This report calls on those who oversee the funding and implementation of PTSD research to reject animal-based research on PTSD and other mental illnesses
In the United States, over 6% of adults are diagnosed with post-traumatic stress disorder (PTSD) at some point in their lives, with higher rates in subpopulations like active-duty service members and childhood trauma survivors. In recent years, the world has faced an unprecedented convergence of traumatic events, from the lingering psychological impacts of the COVID-19 pandemic to escalating gun violence to natural disasters intensified by the climate crisis.
As a result, the global toll on mental health has been devastating. Those with PTSD experience symptoms like flashbacks and uncontrollable thoughts about traumatic events, which can lead to depression, anxiety, impaired sleep, difficulty concentrating, emotional extremes, and violent outbursts. People diagnosed with PTSD also face elevated risks of suicidal ideation, attempted suicide, and death.
Most studies examining the connection between PTSD and suicide focus on veterans, for whom the correlation is especially strong. The link between PTSD and suicide risk has also been observed in firefighters and Emergency Medical Services personnel (Martin et al., 2017), refugees (Ferrada-Noli et al., 1998), and the general population (Giacomoni, 2018). Over the past 15 years, researchers have made considerable progress in understanding and treating PTSD with targeted psychotherapy, as acknowledged by the U.S. Department of Veterans Affairs (VA), Department of Defense (DoD), and the American Psychological Association (APA).
Unfortunately, these effective and evidence-based treatments have not been well integrated into practice. Accessing care can be very costly for individual patients, healthcare organizations, and government agencies, with some estimates suggesting that PTSD and depression in veterans returning from wars in Afghanistan and Iraq cost the United States $923 million over two years (Foa et al., 2013).
Despite mounting evidence that delivering existing therapies to underserved populations could effectively treat PTSD, many scientists and healthcare professionals continue to spend millions of dollars searching for pharmacological treatments that rarely translate to viable human therapies. Many neuropharmacological studies involve animal experiments that subject animals to severe trauma that exceeds their coping abilities, raising significant ethical concerns.
Here, we argue that animal-based PTSD experiments harm animals without adequately helping human patients. As such, funding agencies must redirect resources towards studying and disseminating treatments already known to effectively relieve suffering in people with PTSD.
Evidence-based treatments and therapies for PTSD
Leading health organizations like the World Health Organization and the American Psychological Association recommend psychotherapy as the best treatment for trauma-initiated mental health conditions (WHO, 2013; APA, 2017). Both the VA and DoD also recommend individualized trauma-focused psychotherapies, which help rework perceptions of traumatic memories, over pharmaceutical treatments like benzodiazepines (VA, 2023). A 2016 systematic, multi-center meta-analysis evaluating the relative efficacy of psychotherapy and pharmacotherapy for PTSD found that, as a first-line treatment, psychotherapy is generally more effective than medication (Lee et al., 2016).
In a 2023 survey, the American Psychological Association found that 37% of US adults reported having a mental health diagnosis (APA, 2023). According to the VA, about 5 in 100 adults in the US are diagnosed with PTSD, comprising roughly 13 million adults in 2020. However, a recent report found that 57% of adults with mental health diagnoses do not receive treatment—even though effective, well-validated therapies already exist (Hellebuyck et al., 2018). To best respond to the PTSD crisis, researchers and funding agencies must prioritize bridging the gap between delivering existing effective treatments over developing new therapies.
Exposure therapy
Introduced in Western clinical practice in the mid-twentieth century, exposure therapy is one of the oldest treatments for anxiety and PTSD. Both the American Psychological Association and the National Academies of Sciences, Engineering, and Medicine strongly recommend prolonged exposure therapy (PE) for treating PTSD in adults (APA, 2025; Institute of Medicine, 2012). During PE, a trained therapist helps the patient gradually approach trauma-related memories in a safe setting. For many people, exposure therapy is highly effective, more cost-effective than drug-based interventions, and has a lower dropout rate than pharmacotherapy (Foa et al., 2013; Le et al., 2014; Lee et al., 2016; McLean et al., 2022). Meta-analyses repeatedly identify PE as the most effective tool for treating PTSD (VA, 2023; Cusack et al., 2016).
