Biochemical Changes in Endocannabinoid System are Expressed in Platelets of Female but not Male Migraineurs

Cephalalgia ◽  
2006 ◽  
Vol 26 (3) ◽  
pp. 277-281 ◽  
Author(s):  
LM Cupini ◽  
M Bari ◽  
N Battista ◽  
G Argirò ◽  
A Finazzi-Agrò ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Fatty Acid Amide Hydrolase ◽  
International Headache Society ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Primary Headache ◽  
Well Being ◽  
Human Platelets ◽  
Tension Type Headache ◽  
Primary Headache Disorders

The endogenous cannabinoid anandamide (AEA) plays important roles in modulating pain. Head pain is an almost universal human experience, yet primary headache disorders, such as migraine without aura (MoA) or episodic tension-type headache (ETTH), can represent a serious threat to well-being when frequent and disabling. We assessed the discriminating role of endocannabinoids among patients with ETTH or MoA, and control subjects. We measured the activity of AEA hydrolase and AEA transporter, and the level of cannabinoid receptors in peripheral platelets from MoA, ETTH and healthy controls. Sixty-nine headache patients and 36 controls were selected. Diagnosis of headache type was made according to the International Headache Society criteria. We observed significant sex differences concerning AEA membrane transporter and fatty acid amide hydrolase activity in all groups. An increase in the activity of AEA hydrolase and AEA transporter was found in female but not male migraineurs. Cannabinoid receptors were the same in all groups. Here we show that the endocannabinoid system in human platelets is altered in female but not male migraneurs. Our results suggest that in migraineur women an increased AEA degradation by platelets, and hence a reduced concentration of AEA in blood, might reduce the pain threshold and possibly explain the prevalence of migraine in women. The involvement of the endocannabinoid system in migraine is new and broadens our knowledge of this widespread and multifactorial disease.

Headache Prevalence Among Adolescents — The German DMKG Headache Study

Cephalalgia ◽  
2007 ◽  
Vol 27 (4) ◽  
pp. 347-354 ◽  
Author(s):  
K Fendrich ◽  
M Vennemann ◽  
V Pfaffenrath ◽  
S Evers ◽  
A May ◽  
...  
Keyword(s):  
International Headache Society ◽  
Primary Headache ◽  
Population Based ◽  
Cross Sectional Study ◽  
Tension Type Headache ◽  
Cross Sectional ◽  
Primary Headache Disorders ◽  
Ihs Criteria ◽  
Probable Migraine ◽  
Type Headache

This population-based cross-sectional study examined the 3-month prevalence of headache, migraine and tension-type headache (TTH) among adolescents aged 12-15 years in Germany Students ( n = 3324) from 20 schools completed a questionnaire on general and headache-specific pain which included a sociodemographic module. The headache-specific questionnaire complied with the respective revised criteria of the International Headache Society (IHS). 'Modified criteria' changed the item 'duration' in migraine (>30 min instead of >4 h). The overall 3-month prevalence of headache was 69.4% (boys 59.5%, girls 78.9%), with 4.4% of the adolescents suffering from frequent (≥ 14 days/3 months) and severe (grade 8-10 on a 10-point visual analogue scale) headache and 1.4% (boys 0.9%, girls 1.9%) from headache ≥15 days/month. The 3-month prevalence of migraine was 2.6% (boys 1.6%, girls 3.5%) applying strict IHS criteria and 6.9% (boys 4.4%, girls 9.3%) with modified criteria; 12.6% (boys 8.3%, girls 16.7%) suffered from probable migraine, 0.07% fulfilled the criteria for chronic migraine, 4.5% (boys 4.6%, girls 4.3%) suffered from TTH, 0.2% from chronic TTH and 15.7% (boys 14.5%, girls 16.9%) from probable TTH. Headache and migraine were more common in girls than in boys and in teenagers, especially in girls, aiming at higher education. Recurrent headache and primary headache disorders are common complaints among German adolescents, especially among girls.

scholarly journals The Endocannabinoid System as a Pharmacological Target for New Cancer Therapies

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5701
Author(s):  
Robert Ramer ◽  
Felix Wittig ◽  
Burkhard Hinz
Keyword(s):  
Tumour Cell ◽  
Cannabinoid Receptors ◽  
Epithelial Mesenchymal Transition ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Inhibitory Effect ◽  
Chemotherapeutic Agents ◽  
Preclinical Studies ◽  
Mesenchymal Transition

