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BACKGROUND: The effects of consuming hemp seed protein (HSP) as well as its hydrolysate-derived bioactive peptide (HSP+) on blood pressure (BP) has not, to our knowledge, been investigated in humans. OBJECTIVES: We aimed to investigate how consumption of HSP and its hydrolysate modulates 24-h systolic (SBP) and diastolic BP (DBP) and plasma biomarkers of BP compared with casein. METHODS: In a double-blind, randomized, crossover design trial, 35 adults who had mild hypertension with SBP between 130 and 160 mmHg and DBP ≤110 mmHg were recruited. Participants were randomly assigned to varying sequences of 3 6-wk treatments, 50 g casein/d, 50 g HSP/d, or 45 g HSP plus 5 g HSP-derived bioactive peptides/d (HSP+), separated by a 2-wk washout period. Treatment effects were assessed with a linear mixed model with repeated measures. RESULTS: Compared with casein, after HSP+ consumption, 24-h SBP and 24-h DBP decreased from 135.1 and 80.0 mmHg to 128.1 ± 1.6 (P < 0.0001) and 76.0 ± 1.4 mmHg (P < 0.0001), respectively, whereas these values were 133.5 ± 1.6 and 78.9 ± 1.4 mmHg after HSP consumption (P < 0.0001). There were no differences between the HSP and HSP+ consumption in plasma angiotensin-converting enzyme (ACE) activity, renin, or nitric oxide (NO) concentrations. However, these 2 treatments were able to lower both ACE and renin activities and raise NO concentration in plasma compared with casein. CONCLUSIONS: These results suggest that hemp protein consumption, as well as in combination with bioactive peptides, may have a role in the dietary management of hypertension. This trial was registered at clinicaltrials.gov as NCT03508895.

Research investigating hemp protein consumption on glycemic response is limited. The effects of hemp protein consumption on blood glucose (BG), insulin, and satiety compared with soybean protein and a carbohydrate control were examined. Two acute randomized repeated-measures crossover experiments were conducted. In both, participants consumed the following isocaloric treatments: 40 g of hemp protein (hemp40), 20 g of hemp protein (hemp20), 40 g of soybean protein (soy40), 20 g of soybean protein (soy20), and a carbohydrate control. In experiments 1 (n = 27) and 2 (n = 16), appetite and BG were measured before (0-60 min, pre-pizza) and after a pizza meal (80-200 min, post-pizza). In experiment 1, food intake was measured at 60 min by ad libitum meal; in experiment 2 a fixed meal was provided (based on body weight) and insulin was measured pre-pizza and post-pizza. In both experiments, BG response was affected by treatment (p < 0.01), time (p < 0.001) and time-by-treatment (p < 0.001) from 0-200 min. Protein treatments lowered 0-60-min BG overall mean and area under the curve compared with control (p < 0.05) dose-dependently. In experiment 2, hemp40 and soy40 lowered (p < 0.05) overall mean insulin concentrations compared with hemp20, soy20, and control pre-meal. Results suggest that hemp protein, like soybean, dose-dependently lowers postprandial BG and insulin concentrations compared with a carbohydrate control. Clinical trial registry: NCT02366598 (experiment 1) and NCT02458027 (experiment 2). Novelty: Hemp protein concentrate dose-dependently leads to lower postprandial BG response compared with a carbohydrate control. No differences were seen between hemp and soy protein.

Angelica gigas Nakai (AGN) root is a medicinal herbal widely used in traditional medicine in Korea. AGN root ethanolic extracts have been marketed as dietary supplements in the United States for memory health and pain management. We have recently reviewed the pharmacokinetics (PK) and first-pass hepatic metabolism of ingested AGN supplements in humans for the signature pyranocoumarins decursin (D, Cmax 1x), decursinol angelate (DA, Cmax ~ 10x) and their common botanical precursor and hepatic metabolite decursinol (DOH, Cmax ~ 1000x). Here we update in vivo medicinal activities of AGN and/or its pyranocoumarins and furanocoumarin nodakenin in cancer, pain, memory loss, cerebral ischemia reperfusion stroke, metabolic syndrome and vascular endothelial dysfunctions, anxiety, sleep disorder, epilepsy, inflammatory bowel disease, osteoporosis and osteoarthritis. Given their polypharmacology nature, the pertinent mechanisms of action are likely misrepresented by many cell culture studies that did not consider the drug metabolism knowledge. We report here Rho-associated protein kinases (ROCK1/2) as novel targets for DA and DOH. Combining with published inhibitory activity of DOH on acetylcholinesterase, agonist activity of DOH and antagonist/degrader activity of DA/D on androgen and estrogen receptors, D/DA promoting activity for glutamic acid decarboxylase (GAD)- gamma-aminobutyric acid (GABA) inhibitory axis and inhibition of glutamate dehydrogenase (GDH), monoamine oxidase-A (MAO-A) and transient receptor potential vanilloid 1 (TRPV1), we postulate their contributions to neuro-cognitive, metabolic, oncologic, vascular and other beneficial bioactivities of AGN extracts. A clinical trial is being planned for an AGN extract to manage side effects of androgen deprivation therapy in prostate cancer patients. © 2025. The Author(s).

