Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.
Ontology highlight
ABSTRACT: Background
The "classic" endocannabinoid (eCB) system includes the cannabinoid receptors CB1 and CB2, the eCB ligands anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their metabolic enzymes. An emerging literature documents the "eCB deficiency syndrome" as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system--ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation.Methodology/principal findings
We searched PubMed for clinical trials, observational studies, and preclinical research. Data synthesis was qualitative. Exclusion criteria limited the results to 184 in vitro studies, 102 in vivo animal studies, and 36 human studies. Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids), antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Clinical interventions characterized as "complementary and alternative medicine" also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances--alcohol, tobacco, coffee, cannabis) also modulate the eCB system.Conclusions/significance
Few clinical trials have assessed interventions that upregulate the eCB system. Many preclinical studies point to other potential approaches; human trials are needed to explore these promising interventions.
SUBMITTER: McPartland JM
PROVIDER: S-EPMC3951193 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.
McPartland John M JM Guy Geoffrey W GW Di Marzo Vincenzo V
PloS one 20140312 3
<h4>Background</h4>The "classic" endocannabinoid (eCB) system includes the cannabinoid receptors CB1 and CB2, the eCB ligands anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their metabolic enzymes. An emerging literature documents the "eCB deficiency syndrome" as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system--ways to upregulate cannabin ...[more]
Similar Datasets
Project description:BACKGROUND: Despite abundant bereavement care options, consensus is lacking regarding optimal care for bereaved persons. METHODS: We conducted a systematic review, searching MEDLINE, PsychINFO, CINAHL, EBMR, and other databases using the terms (bereaved or bereavement) and (grief) combined with (intervention or support or counselling or therapy) and (controlled or trial or design). We also searched citations in published reports for additional pertinent studies. Eligible studies had to evaluate whether the treatment of bereaved individuals reduced bereavement-related symptoms. Data from the studies was abstracted independently by two reviewers. RESULTS: 74 eligible studies evaluated diverse treatments designed to ameliorate a variety of outcomes associated with bereavement. Among studies utilizing a structured therapeutic relationship, eight featured pharmacotherapy (4 included an untreated control group), 39 featured support groups or counselling (23 included a control group), and 25 studies featured cognitive-behavioural, psychodynamic, psychoanalytical, or interpersonal therapies (17 included a control group). Seven studies employed systems-oriented interventions (all had control groups). Other than efficacy for pharmacological treatment of bereavement-related depression, we could identify no consistent pattern of treatment benefit among the other forms of interventions. CONCLUSIONS: Due to a paucity of reports on controlled clinical trails, no rigorous evidence-based recommendation regarding the treatment of bereaved persons is currently possible except for the pharmacologic treatment of depression. We postulate the following five factors as impeding scientific progress regarding bereavement care interventions: 1) excessive theoretical heterogeneity, 2) stultifying between-study variation, 3) inadequate reporting of intervention procedures, 4) few published replication studies, and 5) methodological flaws of study design.
