Evaluating opioid analgesic prescribing limits: A narrative review.

PURPOSE: In response to the opioid crisis, opioid analgesic guidelines and prescribing limits have proliferated. The purpose of this narrative review is to examine evidence from studies evaluating the patient or public health impact of federal and state opioid analgesic prescribing guidelines and laws, describe gaps and challenges in current research, and highlight opportunities for improving future research. METHODS: We focused on evidence from a literature review covering 2013 through 2019. We identified 30 studies evaluating opioid analgesic thresholds based on federal policies and guidelines, state laws, and Medicaid state plans that attempt to influence the course of patient care at or when the limit is exceeded (e.g., prior authorization). RESULTS: Most studies evaluated changes in prescribing or dispensing patterns of opioid analgesics, largely finding decreases in prescribing after policy enactment. Fewer studies evaluated patient or public health outcomes beyond changes in prescribing and dispensing patterns; results were infrequently stratified by potentially important sociodemographic and clinical factors. No studies assessed the potential for adverse patient outcomes for which we have emerging evidence of harms. CONCLUSIONS: We describe knowledge gaps and propose opportunities for future research to sufficiently assess the potential impact and unintended consequences of opioid analgesic prescribing laws, regulations, guidelines, and policies.

Trends in Prevalence of Cigarette Smoking Among US Adults With Major Depression or Substance Use Disorders, 2006-2019.

Importance: Tobacco use is highly concentrated in persons with mental illness. Objectives: To assess trends in past-month prevalence of cigarette smoking among adults with vs without past-year depression, substance use disorders (SUDs), or both, using nationally representative data. Design, Setting, and Participants: Exploratory, serial, cross-sectional study based on data from 558 960 individuals aged 18 years or older who participated in the 2006-2019 US National Surveys on Drug Use and Health. Exposure: Past-year major depressive episode (MDE) and SUD using Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria. Main Outcomes and Measures: Past-month self-reported cigarette use, adjusted for sociodemographic characteristics. Results: Of the sampled 558 960 adults, 41.4% (unweighted) were aged 18 to 25 years, 29.8% (unweighted) were aged 26 to 49 years, and 53.4% (unweighted) were women. From 2006 to 2019, the past-month self-reported cigarette smoking prevalence declined significantly among adults with MDE from 37.3% to 24.2% for an average annual percent change of -3.2 (95% CI, -3.5 to -2.8; P < .001), adults with SUD from 46.5% to 35.8% for an average annual percent change of -1.7 (95% CI, -2.8 to -0.6; P = .002), and adults with co-occurring MDE and SUD from 50.7% to 37.0% for an annual average annual percent change of -2.1 (95% CI, -3.1 to -1.2; P < .001). The prevalence declined significantly for each examined age, sex, and racial and ethnic subgroup with MDE and with SUD (all P < .05), except for no significant changes in American Indian or Alaska Native adults with MDE (P = .98) or with SUD (P = .46). Differences in prevalence of cigarette smoking between adults with vs without MDE declined significantly for adults overall from 11.5% to 6.6%, for an average annual percent change of -3.4 (95% CI, -4.1 to -2.7; P < .001); significant average annual percent change declines were also seen for men (-5.1 [95% CI, -7.2 to -2.9]; P < .001); for women (-2.7 [95% CI, -3.9 to -1.5]; P < .001); for those aged 18 through 25 years (-5.2 [95% CI, -7.6 to -2.8]; P < .001); for those aged 50 years or older (-4.7 [95% CI, -8.0 to -1.2]; P = .01); for Hispanic individuals (-4.4 [95% CI, -8.0 to -0.5]; P = .03), and for White individuals (-3.6 [95% CI, -4.5 to -2.7]; P < .001). For American Indian or Alaska Native adults, prevalence did not significantly differ between those with vs without MDE during 2006-2012 but was significantly higher for those with MDE during 2013-2019 (difference, 11.3%; 95% CI, 0.9 to 21.7; P = .04). Differences among those with vs without SUD declined for women for an average annual percent change of -1.8 (95% CI, -2.8 to -0.9; P = .001). Conclusions and Relevance: In this exploratory, serial, cross-sectional study, there were significant reductions in the prevalence of self-reported cigarette smoking among US adults with major depressive episode, substance use disorder, or both, between 2006 and 2019. However, continued efforts are needed to reduce the prevalence further.

Pregnancy and Postpartum Drug Overdose Deaths in the US Before and During the COVID-19 Pandemic.

