Clinical Advances in Multiple Myeloma From ASCO 2025
The coming of age of chimeric antigen receptor (CAR) T-cell therapy, the selection of postinduction therapy on the basis of residual disease activity, and a novel drug delivery system are among the developments in multiple myeloma (MM) presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
Dr Joseph Mikhael, from City of Hope Cancer Center in Phoenix, Arizona, opens with long-term follow-up data from the CARTITUDE-1 trial of ciltacabtagene autoleucel CAR T-cell therapy in heavily pretreated relapsed/refractory MM. One third of patients remained progression free for 5 or more years following a single infusion, offering hope of a cure.
Next, he discusses the MIDAS trial of newly diagnosed MM, in which the treatment choice was driven by residual disease activity after induction therapy. The results indicated that autologous stem cell transplant may not be beneficial in patients with no residual disease activity and could potentially be avoided.
Dr Mikhael then turns to follow-up from PERSEUS, again in newly diagnosed disease. The data showed daratumumab to be a key component of both induction therapy when combined with bortezomib, lenalidomide, dexamethasone, and maintenance therapy in combination with lenalidomide.
In closing, he discusses a German trial that underlined the importance of aggressive treatment in high-risk newly diagnosed MM as well as an analysis of an on-body delivery system for subcutaneous isatuximab that met with patient satisfaction.
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CNN
32 minutes ago
- CNN
Why Kennedy's overhaul of a key CDC committee could lead to ‘vaccine chaos' in the US
Vaccines Federal agencies Children's healthFacebookTweetLink Follow The US Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, or ACIP, will gather this week for its second regular meeting of the year, but this won't be a typical meeting. Two weeks ago, US Health and Human Services Secretary Robert F. Kennedy Jr., who has a history of vaccine skepticism, upended the independent advisory panel and its planned agenda. All 17 of the previous members were dismissed, and eight new ones were added. Presentation topics central to anti-vaccine activists' arguments were placed on the schedule, despite studies and data about safety. The swift changes — and concerns that the committee lacks expertise and has potential conflicts of interest — are so concerning that some public health experts and officials said the country risks shifting into 'vaccine chaos,' with different vaccine recommendations at work, inconsistent access and uncertain insurance coverage. 'This week's meeting of the Advisory Committee on Immunization Practices (ACIP) is likely to mark its end – for now – as a vaccine advisory body,' said the staff and advisers of the Vaccine Integrity Project, a group that's seeking to preserve access to vaccines in the event that the government throttles it, in a viewpoint posted Monday. Dr. Peter Hotez, a pediatrician and co-director of the Texas Children's Hospital Center for Vaccine Development, said that in its new form, 'the ACIP is devoid of any meaningful expertise in vaccines or infectious diseases. It is organized to pursue a pseudoscience agenda. It's a waste of taxpayer dollars that should be dissolved.' It's a startling shift for a group that has been meeting for more than 60 years, and whose recommendations are so trusted that they're often written into state laws. ACIP has played a pivotal role in how vaccines are used in the United States. Like an orchestra conductor, it keeps the vaccine delivery system playing well together: directing doctors and other providers on how to use vaccines, telling insurance companies when to cover vaccines, giving states guidance on which vaccines to purchase, helping cities and counties decide which vaccines are needed for school enrollment and cueing the federal government on which vaccines to purchase for low-income children. 'Those recommendations are made in harmony with the input of a lot of consultants from professional groups so that we all agree then on what the recommendations are,' said Dr. William Schaffner, an infectious disease expert at Vanderbilt University in Nashville who has been participating in ACIP meetings for 40 years, both as a voting member and as a liaison member. 'Then, those recommendations basically become the standard of practice,' Schaffner said. 'So that makes the delivery of vaccines very smoothly functioning. Everybody knows who ought to get the vaccines and then when they get them.' With new uncertainty around ACIP, several groups, including the Vaccine Integrity Project, have taken steps to convene and shape evidence-based recommendations, even without such guidance from the CDC's advisers. Some states — such as Maine, which this year celebrated record-high immunization rates in school-age kids — have also begun to strip vaccine access laws of references to ACIP recommendations. But experts are worried that a cacophony of recommendations, however well-meaning, may be confusing to insurers, health care providers and the public. 'We would have certainly, for a period of time, vaccine chaos,' Schaffner said, 'Because it would be uncertain for the providers and uncertain for the public who would be receiving the vaccines, whether your children, adolescents or adults, what was covered and what was recommended.' Plus, these outside recommendations wouldn't have the force of federal law behind them to compel insurance coverage, said Dr. Fiona Havers, a medical epidemiologist and former senior adviser on vaccine policy at the CDC. Havers recently quit over Kennedy's changes to the committee, saying she no longer had confidence that the data she generated would be viewed objectively or with appropriate scientific rigor. 