헴프 단백
Hemp Protein
📚 관련 논문 (29편)
1. Am J Clin Nutr. 2024 Jul;120(1):56-65. doi: 10.1016/j.ajcnut.2024.05.001. Epub 2024 May 4. Hemp seed protein and its hydrolysate compared with casein protein consumption in adults with hypertension: a double-blind crossover study. Samsamikor M(1), Mackay DS(2), Mollard RC(3), Alashi AM(1), Al
2. Appl Physiol Nutr Metab. 2021 Aug;46(8):887-896. doi: 10.1139/apnm-2020-0907. Epub 2021 Jan 25. Acute effects of hemp protein consumption on glycemic and satiety control: results of 2 randomized crossover trials. Mollard RC(1), Johnston A(1), Serrano Leon A(1), Wang H(1), Jones PJ(2), MacKay
1. Pharm Res. 2025 Jan;42(1):25-47. doi: 10.1007/s11095-024-03809-9. Epub 2025 Jan 8. Angelica gigas Nakai (Korean Dang-gui) Root Alcoholic Extracts in Health Promotion and Disease Therapy - active Phytochemicals and In Vivo Molecular Targets. Lü J(1)(2)(3), Jiang C(4)(5), Drabick JJ(6)(7), Joshi M(6)(7), Perimbeti S(6)(7). Author information: (1)Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. junxuanlu@pennstatehealth.psu.edu. (2)Penn State Cancer Institute, Pennsylvania State University, Hershey, PA, 17033, USA. junxuanlu@pennstatehealth.psu.edu. (3)Center for Cannabis and Natural Product Pharmaceutics, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. junxuanlu@pennstatehealth.psu.edu. (4)Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. (5)Center for Cannabis and Natural Product Pharmaceutics, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. (6)Penn State Cancer Institute, Pennsylvania State University, Hershey, PA, 17033, USA. (7)Department of Medicine Division of Hematology and Oncology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. 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). DOI: 10.1007/s11095-024-03809-9 PMCID: PMC11785709 PMID: 39779619 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Conflict of Interest: All authors declare no actual or perceived conflict of interest.
2. Complement Ther Med. 2024 Dec;87:103107. doi: 10.1016/j.ctim.2024.103107. Epub 2024 Oct 31. Impact of combined plant extracts on long COVID: An exploratory randomized controlled trial. Lukkunaprasit T(1), Satapornpong P(2), Kulchanawichien P(3), Prawang A(3), Limprasert C(3), Saingam W(4), Permsombut C(5), Panidthananon W(6), Vutthipong A(6), Lawanprasert Y(1), Pourpongpan P(7), Wongwiwatthananukit S(8), Songsak T(6), Pradubyat N(9). Author information: (1)Department of Pharmacy Administration, College of Pharmacy, Rangsit University, Pathum Thani, Thailand. (2)Division of General Pharmacy Practice, Department of Pharmaceutical Care, College of Pharmacy, Rangsit University, Pathum Thani, Thailand; Excellence Pharmacogenomics and Precision Medicine Centre, College of Pharmacy, Rangsit University, Pathum Thani, Thailand. (3)Division of Pharmacy Practice, Department of Pharmaceutical Care, College of Pharmacy, Rangsit University, Pathum Thani, Thailand. (4)Drug and Herbal Product Research and Development Center, College of Pharmacy, Rangsit University, Pathum Thani, Thailand. (5)MW Wellness Health Center, Bangkok, Thailand. (6)Department of Pharmacognosy, College of Pharmacy, Rangsit University, Pathum Thani, Thailand. (7)College of Oriental Medicine, Rangsit University, Pathum Thani, Thailand. (8)Department of Pharmacy Practice, The Daniel K. Inouye College of Pharmacy, University of Hawaii'i at Hilo, Hilo, HI, United States. (9)Department of Pharmacology, College of Pharmacy, Rangsit University, Pathum Thani, Thailand. Electronic address: Nalinee.p@rsu.ac.th. 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). Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.ctim.2024.103107 PMID: 39488240 [Indexed for MEDLINE] Conflict of interest statement: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rangsit University (the primary institution of all the authors except CP and SW) had research collaboration with Naree Pharma Group Co., Ltd., the owner of the combined plant extracts used in this study. The company had no role in the study design, conduct, analysis and interpretation of the data, writing of the manuscript, or dissemination of the trial results. The authors declare no conflict of interest. This study was funded by RSU Research Institute (Grant number 51/2565), Rangsit University. The funder had no role in the study design, conduct, analysis and interpretation of the data, writing of the manuscript, or dissemination of the trial results. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
3. Eur J Appl Physiol. 2024 Apr;124(4):1097-1107. doi: 10.1007/s00421-023-05337-7. Epub 2023 Oct 17. Effects of hemp supplementation during resistance training in trained young adults. Kaviani M(1), Shaw KA(2), Candow DG(3), Farthing JP(2), Chilibeck PD(4). Author information: (1)School of Nutrition and Dietetics, Acadia University, Wolfville, NS, B4P 2R6, Canada. (2)College of Kinesiology, University of Saskatchewan, Saskatoon, SK, S7N 5B2, Canada. (3)Faculty of Kinesiology and Health Studies, University of Regina, Regina, SK, S4S 0A2, Canada. (4)College of Kinesiology, University of Saskatchewan, Saskatoon, SK, S7N 5B2, Canada. phil.chilibeck@usask.ca. 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. DOI: 10.1007/s00421-023-05337-7 PMID: 37847288 [Indexed for MEDLINE]