Exposure therapies can be customized for different individuals and cultures, and adapted to various formats. For instance, virtual reality (VR) can simulate environments that safely immerse people in traumatic memories in a controlled setting. Combining virtual reality with exposure therapy (VRE) can enhance emotional engagement and acceptance by maximizing the person’s fears and what they are exposed to during treatment sessions (Difede et al., 2007; Botella et al., 2015; Maples-Keller et al., 2017).
VR also presents an entirely new way to study and understand PTSD. Researchers have recorded brain activity during VRE to refine and study treatment protocols without using animals, revealing information about human-relevant brain function (Freeman et al., 2017; Landowska et al., 2018). Importantly, VR allows for the repeated presentation of potentially distressing scenarios that are objectively safe, helping people learn new thought patterns in a controlled environment. Studies have found that multiple biomarkers of stress, including cortisol levels (Norrholm et al., 2016), galvanic skin response (Katz et al., 2020), and resting heart rate (Bourassa et al., 2020), decrease over the course of a VRE session.
Eye movement desensitization and reprocessing (EMDR)
Eye movement desensitization and reprocessing, or EMDR, was first developed by North American psychologist Francine Shapiro in the late 1980s to help people heal from emotional distress caused by traumatic life experiences. During EMDR sessions, the client recalls traumatic experiences while focusing on an external stimulus, like following the therapist’s finger, hand-tapping, or listening to audio that demands their attention (Shapiro, 2017). The horizontal eye movements imposed by such a rhythmic task can ameliorate the discomfort of recalling traumatic memories. Over time, EMDR aims to reprocess the client’s traumatic memories and recontextualize them as normal (Novo Navarro et al., 2018).
Researchers have proposed several theories to explain the success of EMDR. Results from one large meta-analysis suggest that the eye movements themselves aid in the process of converting negative memories into neutral or positive ones (Lee & Cuijpers, 2013). A more recent review of 87 studies found support for the working memory hypothesis, which proposes that focusing on eye movements and visual memories simultaneously draws from the same limited pool of neural resources, making negative memories less vivid (Landin-Romero et al., 2018). Some evidence suggests that EMDR relieves PTSD symptoms by triggering amygdala deactivation (de Voogd et al., 2018) and activating the cerebellum and the default mode network (Calancie et al., 2018), suppressing fear responses while boosting memory retrieval and relaxation. Eye movements may also engage frontoparietal brain regions involved in autobiographical memory retrieval and emotional regulation, normalizing previously traumatic memories (Harricharan et al., 2019).
Dozens of randomized controlled trials show that EMDR can relieve affective distress, negative beliefs, and physiological arousal in children and adults with PTSD (Foa et al., 2009; Moreno-Alcazar et al., 2017; Chen et al., 2014). Given its demonstrated effectiveness in single-trauma and multiple-trauma victims (Marcus et al., 1997; Marcus et al., 2004), leading health organizations list EMDR as a top-ranked treatment for trauma and PTSD (WHO, 2013; APA, 2025).
Accelerated resolution therapy
Accelerated resolution therapy (ART) is a newer treatment that combines psychotherapy with eye movements through a two-phase approach. In the first phase, the therapist guides the client through recalling a traumatic event. In the second phase, the therapist directs the client to make horizontal eye movements while going through “voluntary memory/image replacement,” releasing pain tied to disturbing memories by rescripting their reactions to them (Kip et al., 2014). Most people experience relief from PTSD symptoms in just a few sessions (Kip et al., 2013). Although research on ART is still relatively limited (Waits et al., 2017), people with PTSD stemming from combat, domestic and child abuse, violent crimes, grief, illness, and divorce have all reported substantial, lasting reductions in symptoms with ART (Kip et al., 2012; 2013; 2014). There is even evidence that ART sessions can reduce physical pain related to the trauma that caused the patient’s PTSD (Kip et al., 2014).
Although ART is less established than therapies like PE and EMDR, existing evidence supports its efficacy, and it is inexpensive, safe, and has a high completion rate. More human-based research exploring ART and similar treatments could provide significant relief to people with PTSD and to the overburdened Department of Veterans Affairs.
