Modifying Naturally Occurring, Nonmammalian-Sourced Biopolymers for Biomedical Applications.

Natural biopolymers have a rich history, with many uses across the fields of healthcare and medicine, including formulations for wound dressings, surgical implants, tissue culture substrates, and drug delivery vehicles. Yet, synthetic-based materials have been more successful in translation due to precise control and regulation achievable during manufacturing. However, there is a renewed interest in natural biopolymers, which offer a diverse landscape of architecture, sustainable sourcing, functional groups, and properties that synthetic counterparts cannot fully replicate as processing and sourcing of these materials has improved. Proteins and polysaccharides derived from various sources (crustaceans, plants, insects, etc.) are highlighted in this review. We discuss the common types of polysaccharide and protein biopolymers used in healthcare and medicine, highlighting methods and strategies to alter structures and intra- and interchain interactions to engineer specific functions, products, or materials. We focus on biopolymers obtained from natural, nonmammalian sources, including silk fibroins, alginates, chitosans, chitins, mucins, keratins, and resilins, while discussing strategies to improve upon their innate properties and sourcing standardization to expand their clinical uses and relevance. Emphasis will be placed on methods that preserve the structural integrity and native biological functions of the biopolymers and their makers. We will conclude by discussing the untapped potential of new technologies to manipulate native biopolymers while controlling their secondary and tertiary structures, offering a perspective on advancing biopolymer utility in novel applications within biomedical engineering, advanced manufacturing, and tissue engineering.

Ultrasound innovations in abdominal radiology: multiparametic imaging in liver transplantation.

PURPOSE: Ultrasound plays a central role in liver transplant evaluation. Acute, subacute, and chronic complications can be readily identified using grayscale and color Doppler ultrasound. Contrast-enhanced ultrasound adds a new dimension to liver transplant evaluation, depicting vascular and parenchymal processes with exquisite detail. In addition, emerging evidence suggests that contrast-enhanced ultrasound may allow for localization of biliary leak in select patients. We aimed to assess the use of multiparametric ultrasound-including grayscale, color and spectral Doppler, and contrast-enhanced ultrasound-in the setting of liver transplantation. METHODS: A literature review was performed using the MEDLINE bibliographic database through the National Library of Medicine. The following terms were searched and relevant citations assessed: "abdominal ultrasound," "contrast-enhanced ultrasound," "liver transplant," and "ultrasound." RESULTS: Grayscale and color Doppler ultrasound represent the mainstay imaging modalities for postoperative liver transplant evaluation. The addition of contrast enhancement plays a complementary role and can provide valuable information related to the allograft vasculature, parenchyma, and biliary tree. The appropriate implementation of grayscale, color Doppler, and contrast-enhanced ultrasound can optimize sensitivity, specificity, and accuracy for the detection of liver transplantation complications, including hepatic artery stenosis, biliary leakage, and infection. CONCLUSION: Multimodal sonographic evaluation is essential to identify postoperative complications in liver transplant recipients. Contrast-enhanced ultrasound may be of value in challenging cases, providing excellent anatomic delineation and reducing the risk of false-positive and false-negative diagnoses. A broad familiarity with appropriate applications of both nonenhanced and contrast-enhanced ultrasound may help radiologists optimize allograft assessment and improve patient outcomes.

Group cohesion and alliance predict cognitive-behavioral group treatment outcomes for youth with anxiety disorders.

