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1.
Chem Biol Interact ; : 111247, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39299374

ABSTRACT

Kratom (Mitragyna Speciosa Korth.) is an indigenous tree native to Southeast Asia whose leaves have been traditionally ingested as a tea and has seen its popularity increase in the United States. Although kratom and its constituents presently have no approved uses by the Food and Drug Administration, its major alkaloids (e.g., mitragynine) have psychoactive properties that may hold promise for the treatment of opioid cessation, pain management, and other indications. 9-O-demethylmitragynine is a major metabolite formed from mitragynine metabolism (36% total metabolism) and displays similar pharmacologic activity. Cytochrome P450 (CYP) 3A has been identified as a major enzyme involved in mitragynine metabolism; however, the in vitro metabolism parameters of 9-O-demethylmitragynine formation are not well defined and a risk of potential drug interactions exists. Using human liver S9 fractions, 9-O-demethylmitragynine formation was generally linear for enzyme concentrations of 0 to 0.25 mg/mL and incubation times of 5 to 20 min. 9-O-demethylmitragynine displayed a Km 1.37 µM and Vmax of 0.0931 nmol/min/mg protein. Known CYP inhibitors and compounds that might be concomitantly used with kratom were assessed for inhibition of 9-O-demethylmitragynine formation. Ketoconazole, a potent CYP3A inhibitor, demonstrated a significant effect on 9-O-demethylmitragynine formation, further indicating CYP3A as a major metabolic pathway. Major cannabinoids (10 µg/mL) displayed minor inhibition of 9-O-demethylmitragynine formation, while all other compounds had minimal effects. Mixtures of physiological achievable cannabinoid concentrations also displayed minor effects on 9-O-demethylmitragynine formation, making a metabolic drug interaction unlikely; however, further in vitro, in vivo, and clinical studies are necessary to fully exclude any risk.

3.
J Clin Psychiatry ; 85(2)2024 May 29.
Article in English | MEDLINE | ID: mdl-38814110

ABSTRACT

Importance: Extensively researched, exposure-focused therapies have dominated the treatment of posttraumatic stress disorder (PTSD). No treatment benefits all patients. Interpersonal psychotherapy (IPT), a nonexposure, affect-focused treatment, has emerged over 2 decades as an alternative evidence-based PTSD intervention.Objective: This narrative review critically assesses IPT outcomes for PTSD. Time limited IPT focuses on affect toleration and the interpersonal consequences of trauma rather than on reconstructing the trauma narrative and exposure to traumatic cues.Evidence Review: The author searched the outcome literature on IPT for adults with syndromal PTSD and drew upon personal involvement in studies since 2001. Subsyndromal PTSD studies and 1 adolescent trial were excluded.Findings: Thirteen published studies of IPT targeted PTSD in individual and group formats for 592 civilians (n = 8, 6 randomized controlled trials [RCTs]) and 187 military veterans (n = 5, 1 RCT). Some trials had methodological limitations. IPT surpassed outcomes of waiting lists and other weak controls and was noninferior to evidence-based PTSD treatments including Prolonged Exposure (n = 2) and sertraline (n = 1). Depression and other outcomes improved. The RCTs demonstrate IPT efficacy for PTSD and allow preliminary exploration of outcome mediators and moderators and differential therapeutics.Conclusion: While the number of studies remains limited, research by multiple investigators in differing populations supports the efficacy of IPT as a non trauma-focused PTSD treatment and justifies its inclusion in PTSD treatment guidelines. More research is necessary to determine how IPT compares to exposure-focused treatments in patient preference, attrition, and response for PTSD comorbid with major depression or due to sexual trauma.


