DARPA is looking for a near-infrared light stimulant to keep soldiers alert without side effects

DARPA’s AWARE program aims to harness the positive effects of stimulants on alertness without negatively affecting mood, restful sleep, and mental health.

DARPA is pursuing a rare program to improve the cognitive performance of military personnel, which is otherwise impaired by fatigue and lack of sleep. The BTO (Biological Technologies Office) held a Proposers’ Day conference on June 17, 2024, where it solicited general ideas from the industry and scientific community for what it calls the AWARE (Alert WARfighter Enablement) program.

Announced in late May, AWARE aims to develop “a drug-device combination that increases alertness after sleep deprivation in humans in a noninvasive manner, without negative side effects such as anxiety, irritability or euphoria, and with reduced addictive potential.” AWARE also includes an ELSI (ethical, legal and societal impacts) plan to discuss the application of the technology in humans.

The new stimulant is said to be a “photoswitchable drug (…) that behaves in the same way as regular (i.e. non-photoswitchable) dextroamphetamine” and is delivered to specific areas of the brain via a device that generates NIR (near-infrared) light (…).” The NIR is intended to “reach regions of the prefrontal cortex responsible for executive functions, working memory and decision-making, while avoiding deep brain structures such as the amygdala and striatum, which are associated with mood swings and euphoria, respectively.”

To foster the pool of innovative proposal concepts, DARPA encourages participation from non-traditional players such as small businesses, academic and research institutions, and first-time government contractors. The program timeline spans three years, with Phase 0, Phase 1, and Phase 2 expected to last 15, nine, and 12 months, respectively.

Current medications

DARPA recognizes the current use of prescription drugs such as modafinil and dextroamphetamine to maintain alertness during long-duration training sessions or missions. Studies have shown that dextroamphetamine “provides better performance on alertness tasks following sleep deprivation.”

The drug achieves this by “increasing the concentration of extracellular dopamine in the brain.” However, it has side effects such as increased irritability or euphoria, which creates suitable conditions for addiction. In addition, dextroamphetamine’s long circulation time of 10 to 12 hours can interfere with sleep, while military personnel are encouraged to take naps at convenient times.

Sedatives used to promote sleep cannot counteract the lingering effects of stimulants, allowing restful sleep when needed. Of course, a cumulative loss of restful sleep impacts not only alertness and cognition, but also metabolism, immune system, and mental health.

“Light” stimulant without side effects

AWARE plans to develop a “photoswitchable version of dextroamphetamine” that is activated only by NIR and enables “high spatial and temporal resolution.” The NIR light protects deep brain structures such as the amygdala and striatum, which are responsible for mood swings and euphoria.

AWARE technology uses temporal selectivity, allowing for reversible activation of the drug exactly when it is needed. In addition, the timing of the NIR light pulses can be used to titrate the dose of activated drug over time, which may further reduce the potential for addiction and other adverse effects. Importantly, the temporal selectivity of “switching the drug from an active to an inactive state” is expected to “facilitate on-demand return from wakefulness and enable restful sleep,” the DARPA document states.

A statement from DARPA quotes AWARE program leader Dr. Pedro Irazouqi as saying: “To achieve the positive effects of stimulants on alertness without the undesirable effects on mood, restful sleep and mental health, a new approach is needed,” said Irazouqi. “AWARE aims to modify currently approved prescription drugs to be photoswitchable – that is, to have the ability to change in response to light – and to develop wearable light emitters to rapidly activate them in a localized area.”

Course program

In Phase 0, teams are assigned to either Technical Areas 1 or 2 (TA1 and TA2) after evaluating various proposals. TA1 aims to develop candidate photoswitchable dextroamphetamine molecules (“PhotoDex”) that are “biologically inert under dark conditions” but activated by “850 nm NIR light.” Teams must also submit Animal Subject Research (ASR) protocols.

TA2 involves the development of “wearable transducers emitting 850 nm NIR light” to reach the human prefrontal cortex noninvasively with “millimeter-level resolution,” demonstrated on a “tissue-like phantom made from human scalp, skull and brain tissue.”

Use on the battlefield

Many tactical military operations have shown that human performance and cognitive ability, rather than technological superiority, often determine the outcome. This trend is evident in the ongoing battles in the Black Sea between Ukrainian unmanned kamikaze boats and the Russian Black Sea Fleet (BSF), as well as in the battle between the US Navy and Houthi missiles in the Red Sea.

Although Ukrainian kamikaze USVs (unmanned surface vessels) are destroyed in large numbers, they occasionally score devastating hits. These attacks are successful because they are planned with unpredictable timing and frequency, keeping Russian guard and gun crews on high alert.

A similar situation is occurring in the Red Sea, Western reports show, where aircraft carrier and destroyer crews are overstretched and have to cope with salvos of Houthi anti-ship missiles (ASBMs), cruise missiles and drones. Sometimes these missiles are intercepted by close-in weapons systems (CIWS) such as the Phalanx, suggesting they have breached the outer layers of defense.

Parth Satam’s career spans a decade and a half between two daily newspapers and two defence policy publications. He believes that war, as a human activity, has causes and consequences that go far beyond the question of which missile and which aircraft flies the fastest. As such, he enjoys analysing military affairs at their intersection with foreign policy, economics, technology, society and history. His work spans the entire spectrum from defence aviation, tactics, military doctrine and theory, personnel issues, West Asian and Eurasian affairs to the energy sector and space.