Knowledge about how to enhance group cognitive behavioral therapy (GCBT) outcomes is needed. In a randomized controlled effectiveness trial, we examined group cohesion (the bond between group members) and the alliance (the client-clinician bond) as predictors of GCBT outcomes. The sample was 88 youth (M age 11.7 years, SD = 2.1; 54.5% girls; 90.7% White) with anxiety disorders. Observers rated group cohesion and alliance in 32 sessions from 16 groups. We examined early group cohesion and alliance (r = .50, p < .001) and group cohesion and alliance change from early to late in treatment in relation to outcomes using generalized estimation equations accounting for nesting within groups (ICCs .31 to .55). The outcomes were diagnostic recovery, clinical severity, and parent- and youth-reported anxiety symptoms, each at post-treatment, 12-months, and 4-years follow-up. There were more significant associations with 4-years follow-up than earlier outcomes. Clinical severity and parent-reported anxiety symptoms were more frequently predicted than diagnostic recovery. Clinician- and parent-reported outcomes were far more frequently significantly predicted by cohesion and alliance than youth-rated outcomes. We conclude that group cohesion and alliance are related but distinct variables, both associated with some GCBT outcomes for as long as 4 years after treatment.

A Single Bout of On-Ice Training Leads to Increased Interlimb Asymmetry in Competitive Youth Hockey Athletes.

Interlimb asymmetry (ILA) refers to an anatomical or physiological imbalance between contralateral limbs, which can influence neuromuscular function. Investigating the influence of neuromuscular fatigue on ILA may be critical for optimizing training programs, injury rehabilitation, and sport-specific performance. The purpose of this study was to determine if a single bout of ice hockey-specific exercise creates or exacerbates lower-limb ILA. Before and after an on-ice training session, 33 youth ice-hockey athletes (14.9 [1.7] y; 11 females) performed 3 repetitions of a maximal vertical countermovement jump (CMJ), an eccentric hamstring contraction, and maximal isometric hip adduction and abduction contractions. Force- and power-related variables were analyzed to determine limb-specific neuromuscular function. The on-ice session reduced maximal isometric hip adduction (left: 7.3% [10.3%]; right: 9.5% [9.6%]) and abduction (left: 4.9% [6.9%]; right: 5.0% [8.1%]) force, but did not impair (P ≥ .10) CMJ performance (jump height, relative peak power, braking duration, and total duration). After the on-ice session, ILA was greater for CMJ propulsive impulse (6.3% [2.9%] vs 5.1% [2.6%]), CMJ braking rate of force development (19.3% [7.6%] vs 15.2% [6.4%]), and peak isometric hip adduction force (6.7% [5.5%] vs 6.1% [4.1%]). In conclusion, hockey-specific exercise leads to increased ILA for multiple force-related metrics, which may be a compensatory mechanism to maintain bilateral task performance when fatigued.

Intracranial meningioma: A review of recent and emerging data on the utility of preoperative imaging for management.

Meningiomas are the most common neoplasms of the central nervous system, accounting for approximately 40% of all brain tumors. Surgical resection represents the mainstay of management for symptomatic lesions. Preoperative planning is largely informed by neuroimaging, which allows for evaluation of anatomy, degree of parenchymal invasion, and extent of peritumoral edema. Recent advances in imaging technology have expanded the purview of neuroradiologists, who play an increasingly important role in meningioma diagnosis and management. Tumor vascularity can now be determined using arterial spin labeling and dynamic susceptibility contrast-enhanced sequences, allowing the neurosurgeon or neurointerventionalist to assess patient candidacy for preoperative embolization. Meningioma consistency can be inferred based on signal intensity; emerging machine learning technologies may soon allow radiologists to predict consistency long before the patient enters the operating room. Perfusion imaging coupled with magnetic resonance spectroscopy can be used to distinguish meningiomas from malignant meningioma mimics. In this comprehensive review, we describe key features of meningiomas that can be established through neuroimaging, including size, location, vascularity, consistency, and, in some cases, histologic grade. We also summarize the role of advanced imaging techniques, including magnetic resonance perfusion and spectroscopy, for the preoperative evaluation of meningiomas. In addition, we describe the potential impact of emerging technologies, such as artificial intelligence and machine learning, on meningioma diagnosis and management. A strong foundation of knowledge in the latest meningioma imaging techniques will allow the neuroradiologist to help optimize preoperative planning and improve patient outcomes.

Shared Decision-Making with Latinx Caregivers During Community Implemented Evidence-Based Practices: Determinants and Associations with Alliance.

