Identifying Variables Associated with Menopause-Related Shame and Stigma: Results from a National Survey Study.

Background: Despite the significance of menopause as a natural biological milestone experienced by approximately half the population, few studies have evaluated factors associated with menopause-related shame and stigma. Given previous research indicating increased shame and stigma are associated with negative outcomes that directly impact health (e.g., reduced access to health care), it is critical to identify variables associated with menopause-related shame and stigma. Materials and Methods: As part of a larger, national survey, 214 perimenopausal (n = 111) and postmenopausal (n = 103) individuals completed self-report questionnaires assessing demographics and menopause-related symptoms, shame, and stigma. Regression analyses examined variables associated with shame and stigma. Results: Over a third of respondents reported feeling shame related to their menopause-related symptoms (37.4%), while the majority of respondents reported feeling stigma associated with symptoms (82.7%). In addition, most respondents endorsed talking about their symptoms with friends, family, partners, or doctors (80.8%), and felt that their peers might experience the same symptoms (93.9%). Regression analyses identified several significant predictor variables; in particular, more severe psychosocial and urogenital symptoms, higher education level, and younger age were significantly associated with greater odds of reporting shame and stigma. Conclusions: Overall, findings suggest that even though menopausal individuals report feeling their symptoms are similar to their peers, shame and stigma are significantly associated with these symptoms, which may be impacted by symptom severity and socioeconomic factors. Results suggest that younger individuals (i.e., those just entering perimenopause) with more education may be more likely to feel shame and stigma, which could inform interventional strategies and improve clinical outcomes.

Clinical and cognitive improvement following full-spectrum, high-cannabidiol treatment for anxiety: open-label data from a two-stage, phase 2 clinical trial.

BACKGROUND: Evidence suggests cannabidiol (CBD) has anxiolytic properties, indicating potential for novel treatment strategies. However, few clinical trials of CBD-based products have been conducted, and none thus far have examined the impact of these products on cognition. METHODS: For the open-label stage of clinical trial NCT02548559, autoregressive linear modeling assessed efficacy and tolerability of four-weeks of 1 mL t.i.d. treatment with a full-spectrum, high-CBD sublingual solution (9.97 mg/mL CBD, 0.23 mg/mL Δ-9-tetrahydrocannabinol) in 14 outpatients with moderate-to-severe anxiety, defined as ≥16 on the Beck Anxiety Inventory (BAI) or ≥11 on the Overall Anxiety Severity and Impairment Scale (OASIS). RESULTS: Findings suggest significant improvement on primary outcomes measuring anxiety and secondary outcomes assessing mood, sleep, quality of life, and cognition (specifically executive function) following treatment. Anxiety is significantly reduced at week 4 relative to baseline (BAI: 95% CI = [-21.03, -11.40], p < 0.001, OASIS: 95% CI = [-9.79, -6.07], p < 0.001). Clinically significant treatment response (≥15% symptom reduction) is achieved and maintained as early as week 1 in most patients (BAI = 78.6%, OASIS = 92.7%); cumulative frequency of treatment responders reached 100% by week 3. The study drug is well-tolerated, with high adherence/patient retention and no reported intoxication or serious adverse events. Minor side effects, including sleepiness/fatigue, increased energy, and dry mouth are infrequently endorsed. CONCLUSIONS: Results provide preliminary evidence supporting efficacy and tolerability of a full-spectrum, high-CBD product for anxiety. Patients quickly achieve and maintain symptom reduction with few side effects. A definitive assessment of the impact of this novel treatment on clinical symptoms and cognition will be ascertained in the ongoing double-blind, placebo-controlled stage.

Cannabidiol (CBD) is a compound found within the Cannabis sativa plant. Previous studies suggest CBD may reduce anxiety. In this clinical trial, 14 patients with anxiety were treated for four-weeks with a cannabis-derived study product with high levels of CBD, administered under their tongue 3 times each day. All patients knew that they were being given CBD. Following four weeks of treatment, patients reported reduced anxiety as well as improvements in mood, sleep, quality of life, and measures reflecting their self-control and ability to think flexibly. Patients did not experience any serious negative effects during the trial. The impact of this product is now being evaluated in more patients with anxiety.

Increased White Matter Coherence Following Three and Six Months of Medical Cannabis Treatment.