'If this process continues to completely fall apart and the professional societies like the American Academy of Pediatrics put out their own schedules, that's fine, and that may be where we're going,' Havers said. 'But I personally would not want to trust my child's access to vaccines or my elderly parents' access to vaccines to the goodwill of the insurance companies to follow those recommendations instead of ACIP's.' Here's what to know about the CDC's vaccine committee ahead of its two-day meeting this week. ACIP is a group of experts — typically with specialties in pediatrics, infectious diseases, public health or vaccines — who make recommendations to the CDC on the use of vaccines. They tend to come from universities or medical schools. Some have been doctors in private practice. There's also typically a consumer representative on the panel. Despite Kennedy's claims when he removed all 17 previous members of the panel this month, members of the committee are closely scrutinized for conflicts of interest, and any conflicts are publicly disclosed. Members also recuse themselves from a vote if they have a financial interest in its outcome. As of Tuesday evening, HHS had not posted updated ethics statements or conflicts of interest reports for the new incoming members. Although the US Food and Drug Administration decides whether immunizations are allowed to be used in the United States, it's the CDC's job to recommend how those products should be used. It does so based on recommendations from ACIP. After a vote, ACIP recommendations are forwarded to the CDC director for approval. The CDC isn't bound by the committee's recommendation but ordinarily follows it. The HHS secretary has the final signoff. The committee typically meets three times a year to vote on the use of vaccines in the US, and more frequently during emergencies like Covid-19, when they met as often as once a week to pore over data from around the world. These meetings, which are public and typically broadcast, can span two or even three days. Kennedy has accused ACIP of being a 'rubber stamp for industry profit-taking agendas,' but the committee hasn't always recommended the use of vaccines, even when they've already gotten approval from the FDA. After data showed that the FluMist nasal spray vaccine had little to no effectiveness during the 2015-16 flu season, the committee said it shouldn't be used during the next two flu seasons. FluMist was again recommended during the 2018-19 season after data demonstrated better effectiveness. In 2023, the first fall and winter season that the RSV vaccine was available for older adults, ACIP recommended it for adults 60 and older with shared decision-making, meaning it was available only after consultation with a health care provider on its risks and benefits. In 2024, ACIP removed the shared clinical decision-making requirement, making it easier to access. The panel recommended that adults 75 and older get one dose of any available RSV vaccine, while adults 60 to 74 needed one only if they were at higher risk of severe RSV infections. After Kennedy dismissed all 17 ACIP members who were appointed during the Biden administration, he replaced them with eight of his own picks. There can be up to 19 voting members, according to ACIP's charter. Most of the new members have little expertise in infectious diseases or vaccines, and some have served as expert witnesses in vaccine injury cases. One has been associated with a group that exaggerates the rare risks and harms of vaccines while casting doubt on their benefits. Another has done studies purporting to show the harms of the Covid-19 vaccines, reporting conclusions that run counter to most other evidence on the safety and effectiveness of these shots. Independent fact checks of these studies suggest that their conclusions may be based on flawed methods. Aside from voting members, there are two more tiers of membership. There are six 'ex-officio' members from government health agencies such as the Centers for Medicare and Medicaid Services and the FDA. The meeting typically hears from these members about policy questions they can help answer. Ex-officio members don't typically vote, but they can do so if there aren't enough voting members to have a quorum – which is defined by the Federal Advisory Committee Act as a majority, or one more than half. The last tier of membership includes the liaison members: non-voting members from the 30 nonprofits and professional groups that are spelled out in the committee's charter. Liaison members may be added by the HHS secretary. These members often speak up during discussions and after voting has taken place. As of Monday night, many of the liaison members had not been sent a video link to participate in the meeting, Schaffner said, when normally they would have gotten that already. Voting members can serve up to four-year terms. They are considered special government employees and subject to federal conflict of interest safeguards. They aren't paid for their service but are compensated for their travel to and from meetings and for their meals. In addition to regular meetings, members of ACIP convene outside of public meetings