OBJECTIVE: The current observational study examined shared decision-making (SDM) with caregivers of Latinx youth within the delivery of multiple evidence-based practices (EBPs) in community mental health services. The aims of the study were to (1) Identify therapist and client factors associated with increased SDM within EBP sessions and (2) Examine the association between SDM and therapeutic alliance between community therapists and Latinx caregivers. METHOD: The Observing Patient Involvement in Decision-Making (OPTION) instrument measured SDM in 210 audio-recorded therapy sessions with 62 community therapists (91.94% female; 69.35% Latinx) and 109 Latinx caregivers (91.43% female) of youth who were an average age of 8.26 years (SD = 3.59). We used the Therapy Process Observational Coding System for Child Psychotherapy-Alliance scale to measure the caregiver-therapist alliance observationally. Multilevel linear regressions were conducted to examine research questions. RESULTS: Greater SDM was observed within sessions where therapists targeted conduct problems versus trauma (B = -8.79, 95% CI[-14.09, -3.49], p = .001). There was a trend that SDM was higher in English-language sessions compared to Spanish. We found that the global measurement of SDM (B = .04, 95% CI[.01, .08], p = .03) and the OPTION item Integrate Preferences (B = .69, 95% CI[.07, 1.32], p = .03) were positively associated with alliance. CONCLUSIONS: SDM may help foster Latinx caregiver engagement within EBP delivery. Provider training in SDM may be warranted with consideration of the specific clinical contexts (e.g., by presenting problem) that are appropriate for collaborative treatment planning. More research is needed to further establish the benefits of SDM in youth psychotherapy.

Utility of Thrombectomy in Nonagenarians: A Scoping Review.

BACKGROUND: Mechanical thrombectomy represents a mainstay of management for acute ischemic stroke in the setting of large vessel occlusion. However, there are no clinical practice guidelines defining the role of thrombectomy at the extremes of age. In this scoping review, we aimed to summarize the existing medical and neurosurgical literature pertaining to mechanical thrombectomy in nonagenarians. The PubMed database was queried using the following terms and relevant citations assessed: "thrombectomy nonagenarian," "thrombectomy age 90," "stroke nonagenarian," and "ischemic stroke thrombectomy." Common measurable outcomes, including mortality, modified Rankin scale (mRS) score, and thrombolysis in cerebral infarction (TICI) scale score, were utilized to compare results. SUMMARY: Thrombectomy was shown to improve functional outcomes in all eight of the studies included in the analysis. Mortality was assessed in only two reported studies, and thrombectomy was shown to provide a mortality benefit in 1 study among patients for whom first-pass reperfusion was achieved. Other outcomes of reported interest included greater early neurologic recovery at discharge and improved functional outcomes at 90 days among nonagenarians who underwent thrombectomy as compared to those who received thrombolytic therapy alone. Nonagenarians with good functional status at baseline were the most likely to have favorable outcomes. KEY MESSAGES: Mechanical thrombectomy improves outcomes among nonagenarians presenting with acute ischemic stroke due to large vessel occlusion. Further large-scale prospective studies are warranted to optimize patient selection and develop clinical practice guidelines specific to this important patient demographic.

Intra-decadal increase in globally-spread Magallana gigas in southern California estuaries.

Introduction and establishment of non-indigenous species (NIS) has been accelerated on a global scale by climate change. NIS Magallana gigas' (formerly Crassostrea gigas') global spread over the past several decades has been linked to warming waters, specifically during summer months, raising the specter of more spread due to predicted warming. We tracked changes in density and size distribution of M. gigas in two southern California, USA bays over the decade spanning 2010-2020 using randomly placed quadrats across multiple intertidal habitats (e.g., cobble, seawalls, riprap) and documented density increases by 2.2 to 32.8 times at 7 of the 8 sites surveyed across the two bays. These increases in density were coincident with 2-4° C increases in median monthly seawater temperature during summer months, consistent with global spread of M. gigas elsewhere. Size frequency distribution data, with all size classes represented across sites, suggest now-regular recruitment of M. gigas. Our data provide a baseline against which to compare future changes in density and abundance of a globally-spread NIS of significant concern.

