The Rhode Island Prescription Drug Monitoring Program (PDMP) requires dispensers with an active Controlled Substance Registration to report Schedule II-V substances and opioid antagonists within 24 hours of dispensing. This database was designed to surveille diversion and identify high-risk prescribing to prevent drug related harms. Using PDMP data from January 1, 2017, to December 31, 2021, opioid, buprenorphine, stimulant, and benzodiazepine dispensing trends were explored. During this time, opioid prescriptions dispensed annually decreased by 27.3% (from 576,421 to 419,220), and benzodiazepine prescriptions dispensed annually decreased by 12.3% (552,430 to 484,496). High-risk prescribing also decreased with opioids prescriptions > 90 daily MME decreasing by 52.1% and instances of overlapping benzodiazepine and opioid prescriptions decreasing by 34.1%. Buprenorphine and stimulant dispensing have increased by 11.1% and 20.7%, respectively. Prevention interventions will continue to educate providers on appropriate prescribing practices and work to further reduce unnecessary prescribing within the state.
Ketamine is a versatile anesthetic that has been widely used off-label to treat a variety of indications. Esketamine, a derivative of ketamine, is FDA-approved to treat treatment-resistant depression. This report compares statewide prescription ketamine and esketamine trends. Using PDMP data from 2017-2023, prescription and prescriber characteristics, and patient demographics were compared between esketamine and ketamine prescriptions. During this time, ketamine prescriptions, patients, and providers rose 55.8%, 30.6%, and 2.8% since 2017. Esketamine prescriptions increased 1289.4% since 2019. In 2023, ketamine prescriptions were primarily in powder form (98.7%) and paid for out-of-pocket (83.9%), whereas esketamine prescriptions were primarily paid for by insurance (80.2%). The proportion of ketamine prescribed in RI but dispensed out-of-state have increased 22% since 2022 (18% of total dispensations). As more people seek treatment for mental health disorders, ketamine and esketamine prescriptions continue to rise. Understanding ketamine and esketamine use can help mitigate associated adverse events.
Introduction Anger can engender action by individuals and groups. It is thus important to understand anger’s behavioral phenotypes and their underlying neural substrates. Here, we introduce a construct we term agentic anger , a negatively valenced internal state that motivates action to achieve risky goals. We evaluate our neurobehavioral model via testable hypotheses in two proof-of-concept studies. Study 1 Methods Study 1 used the Incentive Balloon Analogue Risk Task in a within-subjects, repeated measures design in 39 healthy volunteers to evaluate: (a) impact of blockade of reward on agentic anger, assessed by self-reports of negative activation (NA), (b) impact of achievement of reward on exuberance, assessed by self-reports of positive activation (PA), (c) the interrelationship of these valenced states, and (d) their relationship with personality. Study 1 Results Task-induced NA was positively correlated with task-induced PA, risk-taking on the task and trait Social Potency (SP), a measure of trait agency and reward sensitivity on the Multidimensional Personality Questionnaire Brief-Form. Study 2 Methods Study 2 assessed functional MRI response to stakes for risk-taking in healthy volunteers receiving 20 mg d -amphetamine in a double-blinded, placebo-controlled crossover design ( N = 10 males), providing preliminary information on ventral striatal response to risky rewards during catecholamine activation. Study 2 Results Trait SP and task-induced PA were strongly positively related to catecholamine-facilitated BOLD response in the right nucleus accumbens, a brain region where DA prediction error signal shapes action value and selection. Participants’ task-induced NA was strongly positively related with trait SP and task-induced PA, replicating the findings of Study 1. Discussion Together these results inform the phenomenology and neurobiology of agentic anger, which recruits incentive motivational circuitry and motivates personal action in response to goals that entail risk (defined as exposure to uncertainty, obstacles, potential harm, loss and/or financial, emotional, bodily, or moral peril). Neural mechanisms of agency, anger, exuberance, and risk-taking are discussed, with implications for personal and group action, decision-making, social justice, and behavior change.
Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory-emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits.