BACKGROUND: Long COVID have posed a global health burden since the COVID-19 pandemic. This study aimed to evaluate the efficacy and safety of a combined plant extract (CPE) formulation, containing Citrus aurantifolia, Tiliacora triandra, Cannabis sativa, Alpinia galanga, and Piper nigrum, in participants with long COVID. A newly developed long COVID symptom questionnaire was used to evaluate outcomes. METHODS: This randomized, double-blinded, placebo-controlled trial was conducted at the College of Pharmacy, Rangsit University, Thailand. Participants were randomly assigned to receive either a CPE supplement (4500 mg/day) or a placebo for 7 days. Primary outcomes were changes in C-reactive protein (CRP) levels and the total symptom score (ranging from 0 to 57 points). Secondary outcomes included full recovery/improvement of long COVID symptoms, health-related quality of life (HRQOL), and adverse events. RESULTS: A total of 66 participants were enrolled, with 33 in each group. The CPE supplement did not significantly reduce CRP levels, with a median difference (MD) (95 % CI) of -0.05 (-0.49, 0.39) mg/L compared to placebo. However, the CPE group showed a reduction in the total symptom score [MD (95 % CI) of -4.00 (-7.58, -0.42)], and a reduction in overall moderate to severe symptoms [RR (95 % CI) of 0.57 (0.35, 0.91)], moderate to severe fatigue [RR (95 % CI) of 0.25 (0.08, 0.81)], and moderate to severe post-exertional malaise (PEM) [RR (95 % CI) of 0.35 (0.16, 0.78)]. Changes in HRQOL scores did not differ significantly between groups. Adverse events were mostly mild and resolved by the end of the follow-up period. CONCLUSIONS: Our study suggests potential benefits of the CPE in alleviating moderate to severe long COVID symptoms, particularly fatigue and PEM, with an acceptable safety profile. However, larger-scale trials are necessary to validate these findings, and assessing the reliability of the long COVID symptom questionnaire is essential before its application in future studies. TRIAL REGISTRATION NUMBER: TCTR20230131004 (Registration date: 2023-01-31, Thai Clinical Trials Registry).

PURPOSE: Hemp contains protein with high concentrations of the branched-chain amino acids leucine, isoleucine, and valine and oils that have anti-inflammatory properties. Our purpose was to investigate the effects of hemp supplementation during resistance training in trained young adults. METHODS: Males (n = 22, 29 ± 8y) and females (n = 12, 30 ± 9y) were randomized (double-blind) to receive 60 g/d of hemp (containing 40 g protein and 9 g oil) or 60 g/d of soy (matched for protein and calories) during eight weeks of resistance training (~ 4x/week). Before and after the intervention, participants were assessed for whole-body lean tissue and fat mass (dual-energy X-ray absorptiometry), regional muscle hypertrophy (ultrasound), strength (1-repetition maximum leg press, bench press, biceps curl), voluntary activation (interpolated twitch technique), resting twitch properties (single pulse; 0.5 ms) (before and after a fatigue test), markers of inflammation (Interleukin 6 and C-reactive protein), and bone resorption (urinary N-telopeptides). RESULTS: Hemp supplementation increased elbow flexor muscle thickness in females (2.6 ± 0.4-3.1 ± 0.5 cm, p = 0.012) while soy supplementation increased elbow flexor muscle thickness in males (3.7 ± 0.4-4.0 ± 0.5 cm, p < 0.01). Twitch torque and rate of torque development were preserved after a fatigue test in males consuming hemp compared to males on soy (p < 0.001). CONCLUSION: Overall, hemp provides some sex-specific beneficial effects on measures of muscle accretion and torque under fatiguing conditions in resistance trained young adults. CLINICALTRIALS: gov Identifier: NCT02529917, registered August 11, 2015. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Hemp seed and physical activity (PA) have many benefits for the metabolic and brain health of the body. This study investigated the effects of hemp seed alone and aerobic exercise on metabolic markers, oxidative stress, and neurotrophic factors in young sedentary men. This double-blind, placebo-controlled, randomized clinical trial was conducted on 48 sedentary young men in Tabriz, Iran, from April to August. The researcher in this study randomized all participants into four groups, including (1) hemp seed, (2) hemp seed + PA, (3) PA + placebo, and (4) placebo. Hemp seed supplement was administered in two 1-g capsules daily, and aerobic PA was performed a week thrice. Levels of anthropometric indices, dietary intake, antioxidant markers, lipid profile, fasting blood sugar (FBS), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY), balance, reaction time, and sit-ups were evaluated for all participants at baseline and post-intervention. We used ANOVA and ANCOVA analysis to compare oxidative stress and neurotropic factors in all intervention groups. If the distribution of the response variable was not normal, the non-parametric equivalent of these tests was used (Wilcoxon and Kruskal-Wallis tests). We performed all statistical analyzes using SPSS software version 23, and the significance level was considered 0.05 in all the statistical tests. Aerobic PA with hemp seed consumption caused a significant difference in weight, body mass index, fat mass, high-density lipoprotein, catalase, and BDNF compared with baseline. Also, aerobic PA alone caused significant changes in body weight, fat mass, and triglyceride compared with baseline. Consumption of hemp seeds alone caused a significant increase in high-density lipoprotein levels compared with baseline. At the end of the study, fat mass, total cholesterol, low-density lipoproteins, and BDNF were significantly different between the groups. According to our results, aerobic PA combined with hemp seed consumption may improve anthropometric indices, lipid profile, and BDNF and improve h

Dogs are commonly affected by Osteoarthritis (OA). Different approaches can be used to alleviate animals' symptoms. In this randomised, placebo-controlled and double-blind clinical trial, we performed a three months follow-up study assessing the efficacy of a food supplement containing natural ingredients (Cannabis sativa oil, Boswellia serrata Roxb. Phytosome® and Zingiber officinale extract) in dogs with OA after the interruption of physiotherapy that was performed during the previous three months. Inflammation and oxidative stress were reduced in the treated group (higher glutathione (GSH) and lower C-reactive protein [CRP] levels in blood) as well as chronic pain.

