Australian researchers have found that anthocyanin in dietary supplements shows promise for memory enhancement and support of healthy cognitive aging. A paper is published in Nutritional Research. The researchers describe the result of a study that investigated the association between anthocyanin intake and indices of memory and cognition in forty older adults with mild cognitive impairment. Anthocyanins are flavonoids that provide purple, red, and blue pigmentation in fruits and vegetables, such as blueberries, plums, and cherries. Flavonoids are compounds found in plant-based foods, which have been suggested to support healthy aging of the neurological and cardiovascular systems. Flavonoids regulate blood pressure, and are thought to have anti-inflammatory and anti-oxidative action on neurons. For example, previous human studies have shown that dietary supplements containing Blueberry anthocyanin may support brain health. And supplements containing Bacopa Monnieri flavonoids may enhance memory. The objective of this study was to comprehensively investigate the effects of anthocyanin intake on memory and cognition in older adults with mild cognitive impairment. In particular, the researchers wanted to explore whether cognitive performance differed between consumers of higher and lower anthocyanin doses. Forty participants, 21 men and 19 women, were recruited to take part in an 8-week randomized controlled trial (Australian New Zealand Clinical Trials Registry ACTRN12618001184268 ). All participants were aged 50 or more, with a clinical diagnosis of possible or probable mild cognitive impairment. The primary aim of the trial was to determine whether a cognitive training intervention and anthocyanin supplements would prevent further cognitive decline or improve cognitive performance. The participants consumed different foods containing different amounts of anthocyanin. And they were split into two groups according to their average daily anthocyanin intake. The participants consuming less than 10mg per day were categorized as lower intake consumers. And those consuming more than 10mg per day were categorized as higher intake consumers. The cognitive performance of all participants was evaluated with tests like the Rey Auditory Verbal Learning Test. This is a widely used and well-validated cognitive test. It consists of five consecutive trials in which participants recall a list of 15 words that have been read aloud to them. The results of the study indicate that higher intake anthocyanin consumers demonstrated better memory retention. For example, they recalled between 2 and 3 words more than lower intake anthocyanin consumers after a short delay. Higher anthocyanin intakes were also associated with a slower rate of forgetting, with higher intake consumers forgetting around 2 words less on average after a long delay. Therefore, the hypothesis that higher consumption of anthocyanins is associated with better cognitive performance is confirmed by the study. Thrivous develops Vitality Geroprotector to promote healthy cellular and metabolic function for better aging. Each serving provides a clinical dose of Blueberry anthocyanin, as well as complementary nutrients. As demonstrated by this study, Vitality may also enhance memory retention, decrease forgetfulness, and support healthy brain function for better aging. Get your Vitality today!

Cognition: Learn. Experience. Sense. Think. Store. Recall. Use. Act. Life revolves around acquiring information, turning information into workable knowledge, making decisions, and then acting. Information comes through mental exertion, memories, and sensory input. Our ability to learn, think, and act comes naturally. For the most part, we do not even think about the processes we go through every day. We work, drive, cook meals, play with the dog, etc. And we instinctively know where we are and our next step. I grew up playing ball. In my youth, I had an uncanny ability to read a court. Instinctively I knew how fast I was going, how quick I could turn, where the other players were, where the ball was, and where the holes in the defense were. Middle age has crept up on me. Recently, I shut the door with a flick of my left hand. A move I’ve repeated so many times, I do it without conscious thought. But this time, I shut the door on the fingers of my left hand. I shut it so hard, I ended up losing two fingernails. After I stopped jumping and hollering in pain, my thought was how could I not know in space and time where the door frame was in comparison to the timing of my hand? The only explanation that seemed reasonable was that my brain took a mini vacation. Supporting Cognition The thought of living life with reduced cognitive abilities sounds daunting. After a lifetime of working to embrace the golden years, cognitive decline can cost a great deal more than a couple of fingernails. It robs the potential to learn, experience, create, enjoy, and live life to the fullest. The best way to support cognition for healthy aging is by recognizing and embracing the fact that what you do today influences the rest of your tomorrows. Longitudinal research studies indicate cognitive decline starts much earlier than observable symptoms. Cognitive decline may begin even