Agency Therapeutics:
Why the Frontier Will Target Self-Regulation
September 9, 2026
The distance between intention and action is usually treated as a question of discipline. But hunger, craving, attention, motivation, fear and impulse control emerge from biological systems, and those systems can constrain behavior in ways willpower does not reliably overcome. Medicine already recognizes severe failures of these systems and gives them names: obesity, addiction, ADHD, depression, anxiety and insomnia. What modern medicine is still missing is a therapeutic framework organized around the underlying capacity to overcome dysregulation.
Here we propose Agency Therapeutics: medicines that restore or expand the biological capacity for self-regulation, increasing a person's ability to select, initiate and sustain goal-concordant behavior despite competing internal or external pressures.
These drugs will not share a receptor, a pathway or a modality. Agency is not a molecular mechanism but a therapeutic objective. Agency emerges from interacting physiological systems that regulate energy needs, incentive value, threat, effort, attention and cognitive control. Different drugs can therefore increase agency through different biological routes. A metabolic drug that restores control over appetite, a psychiatric drug that improves motivation or attention, an entactogen that reduces pathological avoidance, and a plasticity-promoting drug that helps adaptive learning persist may have almost nothing in common pharmacologically while moving the same higher-order variable.
The emerging pharmacology points to three broad ways to intervene:
Reduce what has to be resisted. Weaken competing drives such as hunger, craving or excessive fear. Examples include GLP-1s and emerging drugs targeting reward and appetite.
Increase the capacity to act. Improve attention, motivation, inhibition, effort or arousal. Examples include stimulants, monoaminergic drugs and orexin agonists.
Make adaptive change persist. Make healthier behaviors or responses easier to learn and retain, including through neural plasticity and epigenetic regulation. Examples include psychoplastogens, entactogens and HDAC modulators.
I. Why agency matters
Health is usually measured through disease, biomarkers and mortality. But many of the outcomes we care about most depend on something upstream: our capacity to regulate our bodies and minds.
Agency is not simply the ability to make healthy choices. It is the capacity to regulate one's internal state well enough to pursue what matters — to act despite competing impulses, sustain effort toward a delayed reward, approach rather than avoid, and the ability to adapt when circumstances change. These capacities are encoded through repetition and their effects appear across domains we usually study separately: health, relationships, economic participation and, over time, the conditions that shape longevity.
Health: the execution problem
Many major chronic diseases are substantially shaped by behavior. Diet, physical activity, sleep, smoking and alcohol consumption influence cardiometabolic risk and other long-term outcomes [1–5]. Yet knowing what is beneficial does not guarantee the capacity to do it. Adherence to long-term therapies in developed countries averages around 50% [6]. Some of that gap is cost, access and side effects. Some reflects the difficulty of repeatedly performing an action whose benefits may be delayed or imperceptible.
Adherence itself contains several distinct problems: beginning a treatment, implementing it consistently and persisting over time [7]. The same distinction appears outside medicine. A person may understand what they want, initiate it successfully, and still struggle to sustain it when motivation, attention or competing rewards change. Agency is therefore not reducible to knowledge, intention or a laboratory measure of executive function. The relevant question is what someone can reliably do [8].
Psychiatry has effectively built a taxonomy of low agency pathologies: addiction, ADHD, depression, anxiety, binge eating and insomnia name severe breakdowns in the control of appetite, attention, motivation, reward, fear, impulse and arousal. Their overlap suggests that some useful therapeutic targets may sit below the diagnostic categories medicine has built above them.
Reward system under attack
Human reward systems have also come under sustained external attack. Over the past two decades, food and technology have been engineered to exert pressure on many of the same regulatory systems from the opposite side.
Processed foods were designed for compulsion. In a tightly controlled inpatient study, an ultra-processed diet caused participants to consume roughly 500 additional calories per day compared with an unprocessed diet [9]. Hyper-palatable foods combine properties that facilitate rapid consumption and amplify reward [10].
Technology is engineered to manipulate attention and change how we respond to stimuli over time. Variable-ratio reward schedules, infinite scroll, autoplay, notification timing and engagement-optimized ranking are not incidental design choices. They are products of continuous experimentation against human behavior, with growth and retention as the objective function [11].