Contrast-enhanced ultrasound (CEUS) for the characterization of intra-scrotal lesions.

Contrast-enhanced ultrasound (CEUS) has emerged as a promising imaging modality for the characterization of hepatic and renal lesions. However, there is a paucity of data describing the use of CEUS for the evaluation of intra-scrotal pathology. In the following review, we describe the clinical utility of CEUS for the characterization and differentiation of common and uncommon intra-scrotal conditions, including testicular torsion, infection, trauma, and benign and malignant intratesticular and extratesticular neoplasms. In addition, we outline key principles of CEUS and provide case examples from our institution.

The Content of Usual Clinical Care for Youth with Primary Anxiety Problems.

The current study was designed to describe usual clinical care for youth with primary anxiety problems in community mental health centers. The observer-rated Therapy Process Observational Coding System for Child Psychotherapy - Revised Strategies scale (TPOCS-RS), designed to assess therapeutic techniques from five theory-based domains, was used to code sessions (N = 403) from the usual clinical care group of two randomized effectiveness trials: (a) Youth Anxiety Study (YAS) with 21 youth (M age = 10.44 years, SD = 1.91; 49.2% Latinx; 46.6%, 53.4% male) and 16 clinicians (77.5% female; 43.8% White), and (b) Child STEPS Multisite Trial with 17 youth (M age = 10.00 years, SD = 1.87; 58.8% male; 41.2% White) and 13 clinicians (M age = 40.00 years; SD = 9.18; 76.9% female; 61.5% White). The average number of TPOCS-RS items observed per treatment session was more than 10, and multiple techniques were used together in each session. All TPOCS-RS items were observed at least once throughout a clinical case, and most items reoccurred (i.e., observed in two or more sessions). The dosage of TPOCS-RS in all items was below 5 on a 7-point scale. In conclusion, clinicians in both usual care samples used a wide range of techniques from several theory-based domains at a low to medium dose. However, the type and dosage of the techniques used did vary across the two samples.

Sociodemographic Disparities in Sodium-Glucose Co-Transporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists Prescription Patterns Among Patients With Poorly Controlled Diabetes.

Introduction Sodium-glucose co-transporter-2 inhibitors (SGLT2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are novel antihyperglycemic agents that reduce cardiovascular mortality through insulin-independent mechanisms. In this cross-sectional study, we investigated prescription patterns of these drugs and identified inequities in antihyperglycemic utilization. Methods Unique encounters for diabetes care between January 1, 2020, and December 31, 2020, were identified through a systematic query of our healthcare system's database. All patients ≥18 years old with a hemoglobin A1C level of ≥8% were included in the sample. Demographic data, SGLT2I or GLP-1RA prescription status, diabetes-related complications, and mortality were abstracted. Results A total of 2,746 patients were included in the sample. Among these individuals, 670 (24.4%) were prescribed either an SGLT2I or a GLP-1RA (users) and 2,076 (75.6%) were not prescribed either agent (non-users). There were significantly more males than females in the cohort, but there was no significant difference in the sex distribution between users and non-users. Compared to non-users, users were younger (mean age of 65.1 ± 9.4 years versus 66.4 ± 9.9 years, p-value = 0.005), more likely to be non-Hispanic (86.3% versus 13.7%), more likely to live in a middle-income zip code, and have private insurance. The mortality rate was lower among users when compared to non-users, but the difference did not reach statistical significance (2.7% versus 5.5%, p-value = 0.62). SGLT2I use was associated with a 60% lower risk of mortality. Conclusion Ethnicity, median household income, and insurance type influence the likelihood of being prescribed an SGLT2I or a GLP-1RA. Individuals prescribed either agent appear to have better mortality outcomes than those prescribed other medications. Further investigation may reveal underlying causes and potential solutions for disparities in prescription patterns.