Background: Previous studies have demonstrated abnormal white matter (WM) microstructure in recreational cannabis consumers; however, the long-term impact of medical cannabis (MC) use on WM coherence is unknown. Accordingly, this study assessed the longitudinal impact of MC treatment on WM coherence. Given results from preclinical studies, we hypothesized that MC treatment would be associated with increased fractional anisotropy (FA) and reduced mean diffusivity (MD). Methods: As part of a larger, longitudinal investigation, patients interested in treating at least one medical condition with commercially available MC products of their choosing were assessed before initiating MC use (baseline n=37; female=25, male=12) and following three (n=31) and six (n=22) months of treatment. WM coherence was assessed via diffusion tensor imaging for bilateral regions of interest including the genu of the corpus callosum, anterior limb of the internal capsule, external capsule, and anterior corona radiata, as well as an occipital control region not expected to change over time. Results: In MC patients, FA values significantly increased bilaterally in several callosal regions relative to baseline following both 3 and 6 months of treatment; MD values significantly decreased in all callosal regions but only following 6 months of treatment. No significant changes in WM coherence were observed in the control region or in a pilot sample of treatment-as-usual patients (baseline n=14), suggesting that increased WM coherence observed in MC patients may be attributed to MC treatment as opposed to confounding factors. Interestingly, significant reductions in MD values correlated with higher cannabidiol (CBD) exposure but not Δ-9-tetrahydrocannabinol exposure. Conclusions: Overall, MC treatment was associated with increased WM coherence, which contrasts with prior research examining recreational cannabis consumers, likely related to inherent differences between recreational consumers and MC patients (e.g., product choice, age of onset). In addition, increased CBD exposure was associated with reduced MD following 6 months of treatment, extending evidence from preclinical research indicating that CBD may be neuroprotective against demyelination. However, additional research is needed to elucidate the clinical efficacy of MC treatment and the risks and benefits of long-term MC use.

Decreased Amygdalar Activation to NSSI-Stimuli in People Who Engage in NSSI: A Neuroimaging Pilot Study.

In healthy individuals, stimuli associated with injury (such as those depicting blood or wounds) tend to evoke negative responses on both self-report and psychophysiological measures. Such an instinctive aversion makes sense from an evolutionary perspective. However, to engage in nonsuicidal self-injury (NSSI), this natural barrier must be overcome. The Benefits and Barriers model of NSSI predicts that people who engage in NSSI will show diminished aversion to NSSI-related stimuli compared to controls who do not engage in NSSI. We tested this hypothesis in a pilot study assessing 30 adults, 15 of whom reported current skin cutting and 15 of whom had no history of NSSI. Functional magnetic resonance imaging (fMRI) data were collected while participants viewed neutral, positive, and negative images selected from the International Affective Picture System. Participants also viewed NSSI images depicting razors, scalpels, or wounds caused by cutting. Compared to healthy control (HC) participants, the NSSI group showed decreased amygdala and increased cingulate cortex (CC) and orbitofrontal cortex (OFC) activation to NSSI and negative images. They also showed increased amygdalar and OFC activation to positive images. Neither the control group nor the NSSI group demonstrated significant activation within regions more typically associated with reward during any of the conditions; however, positive and negative affect ratings collected throughout the course of the task suggested that none of the affective conditions were viewed as rewarding. Although preliminary, these findings are suggestive of reduced limbic and greater cortical processing of NSSI stimuli in those with a history of this behavior. This has potentially important implications for current models of NSSI as well as for its treatment.

The Impact of Micronutrient Fortified Foods on Cognitive Functioning among Low-Income Children: A Pilot and Feasibility Study.

Brain development continues throughout childhood and requires micronutrients for optimal maturation, but studies have typically examined only a limited number of micronutrients and there has been inconsistent use of validated cognitive measures. This study evaluated the impact of providing low-income children with a daily fortified meal (570 kcal) in the form of a bar and shake containing >75% of the FDA Daily Values for all essential vitamins and minerals, as well as macronutrients (e.g., omega-3 and omega-6 fatty acids and protein), in an afterschool care setting (instead of the usual meal provided) on cognitive functioning. Students aged 8-12 were randomly assigned to intervention (n = 19) or control (n = 16) meals. Students completed the Stroop Color Word Task, Trail Making Test, and Conner's Continuous Performance Task (CPT) at baseline and 3 months post-intervention. Differences in cognitive scores were examined using 2 × 2 mixed model ANOVAs (Stroop and CPT) and ANCOVAs (Trail Making Test). Significant main effects of time indicated improvements in both intervention and control groups, but there were no significant main effects of group or group*time interactions. When the amount of meal consumed was examined, most results became non-significant, suggesting that overall meal consumption significantly impacted the observed results. Overall, this pilot study suggests that there may be limited additional benefits to short-term consumption of micronutrient fortified meals among low-income children in an afterschool care setting, and potential benefits observed may be directly related to the amount of food consumed.