| S-EPMC503393 | biostudies-literature
Project description:BACKGROUND:Primary care settings are uniquely positioned to reach individuals at risk of alcohol use disorder through technology-delivered behavioral health interventions. Despite emerging effectiveness data, few efforts have been made to summarize the collective findings from these delivery approaches. OBJECTIVE:The aim of this study was to review recent literature on the use of technology to deliver, enhance, or support the implementation of alcohol-related interventions in primary care. We focused on addressing questions related to (1) categorization or target of the intervention, (2) descriptive characteristics and context of delivery, (3) reported efficacy, and (4) factors influencing efficacy. METHODS:We conducted a comprehensive search and systematic review of completed studies at the intersection of primary care, technology, and alcohol-related problems published from January 2000 to December 2018 within EBSCO databases, ProQuest Dissertations, and Cochrane Reviews. Of 2307 initial records, 42 were included and coded independently by 2 investigators. RESULTS:Compared with the years of 2000 to 2009, published studies on technology-based alcohol interventions in primary care nearly tripled during the years of 2010 to 2018. Of the 42 included studies, 28 (64%) were randomized controlled trials. Furthermore, studies were rated on risk of bias and found to be predominantly low risk (n=18), followed by moderate risk (n=16), and high risk (n=8). Of the 24 studies with primary or secondary efficacy outcomes related to drinking and drinking-related harms, 17 (71%) reported reduced drinking or harm in all primary and secondary efficacy outcomes. Furthermore, of the 31 studies with direct comparisons with treatment as usual (TAU), 13 (42%) reported that at least half of the primary and secondary efficacy outcomes of the technology-based interventions were superior to TAU. High efficacy was associated with provider involvement and the reported use of an implementation strategy to deliver the technology-based intervention. CONCLUSIONS:Our systematic review has highlighted a pattern of growth in the number of studies evaluating technology-based alcohol interventions in primary care. Although these interventions appear to be largely beneficial in primary care, outcomes may be enhanced by provider involvement and implementation strategy use. This review enables better understanding of the typologies and efficacy of these interventions and informs recommendations for those developing and implementing technology-based alcohol interventions in primary care settings.
| S-EPMC6475823 | biostudies-other
Project description:BackgroundHealthcare costs are increasing rapidly and at an unsustainable rate in many countries, and inpatient hospitalizations are a significant driver of these costs. Clinical decision support (CDS) represents a promising approach to not only improve care but to reduce costs in the inpatient setting. The purpose of this study was to systematically review trials of CDS interventions with the potential to reduce inpatient costs, so as to identify promising interventions for more widespread implementation and to inform future research in this area.MethodsTo identify relevant studies, MEDLINE was searched up to July 2013. CDS intervention studies with the potential to reduce inpatient healthcare costs were identified through titles and abstracts, and full text articles were reviewed to make a final determination on inclusion. Relevant characteristics of the studies were extracted and summarized.ResultsFollowing a screening of 7,663 articles, 78 manuscripts were included. 78.2% of studies were controlled before-after studies, and 15.4% were randomized controlled trials. 53.8% of the studies were focused on pharmacotherapy. The majority of manuscripts were published during or after 2008. 70.5% of the studies resulted in statistically and clinically significant improvements in an explicit financial measure or a proxy financial measure. Only 12.8% of the studies directly measured the financial impact of an intervention, whereas the financial impact was inferred in the remainder of studies. Data on cost effectiveness was available for only one study.ConclusionsSignificantly more research is required on the impact of clinical decision support on inpatient costs. In particular, there is a remarkable gap in the availability of cost effectiveness studies required by policy makers and decision makers in healthcare systems.
| S-EPMC3878492 | biostudies-literature
Project description:Necrotizing enterocolitis (NEC), which is characterized by severe intestinal inflammation and in advanced stages necrosis, is a gastrointestinal emergency in the neonate with high mortality and morbidity. Despite advancing medical care, effective prevention strategies remain sparse. Factors contributing to the complex pathogenesis of NEC include immaturity of the intestinal immune defense, barrier function, motility and local circulatory regulation and abnormal microbial colonization. Interestingly, enteral feeding is regarded as an important modifiable factor influencing NEC pathogenesis. Moreover, breast milk, which forms the currently most effective prevention strategy, contains many bioactive components that are known to support neonatal immune development and promote healthy gut colonization. This systematic review describes the effect of different enteral feeding interventions on the prevention of NEC incidence and severity and the effect on pathophysiological mechanisms of NEC, in both experimental NEC models and clinical NEC. Besides, pathophysiological mechanisms involved in human NEC development are briefly described to give context for the findings of altered pathophysiological mechanisms of NEC by enteral feeding interventions.
| S-EPMC8161173 | biostudies-literature
Project description:BackgroundPrimary care is being encouraged to implement multiprofessional, system level, chronic illness management approaches to depression. We undertook this study to identify and assess the quality of RCTs testing system level depression management interventions in primary care and to determine whether these interventions improve recovery.MethodSearches of Medline and Cochrane Controlled Register of Trials. 'System level' interventions included: multi-professional approach, enhanced inter-professional communication, scheduled patient follow-up, structured management plan.Results11 trials met all inclusion criteria. 10 were undertaken in the USA. Most focussed on antidepressant compliance. Quality of reporting assessed using CONSORT criteria was poor. Eight trials reported an increase in the proportion of patients recovered in favour of the intervention group, yet did not account for attrition rates ranging from 5 to 50%.ConclusionSystem level interventions implemented in the USA with patients willing to take anti-depressant medication leads to a modest increase in recovery from depression. The relevance of these interventions to countries with strong primary care systems requires testing in a randomised controlled trial.
| S-EPMC1559684 | biostudies-literature
Project description:ImportanceThe endocannabinoid system (ECS) is a lipid-based endogenous signaling system. Its relevance to psychosis is through the association between cannabis use and the onset and course of illness and through the antipsychotic properties of cannabidiol, a potential ECS enhancer.ObjectiveTo conduct a systematic review and meta-analysis of the blood and cerebrospinal fluid (CSF) measures of the ECS in psychotic disorders.Data sourcesWeb of Science and PubMed were searched from inception through June 13, 2018. The articles identified were reviewed, as were citations to previous publications and the reference lists of retrieved articles.Study selectionOriginal articles were included that reported blood or CSF measures of ECS activity in patients with psychotic illnesses and in healthy controls.Data extraction and synthesisPRISMA guidelines, independent extraction by multiple observers, and random-effects meta-analysis were used. Heterogeneity was assessed with the I2 index. Sensitivity analyses tested the robustness of the results.Main outcomes and measuresThe clinical relevance of ECS modifications in psychotic disorders was investigated by (1) a quantitative synthesis of the differences in blood and CSF markers of the ECS between patients and healthy controls, and (2) a qualitative synthesis of the association of these markers with symptom severity, stage of illness, and response to treatment.ResultsA total of 18 studies were included. Three individual meta-analyses were performed to identify the differences in ECS markers between people with schizophrenia and healthy controls. Five studies, including 226 patients and 385 controls, reported significantly higher concentrations of anandamide in the CSF of patients than controls (standardized mean difference [SMD], 0.97; 95% CI, 0.67-1.26; P < .001; I2 = 54.8%). In 9 studies, with 344 patients and 411 controls, significantly higher anandamide levels in blood were found in patients, compared with controls (SMD, 0.55; 95% CI, 0.05-1.04; P = .03; I2 = 89.6%). In 3 studies, involving 88 patients and 179 controls, a significantly higher expression of type 1 cannabinoid receptors on peripheral immune cells was reported in patients compared with controls (SMD, 0.57; 95% CI, 0.31-0.84; P < .001; I2 = 0%). Higher ECS tone was found at an early stage of illness in individuals who were antipsychotic naïve or free, and it had an inverse association with symptom severity and was normalized after successful treatment. Moderate to high level of heterogeneity in methods was found between studies.Conclusions and relevanceTesting clinically relevant markers of the ECS in the blood and CSF of people with psychotic illness appears possible, and these markers provide useful biomarkers for the psychotic disorder; however, not all studies accounted for important variables, such as cannabis use.Trial registrationPROSPERO identifier: CRD42018099863.
