to Cannabis Use Disorder and COVID-19 Hospitalization
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Posted 18 Nov 2020

Genetic Liability to Cannabis Use Disorder and COVID-19 Hospitalization
1,051 downloads medRxiv addiction medicine

Alexander S Hatoum, Claire L Morrison, Evan A. Winiger, Emma C Johnson, Arpana Agrawal, Ryan Bogdan

Behavioral and life style factors plausibly play a role in likelihood of being hospitalized for COVID-19. Genetic vulnerability to hospitalization after SARS-CoV2 infection may partially relate to comorbid behavioral risk factors, especially the use of combustible psychoactive substances. Paralleling the COVID-19 crisis has been increasingly permissive laws for recreational cannabis use. Cannabis Use Disorder (CUD) is a psychiatric disorder that is heritable and genetically correlated with respiratory disease, independent of tobacco smoking. By leveraging genome-wide association summary statistics of CUD and COVID-19, we find that at least 1/3rd of the genetic vulnerability to COVID-19 overlaps with genomic liability to CUD (rg=.34, p=0.0003). Genetic causality as a potential mechanism of risk could not be excluded. The association between CUD and COVID-19 remained when accounting for genetics of trying marijuana, tobacco smoking (ever smoking regularly, cigarettes per day, smoking cessation, age of smoking initiation), BMI, fasting glucose, forced expiration volume, education attainment, and Townsend deprivation index. Heavy problematic cannabis use may increase chances of hospitalization due to COVID-19 respiratory complications. Curbing excessive cannabis use may be an essential strategy in COVID-19 mitigation.

11: A genetically-informed study disentangling the relationships between tobacco smoking, cannabis use, alcohol consumption, substance use disorders and respiratory infections, including COVID-19
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Posted 15 Feb 2021

A genetically-informed study disentangling the relationships between tobacco smoking, cannabis use, alcohol consumption, substance use disorders and respiratory infections, including COVID-19
1,043 downloads medRxiv addiction medicine

Daniel B. Rosoff, Joyce Yoo, Falk W Lohoff

BackgroundObservational studies suggest smoking, cannabis use, alcohol consumption, cannabis use, and substance use disorders (SUDs) may play a role in the susceptibility for respiratory infections and disease, including coronavirus 2019 (COVID-2019). However, causal inference is challenging due to comorbid substance use. MethodsUsing genome-wide association study data of European ancestry (data from >1.7 million individuals), we performed single-variable and multivariable Mendelian randomization to evaluate relationships between smoking, cannabis use, alcohol consumption, SUDs, and respiratory infections. ResultsGenetically predicted lifetime smoking was found to be associated with increased risk for hospitalized COVID-19 (odds ratio (OR)=4.039, 95% CI 2.335-6.985, P-value=5.93x10-7) and very severe hospitalized COVID-19 (OR=3.091, 95% CI, 1.883-5.092, P-value=8.40x10-6). Genetically predicted lifetime smoking was also associated with increased risk pneumoniae (OR=1.589, 95% CI, 1.214-2.078, P-value=7.33x10-4), lower respiratory infections (OR=2.303, 95% CI, 1.713-3.097, P-value=3.40x10-8), and several others. Genetically predicted cannabis use disorder (CUD) was associated with increased bronchitis risk (OR=1.078, 95% CI, 1.020-1.128, P-value=0.007). ConclusionsWe provide strong genetic evidence showing smoking increases the risk for respiratory infections and diseases even after accounting for other substance use and abuse. Additionally, we provide find CUD may increase the risk for bronchitis, which taken together, may guide future research SUDs and respiratory outcomes.