in 'work groups' that focus on a specific vaccine or disease of interest. These groups must include at least two voting members but may also consist of liaison and ex-officio members as well as outside experts. They often spend months making deep dives into medical research and present their findings to the voting members of the committee at each meeting. The working groups often look at vaccines that are nearing FDA approval, to be sure they are ready to issue advice shortly after that agency makes the determination that a vaccine is safe and effective. ACIP's recommendations are used in several ways: To guide patient care: ACIP sets what's known as the vaccine schedule, a table that charts out which inoculations should be given by what ages. Many states use these vaccines schedules to set their own policies for school enrollment, for example. To determine insurance coverage: Under the Affordable Care Act, when ACIP recommends a vaccine, it has to be covered by most insurance plans with no co-pays to patients. To determine which vaccines are purchased for the Vaccines for Children (VFC) program: The CDC's Vaccines for Children program bulk purchases vaccines that are then distributed to states, which, in turn, distribute them to doctor's offices. It provides vaccines at no cost to children whose families wouldn't otherwise be able to afford the shots. Roughly half of children in the US get their vaccines through the VFC. To determine coverage by the Vaccine Injury Compensation Program: When ACIP recommends a vaccine for pregnant women and children, it is automatically added to the list of vaccines covered by the Vaccine Injury Compensation Program. As with many medical treatments, the benefits of vaccines come with rare risks. These risks, or adverse events, are maintained on a list by the program, which compensates people who've experienced them and can prove they are linked to a covered vaccine. Because the program shields vaccine manufacturers from lawsuits, it has come under fire from Kennedy, who has said that people should be able to file suit in court for their injuries.
Associated Press
33 minutes ago
- Associated Press
Still top cause of death, the types of heart disease people are dying from is changing
Published [hour]:[minute] [AMPM] [timezone], [monthFull] [day], [year] Research Highlights: Over the past 50 years, overall heart disease death rates have dropped by 66% and deaths from heart attacks have declined by nearly 90%. The types of heart disease people are dying from most often have shifted from heart attacks to an increase in deaths from heart failure, arrhythmias and hypertensive heart disease. Researchers say this shift, in part, is the result of advances in public health measures focused on prevention and life-saving interventions to improve early diagnosis and treatment, allowing people to live longer while managing chronic heart conditions Embargoed until 4 a.m. CT/5 a.m. ET Wednesday, June 25, 2025 ( NewMediaWire ) - June 25, 2025 - DALLAS — While heart disease has been the leading cause of death in the U.S. for over a century, the past 50 years have seen a substantial decrease (66%) in overall age-adjusted heart disease death rates, including a nearly 90% drop in heart attack deaths, according to new research published today in the Journal of the American Heart Association , an open access, peer-reviewed journal of the American Heart Association. During that time, there have been major shifts in the types of heart disease people are dying from, with large increases in deaths from heart failure , arrhythmias and hypertensive heart disease . In an analysis of data from the U.S. Centers for Disease Control and Prevention, researchers reviewed the age-adjusted rates of heart disease deaths among adults ages 25 and older from 1970 to 2022. The analysis found: Over this 52-year period, heart disease accounted for nearly one-third of all deaths (31%). During this time, heart disease death rates decreased substantially, from 41% of total deaths in 1970 to 24% of total deaths in 2022. In 1970, more than half of all people who died from heart disease (54%) died because of a heart attack – a type of acute ischemic heart disease. The age-adjusted death rate decreased 89% by 2022, when less than one-third of all heart disease deaths (29%) were caused by a heart attack. Conversely, during this time, the age-adjusted death rate from all other types of heart disease (including heart failure, hypertensive heart disease and arrhythmia) increased by 81%, accounting for 9% of all heart disease deaths in 1970 and 47% of all heart disease deaths in 2022. 'This distribution shift in the types of heart disease people were dying from the most was very interesting to us,' said the study's first author, Sara King, M.D., a second-year internal medicine resident in the department of medicine at Stanford School of Medicine in Stanford, California. 'This evolution over the past 50 years reflects incredible successes in the way heart attacks and other types of ischemic heart disease are managed. However, the substantial increase in deaths from other types of heart conditions, including heart failure and arrhythmias, poses emerging challenges the medical community must address.' During the decades reviewed: Deaths from arrhythmias had the largest relative increase, with the age-adjusted death rate rising by 450%. However, arrhythmias still accounted for only about 4% of all heart disease deaths in 2022. Arrhythmias occur when electrical impulses to the heart may be too fast, too slow or erratic, causing an irregular heartbeat. Atrial fibrillation is one of the most common types of arrhythmias. The age-adjusted death rate from heart failure — a chronic condition where the heart is unable to pump enough blood to meet the body's needs for blood and oxygen — increased 146%. The rate of deaths from hypertensive heart disease — heart problems that occur because of high blood pressure that is present over a long time — increased by 106%. In addition to analyzing the types of heart disease deaths, the researchers also identified several underlying factors that may account for the shift in deaths from ischemic heart disease to other heart conditions. 'Over the past 50 years, our understanding of heart disease, what causes it and how we treat it has evolved considerably. That's especially true in how we address acute cardiac events that may appear to come on suddenly,' King said. 'From the establishment and increased use of bystander CPR and automated external defibrillators to treat cardiac arrest outside the hospital setting, to the creation of systems of care that promote early recognition of and quick procedural and medical intervention to treat heart attacks, there have been great strides made in helping people survive initial acute cardiac events that were once considered a death sentence.' Other specific advancements noted in the study included: The invention in the 1960s of coronary artery bypass grafting and the formation of coronary care units improved in-hospital and long-term heart disease death rates. Cardiac imaging improved in the 1970s with coronary angiography, which was capitalized by the advent of balloon angioplasty in 1977, followed by coronary stenting to open blocked heart arteries in the 1980s to 1990s. Simultaneously, there was significant development of medical therapies in the 1970s to 1990s, including thrombolytics and aspirin to reduce blockages; beta blockers to treat high blood pressure; renal-angiotensin-aldosterone system inhibitors to slow the progression of heart and kidney disease; and statins to control cholesterol. These advances all contributed to the decline in deaths from treatment and deaths due to a second or subsequent acute cardiac event. At the turn of the 21st century, high-intensity statin therapy to lower cholesterol and dual antiplatelet therapy to reduce clotting were established, as well as landmark 'door-to-balloon' trials that displayed substantial benefits when care to open blocked arteries was expedited. From 2009 to 2022, high-sensitivity troponins that improved the rapid diagnosis of heart attacks and advanced antiplatelet agents to reduce clotting and restore blood flow to the heart further improved death rates, while lipid-lowering therapies such as ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors emerged to improve options for secondary prevention. In addition to medical advances, significant public health strides, such as smoke-free policies, increased emphasis on physical activity and updated practice guidelines that support improved blood pressure and cholesterol management, have driven much of the improvements, according to the report. Study researchers point out that, despite overall reduction in heart disease and the progress in therapies and guidelines, there has been a substantial rise in many CVD risk factors, such as obesity, Type 2 diabetes, hypertension and physical inactivity, in the United States. An aging population is also contributing to an increase in the types of heart disease people are dying from. The report found: From the 1970s to 2022, obesity prevalence has risen from 15% to 40%. Type 2 diabetes including prediabetes, has risen to impact nearly half of all adults in the U.S. in 2020. Hypertension has increased from a prevalence of approximately 30% in 1978 to nearly 50% in 2022. Demographic shifts in the U.S. have also contributed significant changes to the landscape of heart disease mortality. From 1970 to 2022, there has been a notable increase in life expectancy, from 70.9 years to 77.5 years. 'All of these risk factors contribute to an ongoing burden of heart disease, especially as related to heart failure, hypertensive heart disease and arrhythmias,' said senior author of the paper Latha Palaniappan, M.D., M.S., FAHA, associate dean for research and a professor of medicine at Stanford University School of Medicine. 'While heart attack deaths are down by 90% since 1970, heart disease hasn't gone away. Now that people are surviving heart attacks, we are seeing a rise in other forms of heart disease like heart failure. The focus now must be on helping people age with strong, healthy hearts by preventing events, and prevention can start as early as childhood.' 'The American Heart Association has been a leader in both the medical advancements and the policy and guideline initiatives that have contributed to the reduction in overall heart disease deaths,' said Keith Churchwell, M.D., FAHA, the 2024-2025 American Heart Association volunteer president, an associate clinical professor of medicine at Yale School of Medicine in New Haven, Connecticut and an adjunct associate professor of Medicine at the Vanderbilt School of Medicine in Nashville, Tennessee. 