From taboo to treatment: The emergence of psychedelics in the management of pain and opioid use disorder.

The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the possible role of psychedelics in the management of chronic pain and opioid use disorder (OUD), 2 critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long-term opioid therapy who develop marked tolerance to opioid-induced analgesia. Despite the magnitude of this problem, there is a scarcity of controlled studies investigating pain management alternatives for these populations. Drawing from preclinical and human evidence, we highlight the potential of psychedelics to act on shared neurobiological substrates of chronic pain and OUD, potentially reversing pain- and opioid-induced neuroadaptations, such as central sensitization. We elaborate on the multifaceted dimensions of the pain experience (sensory, affective and cognitive) and their intersections that overlap with opioid-related phenomena (opioid craving and withdrawal), hypothesizing how these processes can be modulated by psychedelics. After summarizing the available clinical research, we propose mechanistic insights and methodological considerations for the design of future translational studies and clinical trials, building on a shared clinical and neurobiological understanding of chronic pain and OUD. Our intention is to provide timely perspectives that accelerate the development and exploration of novel therapeutics for chronic pain and OUD amidst the escalating opioid crisis.

Assessing pain in persons with opioid use disorder: Approaches, techniques and special considerations.

Pain and opioid use disorder (OUD) are inextricably linked, as the former can be a risk factor for the development of the latter, and over a third of persons with OUD suffer concomitant chronic pain. Assessing pain among people with OUD is challenging, because ongoing opioid use brings changes in pain responses and most pain assessment tools have not been validated for this population. In this narrative review, we discuss the fundamentals of pain assessment for populations with OUD. First, we describe the biological, psychological and social aspects of the pain experience among people with OUD, as well as how opioid-related phenomena may contribute to the pain experience in this population. We then review methods to assess pain, including (1) traditional self-reported methods, such visual analogue scales and structured questionnaires; (2) behavioural observations and physiological indicators; (3) and laboratory-based approaches, such as quantitative sensory testing. These methods are considered from a perspective that encompasses both pain and OUD. Finally, we discuss strategies for improving pain assessment in persons with OUD and implications for future research, including educational strategies for multidisciplinary teams. We highlight the substantial gaps that persist in this literature, particularly regarding the applicability of current pain assessment methods to persons with OUD, as well as the generalizability of the existing results from adjacent populations on chronic opioid therapy but without OUD. As research linking pain and OUD evolves, considering the needs of diverse populations with complex psychosocial backgrounds, clinicians will be better equipped to reduce these gaps.

Management of Phenibut Use Disorder and Withdrawal in a Geriatric Patient.

Phenibut is a misused substance which has shown an increase in use over the past decade. Marketed as a "dietary supplement," it is not approved in the United States for use and is not regulated by the Food and Drug Administration. The substance, however, is readily available for purchase through online markets. It has a similar drug profile as alcohol, gabapentin and benzodiazepines. Clinical effects of this drug include physiologic dependence, euphoria, anxiolysis, antispasticity, sedation, and possible nootropic properties. While there are emerging new cases of managing phenibut withdrawal, no cases currently feature phenibut addiction and withdrawal management in the geriatric population. Here we discuss such a case of phenibut addiction and withdrawal in a 68-year-old male who initially began misusing phenibut to alleviate anxiety and insomnia precipitated by worsening affective disorder, sedative, hypnotic, or anxiolytic use disorder, and alcohol use disorder.

Methamphetamine-associated catatonia: Case series and systematic review of the literature from 1943-2020.

BACKGROUND: Catatonia due to a general medical condition may result from a variety of causes, including substance intoxication and withdrawal. Stimulants are occasionally associated with catatonia, though there has been little investigation of methamphetamine's relationship to catatonia. Here we present 5 cases of catatonia associated with methamphetamine use and a systematic review of the associated literature from 1943 to 2020. METHODS: We performed a systematic review of the literature and present 5 cases of catatonia evaluated using the Bush-Francis Catatonia Rating Scale and KANNER catatonia rating scale. RESULTS: Methamphetamine use was associated with catatonia in a small number of cases in the literature. However, some of these reports included other possible etiologies. The patients in our case series met DSM-5 criteria for catatonia due to a general medical condition, with all reporting recent methamphetamine use and testing positive for amphetamines on urine drug screen. CONCLUSIONS: Given the ongoing rise in methamphetamine use in the United States, it is important that clinicians understand that methamphetamine use can be associated with catatonia. Patients with methamphetamine-associated catatonia may respond favorably to lorazepam and require shorter hospital stays than other catatonic patients. Lastly, methamphetamine-associated catatonia highlights how alteration in dopamine function and projections may be a critical neural mechanism underlying catatonia in general.

