Mental health impact of the COVID-19 pandemic in U.S. military veterans: a population-based, prospective cohort study.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has caused myriad health, social, and economic stressors. To date, however, no known study has examined changes in mental health during the pandemic in the U.S. military veteran population. METHODS: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, a nationally representative, prospective cohort survey of 3078 veterans. Pre-to-peri-pandemic changes in psychiatric symptoms were evaluated, as well as pre-pandemic risk and protective factors and pandemic-related correlates of increased psychiatric distress. RESULTS: The prevalence of generalized anxiety disorder (GAD) positive screens increased from pre- to peri-pandemic (7.1% to 9.4%; p < 0.001) and was driven by an increase among veterans aged 45-64 years (8.2% to 13.5%; p < 0.001), but the prevalence of major depressive disorder and posttraumatic stress disorder positive screens remained stable. Using a continuous measure of psychiatric distress, an estimated 13.2% of veterans reported a clinically meaningful pre-to-peri-pandemic increase in distress (mean = 1.1 standard deviation). Veterans with a larger pre-pandemic social network size and secure attachment style were less likely to experience increased distress, whereas veterans reporting more pre-pandemic loneliness were more likely to experience increased distress. Concerns about pandemic-related social losses, mental health COVID-19 effects, and housing stability during the pandemic were associated with increased distress, over-and-above pre-pandemic factors. CONCLUSIONS: Although most U.S. veterans showed resilience to mental health problems nearly 1 year into the pandemic, the prevalence of GAD positive screens increased, particularly among middle-aged veterans, and one of seven veterans experienced increased distress. Clinical implications of these findings are discussed.

Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden.

BACKGROUND: Little is known about environmental factors that may influence associations between genetic liability to suicidality and suicidal behavior. METHODS: This study examined whether a suicidality polygenic risk score (PRS) derived from a large genome-wide association study (N = 122,935) was associated with suicide attempts in a population-based sample of European-American US military veterans (N = 1664; 92.5% male), and whether cumulative lifetime trauma exposure moderated this association. RESULTS: Eighty-five veterans (weighted 6.3%) reported a history of suicide attempt. After adjusting for sociodemographic and psychiatric characteristics, suicidality PRS was associated with lifetime suicide attempt (odds ratio 2.65; 95% CI 1.37-5.11). A significant suicidality PRS-by-trauma exposure interaction emerged, such that veterans with higher levels of suicidality PRS and greater trauma burden had the highest probability of lifetime suicide attempt (16.6%), whereas the probability of attempts was substantially lower among those with high suicidality PRS and low trauma exposure (1.4%). The PRS-by-trauma interaction effect was enriched for genes implicated in cellular and developmental processes, and nervous system development, with variants annotated to the DAB2 and SPNS2 genes, which are implicated in inflammatory processes. Drug repurposing analyses revealed upregulation of suicide gene-sets in the context of medrysone, a drug targeting chronic inflammation, and clofibrate, a triacylglyceride level lowering agent. CONCLUSION: Results suggest that genetic liability to suicidality is associated with increased risk of suicide attempt among veterans, particularly in the presence of high levels of cumulative trauma exposure. Additional research is warranted to investigate whether incorporation of genomic information may improve suicide prediction models.

Cannabis use among U.S. military veterans with subthreshold or threshold posttraumatic stress disorder: Psychiatric comorbidities, functioning, and strategies for coping with posttraumatic stress symptoms.