12: Optimal Control Strategy Applied to Dynamic Model of Drug Abuse Incident for Reducing Its Adverse Effects
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Posted 06 May 2020

Optimal Control Strategy Applied to Dynamic Model of Drug Abuse Incident for Reducing Its Adverse Effects
1,039 downloads medRxiv addiction medicine

Md. Haider Ali Biswas, Md. Azmir Ibne Islam

The present world is facing a devastating reality as drug abuse prevails in every corner of a society. The progress of a country is obstructed due to the excessive practice of taking drugs by the young generation. Like other countries, Bangladesh is also facing this dreadful situation. The multiple use of drug substances leads an individual to a sorrowful destination and for this reason, the natural behavior of human mind is disrupted. An addicted individual may regain his normal life by proper monitoring and treatment. The objective of this study is to analyze a mathematical model on the dynamics of drug abuse in the perspective of Bangladesh and reduce the harmful consequences with effective control policies using the idea of optimal control theory. The model has been solved analytically introducing a specific optimal goal. Numerical simulations have also been performed to review the behaviors of analytical findings. The analytical results have been verified with the numerical simulations. The analysis of this paper shows that it is possible to control drug addiction if there is less interaction among general people with the addicted individuals. Family based care, proper medical treatment, awareness and educational programs can be the most effective ways to reduce the adverse effects of drug addiction in a shortest possible time.

13: Clinical and functional connectivity outcomes of 5-Hz repeated transcranial magnetic stimulation as an add-on treatment in cocaine use disorder: a double-blind randomized controlled trial.
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Posted 19 Jul 2020

Clinical and functional connectivity outcomes of 5-Hz repeated transcranial magnetic stimulation as an add-on treatment in cocaine use disorder: a double-blind randomized controlled trial.
1,022 downloads medRxiv addiction medicine

Eduardo A. Garza-Villarreal, Ruth Alcala-Lozano, Sofia Fernandez-Lozano, Erik Morelos-Santana, Alan Dávalos, Viviana Villicaña, Sarael Alcauter, F. Xavier Castellanos, Jorge J. Gonzalez-Olvera

BACKGROUND: Cocaine use disorder (CUD) is a global condition lacking effective treatment. Repeated magnetic transcranial stimulation (rTMS) may reduce craving and frequency of cocaine use, but little is known about its efficacy and neural effects. METHODS: Using a double-blind placebo-controlled randomized clinical trial (RCT) [NCT02986438], we sought to elucidate short- and long-term clinical benefits of 5-Hz rTMS as an add-on to standard treatment in CUD patients and discern underlying functional connectivity effects using magnetic resonance imaging. Forty-four randomly assigned CUD patients completed the 2-week double-blind acute phase [Sham (n=20, 2f/18m) and Active (n=24, 4f/20m)], in which they received 2 daily sessions of rTMS (5,000 pulses) on the left dorsolateral prefrontal cortex. Subsequently, n=20 CUD patients continued to open-label maintenance (2 weekly sessions for up to 6 months). Measures were acquired at baseline, 2 weeks, 3 months and 6 months. RESULTS: Overall, 5-Hz rTMS plus standard treatment for 2 weeks significantly reduced craving and impulsivity in the Active group; decreased impulsivity correlated with improvements in functional connectivity in executive control and default mode networks. Clinical and functional connectivity effects were maintained for 3 months but they dissipated by 6 months. We did not observe reduction of positive cocaine urine tests, however, self-reported frequency and grams consumed for 6 months were reduced. CONCLUSIONS: With this RCT we show that 5-Hz rTMS has potential promise as an adjunctive treatment for CUD and merits further research.

14: The Addiction Risk Factor: A Unitary Genetic Vulnerability Characterizes Substance Use Disorders and Their Associations with Common Correlates
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Posted 28 Jan 2021

The Addiction Risk Factor: A Unitary Genetic Vulnerability Characterizes Substance Use Disorders and Their Associations with Common Correlates
1,017 downloads medRxiv addiction medicine

Alexander S. Hatoum, Emma C Johnson, Sarah M.C. Colbert, Renato Polimanti, Hang Zhou, Raymond K Walters, Joel Gelernter, Howard J. Edenberg, Ryan Bogdan, Arpana Agrawal