Developing non-opioid therapeutics to alleviate pain among persons with opioid use disorder: a review of the human evidence.

The opioid crisis remains a major public health concern, causing significant morbidity and mortality worldwide. Pain is frequently observed among individuals with opioid use disorder (OUD), and the current opioid agonist therapies (OAT) have limited efficacy in addressing the pain needs of this population. We reviewed the most promising non-opioid analgesic therapies for opioid-dependent individuals synthesising data from randomised controlled trials in the Medline database from December 2022 to March 2023. Ketamine, gabapentin, serotoninergic antidepressants, and GABAergic drugs were found to be the most extensively studied non-opioid analgesics with positive results. Additionally, we explored the potential of cannabinoids, glial activation inhibitors, psychedelics, cholecystokinin antagonists, alpha-2 adrenergic agonists, and cholinergic drugs. Methodological improvements are required to advance the development of novel analgesic strategies and establish their safety profile for opioid-dependent populations. We highlight the need for greater integration of experimental pain methods and abuse liability assessments, more granular assessments of prior opioid exposure, greater uniformity of pain types within study samples, and a particular focus on individuals with OUD receiving OAT. Finally, future research should investigate pharmacokinetic interactions between OAT and various non-opioid analgesics and perform reverse translation basic experiments, particularly with methadone and buprenorphine, which remain the standard OUD treatment.

The perceptions of cancer health-care practitioners in New Zealand and the USA toward psychedelic-assisted therapy with cancer patients: A cross-sectional survey.

OBJECTIVES: A resurgence of research investigating the administration of psychedelic compounds alongside psychotherapy suggests that this treatment is a promising intervention for anxiety, depression, and existential distress in people with cancer. However, psychedelic treatment that induces a mind-altering experience potentially poses barriers to vulnerable cancer patients, and health-care practitioners may have concerns about referring their patients to trials investigating this approach. The aim of the current study was to investigate the perceptions of cancer health-care practitioners based in New Zealand and the USA related to psychedelic-assisted therapy. METHODS: This study utilized a cross-sectional survey of cancer health-care practitioners in New Zealand and the USA via convenience sampling to identify their perceptions about the concept of conducting psychedelic-assisted therapy with cancer patients. RESULTS: Participants perceived that (1) psychedelic-assisted therapy has the potential to provide benefit for cancer patients, (2) research in this area across a variety of domains is important, (3) work should consider spiritual and indigenous perspectives of health, and (4) there was willingness to refer patients to trials in this area, especially patients with advanced disease who were no longer going through curative treatment. Participants in the USA had greater awareness of psychedelics than the New Zealand sample; however, New Zealand participants more strongly believed that spiritual/indigenous factors should be considered in psychedelic-assisted therapy. SIGNIFICANCE OF RESULTS: Cancer health-care practitioners in our sample considered research investigating the potential for psychedelic-assisted therapies to be important and may be more open to studies that start in palliative and end-of-life contexts.

Class-A scavenger receptor function and expression in the rainbow trout (Oncorhynchus mykiss) epithelial cell lines RTgutGC and RTgill-W1.

