Complementary and Alternative Medicine for Autism - A Systematic Review.

Complementary and Alternative Medicine (CAM) is a therapeutic option currently used by autistic people with continued interest and uptake. There remains limited evidence regarding the efficacy of CAM use in autism. The aim of this systematic review is to comprehensively review published clinical trials to explore the efficacy of CAM in autism. A systematic literature review of available research published from June 2013 to March 2023 was conducted. Our literature search identified 1826 eligible citations, and duplications removed (n = 694) with 102 articles eligible for title/abstract screening. After full text review, 39 studies were included. The results of this systematic review identified that for autistic people, vitamin and mineral supplements may only be of benefit if there is a deficiency. The results also found that the main interventions used were dietary interventions and nutraceuticals, including targeted supplements, vitamins and minerals, omega 3 s and prebiotics, probiotics and digestive enzymes. The evidence does not support some of the most frequently utilised dietary interventions, such as a Gluten Free Casein Free (GFCF) diet, and the use of targeted nutraceutical supplements may be of benefit, but more conclusive research is still required to direct safe and effective treatment.

Endocannabinoid levels in female-sexed individuals with diagnosed depression: a systematic review.

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent mental health disorder with females experiencing higher rates of depression (11.6%), anxiety (15.7%) and physiological distress (14.5%) than males. Recently, the Endocannabinoid system (ECS) has been proposed to be a key contributing factor in the pathogenesis and symptom severity of MDD due to its role in neurotransmitter production, inflammatory response and even regulation of the female reproductive cycle. This review critically evaluates evidence regarding ECS levels in female-sexed individuals with depressive disorders to further understand ECS role. MATERIALS AND METHODS: A systematic literature review of available research published prior to April 2022 was identified using PubMed (U.S. National Library of Medicine), CINAHL (EBSCO), Web of Science, AMED and Scopus (Elsevier). Studies were included if they reported ECS analysis of female-sexed individuals with depression and were excluded if they did not differentiate results between sexes, assessed mental health conditions other than depression, tested efficacy of endocannabinoid/n-acylethanolamine/cannabis or marijuana administration and that were unable to be translated. Critical appraisal of each included study was undertaken using the Joanna Briggs Institute Critical Appraisal Tool for Systematic Reviews. RESULTS: The 894 located citations were screened for duplicates (n = 357) and eligibility by title and abstract (n = 501). The full text of 33 studies were reviewed, and 7 studies were determined eligible for inclusion. These studies indicated that depressed female-sexed individuals have altered levels of ECS however no significant pattern was identified due to variability of study outcomes and measures, limiting overall interpretation. DISCUSSION: This review suggests potential involvement of ECS in underlying mechanisms of MDD in female sexed-individuals, however no pattern was able to be determined. A major contributor to the inability to attain reliable and valid understanding of the ECS levels in female-sexed individuals with depression was the inconsistency of depression screening tools, inclusion criteria's and analysis methods used to measure eCBs. Future studies need to implement more standardised methodology to gain a deeper understanding of ECS in female-sexed individuals with depressive disorders. TRIAL REGISTRATION : This review was submitted to PROSPERO for approval in April 2022 (Registration #CRD42022324212).

Prevalence of Complementary Medicine Use in Children and Adolescents: A Systematic Review.

INTRODUCTION: The objective of this systematic review was to determine the global prevalence of complementary medicine (CM) use among children and adolescents. METHOD: Seven databases and the reference lists of included studies were searched for pertinent observational studies. Studies were limited to those published in English from July 1, 2013. Included studies were appraised using the JBI checklist for prevalence studies. RESULTS: Twenty studies were eligible for inclusion (385,527 participants). Most studies were assessed as having low risk of bias. Meta-analyses revealed a 23.0% (95% confidence interval, 0.226-0.234; 17 studies) short-term (≤ 12 month) prevalence and a 77.7% (95% confidence interval, 0.760-0.794; six studies) lifetime prevalence of CM use in children and adolescents. Differences in CM use were evident across countries and regions. DISCUSSION: The findings of this review indicate that the use of CM in children and adolescents is high and widespread and may be increasing.

The use of diet for preventing and treating depression in young men: current evidence and existing challenges.

Emerging evidence suggests that diet therapy (nutrients, foods and dietary patterns) could be effective as a potential adjunctive treatment option for major depressive disorder. Numerous mechanisms have been proposed, including the role inflammation, oxidative stress, brain-derived neurotrophic factor, the gastrointestinal tract microbiome and tryptophan/serotonin metabolism. Despite known differences in depression characteristics and treatment responses between males and females, there are limited sex-specific studies examining the role of diet in young men specifically. This is important as young men are often reluctant to seek mental health support, so finding treatment strategies which appeal to this demographic is crucial. This brief report provides an overview of the most recent advances in the use of diet for preventing and treating depression in young men, highlighting existing challenges and opportunities for future research. We recommend that clinicians discuss the role of diet with depressed young men, so that diet may be used alongside current treatment options.

Variations in folate prescriptions for patients with the MTHFR genetic polymorphisms: A case series study.

Background: Over 48.5 million couples are reported with infertility worldwide. Health policy recommends folic acid in women of childbearing age, particularly in preconception and pregnancy which results in women purchasing over-the-counter prenatal multivitamins containing folic acid through pharmacies and other retail outlets. Emerging studies are investigating whether other forms of supplemental folate are more suitable, particularly for those with methylenetetrahydrofolate reductase (MTHFR) polymorphisms. This case series aimed to document variations in forms and dosage of folate prescribed by Australian practitioners to patients with diagnosed infertility and MTHFR polymorphisms. Methods: Australian practitioners were invited to complete a retrospective case report form for patients that presented with unexplained infertility. This case report form documented the form and dose of folate that practitioners were prescribing to their infertility patient with MTHFR polymorphisms, together with their fertility history. Results: Six practitioners submitted case information for 12 patients with diagnosed infertility and MTHFR polymorphisms. All patients had been advised by their practitioner to remove folic acid in supplemental form and were prescribed 5-methyltetrahydrofolate (5-MTHF) or a combination of 5-MTHF and folinic acid, at higher doses than the Australian recommended dose (mean daily maximum prescribed dose: 2325µg). Eleven patients conceived within the treatment period (average treatment of one year) and ten were reported as having a live birth. Conclusion: This case series has highlighted clinical practices that vary from the recommendations by Australian policy. Further research is required to verify the clinical importance of variations in folate prescriptions for women with MTHFR polymorphisms and how folate recommendations may need to change depending on these polymorphisms. This has direct relevance to those prescribing at the pharmacy and retail level, specifically pharmacists and pharmacy assistants.

Nutritional Support During Long COVID: A Systematic Scoping Review.

Introduction: Long COVID is a term that encompasses a range of signs, symptoms, and sequalae that continue or develop after an acute COVID-19 infection. The lack of early recognition of the condition contributed to delays in identifying factors that may contribute toward its development and prevention. The aim of this study was to scope the available literature to identify potential nutritional interventions to support people with symptoms associated with long COVID. Methods: This study was designed as a systematic scoping review of the literature (registration PROSPERO CRD42022306051). Studies with participants aged 18 years or older, with long COVID and who underwent a nutritional intervention were included in the review. Results: A total of 285 citations were initially identified, with five papers eligible for inclusion: two were pilot studies of nutritional supplements in the community, and three were nutritional interventions as part of inpatient or outpatient multidisciplinary rehabilitation programs. There were two broad categories of interventions: those that focused on compositions of nutrients (including micronutrients such as vitamin and mineral supplements) and those that were incorporated as part of multidisciplinary rehabilitation programs. Nutrients included in more than one study were multiple B group vitamins, vitamin C, vitamin D, and acetyl-l-carnitine. Discussion: Two studies trialed nutritional supplements for long COVID in community samples. Although these initial reports were positive, they are based on poorly designed studies and therefore cannot provide conclusive evidence. Nutritional rehabilitation was an important aspect of recovery from severe inflammation, malnutrition, and sarcopenia in hospital rehabilitation programs. Current gaps in the literature include a potential role for anti-inflammatory nutrients such as the omega 3 fatty acids, which are currently undergoing clinical trials, glutathione-boosting treatments such as N-acetylcysteine, alpha-lipoic acid, or liposomal glutathione in long COVID, and a possible adjunctive role for anti-inflammatory dietary interventions. This review provides preliminary evidence that nutritional interventions may be an important part of a rehabilitation program for people with severe long COVID symptomatology, including severe inflammation, malnutrition, and sarcopenia. For those in the general population with long COVID symptoms, the role of specific nutrients has not yet been studied well enough to recommend any particular nutrient or dietary intervention as a treatment or adjunctive treatment. Clinical trials of single nutrients are currently being conducted, and future systematic reviews could focus on single nutrient or dietary interventions to identify their nuanced mechanisms of action. Further clinical studies incorporating complex nutritional interventions are also warranted to strengthen the evidence base for using nutrition as a useful adjunctive treatment for people living with long COVID.

A Mediterranean diet intervention for young men with depression: patient experiences, challenges and benefits (the "AMMEND study") - A cross-sectional study.

BACKGROUND: Recent research has highlighted the beneficial effects of following a Mediterranean diet (MD) for depression. Unfortunately, adherence to specific diets presents many challenges and while previous research has aimed to understand these challenges, the focus has primarily been on weight-loss interventions in patients with obesity or cardiovascular disease. The aim of this study was to understand the experiences and challenges expressed by young men with clinical depression who completed a 12-week Mediterranean diet intervention. METHODS: An online questionnaire was used to collect data from 36 young Australian men aged between 18 and 25 with diagnosed depression who participated in the Mediterranean Diet arm of the Mediterranean Diet for Men with Depression (AMMEND) study. Descriptive analyses were undertaken for each variable with results reported as percentages and frequencies. RESULTS: Positive aspects highlighted by participants included enjoying the taste of foods, being highly motivated to continue with the diet and a perceived benefit to their depressive symptoms. The main challenges included increased cost and time commitment, and the negative attitudes of their friends and family towards the diet. CONCLUSION: We recommend that the influence of friends and family attitudes towards the diet and the impact this has on following a Mediterranean diet in young men be explored further, as this posed a challenge for many of our participants. These results may assist clinicians when promoting a Mediterranean diet to this specific demographic.

Plasma and interstitial levels of endocannabinoids and N-acylethanolamines in patients with chronic widespread pain and fibromyalgia: a systematic review and meta-analysis.

The endocannabinoid system (ECS) is an essential endogenous signaling system that may be involved in the pathophysiology of chronic widespread pain (CWP) and fibromyalgia syndrome (FMS). Further research is required to understand the role of ECS in the development and maintenance of CWP and FMS. We provided the first systematic review and meta-analysis exploring the clinical relevance of ECS alterations in patients with CWP and FMS by comparing plasma and interstitial levels of endocannabinoids and N-acylethanolamines in patients and healthy controls. A systematic search was conducted to identify studies that measured plasma and/or interstitial levels of endocannabinoids and N-acylethanolamines in patients with CWP or FMS and healthy controls. A total of 8 studies were included for qualitative review, and 7 studies were included for meta-analysis. The findings identified increased plasma levels of oleoylethanolamide and stearoylethanolamide in patients with FMS compared with those in controls (P = 0.005 and P < 0.0001, respectively) and increased plasma levels of palmitoylethanolamide and interstitial levels of stearoylethanolamide in patients with CWP compared with those in controls (P = 0.05 and P = 0.001, respectively). There were no significant differences in other ECS parameters. Most studies did not account for variables that may influence ECS function, including cannabis use, concomitant medication, comorbidities, physical activity, stress levels, circadian rhythm, sleep quality, and dietary factors, suggesting that future studies should explore the correlation between these variables and endocannabinoid activity. We highlight the importance of investigating endocannabinoid activity in CWP and FMS because it will underpin future translational research in the area.

International prevalence of consultation with a naturopathic practitioner: a systematic review and meta-analysis.

OBJECTIVES: Naturopathy is a traditional medicine system informed by codified philosophies and principles, and an emphasis on non-pharmacologic therapeutic interventions. While naturopathy is practised by approximately 75 000-100 000 000 naturopathic practitioners in at least 98 countries, little is known about the international prevalence of history of consultation with a naturopathic practitioner. This study reports a systematic review and meta-analysis of studies describing the global prevalence of history of consultation with a naturopathic practitioner by the general population. SETTING: The included literature was identified through a systematic search of eight databases between September and October 2019, as well as the grey literature. PARTICIPANTS: Studies were included if they reported the prevalence rate of consultations with a naturopathic practitioner by the general population. INTERVENTIONS: Survey items needed to report consultations with a naturopathic practitioner as defined in the country where data was collected, and not combine naturopathic consultations with other health services or only report consulations for illness populations. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary measures used for the analysis was consultations in the previous 12 months. Other prevalence timeframes were reported as secondary measures. METHODS: Meta-analysis of prevalence data was conducted using random effects models based on individual countries and WHO world regions. RESULTS: The literature search identified eight manuscripts summarising 14 studies reporting prevalence for inclusion in the review. All included studies had a low risk of bias. Meta-analysis of the included studies by world region found the 12-month prevalence of history of naturopathy consultations ranged from 1% in the Region of the Americas to 6% in the European and Western Pacific Regions. CONCLUSIONS: There are up to sixfold differences in the prevalence of naturopathy consults over 12 months between and within world regions, which may be driven by a range of policy, legislative and social factors. PROSPERO REGISTRATION NUMBER: CRD42020145529.

The effect of a Mediterranean diet on the symptoms of depression in young males (the "AMMEND: A Mediterranean Diet in MEN with Depression" study): a randomized controlled trial.

BACKGROUND: Depression is a common mental health condition that affects 1 in 8 males each year, especially young adults. Young adulthood offers an opportunity for early dietary interventions, with research suggesting that a Mediterranean diet (MD) could be beneficial in treating depression. OBJECTIVES: This study aimed to determine if an MD can improve depressive symptoms in young males with clinical depression. METHODS: A 12-wk, parallel-group, open-label, randomized controlled trial was conducted to assess the effect of an MD intervention in the treatment of moderate to severe depression in young males (18-25 y). Befriending therapy was chosen for the control group. Assessments were taken at baseline, week 6, and week 12. MD adherence was measured with the Mediterranean Diet Adherence Score (MEDAS). The primary outcome measure was the Beck Depression Inventory Scale-version II (BDI-II) and secondary outcome was quality of life (QoL). RESULTS: A total of 72 participants completed the study. After 12 wk, the MEDAS scores were significantly higher in the MD group compared with the befriending group (mean difference: 7.8; 95% CI: 7.23, 8.37; P < 0.001). The mean change in BDI-II score was significantly higher in the MD group compared with the befriending group at week 12 (mean difference: 14.4; 95% CI: 11.41, 17.39; P < 0.001). The mean change in QoL score was also significantly higher in the MD group compared with the befriending group at week 12 (mean difference: 12.7; 95% CI: 7.92, 17.48; P < 0.001). CONCLUSIONS: Our results demonstrate that compared with befriending, an MD intervention leads to significant increases in MEDAS, decreases in BDI-II score, and increases in QoL scores. These results highlight the important role of nutrition for the treatment of depression and should inform advice given by clinicians to this specific demographic population.The trial was registered with Australia and New Zealand Clinical Trials Registry (trial ID ACTRN12619001545156) and has also been registered with the WHO International Clinical Trials Registry Platform (Universal Trial Number U1111-1242-5215).

Complementary medicine visits by palliative care patients: a cross-sectional survey.

BACKGROUND: The paucity of empirical research examining complementary medicine (CM) use in palliative care in France compared with other countries results in a gap in scientific knowledge. This study aims to describe the frequency and the cause of palliative care patients consulting with a CM clinician along with the conventional physicians. METHODS: This study is an observational cross-sectional survey conducted in three palliative care centres in Lyon, France, between July 2017 and May 2018: two tertiary hospitals and one palliative care unit in a private hospital. Inpatients and outpatients visiting the palliative care clinics with a primary diagnosis of cancer were invited to participate in the study. Using a 19-item paper-based survey instrument, we collected data on the participants' personal characteristics, health service utilisation and attitudes towards CM. RESULTS: From the 138 participants meeting the inclusion criteria, 100 (72.4%) were included in the study. On average, they were 62.9 years old (SD 12.4) and the majority were women (60%). The primary cancer site was mostly colorectal (29.0%), breast (15.0%) and gynaecological (11.0%). The most commonly visited CM clinician was the aromatherapist (72.7%), recording more than six consultations (78.1%) for symptom management (21.9%). Visits to an osteopath were reported by 28.6% of patients, and 45.8% of osteopathy users reported visiting an osteopath more than six times for symptom management (62.5%). Participants visiting a naturopath (15.3%) reported less than four visits and indicated symptom management as the most common reason (76.9%). CONCLUSIONS: Our findings show a substantial proportion of palliative care patients visit CM clinicians and primarily seek symptom management from CM clinical care.

Is 6-Shogaol an Effective Phytochemical for Patients With Lower-risk Myelodysplastic Syndrome? A Narrative Review.

Myelodysplastic syndrome (MDS) evolves due to genomic instability, dysregulated signaling pathways, and overproduction of inflammatory markers. Reactive oxygen species contribute to the inflammatory response, which causes gene damage, cellular remodeling, and fibrosis. MDS can be a debilitating condition, and management options in patients with MDS aim to improve cytopenias, delay disease progression, and enhance quality of life. High serum ferritin levels, a source of iron for reactive oxygen species production, correlate with a higher risk of progression to acute myeloid leukemia, and iron overload is compounded by blood transfusions given to improve anemia. 6-shogaol is a natural phenolic compound formed when ginger is exposed to heat and/or acidic conditions, and it has been shown to possess anti-tumor activity against leukemia cell lines and antioxidant effects. This narrative review assessed the potential benefits of this phytochemical in lower-risk MDS patients through examining the current evidence on the pharmacological and therapeutic properties of ginger and 6-shogaol.

A randomised, double-blind, placebo-controlled clinical trial found that a novel herbal formula Urox® (Bedtime Buddy®) assisted children for the treatment of nocturnal enuresis.

BACKGROUND: Nocturnal enuresis or 'bedwetting', is a form of night-time urinary incontinence occurring in younger children. A diagnosis can be socially disruptive and psychologically stressful for a child. The most common strategies used by parents are waking the child during the night to use the bathroom and limiting the child's water intake before going to bed. HYPOTHESIS/PURPOSE: To determine if a herbal capsule formulation taken once daily can reduce incidence and frequency of nocturnal enuresis in children. STUDY DESIGN: This randomised double-blind placebo-controlled trial evaluated the efficacy of an herbal medicine product to reduce the symptoms of nocturnal enuresis. Participants, aged between 6 and 14 years of age, were recruited from the community in Australia. They were randomised via computerised random-number generation at study enrolment to receive one or two oral capsules in the morning of either Urox® (Bedtime Buddy®) or placebo. The Paediatric Quality of life (Pin-Q) was used as a quality-of-life measure and waking wet, fluid intake and urinary urgency per week were monitored. RESULTS: Forty-one children completed the trial with an attrition rate of 16%. There were more males (64.6%) compared to females (35.4%) and the mean age was 8.6 years. Forty-one point seven percentages (41.7%) of participants had improvements in bed wetting by two months which was a highly clinically relevant effect (Cohen's D = 0.98). The primary outcome found that there was a statistically significant reduction in NE (p = 0.034; CI 0.086-2.095) and between groups using longitudinal analysis (p = 0.04, Coefficient -1.12, CI 95% -2.20 - -0.04). In the secondary outcomes, urinary urgency reduced statistically significantly for the intervention (p = 0.002; a reduction of 18.3% difference for Bedtime Buddy compared to an increase of 3.7% for the placebo). CONCLUSION: Urox® (Bedtime Buddy®) may assist children in reducing nocturnal enuresis compared to placebo. In addition, it may assist in reducing daily incontinence and urinary urgency.

A Retrospective Cross-Sectional Cohort Trial Assessing the Prevalence of MTHFR Polymorphisms and the Influence of Diet on Platinum Resistance in Ovarian Cancer Patients.

Ovarian cancer has the lowest survival rate in gynaecologic malignancies with a 5-year survival rate of 43%. Platinum resistance is one of the main drivers of ovarian cancer mortality, of which aberrant methylation has been cited as a significant contributor. Understanding the essential role of the methylenetetrahydrofolate reductase enzyme (MTHFR) on DNA synthesis and repair, and how nutrient status can vastly affect its performance, led to the investigation of MTHFR status and dietary influence on platinum response in epithelial ovarian cancer (EOC) patients. Twenty-five adult female patients who completed first-line platinum-based chemotherapy for primary ovarian cancer were selected from Icon Cancer Centres in Australia. Participants were grouped based on platinum response. A full medical and family history, food frequency questionnaire and single blood test were completed, testing for MTHFR polymorphisms, serum folate, serum and active B12 and homocysteine levels. Nineteen of twenty-five participants had an MTHFR polymorphism. Of those, 20% were compound heterozygous, 12% were heterozygous C677T (CT), 4% homozygous C677T, 12% homozygous A1298C and 28% were heterozygous A1298C (AC). Statistically significant associations were found between dietary zinc (p = 0.0086; 0.0030; 0.0189) and B12 intakes in CT genotypes (p = 0.0157; 0.0030; 0.0068) indicating that zinc or vitamin B12 intakes below RDI were associated with this genotype. There were strong associations of vitamin B6 intakes in AC genotypes (p = 0.0597; 0.0547; 0.0610), and dietary folate in compound heterozygotes with sensitive and partially sensitive disease (p = 0.0627; 0.0510). There were also significant associations between serum folate (p = 0.0478) and dietary B12 (p = 0.0350) intakes above RDI and platinum sensitivity in wild-types as well as strong associations with homocysteine levels (p = 0.0886) and zinc intake (p = 0.0514). Associations with dietary B12 (p = 0.0514) and zinc intakes (p = 0.0731) were also strong in resistant wild types. Results indicate that dietary zinc, B12 and B6 intakes may be associated with platinum sensitivity dependent on MTHFR genotype. These results require further research to clarify the dosages necessary to elicit a response; however, they provide a novel foundation for acknowledging the role of diet on treatment response in EOC.

A Phase 2 Randomised Clinical Trial Assessing the Tolerability of Two Different Ratios of Medicinal Cannabis in Patients With High Grade Gliomas.

BACKGROUND: Cannabis for cancer is very topical and, given the use of illicit cannabis preparations used in this vulnerable population, research investigating standardised, quality-assured medicinal cannabis is critical to inform clinicians and assist patient safety. METHODS: A randomized trial involving adult patients diagnosed with a high-grade glioma, no history of substance abuse, liver or kidney damage or myocardial infarction were eligible for inclusion in a tolerability study on two different ratios of medicinal cannabis. Baseline screening of brain morphology, blood pathology, functional status, and cognition was conducted. A retrospective control group was used for comparison for secondary outcomes. RESULTS: Participants (n=88) were on average 53.3 years old. A paired t-test assessed the Functional Assessment of Cancer Therapy for Brain Cancer (FACT-Br) between groups from baseline to week 12 found that the 1:1 ratio favoured both physical (p=0.025) and functional (p=0.014) capacity and improved sleep (p=0.009). Analysis of changes from baseline to week 12 also found 11% of 61 participants had a reduction in disease, 34% were stable, 16% had slight enhancement, and 10% had progressive disease. No serious adverse events occurred. Side effects included dry mouth, tiredness at night, dizziness, drowsiness. CONCLUSION: This study demonstrated that a single nightly dose of THC-containing medicinal cannabis was safe, had no serious adverse effects and was well tolerated in patients. Medicinal cannabis significantly improved sleep, functional wellbeing, and quality of life. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373556&isReview=true, identifier ACTRN12617001287325.

Safety and Efficacy of Medicinal Cannabis in the Treatment of Fibromyalgia: A Systematic Review.

Background: Fibromyalgia (FMS) is a complex condition that is characterized by various pain syndromes and fatigue, among other symptoms experienced. Current medical treatment of FMS involves both pharmacological and nonpharmacological approaches, but often with ineffective outcomes. Medicinal cannabis has the potential to be a therapeutic option for patients with FMS due to the positive research in chronic pain management. In addition, it has been found to have fewer adverse effects compared with currently available pain medications. This literature review aims at answering whether medicinal cannabis is reported to be safe and effective for the treatment of pain and symptomology experienced by people with FMS. Methods: A systematic review was conducted on human trials utilizing cannabis in FMS. MEDLINE, Embase, CINAHL, AMED, Scopus, and Cochrane CENTRAL were used for databases search, and mesh terms were used for cannabis and FMS. The search was limited to studies conducted from 2000 to 2020. Results: From the 181 citations identified, 10 studies were included after title, abstract, and full text screening occurred. A total of 1136 of patients (intervention n = 945, control n = 108, crossover n = 83) participated in the 10 studies ranging from 9 to 383 patients (mean = 114, median = 36). Of these studies, there were three randomized controlled trials, six observational studies, and one study that compared the management of chronic pain patients with FMS patients. Cannabis was found to be safe and well tolerated in FMS. The main adverse events identified included feeling "high," dizziness/vertigo, dry mouth, cough, red eyes, and drowsiness with no serious adverse events reported. Conclusions: This literature review identified that medical cannabis may be beneficial for some people with FMS. Further studies are required to confirm its efficacy, what type of cannabis is the most effective form to use, and what assessment tools need to be utilized to understand how to quantify clinical outcomes.

Protocol for The International Cohort on Lifestyle Determinants of Health Study: A Longitudinal Investigation of Complementary and Integrative Health Utilization in Postsecondary Education Students.

Objectives: The specific aims are: 1) To characterize the health, wellness, and lifestyle of graduate and undergraduate students, and how these characteristics change over time; 2) To evaluate associations between lifestyle factors and gut microbiota populations and diversity; and 3) To evaluate associations between stress and stress management practices with sleep habits, quality of life, and overall health. Design: The International Cohort on Lifestyle Determinants of Health (INCLD Health) longitudinal cohort study is designed to assess health behaviors and lifestyle practices amongst adults studying complementary and integrative health (CIH) and higher-education students more generally after at least one to six years of exposure to CIH education. INCLD Health will adhere to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines. Settings/Location: Colleges and universities with a CIH focus or interest with the flagship site being the National University of Natural Medicine. Participants: Adults currently enrolled in a college or university with a CIH focus or interest. Outcome Measures: Study visits will be conducted at baseline, 6 months, then every 12 months until the end of each participants' degree program. Measures include anthropometrics; serum and salivary biomarkers of cardiovascular risk, reproductive hormones, and cortisol; nutritional intake measured by a digital food frequency questionnaire; sequencing of fecal microbiota; plus validated questionnaires investigating mood, perceived stress, stress management practices, physical activity, sleep, and wellness. Conclusions: The INCLD Health Study, approved by the NUNM IRB in late 2018, will enroll a unique cohort of adults to characterize the use of CIH practices in relation to short- and long-term health. Our study design provides a breadth of information that could be implemented at multiple sites internationally allowing for comparisons across diverse student cohorts with relatively low cost and personnel.