4. J Food Biochem. 2022 Dec;46(12):e14417. doi: 10.1111/jfbc.14417. Epub 2022 Sep 17. Effects of hemp seed alone and combined with aerobic exercise on metabolic parameters, oxidative stress, and neurotrophic factors in young sedentary men. Mohammadrezaei A(1), Kavakeb A(2), Abbasalizad-Farhangi M(3), Mesgari-Abbasi M(4). Author information: (1)Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. (2)Department of Sport Physiology, Faculty of Physical Education and Sport Sciences, University of Kharazmi, Tehran, Iran. (3)Department of Community Nutrition, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran. (4)Drug-Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 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 health outcomes like cardiovascular comorbidities, oxidative stress, and insulin resistance. PRACTICAL APPLICATIONS: A sedentary lifestyle has numerous health-threatening consequences like cardiovascular comorbidities, oxidative stress, and insulin resistance. The importance of physical activity (PA) in improving these clinical manifestations is well-known; however, the potential benefits of herbal therapy combined with PA in reducing the side effects of a sedentary lifestyle have not been well studied. In the current research, we evaluated the benefits of hemp seed alone and combined with aerobic exercise on metabolic markers, oxidative stress, and neurotrophic factors in young sedentary men for the first time. According to our results, aerobic PA combined with hemp seed consumption improved anthropometric indices, lipid profile, and brain-derived neurotrophic factor among young sedentary men. © 2022 Wiley Periodicals LLC. DOI: 10.1111/jfbc.14417 PMID: 36114824 [Indexed for MEDLINE]
5. Nat Prod Res. 2023 Jun;37(11):1782-1786. doi: 10.1080/14786419.2022.2119967. Epub 2022 Sep 6. Long-term effects of a diet supplement containing Cannabis sativa oil and Boswellia serrata in dogs with osteoarthritis following physiotherapy treatments: a randomised, placebo-controlled and double-blind clinical trial. Gabriele V(1), Bisanzio D(2), Riva A(3), Meineri G(4), Adami R(1), Martello E(5). Author information: (1)Candioli Pharma S.r.l, Beinasco, Italy. (2)RTI International, Washington, DC, USA. (3)Product Research Indena S.p.A, Milano, Italy. (4)Department of Veterinary Sciences, University of Turin, Grugliasco, Italy. (5)Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK. 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. DOI: 10.1080/14786419.2022.2119967 PMID: 36067506 [Indexed for MEDLINE]
6. J Diet Suppl. 2020;17(5):561-586. doi: 10.1080/19390211.2020.1765941. Epub 2020 May 27. Effects of Hemp Extract on Markers of Wellness, Stress Resilience, Recovery and Clinical Biomarkers of Safety in Overweight, But Otherwise Healthy Subjects. Lopez HL(1), Cesareo KR(1), Raub B(1), Kedia AW(1), Sandrock JE(1), Kerksick CM(2), Ziegenfuss TN(1). Author information: (1)The Center for Applied Health Sciences, Stow, OH, USA. (2)Exercise and Performance Nutrition Laboratory, School of Health Sciences, Lindenwood University, St. Charles, MO, USA. 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. DOI: 10.1080/19390211.2020.1765941 PMID: 32456572 [Indexed for MEDLINE]
7. Trials. 2020 Apr 23;21(1):354. doi: 10.1186/s13063-020-4164-z. A double-blind, randomized, crossover trial protocol of whole hemp seed protein and hemp seed protein hydrolysate consumption for hypertension. Samsamikor M(1)(2), Mackay D(1), Mollard RC(1)(2), Aluko RE(3)(4). Author information: (1)Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada. (2)The Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, 196 Innovation Drive, Winnipeg, MB, R3T 2N2, Canada. (3)Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada. rotimi.aluko@umanitoba.ca. (4)The Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, 196 Innovation Drive, Winnipeg, MB, R3T 2N2, Canada. rotimi.aluko@umanitoba.ca. 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 Databank at ClinicalTrials.gov (http://ClinicalTrials.gov). DOI: 10.1186/s13063-020-4164-z PMCID: PMC7181489 PMID: 32326966 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that they have no competing interests.
8. J Anim Physiol Anim Nutr (Berl). 2019 Mar;103(2):525-533. doi: 10.1111/jpn.13052. Epub 2019 Jan 3. Effect of dietary supplementation of hemp (Cannabis sativa) and dill seed (Anethum graveolens) on performance, serum biochemicals and gut health of broiler chickens. Vispute MM(1), Sharma D(2), Mandal AB(2), Rokade JJ(2), Tyagi PK(2), Yadav AS(2). Author information: (1)ICAR-Indian Veterinary Research Institute, Izatnagar, India. (2)ICAR-Central Avian Research Institute, Izatnagar, India. 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. DOI: 10.1111/jpn.13052 PMID: 30604902 [Indexed for MEDLINE]
9. Complement Ther Med. 2015 Oct;23(5):652-7. doi: 10.1016/j.ctim.2015.07.003. Epub 2015 Jul 17. Alteration of delta-6-desaturase (FADS2), secretory phospholipase-A2 (sPLA2) enzymes by Hot-nature diet with co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients. Rezapour-Firouzi S(1), Arefhosseini SR(2), Ebrahimi-Mamaghani M(3), Baradaran B(4), Sadeghihokmabad E(5), Mostafaei S(6), Torbati M(7), Chehreh M(8). Author information: (1)Neurosciences Research Center, University of Medical Sciences at Tabriz, Iran; School of Nutrition and Health, University of Medical Sciences at Tabriz, Iran; Department of Immunology, Microbiology and Genetics, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran. Electronic address: s.rfirozi@gmail.com. (2)School of Nutrition and Health, University of Medical Sciences at Tabriz, Iran; Nutrition Research Center, University of Medical Sciences at Tabriz, Iran. Electronic address: arefhosseinir@tbzmed.ac.ir. (3)School of Nutrition and Health, University of Medical Sciences at Tabriz, Iran. Electronic address: ebrahimimamagani@tbzmed.ac.ir. (4)Immunology Research Center, University of Medical Sciences at Tabriz, Iran. Electronic address: Behzad_im@yahoo.com. (5)Neurosciences Research Center, University of Medical Sciences at Tabriz, Iran. Electronic address: aeass@yahoo.com. (6)Neurosciences Research Center, University of Medical Sciences at Tabriz, Iran. Electronic address: somaiyehmostafaei@yahoo.com. (7)Department of Food Science and Technology Faculty of Nutrition, Food & Drug Organization, University of Medical Sciences at Tabriz, Iran. Electronic address: drtorbati@yahoo.com. (8)Islamic Azad University, Tabriz, Iran. Electronic address: mchehreh@yahoo.com. 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. Copyright © 2015 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.ctim.2015.07.003 PMID: 26365444 [Indexed for MEDLINE]