Importance: Knowledge about characteristics of US pregnancy-associated decedents is needed to guide responses. Objective: To examine individual sociodemographic characteristics and residing county's health care resources and socioeconomic factors among pregnancy-associated overdose decedents in comparison with obstetric decedents and overdose decedents who were not pregnant in the past year. Design, Setting, and Participants: This cross-sectional, exploratory study included 1457 pregnant and postpartum overdose decedents, 4796 obstetric decedents, and 11 205 nonpregnant overdose decedents aged 10 to 44 years from 2018 to 2021. Data were analyzed August 2023. Exposures: Decedents from the 2018-2021 Multiple Cause of Death Files linked to the 2021 Area Health Resources Files and the 2018-2021 County Health Rankings data at the county level. Main Outcomes and Measures: Pregnancy-associated deaths were defined as deaths during pregnancy or within 1 year of pregnancy termination. This study focused on unintentional drug overdoses or drug overdoses with undetermined intent involving the most common psychotropic drugs of misuse. Results: From 2018 to 2021, across the pregnancy-postpartum continuum, pregnancy-associated overdose mortality ratios consistently increased among women aged 10 to 44 years. Mortality ratio more than tripled among pregnant and postpartum women aged 35 to 44 years from 4.9 (95% CI, 3.0-8.0) per 100 000 mothers aged 35 to 44 years with a live birth in January to June 2018 to 15.8 (95% CI, 12.3-20.4) in July to December 2021 (average semiannual percentage changes, 15.9; 95% CI, 8.7-23.6; P < .001). Compared with pregnant obstetric decedents, pregnant overdose decedents had increased odds of being aged 10 to 34 years (75.4% vs 59.5%; range of odds ratios [ORs], 1.8 [95% CI, 1.3-2.5] for ages 10 to 24 years to 2.2 [95% CI, 1.7-2.8] for ages 25 to 34 years), being non-college graduates (72.1% vs 59.4%; range of ORs, 2.7 [95% CI, 1.7-4.3] for those with some college education to 3.9 [95% CI, 2.4-6.1] for those with less than high school education), being unmarried (88.0% vs 62.1%; OR, 4.5; 95% CI, 3.7-6.0), and dying in nonhome, non-health care settings (25.9% vs 4.5%; OR, 2.5; 95% CI, 1.8-3.6) and were associated with decreased odds of dying in health care settings (34.7% vs 77.6%; range of ORs, 0.1 [95% CI, 0.1-0.1] for those who died in hospital inpatient settings to 0.4 [95% CI, 0.3-0.6] for those who died in hospital outpatient/emergency room settings). Conclusions and Relevance: From 2018 to 2021, the mortality ratio more than tripled among pregnant and postpartum women aged 35 to 44 years, consistent with increases in overdose mortality across US populations. Most pregnancy-associated overdose deaths occurred outside health care settings, indicating the need for strengthening community outreach and maternal medical support. To reduce pregnancy-associated overdose mortality, evidence-based interventions are urgently needed at individual, health care, local, and national levels, along with nonpunitive approaches incentivizing pregnant and postpartum women to seek substance use disorder treatments.

Associations of cannabis use, use frequency, and cannabis use disorder with violent behavior among young adults in the United States.

BACKGROUND: Most violent crimes (52 %) are committed by adults aged 18-34, who account for 23 % of the US population and have the highest prevalence of cannabis use and cannabis use disorder (CUD). We examined whether and how associations of cannabis use, use frequency, and CUD with violent behavior (i.e., attacking someone with the intent to harm seriously) vary by sex in U.S. young adults. METHODS: Data were from 113,454 participants aged 18-34 in the 2015-2019 US National Surveys on Drug Use and Health, providing nationally representative data on cannabis use, CUD (using DSM-IV criteria), and violent behavior. Descriptive analyses and bivariate and multivariable logistic regression analyses were conducted. RESULTS: Among U.S. adults aged 18-34, 28.9 % (95 % CI = 28.5-29.2 %) reported past-year cannabis use (with/without CUD), including 20.5 % (95 % CI = 20.2-20.8 %) with non-daily cannabis without CUD, 4.7 % (95 % CI = 4.5-4.8 %) with daily cannabis use without CUD, 2.1 % (95 % CI = 1.9-2.2 %) with non-daily cannabis use and CUD, and 1.7 % (95 % CI = 1.5-1.8 %) with daily cannabis use and CUD. Past-year adjusted prevalence of violent behavior was higher among males with daily cannabis use but without CUD (2.9 %, 95 % CI = 2.4-2.7 %; adjusted prevalence ratio (PR) = 1.7, 95 % CI = 1.3-2.2) and males with daily cannabis use and CUD (3.1 %, 95 % CI = 2.3-4.0 %; adjusted PR = 1.8, 95 % CI = 1.3-2.4) than males without past-year cannabis use (1.7 %, 95 % CI = 1.6-1.9 %). Adjusted prevalence of violent behavior was higher among females with cannabis use regardless of daily cannabis use/CUD status (adjusted prevalence = 1.6-2.4 %, 95 % CIs = 0.9-3.2 %; adjusted PRs = 1.6-2.4, 95 % CI = 1.3-3.2) than females without past-year cannabis use (1.0 %, 95 % CI = 0.9-1.1 %). CONCLUSIONS: Research is needed to ascertain the directionality of the associations between cannabis use and violent behavior and underlying sex-specific mechanism(s). Our results point to complex sex-specific relationships between cannabis use frequency, CUD, and violent behavior and highlight the importance of early screening for and treatment of CUD and of preventive interventions addressing cannabis misuse.