| S-EPMC6552109 | biostudies-literature
Project description:Human immunodeficiency virus (HIV) infection and antiretroviral therapy can independently induce HIV-associated neuropathic pain (HIV-NP). There is a dearth of drugs or therapeutic modalities that can alleviate HIV-NP. Smoked cannabis has been reported to improve pain measures in patients with neuropathic pain. Cannabis, phytocannabinoids, and the endocannabinoids such N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), produce some of their effects via cannabinoid receptors (CBRs). Endocannabinoids are degraded by various enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase. We searched PubMed, Google Scholar, clinicaltrials.gov and clinicaltrialsregister.eu using various key words and their combinations for published papers that studied HIV-NP and cannabis, cannabinoids, or endocannabinoids up to 27th December 2020. All original research articles that evaluated the efficacy of molecules that modulate the endocannabinoid system (ECS) for the prevention and/or treatment of pain in HIV-NP animal models and patients with HIV-NP were included. The PubMed search produced a total of 117 articles, whereas the Google Scholar search produced a total of 9467 articles. Amongst the 13 articles that fulfilled the inclusion criteria 11 articles were found in both searches whereas 2 articles were found in Google Scholar only. The clinicaltrials.gov and clinicaltrialsregister.eu searches produced five registered trials of which three were completed and with results. Ten preclinical studies found that the endocannabinoids (2-AG and AEA), synthetic mixed CB1R/CB2R agonist WIN 55,212-2, a CB2R-selective phytocannabinoid β-caryophyllene, synthetic CB2R-selective agonists (AM1710, JWH015, JWH133 and Gp1a, but not HU308); FAAH inhibitors (palmitoylallylamide, URB597 and PF-3845) and a drug combination of indomethacin plus minocycline, which produces its effects in a CBR-dependent manner, either prevented the development of and/or attenuated established HIV-NP. Two clinical trials demonstrated greater efficacy of smoked cannabis over placebo in alleviating HIV-NP, whereas another clinical trial demonstrated that cannabidivarin, a cannabinoid that does not activate CBRs, did not reduce HIV-NP. The available preclinical results suggest that targeting the ECS for prevention and treatment of HIV-NP is a plausible therapeutic option. Clinical evidence shows that smoked cannabis alleviates HIV-NP. Further research is needed to find out if non-psychoactive drugs that target the ECS and are delivered by other routes than smoking could be useful as treatment options for HIV-NP.
| S-EPMC8211923 | biostudies-literature
Project description:OBJECTIVE: To analyse which interventions are effective in influencing morbidity, quality of life, and healthcare utilization of frequently attending patients (FAs) in primary care. METHODS: A systematic literature search was performed for articles describing interventions on FAs in primary care (Medline, Embase, and PsycINFO). Outcomes were morbidity, quality of life (QoL), and use of healthcare. Two independent assessors selected all randomized clinical trials (RCT) and assessed the quality of the selected RCTs. Results. Five primary care based RCTs were identified. Three RCTs used frequent attendance to select patients at risk of distress, major depression, and anxiety disorders. These RCTs applied psychological and psychiatric interventions and focused on undiagnosed psychiatric morbidity of FAs. Two of them found more depression-free days and a better QoL after treating major depressive disorder in FAs. No other RCT found any positive effect on morbidity or QoL. Two RCTs studied an intervention which focused on reducing frequent attendance. No intervention significantly lowered attendance. Due to the difference in study settings and the variation in methods of selecting patients, meta-analysis of the results was not possible. CONCLUSION: No study showed convincing evidence that an intervention improves QoL or morbidity of frequent attending primary care patients, although a small effect might be possible in a subgroup of depressed frequent attenders. No evidence was found that it is possible to influence healthcare utilization of FAs.
| S-EPMC3406646 | biostudies-other
Project description:The high heterogeneity of psychiatric disorders leads to a lack of diagnostic precision. Therefore, the search of biomarkers is a fundamental aspect in psychiatry to reach a more personalized medicine. The endocannabinoid system (ECS) has gained increasing interest due to its involvement in many different functional processes in the brain, including the regulation of emotions, motivation, and cognition. This article reviews the role of the main components of the ECS as biomarkers in certain psychiatric disorders. Studies carried out in rodents evaluating the effects of pharmacological and genetic manipulation of cannabinoid receptors or endocannabinoids (eCBs) degrading enzymes were included. Likewise, the ECS-related alterations occurring at the molecular level in animal models reproducing some behavioral and/or neuropathological aspects of psychiatric disorders were reviewed. Furthermore, clinical studies evaluating gene or protein alterations in post-mortem brain tissue or in vivo blood, plasma, and cerebrospinal fluid (CSF) samples were analyzed. Also, the results from neuroimaging studies using positron emission tomography (PET) or functional magnetic resonance (fMRI) were included. This review shows the close involvement of cannabinoid receptor 1 (CB1r) in stress regulation and the development of mood disorders [anxiety, depression, bipolar disorder (BD)], in post-traumatic stress disorder (PTSD), as well as in the etiopathogenesis of schizophrenia, attention deficit hyperactivity disorder (ADHD), or eating disorders (i.e. anorexia and bulimia nervosa). On the other hand, recent results reveal the potential therapeutic action of the endocannabinoid tone manipulation by inhibition of eCBs degrading enzymes, as well as by the modulation of cannabinoid receptor 2 (CB2r) activity on anxiolytic, antidepressive, or antipsychotic associated effects. Further clinical research studies are needed; however, current evidence suggests that the components of the ECS may become promising biomarkers in psychiatry to improve, at least in part, the diagnosis and pharmacological treatment of psychiatric disorders.
| S-EPMC7197485 | biostudies-literature
Project description:ImportanceRecent estimates suggest that more than 50% of all deaths worldwide are currently attributable to inflammation-related diseases. Psychosocial interventions may represent a potentially useful strategy for addressing this global public health problem, but which types of interventions reliably improve immune system function, under what conditions, and for whom are unknown.ObjectiveTo address this issue, we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) in which we estimated associations between 8 different psychosocial interventions and 7 markers of immune system function, and examined 9 potential moderating factors.Data sourcesPubMed, Scopus, PsycInfo, and ClinicalTrials.gov databases were systematically searched from February 1, 2017, to December 31, 2018, for all relevant RCTs published through December 31, 2018.Study selectionEligible RCTs included a psychosocial intervention, immune outcome, and preintervention and postintervention immunologic assessments. Studies were independently examined by 2 investigators. Of 4621 studies identified, 62 were eligible and 56 included.Data extraction and synthesisData were extracted and analyzed from January 1, 2019, to July 29, 2019. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed. Data were extracted by 2 investigators who were blind to study hypotheses and analyses, and were then analyzed using robust variance estimation. Analysis included 8 psychosocial interventions (behavior therapy, cognitive therapy, cognitive behavior therapy [CBT], CBT plus additive treatment or mode of delivery that augmented the CBT, bereavement or supportive therapy, multiple or combined interventions, other psychotherapy, and psychoeducation), 7 immune outcomes (proinflammatory cytokine or marker levels, anti-inflammatory cytokine levels, antibody levels, immune cell counts, natural killer cell activity, viral load, and other immune outcomes), and 9 moderating factors (intervention type, intervention format, intervention length, immune marker type, basal vs stimulated markers, immune marker measurement timing, disease state or reason for treatment, age, and sex).Main outcomes and measuresThe primary a priori outcomes were pretest-posttest-control (ppc) group effect sizes (ppc g) for the 7 immunologic outcomes investigated.ResultsAcross 56 RCTs and 4060 participants, psychosocial interventions were associated with enhanced immune system function (ppc g = 0.30, 95% CI, 0.21-0.40; t50.9 = 6.22; P < .001). Overall, being randomly assigned to a psychosocial intervention condition vs a control condition was associated with a 14.7% (95% CI, 5.7%-23.8%) improvement in beneficial immune system function and an 18.0% (95% CI, 7.2%-28.8%) decrease in harmful immune system function over time. These associations persisted for at least 6 months following treatment and were robust across age, sex, and intervention duration. These associations were most reliable for CBT (ppc g = 0.33, 95% CI, 0.19-0.47; t27.2 = 4.82; P < .001) and multiple or combined interventions (ppc g = 0.52, 95% CI, 0.17-0.88; t5.7 = 3.63; P = .01), and for studies that assessed proinflammatory cytokines or markers (ppc g = 0.33, 95% CI, 0.19-0.48; t25.6 = 4.70; P < .001).Conclusions and relevanceThese findings suggest that psychosocial interventions are reliably associated with enhanced immune system function and may therefore represent a viable strategy for improving immune-related health.
| S-EPMC7272116 | biostudies-literature