10. Complement Ther Med. 2013 Oct;21(5):473-80. doi: 10.1016/j.ctim.2013.06.006. Epub 2013 Jul 25. Immunomodulatory and therapeutic effects of Hot-nature diet and co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients. Rezapour-Firouzi S(1), Arefhosseini SR, Mehdi F, Mehrangiz EM, Baradaran B, Sadeghihokmabad E, Mostafaei S, Fazljou SM, Torbati MA, Sanaie S, Zamani F. Author information: (1)Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; School of Nutrition and Health, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: s.rfirozi@gmail.com. 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. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.ctim.2013.06.006 PMID: 24050582 [Indexed for MEDLINE]
11. J Am Coll Nutr. 2008 Feb;27(1):51-8. doi: 10.1080/07315724.2008.10719674. A comparison of fish oil, flaxseed oil and hempseed oil supplementation on selected parameters of cardiovascular health in healthy volunteers. Kaul N(1), Kreml R, Austria JA, Richard MN, Edel AL, Dibrov E, Hirono S, Zettler ME, Pierce GN. Author information: (1)Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada R2H 2A6. 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. DOI: 10.1080/07315724.2008.10719674 PMID: 18460481 [Indexed for MEDLINE]
12. Eur J Nutr. 2006 Dec;45(8):470-7. doi: 10.1007/s00394-006-0621-z. Epub 2006 Nov 10. Effects of hempseed and flaxseed oils on the profile of serum lipids, serum total and lipoprotein lipid concentrations and haemostatic factors. Schwab US(1), Callaway JC, Erkkilä AT, Gynther J, Uusitupa MI, Järvinen T. Author information: (1)Dept. of Clinical Nutrition, University of Kuopio, P.O. Box 1627, 70211, Kuopio, Finland. ursula.schwab@uku.fi 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. DOI: 10.1007/s00394-006-0621-z PMID: 17103080 [Indexed for MEDLINE]
13. Reprod Toxicol. 2025 Sep;136:108978. doi: 10.1016/j.reprotox.2025.108978. Epub 2025 Jun 23. Cannabinoid exposure does not alter estradiol biosynthesis in human KGN granulosa cells. Kadhim L(1), Paquette-Jager S(1), Landry DA(2). Author information: (1)Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada. (2)Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: dlandry5@uottawa.ca. 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. Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.reprotox.2025.108978 PMID: 40562223 [Indexed for MEDLINE] Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
14. J Cannabis Res. 2025 May 14;7(1):25. doi: 10.1186/s42238-025-00279-7. Use of industrial hemp byproducts in ruminants: a review of the nutritional profile, animal response, constraints, and global regulatory environment. Irawan A(1)(2), Buffington H(3), Ates S(1), Bionaz M(4). Author information: (1)Oregon State University, Corvallis, OR, 97331, USA. (2)Universitas Sebelas Maret, Surakarta, 57126, Indonesia. (3)Agriculture Policy Solutions, Loveland, CO, 80538, USA. (4)Oregon State University, Corvallis, OR, 97331, USA. massimo.bionaz@oregonstate.edu. 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 byproducts as feed ingredients, some with no clear regulations, and some countries where a path for the regulation has started, such as the US. Still, no hemp byproducts are yet legal as a feed ingredient for ruminants. © 2025. The Author(s). DOI: 10.1186/s42238-025-00279-7 PMCID: PMC12076842 PMID: 40369700 Conflict of interest statement: Declarations. Ethics approval and consent to participate: Not required. Competing interests: The authors declare no competing interests.
15. Brain Behav. 2024 Jan;14(1):e3340. doi: 10.1002/brb3.3340. Effect of cannabis use on blood levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF): A systematic review and meta-analysis. Shafiee A(1)(2), Rafiei MA(3), Jafarabady K(2), Eskandari A(2), Abhari FS(4), Sattari MA(1), Amini MJ(2), Bakhtiyari M(1). Author information: (1)Department of Psychiatry and Mental Health, Alborz University of Medical Sciences, Karaj, Iran. (2)Student Research Committee, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran. (3)School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (4)School of Pharmacy, Islamic Azad University of Medical Sciences, Tehran, Iran. 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. DOI: 10.1002/brb3.3340 PMCID: PMC10757895 PMID: 38376038 [Indexed for MEDLINE] Conflict of interest statement: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.
16. Sports Health. 2024 Sep-Oct;16(5):695-705. doi: 10.1177/19417381231197389. Epub 2023 Sep 9. Performance-Enhancing Drugs in Healthy Athletes: An Umbrella Review of Systematic Reviews and Meta-analyses. Warrier AA(1), Azua EN(1), Kasson LB(1), Allahabadi S(1), Khan ZA(1), Mameri ES(1), Swindell HW(2), Tokish JM(3), Chahla J(1). Author information: (1)Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois. (2)Department of Orthopedic Surgery, Columbia University Irving Medical Center, New York, New York. (3)Mayo Clinic Arizona, Phoenix, Arizona. 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 physiologic measures. Cannabis may have an ergolytic, instead of ergogenic, effect. DOI: 10.1177/19417381231197389 PMCID: PMC11346223 PMID: 37688400 [Indexed for MEDLINE] Conflict of interest statement: The following author declared potential conflicts of interest: J.C. has received consulting fees from Smith & Nephew, Ossur, and Miach, honoraria from Smith & Nephew, and holds stock in Springloaded and Overture. J.M.T. has received royalties, honoraria, a grant, and a patent from Arthrex, and consulting fees from DePuy Mitek.