Cannabis use is common among individuals with posttraumatic stress disorder (PTSD) symptoms, but its impact on psychiatric symptoms and functioning in this population is unclear. To clarify the clinical and functional correlates of cannabis use in individuals with PTSD symptoms, we analyzed data from the 2019-2020 National Health and Resilience in Veterans Study, a nationally representative survey of U.S. military veterans. Participants with current subthreshold or full PTSD (N = 608) reported on their past-6-month cannabis use and current psychiatric symptoms, functioning, treatment utilization, and PTSD symptom management strategies. Veterans with subthreshold/full PTSD who used cannabis more than weekly were more likely to screen positive for co-occurring depression, anxiety, and suicidal ideation than those who did not use cannabis, ORs = 3.4-3.8, or used cannabis less than weekly, ORs = 2.7-3.7. Veterans who used cannabis more than weekly also scored lower in cognitive functioning than veterans with no use, d = 0.25, or infrequent use, d = 0.71, and were substantially more likely to endorse avoidance coping strategies, ORs = 8.2-12.2, including substance use, OR = 4.4, and behavioral disengagement, ORs = 2.7-9.1, to manage PTSD symptoms. Despite more psychiatric and functional problems, veterans with frequent cannabis use were not more likely to engage in mental health treatment, ORs = 0.87-0.99. The results suggest enhanced cannabis use screening, interventions targeting risky use, and strategies promoting treatment engagement may help ameliorate more severe clinical presentations associated with frequent cannabis use among veterans with subthreshold/full PTSD.

Social withdrawal and psychological well-being in later life: does marital status matter?

Objectives: Personality researchers have found that dispositional traits are typically stabile over the life course, but shyness is one trait that has rarely been examined in later life. Shyness as a global trait has been linked negatively to multiple psychological indices of childhood well-being, including loneliness. Despite the fact that older adults may already be at risk for experiencing heightened loneliness, regret, or decreased fulfillment, research has not assessed these experiences in relation to personality in later life. In the past few decades, research on social withdrawal has moved beyond treating shyness as a global trait and started to examine the multiple motivations behind socially withdrawn behavior.Method: Employing data from 309 older participants of the Huntsman Senior Games, the current study used regression analyses to examine the potential relations between three forms of withdrawal (shyness, avoidance, and unsociability) and loneliness, regret, and fulfillment in later life.Results and Conclusion: Results indicated that shyness, avoidance, and unsociability, respectively, were significantly associated with increased loneliness and regret, and decreased fulfillment. Further, marital status (married, divorced, widowed) moderated links between withdrawal and psychological indices of well-being in later life.

Look Who's Talking: Mediums of Contact Among Mid-to Later-Life Siblings.

Adult siblings maintain contact and remain close to one another. The current study used participants recruited via Amazon Mechanical Turk (n = 491) to conduct regression analyses examining five methods of contact (in person, telephone, email, texting, and social media) predicting sibling closeness and conflict. Further, two- and three-way interactions assessed the role of sibling dyad composition (e.g., women with a sister and women with a brother). Results suggested that as contact in person, through social media, the telephone, or email increased, sibling closeness increased, while increased contact through email indicated less conflict. Assessing sibling dyad composition suggested as telephone contact increased, sibling closeness increased for all sibling dyads, especially for women with a sister compared to men with a brother. In-person and texting contacts were beneficial for women with a brother. Even in mid- to later-life, siblings connect through synchronous and asynchronous mediums, and this contact appears beneficial for sisters.

'I feel like a person has a right to use a product to protect themselves ': a qualitative study of the risk-benefit calculus on women's contraceptive use and choice.

Background Reducing pregnancy risk requires a multidimensional approach to sexual and reproductive health product development. The purpose of this analysis is to identify, compare, and contrast women's pre-use beliefs and attitudes about three different forms of contraceptives: intravaginal rings; spermicide in conjunction with condoms; and oral contraceptive pills - and explore how those attitudes and beliefs, along with actual method-use experience, may affect potential choices in contraceptive method moving forward. The relationship of beliefs and attitudes to their risk-benefit calculations when using these methods was also considered.? METHODS: Women used one or more contraceptive methods, each for 3-6 months. Qualitative data from individual in-depth interviews completed after each 3-month use period were analysed using a summary matrix framework. Data were extracted and summarised into themes. Each woman's experiences were compared among the methods she used; comparisons were also made across participants. RESULTS: The data consist of 33 90-120 min in-depth qualitative interviews from 16 women aged 20-34 years, in which they discussed various elements of their method use experience. One prominent theme was identified: the influence of attitudes and beliefs on the risk-benefit calculus. There were six key elements within the theme: pregnancy prevention; dosing and the potential for user error; side-effects; familiarity; disclosure; and sexual partnerships. CONCLUSIONS: Women weighed perceived risks and benefits in their decision-making and, ultimately, their contraception choices. Understanding women's beliefs and attitudes that contribute to a calculation of risk-benefit can inform the development of sexual and reproductive health products.