Anger can engender action by individuals and groups. It is thus important to understand anger’s behavioral phenotypes and their underlying neural substrates. Here we introduce a construct we term agentic anger, a state that motivates action to achieve risky goals. We test predictions of our neurobehavioral model in two proof-of-concept studies. Study 1 used the Incentive Balloon Analogue Risk Task (iBART) in a within-subjects, repeated measures design in 39 healthy volunteers to evaluate: a) impact of frustrative non-reward on agentic anger, assessed by self-reports of negative activation (NA), b) impact of achieved reward on exuberance, assessed by self-reports of positive activation (PA), c) their interrelationship, and d) their relationship with traits of positive emotion, negative emotion, immersive emotion and impulsivity. Task-induced NA was positively correlated with task-induced PA (r=0.56, p<.001), risk-taking on the task (r=0.27 to 0.36, p≤.05, .01) and trait Social Potency (SP, r=0.34 to 0.35, p<.05), a measure of reward sensitivity on the Multidimensional Personality Questionnaire Brief-Form (MPQ-BF). Study 2 assessed functional MRI response to stakes for risk-taking in healthy volunteers receiving 20 mg d-amphetamine (AMP) in a double-blinded, placebo-controlled crossover design (N = 10 males; 20 MRI scans), providing preliminary information on ventral striatal response to risky rewards during catecholamine (CA) activation. Trait SP and task-induced PA were strongly positively related to AMP-facilitated BOLD response in the right nucleus accumbens, a brain region in which DA prediction error signal shapes action value and selection (SP r=+.60, p=.03; PA r=+.72, p=.02, respectively). Participants’ task-induced NA was also strongly positively related with trait SP (r=0.51; d=1.2) and task-induced PA (r=0.68; d=1.9), replicating the findings of Study 1. Together these results inform the phenomenology and neurobiology of agentic anger, which recruits incentive motivational circuitry and motivates personal action in response to goals that entail risk (defined as exposure to uncertainty, obstacles, potential harm, loss and/or financial, emotional, bodily or moral peril). Neural mechanisms of agency, anger, exuberance and risk-taking are discussed, with implications for personal and group action, decision-making, social justice, and behavior change.
Responding to errors is a critical first step in learning from mistakes, a process that is abnormal in schizophrenia. To gain insight into the neural and molecular mechanisms of error processing, we used functional MRI to examine effects of a genetic variant in methylenetetrahydrofolate reductase (MTHFR 677C>T, rs1801133) that increases risk for schizophrenia and that has been specifically associated with increased perseverative errors among patients. MTHFR is a key regulator of the intracellular one-carbon milieu, including DNA methylation, and each copy of the 677T allele reduces MTHFR activity by 35%.
Prescription stimulant medications are considered a safe and long-term effective treatment for Attention Deficit Hyperactivity Disorder (ADHD). Studies support that stimulants enhance attention, memory, self-regulation and executive function in individuals with ADHD. Recent research, however, has found that many college students without ADHD report misusing prescription stimulants, primarily to enhance their cognitive abilities. This practice raises the question whether stimulants actually enhance cognitive functioning in college students without ADHD. We investigated the effects of mixed-salts amphetamine (i.e., Adderall, 30 mg) on cognitive, autonomic and emotional functioning in a pilot sample of healthy college students without ADHD (n = 13), using a double-blind, placebo-controlled, within-subjects design. The present study was the first to explore cognitive effects in conjunction with mood, autonomic effects, and self-perceptions of cognitive enhancement. Results revealed that Adderall had minimal, but mixed, effects on cognitive processes relevant to neurocognitive enhancement (small effects), and substantial effects on autonomic responses, subjective drug experiences, and positive states of activated emotion (large effects). Overall, the present findings indicate dissociation between the effects of Adderall on activation and neurocognition, and more importantly, contrary to common belief, Adderall had little impact on neurocognitive performance in healthy college students. Given the pilot design of the study and small sample size these findings should be interpreted cautiously. The results have implications for future studies and the education of healthy college students and adults who commonly use Adderall to enhance neurocognition.