'Through the nearly $6 billion dollars the Association has invested in scientific research since 1948, we have enhanced the knowledge of how we diagnose and treat heart disease in almost all forms. We have been a catalyst in collaborations with the public and private sectors in support of public health policies to improve the communities in which people live, work, learn and play. And we know, that by following the prescription of our Life's Essential 8(TM) health measures, we can prevent most heart disease and reduce deaths from heart disease by reducing the health risk factors that contribute to it.' The American Heart Association's Life's Essential 8 is a measure of cardiovascular health that includes eight essential components for ideal heart and brain health – 4 health behaviors and 4 health factors, including: Eat better. Be more active. Quit tobacco. Get healthy sleep. Manage weight. Control cholesterol. Manage blood sugar. Manage blood pressure. 'We've won major battles against heart attacks, however, the war against heart disease isn't over. We now need to tackle heart failure and other chronic conditions that affect people as they age,' King said. 'The cardiology community must prepare to meet this evolving burden through prevention, longitudinal management and multidisciplinary care that supports healthy aging. The next frontier in heart health must focus on preventing heart attacks, and also on helping people age with healthier hearts and avoiding chronic heart conditions later in life.' The authors note several limitations to this study: There is likely substantial differences in these reductions in heart disease deaths by age, sex, race, ethnicity, region and urbanization. The study did not analyze data including these components, and research including these factors should be prioritized in future studies to confirm if these overall trends remain valid in subpopulations. The use of multiple iterations of the International Classification of Diseases (ICD) coding system may allow for potential miscoding and presents challenges in maintaining consistency in comparisons across the years. Particularly prominent is the change from ICD-8 to ICD-9 in the year 1979, where the mortality of several conditions (valvular heart disease, hypertensive heart disease, pulmonary heart disease) dramatically increased. The true burden of ischemic heart disease may be underestimated in the findings presented in this study, since certain conditions including heart failure, cardiomyopathy, arrhythmias and in particular ventricular arrhythmias and cardiac arrest, may be overly simplistic. Many of these cases likely have underlying causes that cannot be precisely differentiated using current or past ICD codes. Co-authors, disclosures and funding sources are listed in the manuscript. Studies published in the American Heart Association's scientific journals are peer-reviewed. The statements and conclusions in each manuscript are solely those of the study authors and do not necessarily reflect the Association's policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. The Association receives more than 85% of its revenue from sources other than corporations. These sources include contributions from individuals, foundations and estates, as well as investment earnings and revenue from the sale of our educational materials. Corporations (including pharmaceutical, device manufacturers and other companies) also make donations to the Association. The Association has strict policies to prevent any donations from influencing its science content. Overall financial information is available here . Additional Resources: ### About the American Heart Association The American Heart Association is a relentless force for a world of longer, healthier lives. Dedicated to ensuring equitable health in all communities, the organization has been a leading source of health information for more than one hundred years. Supported by more than 35 million volunteers globally, we fund groundbreaking research, advocate for the public's health, and provide critical resources to save and improve lives affected by cardiovascular disease and stroke. By driving breakthroughs and implementing proven solutions in science, policy, and care, we work tirelessly to advance health and transform lives every day. Connect with us on , Facebook , X or by calling 1-800-AHA-USA1. For Media Inquiries and AHA/ASA Expert Perspective: 214-706-1173 Cathy Lewis: [email protected] For Public Inquiries: 1-800-AHA-USA1 (242-8721) and
CNN
35 minutes ago
- CNN
On the brink of retirement, this NFL player turned to psychedelics to help with his OCD
While NFL players were in the trenches of a grueling season, Braden Smith was fighting a different battle: the one going on inside his own mind. In the middle of what was meant to be a playoff-contending season for the Indianapolis Colts, Smith instead was consumed with thoughts about his faith. What started out as the formative steps in his religious journey quickly became an all-encompassing struggle. But he wasn't just coming to terms with his faith; he was also learning about his obsessive-compulsive disorder (OCD). In particular, Smith was dealing with religious scrupulosity – a subtype of OCD where individuals become 'overly concerned that something they thought or did might be a sin or other violation of religious or moral doctrine,' as described by the International OCD Foundation. As he dove into learning everything he could about his faith, Smith found difficulties equating his own past and daily actions with what he was reading in the scripture. 'I was having a court case in my mind all the time – pleading myself to the jury – because my mind all the time would be like: 'You know, God can hear your thoughts,'' Smith told CNN Sports. This came to a head last season when it all became too much. The OCD had taken the joy out of football for Smith, so much so that he was suffering 'mental breakdowns' before games and becoming distracted on the field. He told his wife Courtney that he was going to retire as a result of his OCD. Discussions with Courtney led Smith to check himself into a medical facility for treatment, where he spent 48 days and was formerly diagnosed with OCD. After limited improvement, Smith was told brain surgery was an option, but he instead opted to try psychedelic drugs – ibogaine and 5-MeO-DMT – for relief. Ibogaine and 5-MeO-DMT are banned substances in the US – but not on the NFL's prohibited substances list – so Smith traveled to Mexico to have them administered. Together with the drugs and therapy, Smith turned a corner and having returned to the US, plans to continue his football career, despite being unable to continue using the psychedelics at home. And while the 29-year-old said he's in a much better place than a year ago, he's still on an 'ongoing journey' with his OCD and religious scrupulosity. 'I'm still dealing with OCD, still have obstacles to conquer each and every day,' he said. 'It's part of my life. I can't run or hide from it. And I can't fight it either, per se, because the more that I fight, the more that I play into its hand and I just having to accept it for what it is. 'The OCD always wants you to do more and more and more. That's something that's been preached my whole life is doing more. But at this point, I almost have to do less. I have to rest more in it. I have to rest in that love and that grace vs. trying to do more, trying to fight my OCD.' In hindsight, Smith said he's long had OCD tendencies. He remembers eating 36 chewy sweets in one sitting as a child because no matter the number he got to, it wasn't the right number. Unsurprisingly, he was sick as a result. He also recalls having to wash his hands a certain number of times and worrying a curse would be put on him if he was to anger anyone. And his obsessions went to another level when he began his journey into his faith in earnest last year. Previously, Smith describes not 'living' his faith 'all the way,' taking it in 'bits and pieces.' In 2024, though, his life began to revolve around it. In his mind, his OCD took that journey 'in the most literal sense.' 'Especially when you hear a verse like: 'Loving God with your all your heart, mind, body and soul,' I took that literally,' Smith explained. 'Every thought I have has to be perfect and in order to do the things the right way, my mind was telling me all the things that I needed to avoid. And so, naturally, it starts off as a single thought, and then it starts multiplying all these bad thoughts you're not supposed to have.' Smith remembers it starting with an initial feeling of guilt about his previous sins and what his mind deemed to be sinful thoughts. His brain twisted his faith into thinking he was a 'devil worshipper' and he was selling his soul in his quest for perfection. As he explored his own journey into religion, he found a fixation with conducting himself the way literally written in scripture. That, he now understands, is 'impossible' for a regular person. Striving for perfection only exacerbated the sense of guilt. 'I've messed up the first 28 years of my life. Now, I need 28 more years to make up for the last 28 so I can be even with God,' Smith remembers thinking. While it started with a few obsessions, the tidal wave of thoughts grew over time. Smith resorted to compulsive prayer and attempting to reason with the obsessions as a way of bringing about a respite to his struggles. But no matter how many times he would reason with himself – and, in doing so, God – it would come back even stronger. 'You can quiet it. You can silence it. But last year was that time that voice was the predominant voice,' he said. 'It was screaming. I was in the corner, couldn't get a word out because every time I got a word out, my OCD would just scream and put a million different things in your face all the time.' While Smith was going through this journey, it was having a detrimental effect on his personal and professional life. In March 2024 – two months after his son was born – his wife Courtney remembers noticing Smith was diving head-first into his faith. She recalls Smith doing Bible studies at their kitchen table and reading the book over and over. It was only when she noticed her husband 'couldn't get past his past' that she realized something was up. She describes noting it was 'more extreme' than what she had previously experienced. They remember 'Blasphemy against the Holy Spirit' – also known as the unforgivable sin – as a particular stumbling block for Smith due to the unspecified nature of the sin. Smith wasn't able to listen in conversations with his wife about the role of faith filling in the gaps in Christian scripture, at times even questioning her faith. And then one day, Courtney recalls Smith coming home day and saying he has scrupulosity. At first, Courtney thought he was 'being dramatic' because, as she says, she herself had variations of the thoughts he was expressing during her own journey with faith. But with hindsight, she says she didn't understand the intensity of Smith's struggles. His OCD snowballed during the 2024 NFL season with the Colts. Smith said he had 'no desire to play' football at that point because his mind was telling him: 'Why are