Chapter 4. The Chemistry of Behavior: Neurotransmitters and Neuropharmacology

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Emma Yasinski Some genetic risk factors for alcohol use disorder overlap with those for neurodegenerative diseases like Alzheimer’s, scientists reported in Nature Communications on August 20. The study, which relied on a combination of genetic, transcriptomic, and epigenetic data, also offers insight into the molecular commonalities among these disorders, and their connections to immune disfunction. “By meshing findings from genome wide association studies . . . with gene expression in brain and other tissues, this new study has prioritized genes likely to harbor regulatory variants influencing risk of Alcohol Use Disorder,” writes David Goldman, a neurogenetics researcher at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), in an email to The Scientist. “Several of these genes are also associated with neurodegenerative disorders—an intriguing connection because of alcohol’s ability to prematurely age the brain.” Over the past several years, researchers have published a handful of massive genome-wide association studies (GWAS) studies identifying loci—regions of the genome that can contain 10 or more individual genes—that likely influence a person’s risk of developing an alcohol use disorder (AUD). In a study published two years ago, Manav Kapoor, a neuroscientist and geneticist at the Icahn School of Medicine at Mount Sinai and first author on the new paper, and his team found evidence that the immune system might be overactive in people with AUD, but the finding left him with more questions. The first was whether excessive drinking directly causes immune dysfunction, or if instead some people’s genetic makeup puts them at risk for both simultaneously. The second was which of the dozen or so genes at each previous GWAS-identified locus actually influences drinking behaviors. Lastly, he wanted to know if there is a genetic difference between people who consume higher numbers of alcoholic beverages per week but are not diagnosed with AUD and those who have received the diagnosis. © 1986–2021 The Scientist.

Keyword: Alzheimers; Genes & Behavior
Link ID: 27995 - Posted: 09.18.2021

David Kleinfeld My colleagues and I recently found that we were able to train mice to voluntarily increase the size and frequency of seemingly random dopamine impulses in their brains. Conventional wisdom in neuroscience has held that dopamine levels change solely in response to cues from the world outside of the brain. Our new research shows that increases in dopamine can also be driven by internally mediated changes within the brain. Dopamine is a small molecule found in the brains of mammals and is associated with feelings of reward and happiness. In 2014, my colleagues and I invented a new method to measure dopamine in real time in different parts of the brains of mice. Using this new tool, my former thesis student, Conrad Foo, found that neurons in the brains of mice release large bursts of dopamine – called impulses – for no easily apparent reason. This occurs at random times, but on average about once a minute. Pavlov was famously able to train his dogs to salivate at the sound of a bell, not the sight of food. Today, scientists believe that the bell sound caused a release of dopamine to predict the forthcoming reward. If Pavlov’s dogs could control their cue-based dopamine responses with a little training, we wondered if our mice could control their spontaneous dopamine impulses. To test this, our team designed an experiment that rewarded mice if they increased the strength of their spontaneous dopamine impulses. The mice were able to not only increase how strong these dopamine releases were, but also how often they occurred. When we removed the possibility of a reward, the dopamine impulses returned to their original levels. In the 1990s, neuroscientist Wolfram Schultz discovered that an animal’s brain will release dopamine if the animal expects a reward, not just when receiving a reward. This showed that dopamine can be produced in response to the expectation of a reward, not just the reward itself – the aforementioned modern version of Pavlov’s dog. © 2010–2021, The Conversation US, Inc.

Keyword: Drug Abuse; Learning & Memory
Link ID: 27993 - Posted: 09.15.2021

By Husseini Manji, Joseph Hayes Depression affects more than 264 million people of all ages globally. The World Health Organization ranks depression as one of the most debilitating diseases to society. It is the leading cause of disability worldwide and the psychiatric diagnosis most commonly associated with suicide, which accounts for nearly 800,000 deaths globally each year. Individuals suffering from depression may face an inability to manage life’s demands and maintain social connections, affecting all aspects of their experiences, from school and employment to relationships and overall quality of life. When it comes to treatment, approximately one third of those suffering from depression do not respond to two or more antidepressants and are considered treatment-resistant. Treatment-resistant depression is a chronic condition that places an increased emotional, functional and economic burden on the individual, their loved ones and society. It is also associated with greater morbidity, higher health care costs and various comorbid conditions. While a number of antidepressants exist, they all work through changing the levels of brain-signaling molecules called monoaminergic neurotransmitters. New drug development for depression had stalled for a number of years, and many pharmaceutical companies have withdrawn from neuroscience entirely. But recent scientific advances have led to the development of novel antidepressants working via completely different mechanisms. The brain is the most advanced, adaptive information processing system in existence—in large part because of its tremendous plasticity. Scientists have been building upon these neuroscience advances to develop completely novel, rapid-acting antidepressants. In this regard, considerable evidence has demonstrated that the regulation of two receptors—AMPA and NMDA—on many neurons that respond to the neurotransmitter glutamate control changes in the tiny junctions, or synapses, between neurons. © 2021 Scientific American

Keyword: Depression
Link ID: 27991 - Posted: 09.15.2021

By Nora D. Volkow The provisional drug overdose death statistics for 2020 confirmed the addiction field’s worst fears. More people died of overdoses in the United States last year than in any other one-year period in our history. More than 93,000 people died. The increase from the previous year was also more than we’ve ever seen—up 30 percent. These data are telling us that something is wrong. In fact, they are shouting for change. It is no longer a question of “doing more” to combat our nation’s drug problems. What we as a society are doing—putting people with drug addiction behind bars, underinvesting in prevention and compassionate medical care—is not working. Even as we work to create better scientific solutions to this crisis, it is beyond frustrating—it is tragic—to see the effective prevention and treatment tools we already have just not being used. The benefits of providing effective substance use disorder treatments—especially medication for opioid use disorder—are well-known. Yet decades of prejudice against treating substance use disorders with medication has greatly limited their reach, partly accounting for why only 18 percent of people with opioid use disorder receive medications. Historical reluctance to provide these treatments and of insurers to cover them reflects the stigma that has long made people with addiction a low priority. We must eliminate the attitudes and infrastructure barring treating people with substance use disorders. This means making it easier for clinicians to provide life-saving medications, expanding models of care like digital health technologies and mobile clinics that can reach people where they are, and ensuring that payers cover treatments that work. © 2021 Scientific American

Keyword: Drug Abuse
Link ID: 27970 - Posted: 09.01.2021

Emma Yasinski Some genetic risk factors for alcohol use disorder overlap with those for neurodegenerative diseases like Alzheimer’s, scientists reported in Nature Communications on August 20. The study, which relied on a combination of genetic, transcriptomic, and epigenetic data, also offers insight into the molecular commonalities among these disorders, and their connections to immune disfunction. “By meshing findings from genome wide association studies . . . with gene expression in brain and other tissues, this new study has prioritized genes likely to harbor regulatory variants influencing risk of Alcohol Use Disorder,” writes David Goldman, a neurogenetics researcher at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), in an email to The Scientist. “Several of these genes are also associated with neurodegenerative disorders—an intriguing connection because of alcohol’s ability to prematurely age the brain.” Over the past several years, researchers have published a handful of massive genome-wide association studies (GWAS) studies identifying loci—regions of the genome that can contain 10 or more individual genes—that likely influence a person’s risk of developing an alcohol use disorder (AUD). In a study published two years ago, Manav Kapoor, a neuroscientist and geneticist at the Icahn School of Medicine at Mount Sinai and first author on the new paper, and his team found evidence that the immune system might be overactive in people with AUD, but the finding left him with more questions. The first was whether excessive drinking directly causes immune dysfunction, or if instead some people’s genetic makeup puts them at risk for both simultaneously. © 1986–2021 The Scientist.

Keyword: Alzheimers; Genes & Behavior
Link ID: 27966 - Posted: 08.28.2021

Terry Gross Human beings are programmed to approach pleasure and avoid pain. It's an instinct that dates back millions of years, to a time when people needed to actively seek food, clothing and shelter every day, or risk death. But psychiatrist Anna Lembke says that in today's world, such basic needs are often readily available — which changes the equation. "Living in this modern age is very challenging. ... We're now having to cope with: How do I live in a world in which everything is provided?" Lembke says. "And if I consume too much of it — which my reflexes compel me to do — I'm going to be even more unhappy." Lembke is the medical director of addiction medicine at Stanford University and chief of the Stanford Addiction Medicine Dual Diagnosis Clinic. Her new book, Dopamine Nation, explores the interconnection of pleasure and pain in the brain and helps explain addictive behaviors — not just to drugs and alcohol, but also to food, sex and smart phones. Lembke says that her patients who are struggling with substance abuse often believe their addictions are fueled by depression, anxiety and insomnia. But she maintains that the reverse is often true: Addictions can become the cause of pain — not the relief from it. That's because the behavior triggers, among other things, an initial response of the neurotransmitter dopamine, which floods the brain with pleasure. But once the dopamine wears off, a person is often left feeling worse than before. "They start out using the drug in order to feel good or in order to experience less pain," Lembke says. "Over time, with repeated exposure, that drug works less and less well. But they find themselves unable to stop, because when they're not using, then they're in a state of a dopamine deficit." © 2021 npr

Keyword: Drug Abuse; Learning & Memory
Link ID: 27964 - Posted: 08.28.2021

By Virginia Hughes In the 1960s, the drug was given to women during childbirth to dampen their consciousness. In the 1990s, an illicit version made headlines as a “date rape” drug, linked to dozens of deaths and sexual assaults. And for the last two decades, a pharmaceutical-grade slurry of gamma-hydroxybutyrate, or GHB, has been tightly regulated as a treatment for narcolepsy, a disorder known for its sudden sleep attacks. Now, the Food and Drug Administration has approved the drug for a new use: treating “idiopathic hypersomnia,” a mysterious condition in which people sleep nine or more hours a day, yet never feel rested. Branded as Xywav, the medication is thought to work by giving some patients restorative sleep at night, allowing their brains to be more alert when they wake up. It is the first approved treatment for the illness. But some experts say the publicly available evidence to support the new approval is weak. And they worry about the dangers of the medication, which acts so swiftly that its label advises users to take it while in bed. Xywav and an older, high-salt version called Xyrem have a host of serious side effects, including breathing problems, anxiety, depression, sleepwalking, hallucinations and suicidal thoughts. GHB “has serious safety concerns, both in terms of its abuse liability and its addictive potential,” said Dr. Lewis S. Nelson, the director of medical toxicology at Rutgers New Jersey Medical School. An estimated 40,000 people in the United States have been diagnosed with idiopathic hypersomnia, but Dr. Nelson said that many more people with daytime drowsiness might wind up with this diagnosis now that it has an F.D.A.-approved treatment. The disorder’s hallmark symptoms — sleep cravings, long naps and brain fog — overlap with many other conditions. The more people who take the drug, the more opportunity for abuse. “The potential for the scope of use to expand is very real,” Dr. Nelson said. “So that is concerning to me.” © 2021 The New York Times Company

Keyword: Sleep; Drug Abuse
Link ID: 27947 - Posted: 08.14.2021

Christie Wilcox One of the most well-studied synapses in the brain continues to surprise neuroscientists. According to a May 18 study in Nature Communications, mossy fiber synapses, so named because their terminals look a bit like moss growing on the axons, have an unexpected way of regulating the flow of information in the hippocampus: the postsynaptic cells that receive neurotransmitter signals can release their own glutamate to tamp down the transmission from the cell on the presynaptic side. This so-called retrograde signaling was totally unexpected and depends on calcium influx to the postsynaptic cell, meaning researchers might have to rethink the results of past experiments that used in vitro conditions with different calcium availability. The findings are “a big deal” for neuroscientists, says Chris McBain, a synaptic physiologist at the National Institutes of Health who was not involved in the study. “Retrograde glutamatergic signaling is a really rare occurrence in the central nervous system,” he notes, and to find it in mossy fibers “adds another layer of complexity onto one of the most complex synapses.” The researchers behind the new paper, led by neurophysiologist Peter Jonas of the Institute of Science and Technology Austria, were investigating the plasticity of hippocampal neurons, the dynamic changes in connections between cells that contribute to the functioning of neural circuits and that ultimately underlie learning, memory, and other cognitive abilities. János Szabadics, a neurophysiologist at the Institute of Experimental Medicine, Budapest, puts it quite simply: “Without synaptic plasticity, the brain would be just a bag of wires,” he says. © 1986–2021 The Scientist.

Keyword: Learning & Memory
Link ID: 27923 - Posted: 07.24.2021

By Michael Pollan After a half century spent waging war on drugs, Americans seem ready to sue for peace. The 2020 elections brought plenty of proof that voters have leapt ahead of politicians in recognizing both the failures of the drug war and the potential of certain illicit drugs as powerful tools for healing. Ballot initiatives in five states — four of them traditionally red — legalized some form of cannabis use. By substantial margins, Oregon passed two landmark drug reform initiatives: Fifty-nine percent of voters supported Measure 110, which decriminalized the possession of small quantities of all drugs, even hard ones like heroin and cocaine. A second proposal, Measure 109, specifically legalized psilocybin therapy, directing the state’s health department to license growers of so-called magic mushrooms and train facilitators to administer them beginning in 2023. In the past two years, a new drug policy reform movement called Decriminalize Nature has persuaded local governments in a half dozen municipalities, including Washington, D.C., to decriminalize “plant medicines” such as psilocybin, ayahuasca, iboga and the cactuses that produce mescaline. Last month, the California State Senate passed a bill that would make legal the personal possession, use and “social sharing” of psychedelics, including LSD and MDMA, a.k.a. Ecstasy or Molly. Political opposition to all these measures has been notably thin. Neither party, it seems, has the stomach for persisting in a war that has achieved so little while doing so much damage, especially to communities of color and our civil liberties. But while we can now begin to glimpse an end to the drug war, it is much harder to envision what the drug peace will look like. How will we fold these powerful substances into our society and our lives so as to minimize their risks and use them most constructively? The blunt binaries of “Just say no” that have held sway for so long have kept us from having this conversation and from appreciating how different one illicit drug is from another. © 2021 The New York Times Company

Keyword: Drug Abuse; Depression
Link ID: 27907 - Posted: 07.14.2021

By Sheila Kaplan Sales have plunged by $500 million. The work force has been cut by three-quarters. Operations in 14 countries have been abandoned. Many state and local lobbying campaigns have been shut down. Juul Labs, the once high-flying e-cigarette company that became a public health villain to many people over its role in the teenage vaping surge, has been operating as a shadow of its former self, spending the pandemic largely out of the public eye in what it calls “reset” mode. Now its very survival is at stake as it mounts an all-out campaign to persuade the Food and Drug Administration to allow it to continue to sell its products in the United States. The agency is trying to meet a Sept. 9 deadline to decide whether Juul’s devices and nicotine pods have enough public health benefit as a safer alternative for smokers to stay on the market, despite their popularity with young people who never smoked but became addicted to nicotine after using Juul products. Major health organizations, including the American Heart Association, American Lung Association, American Academy of Pediatrics and the American Cancer Society’s Cancer Action Network, have asked the agency to reject Juul’s application. “The stakes are high,” said Eric Lindblom, a senior scholar at the O’Neill Institute for National and Global Health Law at Georgetown University, and a former F.D.A. adviser on tobacco. “If the F.D.A. blows it on this one, they will face public health lawsuits.” Juul is sparing no expense to push back. Last week, the company agreed to pay $40 million to settle just one lawsuit (with North Carolina) out of thousands lodged against it, avoiding a looming jury trial. The company had urgently sought the deal to avoid courtroom testimony from parents and teenagers while the F.D.A. is reviewing its vaping products. © 2021 The New York Times Company

Keyword: Drug Abuse
Link ID: 27889 - Posted: 07.06.2021

By Anil Ananthaswamy “Everything became imbued with a sense of vitality and life and vividness. If I picked up a pebble from the beach, it would move. It would glisten and gleam and sparkle and be absolutely captivating,” says neuroscientist Anil Seth. “Somebody looking at me would see me staring at a stone for hours.” Or what seemed like hours to Seth. A researcher at the UK’s University of Sussex, he studies how the brain helps us perceive the world within and without, and is intrigued by what psychedelics such as LSD can tell us about how the brain creates these perceptions. So a few years ago, he decided to try some, in controlled doses and with trusted people by his side. He had a notebook to keep track of his experiences. “I didn’t write very much in the notebook,” he says, laughing. Instead, while on LSD, he reveled in a sense of well-being and marveled at the “fluidity of time and space.” He found himself staring at clouds and seeing them change into faces of people he was thinking of. If his attention drifted, the clouds morphed into animals. Seth went on to try ayahuasca, a hallucinogenic brew made from a shrub and a vine native to South America and often used in shamanistic rituals there. This time, he had a more emotional trip that dredged up powerful memories. Both experiences strengthened Seth’s conviction that psychedelics have great potential for teaching us about the inner workings of the brain that give rise to our perceptions. He’s not alone. Armed with fMRI scans, EEG recordings, computational models of the brain and reports from volunteers tripping on psychedelics, a small but growing number of neuroscientists are trying to take advantage of these drugs and the hallucinations they induce to better understand how the brain produces perceptions. © 2021 Annual Reviews, Inc