17. Eur J Neurosci. 2023 Sep;58(6):3540-3554. doi: 10.1111/ejn.16122. Epub 2023 Aug 23. Cannabinoid receptor gene CNR1 is downregulated in subcortical brain samples and upregulated in blood samples of individuals with schizophrenia: A participant data systematic meta-analysis. Bloch Priel S(1), Yitzhaky A(2), Gurwitz D(3)(4), Hertzberg L(2)(5). Author information: (1)Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. (2)Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel. (3)Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. (4)Sagol School for Neuroscience, Tel Aviv University, Tel Aviv, Israel. (5)Shalvata Mental Health Center, affiliated with the Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel. 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. DOI: 10.1111/ejn.16122 PMID: 37611908 [Indexed for MEDLINE]
18. Neurosci Biobehav Rev. 2022 Sep;140:104801. doi: 10.1016/j.neubiorev.2022.104801. Epub 2022 Jul 30. Task-independent acute effects of delta-9-tetrahydrocannabinol on human brain function and its relationship with cannabinoid receptor gene expression: A neuroimaging meta-regression analysis. Gunasekera B(1), Davies C(1), Blest-Hopley G(1), Veronese M(2), Ramsey NF(3), Bossong MG(4), Radua J(5), Bhattacharyya S(6); CBE Consortium. Collaborators: Pretzsch C(7), McAlonan G(8), Walter C(9), Lötsch J(10), Freeman T(11), Curran V(12), Battistella G(13), Fornari E(14), Filho GB(15), Crippa JA(16), Duran F(17), Zuardi AW(18). Author information: (1)Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. (2)Department of Neuroimaging, Centre for Neuroimaging Sciences, King's College London, UK; Department of Information Engineering, University of Padua, Italy. (3)Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands. (4)Department of Psychiatry, UMC Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands. (5)Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona, Spain; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. (6)Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. Electronic address: sagnik.2.bhattacharyya@kcl.ac.uk. (7)Department of Forensic and Neurodevelopmental Sciences, Kings' College London, London, UK. (8)Sackler Institute for Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK. (9)Institute of Clinical Pharmacology, Goethe - University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany. (10)Institute of Clinical Pharmacology, Goethe - University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. (11)Clinical Psychopharmacology Unit, University College London, UK; National Addiction Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK; Addiction and Mental Health Group (AIM), Department of Psychology, University of Bath, Bath, UK. (12)Clinical Psychopharmacology Unit, University College London, UK. (13)Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158, USA. (14)CIBM (Centre d'Imagerie Biomédicale), Centre Hospitalier Universitaire Vaudois (CHUV) MR Section, Lausanne, Switzerland; Department of Radiology, Centre Hospitalier Universitaire Vaudois (CHUV), and University of Lausanne, Lausanne, Switzerland. (15)Departamento de Psiquiatria da Faculdade de Medicina da USP, Brazil. (16)Faculdade de Medicina de Ribeirão Preto, Brazil. (17)Pesquisador Científico do Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas da, Brazil. (18)School of Medicine of Ribeirão Preto, University of Sao Paulo, Brazil. 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. Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.neubiorev.2022.104801 PMID: 35914625 [Indexed for MEDLINE]
19. Palliat Med. 2022 Jun;36(6):912-927. doi: 10.1177/02692163221083437. Epub 2022 Mar 31. Efficacy of medicinal cannabis for appetite-related symptoms in people with cancer: A systematic review. Razmovski-Naumovski V(1)(2)(3), Luckett T(3), Amgarth-Duff I(3), Agar MR(1)(2)(3)(4). Author information: (1)South West Sydney Clinical Campuses, School of Medicine & Health, University of New South Wales (UNSW), Sydney, NSW, Australia. (2)Ingham Institute of Applied Medical Research, Sydney, NSW, Australia. (3)IMPACCT - Improving Palliative, Aged and Chronic Care Through Clinical Research and Translation, Faculty of Health, University of Technology Sydney (UTS), NSW, Australia. (4)South West Sydney Local Health District (SWSLHD), Sydney, NSW, Australia. 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. DOI: 10.1177/02692163221083437 PMID: 35360989 [Indexed for MEDLINE]
20. Drugs. 2021 Sep;81(13):1513-1557. doi: 10.1007/s40265-021-01579-x. Epub 2021 Sep 4. Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain. Stella B(1), Baratta F(1), Della Pepa C(1), Arpicco S(1), Gastaldi D(2), Dosio F(3). Author information: (1)Department of Drug Science and Technology, University of Turin, v. P. Giuria, 9, 10125, Turin, Italy. (2)Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy. (3)Department of Drug Science and Technology, University of Turin, v. P. Giuria, 9, 10125, Turin, Italy. franco.dosio@unito.it. 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). DOI: 10.1007/s40265-021-01579-x PMCID: PMC8417625 PMID: 34480749 [Indexed for MEDLINE] Conflict of interest statement: Barbara Stella, Francesca Baratta, Carlo Della Pepa, Silvia Arpicco, Daniela Gastaldi, Franco Dosio have no conflicts of interest that are directly relevant to the content of this article.