Estimated Number of Children Who Lost a Parent to Drug Overdose in the US From 2011 to 2021.

Importance: Parents' overdose death can have a profound short- and long-term impact on their children, yet little is known about the number of children who have lost a parent to drug overdose in the US. Objective: To estimate the number and rate of children who have lost a parent to drug overdose from 2011 to 2021 overall and by parental age, sex, and race and ethnicity. Design, Setting, and Participants: This was a cross-sectional study of US community-dwelling persons using data from the National Survey on Drug Use and Health (2010-2014 and 2015-2019) and the National Vital Statistics System (2011-2021). Data were analyzed from January to June 2023. Exposure: Parental drug overdose death, stratified by age group, sex, and race and ethnicity. Main Outcomes and Measures: Numbers, rates, and average annual percentage change (AAPC) in rates of children losing a parent aged 18 to 64 years to drug overdose, overall and by age, sex, and race and ethnicity. Results: From 2011 to 2021, 649 599 adults aged 18 to 64 years died from a drug overdose (mean [SD] age, 41.7 [12.0] years; 430 050 [66.2%] male and 219 549 [33.8%] female; 62 606 [9.6%] Hispanic, 6899 [1.1%] non-Hispanic American Indian or Alaska Native, 6133 [0.9%] non-Hispanic Asian or Pacific Islander, 82 313 [12.7%] non-Hispanic Black, 485 623 [74.8%] non-Hispanic White, and 6025 [0.9%] non-Hispanic with more than 1 race). Among these decedents, from 2011 to 2021, an estimated 321 566 (95% CI, 276 592-366 662) community-dwelling children lost a parent aged 18 to 64 years to drug overdose. The rate of community-dwelling children who lost a parent to drug overdose per 100 000 children increased from 27.0 per 100 000 in 2011 to 63.1 per 100 000 in 2021. The highest rates were found among children of non-Hispanic American Indian or Alaska Native individuals, who had a rate of 187.1 per 100 000 in 2021, more than double the rate among children of non-Hispanic White individuals (76.5 per 100 000) and non-Hispanic Black individuals (73.2 per 100 000). While rates increased consistently each year for all parental age, sex, and race and ethnicity groups, non-Hispanic Black parents aged 18 to 25 years had the largest AAPC (23.8%; 95% CI, 16.5-31.6). Rates increased for both fathers and mothers; however, more children overall lost fathers (estimated 192 459; 95% CI, 164 081-220 838) than mothers (estimated 129 107; 95% CI, 112 510-145 824). Conclusions and Relevance: An estimated 321 566 children lost a parent to drug overdose in the US from 2011 to 2021, with significant disparities evident across racial and ethnic groups. Given the potential short- and long-term negative impact of parental loss, program and policy planning should ensure that responses to the overdose crisis account for the full burden of drug overdose on families and children, including addressing the economic, social, educational, and health care needs of children who have lost parents to overdose.

Galanin-induced decreases in nucleus accumbens/striatum excitatory postsynaptic potentials and morphine conditioned place preference require both galanin receptor 1 and galanin receptor 2.