Social Withdrawal and Loneliness Among Older Adult Athletes: A Case for Playing Alone.

Some older adults may not receive social connection due to social withdrawal, potentially resulting in loneliness. The purpose of this study was to examine relationships between social withdrawal and loneliness, in the context of sports participation. The authors hypothesized that individuals who are more shy and avoidant would be more lonely than those who are less shy and avoidant, and that those who are unsocial would not necessarily be more lonely. The authors also hypothesized individual sport participation would further exacerbate loneliness over group sport participation. Results from participants in the Huntsman Senior Games (n = 374) indicated that as shyness, avoidance, and unsociability increased, loneliness increased as well. Furthermore, shy athletes in group sports reported higher levels of loneliness than those in individual sports. Although the authors seek to prevent individuals from being lonely in later life, there may be instances where removing oneself from a group is beneficial for mental health.

Biological, Psychological, and Social Predictors of Longevity Among Utah Centenarians.

Studies of longevity among centenarians examine biological, psychological, and social factors, yet few consider these components concurrently. This study explores such factors individually and collectively, as they are related to days lived past the age of 100 years. Data from 268 family members of centenarians identified in the State of Utah between 2008 and 2015 were used in negative binomial models predicting number of days lived among the centenarians. Findings suggested that sleep latency (biological), life satisfaction (psychological), and attachment closeness (social) were predictive factors of more days lived within individual models. When considered together, sleep latency and life satisfaction remained significant predictors of days lived. Although biological factors are commonly considered in relation to longevity, this study further indicates that psychological and social factors may play important roles in life expectancy. Further examination is needed to explore how these factors link additionally to active life expectancy.

Modulation of Dcytb (Cybrd 1) expression and function by iron, dehydroascorbate and Hif-2α in cultured cells.

BACKGROUND: Duodenal cytochrome b (Dcytb) is a mammalian plasma ferric reductase enzyme that catalyses the reduction of ferric to ferrous ion in the process of iron absorption. The current study investigates the relationship between Dcytb, iron, dehydroascorbate (DHA) and Hif-2α in cultured cell lines. METHODS: Dcytb and Hif-2α protein expression was analysed by Western blot technique while gene regulation was determined by quantitative PCR. Functional analyses were carried out by ferric reductase and (59)Fe uptake assays. RESULTS: Iron and dehydroascorbic acid treatment of cells inhibited Dcytb mRNA and protein expression. Desferrioxamine also enhanced Dcytb mRNA level after cells were treated overnight. Dcytb knockdown in HuTu cells resulted in reduced mRNA expression and lowered reductase activity. Preloading cells with DHA (to enhance intracellular ascorbate levels) did not stimulate reductase activity fully in Dcytb-silenced cells, implying a Dcytb-dependence of ascorbate-mediated ferrireduction. Moreover, Hif-2α knockdown in HuTu cells led to a reduction in reductase activity and iron uptake. CONCLUSIONS: Taken together, this study shows the functional regulation of Dcytb reductase activity by DHA and Hif-2α. GENERAL SIGNIFICANCE: Dcytb is a plasma membrane protein that accepts electrons intracellularly from DHA/ascorbic acid for ferrireduction at the apical surface of cultured cells and enterocytes.

Health and psychiatric impairment associated with moral injury, military sexual trauma, and their co-occurrence in U.S. combat veterans.

