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Is cannabis bad for teens? Here’s what the data say

By Anil Oza Krista Lisdahl has been studying cannabis use among adolescents for two decades, and what she sees makes her worried for her teenage son. “I see the data coming in, I know that he is going to come across it,” she says. As a clinical neuropsychologist at the University of Wisconsin–Milwaukee, she sees plenty of young people who have come into contact with the drug to varying degrees, from trying it once at a party to using potent preparations of it daily. The encounters have become more frequent as efforts to legalize cannabis for recreational use intensify around the world. In some of her studies, around one-third of adolescents who regularly use cannabis show signs of a cannabis use disorder — that is, they can’t stop using the drug despite negative impacts on their lives. But she wants more conclusive evidence when it comes to talking about the drug and its risks to young people, including her son. Deciding what to say is difficult, however. Anti-drug messaging campaigns have dwindled, and young people are forced to consider sometimes-conflicting messages on risks in a culture that increasingly paints cannabis and other formerly illicit drugs as harmless or potentially therapeutic. “Teenagers are pretty smart, and they see that adults use cannabis,” Lisdahl says. That makes blanket warnings and prohibitions practically useless. It’s now a decade since the drug was officially legalized for recreational use by adults aged 18 and older in Uruguay, and aged 21 and older in the states of Colorado and Washington. Many other states and countries have followed, and researchers are desperately trying to get a handle on how usage patterns are changing as a result; how the drug impacts brain development; and how cannabis use correlates with mental-health conditions such as depression, anxiety and schizophrenia. The data so far don’t tell clear stories: young people don’t seem to be using in greater numbers than before legalization, but there seem to be trends towards more problematic use. © 2023 Springer Nature Limited

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology; Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 4: Development of the Brain; Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 29041 - Posted: 12.13.2023

Cannabis use linked to higher risk of poor pregnancy outcomes

By Sabrina Malhi Cannabis use is associated with a greater risk of an unhealthy pregnancy outcomes, especially low birth weight, according to a study funded by the National Institutes of Health. While the study did not identity why cannabis use might have these effects, it underscores the potentially damaging impact of the substance on fetal health, the authors say. Many pregnant people use cannabis to help manage symptoms, including nausea and pain. The prevalence of the drug has surged in the past decade as more states have legalized its use for medicine or recreation, and many people believe it is relatively safe. But the impact cannabis has on pregnancy has been understudied. For the new study, researchers analyzed urine samples from more than 9,000 pregnant people between 2010 and 2013 to determine whether cannabis was used at any point during pregnancy, at how many weeks of gestation it was used and the amount. The team measured THC, the psychoactive substance in cannabis, at three different periods roughly tracking with trimesters and used that data to calculate total cannabis exposure throughout the entire pregnancy. Their findings were published in JAMA on Tuesday. The authors determined that pregnant people who used cannabis experienced unfavorable birth outcomes at rates of 25.9 percent, compared with 17.4 percent among those who did not use cannabis. Low birth weight and cannabis use had the strongest association out of all the adverse outcomes, the study found. Low birth weight is defined as weighing less than 5 lbs., 8 ounces at birth. This can lead to a range of health complications and long-term risks, including an increased likelihood of chronic conditions later in life. Experts say the study adds to a growing body of evidence that no amount of cannabis is safe during pregnancy.

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology; Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 4: Development of the Brain; Chapter 13: Memory and Learning
Link ID: 29040 - Posted: 12.13.2023

She Studies How Addiction Hijacks Learning in the Brain

By Yasemin Saplakoglu Erin Calipari comes from a basketball family. Her father, John Calipari, has coached college and professional basketball since 1998, leading six teams to the NCAA Final Four, and her brother coaches men’s basketball at Vanderbilt University in Nashville, Tennessee, where she now works. But when she joined her college team as an undergraduate, she realized her strengths lay elsewhere. “I was fine. I wasn’t great,” she said. “It was pretty clear to me a couple years in that it was not a career path.” Off the court, as a biology major she gravitated toward hormones and neurotransmitters. She grew fascinated with the neurobiology of how and why drugs such as cocaine and opioids are addictive, as she learned about the effects of ecstasy on the serotonin system. “I thought drugs were so cool because they hijack the brain,” she said. “Drugs essentially take the normal systems we have in our body and drive them in a way that makes you want to take drugs again.” After pursuing graduate work in neuroscience, in 2017 Calipari set up her lab at Vanderbilt to explore how addiction is connected to the ways the brain learns and makes decisions. “Deciding what to do and what not to do is really fundamental to everything we do,” Calipari said. “You put your hand on a hot stove, you learn really quickly not to do that again.” Addiction can diminish a person’s ability to learn that drug use is hurting them, and also their ability to learn anything at all. Her world still collides with sports, for instance when she gives talks to athletes about the dangers of substance use. Athletes can be vulnerable to addiction when they are prescribed pain medicines, such as opioids, for injuries. There is a risk of dependence if opioids are taken for long periods of time, even when patients follow doctors’ orders — a fact that has led to a nationwide public health emergency. Tennessee is an epicenter of the opioid epidemic. In 2022, Nashville had the second-highest rate of overdose deaths in the country. All Rights Reserved © 2023