before we reach middle age (40-65 years). It is never too early to make healthy lifestyle choices. In fact, one research study found that “higher intake of B vitamins throughout young adulthood was associated with better cognitive function in middle life.” No matter what your age, making healthy lifestyle choices today supports active cognitive aging. A nutritional diet, appropriate sleep, exercise, and the right dietary supplements act cumulatively to reduce neurotoxins and systemic inflammation. Neurotoxins poison brain cells, neurons, and nerves. Systemic inflammation is associated with a host of health-related issues, including neurodegenerative disorders. Thrivous Clarity and Alpha Stack Doing regular chores around the house keeps the home environment pleasant and in working order. What happens if you neglect the dishes for a week? For one thing, dried gunk is harder to remove, and it takes longer to clean them. The same thing happens inside our body when toxins and inflammation build up. Thrivous Clarity and Alpha Stack is loaded with scientifically backed antioxidants and anti-inflammatories to support healthy cognitive aging. It combats neurotoxins and systemic inflammation on a biochemical level. Along with cognition and healthy cognitive aging, Thrivous Clarity helps boost mood, improve sleep quality, and reduce fatigue. Thrivous Alpha has additional ingredients that further boost cognition and healthy cognitive aging. These scientifically-backed ingredients in Clarity and Alpha Stack support: Current Cognition: Bacopa Monnieri, L Theanine, Rhodiola Rosea, B Vitamins, Alpha GPC, R Alpha Lipoic Acid, Phosphatidylserine, and Ginkgo Biloba Sleep Quality: L Theanine Fighting Fatigue: Rhodiola Rosea, B Vitamins, and Acetyl L Carnitine Mood: L Theanine, Rhodiola Rosea, and Zinc Picolinate Metabolism: B Vitamins and Acetyl L Carnitine Healthy Cognitive Aging (including protecting brain cells and neuromodulators): Acetyl L Carnitine, Alpha GPC, R Alpha Lipoic Acid, and Phosphatidylserine For individuals experiencing or concerned about cognitive issues associated with agin ...

Nanotechnology engineers at UC San Diego have developed microscopic robots, called "microrobots." They can swim around in the lungs, deliver medication, and be used to clear up life-threatening cases of bacterial pneumonia. "Our goal is to do targeted drug delivery into more challenging parts of the body, like the lungs. And we want to do it in a way that is safe, easy, biocompatible and long lasting," says research co-leader Liangfang Zhang in a press release issued by UC San Diego. "That is what we've demonstrated in this work." The engineers had previously developed drug-delivering microrobots that can be safely used in live animals to treat bacterial infections in the stomach and blood. Treating bacterial lung infections is the latest in their line of work. "With an IV injection, sometimes only a very small fraction of antibiotics will get into the lungs. That's why many current antibiotic treatments for pneumonia don't work as well as needed, leading to very high mortality rates in the sickest patients," adds co-author Victor Nizet. "Based on these mouse data, we see that the microrobots could potentially improve antibiotic penetration to kill bacterial pathogens and save more patients' lives." A paper is published in Nature Materials. Engineers report that the microrobots safely eliminated pneumonia-causing bacteria in the lungs of laboratory mice, and resulted in 100% survival. All mice treated with the microrobots survived past 30 days, while untreated mice died within three days. The paper explains that the microrobots are made of algae cells, whose surfaces are speckled with antibiotic-filled nanoparticles. The microrobots leverage the native movement system of the algae cells to swim around and deliver antibiotics directly to the bacteria in the lungs. The nanoparticles containing the antibiotics also contain biomaterials that absorb and neutralize inflammatory molecules produced by the bacteria and the body's immune system. This gives the microrobots the ability to reduce harmful inflammation, which makes them more effective at fighting lung infection. "These results show how targeted drug delivery combined with active movement from the microalgae improves therapeutic efficacy," summarizes research co-leader Joseph Wang. After treatment, the body's immune cells efficiently digest the algae, along with any remaining nanoparticles. Nothing toxic is left behind. The engineers are persuaded that these findings highlight the attractive functions of algae-nanoparticle hybrid microrobots for the delivery of therapeutics to the lungs in intensive care unit settings. The research work will continue with more studies to validate the microrobot treatment, scaling up before testing in larger animals, and eventually in humans. "We're pushing the boundary further in the field of targeted drug delivery," concludes Zhang. This shows that nanoparticle-based medicine is promising and could have a real clinical impact in, say, a decade or two. And it’s worth bearing in mind that the longer-term medical potential of advanced nanotechnology, as described in Eric Drexler’s classic book " Engines of Creation," is huge.

Chinese scientists have developed a new technique for programmable chromosome fusion. And they've used the new technique in the laboratory to produce mice with genetic changes that occur on a million-year evolutionary scale. “One of the goals in synthetic biology is to generate complex multicellular life with designed DNA sequences,” write the scientists in a paper published in Science. “Being able to manipulate DNA at large scales, including at the chromosome level, is an important step toward this goal.” Before this work, chromosome-level genetic engineering had been accomplished only in yeast. But now the scientists applied gene editing to embryonic stem cells and produced laboratory mice with 19 pairs of chromosomes, one pair fewer than is standard in this species. A press release issued by the Chinese Academy of Sciences emphasizes that the findings indicate that chromosome level engineering can be achieved in mammals. And they provide critical insight into how chromosomal rearrangements may influence evolution. “Some engineering mice showed abnormal behavior and postnatal overgrowth, whereas others exhibited decreased fecundity, suggesting that although the change of genetic information was limited, fusion of animal chromosomes could have profound effects,” says LI Zhikun, co-first author of the paper, in the press release. Li adds that the findings show that chromosomal rearrangement “is the driving force behind species evolution and important for reproductive isolation, providing a potential route for large-scale engineering of DNA in mammals.” Using CRISPR, the scientists swapped two genetic chunks of different chromosomes. Two chunks of different chromosomes were artificially fused together, explains SingularityHub, “in a daring experiment that asked: rather than tweaking individual DNA letters or multiple genes, can we retune an existing genomic playbook wholesale, shuffling massive blocks of genetic material around at the same time?” The explainer notes that gene editing is like copy editing, “changing a typo here and there, or fixing multiple grammatical errors with carefully-placed tweaks.” But chromosome-level genetic engineering “is like rearranging multiple paragraphs or shifting complete sections of an article and simultaneously hoping the changes add capabilities that can be passed onto the next generation.” “This means that, for the first time in the world, we have achieved complete chromosomal rearrangement in mammals, making a new breakthrough in synthetic biology,” said Li as reported by South China Morning Post. “This research is a breakthrough in bioengineering technology, helping to understand the impact of large-scale remodelling of mammalian chromosomes, and to gain a deeper understanding of the molecular mechanisms behind growth and development, reproductive evolution, and even the creation of a species.” The scientists are persuaded that this new technology could also help find cures to conditions like infertility and diseases like cancer, “because it lets scientists observe and control the complex activities of chromosomes in mammalian cells.” It seems clear that new discoveries and techniques in DNA engineering are piling up with an accelerating pace. And their impact is likely to be very deep.

Immusoft, a biotechnology company based in Seattle, has announced that the US Food and Drug Administration (FDA) “has agreed to let it move forward with the first study in humans of a new type of gene therapy, using genetically engineered B cells.” The are immune system cells that make antibodies, MIT Technology Review reports. Immusoft plans to harness B cells to treat a rare inherited disease called MPS I. “I feel 100% confident in stating we are the first to get the green light to enter clinical trials,” said Sean Ainsworth, CEO of Immusoft, as reported by MIT Technology Review. A press release issued by Immusoft explains that MPS I is a rare genetic disease that affects the body’s ability to produce an essential enzyme. It results in progressive damage to tissues and organs. Children with MPS I require frequent infusions, which impacts quality of life and is expensive. The disease affects the body’s ability to break down long-chain sugars inside cells. When the sugar chains cannot be broken down and disposed of, they accumulate in the cells and cause progressive damage. This accumulation can happen in the tissues, including the brain. Children affected by the most severe form of the disease rarely live longer than ten years after diagnosis. Severe MPS I occurs in about 1 in 100,000 births. And symptoms appear within a child’s first year of life. In what is referred to as attenuated MPS I, symptoms appear later in childhood. It occurs in about 1 in 500,000 births. Patients with the illness are currently treated with weekly infusions of the missing enzyme. But it’s not enough to cure the disease outright. Immusoft says it can engineer B cells to produce the enzyme instead. “There is a clear need for additional therapies for MPS I, as current interventions are not curative and significant disease related morbidity still exists,” said Paul Orchard, a professor at University of Minnesota who will be the principal investigator on the study. Immusoft’s ISP-001 ( Immune System Programming 001) will be the first engineered B cell therapy to enter into human clinical trials. The ISP technology permits engineering B cells to create biofactories for in vivo therapeutic protein delivery. The concept is to engineer B cells so that they manufacture other proteins instead of antibodies. In other words, ISP modifies a patient’s B cells and instructs the cells to produce gene-encoded medicines. The B cells that are reprogrammed using ISP become miniature drug factories that are expected to persist for many years. “The ISP platform is a first-in-class technology and a pioneering new approach to treat human disease,” said Robert Sikorski, Chief Medical Officer of Immusoft. “It has been rewarding to collaborate with patients, the FDA, investigators, and the Immusoft organization to achieve this important milestone and to launch the first-in-human clinical study.” In the Immusoft press release, Ainsworth refers to the FDA green light as “a historic moment in the field of cell and gene therapies.”

Brazilian researchers have studied the effect of Panax Ginseng on muscle force and muscle excitation during an eccentric-based exercise. They also studied the effect on subsequent muscle damage and delayed-onset muscle soreness. Eccentric-based exercise is defined as exercise that includes repeated muscle contractions under load. More and more athletes use dietary supplements derived from herbs such as Panax Ginseng to reduce exercise-induced muscle damage. It has been reported, for example, that Panax Ginseng supplementation for a week decreases markers of muscle damage after uphill running. Panax Ginseng is considered a legal sport supplement, as it is not listed as a prohibited substance by the World Anti-Doping Agency. The study was motivated by the lack of detailed information about the use of Panax Ginseng to attenuate the effects of a resistance exercise with eccentric emphasis. Resistance training with eccentric emphasis is largely used to enhance muscle force and prevent injuries in athletes. An excessive eccentric workload, however, may have a negative consequence on exercise performance. Based on previous preliminary results, the researchers hypothesized that Panax Ginseng would increase muscle excitation and attenuate perceived effort during the eccentric-based exercise. That, in turn, would mitigate the muscle damage, delayed-onset muscle soreness, and force reduction over the recovery period. A paper is published in Journal of Strength and Conditioning Research. The researchers report the methods and results of a study of the effects of Panax Ginseng supplements on young male athletes. The participants in the study, ten young male runners, sprinters, and jumpers, had been training regularly six times per week and had competed at the national level in the year before the study. The main finding of this study was that Panax Ginseng attenuated perceived effort and increased muscle excitation during a dynamic exercise with eccentric emphasis. The study did not confirm that Panax Ginseng reduced markers of muscle damage and delayed-onset muscle soreness after the eccentric-based exercise. But the study did confirm that Panax Ginseng accelerated the recovery of muscle force and increased the associated muscle excitation. The researchers conclude that an 8-day protocol of Panax Ginseng might be used to improve muscle excitation and accelerate recovery of neuromuscular function after an eccentric exercise. The researchers are persuaded that the results of this study are applicable to young athletes who practice sports with a high eccentric component, and to athletes who compete several times on the same day and/or over consecutive days. Panax Ginseng supplementation at doses of 100 mg per kilogram of body mass, administered in 3 doses a day for 8 days, may accelerate muscle recovery and improve muscle force. Thrivous develops Surge Acute Nootropic to enhance energy and focus. Each serving provides a clinical dose of Panax Ginseng, along with complementary nutrients. As suggested by this study, Thrivous Surge may enhance muscle force and recovery. Purchase Surge online in the Thrivous store today!

In May, City of Hope and Imugene Limited announced that the first patient was dosed in a phase 1 clinical trial evaluating the safety of a new oncolytic (cancer-killing) virus. It's called CF33-hNIS Vaxinia. And it's used in people with advanced solid tumors. The trial is expected to run for two years. City of Hope is one of the largest cancer research and treatment organizations in the United States. And Imugene Limited is a clinical-stage immuno-oncology company. Oncolytic viruses are designed to both selectively kill cancer cells and activate the immune system against cancer cells. They have the potential to improve clinical response and survival. Oncolytic viruses are based on viruses found in nature. The viruses are genetically modified to infect, replicate in, and kill cancer cells, while sparing healthy cells. Oncolytic virus therapy seems to me to be an elegant and very promising approach to cancer therapy. Once perfected in the lab and validated by clinical trials, it could make a real difference to cancer patients. The oncolytic virus developed by City of Hope has been shown to shrink colon, lung, breast, ovarian, and pancreatic cancer tumors. This has been done in preclinical laboratory and animal models. “Our previous research demonstrated that oncolytic viruses can stimulate the immune system to respond to and kill cancer, as well as stimulate the immune system to be more responsive to other immunotherapies, including checkpoint inhibitors,” said principal investigator Daneng Li. “Now is the time to further enhance the power of immunotherapy, and we believe CF33-hNIS has the potential to improve outcomes for our patients in their battle with cancer.” CF33 is a combination of genomic sequences from multiple vaccinia virus strains to generate a new, safer, and more potent virus. The vaccinia virus spreads rapidly from cell to cell and is highly toxic for many types of cancer cells. When combined with an extra gene called hNIS, CF33 is called Vaxinia. hNIS enables imaging to track the virus in vivo and mediate targeted radiotherapy. CF33 with hNIS, along with other genes that enable enhancement of anti-cancer immunotherapy, is called CHECKVacc. “Interestingly, the same characteristics that eventually make cancer cells resistant to chemotherapy or radiation treatment actually enhance the success of oncolytic viruses, such as CF33-hNIS,” said Yuman Fong. Fong played a key role in developing the genetically modified virus. He continued, “We are hoping to harness the promise of virology and immunotherapy for the treatment of a wide variety of deadly cancers.” Last month, Imugene announced that City of Hope had dosed the first patient in cohort 3 in the phase I clinical trial of the CHECKvacc variant. The trial is recruiting patients with triple negative metastatic breast cancer that has spread to other places in the body. “We are pleased with the continued progress being made in this trial,” said Imugene CEO Leslie Chong. CHECKvacc has the potential to improve clinical response and survival in this indication where there are currently no meaningful treatments, and we are eager to deliver on that.”

Do current worries and concerns have you wound up? Are they affecting your concentration or sleep patterns? In my family, such things have wreaked havoc for weeks, causing meltdowns and feelings of being trapped. If you are restless, irritable, easily fatigued, have unexplained stomach pain or headaches, or cannot stem the flow of fearful thoughts, you are not alone. The pandemic, global contentions, supply chain issues, political strife, natural disasters, and other tensions have generated new levels of stress. Are you seeking natural ways to quiet the mind? To enhance feeling calm? And to focus your mind and efforts? Adding Thrivous Clarity and Serenity Stack to your daily routine incorporates scientifically-proven biochemical components to help improve mood, support cognition, fight fatigue, and enhance sleep quality. Clarity and Serenity Stack is designed to enhance mood and well-being along with supporting healthy aging. Breaking Down the Stack The ingredients contained in Thrivous Clarity and Thrivous Serenity have been subject to numerous clinical trials. Clinical trials use established scientific methods, techniques, and controls to generate reliable data. This includes selecting random participants, blind placebo controls, laboratory testing, and established evaluation measures. Not surprisingly, some ingredients contained in Clarity and Serenity have been clinically shown to support the system in more than one way. Thrivous provides links to associated clinical research data on its website for both Clarity and Serenity for public perusal. Here is a tabulated breakdown of the benefits of the ingredients contained in Thrivous Clarity and Serenity Stack. Ingredient Mood Cognition Energy Sleep Healthy Aging * L Theanine is well tolerated in large doses with no observed toxicity. Animal and human trials find improved sleep quality with 250-400 mg of daily L Theanine supplementation. ** Clarity contains 100% or more of the recommended daily value of every B