Subject(s)
Interpersonal Psychotherapy , Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/therapy , Adult
4.
Psychiatry Res ; 336: 115885, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38603979

ABSTRACT

Posttraumatic stress disorder (PTSD) remains prevalent among individuals exposed to the 9/11 World Trade Center (WTC) terrorist attacks. The present study compared an Internet-based, therapist-assisted psychotherapy for PTSD to an active control intervention in WTC survivors and recovery workers with WTC-related PTSD symptoms (n = 105; 75% syndromal PTSD). Participants were randomized to integrative testimonial therapy (ITT), focused on WTC-related trauma, or modified present-centered therapy (I-MPCT), each comprising 11 assigned written narratives. The primary outcome was baseline-to-post-treatment change in PTSD symptoms on the PTSD Checklist for DSM-5 (PCL-5). Secondary measures included PTSD symptom clusters, depressive/anxiety symptoms, functioning, and quality of life. A significant main effect of time was observed for the primary outcome (average "large" effect size improvement, d = 1.49). Significant and "moderate-to-large" main effects of time were also observed for all PTSD symptom clusters, depressive symptoms, quality of life, and mental health-related functioning (d range=0.62-1.33). Treatment and treatment-by-time interactions were not significant. In planned secondary analyses incorporating 3-month follow-up measures, ITT was associated with significantly greater reductions than I-MPCT in PTSD avoidance and negative alterations in cognitions and mood, anxiety, and mental health-related functioning. Both therapies significantly lowered PTSD symptoms, suggesting they may benefit hard-to-reach individuals with chronic WTC-related PTSD symptoms.


Subject(s)
September 11 Terrorist Attacks , Stress Disorders, Post-Traumatic , Survivors , Humans , Stress Disorders, Post-Traumatic/therapy , Male , September 11 Terrorist Attacks/psychology , Female , Adult , Middle Aged , Survivors/psychology , Internet , Treatment Outcome , Quality of Life , Psychotherapy/methods , Internet-Based Intervention
5.
Article in English | MEDLINE | ID: mdl-38565326

ABSTRACT

AIM: Stigma is a major mental healthcare barrier. This study compares the efficacy of two types of brief video interventions, targeting public and self-stigma, in reducing public stigma towards people living with psychosis. We hypothesized both interventions would similarly reduce public stigma and outperform the control group. As a secondary analysis, we explored the effect of familiarity with a person living with serious mental illness (SMI). METHODS: Participants (N = 1215) aged 18-35 recruited through crowdsourcing were assessed pre- and post-intervention and at 30-day follow-up regarding five public stigma domains: social distance, stereotyping, separateness, social restriction and perceived recovery. Both videos present individual narratives using different approaches: the self-stigma video was created through focus groups, while the public stigma video portrays a single person's journey. RESULTS: A 3 × 3 analysis of variance (ANOVA) revealed a significant group-by-time interaction across all five stigma-related domains (p's < .001). Effect sizes (Cohen's d) ranged from 0.29 to 0.52 (baseline to post-intervention), and 0.18 to 0.45 (baseline to 30-day follow-up). The two video interventions did not significantly differ. Linear mixed modelling showed a significant difference between participants familiar and unfamiliar with people living with SMI for the public stigma video, with greater stigma reductions for unfamiliar participants. CONCLUSIONS: This study corroborates previous findings on the positive influence of social contact-based interventions on youth mental health perceptions. Results provide insights into the relationship between public and self-stigma and the impact that familiarity with SMI may have on the efficacy of stigma reduction efforts further validation in diverse groups is needed.

6.
J Clin Psychiatry ; 85(1)2024 03 06.
Article in English | MEDLINE | ID: mdl-38451170

ABSTRACT

Objective: Self-stigma, a phenomenon wherein individuals internalize self-directed negative stereotypes about mental illness, is associated with negative outcomes related to recovery. This randomized controlled study assessed the efficacy of a brief social contact-based video intervention in reducing self-stigma in a large sample of individuals ages 18-35 endorsing an ongoing mental health condition. We hypothesized that the brief video would reduce self-stigma.Methods: In January and February 2023, we recruited and assigned 1,214 participants to a brief video-based intervention depicting a young individual living with mental illness sharing his personal story or to a non-intervention control. In the 2-minute video, informed by focus groups, a young individual described struggles with mental illness symptoms; this was balanced with descriptions of living a meaningful and productive life. Self-stigma assessments (Stereotype Endorsement, Alienation, Stigma Resistance, Perceived Devaluation Discrimination, Secrecy, and Recovery Assessment Scale) were conducted pre- and post-intervention and at 30-day follow-up.Results: A 2 ✕ 3 group-by-time analysis of variance showed that mean self-stigma scores decreased in the intervention arm relative to control across 5 of 6 self-stigma domains: Stereotype Endorsement (P = .006), Alienation (P < .001), Stigma Resistance (P = .004), Secrecy (P < .001), and Recovery Assessment Scale (P < .001). Cohen d effect sizes ranged from 0.22 to 0.46 for baseline to post-intervention changes. Baseline and 30-day follow-up assessments did not significantly differ.Conclusions: A 2-minute social contact-based video intervention effectively yielded an immediate but not a lasting decrease in self-stigma among young individuals with ongoing mental health conditions. This is the first study to examine the effect of a video intervention on self-stigma. Future trials of self-stigma treatment interventions should explore whether combining existing interventions with brief videos enhances intervention effects.Trial Registration: NCT05878470.


