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.

CannaCount: an improved metric for quantifying estimates of maximum possible cannabinoid exposure.

Increasing numbers of individuals have access to cannabinoid-based products containing various amounts of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and other cannabinoids. Exposure to specific cannabinoids likely influences outcomes; however, current methods for quantifying cannabis exposure do not account for the cannabinoid concentrations of the products used. We developed CannaCount, an examiner-driven metric that quantifies estimated maximum possible cannabinoid exposure by accounting for variables related to cannabinoid concentration, duration, frequency, and quantity of use. To demonstrate feasibility and applicability, CannaCount was used to quantify estimated maximum THC and CBD exposure in 60 medical cannabis patients enrolled in a two-year, longitudinal, observational study. Medical cannabis patients reported using a variety of product types and routes of administration. Calculating estimated exposure to THC and CBD was possible for the majority of study visits, and the ability to generate estimated cannabinoid exposure improved over time, likely a function of improved product labeling, laboratory testing, and more informed consumers. CannaCount is the first metric to provide estimated maximum possible exposure to individual cannabinoids based on actual cannabinoid concentrations. This metric will ultimately facilitate cross-study comparisons and can provide researchers and clinicians with detailed information regarding exposure to specific cannabinoids, which will likely have significant clinical impact.

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.

A survey of medical cannabis use during perimenopause and postmenopause.

OBJECTIVE: Expanding access to legal cannabis has dovetailed with increased interest in medical cannabis (MC) use; however, there is a paucity of research examining MC use to alleviate menopause-related symptoms. This survey study assessed patterns of MC use in perimenopausal and postmenopausal individuals. METHODS: Participants (perimenopausal, n = 131; postmenopausal, n = 127) completed assessments of menopause-related symptomatology and cannabis use, including modes of use, type of use, and menopause-related symptoms addressed by MC use. RESULTS: Most participants reported current cannabis use (86.1%) and endorsed using MC for menopause-related symptoms (78.7%). The most common modes of use were smoking (84.3%) and edibles (78.3%), and the top menopause-related symptoms for MC use were sleep disturbance (67.4%) and mood/anxiety (46.1%). Relative to postmenopausal participants, perimenopausal participants reported significantly worse menopause-related symptomatology on the vasomotor and psychosocial subscales of the Menopause-Specific Quality of Life Questionnaire ( P s ≤ 0.04), including greater burden of anxiety ( P = 0.01) and hot flash ( P = 0.04) symptoms. In addition, perimenopausal participants reported higher incidence of depression ( P = 0.03) and anxiety diagnoses ( P < 0.01), as well as increased use of MC to treat menopause-related mood/anxiety symptoms relative to postmenopausal participants ( P = 0.01). CONCLUSIONS: Results suggest that many individuals are currently using MC as an adjunctive treatment for menopause-related symptoms, particularly sleep disturbance and mood/anxiety. Future research should examine the impact of different MC use characteristics (e.g., cannabinoid profiles) on the efficacy of MC use for menopause-related symptoms. Increased severity and prevalence of mood and anxiety symptoms in perimenopausal participants suggest promising targets for clinical trials of cannabinoid-based therapies.

Contemplating cannabis? The complex relationship between cannabinoids and hepatic metabolism resulting in the potential for drug-drug interactions.

The majority of states have fully legalized the use of medical cannabis (MC), and nearly all other states allow limited access to cannabidiol (CBD), a non-intoxicating constituent of cannabis often touted for a range of therapeutic indications. Further, the Agricultural Improvement Act of 2018 legalized hemp-derived products in all 50 states; typically high in CBD, these products are derived from cannabis varieties containing ≤0.3% delta-9-tetrahydrocannabinol (THC) by weight. The recent "green rush" has resulted in a striking increase in cannabis use among patients and consumers who often use a wide variety of novel product types, each with a unique blend of cannabinoid constituents. Importantly, however, several cannabinoids have the potential to cause drug-drug interactions (DDI) with other medications, primarily due to their involvement with the hepatic cytochrome P450 (CYP450) system. This article examines the potential for individual cannabinoids, particularly CBD, to interact with the hepatic metabolic system, which is concerning given its involvement in the metabolism of commonly-prescribed medications. CBD and other cannabinoids are metabolized extensively by the CYP450 system, and also inhibit many of these enzymes, potentially leading to variable serum levels of other medications, as well as variable levels of cannabinoids when other medications modify the system. As access and interest in cannabinoid-based products continues to increase, critical questions remain unanswered regarding their safety. The complex relationship between cannabinoids and the hepatic metabolic system, including common potential DDI resulting from cannabinoid exposure, are explored along with the clinical significance of these potential interactions and monitoring or mitigation strategies.

An Observational, Longitudinal Study of Cognition in Medical Cannabis Patients over the Course of 12 Months of Treatment: Preliminary Results.