The result is an environment where the systems that convert intention into action are under sustained, adaptive pressure, and the individual is expected to compensate with ‘willpower.’
Social connection in the digital age
Agency also determines whether a person can pursue experiences they value, not merely avoid risks. Partnership, family formation and intimacy depend in part on the ability to approach others, tolerate uncertainty, regulate fear and remain engaged.
Americans aged 15 to 24 spend substantially less time in person with friends than the same age group did two decades ago [12]. Social fluency is learned through interaction but those interactions are becoming more rare and harder to sustain. Social isolation and loneliness have medical consequences and have also been associated with changes in cortisol and inflammatory signaling, including IL-6 [13].
Social anxiety disorder has a lifetime prevalence near 12% in U.S. samples, typically begins in adolescence and can persist for decades [14,15]. A person can want intimacy while threat and avoidance repeatedly prevent intention from becoming action. The limitation is not a lack of desire or understanding, but an inability to translate desire into experience.
Current treatment illustrates why the objective must be broader than symptom suppression. SSRIs can reduce anxiety while causing sexual dysfunction that interferes with the intimate life treatment was meant to enable [16]. An Agency Therapeutic would seek to improve adaptive approach while preserving the emotional, sexual and motivational capacities needed to follow through. The goal is not simply less distress, but greater capacity to participate in a life the person values.
Participating in the post-AI economy
Depression and anxiety are estimated to cost the global economy roughly $1 trillion annually in lost productivity, representing approximately 12 billion working days [17,18]. Across diverse countries, presenteeism costs can substantially exceed absenteeism costs [19]. People may be physically present yet unable to reliably direct attention, motivation and follow-through.
Employment has historically supplied external structure: fixed hours, supervisors, defined roles and someone else deciding what happens next. AI is altering that armature. As machines absorb more execution, humans may increasingly be responsible for choosing objectives, evaluating outputs, adapting to unfamiliar problems and deciding what happens next.
That makes agency economically consequential in a broader sense than productivity alone. It influences whether someone can learn a new skill, tolerate the discomfort of incompetence, pursue an opportunity, recover from a setback or sustain a self-directed project. As execution becomes cheaper, the capacity to decide what is worth doing — and to act on that decision — becomes more valuable.
The longevity link
The relationship between sustaining protective behavior and lifespan is well documented. In long-running U.S. cohorts, adherence to five low-risk behaviors was associated with roughly fourteen additional years of life for women and twelve for men at age fifty, compared with adhering to none [1]. A meta-analysis of 148 prospective studies also found that stronger social relationships were associated with a 50% greater likelihood of survival [20].
These findings are usually read as findings about lifestyle and social connection. They can also be read as findings about capacity. If self-regulation influences the ability to sustain protective behaviors, maintain relationships and avoid risks over decades, then improving that capacity could become a route to longevity — not by targeting aging directly, but by changing the biological conditions under which health-relevant decisions are repeatedly made.
There is already a suggestive pharmacological precedent. In a nationwide Swedish cohort of 148,578 people with newly diagnosed ADHD, initiating medication was associated with 21% lower all-cause mortality over two years, driven predominantly by a 25% reduction in deaths from unnatural causes [21]. The study was observational and does not establish causality, but it makes the hypothesis concrete: treatment of a regulatory disorder may influence hard outcomes through decisions no clinical protocol could individually specify.
Agency Therapeutics could therefore become longevity interventions by improving the capacities that shape health, risk and adaptation across a lifetime. Whether that translates into longer life remains to be demonstrated, but the possibility makes agency a consequential therapeutic objective rather than merely a question of performance or lifestyle.
II. Three ways to increase agency
Self-regulation is not merely a behavioral ideal. It is a set of capacities that pharmacology can influence, and existing medicines already act on different parts of the system — though most were developed for a specific diagnosis rather than for agency itself.
Drugs that alter a regulatory system tend to produce effects wider than the indication they were approved for, and the reclassification runs consistently in one direction: what looked like symptomatic treatment, or even enhancement, begins to look preventative as outcome evidence accumulates. GLP-1s are the clearest case, moving from glucose control to cardiovascular and renal outcomes within a decade [22,23]. Ketamine looked like an anesthetic until its effects were found to outlast exposure [33].