Circadian entrainment aftereffects in suprachiasmatic nuclei and peripheral tissues in vitro.

Circadian rhythms are endogenous 24-h rhythms. The suprachiasmatic nuclei (SCN) of the mammalian hypothalamus serve as the master circadian pacemaker, entraining peripheral organs which also demonstrate circadian rhythms. Entrainment to LD cycles of non-24 h duration (T-cycles) induces aftereffects on period that act to bring the intrinsic period closer to the entraining cycle. Both parametric effects, such as changes in endogenous period, and non-parametric effects of light, such as instantaneous phase shifts, act synergistically to accomplish entrainment of the SCN. It is not yet known if entrainment of peripheral oscillators similarly involves both parametric and non-parametric effects. In this study, mPer2(Luc) knockin mice were entrained to either long or short T-cycles, placed into constant darkness (DD) for 3 days to measure behavioral free-running period (FRP), and then PER2::LUC bioluminescence from SCN, spleen, esophagus, lung and thymus was measured in vitro. The FRP of SCN samples was negatively correlated with the FRP of behavioral rhythms, replicating prior results in mPer1-Luc mice. The FRP of the four peripheral oscillators tested did not correlate with behavioral rhythm FRP. Evidence that the SCN may entrain peripheral tissues by shifting phase relationships was observed, in that the phase of PER2::LUC in the SCN relative to peripheral tissues and also to the onset of behavioral activity varied between groups. Our study suggests that aftereffects on FRP may be an emergent property of the system that cannot be explained by the period changes in the system components. Further, we demonstrate that the phase relationship between the rhythm in PER2 in the SCN and these peripheral tissues is altered following T-cycle entrainment.

Made from concentrate? A national web survey assessing dab use in the United States.

BACKGROUND: Cannabis concentrates, including dabs, contain extremely high levels of Δ9-tetrahydrocannabinol (THC). Although these products appear to be gaining popularity among recreational cannabis consumers, little data exists regarding concentrate use in the US. We conducted a national web-based survey to examine patterns of concentrate use, specifically dabbing. METHODS: 4077 respondents completed a survey designed to assess the use of conventional flower cannabis relative to dabs. Individuals provided information about frequency and magnitude of use, and also completed the Marijuana Motives Measure and Severity of Dependence Scale to examine whether dab users have different motives for use and/or demonstrate more severe consequences of use compared to those who only use conventional flower products. RESULTS: 58% of respondents reported they had tried dabs at least once and 36.5% endorsed regular use (once a month or more). Those who use regularly use dabs were significantly more likely to report using for experimentation (feeling "curious") relative to reasons for using conventional flower products. Interestingly, motives reflecting positive effects (i.e., coping, sleep problems, relieving social anxiety) were endorsed more highly for flower use. In addition, regular dab users reported being more worried about their use of cannabis products relative to those who had tried dabs but did not use regularly. CONCLUSIONS: Results indicate that cannabis consumers do not necessarily choose dabs over flower products for positive effects, but rather appear to choose these highly potent products for experimentation. As concentrate use may lead to increased cannabis-related problems, studies directly assessing concentrate users are needed.

Mood disorders.

Despite the prevalence of the mood disorders, the underlying neuropathology is still poorly understood. This article describes abnormalities in brain activation that have been reported in neuroimaging studies of patients with depression and bipolar illness. Functional changes have been identified in regions important for neural networks underlying emotional processing, including frontal, subcortical, and limbic regions. The interpretation of neuroimaging studies in mood disorders is limited by potential confounding factors including medication effects, duration of illness, comorbidity, and gender.

Marijuana Use Predicts Cognitive Performance on Tasks of Executive Function.