OBJECTIVE: Cannabis use has increased dramatically across the country; however, few studies have assessed the long-term impact of medical cannabis (MC) use on cognition. Studies examining recreational cannabis users generally report cognitive decrements, particularly in those with adolescent onset. As MC patients differ from recreational consumers in motives for use, product selection, and age of onset, we assessed cognitive and clinical measures in well-characterized MC patients over 1 year. Based on previous findings, we hypothesized MC patients would not show decrements and might instead demonstrate improvements in executive function over time. METHOD: As part of an ongoing study, MC patients completed a baseline visit prior to initiating MC and evaluations following 3, 6, and 12 months of treatment. At each visit, patients completed a neurocognitive battery assessing executive function, verbal learning/memory, and clinical scales assessing mood, anxiety, and sleep. Exposure to delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) was also quantified. RESULTS: Relative to baseline, MC patients demonstrated significant improvements on measures of executive function and clinical state over the course of 12 months; verbal learning/memory performance generally remained stable. Improved cognitive performance was not correlated with MC use; however, clinical improvement was associated with higher CBD use. Analyses suggest cognitive improvements were associated with clinical improvement. CONCLUSIONS: Study results extend previous pilot findings, indicating that MC patients may exhibit enhanced rather than impaired executive function over time. Future studies should examine distinctions between recreational and MC use to identify potential mechanisms related to cognitive changes and the role of clinical improvement.

No pain, all gain? Interim analyses from a longitudinal, observational study examining the impact of medical cannabis treatment on chronic pain and related symptoms.

Previous studies have demonstrated improvements in pain following short-term medical cannabis (MC) use, suggesting long-term MC treatment may alleviate symptoms associated with chronic pain. The goal of this observational and longitudinal study was to examine patients using MC to treat chronic pain pre versus post MC treatment. These interim analyses included 37 patients with chronic pain evaluated prior to initiation of MC treatment and following 3 and 6 months of MC use; pain, clinical state, sleep, quality of life, and conventional medication use were assessed. Correlation analyses examined the relationship between changes in pain and other clinical measures, assessed the impact of cannabinoid exposure on pain and clinical ratings, and assessed whether baseline cannabis expectancies influenced outcome variables. Additionally, a pilot group of treatment-as-usual patients (n = 9) who did not use MC were examined at baseline and 3 months later. Relative to baseline, following 3 and 6 months of treatment, MC patients exhibited improvements in pain which were accompanied by improved sleep, mood, anxiety, and quality of life, and stable conventional medication use. Reduced pain was associated with improvements in aspects of mood and anxiety. The results generally suggest increased THC exposure was related to pain-related improvement, while increased CBD exposure was related to improved mood. Cannabis expectancies were not related to observed improvements. Pilot analyses revealed that treatment-as-usual patients do not demonstrate the same pattern of improvement. Findings highlight the potential efficacy of MC treatment for pain and underscore the unique impact of individual cannabinoids on specific aspects of pain and comorbid symptoms. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Assessing Cannabis Use Disorder in Medical Cannabis Patients: Interim Analyses from an Observational, Longitudinal Study.

Background: To date, no studies have directly assessed potential cannabis use disorder (CUD) in medical cannabis (MC) patients pre- vs post-MC treatment. Given that MC patients use cannabis for symptom alleviation rather than intoxication, we hypothesized that MC patients would exhibit few symptoms of CUD after initiating MC treatment. Methods: As part of an ongoing observational, longitudinal study, 54 MC patients completed baseline assessments prior to initiating MC use and returned for at least one follow-up assessment after three, six, and/or twelve months of a self-selected MC treatment regimen; detailed MC treatment information was collected and quantified. All patients completed the Cannabis Use Disorder Identification Test - Revised (CUDIT-R) at each visit. Changes in individual items scores and total scores were assessed over time, and we examined whether total CUDIT-R scores correlated with frequency of MC use, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) exposure. Further, Cronbach's alpha analyses were conducted to provide preliminary data regarding the psychometric properties of the CUDIT-R when used among MC patients. Results: Although total CUDIT-R scores increased relative to baseline, on average, ratings fell below the 'hazardous use' threshold at each visit. Analyses of individual items revealed that increases in total scores were primarily attributable to increases in frequency of use and not necessarily other aspects of problematic use. Total CUDIT-R scores were not associated with number of MC uses or CBD exposure, but a significant relationship was detected between increased THC exposure and higher CUDIT-R scores. Importantly however, analyses revealed that the CUDIT-R does not appear to be an appropriate tool for identifying CUD in MC patients. Conclusions: Screening tools specifically designed to assess CUD in MC patients are needed and should distinguish between frequent use and problematic use; exposure to individual cannabinoids must also be considered.

Recreational cannabis use impairs driving performance in the absence of acute intoxication.