BACKGROUND: Military sexual trauma (MST) and moral injury (MI) are associated with adverse psychiatric and health outcomes among military veterans. However, no known population-based studies have examined the incremental burden associated with the co-occurrence of these experiences relative to either alone. METHOD: Cross-sectional data were analyzed from the National Health and Resilience in Veterans Study, a nationally representative sample of 1330 U.S. combat veterans. Veterans reported on history of exposure to MST and potentially morally injurious events (PMIEs). Analyses estimated the lifetime prevalence of MST only, PMIEs only, and co-occurring MST and PMIEs; and examined associations between MST/PMIEs status and psychiatric and physical health comorbidities, functioning, and suicidality. RESULTS: The lifetime weighted prevalence of exposure to MST only, PMIEs only, and co-occurring MST and PMIEs were 2.7%, 32.3%, and 4.5%, respectively. Compared with all other groups, the co-occurring MST + PMIEs group reported greater severity of posttraumatic stress, depression, generalized anxiety, and insomnia symptoms. They also scored lower on measures of physical, mental, and psychosocial functioning, and reported a greater number of chronic medical conditions and somatic complaints. Veterans with co-occurring MST + PMIEs were more than twice as likely as those with MST only to report past-year suicidal ideation. CONCLUSIONS: The co-occurrence of MST and MI is associated with a greater psychiatric and health burden among combat veterans than either experience alone. Results underscore the importance of assessing and treating MST and MI in this population. Findings underscore the importance for future work to parse overlap between morally salient aspects of MST and the concept of moral injury.

Firearm storage practices among military veterans in the United States: Findings from a nationally representative survey.

BACKGROUND: Unsafe storage of firearms is associated with increased risk of suicide.. However, contemporary population-based data on the prevalence and correlates of firearm storage practices among veterans are limited. METHODS: Data were from the 2022 National Health and Resilience in Veterans Study, a nationally representative sample of 2441 veterans. Analyses examined: (1) the prevalence of firearm storage practices; (2) sociodemographic, psychiatric, and clinical characteristics associated with storing firearms loaded and/or in non-secure location; and (3) associations between types of potentially traumatic events and storage practices. RESULTS: More than half of veterans reported owning one or more personal firearms (50.9%). Among firearm owners, 52.9% reported some form of unsafe firearm storage practice (i.e., loaded and/or non-secure location), with 39.9% reporting that they stored one or more firearms loaded. After adjusting for sociodemographic characteristics, major depressive, alcohol and drug use disorders, direct trauma exposures, future suicidal intent, and traumatic brain injury were associated with storing firearms loaded and/or in a non-secure location (ORs = 1.09-7.16). Veterans with a history of specific forms of direct trauma exposure (e.g., physical assault) were more likely to store firearms unsafely. LIMITATIONS: Cross-sectional design precludes causal inference. CONCLUSIONS: Half of U.S. veterans who own firearms store at least one personal firearm loaded and/or in a non-secure location, with approximately four-in-ten keeping a loaded firearm in the home. These high rates underscore the importance of nationwide training initiatives to promote safe firearm storage for all service members and veterans, regardless of risk status, as well as for healthcare professionals working with veterans.

Cannabis use and trauma-focused treatment for co-occurring posttraumatic stress disorder and substance use disorders: A meta-analysis of individual patient data.

High rates of cannabis use among people with posttraumatic stress disorder (PTSD) have raised questions about the efficacy of evidence-based PTSD treatments for individuals reporting cannabis use, particularly those with co-occurring alcohol or other substance use disorders (SUDs). Using a subset of four randomized clinical trials (RCTs) included in Project Harmony, an individual patient meta-analysis of 36 RCTs (total N = 4046) of treatments for co-occurring PTSD+SUD, we examined differences in trauma-focused (TF) and non-trauma-focused (non-TF) treatment outcomes for individuals who did and did not endorse baseline cannabis use (N = 410; 70% male; 33.2% endorsed cannabis use). Propensity score-weighted mixed effects modeling evaluated main and interactive effects of treatment assignment (TF versus non-TF) and baseline cannabis use (yes/no) on attendance rates and within-treatment changes in PTSD, alcohol, and non-cannabis drug use severity. Results revealed significant improvements across outcomes among participants in all conditions, with larger PTSD symptom reductions but lower attendance among individuals receiving TF versus non-TF treatment in both cannabis groups. Participants achieved similar reductions in alcohol and drug use across all conditions. TF outperformed non-TF treatments regardless of recent cannabis use, underscoring the importance of reducing barriers to accessing TF treatments for individuals reporting cannabis use.