Using Adherence and Competence Measures Based on Practice Elements to Evaluate Treatment Fidelity for Two CBT Programs for Youth Anxiety.

Measures designed to assess the quantity and quality of practices found across treatment programs for specific youth emotional or behavioral problems may be a good fit for evaluating treatment fidelity in effectiveness and implementation research. Treatment fidelity measures must demonstrate certain reliability and validity characteristics to realize this potential. This study examines the extent to which two observational measures, the Cognitive-Behavioral Treatment for Anxiety in Youth Adherence Scale (CBAY-A) and the CBAY Competence Scale (CBAY-C), can assess the quantity (the degree to which prescribed therapeutic techniques are delivered as intended) or quality (the competence with which prescribed techniques are delivered) of practices found in two distinct treatment programs for youth anxiety. Treatment sessions (N = 796) from 55 youth participants (M age = 9.89 years, SD = 1.71; 46% female; 55% White) with primary anxiety problems who participated in an effectiveness study were independently coded by raters who coded quantity, quality, and the youth-clinician alliance. Youth received one of three treatments: (a) standard (i.e., cognitive-behavioral therapy program), (b) modular (i.e., a cognitive-behavioral and parent-training program), and (c) usual clinical care. Interrater reliability for the CBAY-A items was good across the standard and modular conditions but mixed for the CBAY-C items. Across the standard and modular conditions, the CBAY-A Model subscale scores demonstrated evidence of construct validity, but the CBAY-C Model subscale scores showed mixed evidence. The results provide preliminary evidence that the CBAY-A can be used across different treatment programs but raise concerns about the generalizability of the CBAY-C.

Survival trends for left and right sided colon cancer using population-based SEER database: A forty-five-year analysis from 1975 to 2019.

BACKGROUND: Survival differences between left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC) has been previously reported with mixed results, with various study periods not accounting for other causes of mortality. PURPOSE: We sought to assess the trends in colon cancer cause- specific survival (CSS) and overall survival (OS) based on sidedness. METHOD: Fine-Gray competing risk and Cox models were used to analyze Surveillance, Epidemiology, and End Results (SEER) population-based cohort from 1975 to 2019. Various interval periods were identified based on the timeline of clinical adoption of modern chemotherapy (1975-1989, interval period A; 1990-2004, B; and 2005-2019, C). RESULTS: Of the 227,637 patients, 50.1% were female and 46.2% were RSCC. RSCC was more common for African Americans (51.5%), older patients (age ≥65; 51.4%), females (50.4%), while LSCC was more common among Whites (53.1%; p < 0.001), younger patients (age 18-49, 64.6%; 50-64, 62.3%; p < 0.001), males (58.1%; p < 0.001). The Median CSS for LSCC and RCC were 19.3 and 16.7 years respectively for interval period A (1975-1989). Median CSS for interval periods B and C were not reached (more than half of the cohort was still living at the end of the follow-up period). Adjusted CSS was superior for LSCC versus RSCC for the most recent interval period C (HR 0.89; 0.86-0.92; p < 0.001). LSCC consistently showed superior OS for all study periods. Stage stratification showed worse CSS for localized and regional LSCC in the earlier study periods, but the risk attenuated over time. However, left sided distant disease had superior CSS per stage for all interval periods. OS was better for LSCC irrespective of stage, with gradual improvement over time. CONCLUSION: LSCC was associated with superior survival compared to right sided tumors. With the adoption of modern chemotherapy regimens, prognosis between LSCC and RSCC became more divergent in favor of LSCC. Colon cancer clinical trials should strongly consider tumor sidedness as an enrollment factor.

Harvesting Silk Fibers from Plodia interpunctella: Role of Environmental Rearing Conditions in Fiber Production and Properties.