Those effects point to three broad strategies.
1. Reduce what has to be resisted
The first strategy changes the competing drive itself. Hunger, craving and pathological fear can become strong enough that maintaining goal-concordant behavior requires continuous effort. Pharmacology can reduce that burden rather than simply demanding more control from the person experiencing it.
Examples
Semaglutide — approved. GLP-1 receptor agonism reduces hunger and food intake, making sustained caloric regulation less dependent on resisting appetite. What makes it instructive here is that a relatively selective intervention produced a therapeutic phenotype far wider than its molecular target: a 20% reduction in major adverse cardiovascular events in people with overweight or obesity and cardiovascular disease but no diabetes [22], a 24% reduction in major kidney outcomes in type 2 diabetes with chronic kidney disease [23], observational associations with lower incidence of several obesity-associated cancers [24,25], and lower risks across several neurological and substance-use outcomes [26]. Most suggestive for this framework, a 2025 randomized trial found reduced alcohol consumption and craving in adults with alcohol-use disorder [27], raising the possibility that the same biology influences other competing rewards. It remains an incomplete model for Agency Therapeutics: profound appetite suppression is not synonymous with better regulation, and whether its broader behavioral effects translate across reward domains remains to be established.
Tirzepatide — approved. Dual GIP/GLP-1 receptor agonism reaches the same functional objective through broader incretin pharmacology and has produced greater sustained weight reduction than semaglutide in a head-to-head trial [28]. Its success demonstrates what can happen when the biological force competing with an intention is reduced, but it was designed around metabolic outcomes rather than agency as a functional endpoint.
Brenipatide — Phase 3. The GIP/GLP-1 receptor co-agonist is in Phase 3 development for alcohol-use disorder and major depressive disorder [29]. The trials may or may not succeed, but the program is unusually relevant to this framework: it tests whether regulatory biology discovered through metabolism can extend into reward and motivation across conventional diagnostic boundaries.
2. Increase the capacity to act
The second strategy works from the other side of the equation. Instead of weakening a competing drive, pharmacology can increase the capacity to act despite it. Attention, motivation, inhibition, effort allocation and arousal are different functions, but each influences whether an intention becomes behavior.
Examples
Conventional ADHD medications — approved. Stimulants provide perhaps the clearest existing evidence that pharmacology can improve attention, initiation and behavioral control, and treatment has been associated with outcomes extending beyond symptom reduction, including lower mortality in observational data [21]. But current stimulants are an imperfect template: amphetamine and methylphenidate carry risks of misuse, abuse and addiction and commonly affect appetite and sleep [30]. A purpose-built Agency Therapeutic would seek to preserve gains in regulatory capacity while reducing offsetting liabilities.
Atomoxetine — approved. Selective norepinephrine reuptake inhibition improves ADHD symptoms without the same abuse liability as conventional stimulants and affects several dimensions of impulsivity [31]. Its limitations also illustrate the opportunity: improving one component of regulation does not necessarily optimize motivation, attention, effort and inhibition together.
Centanafadine — approved. Centanafadine, approved by the FDA in 2026 for ADHD, acts across norepinephrine, dopamine and serotonin transporters [32]. Its profile is particularly relevant to the Agency Therapeutics hypothesis because different monoamines contribute differently to attention, effort, patience and inhibition. Whether that broader transporter profile translates into superior real-world self-regulation remains an empirical question.
3. Make adaptive change persist
The third strategy addresses what happens after successful action. A drug can change what someone is able to do while it is active without changing what they do once it is gone. Another class of interventions may instead increase the probability that an adaptive behavior, association or emotional response is learned strongly enough to persist.
Examples
Ketamine / esketamine — approved in different indications. Ketamine's effects on synaptic plasticity helped establish the possibility that transient pharmacology can produce changes that outlast immediate drug exposure [33]. It only partially fits the framework: antidepressant durability is not itself evidence of increased agency, and dissociation and other acute effects leave substantial room for compounds that promote useful plasticity more selectively.
MDMA — investigational for psychiatric use. MDMA-assisted therapy has produced durable improvement in Phase 3 PTSD studies [34], illustrating how a transient pharmacological state may alter fear, social processing and learning in ways that persist beyond drug exposure. But its acute psychoactive effects, abuse potential and treatment context make it an imperfect general-purpose model for increasing adaptive learning.