Subject(s)
Mental Disorders , Social Stigma , Humans , Mental Disorders/therapy , Research Design , Adolescent , Young Adult , Adult
7.
J Psychiatr Res ; 173: 232-238, 2024 May.
Article in English | MEDLINE | ID: mdl-38554618

ABSTRACT

BACKGROUND: Recently we showed that a brief video-based intervention can improve openness to help-seeking and decrease treatment-related stigma among essential workers, particularly for female and Black individuals viewing demographically matched protagonists. The current randomized controlled trial explored two additional factors which may enhance the efficacy of this intervention: income level, known to be associated with help-seeking, and emotional engagement, which may enhance a person's ability to engage with the intervention. We hypothesized that income level and emotional engagement would correlate with changes in openness to help-seeking ("openness") and stigma. METHODS: Essential workers (N = 1405) randomly viewed a control video or a brief video of an actor portraying an essential worker describing COVID-19-related anxiety and depression and treatment benefits. Openness and stigma were assessed at baseline, post-intervention, and 30-day follow-up, with emotional engagement assessed post-intervention. RESULTS: The brief video intervention demonstrated immediate increases in openness (p < 0.001, Cohen's d = 0.39) and decreases in stigma (p < 0.001, d = 0.14) compared to the control. Reported income level affected neither dependent variable. Participants who scored higher on the emotional engagement scale reported greater change in openness and stigma. LIMITATIONS: Use of a crowdsourcing platform may limit generalizability. CONCLUSIONS: The 3-min video showed modest effect sizes for immediate increased openness and reduced stigma, with greater emotional engagement heightening the effect, suggesting a possible mediator to the intervention. Income level did not affect intervention outcomes. Research should explore the role of income by adding income-related content to the brief-video interventions and assessing whether links to referrals could foster immediate behavioral change. TRIAL REGISTRATION: NCT04964570.


Subject(s)
Depression , Emotions , Humans , Female , Depression/therapy , Depression/psychology , Social Stigma
8.
Breast Cancer Res Treat ; 205(2): 249-256, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38376796

ABSTRACT

PURPOSE: Depression is among the most common comorbid psychiatric disorders of patients with breast cancer. Depression decreases patient quality of life and, if untreated, can adversely affect cancer treatment. We sought to identify treatment barriers for women with breast cancer receiving psychotherapy for depression. Findings may help policy makers and researchers determine funding and design of future studies involving this population, especially in communities with high rates of health disparities. METHODS: We used data from a randomized trial for women with breast cancer and current DSM-IV non-psychotic unipolar major depressive disorder (MDD). Patients were randomly assigned to 12 weeks of one of three psychotherapies and attrition was assessed by whether subjects completed 12 weekly treatment sessions. We used descriptive analyses and logistic regression to identify treatment barriers. R shiny was used to determine study patient residences. RESULTS: Of 134 randomized patients, 84 (62.7%) were Hispanic. Fifty-nine patients (44%) either did not start or dropped out of treatment, 49 (83.1%) of them being Hispanic. Being a Hispanic woman, less educated, and geographically distant from treatment significantly predicted attrition. Single Hispanic mothers had significantly higher attrition risk than married and/or childless women. CONCLUSION: Identifying barriers to treatment is important to improve treatment adherence for patients with concurrent diagnoses of breast cancer and MDD, especially for traditionally underserved minorities. Additional support such as affordable tele-medicine, multi-language assistance, financial aid for transportation and child-care, and allocation of more funds to address some identified barriers deserve consideration to improve treatment adherence and outcomes.