BACKGROUND: Across the nation, growing numbers of individuals are exploring the use of cannabis for medical or recreational purposes, and the proportion of cannabis-positive drivers involved in fatal crashes increased from 8 percent in 2013 to 17 percent in 2014, raising concerns about the impact of cannabis use on driving. Previous studies have demonstrated that cannabis use is associated with impaired driving performance, but thus far, research has primarily focused on the effects of acute intoxication. METHODS: The current study assessed the potential impact of cannabis use on driving performance using a customized driving simulator in non-intoxicated, heavy, recreational cannabis users and healthy controls (HCs) without a history of cannabis use. RESULTS: Overall, cannabis users demonstrated impaired driving relative to HC participants with increased accidents, speed, and lateral movement, and reduced rule-following. Interestingly, however, when cannabis users were divided into groups based on age of onset of regular cannabis use, significant driving impairment was detected and completely localized to those with early onset (onset before age 16) relative to the late onset group (onset ≥16 years old). Further, covariate analyses suggest that impulsivity had a significant impact on performance differences. CONCLUSIONS: Chronic, heavy, recreational cannabis use was associated with worse driving performance in non-intoxicated drivers, and earlier onset of use was associated with greater impairment. These results may be related to other factors associated with early exposure such as increased impulsivity.

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.

The Grass Might Be Greener: Medical Marijuana Patients Exhibit Altered Brain Activity and Improved Executive Function after 3 Months of Treatment.

The vast majority of states have enacted full or partial medical marijuana (MMJ) programs, causing the number of patients seeking certification for MMJ use to increase dramatically in recent years. Despite increased use of MMJ across the nation, no studies thus far have examined the specific impact of MMJ on cognitive function and related brain activation. In the present study, MMJ patients seeking treatment for a variety of documented medical conditions were assessed prior to initiating MMJ treatment and after 3 months of treatment as part of a larger longitudinal study. In order to examine the effect of MMJ treatment on task-related brain activation, MMJ patients completed the Multi-Source Interference Test (MSIT) while undergoing functional magnetic resonance imaging (fMRI). We also collected data regarding conventional medication use, clinical state, and health-related measures at each visit. Following 3 months of treatment, MMJ patients demonstrated improved task performance accompanied by changes in brain activation patterns within the cingulate cortex and frontal regions. Interestingly, after MMJ treatment, brain activation patterns appeared more similar to those exhibited by healthy controls from previous studies than at pre-treatment, suggestive of a potential normalization of brain function relative to baseline. These findings suggest that MMJ use may result in different effects relative to recreational marijuana (MJ) use, as recreational consumers have been shown to exhibit decrements in task performance accompanied by altered brain activation. Moreover, patients in the current study also reported improvements in clinical state and health-related measures as well as notable decreases in prescription medication use, particularly opioids and benzodiapezines after 3 months of treatment. Further research is needed to clarify the specific neurobiologic impact, clinical efficacy, and unique effects of MMJ for a range of indications and how it compares to recreational MJ use.

Splendor in the Grass? A Pilot Study Assessing the Impact of Medical Marijuana on Executive Function.

Currently, 25 states and Washington DC have enacted full medical marijuana (MMJ) programs while 18 states allow limited access to MMJ products. Limited access states permit low (or zero) tetrahydrocannabinol (THC) and high cannabidiol (CBD) products to treat specified conditions such as uncontrolled epilepsy. Although MMJ products are derived from the same plant species as recreational MJ, they are often selected for their unique cannabinoid constituents and ratios, not typically sought by recreational users, which may impact neurocognitive outcomes. To date, few studies have investigated the potential impact of MMJ use on cognitive performance, despite a well-documented association between recreational marijuana (MJ) use and executive dysfunction. The current study assessed the impact of 3 months of MMJ treatment on executive function, exploring whether MMJ patients would experience improvement in cognitive functioning, perhaps related to primary symptom alleviation. As part of a larger longitudinal study, 24 patients certified for MMJ use completed baseline executive function assessments and 11 of these so far have returned for their first follow-up visit 3 months after initiating treatment. Results suggest that in general, MMJ patients experienced some improvement on measures of executive functioning, including the Stroop Color Word Test and Trail Making Test, mostly reflected as increased speed in completing tasks without a loss of accuracy. On self-report questionnaires, patients also indicated moderate improvements in clinical state, including reduced sleep disturbance, decreased symptoms of depression, attenuated impulsivity, and positive changes in some aspects of quality of life. Additionally, patients reported a notable decrease in their use of conventional pharmaceutical agents from baseline, with opiate use declining more than 42%. While intriguing, these findings are preliminary and warrant further investigation at additional time points and in larger sample sizes. Given the likelihood of increased MMJ use across the country, it is imperative to determine the potential impact of short- and long-term treatment on cognitive performance as well as the efficacy of MMJ treatment itself.