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 4: Development of the Brain
Link ID: 29039 - Posted: 12.09.2023

Massive genetic study finds genes linked to cannabis addiction

Lilly Tozer By analysing more than one million people’s genomes, researchers have identified stretches of DNA that could be linked to cannabis addiction. They also found that some of the same regions in the genome are associated with other health conditions, such as lung cancer and schizophrenia. The findings are evidence that cannabis addiction “could have substantial public-health risks if the usage increases”, says Daniel Levey, a medical neuroscientist at Yale University in New Haven, Connecticut, and a co-author of the study, published today in Nature Genetics1. Taking cannabis recreationally is legal in at least 8 countries, and 48 countries have legalized medicinal use of the drug for conditions including chronic pain, cancer and epilepsy. But one-third of people who take cannabis end up becoming addicted, or using the drug in a way that is damaging to their health. Previous studies have suggested that there is a genetic component, and have shown links between problematic cannabis use and some cancers and psychiatric disorders. Weighing the dangers of cannabis Drug taking and addiction can be influenced both by people’s genes and by their environment, which makes them extremely difficult to study, says Levey. But the team was able to build on data from previous work2 by including genetic information from additional sources, predominantly the Million Veteran Program — a US-based biobank with a large genetic database that aims to improve health care for former military service members. The analysis encompassed multiple ethnic groups, a first for a genetic study looking at cannabis misuse. As well as identifying regions of the genome that might be involved, the researchers saw a bi-directional link between excessive cannabis use and schizophrenia, meaning that the two conditions can influence each other. This finding is intriguing, says Marta Di Forti, a psychiatrist-scientist at King’s College London. Cannabis use “is the most preventable risk factor” for schizophrenia, she says, adding that the type of genetic data examined in the study could be used in future to identify and support people at increased risk of developing psychiatric disorders through cannabis use. © 2023 Springer Nature Limited

A Monster’: Super Meth and Other Drugs Push Crisis Beyond Opioids

By Jan Hoffman Dr. Nic Helmstetter crab-walked down a steep, rain-slicked trail into a grove of maple and cottonwood trees to his destination: a dozen tents in a clearing by the Kalamazoo River, surrounded by the detritus of lives perpetually on the move. Discarded red plastic cups. A wet sock flung over a bush. A carpet square. And scattered across the forest floor: orange vial caps and used syringes. Kalamazoo, a small city in Western Michigan, is a way station along the drug trafficking corridor between Chicago and Detroit. In its parks, under railroad overpasses and here in the woods, people ensnared by drugs scramble to survive. Dr. Helmstetter, who makes weekly primary care rounds with a program called Street Medicine Kalamazoo, carried medications to reverse overdoses, blunt cravings and ease withdrawal-induced nausea. But increasingly, the utility of these therapies, developed to address the decades-old opioid crisis, is diminishing. They work to counteract the most devastating effects of fentanyl and heroin, but most users now routinely test positive for other substances too, predominantly stimulants such as cocaine and methamphetamine, for which there are no approved medications. Rachel, 35, her hair dyed a silvery lavender, ran to greet Dr. Helmstetter. She takes the medicine buprenorphine, which acts to dull her body’s yearning for opioids, but she was not ready to let go of meth. “I prefer both, actually,” she said. “I like to be up and down at the same time.” The United States is in a new and perilous period in its battle against illicit drugs. The scourge is not only opioids, such as fentanyl, but a rapidly growing practice that the Centers for Disease Control and Prevention labels “polysubstance use.” Over the last three years, studies of people addicted to opioids (a population estimated to be in the millions) have consistently shown that between 70 and 80 percent also take other illicit substances, a shift that is stymieing treatment efforts and confounding state, local and federal policies. “It’s no longer an opioid epidemic,” said Dr. Cara Poland, an associate professor at the Michigan State University College of Human Medicine. “This is an addiction crisis.” © 2023 The New York Times Company

How Much Coffee Is Too Much Coffee?