Subject(s)
Breast Neoplasms , Comorbidity , Depressive Disorder, Major , Hispanic or Latino , Humans , Female , Breast Neoplasms/psychology , Breast Neoplasms/therapy , Breast Neoplasms/epidemiology , Breast Neoplasms/complications , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/therapy , Hispanic or Latino/statistics & numerical data , Hispanic or Latino/psychology , Middle Aged , Adult , Aged , Psychotherapy/methods , Health Services Accessibility , Quality of Life
9.
Schizophr Bull ; 50(3): 695-704, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38372704

ABSTRACT

BACKGROUND AND HYPOTHESIS: Racial discrimination and public stigma toward Black individuals living with schizophrenia create disparities in treatment-seeking and engagement. Brief, social-contact-based video interventions efficaciously reduce stigma. It remains unclear whether including racial identity experiences in video narrative yields greater stigma reduction. We hypothesized that we would replicate findings showing sustained stigma reduction in video-intervention groups vs control and that Black participants would show greater stigma reduction and emotional engagement than non-Black participants only for a racial-insights video presenting a Black protagonist. STUDY DESIGN: Recruiting using a crowdsourcing platform, we randomized 1351 participants ages 18-30 to (a) brief video-based intervention, (b) racial-insights-focused brief video, or (c) non-intervention control, with baseline, post-intervention, and 30-day follow-up assessments. In 2-minute videos, a young Black protagonist described symptoms, personal struggles, and recovery from schizophrenia, with or without mentioning race-related experiences. STUDY RESULTS: A 3 × 3 ANOVA showed a significant group-by-time interaction for total scores of each of five stigma-related domains: social distance, stereotyping, separateness, social restriction, and perceived recovery (all P < .001). Linear mixed modeling showed a greater reduction in stigma from baseline to post-intervention among Black than non-Black participants in the racial insights video group for the social distance and social restriction domains. CONCLUSIONS: This randomized controlled trial replicated and expanded previous findings, showing the anti-stigma effects of a brief video tailored to race-related experiences. This underscores the importance of personalized, culturally relevant narratives, especially for marginalized groups who, more attuned to prejudice and discrimination, may particularly value identification and solidarity. Future studies should explore mediators/moderators to improve intervention efficacy.


Subject(s)
Black or African American , Schizophrenia , Social Stigma , Adolescent , Adult , Female , Humans , Male , Young Adult , Black or African American/ethnology , Racism , Schizophrenia/ethnology , Schizophrenia/rehabilitation , Video Recording , Racial Groups
10.
Addict Behav ; 153: 107996, 2024 06.
Article in English | MEDLINE | ID: mdl-38394959

ABSTRACT

Early positive subjective effects of cannabis predict the development of cannabis use disorder (CUD). Genetic factors, such as the presence of cytochrome P450 genetic variants that are associated with reduced Δ9-tetrahydrocannabinol (THC) metabolism, may contribute to individual differences in subjective effects of cannabis. Young adults (N = 54) with CUD or a non-CUD substance use disorder (control) provided a blood sample for DNA analysis and self-reported their early (i.e., effects upon initial uses) and past-year positive and negative subjective cannabis effects. Participants were classified as slow metabolizers if they had at least one CYP2C9 or CYP3A4 allele associated with reduced activity. Though the CUD group and control group did not differ in terms of metabolizer status, slow metabolizer status was more prevalent among females in the CUD group than females in the control group. Slow metabolizers reported greater past year negative THC effects compared to normal metabolizers; however, slow metabolizer status did not predict early subjective cannabis effects (positive or negative) or past year positive effects. Post-hoc analyses suggested males who were slow metabolizers reported more negative early subjective effects of cannabis than female slow metabolizers. Other sex-by-genotype interactions were not significant. These initial findings suggest that genetic variation in CYP2C9 and CYP3A4 may have sex-specific associations with cannabis-related outcomes. Slow metabolizer genes may serve as a risk factor for CUD for females independent of subjective effects. Male slow metabolizers may instead be particularly susceptible to the negative subjective effects of cannabis.