We determined the effects of a commercially available, GRAS (Generally Recognized As Safe) by independent conclusion, CBD-containing hemp oil extract on stress resilience, perceived recovery, mood, affect, body composition, and clinical safety markers in healthy human subjects.Methods: Using a randomized, placebo-controlled, double-blind design, 65 overweight, but otherwise healthy men and women (35.2 ± 11.4 years, 28.5 ± 3.3 kg/m2) ingested either Hemp Oil Extract [Hemp, 60 mg/d PlusCBDTM Extra Strength Hemp Extract Oil (15 mg hemp-derived CBD)] or a placebo (PLA) every day for six weeks while continuing to follow their normal diet and physical activity patterns. Outcome variables included changes in stress resilience, a 14-item panel of various psychometric parameters, heart-rate variability, plasma chromogranin A, body composition, and general markers of health. Data were analyzed using mixed factorial ANOVA, t-tests with 95% confidence intervals, and effect sizes (ES).Results: HDL cholesterol significantly improved in the Hemp group (p = 0.004; ES = 0.75). No other statistically significant group x time interaction effects were observed. Statistical tendencies for between-group differences were found for 'I Get Pleasure From Life' (p = 0.06, ES = 0.48) and 'Ability to Cope with Stress' (p = 0.07, ES = 0.46). Sleep quality (Hemp, p = 0.005, ES = 0.54) and sleep quantity (Hemp, p = 0.01, ES = 0.58) exhibited significant within-group changes. All values for hepato-renal function, cardiovascular health, fasting blood lipids, and whole blood cell counts remained within normal clinical limits with no between-group differences over time being identified.Conclusions: Hemp supplementation improved HDL cholesterol, tended to support psychometric measures of perceived sleep, stress response, and perceived life pleasure and was well tolerated with no clinically relevant safety concerns. Registered at clinicaltrials.gov: NCT04294706.

BACKGROUND: Primary hypertension accounts for almost 95% of all cases of high blood pressure and is a major modifiable risk factor for cardiovascular diseases. Lifestyle interventions have been shown to prevent hypertension. One of the prominent potential therapeutic lifestyle strategies to prevent or manage hypertension is increasing dietary protein as a macronutrient or as bioactive peptides. An emerging plant-based protein source that may have anti-hypertensive properties is hemp seed. METHODS/DESIGN: A randomized, double-blind, crossover clinical trial will be conducted on 35 hypertensive participants aged 18-75 years, with a BMI between 18.5 and 40 kg/m2, systolic blood pressure (SBP) between 130 and 160 mmHg and diastolic blood pressure (DBP) ≤ 110 mmHg. The trial will be conducted for a period of 22 weeks and will consist of three treatment periods of 6 weeks, separated by 2-week washout periods. The treatments will be consumed twice a day and consist of 25 g casein, hemp seed protein (HSP), or HSP plus HSP hydrolysate (HSP+). The primary outcome of this trial is 24-h SBP, measured on the first day of first phase and the last day of each phase. Office-measured blood pressure, pulse-wave velocity and augmentation index and anthropometrics will be determined at the first and last days of each period. Also, body composition will be assessed by dual x-ray absorptiometry (DXA) scan on the first day of the first phase and within the last 2 days of each treatment period. Blood samples will be collected on the first and last 2 days of each treatment phase whereas urine samples will be collected on the first day of the first phase plus the last day of each phase to be analyzed for specific biomarkers. DISCUSSION: This trial protocol is designed to evaluate the hypotensive potential of consuming whole HSP, and HSP+, in comparison to casein protein. This study will be the first trial investigating the potential anti-hypertensive benefit of dietary hemp protein plus bioactive peptide consumption in humans. TRIAL REGISTRATION: National Clinical Trial (NCT), ID: NCT03508895. Registered on 28 June 2018. Retrospectively registered on the publicly accessible Registry Data

