Confronting the challenge of failed translation in medications development for substance use disorders.
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ABSTRACT:
SUBMITTER: Negus SS
PROVIDER: S-EPMC8418188 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesIn Ethiopia, little is known about the association between substance use disorders and adherence to antituberculosis (anti-TB) medications. Therefore, the objective of this study was to assess the effect of substance use disorders on adherence to anti-TB medications in Southwest Ethiopia.DesignProspective cohort study.SettingsPatients were recruited from 22 health centres and four hospitals in Southwest Ethiopia.ParticipantsThis study was conducted among 268 patients with TB, aged 18-80 in Southwest Ethiopia between October 2017 and October 2018. At baseline, patients who were exposed substance use disorders (134 patients) and unexposed to substance use disorders (134 patients) were recruited. Patients were followed for 6 months, and data were collected on three occasions.Main outcome measureAdherence to anti-TB medications.ResultsPatients with substance use disorders had consistently higher prevalence of non-adherence than those without, 16.4% versus 3.0% at baseline, 41.7% versus 14.4% at 2-month follow-up and 45.7% versus 10.8% at 6-month follow-up assessments. Patients with khat use disorder were 3.8 times more likely to be non-adherent to anti-TB medications than patients without khat use disorder (Adjusted odds ratio (aOR)=3.8, 95% CI 1.8 to 8.0). Patients who had alcohol use disorder (AUD) were also 3.2 times likely to have poor adherence compared with their counterparts (aOR=3.2, 95% CI 1.6 to 6.6). In addition, being educated (aOR=4.4, 95% CI 1.7 to 11.3), and being merchant (aOR=6.1, 95% CI 1.2 to 30.8) were associated with non-adherence to anti-TB medications.ConclusionKhat and AUDs predict greater likelihood of non-adherence to anti-TB medication. This implies the need to integrate the management for substance use disorders into the existing TB treatment services.
| S-EPMC8258551 | biostudies-literature
Project description:Despite growing interest in the use of evidence-based treatment practices for treating substance use disorders, adoption of medications by treatment programs remains modest. Drawing on resource dependence and institutional theory, this study examined the relationships between adoption of medications by treatment programs and their perceptions about the state policy environment.Data were collected through mailed surveys and telephone interviews with 250 administrators of publicly funded substance abuse treatment programs in the United States between 2009 and 2010. Multiple imputation and multivariate logistic regression were used to estimate the associations between perceptions of the state policy environment and the odds of adopting at least one medication for the treatment of substance use disorders.A total of 91 (37%) programs reported having prescribed any medication for treatment of a substance use disorder. Programs were significantly more likely to have adopted at least one medication if they perceived greater support for medications by the Single State Agency. The odds of adoption were significantly greater if the program was aware that at least one medication was included on their state's Medicaid formulary and that state-contract funding permitted the purchase of medications.States may play significant roles in promoting the adoption of medications, but adequate dissemination of information about state policies and priorities may be vital to further adoption. Future research should continue to study the relationships between the adoption of medications for treating substance use disorders and the evolving policy environment.
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Project description:Environmental contexts that are reliably associated with the use of pharmacologically active substances are hypothesized to contribute to substance use disorders. In this review, we provide an updated summary of parallel preclinical and human studies that support this hypothesis. Research conducted in rats shows that environmental contexts that are reliably paired with drug use can renew extinguished drug-seeking behavior and amplify responding elicited by discrete, drug-predictive cues. Akin to drug-associated contexts, interoceptive drug stimuli produced by the psychopharmacological effects of drugs can also influence learning and memory processes that play a role in substance use disorders. Findings from human laboratory studies show that drug-associated contexts, including social stimuli, can have profound effects on cue reactivity, drug use, and drug-related cognitive expectancies. This translationally relevant research supports the idea that treatments for substance use disorders could be improved by considering drug-associated contexts as a factor in treatment interventions. We conclude this review with ideas for how to integrate drug-associated contexts into treatment-oriented research based on 4 approaches: pharmacology, brain stimulation, mindfulness-based relapse prevention, and cognitive behavioral group therapy. Throughout, we focus on alcohol- and tobacco-related research, which are two of the most prevalent and commonly misused drugs worldwide for which there are known treatments.
