When deadlines loom, we’ve all succumbed to the same fate: an impromptu marathon session, followed by a zombie-like stumble into the next day.
For fighter pilots, the final step isn’t always a choice. Throughout their demanding obligations, pilots must maintain peak mental acuity, even when fatigued from lack of rest – a common reality. For many, therapy becomes their go-to coping mechanism, like a daily dose of caffeine that keeps them grounded. Despite shorter periods of sleep deprivation, pilots may still experience impairments; accordingly, they are typically prescribed more potent stimulants to help them remain alert and focused during extended flight hours.
Despite the energizing benefits that many people associate with caffeine consumption, its excessive use is widely recognized to have undesirable consequences. You get jittery. Your arms begin to shake. As your emotional equilibrium falters, the lingering effects of the initial shock begin to wear off, leaving you increasingly irritable and prone to outbursts. And you then crash.
While prescription stimulants like dextroamphetamine do offer significant benefits, they also come with far more severe adverse consequences. Since the title implies a direct connection to methamphetamine and its potential for addiction, one might assume that the individuals are sharing the same living space with a substance notorious for its destructive power over users. These medications linger within the body, rendering certain brain regions perpetually alert, thereby disrupting sleep patterns and maintaining mental clarity even during rest periods. Individuals taking dextroamphetamine often seek sedatives to alleviate lingering effects, which can exact a significant physical and emotional toll.
As time passes, a chronic lack of restful sleep has a profound effect on memory recall, intellectual acuity, and logical thinking. This chronic stress also severely impairs the body’s natural defenses, metabolic processes, and overall health status.
The medication works in brief, intermittent bursts. What if a mechanism existed to toggle their influence on and off at whim, permitting precise dosing of mental stimulation followed by swift disengagement to ensure unimpeded nocturnal slumber?
A potential solution could involve medications triggered by light exposure to provide targeted relief. In June, the Defense Advanced Research Projects Agency (DARPA) is tasked with developing medications to combat sleep deprivation among fighter pilots. Photopharmacology enables the addition of a reversible, light-activated “molecular tweak” to existing medications like dextroamphetamine.
Sunlight pulses stimulate precise cognitive pathways, unleashing targeted therapeutic effects on command. The majority of non-focused mental regions remain impervious to the dynamic model’s influence, thereby continuing their normal functioning process. As the pilots’ alertness peaks, a single additional pulse of sunlight triggers the cessation of the stimulant, allowing their physical systems sufficient time to process and clear the effects before bedtime.
To bring this visionary concept to life, the newly launched AWARE initiative features a dual-pronged research approach. Will developers create a robust and efficient formulation of dextroamphetamine that can be effectively managed with gentle handling? The second project will focus on designing a wearable device, akin to a helmet, that delivers gentle pulses specifically targeting brain regions associated with alertness and cognitive sharpness.
“To achieve the benefits of stimulants in enhancing alertness without their detrimental effects on mood, restorative sleep, and mental wellbeing, a novel approach is needed to enable targeted activation of the drug,” Dr. Pedro Irazoqui, supervisor of AWARE’s programs, noted that
Mind on Alert
Following an unpleasant night’s rest, many people’s primary objective is to secure a cup of espresso. Caffeine, a stimulant often found in various products, is widely regarded as the most commonly consumed psychoactive substance globally, with an astonishing 80% of North Americans relying on its energizing effects to start their day.
While traditional coffee remains the preferred pick-me-up for many fighter pilots, several countries have created more potent blends to keep their squadrons alert and focused. Originally, the most notorious substances were first synthesized in the latter half of the 19th century.
Recognised globally as methamphetamine, ‘crank’ or ‘velocity’, this highly addictive drug gained notoriety during World War II for its use in keeping soldiers awake, before being widely prohibited worldwide. Currently, dextroamphetamine is used as a prescription medication to enhance alertness and cognitive function in individuals requiring a safer spin-off from traditional stimulants. While efficiency may initially yield euphoric results, it may also fuel irritability, potentially leading to a self-perpetuating cycle of habits.