The present study was carried out to study the effect of different doses of hemp seed alone or in combination with dill seed against antibiotic growth promoter on performance, serum biochemicals and gut health of broiler chickens over a period of 42 days. Total 192 broiler chicks were grouped randomly into six treatments and fed with basal diet (BD) along with different levels of seeds, viz., T1 (BD), T2 (BD + 0.2% HS), T3 (BD + 0.2% HS + 0.3 DS), T4 (BD + 0.3% HS) and T5 (BD + 0.3% HS + 0.3 DS) and T6 (BD + 0.025% Bacitracin Methylene Disalicylate-BMD). The performance traits like feed intake, body weight gain and feed conversion ratio (FCR) and carcass traits like cut-up parts, giblet and abdominal fat yield remained unaffected due to dietary treatments for overall trial period; however, the average feed intake in early phase (0-3 weeks) reduced significantly (p < 0.05) in treatment birds than both controls (T1 & T6). Serum protein concentration remained unchanged, whereas significant (p < 0.05) reduction in serum lipids like triglyceride, LDL and total cholesterol concentration was noticed due to dietary inclusion of seeds. Serum enzymes like AST and ALT concentrations depleted significantly (p < 0.05) treated groups, except at higher seed doses (T5); however, alkaline phosphatase levels were unaffected. Coliform count in caecum and jejunum reduced linearly (p < 0.01) due to seed inclusion, whereas dose-dependent proliferation of lactobacilli was evident (p < 0.01) in caecum and jejunum of treated birds. No effect was observed on the villus height and crypt depth of the jejunal mucosa. To conclude, dietary supplementation of hemp and dill seed could not affect the growth performance and carcass traits; however, it positively altered the serum lipid profile of the birds and improved gut health as well, thereby enhanced overall performance of broiler chickens. © 2019 Blackwell Verlag GmbH.

BACKGROUND: The effect of nutrition and dietary supplements as environmental factors has been suggested as possible factors affecting both disease risk and progression in on the course of multiple sclerosis with complex genetic-risk profiles. This study was aimed to assess regulation of surface-membrane enzymes such as Delta-6-desaturase (FADS2), secretory Phospholipase A2(sPLA2) by hemp seed and evening primrose oils as well as Hot-natured dietary intervention in relapsing remitting multiple sclerosis (RRMS) patients. METHODS AND MATERIALS: In this double blind, randomized trial, 100 RRMS patients with Extended disability status score (EDSS)<6 were allocated into 3 groups: "Group A" who received co-supplemented hemp seed and evening primrose oils along with advised Hot nature diet; "Group B", who received olive oil; "Group C", who received the co-supplemented oils. Clinically EDSS and functional score as well as biochemical parameters [blood cells polyunsaturated fatty acid (PUFA), FADS2, sPLA2] were assessed at baseline and after 6 months. RESULTS: Mean follow-up was 180±2.9SD days (N=65, 23 M and 42 F aged 34.25±8.07 years with disease duration 6.80±4.33 years). There was no significant difference in studies parameters at baseline. After 6 months, significant improvements in EDSS and functional score were found in the groups A and C while EDSS and pyramidal score showed significant increase in group B. Alteration of biochemical parameters showed improvement in groups A and C whereas there was worsening condition for group B after the intervention. CONCLUSION: The co-supplemented hemp seed and evening primrose oils with Hot nature diet can have beneficial effects in improving clinical symptoms and signs in RRMS patients which were confirmed by regulation of surface-membrane enzymes.

BACKGROUND: Multiple sclerosis (MS) is the most chronic and inflammatory disorder. Because of limited efficacy and adverse side effects, identifying novel therapeutic and protective agents is important. This study was aimed to assess the potential therapeutic effects of hemp seed and evening primrose oils as well as Hot-nature dietary intervention on RRMS patients. METHODS AND MATERIALS: In this double blind, randomized trial, 100 MS patients with EDSS<6 were allocated into 3 groups: "Group A" who received co-supplemented hemp seed and evening primrose oils with advised Hot-nature diet, "Group B" who received olive oil, "Group C" who received the co-supplemented oils. Mizadj, clinically EDSS and relapse rate as well as immunological factors (IL-4, IFN-γ and IL-17) were assessed at baseline and after 6 months. RESULTS: Mean follow-up was 180±2.9 SD days (N=65, 23 M and 42 F aged 34.25±8.07 years with disease duration 6.80±4.33 years). There was no significant difference in studies parameters at baseline. After 6 months, significant improvements in Mizadj, EDSS and relapse rate were found in the groups A and C, while the group B showed a border significant decrease in relapse rate. Immunological parameters showed improvement in groups A and C, whereas there was worsening condition for group B after the intervention. CONCLUSION: The co-supplemented hemp seed and evening primrose oils with Hot-nature diet have beneficial effects in improving of clinical score in RRMS patients which were confirmed by immunological findings.

OBJECTIVE: The impact of dietary polyunsaturated fatty acids (PUFAs) of the n-6 and n-3 series on the cardiovascular system is well documented. To directly compare the effects of three dietary oils (fish, flaxseed and hempseed) given in concentrations expected to be self-administered in the general population on specific cardiovascular parameters in healthy volunteers. DESIGN: 86 healthy male and female volunteers completed a 12 week double blinded, placebo controlled, clinical trial. They were randomly assigned to one of the four groups. Subjects were orally supplemented with two 1 gm capsules of placebo, fish oil, flaxseed oil or hempseed oil per day for 12 weeks. RESULTS: Plasma levels of the n-3 fatty acids docosahexanoic acid and eicosapentanoic acid increased after 3 months supplementation with fish oil. Alpha linolenic acid concentrations increased transiently after flaxseed supplementation. However, supplementation with hempseed oil did not significantly alter the concentration of any plasma fatty acid. The lipid parameters (TC, HDL-C, LDL-C and TG) did not show any significant differences among the four groups. Oxidative modification of LDL showed no increase in lag time over the 12 wk period. None of the dietary interventions induced any significant change in collagen or thrombin stimulated platelet aggregation and no increase in the level of inflammatory markers was observed. CONCLUSION: From a consumer's perspective, ingesting 2 capsules of any of these oils in an attempt to achieve cardiovascular health benefits may not provide the desired or expected result over a 3 month period.