| S-EPMC7007469 | biostudies-literature
Project description:Patients who suffer from alcohol use disorders (AUDs) usually go through various socio-behavioral and pathophysiological changes that take place in the brain and other organs. Recently, consumption of unhealthy food and excess alcohol along with a sedentary lifestyle has become a norm in both developed and developing countries. Despite the beneficial effects of moderate alcohol consumption, chronic and/or excessive alcohol intake is reported to negatively affect the brain, liver and other organs, resulting in cell death, organ damage/failure and death. The most effective therapy for alcoholism and alcohol related comorbidities is alcohol abstinence, however, chronic alcoholic patients cannot stop drinking alcohol. Therefore, targeted therapies are urgently needed to treat such populations. Patients who suffer from alcoholism and/or alcohol abuse experience harmful effects and changes that occur in the brain and other organs. Upon stopping alcohol consumption, alcoholic patients experience acute withdrawal symptoms followed by a protracted abstinence syndrome resulting in the risk of relapse to heavy drinking. For the past few decades, several drugs have been available for the treatment of AUDs. These drugs include medications to reduce or stop severe alcohol withdrawal symptoms during alcohol detoxification as well as recovery medications to reduce alcohol craving and support abstinence. However, there is no drug that completely antagonizes the adverse effects of excessive amounts of alcohol. This review summarizes the drugs which are available and approved by the FDA and their mechanisms of action as well as the medications that are under various phases of preclinical and clinical trials. In addition, the repurposing of the FDA approved drugs, such as anticonvulsants, antipsychotics, antidepressants and other medications, to prevent alcoholism and treat AUDs and their potential target mechanisms are summarized.
| S-EPMC5898984 | biostudies-literature
Project description:Addiction is a devastating disorder that produces persistent maladaptive changes to the central nervous system, including glial cells. Although there is an extensive body of literature examining the neuronal mechanisms of substance use disorders, effective therapies remain elusive. Glia, particularly microglia and astrocytes, have an emerging and meaningful role in a variety of processes beyond inflammation and immune surveillance, and may represent a promising therapeutic target. Indeed, glia actively modulate neurotransmission, synaptic connectivity and neural circuit function, and are critically poised to contribute to addictive-like brain states and behaviors. In this review, we argue that glia influence the cellular, molecular, and synaptic changes that occur in neurons following drug exposure, and that this cellular relationship is critically modified following drug exposure. We discuss direct actions of abused drugs on glial function through immune receptors, such as Toll-like receptor 4, as well as other mechanisms. We highlight how drugs of abuse affect glia-neural communication, and the profound effects that glial-derived factors have on neuronal excitability, structure, and function. Recent research demonstrates that glia have brain region-specific functions, and glia in different brain regions have distinct contributions to drug-associated behaviors. We will also evaluate the evidence demonstrating that glial activation is essential for drug reward and drug-induced dopamine release, and highlight clinical evidence showing that glial mechanisms contribute to drug abuse liability. In this review, we synthesize the extensive evidence that glia have a unique, pivotal, and underappreciated role in the development and maintenance of addiction.
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Project description:BACKGROUND:Changes in the use of psychoactive substances and medications and in the occurrence of substance-related disorders enable assessment of the magni- tude of the anticipated negative consequences for the population. METHODS:Trends were analyzed in the consumption of tobacco, alcohol, cannabis and other illegal drugs, analgesics, and hypnotics/sedatives, as well as trends in substance-related disorders, as coded according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The data were derived from nine waves of the German Epidemiological Survey of Substance Abuse (Epidemiologischer Sucht- survey, ESA) from 1995 to 2018. The data were collected in written form or by means of a combination of paper and internet-based questionnaires or telephone interviews. RESULTS:The estimated prevalence rates of tobacco and alcohol consumption and the use of hypnotics/sedatives decreased over time. On the other hand, increasing prevalence rates were observed for the consumption of cannabis and other illegal drugs and the use of analgesics. The trends in substance-related disorders showed no statistically significant changes compared to the reference values for the year 2018, except for higher prevalence rates of nicotine dependence, alcohol abuse and dependence, analgesic dependence, and hypnotic/sedative dependence in the year 2012 only. CONCLUSION:Trends in tobacco and alcohol consumption imply a future decline in the burden to society from the morbidity, mortality, and economic costs related to these substances. An opposite development in cannabis use cannot be excluded. No increase over time was seen in the prevalence of analgesic dependence, but the observed increase in the use of analgesics demands critical attention.
| S-EPMC6804271 | biostudies-literature
Project description:In contrast to traditional pharmacodynamic approaches to treat substance-use disorders (SUDs), the use of biologics (vaccines, monoclonal antibodies, and genetically modified enzymes) is based on a pharmacokinetic principle: reduce the amount of (and, ideally, eliminate) abused drug entering the central nervous system (CNS). Preclinical studies indicate that biologics are effective in both facilitating abstinence and preventing relapse to abused substances ranging from nicotine to heroin. While data are still emerging, the results from multiple clinical trials can best be described as mixed. Nonetheless, these clinical studies have already provided important insights using 'first-generation' tools that may inform the development of effective and commercially viable biologics to treat tobacco-, cocaine-, and methamphetamine-use disorders.