Subject(s)
Cannabis , Marijuana Abuse , Young Adult , Humans , Male , Female , Marijuana Abuse/complications , Sex Characteristics , Cytochrome P-450 CYP3A/genetics , Cytochrome P-450 CYP2C9 , Genotype
11.
Am J Psychother ; 77(3): 104-111, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38247343

ABSTRACT

The authors discuss the two broad domains of affect-focused and exposure-focused psychotherapies, defining the characteristics and potential advantages and disadvantages of each. The two domains differ in their theoretical approaches, structures, and techniques. Exposure-focused therapies have come to dominate research and practice, leading to the relative neglect of affect-focused therapies. When the two approaches have been examined in well-conducted clinical trials, they generally appear to be equally beneficial for treating common mood, anxiety, and trauma disorders, although further research may better define differential therapeutics. The authors argue for better training in affect awareness and tolerance across psychotherapies and use a brief case vignette to illustrate several aspects of these different approaches.


Subject(s)
Implosive Therapy , Humans , Implosive Therapy/methods , Affect , Anxiety Disorders/therapy , Anxiety Disorders/psychology , Mood Disorders/therapy , Mood Disorders/psychology , Psychotherapy/methods , Adult
12.
Med Cannabis Cannabinoids ; 7(1): 1-9, 2024.
Article in English | MEDLINE | ID: mdl-38292071

ABSTRACT

Introduction: Cannabidiol (CBD) is a widely utilized nonpsychoactive cannabinoid available as a prescriptive drug treatment and over-the-counter supplement. In humans, CBD is metabolized and forms the major active metabolite 7-hydroxy-cannabidiol (7-OH-CBD), which is further metabolized to 7-carboxy-cannabidiol (7-COOH-CBD). In the current study, plasma concentrations of CBD, 7-OH-CBD, and 7-COOH-CBD were measured, and the potential influences of sex, race, and body mass index (BMI) on the pharmacokinetic variability were assessed. Methods: Blood samples from a previously conducted CBD drug interaction study in healthy volunteers (n = 12) were utilized. The subjects received orally administered CBD (Epiodiolex®), 750 mg twice daily for 3 days and a single dose on the 4th day. Nine plasma samples were collected, and plasma concentrations of CBD, 7-OH-CBD, and 7-COOH-CBD were analyzed by LC-MS/MS. Peak plasma concentration (Cmax), time to Cmax (Tmax), area under the curve (AUC), and metabolite-to-parent drug exposure ratios (MPR) were calculated. Statistical analysis was performed to determine the correlations of Cmax, AUC, and MPR of CBD, 7-OH-CBD, and 7-COOH-CBD in different sex, race, BMI, and body weight. Results: For CBD, the mean Cmax was 389.17 ± 153.23 ng/mL, and the mean AUC was 1,542.19 ± 488.04 ng/mL*h. For 7-OH-CBD, the mean Cmax was 81.35 ± 36.64 ng/mL, the mean AUC was 364.70 ± 105.59 ng/mL*h, and the mean MPR was 0.25 ± 0.07. For 7-COOH-CBD, the mean Cmax was 1,717.33 ± 769.22 ng/mL, the mean AUC was 9,888.42 ± 3,961.47 ng/mL*h, and the mean MPR was 7.11 ± 3.48. For 7-COOH-CBD, a 2.25-fold higher Cmax was observed in female subjects (p = 0.0155) and a 1.97-fold higher AUC for female subjects (p = 0.0285) with the normalization of body weight. A significant linearity (p = 0.0135) of 7-OH-CBD AUC with body weight in females was observed. No significant differences were identified in Cmax, AUC, and PMR with race and BMI. Conclusion: Observed differences in sex were in agreement with previously reported findings. A larger population pharmacokinetics study is warranted to validate the observed higher Cmax and AUC in females and significant linearity with body weight in females from the current study.