BackgroundSubstance use disorders (SUDs) commonly co-occur with one another and with other psychiatric disorders. They share common features including high impulsivity, negative affect, and lower executive function. We estimate the shared genetic architecture across distinct SUDs, its independence from genetic liability to substance use, and its relation to genetic liability to impulsivity, negative affect, and executive function as well as non-substance psychopathology. MethodsWe tested whether a common genetic factor undergirds liability to problematic alcohol use (PAU), problematic tobacco use (PTU), cannabis use disorder (CUD), and opioid use disorder (OUD) by applying Genomic structural equation modelling to genome-wide association study statistics (Total N = 1,019,521; substance specific Ns range: 82,707-435,563 of European ancestry), while adjusting for the genetics of substance use (Ns = 184,765-632,802). We tested whether shared liability across SUDs is associated with behavioral constructs (risk taking, executive function, neuroticism; Ns = 328,339-427,037) and non-substance use psychopathology (mood/psychotic, compulsive, and early neurodevelopmental disorders). ResultsShared genetic liability to PAU, PTU, CUD, and OUD was characterized by a unidimensional addiction factor (termed a(g)), independent of substance use. OUD and CUD demonstrated the largest loadings. a(g) was associated with risk taking, neuroticism, executive function, and non-substance psychopathology, but retained specific variance (standardized residual= .579). InterpretationA common genetic addictions factor partly explains susceptibility for alcohol, tobacco, cannabis and opioid use disorder. a(g) has unique pathways that are not shared with substance use or non-substance psychopathology, suggesting that addiction is not the linear combination of substance use and psychopathology.

15: Sex differences in opioid and psychostimulant craving and relapse: a critical review
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Posted 31 Mar 2021

Sex differences in opioid and psychostimulant craving and relapse: a critical review
966 downloads medRxiv addiction medicine

Celine Nicolas, Natalie E Zlebnik, Mehdi Farokhnia, Lorenzo Leggio, Satoshi Ikemoto, Yavin Shaham

A widely held dogma in the preclinical addiction field is that females are more vulnerable than males to drug craving and relapse. Here, we first review clinical studies on sex differences in psychostimulant and opioid craving and relapse. Next, we review preclinical studies on sex differences in psychostimulant and opioid reinstatement of drug seeking after extinction of drug self-administration and incubation of drug craving (time-dependent increase in drug seeking during abstinence). We also discuss ovarian hormones role in relapse and craving in humans and animal models and speculate on brain mechanisms underlying their role in cocaine craving and relapse in rodent models. Finally, we discuss imaging studies on brain responses to cocaine cues and stress in men and women. The results of the clinical studies reviewed do not appear to support the notion that women are more vulnerable to psychostimulant and opioid craving and relapse. However, this conclusion is tentative because most of the studies reviewed were correlational, not sufficiently powered, and/or not a priori designed to detect sex differences. Additionally, fMRI studies suggest sex differences in brain responses to cocaine cues and stress. The results of the preclinical studies reviewed provide evidence for sex differences in stress-induced reinstatement and incubation of cocaine craving, but not cue- or cocaine priming-induced reinstatement of cocaine seeking. These sex differences are modulated in part by ovarian hormones. In contrast, the available data do not support the notion of sex differences in craving and relapse/reinstatement for methamphetamine or heroin in rodent models.

16: Polygenic Risk Scores for Alcohol Involvement Relate to Brain Structure in Substance-Naive Children: Results from the ABCD Study
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Posted 28 Jul 2020

Polygenic Risk Scores for Alcohol Involvement Relate to Brain Structure in Substance-Naive Children: Results from the ABCD Study
941 downloads medRxiv addiction medicine

Alexander S Hatoum, Emma C Johnson, David AA Baranger, Sarah E Paul, Arpana Agrawal, Ryan Bogdan

In substance naive children (n=3,013), polygenic risk score (PRS) for problematic alcohol use was associated with lower volume of the frontal pole and greater cortical thickness of the supramarginal gyrus. Several other areas showed nominal significance. These associations suggest that genetic liability to alcohol involvement may manifest as variability in brain structure prior to consumption of the first alcoholic drink and alter brain morphometry during the start of adolescence.