Keyword: Drug Abuse; Vision
Link ID: 27883 - Posted: 06.29.2021

As I lean back in the leather recliner, my limbs feel heavy. The strong dose of ketamine I've just taken is making it harder to move, so I struggle to put on my headphones and eyeshades. Soothing music lulls me into deep relaxation, as my consciousness starts to float away from my body and into a world of swirling lights, colours and images. I'm not at a new-age music festival, or in a seedy underground drug den. This fully-legal experience is taking place under medical supervision at Field Trip Health in Toronto, a clinic that offers psychedelic-assisted therapy for those suffering treatment-resistant mental illnesses like depression and PTSD. The clinic, which was the first of its kind in Canada, opened last year. Since then, similar clinics have opened in Quebec, Alberta, Saskatchewan, B.C., and Nova Scotia. Ketamine was first approved for use in Canada and the U.S. as a general anesthetic more than 50 years ago. Since then it has gained a reputation as a party drug, with names like Special K or Vitamin K. Today, it's increasingly being used as a fast-acting and effective treatment for depression. But it isn't without controversy. I've dealt with bouts of depression and suicidal thoughts for about as long as I can remember. By the fall of 2020, after months of isolation due to the COVID-19 pandemic had taken their toll, my depression was as bad as it had ever been. ©2021 CBC/Radio-Canada.

Keyword: Depression; Drug Abuse
Link ID: 27873 - Posted: 06.26.2021

An analysis of survey data from more than 280,000 young adults ages 18-35 showed that cannabis (marijuana) use was associated with increased risks of thoughts of suicide (suicidal ideation), suicide plan, and suicide attempt. These associations remained regardless of whether someone was also experiencing depression, and the risks were greater for women than for men. The study published online today in JAMA Network Open and was conducted by researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health. “While we cannot establish that cannabis use caused the increased suicidality we observed in this study, these associations warrant further research, especially given the great burden of suicide on young adults,” said NIDA Director Nora Volkow, M.D., senior author of this study. “As we better understand the relationship between cannabis use, depression, and suicidality, clinicians will be able to provide better guidance and care to patients.” The number of adults in the United States who use cannabis more than doubled from 22.6 million in 2008 to 45.0 million in 2019, and the number of daily or near-daily users almost tripled from 3.6 million to 9.8 million in 2019. Over the same time span, the number of adults with depression also increased, as did the number of people who reported suicidal ideation or plan or who died by suicide. To date, however, the relationship between trends in cannabis use and suicidality is not well understood. The current study sought to fill this gap.

Keyword: Depression; Drug Abuse
Link ID: 27866 - Posted: 06.23.2021

By Lenny Bernstein MORGANTOWN, W.Va. — After nearly two decades of hardcore drug addiction — after overdoses and rehabs and relapses, homelessness and dead friends and ruined lives — Gerod Buckhalter had one choice left, and he knew it. He could go on the same way and die young in someone’s home or a parking lot, another casualty in a drug epidemic that has claimed nearly 850,000 people like him. Or he could let a surgeon cut two nickel-size holes in his skull and plunge metal-tipped electrodes into his brain. More than 600 days after he underwent the experimental surgery, Buckhalter has not touched drugs again — an outcome so outlandishly successful that neither he nor his doctors dared hope it could happen. He is the only person in the United States to ever have substance use disorder relieved by deep brain stimulation. The procedure has reversed Parkinson’s disease, epilepsy and a few other intractable conditions, but had never been attempted for drug addiction here. The device, known as a deep brain stimulator, also is recording the electrical activity in Buckhalter’s brain — another innovation that researchers hope will help locate a biomarker for addiction and allow earlier intervention with other people. Buckhalter, 35, is a walking, talking laboratory for the outer edge of drug addiction therapy, a living experiment in what may be possible someday. Yet for all the futuristic prospects, he is also proof of how difficult treatment of addiction remains. Quelling it with a scalpel helps refute the false belief that substance use disorder is a weakness or a moral failing, rather than a brain disease. But it does not address the psychological, social and socioeconomic factors that complicate the disease.

Keyword: Drug Abuse
Link ID: 27859 - Posted: 06.19.2021

By Laura Sanders The key ingredient in the illicit drug known as Ecstasy or Molly may offer profound relief from post-traumatic stress disorder. When paired with intense talk therapy, MDMA drastically eased symptoms in people who had struggled with severe PTSD for years, a new study reports. “This is a big deal,” says Steven Gold, a clinical psychologist in Fort Lauderdale and professor emeritus at Nova Southeastern University in Plantation, Fla. “All other things being equal, the use of psychedelic medication can significantly improve the outcome.” The results, published May 10 in Nature Medicine, are preliminary. But the findings offer hope to the millions of people worldwide who have PTSD, for whom new treatments are desperately needed. Antidepressants such as Zoloft and Paxil are often prescribed, but the drugs don’t work for an estimated 40 to 60 percent of people with PTSD. Ninety people participated in the new study, which took place at 15 clinical sites in the United States, Canada and Israel. All the participants received 15 therapy sessions with therapists trained to guide people as they experienced the drug. Half of the participants received MDMA in three eight-hour therapy sessions; the other half received placebos during three eight-hour therapy sessions. True to its nickname Ecstasy, MDMA evokes feelings of bliss and social connectedness. The participants took the drug (or the placebo) while wearing eye covers and listening to music, and occasionally talking with their therapist about their experience. © Society for Science & the Public 2000–2021.

Keyword: Stress; Drug Abuse
Link ID: 27826 - Posted: 05.19.2021

By Andrew Jacobs It’s been a long, strange trip in the four decades since Rick Doblin, a pioneering psychedelics researcher, dropped his first hit of acid in college and decided to dedicate his life to the healing powers of mind-altering compounds. Even as antidrug campaigns led to the criminalization of Ecstasy, LSD and magic mushrooms, and drove most researchers from the field, Dr. Doblin continued his quixotic crusade with financial help from his parents. Dr. Doblin’s quest to win mainstream acceptance of psychedelics took a significant leap forward on Monday when the journal Nature Medicine published the results of his lab’s study on MDMA, the club drug popularly known as Ecstasy and Molly. The study, the first Phase 3 clinical trial conducted with psychedelic-assisted therapy, found that MDMA paired with counseling brought marked relief to patients with severe post-traumatic stress disorder. The results, coming weeks after a New England Journal of Medicine study that highlighted the benefits of treating depression with psilocybin, the psychoactive ingredient in magic mushrooms, have excited scientists, psychotherapists and entrepreneurs in the rapidly expanding field of psychedelic medicine. They say it is only a matter of time before the Food and Drug Administration grants approval for psychoactive compounds to be used therapeutically — for MDMA as soon as 2023, followed by psilocybin a year or two later. After decades of demonization and criminalization, psychedelic drugs are on the cusp of entering mainstream psychiatry, with profound implications for a field that in recent decades has seen few pharmacological advancements for the treatment of mental disorders and addiction. The need for new therapeutics has gained greater urgency amid a national epidemic of opioid abuse and suicides. © 2021 The New York Times Company

Keyword: Depression; Drug Abuse
Link ID: 27817 - Posted: 05.12.2021

By Rachel Nuwer In an important step toward medical approval, MDMA, the illegal drug popularly known as Ecstasy or Molly, was shown to bring relief to those suffering from severe post-traumatic stress disorder when paired with talk therapy. Of the 90 people who took part in the new study, which is expected to be published later this month in Nature Medicine, those who received MDMA during therapy experienced a significantly greater reduction in the severity of their symptoms compared with those who received therapy and an inactive placebo. Two months after treatment, 67 percent of participants in the MDMA group no longer qualified for a diagnosis of PTSD, compared with 32 percent in the placebo group. MDMA produced no serious adverse side effects. Some participants temporarily experienced mild symptoms like nausea and loss of appetite. “This is about as excited as I can get about a clinical trial,” said Gul Dolen, a neuroscientist at Johns Hopkins University School of Medicine, who was not involved in the research. “There is nothing like this in clinical trial results for a neuropsychiatric disease.” Before MDMA-assisted therapy can be approved for therapeutic use, the Food and Drug Administration needs a second positive Phase 3 trial, which is currently underway with 100 participants. Approval could come as early as 2023. Mental health experts say that this research — the first Phase 3 trial conducted on psychedelic-assisted therapy — could pave the way for further studies on MDMA’s potential to help address other difficult-to-treat mental health conditions, including substance abuse, obsessive compulsive disorder, phobias, eating disorders, depression, end-of-life anxiety and social anxiety in autistic adults. © 2021 The New York Times Company

Keyword: Drug Abuse; Stress
Link ID: 27804 - Posted: 05.05.2021

Ariana Remmel Scientists in search of psychedelic drug treatments have developed a way to determine whether a molecule is likely to cause hallucinations, without testing it on people or animals. Growing evidence suggests that psychedelic compounds, which are active in the brain, have potential to treat psychiatric illnesses such as post-traumatic stress disorder (PTSD), but researchers are trying to find out whether there is a way to keep the beneficial properties of these drugs without the hallucinogenic side effects, which can complicate treatment. It is currently almost impossible to predict whether a potential drug will cause hallucinations before it is tested on animals or people. “That really slows down drug discovery,” says David Olson, a chemical neuroscientist at the University of California, Davis. To address this, a team led by Olson and neuroscientist Lin Tian, also at Davis, designed a fluorescent sensor to predict whether a molecule is hallucinogenic, based on the structure of a brain receptor targeted by psychedelics. Using their approach, the researchers identified a psychedelic-like molecule without hallucinogenic properties that they later found had antidepressant activity in mice1. The discovery adds “more fuel for the fire” of efforts to make drugs from psychedelic-like molecules without side effects, says Bryan Roth, a molecular pharmacologist at the University of North Carolina School of Medicine in Chapel Hill. © 2021 Springer Nature Limited

Keyword: Drug Abuse; Stress
Link ID: 27798 - Posted: 05.01.2021

by Angie Voyles Askham A brain circuit that connects the amygdala to the hypothalamus is essential for deriving pleasure from social interactions, according to a new study in mice. Alterations in this circuit may help explain why autistic people tend to have less social motivation than their non-autistic peers. The release of the neurotransmitter dopamine into the striatum prompts the rewarding feelings that come from stimuli such as food or sex, previous research shows. But it was unclear whether all social reward is processed in that same circuit, or if it occurs in a separate brain area that later links up with the striatum, the brain’s reward center, says lead researcher Weizhe Hong, associate professor of neurobiology and biological chemistry at the University of California, Los Angeles. Hong and his colleagues trained mice on a social test and then altered activity in the animals’ medial amygdala, which has been linked to the regulation of social behaviors. Cells in the area carry information about social reward to the medial preoptic area of the hypothalamus, the team found. And activation of this circuit prompts the release of dopamine in the striatum. “It’s filling a gap that existed” in the field, says Jessica Walsh, assistant professor of pharmacology at the University of North Carolina at Chapel Hill, who was not involved in the study. © 2021 Simons Foundation

Keyword: Autism; Drug Abuse
Link ID: 27793 - Posted: 05.01.2021

By Nambi Ndugga and Austin Frakt American deaths from misuse of substances, including alcohol, have increased over the past two decades, but not uniformly across various demographic groups. Overall rates of alcohol abuse and related deaths have consistently and significantly increased for white non-Hispanic Americans, while Black Americans have experienced a much slower and less significant incline, and some other groups have had declines. More recently, alcohol use has been up during the pandemic, with one study showing a greater increase in misuse among women than among men. (For men, heavy drinking is considered more than four drinks per day and 14 drinks per week, and for women, more than three drinks per day and seven drinks per week, according to the National Institute on Alcohol Abuse and Alcoholism.) “Alcohol kills many more people than many may realize,” said Yusuf Ransome, an assistant professor at Yale’s School of Public Health. “It is a major contributor to deaths linked to physical injuries, interpersonal violence, motor vehicle crashes, self-harm and other harmful outcomes.” One reason for this might be that alcohol is often viewed as socially acceptable. “Alcohol use has been normalized because it is consumed sometimes at family and communal gatherings, casual outings, and that’s the type of drinking that is typically seen or showed within the media,” he said. “We rarely see the long-term health impacts of excessive alcohol use, nor do we show the acute dangers of alcohol misuse and abuse.” Between 2000 and 2016, according to research published in JAMA, alcohol-related deaths continually increased for white men (2.3 percent per year on average) and white women (4.1 percent), with middle-aged white Americans accounting for the highest increase in deaths. Rapid increases during this period in mortality related to alcohol and drugs like opioids among white Americans — particularly those without a college degree — have been termed “deaths of despair.” Sign up for The Upshot Newsletter: Analysis that explains politics, policy and everyday life, with an emphasis on data and charts. © 2021 The New York Times Company

Keyword: Drug Abuse; Stress
Link ID: 27779 - Posted: 04.21.2021