Despite the long history of cannabinoid use for medicinal and ritual purposes, an endogenous system of cannabinoid-controlled receptors, as well as their ligands and the enzymes that synthesise and degrade them, was only discovered in the 1990s. Since then, the endocannabinoid system has attracted widespread scientific interest regarding new pharmacological targets in cancer treatment among other reasons. Meanwhile, extensive preclinical studies have shown that cannabinoids have an inhibitory effect on tumour cell proliferation, tumour invasion, metastasis, angiogenesis, chemoresistance and epithelial-mesenchymal transition (EMT) and induce tumour cell apoptosis and autophagy as well as immune response. Appropriate cannabinoid compounds could moreover be useful for cancer patients as potential combination partners with other chemotherapeutic agents to increase their efficacy while reducing unwanted side effects. In addition to the direct activation of cannabinoid receptors through the exogenous application of corresponding agonists, another strategy is to activate these receptors by increasing the endocannabinoid levels at the corresponding pathological hotspots. Indeed, a number of studies accordingly showed an inhibitory effect of blockers of the endocannabinoid-degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) on tumour development and spread. This review summarises the relevant preclinical studies with FAAH and MAGL inhibitors compared to studies with cannabinoids and provides an overview of the regulation of the endocannabinoid system in cancer.

Diagnosis and Clinical Management of Headaches

CNS Spectrums ◽  
1999 ◽  
Vol 4 (9) ◽  
pp. 32-37
Author(s):  
Daniel P. Greenfield ◽  
Subramanian Hariharan
Keyword(s):  
Clinical Management ◽  
International Headache Society ◽  
Brain Lesion ◽  
Pain Syndrome ◽  
Primary Headache ◽  
Tension Type Headache ◽  
Primary Headaches ◽  
Primary Headache Disorders ◽  
Primary Disorder ◽  
Type Headache

AbstractIn this article, we will first present an overview of the epidemiology and classification of headaches, distinguishing between primary headaches (in which the headache itself is the primary disorder) and secondary headaches (ie, headaches due to an underlying condition, such as a neoplastic and/or space-occupying lesion, a cerebrovascular accident, or other type of structural brain lesion). We will use the current classification system of the International Headache Society, focusing on primary headache disorders (migraine, tension-type headache, cluster headache), which we will discuss from the practical clinical perspectives of diagnosis and clinical management. Throughout this article, we will emphasize the chronicity and periodicity of headaches as a type of chronic pain syndrome.

Endocannabinoid System: Overview and Therapeutic Relevance

2021 ◽  
Author(s):  
Alex Mabou Tagne
Keyword(s):  
Fatty Acid ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Receptor Subtypes ◽  
Monoacylglycerol Lipase ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

The endocannabinoid system (ECS) modulates a variety of physiological processes, attracting considerable attention as a potential target for therapeutic intervention. This complex system is activated by the lipid-derived mediators anandamide and 2-arachidonoyl-sn-glycerol (2-AG), which mainly engage the cannabinoid receptor subtypes 1 (CB1) and 2 (CB2). The biological actions of anandamide and 2-AG are terminated by internalization and intracellular enzymatic hydrolysis catalyzed primarily by the serine hydrolases fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL), respectively. Here, we provide an overview of ECS and discuss the implications for advancing pharmacological tools that interfere with such a system as next-generation therapeutics. This review contains 4 figures, 3 tables and 41 references Keywords: Endocannabinoid; anandamide; 2-Arachidonoyl-sn-glycerol; fatty acid amide hydrolase; monoacylglycerol lipase; cannabinoid receptors; N-acylethanolamine acid amidase; Δ9-tetrahydrocannabinol.

scholarly journals Anandamide Activity and Degradation Are Regulated by Early Postnatal Aging and Follicle-Stimulating Hormone in Mouse Sertoli Cells

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 20-28 ◽  
Author(s):  
Mauro Maccarrone ◽  
Sandra Cecconi ◽  
Gianna Rossi ◽  
Natalia Battista ◽  
Riccardo Pauselli ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Hormonal Regulation ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Membrane Transporter ◽  
Immature Mouse ◽  
Amide Hydrolase

Abstract Anandamide (AEA), a prominent member of the endogenous ligands of cannabinoid receptors (endocannabinoids), is known to adversely affect female fertility. However, a potential role of AEA in male reproductive functions is unknown. Here we report evidence that immature mouse Sertoli cells have the biochemical tools to bind and inactivate AEA, i.e. a functional type-2 cannabinoid receptor (CB2R), a selective AEA membrane transporter, and an AEA-degrading enzyme fatty acid amide hydrolase. We show that, unlike CB2R, the activity of AEA membrane transporter and the activity and expression of FAAH decrease, whereas the apoptosis-inducing activity of AEA increases with age during the neonatal period. We also show that FSH reduces the apoptotic potential of AEA, but not that of its nonhydrolyzable analog methanandamide. Concomitantly, FSH enhances FAAH activity in a manner dependent on mRNA transcription and protein synthesis and apparently involving cAMP. These data demonstrate that Sertoli cells partake in the peripheral endocannabinoid system, and that FSH reduces the apoptotic potential of AEA by activating FAAH. Taken together, it can be suggested that the endocannabinoid network plays a role in the hormonal regulation of male fertility.

scholarly journals Characterisation and localisation of the endocannabinoid system components in the adult human testis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
John E. Nielsen ◽  
Antoine D. Rolland ◽  
Ewa Rajpert-De Meyts ◽  
Christian Janfelt ◽  
Anne Jørgensen ◽  
...  
Keyword(s):  
Germ Cells ◽  
Cannabinoid Receptors ◽  
Reproductive Tract ◽  
Cell Function ◽  
Semen Quality ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Human Testis ◽  
Tissue Samples

Abstract Heavy use of cannabis (marijuana) has been associated with decreased semen quality, which may reflect disruption of the endocannabinoid system (ECS) in the male reproductive tract by exogenous cannabinoids. Components of ECS have been previously described in human spermatozoa and in the rodent testis but there is little information on the ECS expression within the human testis. In this study we characterised the main components of the ECS by immunohistochemistry (IHC) on archived testis tissue samples from 15 patients, and by in silico analysis of existing transcriptome datasets from testicular cell populations. The presence of 2-arachidonoylglycerol (2-AG) in the human testis was confirmed by matrix-assisted laser desorption ionization imaging analysis. Endocannabinoid-synthesising enzymes; diacylglycerol lipase (DAGL) and N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), were detected in germ cells and somatic cells, respectively. The cannabinoid receptors, CNR1 and CNR2 were detected at a low level in post-meiotic germ cells and Leydig- and peritubular cells. Different transcripts encoding distinct receptor isoforms (CB1, CB1A, CB1B and CB2A) were also differentially distributed, mainly in germ cells. The cannabinoid-metabolising enzymes were abundantly present; the α/β-hydrolase domain-containing protein 2 (ABHD2) in all germ cell types, except early spermatocytes, the monoacylglycerol lipase (MGLL) in Sertoli cells, and the fatty acid amide hydrolase (FAAH) in late spermatocytes and post-meiotic germ cells. Our findings are consistent with a direct involvement of the ECS in regulation of human testicular physiology, including spermatogenesis and Leydig cell function. The study provides new evidence supporting observations that recreational cannabis can have possible deleterious effects on human testicular function.

scholarly journals Endocannabinoid System as a Promising Therapeutic Target in Inflammatory Bowel Disease – A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Szymon Hryhorowicz ◽  
Marta Kaczmarek-Ryś ◽  
Aleksandra Zielińska ◽  
Rodney J. Scott ◽  
Ryszard Słomski ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Cannabinoid Receptors ◽  
Intestinal Inflammation ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Unknown Etiology ◽  
Bioactive Lipids ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a general term used to describe a group of chronic inflammatory conditions of the gastrointestinal tract of unknown etiology, including two primary forms: Crohn’s disease (CD) and ulcerative colitis (UC). The endocannabinoid system (ECS) plays an important role in modulating many physiological processes including intestinal homeostasis, modulation of gastrointestinal motility, visceral sensation, or immunomodulation of inflammation in IBD. It consists of cannabinoid receptors (CB1 and CB2), transporters for cellular uptake of endocannabinoid ligands, endogenous bioactive lipids (Anandamide and 2-arachidonoylglycerol), and the enzymes responsible for their synthesis and degradation (fatty acid amide hydrolase and monoacylglycerol lipase), the manipulation of which through agonists and antagonists of the system, shows a potential therapeutic role for ECS in inflammatory bowel disease. This review summarizes the role of ECS components on intestinal inflammation, suggesting the advantages of cannabinoid-based therapies in inflammatory bowel disease.

The endocannabinoid system in bull sperm and bovine oviductal epithelium: role of anandamide in sperm–oviduct interaction

Reproduction ◽  
2009 ◽  
Vol 137 (3) ◽  
pp. 403-414 ◽  
Author(s):  
María Gracia Gervasi ◽  
Maximiliano Rapanelli ◽  
María Laura Ribeiro ◽  
Mariana Farina ◽  
Silvia Billi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cannabinoid Receptors ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Sperm Binding ◽  
Bovine Sperm ◽  
Sperm Release ◽  
Oviductal Epithelium ◽  
Bull Sperm