By Alice Callahan Q: I routinely drink three or four cups of coffee per day, but often wonder if this is too much. Should I consider cutting back? Coffee can be many things: a morning ritual, a cultural tradition, a productivity hack and even a health drink. Studies suggest, for instance, that coffee drinkers live longer and have lower risks of Type 2 diabetes, Parkinson’s disease, cardiovascular conditions and some cancers. “Overall, coffee does more good than bad,” said Rob van Dam, a professor of exercise and nutrition sciences at the Milken Institute School of Public Health at George Washington University. But between your breakfast brew, lunchtime latte and afternoon espresso, is it possible to have too much? And if so, how can you tell? Coffee contains thousands of chemical compounds, many of which may influence health, said Marilyn Cornelis, an associate professor of preventive medicine at Northwestern University Feinberg School of Medicine. But coffee is also the largest source of caffeine for people in the United States, and that’s where most of the risks associated with coffee consumption come from, she said. Having too much caffeine can cause a racing heart, jitteriness, anxiousness, nausea or trouble sleeping, said Jennifer Temple, a professor of exercise and nutrition sciences at the University at Buffalo. But “most people are kind of well tuned with their response to caffeine,” Dr. Cornelis said, and when they begin to experience even mild symptoms of having too much, they cut back. © 2023 The New York Times Company

The Long, Strange History of MDMA

By Taylor Majewski Rachel Nuwer’s “I Feel Love: MDMA and the Quest for Connection in a Fractured World,” is clearly aimed at a broad audience. It will resonate with readers who have experienced MDMA recreationally, probably at a rave, or therapeutically, probably to heal the emotional aftereffects of deep-seated trauma. Or both. But it’s also intended for readers who have never touched the drug, colloquially known as ecstasy or molly. Perhaps it’s especially for them. “I Feel Love” belongs to a growing family of nonfiction accounts of the fraught history of psychedelics and why, through compelling anecdotes and the latest science, we should reconsider them. Nuwer, a science journalist, chronicles the hopeful story of something both small and large — MDMA, the compound, and MDMA, the drug that’s repeatedly brought humans together across decades, continents, politics, and moral panics. The book is a natural successor to Michael Pollan’s 2018 bestseller “How to Change Your Mind,” which covered the mystical and medical benefits of LSD and psilocybin, and paved the way for a psychedelic renaissance of sorts, Nuwer writes in the introduction, “no such modern telling exists for MDMA.” Now, it does. “I Feel Love” is, above all, a time capsule. Nuwer begins with a crucial asterisk: “MDMA, also known as Ecstasy or Molly, is currently an illegal drug.” Today, most journalism around psychedelics is stipulated with this simple fact. Despite their potential to heal, drugs like psilocybin, LSD, and MDMA are still classified as Schedule I, the Drug Enforcement Administration’s highest category for controlled substances with no medical use, with a high potential for abuse. For MDMA specifically, that might be about to change.

Dopamine is a brain chemical famously linked to mood and pleasure − but multiple types

Kimberlee D'Ardenne Dopamine seems to be having a moment in the zeitgeist. You may have read about it in the news, seen viral social media posts about “dopamine hacking” or listened to podcasts about how to harness what this molecule is doing in your brain to improve your mood and productivity. But recent neuroscience research suggests that popular strategies to control dopamine are based on an overly narrow view of how it functions. Dopamine is one of the brain’s neurotransmitters – tiny molecules that act as messengers between neurons. It is known for its role in tracking your reaction to rewards such as food, sex, money or answering a question correctly. There are many kinds of dopamine neurons located in the uppermost region of the brainstem that manufacture and release dopamine throughout the brain. Whether neuron type affects the function of the dopamine it produces has been an open question. Recently published research reports a relationship between neuron type and dopamine function, and one type of dopamine neuron has an unexpected function that will likely reshape how scientists, clinicians and the public understand this neurotransmitter. Dopamine is involved with more than just pleasure. Dopamine neuron firing Dopamine is famous for the role it plays in reward processing, an idea that dates back at least 50 years. Dopamine neurons monitor the difference between the rewards you thought you would get from a behavior and what you actually got. Neuroscientists call this difference a reward prediction error. Understand new developments in science, health and technology, each week Eating dinner at a restaurant that just opened and looks likely to be nothing special shows reward prediction errors in action. If your meal is very good, that results in a positive reward prediction error, and you are likely to return and order the same meal in the future. Each time you return, the reward prediction error shrinks until it eventually reaches zero when you fully expect a delicious dinner. But if your first meal was terrible, that results in a negative reward prediction error, and you probably won’t go back to the restaurant. Dopamine neurons communicate reward prediction errors to the brain through their firing rates and patterns of dopamine release, which the brain uses for learning. They fire in two ways. © 2010–2023, The Conversation US, Inc.