An exploration of happiness, anxiety symptoms, and depressive symptoms among older adults during the coronavirus pandemic.

The COVID-19 pandemic has affected millions of people worldwide. Because of the challenges associated with the pandemic, universal levels of happiness have likely depleted. We know little about how those with prior existing mental health concerns have responded to the pandemic. Using cross-sectional (study 1; N = 1,366) and longitudinal (study 2; N = 262) data, we utilized a stress and resilience perspective to explore mental health symptoms and happiness among older adults before and after the declaration of the pandemic. Results for both studies indicated higher levels of depression and anxiety symptoms predicted lower levels of happiness; however, for those who indicated higher levels of mental health symptoms, post-pandemic declaration happiness levels were higher than pre-pandemic happiness levels. Findings suggest that resilience may be learned throughout a lifetime, and that experiences from prior stressors may show benefits in responding to future ones, even among vulnerable populations.

Amino Acid Analyses of Plant Foods Used in the Dietary Management of Inherited Amino Acid Disorders.

A low amino acid (AA)/protein diet is the principal treatment for many inherited amino acid disorders (IMDs). Due to their low AA content, plant foods constitute an essential part of diet therapy. However, data on their AA composition are limited, which leads to an estimation of AA intake from protein content rather than an accurate calculation of true AA intake. This study describes the AA content of a total of 73 plant foods (fruits, n = 12; vegetables, n = 51; and other plant foods, n = 10), with the analysis commissioned by the UK National Society for Phenylketonuria (NSPKU) over 15 years. For all fruits and some vegetables (e.g., rocket, watercress and pea shoots), raw samples were used during analysis. All other vegetables were cooked prior to analysis to represent the usual condition of the food at the time of serving. AA analysis was performed with ion exchange chromatography. The median percentage of protein was 2.0% [0.6-5.4%] for the fruits and vegetables analysed (n = 56), although higher in vegetables than in fruits. Each of the five reported AAs (leucine, lysine, phenylalanine, tyrosine, and methionine) supplied 1-5% per g of protein content. From the heterogeneous range of plant foods analysed, the AA/protein ratios differed significantly (2-5% in fruits and 1-9% in vegetables). There was a strong correlation between the amounts of each of the five AAs in the plant foods, but only a small, moderate correlation between the protein and AA content. Overall, this study provides data on the AA content of several plant foods, which are suitable for patients treated with a low AA/protein diet, including many novel plant options. However, only a limited range of fruits and vegetables were analysed due to the high costs of analysis. Hence, more extensive studies with an increased number of plant foods prepared by different cooking methods and replicate samples are necessary, particularly to examine the relationship between the protein and AA content in depth.

Childhood Sexual Abuse and Military Sexual Trauma Interact to Increase Suicide Risk: Results from a Nationally Representative Veteran Sample.

Childhood sexual abuse (CSA) and military sexual trauma (MST) are prevalent among veterans. Such exposures are associated with adverse mental-health sequelae, including elevated risk for suicidal thoughts and behaviors. Nonetheless, prior studies have largely focused upon discrete experiences of CSA or MST in circumscribed samples. In the current study, we analyzed data from a large, nationally representative sample of 4,069 US military veterans to examine main and interactive effects of CSA and MST in relation to suicidal thoughts and behaviors. After accounting for sociodemographics, psychiatric comorbidity, and trauma-related characteristics, we detected a significant interaction between MST and CSA as it related to report of past-year suicidal ideation, lifetime suicide attempt, and risk for future suicide attempt. These findings underscore the impact of sexual trauma throughout the lifespan, highlighting the continued importance of screening for trauma exposure and connecting veterans to appropriate, evidence-based treatment to decrease their risk for suicidal thoughts and behaviors.