17: Neuroscience-Informed Psychoeducation for Recovery (NIPER): A Program to Promote Metacognition in People with Substance Use Disorders
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Posted 23 Jun 2020

Neuroscience-Informed Psychoeducation for Recovery (NIPER): A Program to Promote Metacognition in People with Substance Use Disorders
940 downloads medRxiv addiction medicine

Tara Rezapour, Mohammad Barzegari, Elham Sharifi, Nastaran Malmir, Hamid Reza Ghiasvand, Mohammad Salehi, Alireza Noroozi, Hamed Ekhtiari

Background: A brief neuroscience-informed psychoeducation program (neuroscience-informed psychoeducation for recovery, NIPER) was developed to promote awareness (metacognition) in the main cognitive domains affected by drug and alcohol use to increase willingness to invest time and effort in the brain and cognition recovery process. The primary aim of this study was to determine the feasibility and acceptability of the NIPER program and its potential effectiveness in terms of increasing metacognition, psychological wellbeing and willingness for the brain and cognition recovery programs among people with substance use disorders (SUDs). Methodology: 56 individuals with SUDs recruited from four outpatient treatment centres in Tehran, Iran and attended four 90-min sessions delivered weekly adjunct to their treatment as usual. The effectiveness was measured in terms of metacognition, and psychological wellbeing at baseline and at the end of the program. Rate of adherence and participation as well as willingness to continue with brain and cognition recovery programs were measured as feasibility outcomes. Results: A total of 51 participants completed the study. Compared to the baseline assessments, participants reported significantly higher problems in dimensions of attention, memory, inhibitory control, decision making, motor/speech, interocpetion and insight, as well as higher level of psychological wellbeing (t=4.66. p<0.001). In terms of feasibility outcomes, the adherence and participation rates were found above 85%. The majority of participants expressed their high willingness to continue the brain and cognition recovery programs (86.2%) and introduce NIPER to their peers (98%). Conclusion: Taking into account the results in terms of feasibility and preliminary effectiveness of NIPER in clinical context of addiction treatment, we consider NIPER as a potentially beneficial interventions to be offered to people with SUD to increase their awareness and engage them to the brain and cognition recovery process. The clinical efficacy of the intervention should be tested in future randomized clinical trials.

18: Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders
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Posted 12 Jan 2022

Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders
863 downloads medRxiv addiction medicine

Alexander S. Hatoum, Sarah MC Colbert, Emma C Johnson, Spencer B Huggett, Joseph D. Deak, Gita A Pathak, Mariela V Jennings, Sarah E Paul, Nicole R. Karcher, Isabella Hansen, David AA Baranger, Alexis Edwards, Andrew David Grotzinger, Substance Use Disorder Working Group of the Psychiatric Genomics Consortium, Elliot M Tucker-Drob, Henry Kranzler, Lea K Davis, Sandra Sanchez-Roige, Renato Polimanti, Joel Gelernter, Howard J Edenberg, Ryan Bogdan, Arpana Agrawal

Genetic liability to substance use disorders can be parsed into loci conferring general and substance-specific addiction risk. We report a multivariate genome-wide association study that disaggregates general and substance-specific loci for problematic alcohol use, problematic tobacco use, and cannabis and opioid use disorders in a sample of 1,025,550 individuals of European and 92,630 individuals of African descent. Nineteen loci were genome-wide significant for the general addiction risk factor (addiction-rf), which showed high polygenicity. Across ancestries PDE4B was significant (among others), suggesting dopamine regulation as a cross-trait vulnerability. The addiction-rf polygenic risk score was associated with substance use disorders, psychopathologies, somatic conditions, and environments associated with the onset of addictions. Substance-specific loci (9 for alcohol, 32 for tobacco, 5 for cannabis, 1 for opioids) included metabolic and receptor genes. These findings provide insight into the genetic architecture of general and substance-specific use disorder risk that may be leveraged as treatment targets.