The neuropeptide galanin has been shown to alter the rewarding properties of morphine. To identify potential cellular mechanisms that might be involved in the ability of galanin to modulate opiate reward, we measured excitatory postsynaptic potentials (EPSPs), using both field and whole-cell recordings from striatal brain slices extracted from wild-type mice and mice lacking specific galanin receptor (GalR) subtypes. We found that galanin decreased the amplitude of EPSPs in both the dorsal striatum and nucleus accumbens. We then performed recordings in slices from knockout mice lacking either the GalR1 or GalR2 gene, and found that the ability of galanin to decrease EPSP amplitude was absent from both mouse lines, suggesting that both receptor subtypes are required for this effect. In order to determine whether behavioral responses to opiates were dependent on the same receptor subtypes, we tested GalR1 and GalR2 knockout mice for morphine conditioned place preference (CPP). Morphine CPP was significantly attenuated in both GalR1 and GalR2 knockout mice. These data suggest that mesolimbic excitatory signaling is significantly modulated by galanin in a GalR1-dependent and GalR2-dependent manner, and that morphine CPP is dependent on the same receptor subtypes.

Patterns and Characteristics of Nicotine Dependence Among Adults With Cigarette Use in the US, 2006-2019.

Importance: Nicotine dependence increases the risk of persistent smoking, which is the leading preventable cause of morbidity and death. However, evidence regarding the associations of nicotine dependence with age, psychiatric conditions, and sociodemographic characteristics is limited. Objective: To assess whether and how nicotine dependence among US adults with cigarette use varies by year, age, psychiatric comorbidities, and sociodemographic characteristics. Design, Setting, and Participants: This exploratory serial cross-sectional study used data from 152 354 US community-dwelling individuals 18 years or older who participated in the 2006-2019 National Surveys on Drug Use and Health. Data analyses were conducted from January 15 to February 15, 2023. Exposure: Past-month cigarette use. Past-year major depressive episode (MDE) and/or substance use disorder (SUD) based on criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), Text Revision. Main Outcomes and Measures: Past-month nicotine dependence based on criteria from the Nicotine Dependence Syndrome Scale or the Fagerström Test of Nicotine Dependence. Results: Among 152 354 adults with past-month cigarette use (54.1% male; 40.2% aged 18-34 years; 29.0% aged 35-49 years; 69.8% non-Hispanic White), the adjusted prevalence of nicotine dependence decreased from 59.52% (95% CI, 57.93%-61.10%) in 2006 to 56.00% (95% CI, 54.38%-57.60%) in 2019 (average annual percentage change [AAPC], -0.4%; 95% CI, -0.5% to -0.4%; P < .001) and among each examined age group, except for stability among those aged 18 to 25 years (AAPC, -0.5%; 95% CI, -1.4% to 0.4%; P = .27). Compared with those 50 years and older with past-month cigarette smoking, the adjusted prevalence of nicotine dependence among those aged 18 to 49 years was 32% lower for those aged 18 to 25 years (adjusted risk ratio [ARR], 0.68; 95% CI, 0.66-0.70), 18% lower for those aged 26 to 34 years (ARR, 0.82; 95% CI, 0.80-0.84), and 6% lower for those aged 35 to 49 years (ARR, 0.94; 95% CI, 0.92-0.96). The adjusted prevalence of nicotine dependence varied by age, MDE and/or SUD status, and sociodemographic characteristics. For example, by 2019, prevalence was 41.27% (95% CI, 39.21%-43.37%) among those aged 18 to 25 years and 64.43% (95% CI, 60.98%-67.74%) among those 50 years and older. Differences in nicotine dependence prevalence between those with co-occurring MDE and SUD and those without both conditions were more than 2 times larger for those 50 years and older vs those aged 18 to 49 years (eg, ages ≥50 years vs 18-25 years: 18.69 percentage point difference [83.32% vs 64.63%] vs 7.67 percentage point difference [48.88% vs 41.21%]; P < .001). Conclusions and Relevance: In this cross-sectional study, there were significant reductions in nicotine dependence prevalence from 2006 to 2019 among US adults with cigarette use and all examined subgroups 26 years and older. Adults 50 years and older (especially those with MDE and/or SUD) had the highest nicotine dependence prevalence compared with other age groups, highlighting the importance of assisting with smoking cessation efforts and addressing nicotine dependence for this older population. Evidence-based tobacco cessation strategies tailored to age and comorbidities are needed.

Racial inequities and addiction research.