Other evidence-based treatments
Other treatments, like cognitive writing therapy (Ruward and Lange, 2016), group therapy (Schwartze et al., 2020), and narrative exposure therapy (Lely et al., 2019), also aim to help people with PTSD re-experience their initial trauma, normalize or recontextualize the memory, and cope with it. All existing evidence-based therapies for PTSD tap into the human brain’s capacity for rich visualization, using exposure to negative trauma memories as an opportunity to reprocess and normalize traumatic memories. The key to successfully applying cognitive therapy is adapting it to the client’s needs; client participation and compliance are the first steps toward a positive treatment outcome. These therapies can also be expanded or adapted to include people who prefer different types of procedures and therapy styles.
Lack of dissemination of existing, evidence-based therapies
Despite the success and widespread endorsement of PE, VRE, EDMR, and ART as first-line treatments for PTSD, they remain largely underused. The disconnect between existing, evidence-backed treatment options and people who need them is not unique to PTSD. According to the 2019 State of Mental Health in America report, about 20% of adults don’t receive any mental health support at all. Cost is a major barrier: over 58% of adults who thought they needed mental health care in 2022 said they didn’t receive it because it was too expensive (Substance Abuse and Mental Health Services Administration, 2022).
Barriers to delivering care exist at the patient, provider, and institutional levels. Individuals with mental illnesses may be concerned about mental health stigma, may have lost wages or health insurance, or may not be near or aware of existing resources. Providers may lack appropriate training or sufficient resources, (Phillips and Tucker, 2023), and may resist or not be aware of effective therapy approaches due to commitment to current practice (Foa et al., 2013).
Nevertheless, clinicians and their professional associations increasingly urge public health stakeholders to integrate evidence-based therapies into clinical settings (Foa et al., 2013; Rauch et al., 2023). Telehealth and other internet-based technologies present one expedient, low-cost solution to delivering high-quality care that can be as effective as in-person therapy (Bellanti et al., 2022). If declared a research priority, supporting these therapies could address gaps in care. Given the abundance of professional endorsements for these therapies and the pressing need among large populations of people with PTSD, shifting funding priorities away from animal-based studies promises to drastically address the suffering of thousands of people while reducing the burden of PTSD on the healthcare system. To address these obstacles, funding agencies must help dissolve barriers between existing treatments and the people who need them.
Human-centered PTSD research
Many scientists argue that animals are necessary for studying the neurobiological underpinnings of PTSD and developing treatments. However, there is abundant evidence that animal research often fails to translate beyond preclinical studies, and animal models of PTSD are especially problematic. While humans share a large percentage of our genome with common model organisms like mice and monkeys, this does not guarantee that data from non-human species will accurately predict human outcomes.
In humans, PTSD symptoms like nightmares, flashbacks, and pervasive negative thoughts involve subjective experiences that must be verbally communicated to a health care practitioner. These kinds of symptoms cannot be quantified in animals through behavioral observation alone, and attempting to do so can introduce bias and irreproducibility. Without being able to communicate with animals directly, it isn’t possible to interpret their subjective experiences or to understand whether their responses to trauma are comparable to those in humans with PTSD (Steimer, 2011; Aspesi and Pinna, 2019). Consequently, psychiatric drug discovery programs often fail to bring new treatments to market, leading many pharmaceutical companies to withdraw from psychiatry altogether (Richter-Levin et al., 2018).
Increasingly, scientists agree that using animals to model human PTSD poses serious shortcomings. Yet, instead of rejecting them, many researchers continue to try to “improve” animal models. Here, we argue that researchers will benefit more from replacing animals with human-centered techniques. Neuroimaging and AI-driven computational methods have the potential to accelerate relevant, translatable findings to directly help people with PTSD, and may also uncover novel research questions that might otherwise remain unexplored.
Non-invasive neuroimaging techniques
Several neuroimaging methods have been used by hospitals, universities, and other research institutions for decades, and are already used to noninvasively study the neural mechanisms of PTSD in humans. These tools are safe for most people and are widely used across diverse populations with few adverse effects (Angus-Leppan, 2006; Hawkinson et al., 2012; Silberstein, 2014).
Functional magnetic resonance imaging (fMRI)
One of the most common human neuroimaging methods is functional magnetic resonance imaging, or fMRI. Magnetic resonance imaging uses powerful magnets to force protons in the body to spin, releasing energy that sensors can detect and use to create images of bone, muscle, and other tissues (National Institutes of Biomedical Imaging and Bioengineering). Functional MRI tracks the flow of oxygenated blood to the brain while a participant performs a task inside the scanner. As neural signaling burns energy, oxygenated blood flow to that brain region increases. By analyzing this blood oxygen level dependent (BOLD) signal over time, researchers can detect when specific brain regions activate during cognitive tasks (Glover, 2012). By using fMRI to compare BOLD responses in people with and without PTSD, researchers can learn what parts of the brain are most affected by the disorder and test how the brain reacts to psychotherapy.