Vitamin. Bacopa Monnieri (Clarity 320 mg) X X L Theanine* (Clarity 200 mg & Serenity 200 mg) X X X Rhodiola Rosea (Clarity 170 mg) X X X B Vitamins (Clarity**) X X Zinc (Clarity 11 mg) X X Ashwagandha (Serenity 300 mg) X X X Magnesium (Serenity 150 mg) X X X Melatonin (Serenity 5 mg) X X X Thrivous formulations use the latest scientific research at clinically-proven effective dosages. Clarity and Serenity Stack provides the best vitamin, mineral, and herbal combination to enhance mood, cognition, and healthy brain aging. Instead of hiding ingredient amounts in blends, Thrivous openly states product formulations for educated consumer consumption. Here at Thrivous, we believe informed consumers can better manage their well-being for healthy and happy living. More in-depth information regarding the formulation of Clarity and Serenity can be found in these articles: Enhance Cognitive Function with Thrivous Clarity Promote Restorative Sleep with Thrivous Serenity Make the Stack Work for You Clarity and Serenity Stack works best when taken in the following manner: Morning Dose: Take 2 Clarity capsules with your first meal of the day. The ingredients in Clarity normally take effect within one hour. Clarity becomes most effective within 2-3 months of daily use. Clarity is designed to be taken daily. Evening Dose: Take 2 Serenity capsules approximately an hour before heading to bed. The ingredients in Serenity normally take effect within 1 hour. Serenity is designed to be used nightly. Performance Days: We all have days when we need to perform at our absolute best. These days include exam days, presentation days, competition days, audition days, etc. On performance days, link the power of Thrivous Clarity with Thrivous Surge for an additional energy and focus boost. Surge is designed to be used occasionally. The Power of the Stack Mental health looms large in my immediate family. Linking cognitive therapy strategies with the regular use of Ashwagandha, L Theanine, Magnes ...

Scientists in China and Singapore have developed a novel artificial neuron. It can both release and receive dopamine. And it opens the door to using chemical signals in brain-machine interfaces (BMIs). “The brain’s native language is chemical, but current brain-machine interfaces all use an electrical language,” says Benhui Hu (Nanjing Medical University), as reported by New Scientist. “So we devised an artificial neuron to duplicate the way a real neuron communicates.” Organic neurons in the brain communicate by exchanging chemicals called " neurotransmitters " along communication channels called "synapses." A paper is published in Nature Electronics. The scientists describe an artificial neuron that can receive and release the neurotransmitter dopamine. The artificial neuron detects dopamine using an electrochemical sensor with a graphene and carbon nanotube electrode. If enough dopamine is detected by the sensor, a memristor triggers the release of more dopamine at the other end through a heat-activated hydrogel. The memristor can change the threshold strength of the input dopamine signal that is required to trigger the release of output dopamine. This is similar to how neurons in the brain change how much neurotransmitter is sent between connections in response to external stimuli. Such plasticity is essential for learning. “To chemically communicate with biological neurons, bioelectronics should at least possess three basic functionalities: neurotransmitter recognition, synaptic plasticity, and firing of action potentials and releasing of neurotransmitters,” note the scientists in the paper. The system responds to dopamine and releases dopamine in a chemical communication loop similar to the chemical communications between organic neurons. Experimenting with rat brain cells in the lab, the scientists have shown that the artificial neuron can trigger the controllable movement of a rat leg and robotic hand. “The scientists connected the chip to a nerve in a mouse’s leg,” explains SingularityHub. “Depending on the level of dopamine, the leg flexed... in another proof of concept, the team hooked up the chip to a robotic hand.” “This actually has quite a lot of potential for expanding into more sophisticated learning systems,” comments Yoeri van de Burgt (Eindhoven University of Technology), as reported by New Scientist. “You can do a lot of new cool things here.” The scientist explains that the current device is too big for applications to BMIs. But it could be used in prosthetic devices. Looking farther ahead, this research program could enable future BMIs to use chemical communications besides electric communications. “Such chemical BMIs could complement electrical BMIs, potentially allowing neuronal information to be correctly and comprehensively interpreted for use in neuroprosthetics, human-machine interactions, and cyborg construction,” say the scientists as reported by SingularityHub. There’s also the possibility that electrical BMIs could be unable to “comprehensively interpret human consciousness.” In this case, BMIs able to use the brain’s native chemical information could boost consciousness studies.