Sex Differences in the Pharmacokinetics of Cannabidiol and Metabolites Following Oral Administration of a Cannabidiol-Dominant Cannabis Oil in Healthy Adults.

Introduction: Oral cannabidiol (CBD) product use is increasingly growing among women; however, there is a lack of data on sex differences in the pharmacokinetics (PKs) of CBD and its primary metabolites, 7-hydroxy-CBD (7-OH-CBD) and 7-carboxy-CBD (7-COOH-CBD), after repeated doses. Materials and Methods: The present study is a secondary analysis of data from a randomized, double-blind, placebo-controlled multiple-dose trial of a commercially available, CBD-dominant oral cannabis product. Healthy participants (n=17 males and 15 females) were randomized to receive 120 to 480 mg of CBD daily for 7 days. Dosing groups were pooled for all analyses due to sample size limitations. Analyses compared plasma PK parameters by sex, day, and sex×day. Results: For raw PK parameters for CBD and metabolites, there were no statistically significant effects of sex×day or sex (all p-values >0.05). For metabolite-to-parent ratios (MPRs) of AUC0-t, there were significant effects of the sex×day interactions for 7-OH-CBD (F=6.89, p=0.016) and 7-COOH-CBD (F=5.96, p=0.021). For 7-OH-CBD, follow-up analyses showed significant simple effects of day within females (t=4.13, p<0.001), but not within males (t=0.34, p=0.73), such that 7-OH-CBD MPRs increased significantly from day 1 to 7 for females, but not for males. For 7-COOH-CBD, follow-up analyses revealed significant simple effects of day within females (t=8.24, p<0.001) and males (t=5.20, p<0.001), therefore 7-COOH-CBD MPRs increased significantly from day 1 to 7 in both sexes, but the increase was significantly greater among females than among males. Within dosing days, there were no statistically significant simple effects of sex on MPRs of 7-OH-CBD or 7-COOH-CBD. Conclusions: Females exhibited greater relative exposure to CBD metabolites in plasma over time, which may reflect sex differences in CBD metabolism or elimination. Further research assessing the safety implications of higher relative exposure to CBD metabolites over longer periods of time is warranted to mirror typical consumer use patterns.

Firearm Ownership Among a Nationally Representative Sample of U.S. Veterans.

INTRODUCTION: This study aimed to identify the prevalence and correlates of firearm ownership in a large, contemporary, nationally representative sample of U.S. military veterans. METHODS: Data were analyzed from the 2022 National Health and Resilience in Veterans Study (N=2,326; mean age=60.2 years). Weighted independent-sample t-tests and chi-square analyses were conducted to compare veterans who did with those who did not report firearm ownership on sociodemographic, military, and psychiatric variables. A multivariable logistic regression analysis using backward elimination was conducted to identify the characteristics independently associated with firearm ownership, and a relative importance analysis was conducted to quantify the relative variance in firearm ownership that was explained by each of the statistically significant main effects. RESULTS: Of the total 2,326 veterans, 1,217 (weighted 50.9%, 95% CI=48.0%, 53.9%) reported owning any firearms. Male sex, conservative political ideology, living in rural area, home ownership, cumulative trauma burden, and lifetime history of alcohol use disorder were most strongly associated with firearm ownership. CONCLUSIONS: This study provides an updated characterization of the prevalence and correlates of firearm ownership among the U.S. veterans. Results of this nationally representative study suggest that firearm ownership in this group may be higher than previously reported and underscore the importance of targeted suicide prevention efforts promoting firearm safety among vulnerable segments of this population.

Factors associated with remission of suicidal thoughts and behaviors in U.S. military veterans with a history of suicide attempt.