What accounts for variation across racial and ethnic groups in drug use and harms related to substance use? While explanatory mechanisms for racial and ethnic disparities include differential access to and use of health services, a myriad of other factors, including racism and historical trauma, contribute to drug-related disparities. Furthermore, the addiction scientific workforce, like the full biomedical research enterprise, lacks diversity. This deficit undercuts U.S. scientific leadership and is a major challenge for the field. To address these entrenched problems, the National Institute on Drug Abuse (NIDA) is prioritizing research on health disparities and supporting multiple efforts to enhance scientific workforce diversity. Studies on substance use trends and emerging threats must measure disparities and track progress in reducing disparities, but also acknowledge the limitations of race and ethnicity-based data. Researchers must take the bold step of proposing studies that elucidate causal mechanisms which have the potential to be ameliorated by novel policies and practices. Critically, the impact of racism on all aspects of the substance use trajectory must be assessed to better tailor prevention, harm reduction, treatment, and recovery-support interventions to the specific circumstances of those who need them. Particular attention should be given to people who are incarcerated, who are experiencing homelessness, and who have a history of adverse childhood experiences. Training the next generation of the addiction science workforce needs to address structural barriers to participation with partnerships between funders, such as NIDA, and grantee organizations.

Mental health conditions and receipt of mental health care by illicit lysergic acid diethylamide (LSD) use status among young adults in the United States.

AIM: To examine prevalence of mental health conditions and receipt of mental health care (MHC) by illicit lysergic acid diethylamide (LSD) use status (past-year; lifetime without-past-year; never) among young adults. DESIGN: Cross-sectional, annual survey data from 2015 to 2019 National Surveys on Drug Use and Health (NSDUH). SETTING: United States. PARTICIPANTS: A total of 69 916 NSDUH participants ages 18 to 25. MEASUREMENTS: Outcomes included past-year serious psychological distress (SPD), suicidal ideation, Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV major depressive episode (MDE), any mental illness, serious mental illness, receipt of mental health care (MHC, inpatient/outpatient or receipt of prescription medications), and number of days of being unable to work or attend normal activities because of mental health conditions. FINDINGS: Multivariable analyses found that compared with those who never used illicit LSD, adults with past-year illicit LSD use had greater risk of suicidal ideation (adjusted risk ratio [ARR] = 1.2, 95% CI = 1.06-1.41), SPD (ARR = 1.2, 95% CI = 1.04-1.28), MDE (ARR = 1.3, 95% CI = 1.17-1.52), and any/serious mental illness (ARRs = 1.2-1.3, 95% CI = 1.02-1.41) and reported missing more days because of mental health conditions (adjusted incidence rate ratio = 1.6, 95% CI = 1.31-1.86). Lifetime (without past-year) use showed similar, although less consistent, associations. Compared with those never using illicit LSD, adults with past-year use were less likely to receive prescription medications for MHC (ARR = 0.7, 95% CI = 0.60-0.84) and to receive overall MHC (ARR = 0.7, 95% CI= 0.64-0.84). Compared with those using in the past-year, adults with lifetime (without past-year) use were more likely to receive prescription medications for MHC (ARR = 1.2, 95% CI = 1.01-1.46) and receive overall MHC (ARR = 1.2, 95% CI = 1.03-1.45). CONCLUSIONS: Young adults with past-year illicit lysergic acid diethylamide use have elevated prevalence of mental health conditions and are less likely to receive prescription medications for mental health care and overall mental health care. Regardless of past-year use status, young adults with lifetime illicit lysergic acid diethylamide use may benefit from mental illness prevention and interventions.

Somatostatin signaling in neuronal cilia is critical for object recognition memory.

Most neurons possess a single, nonmotile cilium that projects out from the cell surface. These microtubule-based organelles are important in brain development and neurogenesis; however, their function in mature neurons is unknown. Cilia express a complement of proteins distinct from other neuronal compartments, one of which is the somatostatin receptor subtype SST(3). We show here that SST(3) is critical for object recognition memory in mice. sst3 knock-out mice are severely impaired in discriminating novel objects, whereas they retain normal memory for object location. Further, systemic injection of an SST(3) antagonist (ACQ090) disrupts recall of familiar objects in wild-type mice. To examine mechanisms of SST(3), we tested synaptic plasticity in CA1 hippocampus. Electrically evoked long-term potentiation (LTP) was normal in sst3 knock-out mice, while adenylyl cyclase/cAMP-mediated LTP was impaired. The SST(3) antagonist also disrupted cAMP-mediated LTP. Basal cAMP levels in hippocampal lysate were reduced in sst3 knock-out mice compared with wild-type mice, while the forskolin-induced increase in cAMP levels was normal. The SST(3) antagonist inhibited forskolin-stimulated cAMP increases, whereas the SST(3) agonist L-796,778 increased basal cAMP levels in hippocampal slices but not hippocampal lysate. Our results show that somatostatin signaling in neuronal cilia is critical for recognition memory and suggest that the cAMP pathway is a conserved signaling motif in cilia. Neuronal cilia therefore represent a novel nonsynaptic compartment crucial for signaling involved in a specific form of synaptic plasticity and in novelty detection.