21. Dev Med Child Neurol. 2021 Sep;63(9):1038-1050. doi: 10.1111/dmcn.14874. Epub 2021 Mar 27. Pharmacological and neurosurgical interventions for individuals with cerebral palsy and dystonia: a systematic review update and meta-analysis. Bohn E(1)(2), Goren K(1)(2), Switzer L(1)(2), Falck-Ytter Y(3), Fehlings D(1)(2). Author information: (1)Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada. (2)Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada. (3)Division of Gastroenterology and Hepatology, Veteran Affairs North East Ohio Health Care System, Case Western Reserve University, Cleveland, OH, USA. 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 Diciembre del 2015 para intervenciones farmacológicas y neuroquirúrgicas entre individuos con parálisis cerebral (PC) y distonía. MÉTODO: Se actualizaron las búsquedas (desde Enero 2016 hasta Mayo del 2020) para baclofeno oral, trihexifenidilo, benzodiacepinas, clonidina, gabapentina, levodopa, neurotoxina botulinica (BoNT), baclofeno intratecal (ITB), y estimulación cerebral profunda (DBS), y desde el inicio de la base de datos para el cannabis medicinal. Los estudios elegibles incluyeron al menos 5 individuos con PC y distonía e informaron sobre distonía, logro de metas, función motora, dolor/comorbilidad, facilidad para brindar cuidados, calidad de vida (QoL) o eventos adversos. La certeza de la evidencia se evaluó mediante GRADE. RESULTADOS: Diez y nueve estudios reunieron los criterios de inclusión (2 trihexifenidilo, uno clonidina, 2 BoNT, 9 ITB, 6 DBS). Cuando se combinan con los de la revisión sistemática original, dan un total de 46 estudios (cuatro aleatorios, 42 no aleatorios) que comprenden 915 participantes. Evidencia de certeza muy baja apoyó la mejoría de la distonía (clonidina, BoNT, ITB, DBS). La certeza baja a una muy baja apoyó una mejor función motora (DBS), dolor/comorbilidad (clonidina, BoNT, ITB, DBS), facilidad de cuidado (clonidina, BoNT, ITB) y CdV (ITB, DBS). Trihexifenidilo, clonidina, BoNT, ITB y DBS pueden aumentar los eventos adversos. No se identificaron estudios para benzodiacepinas, gabapentina, baclofeno oral, y cannabis medicinal. INTERPRETACIÓN: La evidencia que evalúa el uso de opciones de manejo farmacológico y neuroquirúrgico para personas con parálisis cerebral y distonía se limita a evidencia entre baja y muy baja certeza. Publisher: OBJETIVO: Atualizar uma revisão sistemática da evidência publicada até dezembro de 2015 para intervenções farmacológicas/neurocirúrgicas entre indivíduos com paralisia cerebral (PC) e distonia. MÉTODO: As buscas foram atualizadas (Janeiro 2016 a Maio 2020) quanto a baclofeno oral, triexifenidil, benzodiazepínicos, clonidina, gabapentina, levodopa, neurotoxina botulínica (NTBo), baclofeno intratecal (BIT), e estimulação cerebral profunda (ECB), e desde o início da base de dados para cannabis medicinal. Estudos elegíveis incluíram ao menos cinco indivíduos com PC e dystonia, e reportaram os objetivos atingidos, função motora, dor/conforto, facilidade do cuidado, qualidade de vida (QV), ou efeitos adversos. A certeza da evidência foi avaliada usando GRADE. RESULTADOS: Dezenove novos estudos atenderam aos critérios de inclusão (dois com triexifenidil 1 com clonidina, dois com NTBo, nove com BIT e seis com ECB), dando um total de 46 estudos (quatro randomizados, 42 não randomizados) compreendendo 915 participantes quando combinados com aqueles da revisão sistemática original. Evidência com certeza muito baixa suporta a melhora da distonia (clonidina, BIT, ECB) e atingimento de objetivos (clonidina, NTBo, BIT, ECB). Evidência com certeza baixa a muito baixa apóia melhora da função motora (ECB), dor/conforto (clonidina, NTBo, BIT, ECB), facilidade de cuidado (clonidina, NTBo, BIT), e QV (BIT, ECB). Triexifenidil, clonidina, NTBo, BIT, e ECB podem aumentar efeitos adversos. Não foram identificados estudos com benzodiazepínicos, gabapentina, baclofeno oral, e cannabis medicinal. INTERPRETAÇÃO: A evidência avaliando o uso de opções de manejo farmacológico e cirúrgico para indivíduos com PC e distonia é limitada a certeza baixa e muito baixa. © 2021 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press. DOI: 10.1111/dmcn.14874 PMCID: PMC8451898 PMID: 33772789 [Indexed for MEDLINE]
22. Am J Drug Alcohol Abuse. 2020;46(1):22-30. doi: 10.1080/00952990.2019.1636384. Epub 2019 Aug 1. Convergent functional genomics of cocaine misuse in humans and animal models. Forero DA(1)(2), González-Giraldo Y(3). Author information: (1)Laboratory of NeuroPsychiatric Genetics, Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia. (2)Health Sciences, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia. (3)Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia. 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. DOI: 10.1080/00952990.2019.1636384 PMID: 31368821 [Indexed for MEDLINE]
23. Sci Rep. 2019 May 14;9(1):7339. doi: 10.1038/s41598-019-43861-9. Genetic variation in CADM2 as a link between psychological traits and obesity. Morris J(1), Bailey MES(2), Baldassarre D(3)(4), Cullen B(1), de Faire U(5), Ferguson A(1), Gigante B(5)(6), Giral P(7), Goel A(8)(9), Graham N(1), Hamsten A(10), Humphries SE(11), Johnston KJA(1)(2)(12), Lyall DM(1), Lyall LM(1), Sennblad B(13), Silveira A(10), Smit AJ(14), Tremoli E(4)(15), Veglia F(4), Ward J(1), Watkins H(8)(9), Smith DJ(1), Strawbridge RJ(16)(17). Author information: (1)Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK. (2)School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. (3)Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy. (4)Centro Cardiologico Monzino, IRCCS, Milan, Italy. (5)Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. (6)Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd University Hospital, Stockholm, Sweden. (7)Assistance Publique-Hopitaux de Paris, Service Endocrinologie-Metabolisme, Groupe Hôpitalier Pitie-Salpetriere, Unités de Prévention Cardiovasculaire, Paris, France. (8)Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. (9)Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. (10)Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. (11)Centre for Cardiovascular Genetics, Institute Cardiovascular Science, University College London, London, UK. (12)Division of Psychiatry, College of Medicine, University of Edinburgh, Edinburgh, UK. (13)Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (14)Department of Medicine, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands. (15)Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy. (16)Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK. rona.strawbridge@glasgow.ac.uk. (17)Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. rona.strawbridge@glasgow.ac.uk. 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. DOI: 10.1038/s41598-019-43861-9 PMCID: PMC6517397 PMID: 31089183 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no competing interests.