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology; Chapter 18: Attention and Higher Cognition
Related chapters from MM:Chapter 4: Development of the Brain; Chapter 14: Attention and Higher Cognition
Link ID: 28917 - Posted: 09.21.2023

Will ‘Poor Man’s Cocaine’ Fuel the Next U.S. Drug Crisis?

By Jim Crotty The opioid crisis continues to rage across the U.S., but there are some positive, if modest, signs that it may be slowing. Overdose deaths due to opioids are flattening in many places and dropping in others, awareness of the dangers of opioid abuse continues to increase, and more than $50 billion in opioid settlement funds are finally making their way to state and local governments after years of delay. There is still much work to be done, but all public health emergencies eventually subside. Then what? First, it’s important to realize that synthetic opioids like fentanyl will never fully disappear from the drug supply. They are too potent, too addictive, and perhaps most importantly, too lucrative. Opioids, like Covid-19, are here to stay, consistently circulating in the community but at more manageable levels. More alarming is what may take its place. Since 2010, overdoses involving both stimulants and fentanyl have increased 50-fold. Experts suggest this dramatic rise in polysubstance use represents a “fourth wave” in the opioid crisis, but what if it is really the start of a new wave of an emerging stimulant crisis? Substance abuse tends to move in cycles. Periods with high rates of depressant drug use (like opioids) are almost always followed by ones with high rates of stimulant drug use (like methamphetamine and cocaine), and vice versa. The heroin crisis of the 1960s and 1970s was followed by the crack epidemic of the 1980s and 1990s, which gave way to the current opioid epidemic. As the think tank scholar Charles Fain Lehman quipped, “As with fashion, so with drugs — whatever the last generation did, the next generation tends to abhor.” The difference now is the primacy of synthetic drugs — that is, illicit substances created in a lab that are designed to mimic the effects of naturally occurring drugs.

Psychedelic drug MDMA moves closer to US approval following success in PTSD trial

Sara Reardon The psychedelic drug MDMA, also known as ecstasy or molly, has passed another key hurdle on its way to regulatory approval as a treatment for mental illness. A second large clinical trial has found that the drug — in combination with psychotherapy — is effective at treating post-traumatic stress disorder (PTSD). The results allow the trial’s sponsor to now seek approval from the US Food and Drug Administration (FDA) for MDMA’s use as a PTSD treatment for the general public, which might come as soon as next year. “It’s an important study,” says Matthias Liechti, a psychopharmacologist who studies MDMA at the University of Basel in Switzerland, but who was not involved with the trial or its sponsor. “It confirms MDMA works.” In June, Australia became the first country to allow physicians to prescribe MDMA for treating psychiatric conditions. MDMA is illegal in the United States and other countries because of the potential for its misuse. But the Multidisciplinary Association for Psychedelic Studies (MAPS), a non-profit organization in San Jose, California, has long been developing a proprietary protocol for using MDMA as a treatment for PTSD and other disorders. MAPS has been campaigning for its legalization — a move that could encourage other countries to follow suit. In 2021, researchers sponsored by MAPS reported the results of a study1 in which 90 people received a form of psychotherapy developed by the organization alongside either MDMA or a placebo. After three treatment sessions, 67% of those who received MDMA with therapy no longer qualified for a PTSD diagnosis, compared with 32% of those who received therapy and a placebo. The results were widely hailed as promising, but the FDA typically requires two placebo-controlled trials before a drug can be approved. The results of a second trial, involving 104 further individuals with PTSD and published on 14 September in Nature Medicine2, were similar to those of the original: 71% of people who received MDMA alongside therapy lost their PTSD diagnosis, compared with 48% of those who received a placebo and therapy. © 2023 Springer Nature Limited