13.
Psychiatr Serv ; : appips20230215, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38088037

ABSTRACT

OBJECTIVE: This study aimed to compare the efficacy of two brief video interventions in reducing mental health-related stigma: one featuring a person with lived experience of mental illness, the other featuring an actor guided by focus groups of individuals with lived experience. METHODS: Participants (N=1,216) ages 18-30 were randomly assigned to an intervention group or a control group. The intervention groups viewed one of two 2-minute videos in which a young Black protagonist describes symptoms, struggles, and personal recovery related to schizophrenia. Five domains of stigma were assessed at baseline, postintervention, and a 30-day follow-up. RESULTS: Stigma scores were lower across all five domains in both intervention groups (vs. control), and noninferiority analyses found no difference between the two videos (all p<0.001). CONCLUSIONS: This study enhanced prior findings showing similar efficacy of the two videos and illustrated opportunities for people with mental illness to share their personal stories without public exposure.

14.
J Clin Psychiatry ; 85(1)2023 Nov 22.
Article in English | MEDLINE | ID: mdl-38019593

ABSTRACT

Background: Posttraumatic stress disorder (PTSD) is prevalent after surviving sudden cardiac arrest (SCA). SCA-induced PTSD is associated with increased mortality and cardiovascular risk, yet no psychotherapeutic treatment has been developed and tested for this population. Exposure therapy is standard treatment for PTSD, but its safety and efficacy remain unconfirmed for SCA survivors: current protocols do not address their specific disease course and have high attrition. Mindfulness-based interventions are typically well-tolerated and have shown promise in reducing PTSD symptoms from other traumas.Objective: This study sought to determine feasibility, safety, and preliminary efficacy of acceptance and mindfulness-based exposure therapy (AMBET), a novel SCA-specific psychotherapy protocol combining mindfulness and exposure-based interventions with cardiac focused psychoeducation to reduce symptoms and improve health behaviors in patients with post-SCA PTSD.Methods: We conducted an open feasibility pilot study from January 2021 to April 2022 with a small sample (N = 11) of SCA survivors meeting DSM-5 PTSD criteria. AMBET comprised eight 90-minute remotely delivered individual sessions. Clinical evaluators assessed PTSD symptoms using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at baseline, midpoint, posttreatment, and 3-month follow-up.Results: Ten (91%) of 11 enrolled patients completed treatment. Satisfaction was high and patients reported no adverse events. PTSD symptoms significantly improved statistically (P < .001) and clinically with large effect sizes (g = 1.34-2.21) and treatment gains sustained at 3-month follow-up. Posttreatment, 80% of completers (n = 8) showed significant treatment response, 70% (n = 7) with PTSD diagnostic remission. No patient reported symptom increases.Conclusions: This initial trial found AMBET feasible, safe, and potentially efficacious in reducing PTSD following SCA. These encouraging pilot results warrant further research.Trial Registration: ClinicalTrials.gov identifier: NCT04596891.


Subject(s)
Heart Arrest , Implosive Therapy , Mindfulness , Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/therapy , Stress Disorders, Post-Traumatic/diagnosis , Implosive Therapy/methods , Pilot Projects , Feasibility Studies , Death, Sudden, Cardiac , Treatment Outcome
15.
Chem Biol Interact ; 384: 110715, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37716419

ABSTRACT

Kratom, (Mitragyna Speciosa Korth.) is a plant indigenous to Southeast Asia whose leaves are cultivated for a variety of medicinal purposes and mostly consumed as powders or tea in the United States. Kratom use has surged in popularity with the lay public and is currently being investigated for possible therapeutic benefits including as a treatment for opioid withdrawal due to the pharmacologic effects of its indole alkaloids. A wide array of psychoactive compounds are found in kratom, with mitragynine being the most abundant alkaloid. The drug-drug interaction (DDI) potential of mitragynine and related alkaloids have been evaluated for effects on the major cytochrome P450s (CYPs) via in vitro assays and limited clinical investigations. However, no thorough assessment of their potential to inhibit the major hepatic hydrolase, carboxylesterase 1 (CES1), exists. The purpose of this study was to evaluate the in vitro inhibitory potential of kratom extracts and its individual major alkaloids using an established CES1 assay and incubation system. Three separate kratom extracts and the major kratom alkaloids mitragynine, speciogynine, speciociliatine, paynantheine, and corynantheidine displayed a concentration-dependent reversible inhibition of CES1. The experimental Ki values were determined as follows for mitragynine, speciociliatine, paynantheine, and corynantheidine: 20.6, 8.6, 26.1, and 12.5 µM respectively. Speciociliatine, paynantheine, and corynantheidine were all determined to be mixed-type reversible inhibitors of CES1, while mitragynine was a purely competitive inhibitor. Based on available pharmacokinetic data, determined Ki values, and a physiologically based inhibition screen mimicking alkaloid exposures in humans, a DDI mediated via CES1 inhibition appears unlikely across a spectrum of doses (i.e., 2-20g per dose). However, further clinical studies need to be conducted to exclude the possibility of a DDI at higher and extreme doses of kratom and those who are chronic users.