Suicide is a major public health problem in U.S. military veterans, but little is known about factors associated with remission from suicide attempts in this population. We aimed to identify risk and protective correlates of remission from suicidal thoughts and behavior (STB) in U.S. veterans with a prior suicide attempt. Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study survey. A broad range of sociodemographic, military, physical and mental health, and psychosocial variable were assessed. Purpose in life, dispositional gratitude, and conscientiousness emerged as independent correlates of STB remission (24.3%-40.3% of explained variance), even after accounting for other relevant risk and protective factors. While the cross-sectional nature of the study precludes the ability to determine whether the identified protective factors are causally related to STB remission, results suggest three potentially modifiable targets for suicide prevention efforts in veterans. Longitudinal studies are needed to better understand the role of purpose in life, dispositional gratitude, and conscientiousness in promoting remission from STBs in veterans and other populations at risk for suicide.

Dietetic Management of Adults with Phenylketonuria (PKU) in the UK: A Care Consensus Document.

There is an increasing number of adults and elderly patients with phenylketonuria (PKU) who are either early, late treated, or untreated. The principal treatment is a phenylalanine-restricted diet. There is no established UK training for dietitians who work with adults within the specialty of Inherited Metabolic Disorders (IMDs), including PKU. To address this, a group of experienced dietitians specializing in IMDs created a standard operating procedure (SOP) on the dietetic management of adults with PKU to promote equity of care in IMD dietetic services and to support service provision across the UK. The group met virtually over a period of 12 months until they reached 100% consensus on the SOP content. Areas of limited evidence included optimal blood phenylalanine reporting times to patients, protein requirements in older adults, management of weight and obesity, and management of disordered eating and eating disorders. The SOP does not include guidance on maternal PKU management. The SOP can be used as a tool for training dietitians new to the specialty and to raise the standard of education and care for patients with PKU in the UK.

Serum Markers of Bone Turnover Following Controlled Administration of Two Medical Cannabis Products in Healthy Adults.

Introduction: Cannabidiol (CBD) has been shown to maintain bone integrity in pre-clinical models, but little is known about the effects of delta-9-tetrahydrocannabinol (THC) on bone turnover. In this study we explored the effects of two oral medical cannabis products on normal bone homeostasis through evaluation of markers of bone resorption (carboxyl-terminal collagen crosslinks, CTx) and bone formation (procollagen type 1 N-terminal propeptide, P1NP; alkaline phosphatase, ALP). Methods: This study is an analysis of secondary data from two Phase 1 double-blind, placebo-controlled trials of Spectrum Yellow (0.9 mg THC, 20 mg CBD/mL of oil) and Spectrum Red (2.5 mg THC, 0.3 mg CBD/softgel). Healthy participants (n=38 men, 45 women) were randomized to receive 5-20 mg THC (CBD levels varied as a function of administered product) or placebo daily (BID) for 7 days. Bone markers were assessed at baseline, upon completion of product administration (day 8), and after a 5-day washout (day 13). Results: All bone markers were significantly higher in men at baseline (p≤0.008). For CTx, there was a significant day×group interaction (F=3.23, p=0.04); CTx levels were significantly lower in participants treated with Spectrum Red (b=-164.28; 95% confidence interval [CI], -328 to -0.29; p=0.04) and marginally lower in participants treated with Spectrum Yellow (b=-157.31; 95% CI, -323 to 8.68; p=0.06) versus placebo on day 8. For P1NP and ALP, there were no significant differences between treatments across study days. Bone marker values outside the reference range (RR) were observed; CTx > RR (n=71) was predominantly (85.9%) observed in male participants, whereas P1NP > RR (n=100) was more evenly distributed between sexes (53.0% in men). These were not considered clinically significant and did not differ between treatment groups. Conclusions: These are the first interventional human data on the effect of cannabinoids on biomarkers of bone turnover. Short-term treatment with CBD- or THC-dominant medical cannabis products resulted in attenuation of a marker of bone resorption. Although the attenuation was not clinically significant, this finding may be indicative of protective properties of cannabinoids in bone. Further research over longer dosing durations in individuals exhibiting bone-specific conditions (e.g., osteoporosis) is warranted. ClinicalTrials.gov IDs: ACTRN12619001723178 and ACTRN12619001450101.