Related chapters from BN: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders; Chapter 15: Emotions, Aggression, and Stress
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders; Chapter 11: Emotions, Aggression, and Stress
Link ID: 28911 - Posted: 09.16.2023

Cannabis Use Disorder Is ‘Common’ Among Marijuana Users

By Matt Richtel More than one-fifth of people who use cannabis struggle with dependency or problematic use, according to a study published on Tuesday in The Journal of the American Medical Association Network Open. The research found that 21 percent of people in the study had some degree of cannabis use disorder, which clinicians characterize broadly as problematic use of cannabis that leads to a variety of symptoms, such as recurrent social and occupational problems, indicating impairment and distress. In the study, 6.5 percent of users suffered moderate to severe disorder. Cannabis users who experience more severe dependency tended to be recreational users, whereas less severe but still problematic use was associated roughly equally with medical and recreational use. The most common symptoms among both groups were increased tolerance, craving, and uncontrolled escalation of cannabis use. ImageA person holding a lit joint while bags of cannabis sit on a black table in the Cannabis use is rising nationwide as more states have legalized it. The new findings align with prior research, which has found that around 20 percent of cannabis users develop cannabis use disorder. The condition can be treated with detoxification and abstinence, therapies and other treatments that work with addictive behaviors. The new study drew its data from nearly 1,500 primary care patients in Washington State, where recreational use is legal, in an effort to explore the prevalence of cannabis use disorder among both medical and nonmedical users. The research found that 42 percent of cannabis users identified themselves solely as medical users; 25 percent identified as nonmedical users, and 32 percent identified as both recreational and medical users. © 2023 The New York Times Company

Rising number of overdose deaths involve mix of opioids with cocaine, meth

By David Ovalle The evolving overdose crisis in the United States is making another lethal turn, federal disease trackers reported Wednesday: Increasingly, people dying from opioids are also using stimulants such as cocaine and methamphetamine. An analysis by the Centers for Disease Control and Prevention shows that between 2011 and 2021, the age-adjusted rate of overdose deaths involving opioids and cocaine nearly quintupled, far outpacing the rate of deaths involving only cocaine. In 2021 alone, nearly 80 percent of the 24,486 cocaine overdose deaths recorded in the United States also involved an opioid. Experts say it represents the latest wave of the nation’s drug epidemic. For many users injecting or smoking fentanyl for some time, “adding a stimulant makes the drug feel like it did in the beginning,” said Daniel Ciccarone, a professor of addiction medicine at the University of California at San Francisco who has been studying the simultaneous use of stimulants and opioids. The federal analysis adds clarity to the staggering number of drug poisonings, largely driven by fentanyl, which can be up to 50 times more powerful than heroin. The CDC estimates that in 2022, more than 110,000 people succumbed to overdoses, edging past the previous year but representing a plateau from earlier spikes. Preliminary CDC data also suggest a slight increase in deaths in 2022 involving opioids taken with cocaine and psychostimulants such as meth. “These aren’t mutually exclusive categories. Someone can die of more than one drug,” said CDC researcher Merianne Rose Spencer, who led the analysis. The international cocaine market has thrived despite shutdowns associated with the coronavirus pandemic, according to the U.N.’s Global Report on Cocaine 2023, with record production in Latin America, new trafficking hubs in Africa and increased seizures.

Medications for opioid use disorder — MOUD — and adolescents

By Tammy Worth In two decades as a pediatrician, Jason Reynolds has had no success treating patients with opioid use disorder by sending them to rehab. But five years ago, when his Massachusetts practice, Wareham Pediatric Associates PC, became the first in the state to offer medication therapy to adolescent patients, he saw dramatic results. The first patient he treated with medication, a young man named Nate, had overdosed on opioids twice in the 24-hour period before seeing Reynolds. But that patient has had no opioid relapses since starting drug therapy. Reynolds’ success received a lot of media attention, and one interviewer, he recalls, asked Nate if any of his friends would also consider starting the treatment. Reynolds is among a small minority of pediatricians using medication to treat opioid use disorder in adolescents. Fewer than 2 percent of all physicians prescribing the medications are pediatricians, and many youth rehabilitation facilities don’t offer them at all. Medication for opioid use disorder (MOUD) uses buprenorphine or methadone to reduce cravings and withdrawal symptoms, or naltrexone to block the high that users would otherwise get if they decided to use opioids. Though MOUD is often used to treat adults, several barriers have prevented it from being adopted more widely for youth. Reynolds and a handful of other practitioners across the country are now working to provide education and training to other health care providers, hoping to increase use of this life-saving treatment. Opioid use among US youth is on the rise nationally, with diagnoses increasing from 0.26 per 100,000 person-years in 2001 to 1.51 in 2014. Overdose deaths have also spiked, more than doubling among youth ages 14 to 18, from 492 in 2019 to 1,146 in 2021. © 2023 Annual Reviews