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Project description:While the majority of youth who experiment with alcohol and drugs do not develop problematic levels of use, 5% of adolescents and 15% of young adults meet criteria for a substance use disorder (SUD). Pharmacotherapy, in combination with behavioral interventions, has the potential to increase the likelihood of successful treatment for youth struggling with SUD; however, the literature in this area is limited. To date, there are no Food and Drug Administration (FDA)-approved medications for adolescent SUD, other than buprenorphine, which has been approved down to 16 years of age for opioid use disorder. Despite alcohol and cannabis being the most commonly used substances during adolescence, only three medications have been tested among this demographic, and only two have warranted further study (i.e., naltrexone for alcohol and N-acetylcysteine for cannabis use disorder). Although less common in adolescents and young adults, the most promising pharmacological findings for this age group are for opioid (buprenorphine) and tobacco (bupropion and varenicline) use disorders. In addition, despite the recent marked increases in electronic nicotine delivery systems (i.e., vaping) among youth, treatment strategies are still in their infancy and no recommendation exists for how to promote cessation for youth vaping. Current findings are limited by: small, demographically homogeneous samples; few trials, including a substantial number of youth younger than 18; low retention; medication adherence rates; and minimal information on effective dosing levels and long-term outcomes. Overall, pharmacotherapy may be a potentially effective strategy to increase treatment effects; however, more rigorous research trials are warranted before FDA approval would be granted for any of the potential adjunctive medications in this age group.
| S-EPMC6727439 | biostudies-literature
Project description:Substance use disorders represent a serious public health and social issue worldwide. Recent advances in our understanding of the neurobiological basis of the addictive processes have led to the development of a growing number of pharmacological agents to treat addictions. Despite this progress, there are no approved pharmacological treatments for cocaine, methamphetamine and cannabis addiction. Moving treatment development to the next stage will require novel ways of approaching substance use disorders. One such novel approach is to target individual vulnerabilities, such as cognitive function, sex differences and psychiatric comorbidities. This review provides a summary of promising pharmacotherapies for alcohol, opiate, stimulant and nicotine addictions. Many medications that target positive and negative reinforcement of drugs, as well as individual vulnerabilities to addiction, are in different phases of development. Clinical trials testing the efficacy of these medications for substance use disorder are warranted.
| S-EPMC4014020 | biostudies-literature
Project description:Substance use disorders (SUDs) are prevalent and result in an array of negative consequences. They are influenced by genetic factors (h2 = ~50%). Recent years have brought substantial progress in our understanding of the genetic etiology of SUDs and related traits. The present review covers the current state of the field for SUD genetics, including the epidemiology and genetic epidemiology of SUDs, findings from the first-generation of SUD genome-wide association studies (GWAS), cautions about translating GWAS findings to clinical settings, and suggested prioritizations for the next wave of SUD genetics efforts. Recent advances in SUD genetics have been facilitated by the assembly of large GWAS samples, and the development of state-of-the-art methods modeling the aggregate effect of genome-wide variation. These advances have confirmed that SUDs are highly polygenic with many variants across the genome conferring risk, the vast majority of which are of small effect. Downstream analyses have enabled finer resolution of the genetic architecture of SUDs and revealed insights into their genetic relationship with other psychiatric disorders. Recent efforts have also prioritized a closer examination of GWAS findings that have suggested non-uniform genetic influences across measures of substance use (e.g. consumption) and problematic use (e.g. SUD). Additional highlights from recent SUD GWAS include the robust confirmation of loci in alcohol metabolizing genes (e.g. ADH1B and ALDH2) affecting alcohol-related traits, and loci within the CHRNA5-CHRNA3-CHRNB4 gene cluster influencing nicotine-related traits. Similar successes are expected for cannabis, opioid, and cocaine use disorders as sample sizes approach those assembled for alcohol and nicotine.
| S-EPMC8477224 | biostudies-literature