Silk fibers are produced by a wide variety of insects. The silkworm Bombyx mori (Bombyx) was domesticated because the physical properties of its silk fibers were amenable to the production of fine textiles. Subsequently, engineers have regenerated silk fibroin to form biomaterials. The monocular focus on Bombyx silk has underutilized the expanse of diverse silk proteins produced by more than 100,000 other arthropods. This vast array of silk fibers could be utilized for biomedical engineering challenges if sufficient rearing and purification processes are developed. Herein, we show that the moth, Plodia interpunctella (Plodia), represents an alternative silk source that is easily reared in highly regulated culture environments allowing for greater consistency in the silk produced. We controlled the temperature, resource availability (larvae/gram diet), and population density (larvae/mL) with the goal of increasing silk fiber production and improving homogeneity in Plodia silk proteins. We determined that higher temperatures accelerated insect growth and reduced life cycle length. Furthermore, we established initial protocols for the production of Plodia silk with optimal silk production occurring at 24 °C, with a resource availability of 10 larvae/gram and a population density of 0.72 larvae/mL. Population density was shown to be the most prominent driving force of Plodia silk mat formation among the three parameters assessed. Future work will need to link gene expression, protein production and purification, and resulting mechanical properties as a function of environmental cues to further transition Plodia silk into regenerated silk fibroin biomaterials.

Psychedelic Therapy: A Primer for Primary Care Clinicians-Psilocybin.

BACKGROUND: The primary psychoactive drug in magic mushrooms, psilocybin, induces profound alterations in consciousness through the 5-HT2A receptor. This review consolidates current research findings to elucidate the pharmacology, safety profile, and clinical applications of psilocybin. AREAS OF UNCERTAINTY: Despite initial concerns that psilocybin could cause psychosis, contemporary research has demonstrated that psilocybin is generally safe. The most common adverse effects are nausea and headache, yet both tend to be transient. Serious adverse events can generally be avoided in controlled settings such as clinical trials. However, in the largest clinical trial to date, there were a total of 7 reported cases of suicidal ideation, up to 12 weeks after receiving a single 25 mg dose of psilocybin. That being said, all 7 cases did not respond to the treatment. Although selective serotonin reuptake inhibitors may blunt the hallucinogenic qualities of psilocybin, preliminary research suggests that they may enhance its antidepressant effects. THERAPEUTIC ADVANCES: In clinical trials, psilocybin has shown promise for treating major depressive disorder and treatment-resistant depression. Initial studies indicated that 42%-57% of patients underwent remission after psilocybin-assisted therapy, which suggests that psilocybin is more effective than existing antidepressant medications. Clinical data have also demonstrated that psilocybin can manage substance use disorders and end-of-life anxiety with clinical outcomes that are sustained for months and sometimes years after 1 or 2 doses. LIMITATIONS: However, larger Phase II trials with more than 100 depressed participants have shown a much smaller remission rate of 25%-29%, though these studies still observed that psilocybin causes a significant reduction in depressive symptoms. CONCLUSIONS: Aside from ketamine, psilocybin is the most clinically well-researched psychedelic drug, with trials that have enrolled hundreds of participants and multiple therapeutic applications. Phase III trials will determine whether psilocybin lives up to the promise that it showed in previous clinical trials.

Current Trends and Applications of PET/MRI Hybrid Imaging in Neurodegenerative Diseases and Normal Aging.

Dementia is a significant global health issue that is exacerbated by an aging population. Imaging plays an established role in the evaluation of patients with neurocognitive disorders such as dementia. In current clinical practice, magnetic resonance imaging (MRI) and positron emission tomography (PET) are primary imaging modalities used separately but in concert to help diagnose and classify dementia. The clinical applications of PET/MRI hybrid imaging in dementia are an active area of research, particularly given the continued emergence of functional MRI (fMRI) and amyloid PET tracers. This narrative review provides a comprehensive overview of the rationale and current evidence for PET/MRI hybrid dementia imaging from 2018 to 2023. Hybrid imaging offers advantages in the accuracy of characterizing neurodegenerative disorders, and future research will need to address the cost of integrated PET/MRI systems compared to stand-alone scanners, the development of new biomarkers, and image correction techniques.