CIA experiments, Mormon ravers and reformed racists: the untold history of MDMA

Alaina Demopoulos It was in 1975, when Carl Resnikoff and his girlfriend, Judith Gipson, took a bucolic ferry ride to Sausalito, a city located on the north end of Golden Gate Bridge, that a revolution in youth culture, music, emotion and imagination would take place. It was on that ride that the two undergraduates took capsules filled with MDMA powder for the very first time. Resnikoff, a biophysics major at Berkeley, had synthesized the drug himself. As the boat cut through the water of the San Francisco Bay, Gipson began to feel “a floating sense of euphoria … like some guy could come walking up to us asking for help and his guts are spilling out, and we’d be grooving on how beautiful it was.’” According to Rachel Nuwer’s book I Feel Love: MDMA and the Quest for Connection in a Fractured World, Resnikoff and his girlfriend’s romp was the first-ever documented instance of people taking MDMA recreationally. Nuwer is a science journalist who covered clinical trials for MDMA use in treating post-traumatic stress disorder (PTSD). While cannabis and psilocybin have undergone rebrands of late, going from countercultural tokens to the mainstream, she believes that the public is starting to open up to MDMA, too. “MDMA deserves its own story,” Nuwer said. “I wanted to bring together the history, culture, politics and science of the drug all in one place. This book is for anyone who’s interested in the drug, whether it’s someone who’s taken it 500 times on the dancefloor or who’s using it therapeutically for the first time.” Nuwer believes that MDMA will “follow the path of cannabis”, becoming legal medicinally first, then decriminalized, and perhaps fully legalized for all types of use. That cycle may have already started: three clinical trials have found that MDMA, which is also called ecstasy, can speed the recovery of PTSD. FDA approval for therapeutic use could come as early as next year. © 2023 Guardian News & Media Limited

How the Brain Protects Itself From Blood-Borne Threats

By Yasemin Saplakoglu Enough pints of beer can have you falling off your bar stool or loudly reciting lyrics to early 2000s jams to total strangers, because alcohol can get past one of the strongest defenses in the body. If you’ve ever been drunk, high or drowsy from allergy medication, you’ve experienced what happens when some molecules defeat the defense system called the blood-brain barrier and make it into the brain. Embedded in the walls of the hundreds of miles of capillaries that wind through the brain, the barrier keeps most molecules in the blood from ever reaching sensitive neurons. Much as the skull protects the brain from external physical threats, the blood-brain barrier protects it from chemical and pathogenic ones. While it’s a fantastic feat of evolution, the barrier is very much a nuisance for drug developers, who have spent decades trying to selectively overcome it to deliver therapeutics to the brain. Biomedical researchers want to understand the barrier better because its failures seem to be the key to some diseases and because manipulating the barrier could help improve the treatment of certain conditions. It’s really there to control the environment for proper brain function. “We’ve learned a lot over the last decade,” said Elizabeth Rhea, a research biologist at the University of Washington Medicine Memory and Brain Wellness Center. But “we’re definitely still facing challenges in getting substrates and therapeutics across.” Protection, but Not a Fortress Like the rest of the body, the brain needs circulating blood to deliver essential nutrients and oxygen and to carry away waste. But blood chemistry constantly fluctuates, and brain tissue is extremely sensitive to its chemical environment. Neurons rely on precise releases of ions to communicate — if ions could flow freely out of the blood, that precision would be lost. Other types of biologically active molecules can also twang the delicate neurons, interfering with thoughts, memories and behaviors. All Rights Reserved © 2023