OBJECTIVE: Despite growing evidence that chronic marijuana use is associated with cognitive impairment, particularly when use is initiated at an early age, national trends demonstrate significant decreases in the perceived risk of marijuana corresponding with increased use, especially among youth. The current study assessed the impact of marijuana use on executive function and whether patterns of marijuana use, including earlier age at onset, higher frequency, and increased magnitude of use, predict impairment. METHOD: Forty-four chronic, heavy marijuana smokers (37 male, 7 female) and 32 healthy, nonsmoking control participants (20 male, 12 female) recruited from the Greater Boston area completed two assessments of executive function: the Stroop Color Word Test and Wisconsin Card Sorting Test (WCST). RESULTS: Marijuana smokers had poorer executive function relative to control participants, a between-group difference that was primarily driven by individuals with early onset of marijuana use (before age 16; n = 21); significance remained even when controlling for frequency and magnitude of use. Further, earlier age at marijuana onset and increased marijuana use predicted poorer neurocognitive performance, and perseverative errors on the WCST significantly predicted marijuana group membership. CONCLUSIONS: These findings underscore the impact of early onset of marijuana use on executive function impairment independent of increased frequency and magnitude of use. In addition, poorer performance on the WCST may serve as a neuropsychological marker for heavy marijuana users. These results highlight the need for additional research to identify predictors associated with early marijuana use, as exposure to marijuana during a period of developmental vulnerability may result in negative cognitive consequences.

Citicoline Treatment Improves Measures of Impulsivity and Task Performance in Chronic Marijuana Smokers: A Pilot BOLD fMRI Study.

OBJECTIVE: Citicoline is an endogenous nucleotide that has historically been used to treat stroke, traumatic brain injury, and cognitive dysfunction. Research has also shown that citicoline treatment is associated with improved cognitive performance in substance-abusing populations. We hypothesized that marijuana (MJ) smokers who received citicoline would demonstrate improvement in cognitive performance as well as increased neural efficiency during tasks of cognitive control relative to those who received placebo. METHOD: The current study tested this hypothesis by examining the effects of citicoline in treatment-seeking chronic MJ smokers. In an 8-week double-blind, placebo-controlled study, 19 MJ smokers were randomly assigned via a double-blind procedure to the citicoline (8 Males, 2 Females) or placebo group (9 Males, 0 Females). All participants completed fMRI scanning at baseline and after 8 weeks of treatment during two cognitive measures of inhibitory processing, the Multi Source Interference Test (MSIT) and Stroop Color Word Test, and also completed the Barratt Impulsiveness Scale (BIS-11), a self-report measure of impulsivity. RESULTS: Following the 8 week trial, MJ smokers treated with citicoline demonstrated significantly lower levels of behavioral impulsivity, improved task accuracy on both the MSIT and Stroop tasks, and exhibited significantly different patterns of brain activation relative to baseline levels and relative to those who received placebo. CONCLUSIONS: Findings suggest that citicoline may facilitate the treatment of MJ use disorders by improving the cognitive skills necessary to fully engage in comprehensive treatment programs.

Worth the wait: effects of age of onset of marijuana use on white matter and impulsivity.

RATIONALE: Marijuana (MJ) use continues to rise, and as the perceived risk of using MJ approaches an all-time historic low, initiation of MJ use is occurring at even younger ages. As adolescence is a critical period of neuromaturation, teens and emerging adults are at greater risk for experiencing the negative effects of MJ on the brain. In particular, MJ use has been shown to be associated with alterations in frontal white matter microstructure, which may be related to reports of increased levels of impulsivity in this population. OBJECTIVES: The aim of this study was to examine the relationship between age of onset of MJ use, white matter microstructure, and reported impulsivity in chronic, heavy MJ smokers. METHODS: Twenty-five MJ smokers and 18 healthy controls underwent diffusion tensor imaging and completed the Barratt Impulsiveness Scale. MJ smokers were also divided into early onset (regular use prior to age 16) and late onset (age 16 or later) groups in order to clarify the impact of age of onset of MJ use on these variables. RESULTS: MJ smokers exhibited significantly reduced fractional anisotropy (FA) relative to controls, as well as higher levels of impulsivity. Earlier MJ onset was also associated with lower levels of FA. Interestingly, within the early onset group, higher impulsivity scores were correlated with lower FA, a relationship that was not observed in the late onset smokers. CONCLUSIONS: MJ use is associated with white matter development and reported impulsivity, particularly in early onset smokers.

Altered affective processing in bipolar disorder: an fMRI study.