BACKGROUND: Both hempseed oil (HO) and flaxseed oil (FO) contain high amounts of essential fatty acids (FAs); i.e. linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3), but almost in opposite ratios. An excessive intake of one essential FA over the other may interfere with the metabolism of the other while the metabolisms of LA and ALA compete for the same enzymes. It is not known whether there is a difference between n-3 and n-6 FA of plant origin in the effects on serum lipid profile. AIM OF THE STUDY: To compare the effects of HO and FO on the profile of serum lipids and fasting concentrations of serum total and lipoprotein lipids, plasma glucose and insulin, and haemostatic factors in healthy humans. METHODS: Fourteen healthy volunteers participated in the study. A randomised, double-blind crossover design was used. The volunteers consumed HO and FO (30 ml/day) for 4 weeks each. The periods were separated by a 4-week washout period. RESULTS: The HO period resulted in higher proportions of both LA and gamma-linolenic acid in serum cholesteryl esters (CE) and triglycerides (TG) as compared with the FO period (P < 0.001), whereas the FO period resulted in a higher proportion of ALA in both serum CE and TG as compared with the HO period (P < 0.001). The proportion of arachidonic acid in CE was lower after the FO period than after the HO period (P < 0.05). The HO period resulted in a lower total-to-HDL cholesterol ratio compared with the FO period (P = 0.065). No significant differences were found between the periods in measured values of fasting serum total or lipoprotein lipids, plasma glucose, insulin or hemostatic factors. CONCLUSIONS: The effects of HO and FO on the profile of serum lipids differed significantly, with only minor effects on concentrations of fasting serum total or lipoprotein lipids, and no significant changes in concentrations of plasma glucose or insulin or in haemostatic factors.

Steroidogenesis is essential for ovarian physiology and reproductive health. Regulated by hormonal signals, it is susceptible to external modulators, notably environmental exposures. As cannabis becomes more accessible globally, its use among women of reproductive age has increased, yet the implications for reproductive endocrinology remain poorly understood and contradictory. In this study, we investigated whether cannabinoids modulate basal or stimulated estradiol secretion in the human granulosa cell line KGN. To characterize the endocannabinoid system (ECS) in these cells, we performed a meta-analysis of publicly available RNA sequencing datasets, revealing expression of key ECS components. KGN cells were cultured with or without cannabinoids in the presence of protein kinase activators, PKA (FSK), PKB (SC79), and PKC (PMA). Following cannabinoid and kinase stimulations, the media were collected and analyzed for estradiol concentrations via ELISA. We observed no significant changes in basal or activated estradiol secretion in response to THC or CBD. These findings were supported by RT-qPCR analysis showing no alteration in the expression of CYP19A1, the gene encoding aromatase, which catalyzes the conversion of androgens to estrogens in granulosa cells. Although cannabinoids have been shown to influence sex hormones in vivo, our data suggest that these effects are not mediated at the granulosa cell level. This study contributes to a better understanding of how cannabinoids may interact with ovarian steroidogenesis and reproductive function.

BACKGROUND: The legalization of industrial hemp, Cannabis sativa L., which contains < 0.3% ∆9-tetrahydrocannabinol (∆9-THC), in many countries, has led to a significant rise in its cultivation. Consequently, byproducts derived from industrial hemp processing have resulted in numerous emerging potential feed ingredients, including hempseed byproduct (HSB; hempseed cake or hempseed meal) from seed processing, hemp hurds, and hemp stalk from fiber processing, and spent hemp biomass (SHB) from cannabinoids extraction. Research to assess the potential use of these byproducts as animal feed is progressing. METHOD: We provide an overview of the nutritional characteristics of the various hemp byproducts and provide a meta-analysis of 26 empirical studies investigating the use of hemp byproducts on ruminants. Using those studies, we delved into a comprehensive assessment regarding the effects of HSB and SHB on the health and performance of the animals. RESULTS: Overall, HSB and SHB possess excellent nutritional profiles due to their high protein content and, particularly for HSB, desirable fatty acids profile can partially replace protein-source ingredients such as soybean meal, dried distillers' grains with soluble, canola meal, and alfalfa in the diets of ruminants. These byproducts contain diverse phytochemicals with antioxidants, anti-inflammatory, and antimicrobial properties. Data do not reveal any significant concern for the health of the animals fed hemp byproducts and, with few exceptions, the data do not indicate a substantial effect on performance; dietary inclusion of HSB, however, has a deleterious impact on rumen fermentation and nutrient digestibility when given as raw HSB without dehulling, reducing the growth performance of meat-producing ruminants. On the other hand, SHB has low palatability overall but does not impair production performance. CONCLUSIONS: Although they can be promising feed ingredients for ruminants, their present use as feed ingredients is limited by the residuals of THC and CBD. Our comprehensive review of the current legal status of hemp byproducts worldwide highlighted a complex scenario with some countries allowing the use of hemp