Anandamide binds to cannabinoid receptors and plays several central and peripheral functions. The aim of this work was to study the possible role for this endocannabinoid in controlling sperm–oviduct interaction in mammals. We observed that bull sperm and bovine oviductal epithelial cells express cannabinoid receptors, CB1 and CB2, and fatty acid amide hydrolase, the enzyme that controls intracellular anandamide levels. A quantitative assay to determine whether anandamide was involved in bovine sperm–oviduct interaction was developed. R(+)-methanandamide, a non-hydrolysable anandamide analog, inhibited sperm binding to and induced sperm release from oviductal epithelia. Selective CB1 antagonists (SR141716A or AM251) completely blocked R(+)-methanandamide effects. However, SR144528, a selective CB2 antagonist, did not exert any effect, indicating that only CB1 was involved in R(+)-methanandamide effect. This effect was not caused by inhibition of the sperm progressive motility or by induction of the acrosome reaction. Overall, our findings indicate for the first time that the endocannabinoid system is present in bovine sperm and oviductal epithelium and that anandamide modulates the sperm–oviduct interaction, by inhibition of sperm binding and induction of sperm release from oviductal epithelial cells, probably by activating CB1 receptors.

A Practical Approach to Headache Treatment

2007 ◽  
Vol 20 (2) ◽  
pp. 123-136
Author(s):  
Tarvez Tucker
Keyword(s):  
Health Care Providers ◽  
International Headache Society ◽  
Medication Overuse Headache ◽  
Primary Headache ◽  
Tension Type Headache ◽  
Warning Signs ◽  
World Health ◽  
Primary Headaches ◽  
Care Providers ◽  
Primary Headache Disorders

The World Health Organization cites migraine headache as one of the 20 most disabling medical conditions. This article focuses on the diagnosis and treatment of the primary headache disorders, with special emphasis on migraine, the headache most likely to bring patients to physicians and pharmacists. This review begins with the warning signs of the ominous headache, which, although rare, can herald a life-threatening condition. Clinical characteristics of the primary headache types, migraine, tension-type headache, and cluster headache, are described. Although many individuals believe their headaches are “sinus,” or “stress or tension-induced,” most of the characteristics of these types of headaches actually meet International Headache Society criteria for migraine. Treatments of primary headaches, including acute therapies, abortive agents, and prophylactic medications, are uniquely specific for each headache syndrome. Chronic daily headache patients compose only 4% of the population yet make up the largest percentage of patients who seek treatment at specialty headache centers. Medication-overuse headache, the syndrome in which medications taken for the relief of headache actually foster future headaches, offers a particular challenge to health care providers, as does narcotic use in headache therapy. Complementary and alternative treatments proven efficacious in the treatment of primary headache are also described.

scholarly journals Role of the endocannabinoid system in the mechanisms involved in the LPS-induced preterm labor

Reproduction ◽  
2015 ◽  
Vol 150 (6) ◽  
pp. 463-472 ◽  
Author(s):  
María Victoria Bariani ◽  
Ana Paula Domínguez Rubio ◽  
Maximiliano Cella ◽  
Juliana Burdet ◽  
Ana María Franchi ◽  
...  
Keyword(s):  
Preterm Labor ◽  
Cannabinoid Receptors ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Preterm Births ◽  
Intrauterine Infection ◽  
Mrna Levels ◽  
Uterine Contractions ◽  
Amide Hydrolase

Prematurity is the leading cause of perinatal morbidity and mortality worldwide. There is a strong causal relationship between infection and preterm births. Intrauterine infection elicits an immune response involving the release of inflammatory mediators like cytokines and prostaglandins (PG) that trigger uterine contractions and parturition events. Anandamide (AEA) is an endogenous ligand for the cannabinoid receptors CB1 and CB2. Similarly to PG, endocannabinoids are implicated in different aspects of reproduction, such as maintenance of pregnancy and parturition. Little is known about the involvement of endocannabinoids on the onset of labor in an infectious milieu. Here, using a mouse model of preterm labor induced by lipopolysaccharide (LPS), we explored changes on the expression of components of endocannabinoid system (ECS). We have also determined whether AEA and CB antagonists alter PG production that induces labor. We observed an increase in uterineN-acylphosphatidylethanolamine-specific phospholipase D expression (NAPE-PLD, the enzyme that synthesizes AEA) upon LPS treatment. Activity of catabolic enzyme fatty acid amide hydrolase (FAAH) did not change significantly. In addition, we also found that LPS modulated uterine cannabinoid receptors expression by downregulatingCb2mRNA levels and upregulating CB1 protein expression. Furthermore, LPS and AEA induced PGF2a augmentation, and this was reversed by antagonizing CB1 receptor. Collectively, our results suggest that ECS may be involved in the mechanism by which infection causes preterm birth.

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