BACKGROUND: Previous studies have reported that patients with bipolar disorder (BPD) exhibit altered emotional processing and regulation. However, results remain largely inconsistent across studies. The aim of the current study was to further examine affective processing in patients with bipolar disorder. METHODS: Twenty-three patients diagnosed with BPD (Type I) and 18 healthy matched controls completed a backward-masked affect paradigm while undergoing functional magnetic resonance imaging. Participants also completed a computerized, overt task of facial emotional discrimination after scanning. RESULTS: Results demonstrated altered affective processing of happy and fearful stimuli in bipolar participants in the amygdala, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC) relative to controls. BPD participants also displayed significant deficits in identifying fearful facial affect. LIMITATIONS: This study has a moderate sample size, and the patients with BPD were significantly older than the healthy control participants; this did not appear to impact results, and although statistically significant, it is not likely biologically significant. CONCLUSIONS: These findings may have implications for patients with BPD, as altered affective processing could result in deficits in reading social cues.

Age of onset of marijuana use and executive function.

Marijuana (MJ) remains the most widely abused illicit substance in the United States, and in recent years, a decline in perceived risk of MJ use has been accompanied by a simultaneous increase in rates of use among adolescents. In this study, the authors hypothesized that chronic MJ smokers would perform cognitive tasks, specifically those that require executive function, more poorly than control subjects and that individuals who started smoking MJ regularly prior to age 16 (early onset) would have more difficulty than those who started after age 16 (late onset). Thirty-four chronic, heavy MJ smokers separated into early and late onset groups, and 28 non-MJ smoking controls completed a battery of neurocognitive measures. As hypothesized, MJ smokers performed more poorly than controls on several measures of executive function. Age of onset analyses revealed that these between-group differences were largely attributed to the early onset group, who were also shown to smoke twice as often and nearly 3 times as much MJ per week relative to the late onset smokers. Age of onset, frequency, and magnitude of MJ use were all shown to impact cognitive performance. Findings suggest that earlier MJ onset is related to poorer cognitive function and increased frequency and magnitude of MJ use relative to later MJ onset. Exposure to MJ during a period of neurodevelopmental vulnerability, such as adolescence, may result in altered brain development and enduring neuropsychological changes.

Age of onset of marijuana use impacts inhibitory processing.

Difficulties in the ability to successfully inhibit impulsive behaviors have been reported in marijuana (MJ) smokers, yet few studies have made direct comparisons between early (prior to age 16) and late (age 16 or later) onset MJ smokers, specifically during behavioral inhibition tasks. The current study utilized the Multi-Source Interference Task (MSIT) during functional magnetic resonance imaging (fMRI) in chronic, heavy MJ smokers and healthy non-MJ smoking controls which revealed a more focal pattern of anterior cingulate activity in controls relative to smokers. Early onset smokers had more focal activation but tended to make more errors of commission relative to late onset smokers, suggesting a possible neural adaptation despite difficulty with behavioral inhibition. Further investigation is warranted, as early exposure to MJ may result in reorganization of critical brain regions.

Why so impulsive? White matter alterations are associated with impulsivity in chronic marijuana smokers.

Difficulty monitoring and inhibiting impulsive behaviors has been reported in marijuana (MJ) smokers; neuroimaging studies, which examined frontal systems in chronic MJ smokers, have reported alterations during inhibitory tasks. Diffusion tensor imaging (DTI) provides a quantitative estimate of white matter integrity at the microstructural level. We applied DTI, clinical ratings, and impulsivity measures to explore the hypotheses that chronic, heavy MJ smokers would demonstrate alterations in white matter microstructure and a different association between white matter measures and impulsivity relative to nonsmoking control subjects (NS). Fractional anisotropy (FA), a measure of directional coherence, and trace, a measure of overall diffusivity, were calculated for 6 locations including bilateral frontal regions in 15 chronic MJ smokers and 15 NS. Subjects completed clinical rating scales, including the Barratt Impulsivity Scale (BIS). Analyses revealed significant reductions in left frontal FA in MJ smokers relative to NS and significantly higher levels of trace in the right genu. MJ smokers also had significantly higher BIS total and motor subscale scores relative to NS, which were positively correlated with left frontal FA values. Finally, age of onset of MJ use was positively correlated with frontal FA values and inversely related to trace. These data represent the first report of significant alterations in frontal white matter tracts associated with measures of impulsivity in chronic MJ smokers. Early MJ use may result in reduced FA and increased diffusivity, which may be associated with increased impulsivity, and ultimately contribute to the initiation of MJ use or the inability to discontinue use.