24. Int J Environ Res Public Health. 2018 Nov 29;15(12):2691. doi: 10.3390/ijerph15122691. The Effects of Substance Abuse on Blood Glucose Parameters in Patients with Diabetes: A Systematic Review and Meta-Analysis. Ojo O(1), Wang XH(2), Ojo OO(3), Ibe J(4). Author information: (1)Department of Adult Nursing and Paramedic Science, University of Greenwich, London SE9 2UG, UK. o.ojo@greenwich.ac.uk. (2)The School of Nursing, Soochow University, Suzhou 215006, China. wangxiaohua@suda.edu.cn. (3)University Hospital, Lewisham High Street, London SE13 6LH, UK. eseojo1@gmail.com. (4)Department of Family Care & Mental Health, University of Greenwich, London SE9 2UG, UK. J.C.Ibe@greenwich.ac.uk. 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 value was slightly lower with respect to postprandial blood glucose, this was slightly higher in relation to HbA1c in the substance abuse group compared with control. On the other hand, the effect of substance abuse on fasting blood glucose was significant (p = 0.03) compared with control, but this was attenuated following a sensitivity test. A range of factors including eating habits, characteristics of drugs, erratic lifestyle of patients may explain the outcome of this review. There is the need for randomised controlled trials that will include diet and medication history in order to fully understand the effect of substance abuse on blood glucose parameters in patients with diabetes. DOI: 10.3390/ijerph15122691 PMCID: PMC6313386 PMID: 30501025 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest.
25. Transl Psychiatry. 2016 Mar 29;6(3):e769. doi: 10.1038/tp.2016.36. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium. Stringer S(1)(2), Minică CC(3), Verweij KJ(3)(4)(5), Mbarek H(3), Bernard M(6), Derringer J(7), van Eijk KR(8), Isen JD(9), Loukola A(10), Maciejewski DF(5), Mihailov E(11), van der Most PJ(12), Sánchez-Mora C(13)(14)(15), Roos L(16), Sherva R(17), Walters R(18)(19)(20), Ware JJ(21)(22), Abdellaoui A(3), Bigdeli TB(23), Branje SJ(24), Brown SA(25), Bruinenberg M(26), Casas M(14)(15)(27), Esko T(11), Garcia-Martinez I(13)(14), Gordon SD(28), Harris JM(16), Hartman CA(29), Henders AK(28), Heath AC(30), Hickie IB(31), Hickman M(21), Hopfer CJ(32), Hottenga JJ(3), Huizink AC(5), Irons DE(9), Kahn RS(8), Korhonen T(10)(33)(34), Kranzler HR(35), Krauter K(36), van Lier PA(5), Lubke GH(3)(37), Madden PA(30), Mägi R(11), McGue MK(9), Medland SE(28), Meeus WH(24)(38), Miller MB(9), Montgomery GW(28), Nivard MG(3), Nolte IM(12), Oldehinkel AJ(39), Pausova Z(6)(40), Qaiser B(10), Quaye L(16), Ramos-Quiroga JA(14)(15)(27), Richarte V(14), Rose RJ(41), Shin J(6), Stallings MC(42), Stiby AI(21), Wall TL(43), Wright MJ(28), Koot HM(5), Paus T(44)(45)(46), Hewitt JK(42), Ribasés M(13)(14)(15), Kaprio J(10)(34)(47), Boks MP(8), Snieder H(12), Spector T(16), Munafò MR(21)(48), Metspalu A(11), Gelernter J(49), Boomsma DI(3)(4), Iacono WG(9), Martin NG(28), Gillespie NA(23)(28), Derks EM(2), Vink JM(3)(50). Author information: (1)Department of Complex Trait Genetics, VU Amsterdam, Center for Neurogenomics and Cognitive Research, Amsterdam, The Netherlands. (2)Department of Psychiatry, Academic Medical Centre, Amsterdam, The Netherlands. (3)Department of Biological Psychology/Netherlands Twin Register, VU University, Amsterdam, The Netherlands. (4)Neuroscience Campus Amsterdam, Amsterdam, The Netherlands. (5)Department of Developmental Psychology and EMGO Institute for Health and Care Research, VU University, Amsterdam, The Netherlands. (6)The Hospital for Sick Children Research Institute, Toronto, Canada. (7)Department of Psychology, University of Illinois Urbana-Champaign, Champaign, IL, USA. (8)Department of Human Neurogenetics, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. (9)Department of Psychology, University of Minnesota, Minneapolis, MN, USA. (10)Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland. (11)Estonian Genome Center, University of Tartu, Tartu, Estonia. (12)Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. (13)Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. (14)Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain. (15)Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain. (16)Twin Research and Genetic Epidemiology, King's College London, London, UK. (17)Biomedical Genetics Department, Boston University School of Medicine, Boston, MA, USA. (18)Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. (19)Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. (20)Department of Medicine, Harvard Medical School, Boston, MA, USA. (21)School of Social and Community Medicine, University of Bristol, Bristol, UK. (22)MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK. (23)Department of Psychiatry, Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA, USA. (24)Research Centre Adolescent Development, Utrecht University, Utrecht, The Netherlands. (25)Department of Psychology and Psychiatry, University of California San Diego, La Jolla, CA, USA. (26)The LifeLines Cohort Study, University of Groningen, Groningen, The Netherlands. (27)Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. (28)Genetic Epidemiology, Molecular Epidemiology and Neurogenetics Laboratories, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. (29)Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. (30)Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. (31)Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia. (32)Department of Psychiatry, University of Colorado Denver, Aurora, CO, USA. (33)Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. (34)Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland. (35)Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. (36)Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO, USA. (37)Department