Subject(s)
Mitragyna , Humans , Plant Extracts/pharmacology , Carboxylic Ester Hydrolases
17.
Psychiatr Serv ; 74(10): 1010-1018, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37042105

ABSTRACT

OBJECTIVE: Emerging cross-sectional data indicate that essential workers in the COVID-19 era face increased mental health risks. This study longitudinally examined clinical symptoms of generalized anxiety disorder, depression, and posttraumatic stress disorder (PTSD) among U.S. essential workers, including health care workers and workers in indispensable occupations such as manufacturing, food industry, construction, transportation, hospitality, and emergency services, during the COVID-19 pandemic. The authors anticipated high symptom levels and greater symptom severity among women versus men and among younger adults compared with older adults. Analyses also explored the association between COVID-19 vaccination status and clinical symptoms. METHODS: This four-wave online survey study assessed clinical symptoms in a convenience sample of 4,136 essential workers at baseline and 14, 30, and 90 days between August and December 2021. Symptoms of anxiety, depression, and PTSD were measured with the Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Primary Care PTSD Screen instruments, respectively. RESULTS: At every time point, 74%-78% of respondents reported symptoms of anxiety and depression, which were highest among younger adults (ages 18-22 years), females, and transgender respondents. Vaccinated participants had slightly higher symptom levels than unvaccinated respondents. Rates of clinical symptoms did not change significantly over time. CONCLUSIONS: Essential workers consistently reported symptoms of generalized anxiety, depression, or PTSD, especially younger adult, female, and transgender participants. The overwhelming and unprecedented nature of the COVID-19 pandemic underscores the need to offer mental health care to essential workers, especially those in these subgroups. Employers and administrators should support and proactively encourage employees to access care when needed.


Subject(s)
COVID-19 Vaccines , COVID-19 , Male , Female , Humans , Aged , Cross-Sectional Studies , Depression/epidemiology , Pandemics/prevention & control , COVID-19/epidemiology , Anxiety Disorders/epidemiology , Anxiety/epidemiology , Health Personnel
18.
J Behav Ther Exp Psychiatry ; 78: 101805, 2023 03.
Article in English | MEDLINE | ID: mdl-36435547

ABSTRACT

BACKGROUND AND OBJECTIVES: Research has examined reductions in patient distress recounting trauma narratives in Prolonged Exposure (PE) for posttraumatic stress disorder (PTSD). It remains unclear whether changes in distress and avoidance related to environmental trauma reminders matter in PE and other PTSD treatments, including non-exposure Interpersonal Psychotherapy (IPT). METHODS: Data came from adults with chronic PTSD (N = 92) who completed a treatment trial comparing PE, IPT, and Relaxation Therapy (RT). We employed the Self-Initiated In-Vivo Exposure Scale (SIIVES), which measures patient distress from and avoidance of situational trauma reminders, to calculate reliable change in distress and avoidance. PTSD symptoms, depression, quality of life, and functioning assessments were collected before and after 14 weeks of treatment. RESULTS: Overall, 48.1% of patients experienced reliable change in avoidance, while 51.9% showed reliable change in distress. Rates of reliable change did not differ by treatment group, although PE appeared to achieve reliable change earlier. Only one baseline characteristic predicted reliable change: patients with comorbid depression were less likely to reliably change in avoidance. At post-treatment, patients achieving reliable change had lower PTSD severity and depression and increased quality of life and social functioning. Statistical modeling revealed that changes in distress and avoidance related to subsequent reduction in PTSD symptoms in all three treatment groups, though this relationship appeared strongest in PE. LIMITATIONS: The sample was relatively small. CONCLUSIONS: Change in avoidance and distress associated with situational trauma reminders was associated with a range of clinical outcomes and may represent important factors in multiple PTSD psychotherapies.