The Air Force has enabled various types of chemical medication, including those designed to combat fatigue as well. Research has revealed that this medication can significantly boost various cognitive functions, including spatial navigation, working memory, and sustained attention, even in individuals who are severely sleep-deprived. Unlike amphetamines, these medications have a lower potential for addiction, offering a more calming experience without the typical nervous energy. However, these substances will often lead to severe physical and mental symptoms, including rapid heartbeat, excessive perspiration, and, in rare cases, vivid hallucinations.
Mildly activated medications may also serve as a viable alternative option. These medications possess a molecular “light-switch” component that reacts to pulses of sunlight. The addition of this new modification will seamlessly integrate with existing medications, rendering it a straightforward endeavour, much like the combination with dextroamphetamine.
After being bombarded by a diverse array of solar radiations. When exposed to certain conditions, this chemical molecule transforms into a form that enables it to bind to its typical receptors, characteristic of its “active” or “native” state. Different configurations inactivate it.
While mild-activated medications have shown promise in cell-based studies, their delivery to the brain poses a significant challenge due to the skull’s protective barrier. While attempting to illuminate the cranium with a flashlight would not access the mind, nor is invasive neurosurgery an option, it’s essential to note that we’re already equipped with the most advanced cognitive tool: our brain.
There’s a workaround. Infrared rays of sunlight, operating at lower intensities, are safely absorbed by the human body and can penetrate deeply into tissues, traversing the skull and entering the brain. Developed a range of hypothetical toggle options potentially triggered by infrared light. Recent breakthroughs in AI could potentially streamline the process of designing “a photoswitchable model of dextroamphetamine that remains inactive unless activated by near-infrared light,” a concept proposed by DARPA.
This innovative headpiece functions as a programmable light-emitting device, emitting infrared radiation to specific areas of the brain associated with alertness, cognition, and decision-making processes. As time passes, personalization may become a reality, allowing individuals to receive precisely the amount of stimulation needed to maintain optimal alertness.
Despite its limitations, the technique still releases a controlled dose of stimulants through a timed-release tablet, restricting the medication’s effects to a specific period and location. While personalized dosages and lightweight controllers can facilitate heightened alertness without accompanying nervousness, irritability, or euphoria on an individual basis. By shutting down the medication, the brain is able to fully “unwind” and relax during a restful night’s sleep.
A Three-12 months Plan
The AWARE program is expected to conclude within a three-year timeframe. DARPA is soliciting proposals that align with the system’s dual goals: developing a light-activated dextroamphetamine, codenamed PhotoDex, which can be rapidly toggled on and off in response to near-infrared illumination. Before moving forward with human studies, all potential medications are initially tested and validated in animal models.
The envisioned headset setup aims to emit precise infrared light, accurately targeting specific brain regions with millimeter-level resolution, comparable to MRI-based brain scans. Within a few years, the company tasked with designing wearable headsets for virtual reality experiences did not provide specific guidelines on the design requirements – leaving room for creativity in terms of connectivity options (wired or wireless), power source, and activation mechanisms for the LED light beams that enhance the immersive experience.
“The prospect is compelling, yet recent breakthroughs in phototherapy development and lighting technology offer solid grounds for optimism about future possibilities,” Dr. David Lawrence at the University of North Carolina, whose apathy towards the institution’s mission is palpable.
While photoswitchable medications have shown promise in research settings, they have not yet received regulatory approval for human use. If the AWARE program proceeds as planned, it could potentially unlock a novel pathway for targeted drug therapy, benefiting not only individuals struggling with sleep disorders but also those grappling with various neurological conditions. The mission is acutely aware of the moral, ethical, and societal connotations, and has formulated a plan to engage in a thoughtful discussion regarding the technology’s utilization.