Scientists have used fMRI data to track neural activity during trauma-related memory recall (Sadeh et al., 2014; Thome et al., 2019). Neuroimaging studies have reported increased activation of the amygdala, which processes fear, and decreased prefrontal cortex activity in people with PTSD, in addition to weakened connections between brain regions responsible for detecting threats and regulating emotions (Jowf et al., 2023). This method has also revealed changes in the brain structure of PTSD patients, including reduced cortical thickness and gray matter volume (Sadeh et al., 2015; Crombie et al., 2021; Li et al., 2022). Reduced hippocampal activation within 24 hours of trauma exposure may even predict future PTSD symptom severity (van Rooij et al., 2018). Meta-analyses have also revealed that the brains of people with PTSD show distinct activation patterns across neural networks involved in memory, fear, emotional regulation, and decision making (Stark et al., 2015).
Importantly, fMRI can also be used to study how different psychotherapies and medications affect the brains of people with PTSD, providing valuable information about treatment efficacy. One clinical trial observed that connections were strengthened between brain regions involved in emotional reactivity and regulation following one month of prolonged exposure treatment (Fonzo et al., 2017). Other studies have observed upregulation of the medial prefrontal cortex, which is important for suppressing fear (Manthey et al., 2021), providing further evidence that therapy alone can directly impact neural activity. On the pharmaceutical side, fMRI has been used to image BOLD signals in people taking paroxetine, an SSRI antidepressant (MacNamera et al., 2015) and the beta blocker propranolol (Very et al., 2025), allowing researchers to predict how well a drug might relieve PTSD symptoms for a given individual (Sheynin et al., 2020).
Positron emission tomography (PET)
Positron emission tomography (PET) measures radioactivity emitted by a tracer injected into the bloodstream. Depending on the specific tracer used, PET can track chemical neurotransmitters like dopamine or glucose consumption as a proxy measure for neural activity. While PET was the dominant technique in early neuroimaging research, MRI studies—which don’t require injections or radiation exposure—have gradually replaced PET in many cognitive neuroscience experiments. However, PET remains valuable for studying molecular pathways involved in psychiatric disorders like PTSD (Sander and Hesse, 2018).
For example, by imaging the brains of dozens of people with and without PTSD, researchers found that people with PTSD tended to have more available metabotropic glutamate receptors than controls, highlighting a potential target for new medications (Holmes et al., 2017). Other PET studies have reported connections between PTSD and increased neuroimmune suppression (Bhatt et al., 2020), vascular inflammation (Toczek et al., 2021), and abnormal cannabinoid signaling, which affects stress responses (Neumeister et al., 2013).
Electroencephalography
Electroencephalography, or EEG, measures electrical activity in the brain via electrodes placed on the scalp. Although EEG does not provide the same level of spatial resolution as fMRI, it has much higher temporal resolution, capturing changes in brain activity on a millisecond timescale. EEG is noninvasive, safe, and well-suited for measuring the relative strength of different neural oscillations, or brainwaves, which reflect coordinated activity across different brain regions. Evidence from several studies suggests that EEG results can serve as a biomarker for PTSD severity (Lobo et al., 2015). PTSD symptom severity is associated with weaker alpha band oscillations, which are normally associated with relaxed wakefulness and focus (Taghva et al., 2015; Lobo et al., 2015), and abnormal theta rhythms, which play an important role in memory processing and emotional regulation (Toll et al., 2020). EEG studies have also found evidence of abnormal sleep patterns in PTSD patients (Neylan et al., 2006).
Post-mortem brain tissue analysis
In the early 2000s, many prominent researchers called for the establishment of a post-mortem human brain bank dedicated to PTSD Friedman and Harris, 2004). Since then, the VA’s National PTSD Brain Bank, launched in 2014, has collected and distributed brain tissue to support human-centered research studying how PTSD changes neuroanatomy (Friedman et al., 2017). The Harvard Brain Tissue Resource Center and the NIH Human Brain Collection Core also collect brain tissue from people diagnosed with PTSD, among other psychiatric diseases (Deep-Soboslay, 2011; NIH, 2024). These resources provide access to a variety of human brain tissues for genetic and histological studies. For example, through postmortem tissue analysis, investigators identified astroglia scarring associated with traumatic brain injury and PTSD (Shively et al., 2016).