Your body naturally produces opioids without causing addiction or overdose

John Michael Streicher Opioid drugs such as morphine and fentanyl are like the two-faced Roman god Janus: The kindly face delivers pain relief to millions of sufferers, while the grim face drives an opioid abuse and overdose crisis that claimed nearly 70,000 lives in the U.S. in 2020 alone. Scientists like me who study pain and opioids have been seeking a way to separate these two seemingly inseparable faces of opioids. Researchers are trying to design drugs that deliver effective pain relief without the risk of side effects, including addiction and overdose. One possible path to achieving that goal lies in understanding the molecular pathways opioids use to carry out their effects in your body. How do opioids work? The opioid system in your body is a set of neurotransmitters your brain naturally produces that enable communication between neurons and activate protein receptors. These neurotransmitters include small proteinlike molecules like enkephalins and endorphins. These molecules regulate a tremendous number of functions in your body, including pain, pleasure, memory, the movements of your digestive system and more. Analysis of the world, from experts Opioid neurotransmitters activate receptors that are located in a lot of places in your body, including pain centers in your spinal cord and brain, reward and pleasure centers in your brain, and throughout the neurons in your gut. Normally, opioid neurotransmitters are released in only small quantities in these exact locations, so your body can use this system in a balanced way to regulate itself. The opioids your body produces and opioid drugs bind to the same receptors. The problem comes when you take an opioid drug like morphine or fentanyl, especially at high doses for a long time. These drugs travel through the bloodstream and can activate every opioid receptor in your body. You’ll get pain relief through the pain centers in your spinal cord and brain. But you’ll also get a euphoric high when those drugs hit your brain’s reward and pleasure centers, and that could lead to addiction with repeated use. When the drug hits your gut, you may develop constipation, along with other common opioid side effects. Targeting opioid signal transduction How can scientists design opioid drugs that won’t cause side effects? One approach my research team and I take is to understand how cells respond when they receive the message from an opioid neurotransmitter. Neuroscientists call this process opioid receptor signal transduction. Just as neurotransmitters are a communication network within your brain, each neuron also has a communication network that connects receptors to proteins within the neuron. When these connections are made, they trigger specific effects like pain relief. So, after a natural opioid neurotransmitter or a synthetic opioid drug activates an opioid receptor, it activates proteins within the cell that carry out the effects of the neurotransmitter or the drug. © 2010–2023, The Conversation US, Inc.

Related chapters from BN: Chapter 8: General Principles of Sensory Processing, Touch, and Pain; Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 4: Development of the Brain
Link ID: 28809 - Posted: 06.03.2023

There’s medicine to quiet his opioid cravings. Getting it can be hard.

By David Ovalle It had been four days since Kevin Hargrove last took the medication that stilled his dangerous cravings. He awoke with a queasy stomach and achy muscles, then vomited on the sidewalk as he set off from his encampment under a D.C. bridge this month. Hargrove recently changed his Medicare-funded insurance company and was unable to fill his prescription for buprenorphine, the medication he has taken for years to treat his opioid addiction. The withdrawals proved too much. The 66-year-old found a dealer on the street, paid $6 for two pills he believed were codeine painkillers and washed them down with a can of Olde English 800 malt liquor. Less than an hour later, Hargrove passed out inside his sister’s Columbia Heights apartment, overdosing on what was suspected to be fentanyl. “Don’t tell me!” his sister cried. “You’ve been doing so well!” Hargrove’s story illustrates the challenges often faced by those struggling with opioid addiction — especially people of color — in receiving buprenorphine, a medication that public health experts believe should play a critical role in curbing an addiction-and-overdose crisis fueled by fentanyl. His overdose happened this month as a newly published national study from the Harvard T.H. Chan School of Public Health showed that White patients are up to 80 percent more likely to receive buprenorphine than Black patients, and that Black patients receive a more limited supply. “There are lots of totally counterproductive insurance restrictions on this drug, particularly for populations in which the need is the greatest,” said the study’s lead author, Michael L. Barnett, an associate professor of health policy and management at Harvard’s School of Public Health.