Psychedelic Therapy: A Primer for Primary Care Clinicians-Historical Perspective and Overview.

BACKGROUND: Psychedelic drugs have recently emerged as plausibly effective pharmacological agents for the management of depression, anxiety, and other neuropsychiatric conditions, including those that are treatment-resistent. The latter half of the 20th century marked a revolution in the treatment of mental illnesses, exemplified by the introduction of selective serotonin reuptake inhibitors and other pharmacological agents. Nevertheless, mental illness remains a major public health crisis, affecting nearly one billion individuals worldwide. AREAS OF UNCERTAINTY: Because of the decades-long status of several psychedelics as Schedule I drugs, there have not been very many large, double-blind, randomized controlled trials of psychedelics. Owing to small sample sizes, there may be rare yet serious adverse events that have not been reported in the clinical trials thus far. THERAPEUTIC ADVANCES: Esketamine, a dissociative hallucinogen drug, was approved for the management of major depressive disorder by the Food and Drug Administration in 2019. As of January 2024, two Phase III trials of 3,4-methylenedioxymethamphetamine (MDMA), a synthetic drug that inhibits the serotonin transporter, have been completed; the results indicate that MDMA is superior to existing pharmacological treatments for post-traumatic stress disorder. A phase III trial of psilocybin, a naturally occurring serotonin receptor partial agonist, is currently underway. The following series details the current state of research in psychedelic therapeutics, including lysergic acid diethylamide (LSD), N-N-dimethyltryptamine (DMT) and ayahuasca, psilocybin, ibogaine, MDMA, and ketamine. LIMITATIONS: While initial clinical trials of psychedelics for depression were very promising, trials of psilocybin with larger sample sizes (100+ participants) suggest that its remission rate is 25%-29%. This is about the same as the remission rate of antidepressants, which is roughly 30% according to the landmark STAR*D trial. CONCLUSIONS: Psychedelic drugs and structural derivatives offer a great deal of promise for the management of a wide range of psychiatric morbidities. It is imperative that clinicians become familiar with these novel agents and learn how to integrate psychedelic therapy with the rest of their care through open communication and referral.

Psychedelic Therapy: A Primer for Primary Care Clinicians-Lysergic Acid Diethylamide (LSD).

BACKGROUND: Lysergic acid diethylamide (LSD) is a hallucinogenic agent. In the mid-20th century, it was used to augment psychoanalysis and to treat alcohol use disorder. However, LSD was banned in 1970 in part because of concerns that it could bring about or exacerbate mental illness. Its therapeutic potential remains incompletely understood. AREAS OF UNCERTAINTY: While uncontrolled recreational use of LSD can, in rare instances, lead to long-term psychosis, adverse events in clinical trials of LSD, such as anxiety, headache, and nausea, have almost always been mild and transient. Serious adverse events, such as intense panic, suicidal ideation, and psychosis, were reported in either none or very few of the participants. However, patient selection criteria, optimal dosing strategy, and appropriate clinical follow-up guidelines remain to be established. THERAPEUTIC ADVANCES: Preliminary data suggest that LSD may be effective for the management of alcohol use disorder, anxiety, and depression. In trials of LSD for treating anxiety and depression associated with life-threatening illnesses, 77% of participants demonstrate durable relief at 1 year post-treatment. Top-line data from a large-scale phase IIb trial (n = 198) indicate that 50% of participants experience remission from generalized anxiety disorder after a single 100 µg dose of LSD. According to a meta-analysis of RCTs on LSD from the mid-20th century, single-dose regimens of LSD significantly improve alcohol use disorder (P < 0.0003) with an odds ratio (OR) of 1.96. LIMITATIONS: Only one large-scale clinical trial (>50 participants) has been conducted on LSD in the contemporary era of psychedelic research. Further studies with large sample sizes are needed to explore potential clinical applications. CONCLUSIONS: Preliminary data suggest that LSD may be one of the most potent treatments for anxiety in patients both with and without a life-threatening illness. LSD may also be beneficial for treating depression and substance use disorders.