By examining post-mortem tissue, researchers can trace how changes in gene expression translate to cellular and molecular alterations in the brains of people diagnosed with PTSD. Recent studies have identified extensive molecular changes and transcriptomic remodeling specific to certain brain regions (Girgenti et al., 2021). Notably, researchers have identified significant molecular markers—such as reduced expression of immune-related genes like TSPO—and validated these findings in living patients using PET imaging with a radiotracer targeting the same proteins (Bhatt et al., 2020). In a recent review of next-generation gene sequencing technology, researchers argued that human postmortem transcriptome studies like these “promise the best source of information to unravel the complex brain molecular underpinnings of PTSD” (Girgenti and Duman, 2018).
PTSD biomarkers
Biomarkers are measurable substances or symptoms that indicate the presence of a specific condition. Researchers have identified several potential biomarkers for diagnosing and measuring PTSD in its earliest, most treatable stages, including cortisol levels, patterns of EEG activity, and genetic markers (National Academies, 2012).
PTSD biomarkers are related to other anxiety disorders and can predict patient outcomes. For instance, the stress hormone cortisol tends to be highly elevated in people with panic disorder, generalized anxiety disorder, specific phobias, and social anxiety disorder (Elnazer and Baldwin, 2014). Perhaps counterintuitively, this does not seem to be the case with PTSD. Rather, PTSD is associated with lower baseline cortisol levels, impairing the body’s natural ability to regulate stress responses (Meewisse et al., 2007; Yehuda and Seckle, 2011). For instance, people with higher cortisol reactivity—a larger, faster cortisol spike in response to stress exposure—may have worse outcomes in VR exposure therapy than others (Norrholm et al., 2016). Given the relationship between cortisol and PTSD symptoms, initial assessments of cortisol levels after trauma could inform treatment.
Differences in brain structure and connectivity may also predict PTSD symptoms. Neuroimaging studies across hundreds of people with PTSD report increased cortical thickness in brain regions related to hypervigilance and emotional regulation (Li et al., 2022). Another study of over 4,000 adults reported that people with PTSD tended to have smaller cerebellums than controls (Huggins et al., 2024). Other proposed biomarkers include neural inflammation (Kim et al., 2019), heightened levels of stress hormone norepinephrine (Pan et al., 2018), amygdala hyperactivity (Voogd et al., 2025), and reduced brain mass in networks responsible for memory, processing sensory information, and emotional responses (Hu et al., 2018). The strength of certain neural networks, including the connection between the prefrontal cortex and PTSD-related regions like the amygdala and the hippocampus, also predicts someone’s likelihood of experiencing PTSD symptoms (Harnett et al., 2021; Sheynin et al., 2024; Siddigi et al., 2024).
Recently, scientists pinpointed 95 regions of the human genome linked to the risk of developing PTSD (Nievergelt et al., 2024). Using only a saliva sample, genetic studies have revealed several predictors of PTSD that could be used to identify people who are more likely to experience symptoms after trauma (Sheerin et al., 2017; Stein et al., 2021). Studies combining neuroimaging with genetic analysis have found links between the expression of specific genes, PTSD symptoms, and abnormalities in the hippocampus and prefrontal cortex (Miller et al., 2015; McNerney et al., 2018; Logue et al., 2021).
Inducing trauma in animals for PTSD research
PTSD research on mice and rats
The vast majority of preclinical PTSD research is conducted on rats and mice (Steimer, 2011; Whitaker et al., 2015), despite scientists’ inability to assess how well they model certain symptoms like intrusive thoughts or nightmares. Rather, rodent models of PTSD mainly convey the approximate human responses to chronic stressors. These stressors can be physical, like electric shocks, restraints, or forced submersion in water; or social, like being exposed to a predator’s scent (Verbitsky et al., 2020). Notably, none of these procedures directly correlate with the human experiences that result in PTSD. Occasionally, these methods can injure the animal, both causing undue harm and confounding results (Finnell et al., 2017).