α4ß2 nicotinic acetylcholine receptor partial agonists with low intrinsic efficacy have antidepressant-like properties.

Previous studies have suggested that treatment with antagonists or partial agonists of nicotinic acetylcholine receptors containing the ß2-subunit (ß2 nAChRs) results in antidepressant-like effects. In this study, we tested three novel compounds with different affinity and functional efficacy at α4ß2 nAChRs, which were synthesized as part of nAChR discovery projects at Pfizer, in the tail-suspension, forced-swim, and novelty-suppressed feeding tests of antidepressant efficacy. All compounds tested reduced immobility in the forced-swim test and one of the compounds also reduced immobility in the tail-suspension test. All the compounds appeared to affect food intake on their own, with two compounds reducing feeding significantly in the home cage, precluding a clear interpretation of the results in the novelty-suppressed feeding test. None of the compounds altered locomotor activity at the doses and time points used here. Therefore, a subset of these compounds has pharmacological and behavioral properties that demonstrate the potential of nicotinic compounds as a treatment of mood disorders. Further development of nicotinic-based antidepressants should focus on increasing nAChR subtype selectivity to obtain consistent antidepressant properties with an acceptable side-effect profile.

Trends in and Characteristics of Buprenorphine Misuse Among Adults in the US.

Importance: There is a lack of empirical research regarding misuse of buprenorphine hydrochloride. Objective: To identify prescription opioids that are most frequently misused, assess differences in motivations for misuse between buprenorphine and nonbuprenorphine prescription opioids, and examine trends in and factors associated with buprenorphine misuse among individuals with or without opioid use disorder (OUD). Design, Setting, and Participants: This survey study used nationally representative data on past-year prescription opioid use, misuse, OUD, and motivations for the most recent misuse from the 2015-2019 National Survey on Drug Use and Health (NSDUH). Participants included 214 505 civilian, noninstitutionalized adult NSDUH respondents. Data were collected from January 2015 to December 2019 and analyzed from February 15 to March 15, 2021. Main Outcomes and Measures: Buprenorphine use, misuse, and OUD. Misuse was defined as use "in any way that a doctor [physician] did not direct you to use them, including (1) use without a prescription of your own; (2) use in greater amounts, more often, or longer than you were told to take them; or (3) use in any other way a doctor did not direct you to use them." Results: The 214 505 respondents included in the analysis represented an estimated annual average 246.7 million US adults during 2015-2019 (51.7% [95% CI, 51.4%-52.0%] women; 13.9% [95% CI, 13.7%-14.1%] aged 18-25 y; 40.6% [95% CI, 40.3%-41.0%] aged 26-49 y; 45.5% [95% CI, 45.0-45.9%] aged ≥50 y). In 2019, an estimated 2.4 (95% CI, 2.2-2.7) million US adults used buprenorphine, and an estimated 0.7 (95% CI, 0.5-0.9) million misused buprenorphine compared with an estimated 4.9 (95% CI, 4.4-5.4) million and an estimated 3.0 (95% CI, 2.7-3.2) million who misused hydrocodone and oxycodone, respectively. Prevalence of OUD with buprenorphine misuse trended downward during the period from 2015 to 2019. "Because I am hooked" (27.3% [95% CI, 21.6%-33.8%]) and "to relieve physical pain" (20.5% [95% CI, 14.0%-29.0%]) were the most common motivations for the most recent buprenorphine misuse among adults with OUD. Adults who misused buprenorphine were more likely to report using prescription opioids without having their own prescriptions than those who misused nonbuprenorphine prescription opioids (with OUD: 71.8% [95% CI, 66.4%-76.6%] vs 53.2% [95% CI, 48.5%-57.8%], P < .001; without OUD: 74.7% [95% CI, 68.7%-79.9%] vs 60.0% [58.1%-61.8%], P < .001). Among adults with past-year OUD who used buprenorphine, multivariable multinomial logistic regression results indicated that buprenorphine misuse was associated with being 24 to 34 (adjusted odds ratio [AOR], 2.9 [95% CI, 1.4-5.8]) and 35 to 49 (AOR, 2.3 [95% CI, 1.2-4.5]) years of age, residing in nonmetropolitan areas (AOR, 1.8 [95% CI, 1.0-3.0]), and polysubstance use (eg, past-year prescription stimulant use disorder; AOR, 3.9 [95% CI, 1.3-11.2]) but was negatively associated with receiving treatment for drug use only (AOR, 0.4 [95% CI, 0.3-0.7]). Conclusions and Relevance: These findings suggest that among adults with OUD, prevalence of buprenorphine misuse trended downward from 2015 to 2019. In 2019, nearly three-fourths of US adults reporting past-year buprenorphine use did not misuse their prescribed buprenorphine, and most who misused reported using prescription opioids without having their own prescriptions. These findings underscore the need to pursue actions that expand access to buprenorphine-based OUD treatment, to develop strategies to monitor and reduce buprenorphine misuse, and to address associated conditions (eg, suicide risk, co-occurring mental illness, and polysubstance use).