19: Rise and Regional Disparities in Buprenorphine Utilization in the United States
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Posted 09 Sep 2019

Rise and Regional Disparities in Buprenorphine Utilization in the United States
834 downloads medRxiv addiction medicine

Amir Azar R. Pashmineh, Alexandra Cruz-Mullane, Jaclyn C. Podd, Warren S. Lam, Suhail H. Kaleem, Laura B. Lockard, Mark R. Mandel, Daniel Y. Chung, Corey S. Davis, Stephanie D. Nichols, Kenneth L McCall, Brian J. Piper

AimsBuprenorphine is an opioid partial-agonist used to treat Opioid Use Disorders (OUD). While several state and federal policy changes have attempted to increase buprenorphine availability, access remains well below optimal levels. This study characterized how buprenorphine utilization in the United States has changed over time and whether there are regional disparities in distribution. MeasurementsBuprenorphine weights distributed from 2007 to 2017 were obtained from the Drug Enforcement Administration. Data was expressed as the percent change and as the mg per person in each state. Separately, the formulations for prescriptions covered by Medicaid (2008 to 2018) were examined. FindingsBuprenorphine distributed to pharmacies increased about seven-fold (476.8 to 3,179.9 kg) while the quantities distributed to hospitals grew five-fold (18.6 to 97.6 kg) nationally from 2007 to 2017. Buprenorphine distribution per person was almost 20-fold higher in Vermont (40.4 mg/person) relative to South Dakota (2.1 mg/person). There was a strong association between the number of waivered physicians per 100K population and distribution per state (r(49) = +0.76, p < .0005). The buprenorphine/naloxone sublingual film (Suboxone) was the predominant formulation (92.6% of 0.31 million Medicaid prescriptions) in 2008 but this accounted for less than three-fifths (57.3% of 6.56 million prescriptions) in 2018. ConclusionsAlthough buprenorphine availability has substantially increased over the last decade, distribution was very non-homogenous across the US.

20: The role of social network support on treatment outcomes for medication for opioid use disorder: a systematic review
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Posted 20 Jul 2020

The role of social network support on treatment outcomes for medication for opioid use disorder: a systematic review
831 downloads medRxiv addiction medicine

Navin Kumar, William Oles, Benjamin Howell, Kamila Janmohamed, Selena T. Lee, Melissa C. Funaro, Patrick G. O’Connor, Marcus Alexander

Background. Despite the possible influence of social network support on medication for opioid use disorder (MOUD) treatment, there has been no systematic evaluation of the scientific evidence on the effectiveness of social network support on MOUD. Methods. We searched electronic research databases, specialist journals and grey literature till February 2020. We included experimental and observational studies regarding individuals receiving MOUD, and intersections with social network support. Results. Of 4116 articles screened, we identified 41 studies meeting inclusion criteria. Nineteen studies reported treatment retention/adherence as a MOUD outcome. Three were experimental and 16 were observational. Seventeen studies indicated that social network support was related to improved MOUD treatment retention/adherence. Of the studies with statistically significant results, 12 involved family social network support, while five focused on combined family and peer social network support. Twenty-two studies reported reduced drug use/abstinence as a MOUD outcome. Ten were experimental and 12 were observational. Sixteen studies indicated that social network support was related to reduced drug use/abstinence. Of the studies with statistically significant results, 13 involved family social network support, while three focused on either peer network support or combined family and peer network support. Conclusions. Although evidence was limited, social network support was associated with MOUD treatment outcomes. Interventions around social network support could potentially augment MOUD treatment outcomes. Despite the variety of outcomes and social network support, we suggest the key role of social network support on broad MOUD outcomes.

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