HDAC modulation — experimental. Histone acetylation offers a mechanistically different route to persistence. In a 2026 randomized, triple-blind human study, sodium butyrate moderately improved retrieval of fear-extinction memory seven days later [35]. The evidence is extremely early, but the result is unusually aligned with the framework: rather than continuously producing a state, pharmacology altered how well an adaptive experience was retained.
The point of these examples is not that existing drugs should simply be relabeled as Agency Therapeutics. They show that each component of the framework is pharmacologically tractable and, equally importantly, where existing drugs leave room for therapies designed around agency from the outset. The most interesting drugs may eventually increase agency in more than one way.
III. Why this becomes one of the largest categories in medicine
Pharmaceutical markets have historically been bounded by diagnosis. A drug's addressable population is the number of people who cross a clinical threshold. Agency Therapeutics broaden that boundary by treating meaningful dysregulation itself as a legitimate therapeutic problem — not because everyone should be medicated, but because impaired regulation can affect health and function long before it becomes severe enough to acquire a diagnosis.
This would not create demand for pharmacological self-regulation from scratch. Two of the clearest existing examples — incretin agonists and ADHD treatment — already support large pharmaceutical markets. What is new is recognizing them as manifestations of a broader therapeutic demand.
Incretins provide the most dramatic evidence. In 2025, Lilly generated approximately $36.5 billion from tirzepatide alone: $23.0 billion from Mounjaro and $13.5 billion from Zepbound, together accounting for 56% of company revenue [36]. Novo Nordisk generated $23 billion from GLP-1 diabetes therapies and $12 billion from obesity care in the same year [37]. These are extraordinary numbers for drugs whose defining consumer experience is, in part, that a behavior previously requiring persistent restraint becomes substantially easier.
Willingness to pay is especially visible here because much of the obesity uptake occurred despite substantial out-of-pocket cost and uneven insurance coverage [22,23]. The lesson is that individuals and institutions assign substantial value to pharmacology that changes a regulatory system when doing so makes a consequential objective easier to achieve.
ADHD treatment provides an older and mechanistically different precedent. For decades, patients, parents, insurers and health systems have paid for medicines that improve attention, impulse control and the capacity to sustain goal-directed behavior — despite meaningful limitations of current stimulants, including effects on sleep and appetite and risks of misuse, abuse and addiction [30].
Capital is also moving toward the next generation of this pharmacology well before approval. In 2024, Harmony Biosciences paid $25.5 million upfront for rights to a preclinical orexin-2 receptor agonist, with up to $367.5 million in development, regulatory and commercial milestones [38] — a different route to arousal and wakefulness than conventional stimulant pharmacology. In 2025, AbbVie acquired Gilgamesh's Phase 2 bretisilocin program in a deal worth up to $1.2 billion, including $906 million upfront and up to $300 million in development milestones [39]. Bretisilocin is a short-acting serotonin 5-HT2A receptor agonist and releaser being developed for major depressive disorder, designed in part to address limitations of longer-acting classic psychedelic compounds.
Neither transaction validates Agency Therapeutics as a category, and neither asset was developed under this framework. They demonstrate something narrower but important: substantial pharmaceutical value is already being assigned to new ways of modifying arousal, cognition, plasticity and other biological systems that influence the capacities described here.
Agency Therapeutics generalize that proposition. If regulatory capacity influences adherence, substance use, sleep, physical activity, social behavior, learning and other determinants of health and function, the opportunity is not one diagnosis or one mechanism. It is the set of conditions where biology repeatedly constrains a person's ability to act in accordance with their intentions.
IV. Designing Agency Therapeutics
The drugs described above were not designed as Agency Therapeutics. Their broader effects were discovered after the fact, or they improve one regulatory capacity at the expense of another. GLP-1s revealed effects extending far beyond glucose control. SSRIs illustrate the opposite problem: reducing anxiety while sometimes impairing sexual function required for the same intimate life treatment was meant to enable [16].
