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THE GROWING MENTAL ILLNESS PANDEMIC, PARTICULARLY AMONG ADOLESCENTS, IS A MASSIVE CHALLENGE FOR THE NEXT GENERATION OF HEALTHCARE PROVIDERS. IN ADDITION, AN AGING POPULATION NEEDS MORE WAYS TO SLOW AGE-RELATED COGNITIVE DECLINE. WE ARE REACHING A CRITICAL MASS OF EMERGING NEUROSCIENCE RESEARCH THAT WILL BOOST OUR KNOWLEDGE OF THE HUMAN BRAIN AND GENERATE EXCITING AND INNOVATIVE THERAPIES AT A FAST CLIP. WILL IT BE ENOUGH?

Solutions: Time Honored + Cutting Edge

OUT WITH CONVENTIONAL PSYCHOTROPICS, IN WITH PSYCHEDELICS

SSRIs like Prozac and Zoloft work for only about half the people who take them and have side effects that include an increased risk of suicidality in some patients. Other antidepressants also fail in too many patients. These therapeutics do work for some people, but we have been relying on and overprescribing them for decades while few alternatives were being developed.

But now, shelved or illegal—and in some cases, ancient—treatments are emerging and will likely provide relief for millions. These are psychoactive compounds derived from plants, including psilocybin (“magic mushrooms”), peyote, cannabis and mescaline as well as synthetic drugs like LSD, ketamine and MDMA.

Psychedelic molecules combined with behavioral therapy are showing efficacy as treatments for depression and other mental illnesses. Clinical trials remain mostly small but are quickly expanding as medicine reevaluates substances that were mostly banned during the “war on drugs” from the 1970s to the 1990s. By 2030, these drugs are likely to be fully legalized in many states for medical use—likely starting with the states that first legalized medical cannabis—and will be used alongside traditional psychotropics.

Psychedelic-assisted psychotherapy uses talk therapy along with psychedelics to treat patients, and encourages the use and interpretation of hallucinogenic effects. More traditional therapists administer the drugs looking for the physiological healing effects while considering the “journeys,” or “trips,” to be an undesirable side effect. Both approaches are likely to proliferate in the coming years. Venture money is piling in: Compass Pathways and other startups are attempting to patent everything from modified psychedelic molecules to hand-holding during therapy sessions.

Psychedelics are a gamechanger for treating mental illness and for people with simple anxiety, and will likely become as mainstream, or more so, than traditional psychotropics in coming years.

Phil Wolfson, MD

Psychiatrist and author of The Ketamine Papers

NONCHEMICAL DIGITAL SOLUTIONS (“EXPERIENTIAL MEDICINE”)

In 2020, for the first time ever, the FDA approved a video game to treat a mental health condition—in this case, ADHD in children. Invented in the lab of neurologist Adam Gazzaley at UCSF and developed by Akili, the game EndeavorRx is prescribed by physicians and played on an iPad, with results that match the effectiveness of Ritalin and other traditional chemical treatments, with none of the side effects. Digital prescriptions will proliferate for other conditions including PTSD and phobias as numerous companies work to develop new products, and Gazzaley and other researchers develop full-immersion games that use body sensors and technology to create virtual reality experiences—part of a new neuropsychiatric field that Gazzaley calls “experiential medicine.”

LEARNING TO BE CALMER: MINDFULNESS

Even before Covid-19, millions of people were turning to meditation apps, yoga classes and lessons in intentional breathing to battle stress and anxiety. Thousands of companies now offer health coaching, massages and self-assessment questionnaires. (For more on mindfulness see the Wellness and Nutrition section.)

Hopefully this big experiment in mindfulness will end up being a pandemic silver lining for the future, for business and for our kids.

Camille Preston, PhD

Founder and CEO, Aim Leadership

UNLOCKING THE BRAIN’S SECRETS WITH PRECISION NEUROSCIENCE

Basic neuroscience research is booming, unveiling how the brain is wired and how it functions, with projects like the Brain Atlas, which is setting out to map the approximately 200 billion brain cells in a human by type and function. Surgical techniques to repair damaged brains will get safer and more sophisticated, with an increase in the use of robotic systems for precision surgeries.

Nanobots—devices and machines thousands of times smaller than the width of a human hair—hold great promise in many healthcare applications. Most of the cellular processes in our bodies, after all, happen at nanoscale. For instance, smart pills with nanoscale sensors that wirelessly send out data will be used to diagnose a variety of conditions. MIT researchers are creating drug-carrying nanoparticles that can cross the blood–brain barrier to target cancer cells and destroy them without damaging other tissue.

Precision neuroscience, aided by biodata and artificial intelligence, measures biomarkers that reveal personalized details of brain health and the structural differences in people’s brains (biotypes). This will yield specific therapies targeted to each patient— including Alzheimer’s and neurodegenerative diseases.

We have identified eight distinct ways that brain circuits can get disrupted or stuck, which I call ‘biotypes.‘ We‘re identifying more than just the architecture of the brain, but also insights into how we reflect, how we control our thoughts, how we feel, how we regulate our emotions. We can now quantify those circuits.

—Leanne Williams, PhD

Neuroscientist, Stanford University

DE-AGING THE BRAIN

Alzheimer’s remains irreversible even as patients are expected to double by 2050. Drugs with promise to stem this brain-health crisis are often being approved through the FDA’s Accelerated Approval Program. Several drug candidates, most of which centered on removing protein tangles and plaque in the brain, have proven ineffective.

Recently approved Lequembi, however, has shown promise in slowing the progression of the illness. Rudy Tanzi and his team at Harvard and Massachusetts General are investigating the role of pathogens in neurodegenerative disease and developing ways to combat Alzheimer’s with antibiotics and antivirals.

Protecting delicate young brains from injuries that can later lead to dementia is already a hot issue in football, soccer and other activities where heads are knocked around. This is driving innovation in rules and equipment—and may see the end of youth contact sports like football. Likewise, fun but dangerous playground structures like metal jungle gyms have mostly disappeared.

To prevent Alzheimer’s in my son’s generation, we’re looking at early detection and developing therapies that will one day work like statins for the heart to lower risk, or possibly a vaccine. This is coming.

Rudy Tanzi, PhD

Professor of Neurology, Harvard University; Vice-Chair of Neurology, Massachusetts General Hospital

HARDWARE AND SOFTWARE: SYNTHETIC FIXES TO REPAIR OUR GRAY MATTER

The marriage of hardware and flesh in the brain will build on successes with neural prosthetics that help control seizures and tremors, to the point that patients start to ask for enhancement over baseline. Hearing prosthetics will evolve into one of the bestselling consumer devices ever. Optical implants that restore sight will also improve enough to become consumer-friendly. So will implanted electrodes that can reinvigorate neuronal synapses in the motor cortex in people who are paralyzed, allowing them to use prosthetic limbs and to operate computers and machines by thinking. (For more on prosthetic advances, see the Make Me Bionic section.)

Gene editing and regenerative technologies to repair damaged cells in the brain are in the early stages of FDA-sanctioned human trials. Hundreds of gene therapy products are currently in animal and in human testing, with a handful already approved by the FDA for diseases like macular degeneration. After some early gene therapy mishaps, physicians and regulators will remain cautious, but gene therapies will become more common in the next 15-plus years to treat genetic-based neural and other diseases, including Huntington’s, Alzheimer’s, sickle cell anemia and AIDS.

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