Class A scavenger receptors (SR-As) are cell surface receptors that bind a range of ligands, including modified low-density lipoproteins (mLDLs) and nucleic acids. Due to their ability to bind extracellular dsRNA, SR-As play an important role in the viral dsRNA initiated immune pathway. Most research on SR-As has focused on mammalian models, and there has been limited research on SR-As in fish. Thus, the presence of functional class A scavenger receptors (SR-As) were investigated in the rainbow trout cell lines, RTgutGC and RTgill-W1. SR-A ligand binding was assessed using fluorescently labeled acetylated-low density lipoprotein (acLDL) and synthetic dsRNA, polyinosinic:polycytidylic acid (poly IC), in combination with a series of known SR-A competitive ligands: fucoidan, dextran sulfate (DxSO4) and polyinosinic acid (poly I). Both cell lines were able to bind acLDL, which was blocked by SR-A competitive ligands. In RTgutGC, acLDL and poly IC competed for binding to the same surface receptor; however, in RTgill-W1 they did not. Poly IC-fluorescein binding was blocked by SR-A competitive ligands in RTgutGC but not RTgill-W1, suggesting an SR-A dependent dsRNA uptake mechanism in RTgutGC and an SR-A-independent update mechanism in RTgill-W1. Both cell lines responded to extracellular dsRNA treatment with the up-regulation of interferons (IFNs) and interferon stimulated genes (ISGs) as measured by quantitative (q)RT-PCR; however, RTgutGC expressed significantly higher transcript levels for both IFNs and ISGs compared with RTgill-W1 following extracellular poly IC treatment. Expression of SR-As, specifically a SCARA4-like sequence, was identified at the transcript level in both cell lines. These results suggest that both RTgill-W1 and RTgutGC express functional SR-As that are able to bind the classic SR-A ligand, acLDL. Although they both express SCARA4, the full SR-A expression profile; however, is likely different between the cell lines, as dsRNA uptake appears to be SR-A dependent in RTgutGC but SR-A-independent in RTgill-W1. Also, dsRNA uptake via SR-As appears to mediate a more robust antiviral response compared with a SR-A independent method of uptake. This study is the first to identify functional SR-As in rainbow trout epithelial cells, and contributes not only to a better understanding of modified LDL transport but also innate immunity in these economically important animals.

The Zero Suicide Model in Addiction Treatment Settings: Recognizing the Need for Feasibility and Implementation Data.

The Zero Suicide (ZS) model is a promising approach for preventing all suicides across health care settings. ZS provides guidelines for health care systems to implement best practices in suicide prevention. Patients with substance use disorders are at increased risk for suicide, but no known research has investigated how to integrate the ZS model into addiction treatment settings. This Open Forum encourages clinicians and researchers to integrate ZS into such settings and to study its feasibility and effectiveness. ZS integration into addiction treatment may improve both suicide and addiction outcomes, but additional research is needed.

All a-BORG! The Dangerous Drinking Trend Steamrolling Across Social Media and College Campuses.

ABSTRACT: Black out rage gallons (BORGs) are a troublesome drinking pattern emerging on social media platforms. The prevalence of BORGs has been increasing on college campuses and is demonstrating significant consequences. There is no known research on BORGs in addiction treatment settings. We suggest that future research will be necessary to understand their implication. Troublesome binge drinking is not a new problem among colleges. However, social media has seemed to ignite such trends.

Wernicke's encephalopathy treated with high dose intravenous thiamine: a case report.

Wernicke's encephalopathy (WE) is a dangerous and potentially fatal neurological condition associated with thiamin deficiency. The standard treatment for WE is intravenous (IV) thiamin, but limited research describes optimal dosing. We present a case of a 40-year-old male with severe alcohol use disorder (AUD) and chronic malnourishment who developed WE. Upon administration of 100 mg IV thiamin, symptoms of WE persisted, but when the dose was increased to 500 mg, altered mental status and ophthalmoplegia resolved rapidly. IV thiamin is a reliable and low-risk treatment for WE, even when administered at high doses. High-dose IV thiamin (i.e., >/100 mg) can treat neurological symptoms and cognitive dysfunction in WE and should be considered for first-line treatment. Further study of WE diagnostic and treatment guidelines is warranted to maximize recovery potential.

Changes in Emergency Department Utilization in Vulnerable Populations After COVID-19 Shelter-in-Place Orders.

OBJECTIVES: This study aims to compare emergency department (ED) utilization and admission rates for patients with a history of mental health (MH) disorders, substance use disorders (SUDs), and social determinants of health (SDOH) before and after implementing COVID-19 shelter-in-place (SIP) orders. METHODS: This was a retrospective, multicenter study leveraging electronic medical record (EMR) data from 20 EDs across a large Midwest integrated healthcare system from 5/2/2019 to 12/31/2019 (pre-SIP) and from 5/2/2020 to 12/31/2020 (post-SIP). Diagnoses were documented in the patient's medical records. Poisson and logistic regression models were used to evaluate ED utilization and admission rate changes. RESULTS: A total of 871,020 ED encounters from 487,028 unique patients were captured. Overall, 2,572 (0.53%) patients had a documented Z code for SDOH. Patients with previously diagnosed MH disorders or SUDs were more likely to seek ED care after the SIP orders were implemented (risk ratio (RR): 1.20, 95% confidence interval (CI): 1.18-1.22, p<0.001), as were patients with SDOH (RR: 2.37, 95% CI: 2.19-2.55, p<0.001). Patients with both previously diagnosed MH disorders or SUDs and a documented SDOH had even higher ED utilization (RR: 3.31, 95% CI: 2.83-3.88, p<0.001) than those with either condition alone. Patients with MH disorders and SUDs (OR: 0.89, 95% CI: 0.86-0.92, p<0.001) or SDOH (OR: 0.67, 95% CI: 0.54-0.83, p<0.001) were less likely to be admitted post-SIP orders, while patients with a history of diseases of physiologic systems were more likely to be admitted. CONCLUSION: Vulnerable populations with a history of MH disorders, SUDs, and SDOH experienced increased ED utilization but a lower rate of hospital admissions after the implementation of SIP orders. The findings highlight the importance of addressing these needs to mitigate the impact of public health crises on these populations.

Diagnosis and treatment of Wernicke's encephalopathy: A systematic literature review.

BACKGROUND: Wernicke's encephalopathy (WE) is a serious neurological disorder that is underdiagnosed. Despite limited clinical guidelines, the standard use of intravenous (IV) thiamine is underutilized and remains an area of research deserving much attention. OBJECTIVES: We conducted a systematic review using Medline, Embase, and CENTRAL databases to identify and summarize the literature on IV thiamine treatment in WE. Human studies with WE patients who received ≥100 mg of thiamine IV met inclusion criteria. Randomized controlled trials, cross-sectional studies, and case reports were included. RESULTS: A total of 27 studies were included: 20 case reports, five retrospective studies, one prospective study and one randomized control trial. Of the case reports, 11 (55%) cases were female, and the average age of all cases was 45 years (SD = 15). The other seven studies included 688 patients; the average age was 52 years (SD = 9), and 266 (38.7%) were female. Among the case reports, neurological and clinical findings were used to diagnose WE in 16 (80%) cases. MRI was utilized to diagnose 15 (75%) cases. 500 mg IV thiamine TID was reported in 12 case reports (60%). 18 (90%) of case reports had partial or complete resolution of symptoms following IV thiamine. CONCLUSION: IV thiamine can alleviate neurological symptoms, cognitive dysfunction, and brain imaging lesions associated with WE. We found key limitations in the evidence for IV thiamine and diagnostic standards for WE. Future targeted research should establish clear diagnostic and treatment guidelines for WE to prevent this serious condition from being underdiagnosed or undertreated.

Adverse Childhood Experiences (ACEs) in Unhoused Children Increase Odds of Psychiatric Illness, Physical Illness, and Psychiatric Admission.

Unhoused children and adolescents have high rates of adverse childhood experiences (ACEs). The objective of this study was to characterize a large cohort of unhoused children and investigate rates of psychiatric diagnoses, medical diagnoses, and utilization of emergency department (ED) resources depending on the presence of additional documented ACEs. A retrospective cohort of all unhoused children who presented to the ED of a large Midwestern health system from January 2014 to July 2019 were included. Unhoused status was determined by address field or ICD-10 code for homelessness (Z59.0). Demographics and ED visits were extracted from the electronic health record. Past medical history, ACEs, chief complaint (CC), length of stay (LOS), imaging, and labs were extracted by chart review. T-tests, chi square tests, and Fisher's exact tests were completed for each sub-analysis. Unhoused children with at least one additional ACE had higher odds of the following psychiatric disorders: depression (OR = 5.2, 95% CI = 3.4- 7.9), anxiety (OR = 3.4, 95% CI = 32.1-5.5), behavioral disorder (OR = 7.2, 95% CI = 35.1- 10.4), psychoses (OR = 6.0, 1.9-18.4), bipolar disorder (OR = 19.8, 95% CI = 34.6-84.9), suicidal ideation (OR = 8.0, 95% CI = 34.8-13.4), post-traumatic stress disorder (OR = 10.1, 95% CI = 35.4-18.6), and attention deficit hyperactive disorder (OR = 4.1, 3.0-5.7). Patients with additional documented ACEs were also more likely to have a prior psychiatric admission (p < 0.001). Unhoused children and adolescents with exposure to additional documented ACEs are more likely to have some serious psychiatric and medical diagnoses compared to other unhoused children.

Emergency services utilization by patients with alcohol-associated hepatitis: An analysis of national trends.

BACKGROUND: Hospitalization and mortality in patients with alcohol-associated hepatitis (AH), a severe form of liver disease, continue to increase over time. Given the severity of the illness, most hospitalized patients with AH are admitted from the emergency department (ED). However, there are no data on ED utilization by patients with AH. Thus, the Nationwide Emergency Department Sample (NEDS) dataset was analyzed to determine the ED utilization for AH. METHODS: Temporal trends (2016-2019) and outcomes of ED visits for AH were determined. Primary or secondary AH diagnoses were based on coding priority. Numbers of patients evaluated in the ED, severity of disease, complications of liver disease, and discharge disposition were analyzed. Crude and adjusted rates were examined, and temporal trends evaluated using logistic regression with orthogonal polynomial contrasts for each year. RESULTS: There were 466,014,370 ED visits during 2016-2019, of which 448,984 (0.096%) were for AH, 85.0% of which required hospitalization. The rate of visits for AH (primary and secondary) between 2016 and 2019 increased from 85 to 106.8/100,000 ED visits. The rate of secondary AH increased more than the rate of primary AH (from 68.6 to 86.5 vs. from 16.4 to 20.3/100,000 ED visits). Patients aged 45-64 years had the highest rate of ED visits for AH, which decreased during the study period, while the rate of ED visits for AH increased in those aged 25-44 years (from 38.5% to 42.9%). The severity of disease (ascites, hepatic encephalopathy, and acute kidney injury) also increased over time. Medicaid and private insurance were the most common payors for patients seeking care in the ED for AH. CONCLUSIONS: Temporal trends show an overall increase in ED utilization rates for AH, more patients requiring hospitalization, and an increase in the proportion of younger patients presenting to the ED with AH.

A computational account of the development and evolution of psychotic symptoms.

The mechanisms of psychotic symptoms like hallucinations and delusions are often investigated in fully-formed illness, well after symptoms emerge. These investigations have yielded key insights, but are not well-positioned to reveal the dynamic forces underlying symptom formation itself. Understanding symptom development over time would allow us to identify steps in the pathophysiological process leading to psychosis, shifting the focus of psychiatric intervention from symptom alleviation to prevention. We propose a model for understanding the emergence of psychotic symptoms within the context of an adaptive, developing neural system. We will make the case for a pathophysiological process that begins with cortical hyperexcitability and bottom-up noise transmission, which engenders inappropriate belief formation via aberrant prediction error signaling. We will argue that this bottom-up noise drives learning about the (im)precision of new incoming sensory information because of diminished signal-to-noise ratio, causing an adaptive relative over-reliance on prior beliefs. This over-reliance on priors predisposes to hallucinations and covaries with hallucination severity. An over-reliance on priors may also lead to increased conviction in the beliefs generated by bottom-up noise and drive movement toward conversion to psychosis. We will identify predictions of our model at each stage, examine evidence to support or refute those predictions, and propose experiments that could falsify or help select between alternative elements of the overall model. Nesting computational abnormalities within longitudinal development allows us to account for hidden dynamics among the mechanisms driving symptom formation and to view established symptomatology as a point of equilibrium among competing biological forces.

Leveraging neuroscience education to address stigma related to opioid use disorder in the community: a pilot study.

Opioid use disorder (OUD) and overdose deaths are a public health crisis. One contributing factor is stigma towards people who use opioids. We developed and conducted a public-facing, half-day educational event designed to challenge misperceptions about OUD from a contemporary neuroscience perspective. Participants engaged with three different resources on the neurobiology of addiction, and, at the end of the event, they rated its effectiveness. We also collected and compared pre- and post-event composite OUD stigma scales. Participants rated our approach and the overall event as highly effective. Additionally, OUD stigma scores were lower immediately following the event, and this decrease was primarily driven by decreased internalized stigma. Here, we demonstrate an effective proof-of-concept that an accessible, public-facing, neuroscience education event may reduce OUD stigma in the community.

Key Updates to Understanding Roles of Childhood Trauma in Overall Health.

While adverse childhood experiences and trauma, including childhood abuse and neglect, have often been viewed from the lens of psychiatry, their influence on physical health, health behaviors, and factors that moderate health now garner more attention. This article reviews recent literature that has changed clinical and social viewpoints on child abuse and neglect and can be used as a primer to better understand (1) influences of child abuse and neglect on physical illness; (2) critical diagnostic advances relevant to persons who have experienced child abuse and neglect; and (3) ethical, research, and practical questions generated by these new understandings.

Cognitive, imaging, and psychiatric changes associated with chronic toluene use: case report and literature review.

Inhalant misuse and inhalant use disorder are global public health concern that impacts adolescents but can occur throughout life. Toluene is the most commonly misused inhalant. Toluene use leads to significant neuroanatomic, cognitive, and psychiatric deficits. The purpose of this study was to review and summarize the effects of toluene and present a case of a middle-aged patient with an inhalant use disorder. A literature review was conducted to evaluate imaging, neurocognitive, and psychiatric consequences of toluene misuse. The common imaging findings amongst those who misuse toluene were cerebral and cerebellar atrophy, ventricular dilation, loss of gray-white matter differentiation, corpus callosum thinning, and diffuse white matter changes. Concerning cognition, toluene misusers were shown to have deficits in intelligence, attention, memory, visuospatial function, and complex cognition. In addition, toluene users also commonly presented with apathy, flat affect, hallucinations, delusions, anxiety, depression, and insomnia. The neuroanatomical, neurocognitive, and psychiatric effects of toluene misuse are profound. These deficits can make inhalant use disorder difficult to treat. Therefore, evidence-based treatments that recognize and address these domain-specific neurocognitive deficits are needed.

Three Cases of Reported Improvement in Microsmia and Anosmia Following Naturalistic Use of Psilocybin and LSD.

Cultural awareness of anosmia and microsmia has recently increased due to their association with COVID-19, though treatment for these conditions is limited. A growing body of online media claims that individuals have noticed improvement in anosmia and microsmia following classic psychedelic use. We report what we believe to be the first three cases recorded in the academic literature of improvement in olfactory impairment after psychedelic use. In the first case, a man who developed microsmia after a respiratory infection experienced improvement in smell after the use of 6 g of psilocybin containing mushrooms. In the second case, a woman with anosmia since childhood reported olfactory improvement after ingestion of 100 µg of lysergic acid diethylamide (LSD). In the third case, a woman with COVID-19-related anosmia reported olfactory improvement after microdosing 0.1 g of psilocybin mushrooms three times. Following a discussion of these cases, we explore potential mechanisms for psychedelic-facilitated improvement in olfactory impairment, including serotonergic effects, increased neuroplasticity, and anti-inflammatory effects. Given the need for novel treatments for olfactory dysfunction, increasing reports describing improvement in these conditions following psychedelic use and potential biological plausibility, we believe that the possible therapeutic benefits of psychedelics for these conditions deserve further investigation.

Bibliometric Analysis of Academic Journal Articles Reporting Results of Psychedelic Clinical Studies.

Following a decades long period of investigational dormancy, there is renewed interest in employing psychedelics as psychiatric treatments. The academic journals, institutions, and countries that have helped sustain clinical psychedelic research and the evolution of the literature on clinical studies of psychedelics have only recently begun to be investigated. To expand upon this work, we conducted a bibliometric analysis of clinical studies of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), ayahuasca, dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), ibogaine, mescaline, 3,4-methylenedioxymethamphetamine (MDMA), and psilocybin published from 1965-2021. Our search revealed 394 relevant articles. After a lull from the 1970s-1990s, publications in this area have resurged. Studies most frequently focused on MDMA (49%), LSD (19%), psilocybin (18%), and ayahuasca (7%). A subanalysis of studies from 1965 to 2009 ("Older cohort") compared to 2010-2021 ("Recent cohort") revealed that the Recent cohort had a higher proportion of studies investigating psychedelics' therapeutic applications and a lower proportion of studies investigating the effects of psychedelics on people using them in non-research settings. Compared to the Older cohort, psilocybin studies increased proportionally in the Recent cohort, while DMT and mescaline studies decreased. Network analyses of inter-country collaborations suggested that psychedelic researchers in the United Kingdom have the most diverse international collaborations.