of Psychology, University of Notre Dame, Notre Dame, IN, USA. (38)Developmental Psychology, Tilburg University, Tilburg, The Netherlands. (39)Interdisciplinary Center for Pathology and Emotion Regulation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. (40)Department of Physiology and Nutritional Sciences, University of Toronto, Toronto, ON, Canada. (41)Department of Psychological and Brain Sciences, Indiana University Bloomington, Bloomington, IN, USA. (42)Department of Psychology and Neuroscience, Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA. (43)Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. (44)Rotman Research Institute, Baycrest, Toronto, ON, Canada. (45)Department of Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada. (46)Center for the Developing Brain, Child Mind Institute, New York, NY, USA. (47)Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland. (48)UK Centre for Tobacco and Alcohol Studies and School of Experimental Psychology, University of Bristol, Bristol, UK. (49)Department of Psychiatry, Genetics, and Neurobiology, Yale University School of Medicine and VA CT, West Haven, CT, USA. (50)Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands. 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. DOI: 10.1038/tp.2016.36 PMCID: PMC4872459 PMID: 27023175 [Indexed for MEDLINE]
26. Ann Med. 2016;48(3):128-41. doi: 10.3109/07853890.2016.1145794. Epub 2016 Feb 25. Cannabinoids: Medical implications. Schrot RJ(1)(2), Hubbard JR(3)(4). Author information: (1)a Veterans' Administration Medical Center, Outpatient Clinic , Tampa , FL , USA ; (2)b Department of Family Medicine , University of South Florida, Morsani College of Medicine , Tampa , FL , USA ; (3)c Psychiatry South , Tuscaloosa , AL , USA ; (4)d Indian Rivers Mental Health Clinic , Tuscaloosa , AL , USA. 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. DOI: 10.3109/07853890.2016.1145794 PMID: 26912385 [Indexed for MEDLINE]
27. Behav Genet. 2016 Mar;46(2):151-69. doi: 10.1007/s10519-015-9737-3. Epub 2015 Sep 21. Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts. Schwantes-An TH(1)(2), Zhang J(1)(3), Chen LS(4), Hartz SM(4), Culverhouse RC(5), Chen X(6), Coon H(7), Frank J(8), Kamens HM(9)(10)(11), Konte B(12), Kovanen L(13), Latvala A(14), Legrand LN(15), Maher BS(16), Melroy WE(9)(10), Nelson EC(4), Reid MW(17), Robinson JD(18), Shen PH(19), Yang BZ(20), Andrews JA(17), Aveyard P(21), Beltcheva O(22), Brown SA(23), Cannon DS(7), Cichon S(24)(25), Corley RP(9), Dahmen N(26), Degenhardt L(27)(28), Foroud T(29), Gaebel W(30), Giegling I(12), Glatt SJ(31), Grucza RA(4), Hardin J(32), Hartmann AM(12), Heath AC(4), Herms S(24)(25), Hodgkinson CA(19), Hoffmann P(24)(25), Hops H(17), Huizinga D(33), Ising M(34), Johnson EO(35), Johnstone E(36), Kaneva RP(22), Kendler KS(6), Kiefer F(37), Kranzler HR(38), Krauter KS(9)(39), Levran O(40), Lucae S(34), Lynskey MT(41), Maier W(42), Mann K(43), Martin NG(44), Mattheisen M(24)(45)(46), Montgomery GW(44), Müller-Myhsok B(34), Murphy MF(47), Neale MC(6), Nikolov MA(4)(22), Nishita D(32), Nöthen MM(24), Nurnberger J(48), Partonen T(13), Pergadia ML(4), Reynolds M(49), Ridinger M(50)(51), Rose RJ(52), Rouvinen-Lagerström N(13), Scherbaum N(53), Schmäl C(43), Soyka M(54)(55), Stallings MC(9)(56), Steffens M(57), Treutlein J(8), Tsuang M(23), Wall TL(23), Wodarz N(50), Yuferov V(40), Zill P(58), Bergen AW(32), Chen J(6), Cinciripini PM(18), Edenberg HJ(59), Ehringer MA(9)(10), Ferrell RE(60), Gelernter J(20)(61)(62), Goldman D(19), Hewitt JK(9)(56), Hopfer CJ(63), Iacono WG(15), Kaprio J(13)(14)(64), Kreek MJ(40), Kremensky IM(22), Madden PA(4), McGue M(15), Munafò MR(65), Philibert RA(66), Rietschel M(8), Roy A(67), Rujescu D(12), Saarikoski ST(13), Swan GE(68), Todorov AA(4), Vanyukov MM(49), Weiss RB(69), Bierut LJ(4), Saccone NL(70). Author information: (1)Department of Genetics, Washington University School of Medicine, 4523 Clayton Avenue, Campus Box 8232, St. Louis, MO, 63110, USA. (2)Genometrics Section, Computational and Statistical Genomics Branch, Division of Intramural Research, National Human Genome Research Institute, US National Institutes of Health (NIH), Baltimore, MD, 21224, USA. (3)Key Laboratory of Brain Function and Disease, School of Life Sciences, Chinese Academy of Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, China. (4)Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA. (5)Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA. (6)Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 23298, USA. (7)Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, 84108, USA. (8)Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany. (9)Institute for Behavioral Genetics, University of Colorado, Boulder, CO, 80309, USA. (10)Department of Integrative Physiology, University of Colorado, Boulder, CO, 80309, USA. (11)Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, 16802, USA. (12)Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), Germany. (13)Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, 00271, Finland. (14)Department of Public Health, University of Helsinki, Helsinki, 00014, Finland. (15)Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USA. (16)Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA. (17)Oregon Research Institute, Eugene, OR, 97403, USA. (18)Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. (19)Section of Human Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA. (20)Department of Psychiatry, Yale University, New Haven, CT, 06516, USA. (21)Department of Primary Care Health Sciences, University of Oxford, Oxford, OX2 6GG, United Kingdom. (22)Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 