Psychedelic Therapy: A Primer for Primary Care Clinicians-Ibogaine.

BACKGROUND: Ibogaine is a plant-derived alkaloid that has been used for thousands of years in rites of passage and spiritual ceremonies in West-Central Africa. In the West, it has primarily been used and studied for its anti-addictive properties and more recently for other neuropsychiatric indications, including post-traumatic stress disorder, depression, anxiety, and traumatic brain injury. AREAS OF UNCERTAINTY: Ibogaine requires careful patient screening and monitoring because of significant safety issues. There is potential for cardiotoxicity (prolonged QT interval); without rigorous screening, fatal arrhythmias may occur. However, preliminary research suggests that co-administration of ibogaine with magnesium may mitigate cardiotoxicity. Additionally, ibogaine may have dangerous interactions with opiates, so patients who receive ibogaine treatment for opioid use disorder must withdraw from long-acting opioids. Other potential concerning effects of ibogaine include rare incidences of mania or psychosis. Anticipated transient effects during ibogaine treatment can include ataxia, tremors, and gastrointestinal symptoms. THERAPEUTIC ADVANCES: Robust effects after a single treatment with ibogaine have been reported. In open-label and randomized controlled trials (RCTs), ibogaine reduces heroin and opioid cravings by upwards of 50%, up to 24 weeks after the treatment. An observational study of 30 Special Operations Forces veterans with mild traumatic brain injury reported that 86% were in remission from post-traumatic stress disorder, 83% from depression, and 83% from anxiety, one month after a single-dose ibogaine treatment. LIMITATIONS: Although there are several observational and open-label studies, there is only a single double-blind, placebo-controlled RCT on ibogaine. More RCTs with large sample sizes must be conducted to support ibogaine's safety and efficacy. CONCLUSIONS: Given the promising preliminary findings, ibogaine could potentially fill a much-needed gap in treatments for challenging conditions, including opioid dependence. Ibogaine's remarkable effects in traditionally treatment-resistant, combat-exposed individuals hints at its potential in broader populations with physical and psychological trauma.

Psychedelic Therapy: A Primer for Primary Care Clinicians-N,N-Dimethyltryptamine and Ayahuasca.

BACKGROUND: N,N-dimethyltryptamine (DMT) is a naturally occurring serotonergic psychedelic found in natural plants around the globe. As the main psychoactive component in ayahuasca, which also contains monoamine oxidase inhibitors, DMT has been consumed as plant-based brew by indigenous peoples for centuries. Further research is required to delineate the therapeutic utility of DMT. AREAS OF UNCERTAINTY: Although previous research has shown that DMT is synthesized endogenously, it may not be produced at physiologically relevant concentrations. Additionally, the phenomenological similarities between the DMT-induced state and near-death experiences led to the popular hypothesis that endogenous DMT is released during the dying process. However, this hypothesis continues to be debated. Generally, DMT and ayahuasca seem to be physiologically and psychiatrically safe, although ayahuasca is known to cause transient vomiting. THERAPEUTIC ADVANCES: A double-blind, randomized controlled trial showed that, within 1 week, ayahuasca causes remission in 36% of patients with treatment-resistant depression. According to top-line results from a recent phase IIa trial, 57% of patients with major depressive disorder experienced remission 12 weeks after receiving a single intravenous dose of DMT. LIMITATIONS: There has only been a single published double-blind randomized controlled trial on ayahuasca and 2 on DMT. All clinical trials have had small sample sizes (≤34 participants). DMT requires further research to understand its therapeutic and clinical potential as a psychedelic. CONCLUSIONS: Preliminary evidence indicates that ayahuasca and DMT may be more effective than existing antidepressants for treating major depressive disorder and treatment-resistant depression.