Designing Agency Therapeutics intentionally means starting with a more complete description of the desired outcome. The objective is not maximum appetite suppression, stimulation, inhibition or plasticity, but better regulation: increasing the capacity to pursue adaptive, goal-concordant behavior without unnecessarily degrading other functions.
Could an antidepressant improve mood while preserving sexual function? Could a compound restore motivation without the sleep, cardiovascular or abuse liabilities of conventional stimulants? Could a plasticity-promoting drug make adaptive learning more durable without indiscriminately reinforcing whatever is learned?
These are multi-objective discovery problems. The desired human phenotype should determine the pharmacology. Sometimes that may mean a selective intervention at a powerful upstream node. In other cases it may require balancing activity across several targets. Multi-target design is one strategy for producing a desired profile although not a defining feature of Agency Therapeutics.
Where NOVA is looking
If agency emerges from multiple interacting biological systems, there is unlikely to be a single "agency target." Our current programs instead begin with biological systems that map onto different components of the framework and use them as starting points for testing the broader thesis.
Monoamine systems shape attention, effort, patience, motivation, reward and behavioral control. VMAT2 regulates vesicular monoamine storage and release [40,41]. DAT, NET and SERT govern the persistence and distribution of monoamine signaling. None of these is "the agency target." They are intervention points into different dimensions of the phenotype.
Dopamine makes the distinction concrete. Reducing nucleus accumbens dopamine can sharply reduce willingness to work for a reward while leaving the reward itself desirable [42,43]. Norepinephrine contributes differently through attention and inhibitory control [31,44]. Serotonin contributes patience and behavioral inhibition [45,46]. Taken together, the monoamine transporters offer several points at which the capacity to turn intention into action might be tuned.
This is why our internal pipeline is increasingly organized around profiles rather than isolated targets. A molecule acting across DAT, NET and SERT, for example, could be tuned toward a desired ratio of activity rather than maximizing inhibition at one transporter.
The objective is not polypharmacology for its own sake. Undirected promiscuity produces dirty drugs with unpredictable liabilities. More targets are not necessarily better. What matters is specified pharmacology: potent here, moderate there, deliberately silent somewhere else, while preserving safety and drug-like properties.
HDACs address a different part of the framework. If monoamine systems influence what someone can do in a given state, epigenetic regulation may influence whether what happens in that state leaves a durable trace. Histone acetylation is involved in memory formation and plasticity [47], and the human sodium-butyrate result provides an early example of pharmacologically improving retention of adaptive learning [35].
The two target families therefore approach agency at different points: one asks whether pharmacology can improve the capacity to act; the other whether it can make adaptive change more likely to persist. They are starting points rather than boundaries for the pipeline.
NOVA gives us a way to search these design spaces at scale. Competitions can explore chemical spaces and discovery methods in parallel, while our internal pipeline translates submissions into specific hits for experimental validation and development. As evidence accumulates, the same system can expand into new targets, modalities and combinations of the three routes described above.
The scientific objective is not to discover "the agency target." It is to make agency a deliberate discovery objective and systematically search the biological design space underlying it.
Conclusion
What we call willpower is partly a downstream output of biological systems governing reward, motivation, attention, threat and control. Those systems can be targeted.
But agency matters beyond any single behavior. It influences whether someone can pursue a long-term goal over an immediate reward, approach another person despite fear, mobilize effort when motivation is low, adapt when circumstances change, learn from an experience and carry that change forward. Over a lifetime, those capacities shape health, relationships, work, learning, independence and the range of choices a person is actually able to make.
Medicine has traditionally intervened once failures of these systems become severe enough to earn a diagnosis, and measured success largely within the boundaries of that diagnosis. Agency Therapeutics propose a broader therapeutic objective: improve the biological capacity for self-regulation itself while preserving the other functions that make that capacity useful.
The implications may also outlast the immediate pharmacology. Experience changes biology. Repeated behavior and learning remodel neural circuits, and some adaptive changes are stabilized through longer-lived molecular and epigenetic processes. A medicine that changes what a person is able to repeatedly do, learn or reinforce may therefore alter not only a transient state, but the biological substrate on which future behavior is built.
This is especially important because many of the determinants of health and human experience are cumulative. The relevant endpoint is not maximal control or optimization for its own sake, but greater capacity to pursue self-endorsed goals without unnecessarily sacrificing health, reward, intimacy, flexibility or other dimensions of a well-functioning life.
References
Li Y, Pan A, Wang DD, et al. Impact of healthy lifestyle factors on life expectancies in the US population. Circulation. 2018;138(4):345–355. doi:10.1161/CIRCULATIONAHA.117.032047.
Ludwig DS, Aronne LJ, Astrup A, et al. The carbohydrate-insulin model: a physiological perspective on the obesity pandemic. Am J Clin Nutr. 2021;114(6):1873–1885. doi:10.1093/ajcn/nqab270.
Lee IM, Shiroma EJ, Lobelo F, et al. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet. 2012;380(9838):219–229. doi:10.1016/S0140-6736(12)61031-9.
Cappuccio FP, D'Elia L, Strazzullo P, Miller MA. Quantity and quality of sleep and incidence of type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care. 2010;33(2):414–420. doi:10.2337/dc09-1124.
Cappuccio FP, Cooper D, D'Elia L, Strazzullo P, Miller MA. Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. Eur Heart J. 2011;32(12):1484–1492. doi:10.1093/eurheartj/ehr007.
World Health Organization. Adherence to Long-Term Therapies: Evidence for Action. Geneva: World Health Organization; 2003.
Kronish IM, Thorpe CT, Voils CI. Measuring the multiple domains of medication nonadherence: findings from a Delphi survey of adherence experts. Transl Behav Med. 2021;11(1):104–113. doi:10.1093/tbm/ibz133.
Lyon RE, Rizeq J, Flora DB, Martinussen R, Andrade BF, Toplak ME. Age-related variance in performance versus ratings of attention and impulse regulation in children: implications for the assessment of ADHD. Brain Sci. 2022;12(8):1033. doi:10.3390/brainsci12081033.
Hall KD, Ayuketah A, Brychta R, et al. Ultra-processed diets cause excess calorie intake and weight gain: an inpatient randomized controlled trial of ad libitum food intake. Cell Metab. 2019;30(1):67–77.e3. PMID: 31105044.
Fazzino TL, Rohde K, Sullivan DK. Hyper-palatable foods: development of a quantitative definition and application to the US food system database. Obesity. 2019;27(11):1761–1768. doi:10.1002/oby.22639.
Montag C, Lachmann B, Herrlich M, Zweig K. Addictive features of social media/messenger platforms and freemium games against the background of psychological and economic theories. Int J Environ Res Public Health. 2019;16(14):2612. doi:10.3390/ijerph16142612.
U.S. Surgeon General. Our Epidemic of Loneliness and Isolation: The Healing Effects of Social Connection and Community. 2023.
Zilioli S, Jiang Y. Endocrine and immunomodulatory effects of social isolation and loneliness across adulthood. Psychoneuroendocrinology. 2021;128:105194. doi:10.1016/j.psyneuen.2021.105194.
Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the NCS-R. Arch Gen Psychiatry. 2005;62:593–602.
Ruscio AM, Brown TA, Chiu WT, et al. Social fears and social phobia in the USA: results from the NCS-R. Psychol Med. 2008;38:15–28.
Sexual dysfunction associated with SSRIs in adults with depression: systematic review and meta-analysis. Eur J Clin Pharmacol. 2026. doi:10.1007/s00228-026-04011-z.
World Health Organization. Guidelines on Mental Health at Work. Geneva: World Health Organization; 2022.
World Health Organization/International Labour Organization. Joint news release. 28 September 2022.
Evans-Lacko S, Knapp M. Global patterns of workplace productivity for people with depression. Soc Psychiatry Psychiatr Epidemiol. 2016. PMCID: PMC5101346.
Holt-Lunstad J, Smith TB, Layton JB. Social relationships and mortality risk: a meta-analytic review. PLoS Med. 2010;7(7):e1000316. PMID: 20668659.
Li L, Zhu N, Zhang L, et al. ADHD pharmacotherapy and mortality in individuals with ADHD. JAMA. 2024;331(10):850–860. doi:10.1001/jama.2024.0851.
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389:2221–2232.
Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in type 2 diabetes. N Engl J Med. 2024.
GLP-1 receptor agonist use and cancer risk in obese nondiabetic adults. Ann Oncol. 2026. doi:10.1016/j.annonc.2026.02.011.
Dai H, Li Y, Lee YA, et al. GLP-1 receptor agonists and cancer risk in adults with obesity. JAMA Oncol. 2025;11(10):1186–1193. doi:10.1001/jamaoncol.2025.2681.
Xie Y, Choi T, Al-Aly Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nat Med. 2025. doi:10.1038/s41591-024-03412-w.
Hendershot CS, et al. Once-weekly semaglutide in adults with alcohol use disorder. JAMA Psychiatry. 2025. doi:10.1001/jamapsychiatry.2024.4789.
Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025. doi:10.1056/NEJMoa2416394.
Eli Lilly and Company. Brenipatide (LY3537031) clinical development program: RENEW studies and Lilly clinical development pipeline. Accessed September 2026.
U.S. Food and Drug Administration. FDA updating warnings to improve safe use of prescription stimulants used to treat ADHD and other conditions. 11 May 2023.
Robinson ESJ, Eagle DM, Economidou D, et al. Similar effects of atomoxetine on three distinct forms of impulsivity in the rat. Neuropsychopharmacology. 2008. PMID: 17637611.
Otsuka Pharmaceutical Co., Ltd. Otsuka receives FDA approval for SIMTRIYO (centanafadine) for the treatment of attention-deficit/hyperactivity disorder in adults and pediatric patients aged 6 years and older. 24 July 2026.
Krystal JH, Kavalali ET, Monteggia LM. Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms. Neuropsychopharmacology. 2024;49:41–50. doi:10.1038/s41386-023-01629-w.
Mitchell JM, Ot'alora G M, van der Kolk B, et al. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nat Med. 2023;29:2473–2480. doi:10.1038/s41591-023-02565-4.
Ribbens C, Peeters L, Van Oudenhove L, Vervliet B, Dalile B. The HDAC inhibitor sodium butyrate moderately enhances long-term fear extinction memory retrieval in humans. Mol Psychiatry. 5 August 2026. doi:10.1038/s41380-026-03802-1.
Eli Lilly and Company. Annual Report 2025. Mounjaro and Zepbound worldwide revenue. 2026.
Novo Nordisk. Annual Report 2025. 2026.
Harmony Biosciences. Harmony Biosciences announces exclusive agreement to develop and commercialize TPM-1116, a highly potent and selective oral orexin-2 receptor agonist. 11 April 2024.
AbbVie Inc. 2025 Annual Report. Acquisition of Gilgamesh Pharmaceuticals and bretisilocin (ABBV-2505). 2026.
Lohr KM, Bernstein AI, Stout KA, et al. Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo. Proc Natl Acad Sci U S A. 2014;111(27):9977–9982. doi:10.1073/pnas.1402134111.
Wang Y, Zhang P, Chao Y, et al. Transport and inhibition mechanism for VMAT2-mediated synaptic vesicle loading of monoamines. Cell Res. 2024;34:47–57. doi:10.1038/s41422-023-00906-z.
Salamone JD, Ecevitoglu A, Carratala-Ros C, et al. Complexities and paradoxes in understanding the role of dopamine in incentive motivation and instrumental action. Brain Res Bull. 2022;182:57–66. PMID: 35151797.
Salamone JD, Correa M. The neurobiology of activational aspects of motivation. Annu Rev Psychol. 2024. doi:10.1146/annurev-psych-020223-012208.
Bymaster FP, Katner JS, Nelson DL, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat. Neuropsychopharmacology. 2002;27:699–711.
Miyazaki K, Miyazaki KW, Sivori G, et al. Serotonergic projections to orbitofrontal and medial prefrontal cortices differentially modulate waiting for future rewards. Sci Adv. 2020. doi:10.1126/sciadv.abc7246.
Worbe Y, Savulich G, Voon V, et al. Serotonin depletion induces "waiting impulsivity" on the human four-choice serial reaction time task. Neuropsychopharmacology. 2014. doi:10.1038/npp.2013.351.
Peixoto L, Abel T. The role of histone acetylation in memory formation and cognitive impairments. Neuropsychopharmacology. 2013;38(1):62–76. doi:10.1038/npp.2012.86.