Associations of Suicidality Trends With Cannabis Use as a Function of Sex and Depression Status.

Importance: During the past decade, cannabis use among US adults has increased markedly, with a parallel increase in suicidality (ideation, plan, attempt, and death). However, associations between cannabis use and suicidality among young adults are poorly understood. Objective: To determine whether cannabis use and cannabis use disorder (CUD) are associated with a higher prevalence of suicidality among young adults with or without depression and to assess whether these associations vary by sex. Design, Setting, and Participants: This survey study examined data from 281 650 adults aged 18 to 34 years who participated in the National Surveys on Drug Use and Health. Data were collected from January 1, 2008, to December 31, 2019. Exposures: Prevalence of past-year daily or near-daily cannabis use (≥300 days in the past year), CUD, and major depressive episode (MDE). Past-year CUD and MDE were based on DSM-IV diagnostic criteria. Main Outcomes and Measures: Past-year suicidal ideation, plan, and attempt. Results: Among the 281 650 adults aged 18 to 34 (men, 49.9% [95% CI, 49.6%-50.2%]; women, 50.1% [95% CI, 49.8%-50.4%]) included in the analysis, past-year suicidal ideation and plan along with daily cannabis use increased among all examined sociodemographic subgroups (except daily cannabis use among current high-school students), and past-year suicide attempt increased among most subgroups. National trends in adjusted prevalence of past-year suicidal ideation, plan, and attempt varied by daily and nondaily cannabis use and CUD among adults with or without MDE. After controlling for MDE, CUD, cannabis use status, and potential confounding factors, the adjusted prevalence of suicidal ideation, plan, and attempt increased 1.4 to 1.6 times from the 2008-2009 to 2018-2019 periods (adjusted risk ratio [ARR] for suicidal ideation, 1.4 [95% CI, 1.3-1.5]; ARR for suicide plan, 1.6 [95% CI, 1.5-1.9]; ARR for suicide attempt, 1.4 [95% CI, 1.2-1.7]), with 2008 to 2009 as the reference period. Past-year CUD, daily cannabis use, and nondaily cannabis use were associated with a higher prevalence of past-year suicidal ideation, plan, and attempt in both sexes (eg, among individuals without MDE, prevalence of suicidal ideation for those with vs without CUD was 13.9% vs 3.5% among women and 9.9% vs 3.0% among men; P < .001), but significantly more so in women than men (eg, suicide plan among those with CUD and MDE was 52% higher for women [23.7%] than men [15.6%]; P < .001). Conclusions and Relevance: From 2008 to 2019, suicidal ideation, plan, and attempt increased 40% to 60% over increases ascribed to cannabis use and MDE. Future research is needed to examine this increase in suicidality and to determine whether it is due to cannabis use or overlapping risk factors.

Methamphetamine Use, Methamphetamine Use Disorder, and Associated Overdose Deaths Among US Adults.