you doing this? Would God want you doing this? What purpose does this serve? How does this serve others? You're playing a violent game.' The battle his mind was going through was taking away his joy for a game he'd played for years. His brain was telling him that there was no light at the end of the tunnel and that 'nothing good is going to happen so why waste your time on your family, on your profession?' The hours leading up to a game would bring about feelings of panic for Smith, knowing he'd be away from his family and that doing his compulsions would be harder. He remembers one particular game where he had a 'mental breakdown' in the hours proceeding it and had to be consoled in the locker room. Although he managed to play later that day, he talked to Courtney afterwards and questioned whether continuing his career was the right decision. Even in the midst of games, Smith would be battling his own mind. He remembers his OCD popping up during a two-minute drive in the fourth quarter of a game, saying: 'You can win the game, but you need to sell your soul to the devil.' The inner battle between Smith and his OCD would reverberate around his head all while an NFL contest went on around him. Smith's struggles got to a point where he told Courtney he was going to retire, an announcement which shocked her because of Smith's love of the game. As it so happens, Smith talked to one of his teammates who also had scrupulosity, which offered some reassurance that this was an issue they could treat. 'I didn't feel hopeless,' Courtney told CNN Sports. The Colts permitted Smith to miss the final five games of the 2025 season to allow him to get better; the offensive lineman thanks the franchise for paying the majority of his contract during that time when they had no obligation to do so as he was on the Non-Football Injury/Illness list. The Smith's made the decision for Smith to go to a facility for treatment. During his 48 days there, Smith described getting marginally better in the short-term but not enough to return to his normal life. This lack of positive progress rang alarm bells with Courtney who, after talking to a therapist Smith had been working with, said that brain surgery would be the next option. Courtney was adamant that surgery would not happen. Instead, they decided Smith would travel to Mexico for treatment and, in particular, to see if the use of ibogaine and 5-MeO-DMT would help. He emphasized the importance of trying the psychedelic drug in a controlled environment among a group of people on their own journeys with therapeutic treatments surrounded by medical professionals. The ibogaine and 5-MeO-DMT – they are used in a five day treatment, first the ibogaine and, after a one day break, then the 5-MeO-DMT – and learning about the skill of mindfulness helped provide a breakthrough for Smith. 'It opened doors into my mind,' he explained. 'It's that greater self-awareness and seeing the OCD for what it is,' he said. 'It is OCD. These are obsessions. These fears, they're not real. 'And it takes some time to rewire my brain that way and the ibogaine gave me that blank slate to be able to actually do that, whereas I wasn't able to do that before because my mind was so rigid.' Last year, a study of 30 military veterans with a history of traumatic brain injury (TBI) found depression, anxiety and post-traumatic stress disorder symptoms improved immediately after treatment with ibogaine. The study, published in Nature Medicine, said they were treated in Mexico and none experienced adverse events. The state of Texas recently approved $50 million to study ibogaine. Research into ibogaine has shown promising results but remains limited. There are potential risks to using the psychedelic, including risks of serious cardiac effects, and side effects such as nausea and tremors. Since opening up about his journey and use of psychedelics as treatment, Smith has received plenty of positive feedback from others in similar situations looking for a beacon of hope. The Colts offensive tackle stresses that he can't heal anyone specifically, but does appreciate that his story can help people if they're struggling for solutions like he was. Smith, a 2018 second-round draft pick, has returned to the field in preparation of the new season, having agreed to a restructuring of his contract in March. His past 18 months have seen growth, reckoning and realization. His journey is not complete, he said, but he is in a much stronger position to be able to cope with the challenges thrown his way and continue his faith journey. And for those who might be in a similar position, Smith stresses the importance of speaking to loved ones, no matter the 'vulnerability' that comes with opening up. 'All these things I've gone through in my head, it's very uncomfortable. And the thing I always worried about was like: 'What if someone confirms my fears for me? Or I get the wrong response?'' Smith told CNN Sports. 'It's not something you want to talk to just anyone about. Go to a loved one you trust and open up about it and they probably have more clarity than you at the time and maybe they'll be able to see it for what it is. 'In my case, my wife was the one that was getting me the help. I was ashamed to get help. I was ashamed to open up. I was going crazy. My head wasn't in a good space. So I think really leaning on a loved one was really helpful. It does seem taboo but at the same time, if you don't talk about, you don't get anything out of it and nothing can happen.'