Addiction Treatment Medicine Is Vastly Underprescribed, Especially by Race

By Jan Hoffman Despite the continuing rise in opioid overdose deaths, one of the most effective treatments for opioid addiction is still drastically underprescribed in the United States, especially for Black patients, according to a large new study. From 2016 through 2019, scarcely more than 20 percent of patients diagnosed with opioid use disorder filled prescriptions for buprenorphine, the medication considered the gold standard in opioid addiction treatment, despite repeated visits to health care providers, according to the study, which was published Wednesday in the New England Journal of Medicine. Within six months following a high-risk event like an overdose, white patients filled buprenorphine prescriptions up to 80 percent more often than Black patients, and up to 25 percent more often than Latino patients, the study found. Rates of use for methadone, another effective treatment, were generally even lower. “It was disheartening to see that buprenorphine or methadone treatments were so low, even among patients who just left the hospital with an overdose or other addiction-related issue,” said Dr. Michael L. Barnett, the lead author, who teaches health policy and management at Harvard. “And not only that, but people of color received lifesaving treatment at a fraction of the rate that white patients did.” Access to medical care, a reason often used to explain racial disparities in treatment, was not necessarily at work here, said Dr. Barnett, an associate professor at the Harvard T.H. Chan School of Public Health. Noting that all the patients regardless of race encountered doctors roughly once a month, he said, “There are two mechanisms left that could explain disparities this large. One is where people of color get their health care, which we know is highly segregated, and another is racial differences in patient trust and demand for buprenorphine.“ Buprenorphine, often marketed under the brand name Suboxone, is a synthetic opioid that satisfies a patient’s cravings for other opioids and prevents withdrawal, without providing a high. It was approved for addiction treatment by the Food and Drug Administration more than two decades ago, but still faces some resistance and stigma because it, too, is an opioid. © 2023 The New York Times Company

Can brains bounce back? Recovering addicts turn to science to map the effects of meth

Tess McClure Every few months, Cohen “Coey” Irwin lies on his back and lets the walls close in. Lights move overhead, scanning over the tattoos covering his cheeks. He lies suspended, his head encased by a padded helmet, ears blocked, as his body is shunted into a tunnel. The noise begins: a rhythmic crashing, loud as a jackhammer. For the next hour, an enormous magnet will produce finely detailed images of Irwin’s brain. Irwin has spent much of his adult life addicted to smoking methamphetamine – or P, as the drug is known in New Zealand. He knows its effects intimately: the euphoria, the paranoia, the explosive violence, the energy, the tics that run through his neck and lips. Stepping outside the MRI machine, however, he can get a fresh view for the first time – looking in from the outside at what the drug has done to his internal organs. New Zealanders are some of the world’s biggest meth takers: wastewater testing has placed it in the top four consumers worldwide. The country’s physical isolation – 4,000km from the nearest major ports – makes importing hard drugs challenging and costly, but meth can be manufactured relatively cheaply and easily, and is derived from available pharmaceuticals. Almost a third of middle-aged New Zealanders have tried the drug, a University of Otago study found in 2020. In the backroom of Mātai research centre, Irwin thinks back to when it all started. He was a teenager when he tried P for the first time – trying to impress a girl on New Year’s Eve, in his home town of Porirua, Wellington. The girlfriend didn’t last, but the drug was love at first puff, he says, and would become one of the defining relationships of his life. “I remember it was the next day, the sun had risen, I was still awake with the people at the table I’d been smoking with. And I was instantly trying to find ways: how can we make money to get more?” Within a few years, he would be smoking every day. © 2023 Guardian News & Media Limited

Fentanyl deaths have spiked among U.S. children and teens

By Aimee Cunningham Fentanyl, a deadly synthetic opioid, is killing a growing number of children and teens in the United States. More than 1,500 kids under the age of 20 died from fentanyl in 2021, four times as many as in 2018, says epidemiologist Julie Gaither of the Yale School of Medicine, who will present the data May 1 at the Pediatric Academic Societies meeting in Washington, D.C. The fentanyl deaths account for nearly all of the opioid-related deaths in this age group in 2021. Fentanyl is a lab-made opioid used for pain treatment that is 30 to 50 times more potent than heroin, making it lethal at a much smaller dose. The drug is also manufactured and sold illegally and is increasingly found contaminating counterfeit prescription drugs, or entirely replacing the drug a buyer expects to get (SN: 5/1/18). “That’s primarily the story of what’s happening among teenagers,” says pediatrician and addiction provider Sarah Bagley of the Boston University Chobanian & Avedisian School of Medicine. They intend to purchase and use one kind of drug or substance but unknowingly ingest fentanyl. “People are not anticipating that they are going to be exposed to fentanyl, and then they are, and that results in an overdose.” Some of the signs that a person is experiencing an overdose include falling asleep, losing consciousness, gurgling or choking sounds and weak or no breathing. “This change in the drug supply, where you just have a much more potent opioid, is really driving it all,” says Bagley, who was not involved in the work. © Society for Science & the Public 2000–2023.

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