Importance: Mortality associated with methamphetamine use has increased markedly in the US. Understanding patterns of methamphetamine use may help inform related prevention and treatment. Objective: To assess the national trends in and correlates of past-year methamphetamine use, methamphetamine use disorder (MUD), injection, frequent use, and associated overdose mortality from 2015 to 2019. Design, Setting, and Participants: This cross-sectional study analyzed methamphetamine use, MUD, injection, and frequent use data from participants in the 2015 to 2019 National Surveys on Drug Use and Health (NSDUH). Mortality data were obtained from the 2015 to 2019 National Vital Statistics System Multiple Cause of Death files. Exposures: Methamphetamine use. Main Outcomes and Measures: Methamphetamine use, MUD, injection, frequent use, and overdose deaths. Results: Of 195 711 NSDUH respondents aged 18 to 64 years, 104 408 were women (weighted percentage, 50.9%), 35 686 were Hispanic individuals (weighted percentage, 18.0%), 25 389 were non-Hispanic Black (hereafter, Black) individuals (weighted percentage, 12.6%), and 114 248 were non-Hispanic White (hereafter, White) individuals (weighted percentage, 60.6%). From 2015 to 2019, overdose deaths involving psychostimulants other than cocaine (largely methamphetamine) increased 180% (from 5526 to 15 489; P for trend <.001); methamphetamine use increased 43% (from 1.4 million [95% CI, 1.2-1.6 million] to 2.0 million [95% CI, 1.7-2.3 million]; P for trend = .002); frequent methamphetamine use increased 66% (from 615 000 [95% CI, 512 000-717 000] to 1 021 000 [95% CI, 860 000-1 183 000]; P for trend = .002); methamphetamine and cocaine use increased 60% (from 402 000 [95% CI, 306 000-499 000] to 645 000 [95% CI, 477 000-813 000]; P for trend = .001); and MUD without injection increased 105% (from 397 000 [95% CI, 299 000-496 000] to 815 000 [95% CI, 598 000-1 033 000]; P for trend = .006). The prevalence of MUD or injection surpassed the prevalence of methamphetamine use without MUD or injection in each year from 2017 to 2019 (60% to 67% vs 37% to 40%; P for trend ≤.001). Adults with MUD or using injection were more likely to use methamphetamine frequently (52.68%-53.84% vs 32.59%; adjusted risk ratio, 1.62-1.65; 95% CI, 1.35-1.94). From 2015 to 2019, the adjusted prevalence of MUD without injection more than tripled among heterosexual women (from 0.24% to 0.74%; P < .001) and lesbian or bisexual women (from 0.21% to 0.71%; P < .001) and more than doubled among heterosexual men (from 0.29% to 0.79%; P < .001) and homosexual or bisexual men (from 0.29% to 0.80%; P = .007). It increased over 10-fold among Black individuals (from 0.06% to 0.64%; P < .001), nearly tripled among White individuals (from 0.28% to 0.78%; P < .001), and more than doubled among Hispanic individuals (from 0.39% to 0.82%; P < .001). Risk factors for methamphetamine use, MUD, injection, and frequent use included lower educational attainment, lower annual household income, lack of insurance, housing instability, criminal justice involvement, comorbidities (eg, HIV/AIDS, hepatitis B or C virus, depression), suicidal ideation, and polysubstance use. Conclusions and Relevance: This cross-sectional study found consistent upward trends in overdose mortality, greater risk patterns of methamphetamine use, and populations at higher risk for MUD diversifying rapidly, particularly those with socioeconomic risk factors and comorbidities. Evidence-based prevention and treatment interventions are needed to address surges in methamphetamine use and MUD.

Prevention and Treatment of Opioid Misuse and Addiction: A Review.

Importance: More than 42 000 Americans died of opioid overdoses in 2016, and the fatalities continue to increase. This review analyzes the factors that triggered the opioid crisis and its further evolution, along with the interventions to manage and prevent opioid use disorder (OUD), which are fundamental for curtailing the opioid crisis. Observations: Opioid drugs are among the most powerful analgesics but also among the most addictive. The current opioid crisis, initially triggered by overprescription of opioid analgesics, which facilitated their diversion and misuse, has now expanded to heroin and illicit synthetic opioids (fentanyl and its analogues), the potency of which further increases their addictiveness and lethality. Although there are effective medications to treat OUD (methadone hydrochloride, buprenorphine, and naltrexone hydrochloride), these medications are underused, and the risk of relapse is still high. Strategies to expand medication use and treatment retention include greater involvement of health care professionals (including psychiatrists) and approaches to address comorbidities. In particular, the high prevalence of depression and suicidality among patients with OUD, if untreated, contributes to relapse and increases the risk of overdose fatalities. Prevention interventions include screening and early detection of psychiatric disorders, which increase the risk of substance use disorders, including OUD. Conclusions and Relevance: Although overprescription of opioid medications triggered the opioid crisis, improving opioid prescription practices for pain management, although important for addressing the opioid crisis, is no longer sufficient. In parallel, strategies to expand access to medication for OUD and improve treatment retention, including a more active involvement of psychiatrists who are optimally trained to address psychiatric comorbidities, are fundamental to preventing fatalities and achieving recovery. Research into new treatments for OUD, models of care for OUD management that include health care, and interventions to prevent OUD may further help resolve the opioid crisis and prevent it from happening again.

Use of Medication for Opioid Use Disorder Among Adults With Past-Year Opioid Use Disorder in the US, 2021.

This cross-sectional study uses data from the 2021 National Survey on Drug Use and Health to estimate the receipt of medication for opioid use disorder among US adults with past-year opioid use disorder.