BACKGROUND: The impact of cannabis uses on blood levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) remains uncertain, with conflicting findings reported in the literature. BDNF and NGF both are essential proteins for neuron's growth, and their dysregulation is seen in various mental disorders. This study aims to evaluate the relationship between cannabis usage and BDNF and NGF levels due to their potential implications for mental health. METHODS: A comprehensive search of electronic databases was performed using appropriate MeSH terms and keywords. Inclusion criteria comprised human studies investigating the relationship between cannabis use and BDNF and NGF levels. RESULTS: A total of 11 studies met the inclusion criteria and were included. The pooled analysis revealed a nonsignificant association between cannabis use and dysregulated blood levels of BDNF (random-effects model, standardized mean differences [SMD] = .26, 95% CI -.34 to .76, p = .40). The results of our subgroup analysis based on BDNF source showed a nonsignificant between-group difference. For NGF levels, four studies were included, the pooled analysis revealed a nonsignificant association between cannabis use and dysregulated blood levels of NGF (random-effects model, SMD = -.60, 95% CI -1.43 to -.23, p = .16). In both analyses, high heterogeneity was observed among the included studies which is a notable limitation to current meta-analysis. CONCLUSION: This systematic review highlights the need for further research to elucidate the relationship between cannabis use and these neurotrophic factors. A better understanding of these associations can contribute to our knowledge of the neurobiological effects of cannabis and inform potential implications for mental health, cognitive function, and neurodegenerative disorders. © 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.

CONTEXT: Many clinicians, trainers, and athletes do not have a true understanding of the effects of commonly used performance-enhancing drugs (PEDs) on performance and health. OBJECTIVE: To provide an evidence-based review of 7 commonly used pharmacological interventions for performance enhancement in athletes. DATA SOURCES: PubMed and Scopus databases were searched on April 8, 2022. STUDY SELECTION: Systematic reviews (SRs) and meta-analyses (MAs) assessing the performance-enhancing effects of the following interventions were included: androgenic anabolic steroids (AAS), growth hormone (GH), selective androgen receptor modulators (SARMs), creatine, angiotensin-converting enzyme (ACE)-inhibitors, recombinant human erythropoietin (rHuEPO), and cannabis. STUDY DESIGN: Umbrella review of SRs and MAs. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: Primary outcomes collected were (1) body mass, (2) muscle strength, (3) performance, and (4) recovery. Adverse effects were also noted. RESULTS: A total of 27 papers evaluating 5 pharmacological interventions met inclusion criteria. No studies evaluating SARMs or ACE-inhibitors were included. AAS lead to a 5% to 52% increase in strength and a 0.62 standard mean difference in lean body mass with subsequent lipid derangements. GH alters body composition, without providing a strength or performance benefit, but potential risks include soft tissue edema, fatigue, arthralgias, and carpel tunnel syndrome. Creatine use during resistance training can safely increase total and lean body mass, strength, and performance in high-intensity, short-duration, repetitive tasks. Limited evidence supports rHuEPO benefit on performance despite increases in both VO2max and maximal power output, and severe cardiovascular risks are documented. Cannabis provides no performance benefit and may even impair athletic performance. CONCLUSION: In young healthy persons and athletes, creatine can safely provide a performance-enhancing benefit when taken in controlled doses. AAS, GH, and rHuEPO are associated with severe adverse events and do not support a performance benefit, despite showing the ability to change bodily composition, strength, and/or physio

Cannabis use leads to symptom exacerbation in schizophrenia patients, and endocannabinoid ligands have been studied as tentative schizophrenia therapeutics. Here, we aimed to characterise the connection between schizophrenia and the cannabinoid receptor 1 gene (CNR1) and explore possible mechanisms affecting its expression in schizophrenia. We performed a participant data systematic meta-analysis of CNR1 gene expression and additional endocannabinoid system genes in both brain (subcortical areas) and blood samples. We integrated eight brain sample datasets (overall 316 samples; 149 schizophrenia and 167 controls) and two blood sample datasets (overall 90 samples; 53 schizophrenia and 37 controls) while following the PRISMA meta-analysis guidelines. CNR1 was downregulated in subcortical regions and upregulated in blood samples of patients with schizophrenia. CNR2 and genes encoding endocannabinoids synthesis and degradation did not show differential expression in the brain or blood, except fatty acid amide hydrolase (FAAH), which showed a downregulation trend in blood. In addition, the brain expression levels of CNR1 and three GABA receptor genes, GABRA1, GABRA6 and GABRG2, were positively correlated (R = .57, .36, .54; p = 2.7 × 10-14 , 6.9 × 10-6 and 1.1 × 10-12 , respectively). Brain CNR1 downregulation and the positive correlation with three GABA receptor genes suggest an association with GABA neurotransmission and possible effects on negative schizophrenia symptoms. Further studies are required for clarifying the opposite CNR1 dysregulation in the brain and blood of schizophrenia patients and the potential of endocannabinoid ligands as schizophrenia therapeutics. © 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The neurobiological mechanisms underlying the effects of delta-9-tetrahydrocannabinol (THC) remain unclear. Here, we examined the spatial acute effect of THC on human regional brain activation or blood flow (hereafter called 'activation signal') in a 'core' network of brain regions from 372 participants, tested using a within-subject repeated measures design under experimental conditions. We also investigated whether the neuromodulatory effects of THC are related to the local expression of the cannabinoid-type-1 (CB1R) and type-2 (CB2R) receptors. Finally, we investigated the dose-response relationship between THC and key brain substrates. These meta-analytic findings shed new light on the localisation of the effects of THC in the human brain, suggesting that THC has neuromodulatory effects in regions central to many cognitive tasks and processes, related to dose, with greater effects in regions with higher levels of CB1R expression.