1431, Sofia, Bulgaria. (23)Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA. (24)Department. of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn, Bonn, 53127, Germany. (25)Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, 4003, Switzerland. (26)Ökumenisches Hainich-Klinikum, Mühlhausen/Thüringen, Germany. (27)National Drug and Alcohol Research Centre, University of New South Wales, Randwick, NSW, 2031, Australia. (28)School of Population and Global Health, University of Melbourne, Melbourne, 3010, Australia. (29)Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. (30)University of Düsseldorf, 40225, Düsseldorf, Germany. (31)Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, 13210, USA. (32)Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA, 94025, USA. (33)Institute of Behavioral Science, University of Colorado, Boulder, CO, 80309, USA. (34)Max-Planck-Institute of Psychiatry, 80804, Munich, Germany. (35)Behavioral Health Research Division, Research Triangle Institute International, Durham, NC, 27709, USA. (36)Department of Oncology, University of Oxford, Oxford, OX3 7DQ, United Kingdom. (37)Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany. (38)Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. (39)Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, 80309, USA. (40)Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, 10065, USA. (41)Addictions Department, Institute of Psychiatry, King's College London, London, SE5 8BB, UK. (42)University of Bonn, 53113, Bonn, Germany. (43)Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany. (44)Department of Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, 4029, Australia. (45)Harvard School of Public Health, Boston, MA, 02115, USA. (46)Aarhus University, Aarhus, 8000, Denmark. (47)Childhood Cancer Research Group, University of Oxford, Oxford, OX3 7LG, UK. (48)Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. (49)Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, 15213, USA. (50)Department of Psychiatry, University Medical Center Regensburg, University of Regensburg, 8548, Regensburg, Germany. (51)Psychiatric Hospital, Konigsfelden, Windisch, Switzerland. (52)Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, 47405, USA. (53)Addiction Research Group at the Department of Psychiatry and Psychotherapy, LVR Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany. (54)Department of Psychiatry, University of Munich, 3860, Munich, Germany. (55)Private Hospital Meiringen, Meiringen, Switzerland. (56)Department of Psychology & Neuroscience, University of Colorado, Boulder, CO, 80309, USA. (57)Research Department, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany. (58)University of Munich, Munich, Germany. (59)Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. (60)Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, 15261, USA. (61)Department of Genetics, Yale University, New Haven, CT, 06516, USA. (62)Department of Neurobiology, Yale University, New Haven, CT, 06516, USA. (63)Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. (64)Institute for Molecular Medicine FIMM, University of Helsinki, 00014, Helsinki, Finland. (65)MRC Integrative Epidemiology Unit, UK Centre for Tobacco and Alcohol Studies, and School of Experimental Psychology, University of Bristol, Bristol, BS8 1TU, UK. (66)Department of Psychiatry, University of Iowa, Iowa City, IA, 52242, USA. (67)Psychiatry Service, Department of Veteran Affairs, New Jersey VA Health Care System, East Orange, NJ, 07018, USA. (68)Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, 94304, USA. (69)Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA. (70)Department of Genetics, Washington University School of Medicine, 4523 Clayton Avenue, Campus Box 8232, St. Louis, MO, 63110, USA. nlims@genetics.wustl.edu. 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. DOI: 10.1007/s10519-015-9737-3 PMCID: PMC4752855 PMID: 26392368 [Indexed for MEDLINE] Conflict of interest statement: Conflict of Interest Disclosures: Dr. Bierut is listed as an inventor on Issued U.S. Patent 8,080,371, “Markers for Addiction” covering the used of certain SNPs in determining the diagnosis, prognosis, and treatment of addiction, and served as a consultant for Pfizer in 2008. Dr. NL Saccone is the spouse of Dr. SF Saccone, who is also listed as an inventor on the above patent. Dr. Cinciripini served on the scientific advisory board of Pfizer, conducted educational talks sponsored by Pfizer on smoking cessation (2006–2008), and has received grant support from Pfizer. Dr. Degenhardt has no relevant disclosures for this specific project; however, for general pharmaceutical company disclosures, Dr. Degenhardt has received untied educational grants from Reckitt Benckiser to conduct post-marketing surveillance of the diversion and injection of opioid substitution therapy medications in Australia. Although these activities are unrelated to the current study, Dr. Kranzler has been a consultant or advisory board member for Alkermes, Lilly, Lundbeck, Otsuka and Pfizer; he is also a member of the American Society of Clinical Psychopharmacology's Alcohol Clinical Trials Initiative, which is supported by Ethypharm, Lilly, Lundbeck, AbbVie, and Pfizer. Dr. Ridinger is member of the advisory board of Lundbeck referring to Nalmefene. Prof. Dr. N. Scherbaum received honoraria for several activities (advisory boards, lectures, manuscripts and educational material) by the factories Sanofi-Aventis, Reckitt-Benckiser, Lundbeck, and Janssen-Cilag. During the last three years he participated in clinical trials financed by the pharmaceutical industry. The remaining authors declare no conflict of interest.
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