Nootropics are substances that enhance cognition and support healthy brain function. Sometimes people refer to them as "smart drugs" or the "limitless pill." They include various foods, nutraceuticals (supplements), and pharmaceuticals (drugs). Unfortunately none comes close to enabling any fiction-inspired capacities of superintelligence (yet), but some may make a practical difference for many people. I’ve used several nootropics for years. And I’m exploring ways to incorporate others into my diet, if they’re applicable to my personal situation and meet a few general criteria: First, I look for nootropics supported by multiple studies on humans – not just anecdotal evidence, one study, or studies on non-human animals. Although I've nothing against the health benefits of placebo, I prefer knowing that something more than only placebo is at work. Second, I look for nootropics with the highest ratios of efficacy to expense. Given innumerable options and a limited budget, I want to do more than just empty my wallet. Third, I look for nootropics that are legal and generally safe. If it'll put me in a hospital or a prison, it’s not worth it. Based on those criteria, I’ve compiled a list of top tier natural nootropics that actually work. These are, to the best of my knowledge, the most well-researched and effective nootropics available in the United States without a prescription. This information is for educational purposes only. It is not medical advice. Please consult a physician before and during use of these and other nootropics. 1) Ashwagandha Ashwagandha, also known as Withania Somnifera, is a plant in the nightshade family and cultivated in Asia. Supplements may enhance relaxation, according to multiple peer-reviewed, double-blind, placebo-controlled studies: Langade D, Kanchi S, Salve J, Debnath K, Ambegaokar D. Cureus. 2019 Sep 28;11(9):e5797. doi: 10.7759/cureus.5797. PMID: 31728244; PMCID: PMC6827862. Lopresti AL, Smith SJ, Malvi H, Kodgule R. Medicine (Baltimore). 2019 Sep;98(37):e17186. doi: 10.1097/MD.0000000000017186. PMID: 31517876; PMCID: PMC6750292. Salve J, Pate S, Debnath K, Langade D. Cureus. 2019 Dec 25;11(12):e6466. doi: 10.7759/cureus.6466. PMID: 32021735; PMCID: PMC6979308. Chengappa KNR, Brar JS, Gannon JM, Schlicht PJ. J Clin Psychiatry. 2018 Jul 10;79(5):17m11826. doi: 10.4088/JCP.17m11826. PMID: 29995356. Choudhary D, Bhattacharyya S, Joshi K. J Evid Based Complementary Altern Med. 2017 Jan;22(1):96-106. doi: 10.1177/2156587216641830. Epub 2016 Apr 6. PMID: 27055824; PMCID: PMC5871210. Chandrasekhar K, Kapoor J, Anishetty S. Indian J Psychol Med. 2012 Jul;34(3):255-62. doi: 10.4103/0253-7176.106022. PMID: 23439798; PMCID: PMC3573577. Cooley K, Szczurko O, Perri D, Mills EJ, Bernhardt B, Zhou Q, Seely D. PLoS One. 2009 Aug 31;4(8):e6628. doi: 10.1371/journal.pone.0006628. PMID: 19718255; PMCID: PMC2729375. Mahdi AA, Shukla KK, Ahmad MK, Rajender S, Shankhwar SN, Singh V, Dalela D. Evid Based Complement Alternat Med. 2009 Sep 29;2011:576962. doi: 10.1093/ecam/nep138. Epub ahead of print. PMID: 19789214; PMCID: PMC3136684. Andrade C, Aswath A, Chaturvedi SK, Srinivasa M, Raguram R. Indian J Psychiatry. 2000 Jul;42(3):295-301. PMID: 21407960; PMCID: PMC2958355. Ashwagandha supplements may also enhance energy, motivation, social functioning, and subjective well-being. Evidence for these effects may not be as reliable. See the Ashwagandha article at Examine.com for more studies and details. The KSM-66® extract of Ashwagandha is an ingredient in Thrivous Serenity Nightly Nootropic. 2) Bacopa Monnieri Bacopa Monnieri is a perennial creeping herb native to wetlands worldwide. Supplements may enhance memory, according to multiple peer-reviewed, double-blind, placebo-controlled studies: Benson S, Downey LA, Stough C, Wetherell M, Zangara A, Scholey A. Phytother Res. 2014 Apr;28(4):551-9. doi: 10.1002/ptr.5029. Epub 2013 Jun 21. PMID: 23788517. Downey LA, Kean J, Nemeh F, Lau A, Poll A, Gregory R, Murray M, Rour ...