BACKGROUND: Anorexia (loss of appetite) is a prevalent and distressing symptom in people with cancer, with limited effective interventions. Medicinal cannabis has shown promise in improving appetite-related symptoms in people with cancer. AIM: To assess the efficacy of medicinal cannabis for improving appetite-related symptoms in people with cancer, considering measures and outcomes, interventions and toxicity. DESIGN: Systematic review with narrative approach to synthesis and meta-analysis. DATA SOURCES: Databases (MEDLINE, CINAHL, CENTRAL), websites and trials registries were searched from inception to February 2021. Included studies were randomised controlled trials (RCT) in English peer-reviewed journals comparing medicinal cannabis with placebo and/or another intervention. Study quality was assessed using the Cochrane risk of bias tool. RESULTS: Five studies were included that compared medicinal cannabis interventions (dronabinol, nabilone and cannabis extract) either with placebo (n = 4) or megestrol acetate (n = 1). Measures and trial endpoints varied, but efficacy was demonstrated in one trial only, in which dronabinol significantly improved chemosensory perception and other secondary outcomes (taste of food, premeal appetite, proportion of calories consumed as protein) compared with placebo. Cannabis interventions were generally well tolerated across studies, regardless of the product or dose, although the comprehensive measurement of toxicities was limited. CONCLUSION: Evidence from RCTs that medicinal cannabis increases appetite in people with cancer is limited. Measures, outcomes and interventions were variable, and toxicities have not been comprehensively evaluated. Future research should carefully consider biological mechanisms to guide more nuanced selection of endpoints and interventions, including product, dose and administration.

The field of Cannabis sativa L. research for medical purposes has been rapidly advancing in recent decades and a growing body of evidence suggests that phytocannabinoids are beneficial for a range of conditions. At the same time impressing development has been observed for formulations and delivery systems expanding the potential use of cannabinoids as an effective medical therapy. The objective of this review is to present the most recent results from pharmaceutical companies and research groups investigating methods to improve cannabinoid bioavailability and to clearly establish its therapeutic efficacy, dose ranges, safety and also improve the patient compliance. Particular focus is the application of cannabinoids in pain treatment, describing the principal cannabinoids employed, the most promising delivery systems for each administration routes and updating the clinical evaluations. To offer the reader a wider view, this review discusses the formulation starting from galenic preparation up to nanotechnology approaches, showing advantages, limits, requirements needed. Furthermore, the most recent clinical data and meta-analysis for cannabinoids used in different pain management are summarized, evaluating their real effectiveness, in order also to spare opioids and improve patients' quality of life. Promising evidence for pain treatments and for other important pathologies are also reviewed as likely future directions for cannabinoids formulations. © 2021. The Author(s).

AIM: To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and dystonia. METHOD: Searches were updated (January 2016 to May 2020) for oral baclofen, trihexyphenidyl, benzodiazepines, clonidine, gabapentin, levodopa, botulinum neurotoxin (BoNT), intrathecal baclofen (ITB), and deep brain stimulation (DBS), and from database inception for medical cannabis. Eligible studies included at least five individuals with CP and dystonia and reported on dystonia, goal achievement, motor function, pain/comfort, ease of caregiving, quality of life (QoL), or adverse events. Evidence certainty was evaluated using GRADE. RESULTS: Nineteen new studies met inclusion criteria (two trihexyphenidyl, one clonidine, two BoNT, nine ITB, six DBS), giving a total of 46 studies (four randomized, 42 non-randomized) comprising 915 participants when combined with those from the original systematic review. Very low certainty evidence supported improved dystonia (clonidine, ITB, DBS) and goal achievement (clonidine, BoNT, ITB, DBS). Low to very low certainty evidence supported improved motor function (DBS), pain/comfort (clonidine, BoNT, ITB, DBS), ease of caregiving (clonidine, BoNT, ITB), and QoL (ITB, DBS). Trihexyphenidyl, clonidine, BoNT, ITB, and DBS may increase adverse events. No studies were identified for benzodiazepines, gabapentin, oral baclofen, and medical cannabis. INTERPRETATION: Evidence evaluating the use of pharmacological and neurosurgical management options for individuals with CP and dystonia is limited to between low and very low certainty. What this paper adds Meta-analysis suggests that intrathecal baclofen (ITB) and deep brain stimulation (DBS) may improve dystonia and pain. Meta-analysis suggests that DBS may improve motor function. Clonidine, botulinum neurotoxin, ITB, and DBS may improve achievement of individualized goals. ITB and DBS may improve quality of life. No direct evidence is available for oral baclofen, benzodiazepines, gabapentin, or medical cannabis. Publisher: OBJETIVO: Actualizar una revisión sistemática sobre evidencia publicada hasta Diciemb

Background: Data from the Global Burden of Disease Study 2016 recently estimated that after opioid and cannabis use disorders, cocaine use disorders were among the most common, with around 5.8 million cases around the world. Several genome-wide expression studies (GWES) for cocaine misuse have been carried out in brain tissues from patients and controls and in mouse and rat models.Objectives: In the current work, we used a convergent functional genomics approach to identify novel candidate genes and pathways for cocaine misuse.Methods: We carried out meta-analyses for available GWES for cocaine misuse in humans and mouse and rat models (three, four, and two GWES, respectively). Multiple lines of evidence (GWES, genome-wide association and epigenomic data) were integrated to prioritize top candidate genes, and a functional enrichment analysis was carried out.Results: Several top candidate genes supported by multiple lines of genomic evidence, and with known roles in brain plasticity, were identified: APP, GRIN2A, GRIN2B, KCNA2, MAP4, PCDH10, PPP3CA, SNCB, and SV2C. An enrichment of genes regulated by the AP1 transcription factor was found.Conclusion: This is the first meta-analysis of GWES for cocaine misuse in humans and mouse and rat models. The analysis of convergence of multiple lines of genome-wide evidence identified novel candidate genes and pathways for cocaine misuse, which are of basic and clinical importance.