Subject(s)
Implosive Therapy , Stress Disorders, Post-Traumatic , Adult , Humans , Stress Disorders, Post-Traumatic/therapy , Stress Disorders, Post-Traumatic/complications , Quality of Life , Relaxation Therapy , Comorbidity
19.
Psychiatr Serv ; 74(2): 119-126, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36097721

ABSTRACT

OBJECTIVE: Many health care workers avoid seeking mental health care, despite COVID-19-related increases in risk of psychopathology. This study assessed the effects of two versions (distinguished by the race of the protagonist) of a brief social contact-based video on treatment-seeking intention and stigma toward mental health services among U.S. health care workers. METHODS: Participants (N=1,402) were randomly assigned to view a 3-minute video in which a Black or White female nurse described struggles with COVID-19-related anxiety and depression, barriers to care, and how therapy helped, or to view a control video unrelated to mental health. Half of the participants receiving the intervention watched the same video (i.e., booster) again 14 days later. Treatment-seeking intention and treatment-related stigma were assessed at baseline, postintervention, and 14- and 30-day follow-ups. RESULTS: Both intervention videos elicited an immediate increase in treatment-seeking intention in the intervention groups (p<0.001, effect size [ES]=21%), with similar effects among those who watched the booster video (p=0.016, ES=13%) and larger effects among those who had never sought treatment (p<0.001, ES=34%). The increased effects were not sustained 14 days after the initial video or at 30-day follow-up. The results showed an immediate reduction in stigma, but with no booster effect. The race of the protagonist did not influence outcomes. CONCLUSIONS: This easily administered intervention could increase the likelihood of care seeking by proactively encouraging health care workers with mental health challenges to pursue treatment. Future studies should examine whether the inclusion of linkable referrals to mental health services helps to increase treatment-seeking behavior.


Subject(s)
COVID-19 , Mental Health Services , Humans , Female , Intention , Mental Health , Crisis Intervention , Patient Acceptance of Health Care/psychology , Social Stigma
20.
Psychiatr Serv ; 74(3): 229-236, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36254455

ABSTRACT

OBJECTIVE: Confronting stigma early in life could enhance treatment seeking. In two randomized controlled trials (RCTs), one focused on psychosis and the other on adolescent depression, the efficacy and equivalence of brief social contact-based videos were evaluated and compared with a control condition. The outcomes of interest were changes in illness-related stigma and treatment-seeking intention. The hypotheses were that the intervention videos would show greater efficacy than control conditions and that traditional and selfie videos would demonstrate similar efficacy. METHODS: Young adults (study 1, N=895) and adolescents (study 2, N=637) were randomly assigned to view intervention videos (in traditional or selfie styles) or to a control condition. In short videos (58-102 seconds), young presenters humanized their illness by emotionally describing their struggles and discussing themes of recovery and hope. RESULTS: Repeated-measures analyses of variance and paired t tests showed significant differences in stigma and treatment seeking between the intervention and control groups and similar efficacy of the traditional and selfie videos. Cohen's d effect sizes ranged from 0.31 to 0.76 for changes in stigma from baseline to 30-day follow-up in study 1 and from 0.13 to 0.47 for changes from baseline to postintervention in study 2. CONCLUSIONS: The RCTs demonstrated the efficacy of brief videos, both traditional and selfie, in reducing illness-related stigma among young adults and adolescents and in increasing treatment-seeking intention among adolescents. Future studies should explore the effects of brief videos presented by social media influencers on mental health stigma and treatment engagement.


Subject(s)
Psychotic Disorders , Social Stigma , Young Adult , Humans , Adolescent , Randomized Controlled Trials as Topic , Mental Health , Follow-Up Studies
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