Electric shock
To elicit learned helplessness—giving up after facing repeated seemingly-insurmountable challenges—rodents are often exposed to inescapable and unpredictable electrical shocks to their sensitive hands and feet (Conoscenti and Fanselow, 2019). Scientists commonly place rats and mice into “shock boxes,” or metal-floored cages that electrocute them randomly until they freeze and stop trying to escape (e.g., Cohen et al., 2004; McGowan et al., 2017). When previously-shocked rodents return to the shock box, they generally freeze, crouch near the back wall of the box, and accelerate their breathing—signs of heightened fear that researchers typically describe as “PTSD-like” symptoms (Schöner et al., 2017). Other paradigms have one animal watch another get shocked to mirror indirectly acquired fear memories of humans with bystander PTSD (Navabpour et al., 2024).
Simulated drowning
The Morris water maze is a behavioral task testing learning and spatial memory in mice and rats (Brandeis et al., 1989). Normally, it consists of a basin of deep water with small, hidden platforms providing rest at various points throughout the body of water. Many neurobiologists and behaviorists use the maze to study how injury or drugs affect the animal’s ability to find the hidden platforms (Hooge and De Deyn, 2001). Rats and mice are naturally proficient swimmers, but swimming under forced or constrained circumstances is very stressful for them.
When studying PTSD, researchers often remove all the platforms so there is no possibility of rest or relief. In this forced swim test, animals are left to struggle until they become immobile, generally considered a sign of despair (Yankelevitch-Yahav et al., 2015). Another variation, called “underwater trauma,” involves holding the animal underwater with a metal net for about thirty seconds, simulating the threat of drowning (Wang et al., 2000). Some researchers argue that underwater drowning is more ethologically relevant than electric shocks, because it simulates a threat that rodents would naturally experience in the wild (Schöner et al., 2017).
Restraint, immobilization, and other physical stressors
Restraint-based methods are often used to induce stress in rodents (Molina et al., 2023). Animals may be placed in Plexiglas or wire mesh tubes (Gameiro et al., 2006), tethered to wooden boards (Armaria et al., 2004), or held in a conical bag called a “DecapiCone” (Kedia and Chattarji, 2014). While animals initially struggle, they eventually freeze, a response considered an indicator of PTSD-like symptoms. In more extreme cases, researchers expose rodents to a natural predator, like a cat, in a confined area (e.g. Adamec, 1997).
More severe protocols subject animals to a combination of stressors: multiple hours of restraint, followed by a forced swim test, then exposure to diethyl ether that results in a loss of consciousness (Whitaker et al., 2015). Afterwards, they are left undisturbed for seven days, theoretically representing an incubation period thought to be essential for the development of PTSD-like symptoms. Another version of this procedure exposes rodents to one of those stressors every day for six days, several weeks in a row. Researchers recognize how inhumane these experiments are but justify them by comparing them to chronic stress conditions experienced by human military personnel with PTSD (Goswami et al., 2013).
Social stress
Rats have strong social bonds and require stable, social housing conditions to stay healthy (Balcombe, 2006). Knowing this, researchers can induce stress in rodents by disrupting their family and social lives (Koolhaas et al., 2016). To model early life stressors like childhood neglect, which are known to increase PTSD risk in humans, researchers separate mothers from their babies for several hours a day for weeks after birth, making them more fearful as adults (Heim et al., 1997; Kalinichev et al., 2002). Other methods force animals to be unnaturally aggressive, or to face aggressive attacks that they would normally avoid (e.g. Oliveira et al., 2022; Pizarro et al., 2004; Pulliam et al., 2010; Hammamieh et al., 2012).
Social stress can also be induced by socially isolating rodents for several weeks (Pinna, 2019), eliciting heightened anxiety-like behavior and aggression (Locci and Pinna, 2019; Charuvastra and Cloitre, 2008). It should be noted that the lifespan of a mouse or rat is much shorter than a human—weeks of isolation may feel much longer to a rodent, and to our knowledge, animal studies of PTSD do not take this into account.
Environmental stress
Chronic stressors, like reversing the natural day-night cycle with artificial lighting or increasing housing density, can also disrupt normal behavior in rodents, impairing sleep and causing weight loss (Willner et al., 1987). Some paradigms subject animals to more extreme environmental stressors like loud and distressing noises, food deprivation, or the pervasive scent of a predator—occasionally alongside other physical and social stressors (e.g. Blanco et al., 2017).
PTSD research with other animals
While mice and rats are the most common animal models of PTSD, other species are also used. Nonhuman primates, particularly rhesus macaques, are commonly used to model psychiatric disorders (Maior et al., 2021). During experiments, researchers typically restrain macaques in a restraint chair that confines their entire body from the neck down. Once restrained, researchers can record or stimulate neural activity from electrodes implanted in the brain, or deliver drugs directly to brain tissue, and observe behavior.
As in rodent studies, researchers induce stress by exposing macaques to startling, unpleasant stimuli like loud noises (Aguilar et al., 2018) eliciting behaviors like cowering, escape attempts, howling, and attacking objects (DesJardin et al., 2013; Forcelli et al., 2016). One recent experiment exposed “food regulated” macaques monkeys to uncontrollable stress by having them succeed at multiple complex trials to attain a food reward. Monkeys were alternately injected with a benzodiazepine sedative and nebivolol, a beta blocker, to measure “the major role of stress in exacerbating the symptoms of cognitive disorders” such as PTSD. (Joyce et al., 2024). After attempts to induce PTSD in primates for over 60 years, results have been indeterminate, contradictory, and have not translated to humans.
The cost of PTSD research on animals
Animal-based PTSD research consumes substantial taxpayer funding while delivering limited meaningful advances for human mental health. In 2023, the National Institutes of Health (NIH) reported 356 active projects under the PTSD spending category, totaling roughly $148 million dollars. Of these projects, 59 used animals (mice, rats, or nonhuman primates), representing about 14% of total research spending, or $20.5 million.
Unlike many animal studies, human-centered projects can more directly translate to quality-of-life improvements for people with PTSD. Many promising treatments for neurological and psychiatric disorders that work in animal studies fail when tested in humans. For example, despite decades of research in stroke medicine, animal studies have failed to discover any neuroprotective treatments for humans.
Similar failures across pharmacology have contributed to a decline in support for animal research and prompted both the NIH and the US Food and Drug Administration (FDA) to announce plans to phase out animal research in April 2025. The NIH later announced that moving forward, they will no longer award funding to grant proposals that rely solely on animal testing.
Increasingly, pharmaceutical and biotechnology companies, including Emulate, Vivodyne, and Parallel Bio, are investing heavily in human-centered research strategies. Even Charles River Laboratories, the largest supplier of lab animals in the US, launched a project to reduce reliance on animal testing in 2024. The percentage of PTSD-related research funding devoted to animal studies has already declined slightly over the past decade, and this trend will likely continue if the federal government follows through on their recent commitments to prioritize alternative methods.
The most cost-effective and ethical use of PTSD research funding is expanding access to proven psychotherapies and providing therapists and counselors with the training they need to best support people with PTSD. Basic science funding should be granted to researchers seeking to understand PTSD neuropathology in humans. Research consistently demonstrates that this investment pays for itself. One cost analysis found that successful completion of psychotherapy for PTSD significantly reduced mental health care costs for a sample of 70 veterans, outweighing the initial cost of providing those services by roughly $2,000 per person. According to the National Center for PTSD, roughly 13 million Americans had PTSD in 2020. Providing those millions of people with effective care would save taxpayers hundreds of millions of dollars per year.
Conclusion
To study a psychiatric disorder characterized by heightened anxiety and stress in response to a traumatic event, any animal model of the disorder must be exposed to trauma. Thus, not only is PTSD research in animals harmful, but the harm is inseparable from research methods. Yet, across neuropsychiatric research, the translational value of animal studies is difficult to prove. For all the suffering, animal models of PTSD fail to capture the complexity of human neuropsychiatric disorders like PTSD and have yielded little human-relevant insight.
Moving forward, researchers need to seriously question the ethics and validity of animal models when designing future studies (Meijboom et al., 2020; Seifrad and Haghpanah, 2019). Importantly, funders and stakeholders must acknowledge the shortcomings and cruelty of animal experiments, which cost millions of dollars in funding that could be better spent directly studying PTSD in humans. We urge funding organizations to account for the invalidity of animal models of PTSD and to redirect funding from these projects towards ethical, effective, and human-centered research. It is up to lawmakers and funders to ensure that science remains bound to the ideal of promoting human health. Eliminating animal research in PTSD and other mental illnesses is essential to accomplishing this goal.