CADM2 has been associated with a range of behavioural and metabolic traits, including physical activity, risk-taking, educational attainment, alcohol and cannabis use and obesity. Here, we set out to determine whether CADM2 contributes to mechanisms shared between mental and physical health disorders. We assessed genetic variants in the CADM2 locus for association with phenotypes in the UK Biobank, IMPROVE, PROCARDIS and SCARFSHEEP studies, before performing meta-analyses. A wide range of metabolic phenotypes were meta-analysed. Psychological phenotypes analysed in UK Biobank only were major depressive disorder, generalised anxiety disorder, bipolar disorder, neuroticism, mood instability and risk-taking behaviour. In UK Biobank, four, 88 and 172 genetic variants were significantly (p < 1 × 10-5) associated with neuroticism, mood instability and risk-taking respectively. In meta-analyses of 4 cohorts, we identified 362, 63 and 11 genetic variants significantly (p < 1 × 10-5) associated with BMI, SBP and CRP respectively. Genetic effects on BMI, CRP and risk-taking were all positively correlated, and were consistently inversely correlated with genetic effects on SBP, mood instability and neuroticism. Conditional analyses suggested an overlap in the signals for physical and psychological traits. Many significant variants had genotype-specific effects on CADM2 expression levels in adult brain and adipose tissues. CADM2 variants influence a wide range of both psychological and metabolic traits, suggesting common biological mechanisms across phenotypes via regulation of CADM2 expression levels in adipose tissue. Functional studies of CADM2 are required to fully understand mechanisms connecting mental and physical health conditions.

Background: People who abuse substances are at increased risk of metabolic syndrome and diabetes resulting partly from increased cell damage and due to the effects of opioids on glucose homeostasis. Therefore, people with diabetes who abuse substances may carry greater health risks than the general population resulting from their effect on glucose metabolism. These substances may be in the form of cannabis, hallucinogens, opioids, and stimulants. Therefore, the aim of this review was to evaluate the effects of substance abuse on blood glucose parameters in patients with diabetes. Method: Databases including Embase, Psycho-Info, Google Scholar and PubMed were searched systematically for relevant articles from database inception to May 2018. Search terms including medical subject headings (MeSH) based on the Population, Intervention, Comparator and Outcomes (PICO) framework was used to access the databases. Eligible articles were selected based on set inclusion and exclusion criteria. The articles reviewed were evaluated for quality and meta-analysis and sensitivity analysis were carried out using the Review Manager (RevMan 5.3, The Cochrane Collaboration, Copenhagen, Denmark). The Random effects model was used for the data analysis. Results: Twelve studies which met the inclusion criteria were included in the systematic review, while nine articles were selected for the meta-analysis. The results of the meta-analysis showed that substance abuse does not have significant effects (p > 0.05) on postprandial blood glucose and glycated haemoglobin in patients with diabetes. With respect to the effect of substance abuse on fasting blood glucose, while this was significant (p < 0.05) following meta-analysis, the results of the sensitivity test did not demonstrate any significant difference (p > 0.05) between patients who abused substances compared with control. This would suggest that the effect of substance abuse on fasting blood glucose in these patients was not very reliable or not consistent. Conclusions: The effect of substance abuse on glycated haemoglobin and postprandial blood glucose in patients with diabetes was not significant. In the meta-analysis, while the

Comment in Mol Psychiatry. 2016 Jun;21(6):733-5. doi: 10.1038/mp.2016.14. Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10(-8)) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.

Herbal cannabis has been used for thousands of years for medical purposes. With elucidation of the chemical structures of tetrahydrocannabinol (THC) and cannabidiol (CBD) and with discovery of the human endocannabinoid system, the medical usefulness of cannabinoids has been more intensively explored. While more randomized clinical trials are needed for some medical conditions, other medical disorders, like chronic cancer and neuropathic pain and certain symptoms of multiple sclerosis, have substantial evidence supporting cannabinoid efficacy. While herbal cannabis has not met rigorous FDA standards for medical approval, specific well-characterized cannabinoids have met those standards. Where medical cannabis is legal, patients typically see a physician who "certifies" that a benefit may result. Physicians must consider important patient selection criteria such as failure of standard medical treatment for a debilitating medical disorder. Medical cannabis patients must be informed about potential adverse effects, such as acute impairment of memory, coordination and judgment, and possible chronic effects, such as cannabis use disorder, cognitive impairment, and chronic bronchitis. In addition, social dysfunction may result at work/school, and there is increased possibility of motor vehicle accidents. Novel ways to manipulate the endocannbinoid system are being explored to maximize benefits of cannabinoid therapy and lessen possible harmful effects.

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses.