An ''N''-acylethanolamine (NAE) is a type of
fatty acid amide
Fatty acid amides (FAAs) are amides formed from a fatty acid and an amine. In nature, many FAAs have ethanolamine as the amine component. Also known as ''N''-acylethanolamines, they contain the functionality RC(O)N(H)CH2CH2OH. A well known exa ...
where one of several types of
acyl groups
In chemistry, an acyl group is a moiety derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids. It contains a double-bonded oxygen atom and an alkyl group (). In organic chemistry, the acyl group (IUPAC ...
is linked to the nitrogen atom of
ethanolamine, and highly
metabolic formed by intake of
essential fatty acids
Essential fatty acids, or EFAs, are fatty acids that humans and other animals must ingest because the body requires them for good health but cannot synthesize them.
Only two fatty acids are known to be essential for humans: alpha-linolenic ...
through
diet
Diet may refer to:
Food
* Diet (nutrition), the sum of the food consumed by an organism or group
* Dieting, the deliberate selection of food to control body weight or nutrient intake
** Diet food, foods that aid in creating a diet for weight loss ...
by 20:4, n-6 and 22:6, n-3 fatty acids,
and when the body is
physically and
psychologically
Psychology is the scientific study of mind and behavior. Psychology includes the study of conscious and unconscious phenomena, including feelings and thoughts. It is an academic discipline of immense scope, crossing the boundaries between t ...
active,
and the
endocannabinoid signaling system (ECS) is the major pathway by which NAEs exerts its physiological effects in animal cells with similarities in plants, and the metabolism of NAEs is an integral part of the ECS. These
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
s conceptually can be formed from a
fatty acid and ethanolamine with the release of a molecule of
water, but the known biological synthesis uses a
specific phospholipase D to cleave the
phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
unit from
''N''-acylphosphatidylethanolamines. Another route relies on the
transesterification of acyl groups from
phosphatidylcholine
Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup.
They are a major component of biological membranes and can be easily obtained from a variety of readily available sources, such as egg yolk or soybea ...
by an
''N''-acyltransferase (NAT) activity. The suffixes ''-
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent suc ...
'' and ''-
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
'' in these names each refer to the single nitrogen atom of ethanolamine that links the compound together: it is termed "amine" in ethanolamine because it is considered as a free terminal nitrogen in that subunit, while it is termed "amide" when it is considered in association with the adjacent
carbonyl group
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...
of the acyl subunit. Names for these compounds may be encountered with either "amide" or "amine" varying by author.
Examples
Examples of ''N''-acylethanolamines include:
[The list and references provided are based on background discussion in ]
*
Anandamide
Anandamide (ANA), also known as ''N''-arachidonoylethanolamine (AEA), is a fatty acid neurotransmitter. Anandamide was the first endocannabinoid to be discovered: it participates in the body's endocannabinoid system by binding to cannabinoid rece ...
(''N''-arachidonoylethanolamine; NAE) or arachidonoylethanolamine (AEA:
C22 H37 NO2; 20:
4,
ω-6) is the amide of
arachidonic acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...
(C
20H
32 O2; 20:4, ω-6) and
ethanolamine (MEA: C
2H
7NO). It is the ligand of both
cannabinoid receptor
Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid recept ...
s and
vanilloid receptor
TRPV is a family of transient receptor potential cation channels (TRP channels) in animals. All TRPVs are highly calcium selective.
TRP channels are a large group of ion channels consisting of six protein families, located mostly on the plasma ...
that attenuates
pain sensation.
Where binding to cannabinoid receptors is coupled to
nitric oxide
Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its ch ...
(NO) release in the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
of
invertebrates
Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...
and in peripheral
immune cells of both invertebrates and humans.
* ''N''-
Palmitoylethanolamine (PEA: C
18H
37NO
2; 16:0) is the amide of
palmitic acid (C
16H
32O
2; 16:0) and ethanolamine. It is a ligand at
CB2 receptors.
It has
anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as op ...
activity and also attenuates pain sensation in mammals.
NAE 16:0 has also been identified in plants including corn, and seeds of cotton, okra, tomato, castor bean, soya bean and peanuts,
but its physiological functions remain unknown,
* ''N''-
Oleoylethanolamine (OEA: C
20H
39NO
2; 18:1,
ω-9) is the amide of
oleic acid (C
18H
34O
2; 18:1) and ethanolamine. It has
anorexic
Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...
effects and enables fat breakdown by stimulating
PPAR-alpha.
In plants, NAE 18:1 is present abundantly in dry seeds and levels decline during seed imbibition,
but its physiological functions are yet to be elucidated. In
humans, plasma OEA levels are also found positively correlated with positive
mood and
emotions.
[ Material was copied from this source, which is available under ]
Creative Commons Attribution 4.0 International License
OEA acting mostly at
peroxisome proliferator‐activated receptor‐α (PPAR‐α)
nuclear receptors and, to some extent,
TRPV1 channels.
* ''N-''
Stearoylethanolamine (SEA: C
20H
41NO
2; 18:0) is the amide of
stearic acid (C
18H
36O
2) and ethanolamine (MEA: C
2H
7NO). It has pro-
apoptotic
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes includ ...
activity. It operates independently of the known cannabinoid and vanilloid receptors targeted by anandamide.
It is an inhibitor of the
sphingolipid signaling pathway, via specific
ceramidase
Ceramidase (, ''acylsphingosine deacylase'', ''glycosphingolipid ceramide deacylase'') is an enzyme which cleaves fatty acids from ceramide, producing sphingosine (SPH) which in turn is phosphorylated by a sphingosine kinase to form sphingosine- ...
inhibition (ceramidase converts
ceramide
Ceramides are a family of waxy lipid molecules. A ceramide is composed of N-acetylsphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make u ...
to
sphingosine
Sphingosine (2-amino-4-trans-octadecene-1,3-diol) is an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phospholip ...
) and blocks the effects of
TNF- and arachidonic acid on intracellular
Ca2+ concentration.
* N-Linoleoyl ethanolamide (MEA: C
20H
37NO
2; 18:2, ω-6) or Anandamide (18:2, n-6) is the
ethanolamide of
linoleic acid
Linoleic acid (LA) is an organic compound with the formula COOH(CH2)7CH=CHCH2CH=CH(CH2)4CH3. Both alkene groups are ''cis''. It is a fatty acid sometimes denoted 18:2 (n-6) or 18:2 ''cis''-9,12. A linoleate is a salt or ester of this acid.
L ...
(LA:
C18 H32 O2; 18:
2,
ω-6) and its metabolized incorporated
ethanolamine (MEA: C
2H
7NO), is the first natural inhibitor of
fatty acid amide hydrolase (FAAH) discovered, also derives from
hydroperoxides
Hydroperoxides or peroxols are compounds containing the hydroperoxide functional group (ROOH). If the R is organic, the compounds are called organic hydroperoxides. Such compounds are a subset of organic peroxides, which have the formula ROOR. O ...
of NAE 20:4 (AEA) or its
linoleoyl analogues by
lipoxygenase
Lipoxygenases () are a family of (non-heme) iron-containing enzymes most of which catalyze the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene into cell signaling agents that serve diverse roles as a ...
action.
* ''N-''
Docosahexaenoyl ethanolamine (DHEA: C
24H
37NO
2; 22:6, ω-3), or Anandamide (22:6, n-3) "synaptamide", is the amide of
docosahexaenoic acid (DHA: C
22H
32O
2; 22:6,
ω-3) and ethanolamine (MEA: C
2H
7NO). It can act at CB2 receptors,
and have anti-proliferative effects on prostate cancer cell lines and promotes
synaptogenesis,
neurogenesis and
neuritogenesis,
and as an endogenous
metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
of DHA, it promotes
brain development
The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The fi ...
and function.
*''N''-
Docosatetraenoylethanolamine (DEA: C
24H
41NO
2; 22:4,ω-6) act on the CB1 receptor,
and possible CB2.
*''N''-
Eicosapentaenoylethanolamide (EPEA: C
22H
35NO
2; 20:5, ω-3) or Anandamide (20:5, n-3). It is the amide of
eicosapentaenoic acid (EPA: C
20H
30O
2; 20:5, n-3), that can act on CB2 receptors in combination with
PPAR-gamma to decrease
LPS induced
adipocyte
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. ...
IL-6 and
MCP-1 levels.
*''N''-
homo-gamma-linolenoylethanolamine, or Anandamide (20:3,n-6) (HGLEA: C
22H
39NO
2; 20:3,ω-6).
These bioactive lipid amides are generated by the membrane enzyme
NAPE-PLD, and natural
bile acids
Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts.
Primar ...
regulate this essential process.
An ''in vivo'' active NAPE-PLD inhibitor called LEI-401 was found to be
CNS-active, and modulated NAE
biosynthesis
Biosynthesis is a multi-step, enzyme- catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecule ...
. It had similar effects as a cannabinoid
CB1 receptor
antagonist, which could be reversed by co-treatment with a
FAAH
Fatty acid amide hydrolase or FAAH (, oleamide hydrolase, anandamide amidohydrolase) is a member of the serine hydrolase family of enzymes. It was first shown to break down anandamide in 1993. In humans, it is encoded by the gene ''FAAH''.;
Fun ...
inhibitor.
At least two pathways distinct from NAPE-PLD have been proposed as metabolic pathways for NAE 20:4 (AEA) formation. One pathway involves the double-''O''-
deacylation of
NAPEs by
α,β-hydrolase (ABHD4) to form
glycerophospho-''N''-acylethanolamines (GP-NAEs), followed by conversion of these intermediates to NAEs by glycero
phosphodiesterase
A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, ''phosphodiesterase'' refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many oth ...
-1 (GDE1). Another pathway utilizes a
phospholipase C (PLC) to produce phopho-''N''-arachidonoylethanolamine (pAEA) from NAPE, widely found in
phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
s, followed by conversion of pAEA into NAE 20:4 (AEA) by
phosphatase
In biochemistry, a phosphatase is an enzyme that uses water to cleave a phosphoric acid monoester into a phosphate ion and an alcohol. Because a phosphatase enzyme catalyzes the hydrolysis of its substrate, it is a subcategory of hydrolases. P ...
s such as
PTPN22
Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a cytoplasmatic protein encoded by gene ''PTPN22'' and a member of PEST family of protein tyrosine phosphatases. This protein is also called "PEST-domain Enriched Phosphatase" ("PEP") o ...
and
SHIP1
Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1 (SHIP1) is an enzyme with phosphatase activity. SHIP1 is structured by multiple domain and is encoded by the ''INPP5D'' gene in humans. SHIP1 is expressed predominantly ...
.
The effects of NAE 20:4 (AEA) and another
endocannabinoid 2-Arachidonoylglycerol
2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is present ...
(2-AG: C
23H
38O
4; 20:4, ω-6) is found to be enhanced by “
entourage compounds”, NAEs that inhibit their
hydrolysis via substrate competition, and thereby prolong their action. These compounds include ''N''-palmitylethanolamide (PEA, NAE 16:0), ''N''-oleoylethanolamide (SEA, NAE 18:0), and ''cis''-9-octadecenoamide (OEA, oleamide, NAE 18:1).
[ Text was copied from this source, which is available under ]
Creative Commons Attribution 4.0 International License
All are members of the endocannabinoidome, a complex
lipid signaling system composed of more than 100 of fatty acid-derived mediators and their receptors, its
anabolic
Anabolism () is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breakin ...
and
catabolic
Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipids, ...
enzymes of more than 50
proteins, which are deeply involved in the control of
energy metabolism
Bioenergetics is a field in biochemistry and cell biology that concerns energy flow through living systems. This is an active area of biological research that includes the study of the transformation of energy in living organisms and the study of ...
and its
pathological
Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in th ...
deviations, as well as
immunosuppression,
and some NAE members, do not activate the CB1 and CB2 receptors efciently, but instead activate other receptors (e.g.
peroxisome proliferator-activated receptors
In the field of molecular biology, the peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. PPARs play essential roles in the reg ...
(PPAR)-
α/
γ,
G-protein coupled receptors
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
(GPR)
55,
110
110 may refer to:
*110 (number), natural number
*AD 110, a year
*110 BC, a year
* 110 film, a cartridge-based film format used in still photography
*110 (MBTA bus), Massachusetts Bay Transportation Authority bus route
*110 (song), 2019 song by Cap ...
,
118 118 may refer to:
*118 (number)
*AD 118
*118 BC
*118 (TV series)
*118 (film)
*118 (Tees) Corps Engineer Regiment
*118 (Tees) Field Squadron, Royal Engineers
See also
*11/8 (disambiguation)
*Oganesson
Oganesson is a synthetic chemical element wi ...
,
119
119 may refer to:
* 119 (number), a natural number
* 119 (emergency telephone number)
* AD 119, a year in the 2nd century AD
* 119 BC, a year in the 2nd century BC
* 119 (album), 2012
* 119 (NCT song)
*119 (Show Me the Money song)
* 119 (film), a ...
,
TRPV1 channels), known to counteract metabolic disorders in animal models, by
gut bacterial families (e.g.
Veillonellaceae
The Veillonellaceae are a family of the Clostridia, formerly known as Acidaminococcaceae. Bacteria in this family are grouped together mainly based on genetic studies, which place them among the Bacillota. Supporting this placement, several s ...
,
Peptostreptococcaceae
The Peptostreptococcaceae are a family of Gram-positive bacteria in the class Clostridia.
Several members of the Peptostreptococcaceae are well known inhabitants of the digestive tract.
Microbiome studies of animal feces have corroborated thi ...
and
Akkermansia
''Akkermansia'' is a genus in the phylum Verrucomicrobiota ( Bacteria). The genus was first proposed by Derrien '' et al.'' (2004), with the type species ''Akkermansia muciniphila'' (gen. nov., sp. nov).
Etymology
The name ''Akkermansia'' d ...
ceae) associated with variations in most NAEs and omega3-derived 2-
monoacylglycerols (2‑MAGs), congeners of 2-AG, as gut microbiota communities and the host endocannabinoidome also seem to be interrelated in a mutual crosstalk controlling whole body metabolism.
NAE's are also involved in modulation of different physiological processes such as
pain,
stress,
anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
,
appetite
Appetite is the desire to eat food items, usually due to hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced by satiety. Appetite exists in all higher life-forms, and serves to regul ...
,
cardiovascular
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, t ...
function and
inflammation. A study suggest the presence of an endogenous NAE tone control
emotional
behavior
Behavior (American English) or behaviour (British English) is the range of actions and mannerisms made by individuals, organisms, systems or artificial entities in some environment. These systems can include other systems or organisms as we ...
.
Raphael Mechoulam that described and named Anandamide in 1992. He said:
Beyond
vertebrates NAEs are also found to have signaling roles in more primitive
organism, implicated as
metabolic signals that coordinate
nutrient status and
lifespan determination in ''
Caenorhabditis elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
'', and detected in organisms as diverse as
yeast (''
Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been ...
''),
freshwater fish
Freshwater fish are those that spend some or all of their lives in fresh water, such as rivers and lakes, with a salinity of less than 1.05%. These environments differ from marine conditions in many ways, especially the difference in levels of s ...
(''
Esox lucius'' and ''
Cyprinus carpio
The Eurasian carp or European carp (''Cyprinus carpio''), widely known as the common carp, is a widespread freshwater fish of eutrophic waters in lakes and large rivers in Europe and Asia.Fishbase''Cyprinus carpio'' Linnaeus, 1758/ref>Arkive Th ...
''),
bivalve mollusc (''
Mytilus galloprovincialis
The Mediterranean mussel (''Mytilus galloprovincialis'') is a species of bivalve, a marine mollusc in the family Mytilidae. It is an invasive species in many parts of the world, and also an object of aquaculture.
Systematics
''Mytilus gallopro ...
''),
protist
A protist () is any eukaryotic organism (that is, an organism whose cells contain a cell nucleus) that is not an animal, plant, or fungus. While it is likely that protists share a common ancestor (the last eukaryotic common ancestor), the exclu ...
s (''
Tetrahymena thermophila''),
slime mold (''
Dictyostelium discoideum''),
microbes such as
bacteria,
fungi, and
viruses, are all organisms that appear to regulate their endogenous NAE levels via similar enzymatic machinery as
mammalian vertebrates, show a widespread occurrence of NAEs, from
single-celled organisms to humans, and a highly conserved role for this group of
lipids in
cell signaling
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
.
Studies in
amphibian
Amphibians are four-limbed and ectothermic vertebrates of the class Amphibia. All living amphibians belong to the group Lissamphibia. They inhabit a wide variety of habitats, with most species living within terrestrial, fossorial, arborea ...
s and
birds show that endocannabinoid signaling may function as a
behavior
Behavior (American English) or behaviour (British English) is the range of actions and mannerisms made by individuals, organisms, systems or artificial entities in some environment. These systems can include other systems or organisms as we ...
al switch, allowing redirection from less- to more-essential behaviors in response to
emergent environmental change Environmental change is a change or disturbance of the environment most often caused by human influences and natural ecological processes. Environmental changes include various factors, such as natural disasters, human interferences, or animal ...
s,
and provide evidence of cannabinoid modulation of
aggression
Aggression is overt or covert, often harmful, social interaction with the intention of inflicting damage or other harm upon another individual; although it can be channeled into creative and practical outlets for some. It may occur either reacti ...
,
emesis
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteritis ...
,
feeding behavior,
locomotor activity
Animal locomotion, in ethology, is any of a variety of methods that animals use to move from one place to another. Some modes of locomotion are (initially) self-propelled, e.g., running, swimming, jumping, flying, hopping, soaring and gliding. Th ...
, reproductive behaviors,
vocal learning,
sensory perception and
stress response
The fight-or-flight or the fight-flight-or-freeze response (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first des ...
s.
NAE and the reproductive system
Several researches have found, that NAE, and especially 20:4 anandamide (AEA:
C22 H37 NO2; 20:
4,
ω-6), is a part of the
reproductive system
The reproductive system of an organism, also known as the genital system, is the biological system made up of all the anatomical organs involved in sexual reproduction. Many non-living substances such as fluids, hormones, and pheromones are ...
,
[ Text was copied from this source, which is available under ]
Creative Commons Attribution 2.0 Generic (CC BY 2.0)
license. and play a fundamental role for a healthy and successful
pregnancy.
A 2006 report from the Pediatrics Department at
Vanderbilt University characterized NAE 20:4 (AEA) as “an emerging concept in
female reproduction”, because they found a “cannabinoid sensor” mechanism to influence several crucial steps during early pregnancy.
The Vanderbilt research team termed this “endocannabinoid signaling in preimplantation embryo development and activation”, because, one of the first things the
fertilized
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proc ...
embryo must do, is to attach itself to the lining of the
uterus, and without becoming attached to the
uterine wall
The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the hollow organ, organ in the female reproductive system, reproductive system of most female mammals, including humans that accommodates the embryonic development, embryonic an ...
, which forms the
umbilical cord
In placental mammals, the umbilical cord (also called the navel string, birth cord or ''funiculus umbilicalis'') is a conduit between the developing embryo or fetus and the placenta. During prenatal development, the umbilical cord is physiologi ...
, there will be no pregnancy. NAE 20:4 (AEA) play a key role, because, for the embryo to become attached to the lining of the uterus, a particular amount (temporary reduction by high
Fatty acid amide hydrolase FAAH) of NAE 20:4 (AEA), present at the
uterine lining
The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer ...
(endometrium), is necessary for the fertilized embryo can attach itself to the uterine wall. NAE 20:4 (AEA) uses the CB1 receptors, that are at high levels on the
blastocyst
The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...
(fertilized egg), to this attachment. So the amount of NAE 20:4 (AEA) directs the outcome of the attachment to the uterine wall via CB1, and thereby, the outcome of pregnancy,
by
synchronizing
Synchronization is the coordination of events to operate a system in unison. For example, the conductor of an orchestra keeps the orchestra synchronized or ''in time''. Systems that operate with all parts in synchrony are said to be synchronou ...
trophoblast differentiation and uterine preparation to the receptive state.
However, low FAAH expression and high NAE 20:4 (AEA) levels at the interimplantation sites, prior to successful implantation, have been reported, and a later possible
miscarriage
Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
, as AEA levels are inversely correlated with FAAH levels in
peripheral blood mononuclear cells (PMNCs) and FAAH levels are found lower in women who consequently miscarry compared with those who progress beyond the
first trimester
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
. A consequence also fund in women undergoing ''in vitro''
fertilization
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
and
embryo transfer, as low activity of FAAH in PMNCs and high plasma AEA levels after embryo transfer show failure to achieve a successful pregnancy. As well, high AEA level also inhibits
BeWo trophoblast cell proliferation, in a dose-dependent manner, ''via'' the
CB2 receptor
The cannabinoid receptor type 2, abbreviated as CB2, is a G protein-coupled receptor from the cannabinoid receptor family that in humans is encoded by the ''CNR2'' gene. It is closely related to the cannabinoid receptor type 1 (CB1), which is l ...
, suggest that FAAH acts as a barrier to the AEA
maternal-
fetal transfer. So, high plasma AEA levels can be used as a marker of early pregnancy loss in patients with threatened miscarriage, as altered modulation of the ECS contribute to the
spontaneous pregnancy loss.
This is in line with a study of 50 women, where NAE 20:4 (AEA)
hydrolase
Hydrolase is a class of enzyme that commonly perform as biochemical catalysts that use water to break a chemical bond, which typically results in dividing a larger molecule into smaller molecules. Some common examples of hydrolase enzymes are este ...
activity was lower in the seven women who
miscarried
Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
than in the 43 who did not (60.43 pmol/min per mg protein
D 29.34vs 169.60 pmol/min per mg protein
0.20 and another study showing that all 15 women in the low AEA hydrolase group had miscarriages, compared with one of the 105 women with high concentrations at or above the threshold of hydrolase.
An earlier 2004 research in to the course of
ectopic pregnancy
Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women have both of these symptoms. ...
, a result of embryo retention in the
fallopian tube, found that decoupled cannabinoid receptor CB1, can cause retention of embryos in the mouse
oviduct
The oviduct in mammals, is the passageway from an ovary. In human females this is more usually known as the Fallopian tube or uterine tube. The eggs travel along the oviduct. These eggs will either be fertilized by spermatozoa to become a zygote, o ...
, and lead to pregnancy failure, as either silencing or amplification of NAE 20:4 (AEA) signaling ''via'' CB1 receptors causes oviductal retention or blastocyst incompetence for implantation. The report estimates that aberrant cannabinoid signaling impedes coordinated oviductal
smooth muscle contraction
Contraction may refer to:
Linguistics
* Contraction (grammar), a shortened word
* Poetic contraction, omission of letters for poetic reasons
* Elision, omission of sounds
** Syncope (phonology), omission of sounds in a word
* Synalepha, merged ...
and relaxation, which are crucial to normal oviductal embryo transport. This was also seen in wild-type mice treated with
methanandamide
Methanandamide (AM-356) is a synthetically created stable chiral analog of anandamide. Its effects have been observed to act on the cannabinoid receptors (specifically on CB1 receptors, which are part of the central nervous system) found in d ...
(AM-356; C
23H
39NO
2, 20:4, n6), and thereby concluded, that a colocalization of CB1 in the oviduct muscularis implicate a basal endocannabinoid tone of NAE 20:4 (AEA) is needed for oviductal
motility and for normal journey of embryos into the uterus.
Another 2004 study published in the ''
American Journal of Obstetrics and Gynecology
The ''American Journal of Obstetrics and Gynecology'' (AJOG) is a peer reviewed journal of obstetrics and gynecology. It is popularly called the "Gray Journal". Since 1920, AJOG has continued the American Journal of Obstetrics and Diseases of Wom ...
'' find NAE 20:4 (AEA) and the
phytocannabinoid
Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...
Δ9-tetrahydrocannabinol (THC:
C21 H30 O2), that can mimic NAE 20:4 (AEA) by direct activation at CB1 and
CB2 receptors,
and able to switch from
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
to
antagonist depending on firing rate, to exert a direct relaxant effect on human pregnant
myometrium ''in vitro'', with equal potency for both compounds, which was mediated through the CB1 receptor. This means that the middle layer of the
uterine wall
The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the hollow organ, organ in the female reproductive system, reproductive system of most female mammals, including humans that accommodates the embryonic development, embryonic an ...
is modulated by NAE 20:4 (AEA) as well.
Likewise, there is also demonstrated CB1 expression in the first trimester
placenta characterized by a
spatial-temporal modulation. But, at
term, there is found lack of FAAH and high CB1 expression at placental
villous tissue of non-laboring compared with
laboring.
After birth, CB1 receptors appears to be critical for
milk sucking by
newborn
An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...
, as it apparently activate
oral
The word oral may refer to:
Relating to the mouth
* Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid
** Oral administration of medicines
** Oral examination (also known as an oral exam or or ...
-motor musculature, by
2-AG
2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is present ...
(C
23H
38O
4; 20:4 ω-6) in the
breast milk
Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by mammary glands located in the breast of a human female. Breast milk is the primary source of nutrition for newborns, containing fat, protein, carbohydrates ( lact ...
, activation, as elevated levels of 2-AG modulate infant
appetite
Appetite is the desire to eat food items, usually due to hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced by satiety. Appetite exists in all higher life-forms, and serves to regul ...
and health, as well as NAE 20:4 (AEA) act as an
neuroprotectant, also by providing
retrograde signaling
Retrograde signaling in biology is the process where a signal travels backwards from a target source to its original source. For example, the nucleus of a cell is the original source for creating signaling proteins. During retrograde signaling, ins ...
in the developing
postnatal
The postpartum (or postnatal) period begins after childbirth and is typically considered to end within 6 weeks as the mother's body, including hormone levels and uterus size, returns to a non-pregnant state. The terms puerperium, puerperal perio ...
brain, with observations suggest that children may be less prone to psychoactive side effects of Δ
9-tetrahydrocannabinol (THC: C
21H
30O
2) or endocannabinoids than adults, as very low
density of CB1, suggest a promising future for
cannabinoids
Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid te ...
in
pediatric
Pediatrics ( also spelled ''paediatrics'' or ''pædiatrics'') is the branch of medicine that involves the medical care of infants, children, adolescents, and young adults. In the United Kingdom, paediatrics covers many of their youth until the ...
medicine for conditions including non-organic
failure-to-thrive and
cystic fibrosis.
Mood
As the
euphoric
Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and danc ...
feeling
Feelings are subjective self-contained phenomenal experiences. According to the ''APA Dictionary of Psychology'', a feeling is "a self-contained phenomenal experience"; and feelings are "subjective, evaluative, and independent of the sensation ...
described after
running
Running is a method of terrestrial locomotion allowing humans and other animals to move rapidly on foot. Running is a type of gait characterized by an aerial phase in which all feet are above the ground (though there are exceptions). This i ...
, called the "
runners high" is, at least in part, due to increased circulating endocannabinoids (eCBs), and these lipid signaling molecules are involved in
reward
Reward may refer to:
Places
* Reward (Shelltown, Maryland), a historic home in Shelltown Maryland
* Reward, California (disambiguation)
* Reward-Tilden's Farm, a historic home in Chestertown Maryland
Arts, entertainment, and media
* "Rewa ...
,
appetite
Appetite is the desire to eat food items, usually due to hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced by satiety. Appetite exists in all higher life-forms, and serves to regul ...
,
mood,
memory and
neuroprotection
Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal los ...
, an analysis of endocannabinoid concentrations and moods after
singing,
dancing
Dance is a performing art form consisting of sequences of movement, either improvised or purposefully selected. This movement has aesthetic and often symbolic value. Dance can be categorized and described by its choreography, by its repertoire ...
,
exercise and
reading
Reading is the process of taking in the sense or meaning of letters, symbols, etc., especially by sight or touch.
For educators and researchers, reading is a multifaceted process involving such areas as word recognition, orthography (spelling) ...
in healthy volunteers, showed that singing increased plasma levels of anandamide (AEA) by 42%, palmitoylethanolamine (PEA) by 53% and oleoylethanolamine (OEA) by 34%, and improved
positive mood and
emotions. Dancing did not affect eCB levels, but decreased negative mood and emotions. Cycling increased OEA levels by 26%, and reading increased OEA levels by 28%. All the ethanolamines were positively correlated with
heart rate. As so, the plasma OEA levels were positively correlated with positive mood and emotions, and AEA levels were seen positively correlated with
satiation.
NAE and endocannabinoids is an integral component of
stress recovery, both centrally and peripherally, through regulation of the
HPA axis HPA may refer to:
Organizations
* Harry Potter Alliance, a charity
* Halifax Port Authority, Canada
* Hamburg Port Authority, Germany
* Hawaii Preparatory Academy, a school in Hawaii, US
* Health Protection Agency, UK
* Heerespersonalamt, the ...
, and reduction in circulating NAE 20:4 (AEA) content in
major depression
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introd ...
, and exposure to stress, is found to increase inflammatory markers by down-regulating the circulating content of the endogenous anti-inflammatory molecules, through their activation of
PPAR-α, palmitoylethanolamine (PEA: C
18H
37NO
2; 16:0) and
Oleoylethanolamine (OEA: C
20H
39NO
2; 18:1,
ω-9), as NAE
catabolism
Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipids, ...
is accelerated by stress and by the same
FAAH
Fatty acid amide hydrolase or FAAH (, oleamide hydrolase, anandamide amidohydrolase) is a member of the serine hydrolase family of enzymes. It was first shown to break down anandamide in 1993. In humans, it is encoded by the gene ''FAAH''.;
Fun ...
catabolic pathway.
Administration of CB
1 receptor antagonists
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rec ...
to humans has been found to increase indices of
depression and
anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
. Accordingly, the deficit in circulating endocannabinoids and activation of CB1, documented in individuals with major depression, may contribute to the emotional
sequelae associated with this disease. And it is therfore speculated, that this reduction in circulating endocannabinoid and NAE content in depression may be associated with the increased rates of
inflammation,
cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
and
autoimmune dysfunction seen in this disease.
Longevity
A study of 42 eighty years old (
octogenarians) humans living in the east-central mountain area of
Sardinia, a High-Longevity Zone (HLZ) in
Italy, have found, that the endocannabinoidome related circulating NAEs and familiar fatty acids are associated with a
longer
"Longer" is a song written and recorded by the American singer-songwriter Dan Fogelberg and released in 1979 by Full Moon Records and Epic Records. The song can be found on Fogelberg's 1979 album ''Phoenix''. It was also included on his 1982 gre ...
human life or
longevity
The word " longevity" is sometimes used as a synonym for " life expectancy" in demography. However, the term ''longevity'' is sometimes meant to refer only to especially long-lived members of a population, whereas ''life expectancy'' is always ...
, as increased
conjugated linoleic acid
Conjugated linoleic acids (CLA) are a family of isomers of linoleic acid. In principle, 28 isomers are possible. CLA is found mostly in the meat and dairy products derived from ruminants. The two C=C double bonds are conjugated (i.e., separated ...
(CLA: C
18H
32O
2; 18:
2, n-6) and
heptadecanoic acid
Margaric acid, or heptadecanoic acid, is a saturated fatty acid. Its molecular formula is CH3(CH2)15CO2H. Classified as an odd-chain fatty acid, it occurs as a trace component of the fat and milkfat of ruminants. Salts and esters of margaric acid ...
(C
17H
34O
2; 17:0), elevated
palmitoleic acid (POA; C
16H
30O
2; 16:1, n-7), a
conjugate acid
A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed when an acid donates a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as in the reverse reaction it loses a ...
of a palmitoleate (C
16H
29O
2; 16:1, n-7), where n-7 fatty acids are precursors for the production of omega-4 fatty acids like palmitolinoleic acid (16:2), and a significantly increased level of NAE 22:6 (DHEA: C
24H
37NO
2; 22:6, n-3), the metabolite of
DHA (C
22H
32O
2; 22:6, n-3), and the two endocannabinoids NAE 20:4 (AEA:
C22 H37 NO2; 20:
4,
ω-6) and
2-arachidonoyl-glycerol (2-AG: C
23H
38O
4; 20:4, n-6), as well of increased NAE 18:1 (OEA: C
20H
39NO
2; 18:1,
ω-9), the amide of
palmitic acid (C
16H
32O
2; 16:0) and
ethanolamine (MEA: C
2H
7NO), and increase of 2-linoleoyl-glycerol (2-LG; C
21H
38O
4; 18:2, n-6), derived from
linoleic acid
Linoleic acid (LA) is an organic compound with the formula COOH(CH2)7CH=CHCH2CH=CH(CH2)4CH3. Both alkene groups are ''cis''. It is a fatty acid sometimes denoted 18:2 (n-6) or 18:2 ''cis''-9,12. A linoleate is a salt or ester of this acid.
L ...
(LA: C
18H
32O
2; 18:2, n-6), can indicate a metabolic pattern potentially protective from adverse chronic conditions, and show a suitable
physiological
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...
metabolic pattern, that may counteract the adverse stimuli leading to age-related disorders such as neurodegenerative and metabolic diseases.
It is found that
3T3-L1 3T3-L1 is a cell line derived from (mouse) 3T3 cells that is used in biological research on adipose tissue. 3T3-L1 cells have a fibroblast-like morphology, but, under appropriate conditions, the cells differentiate into an adipocyte-like phenotype. ...
adipocyte
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. ...
s
convert
Conversion or convert may refer to:
Arts, entertainment, and media
* "Conversion" (''Doctor Who'' audio), an episode of the audio drama ''Cyberman''
* "Conversion" (''Stargate Atlantis''), an episode of the television series
* "The Conversion" ...
eicosapentaenoic acid (EPA: C
20H
30O
2; 20:5, ω-3) to NAE 20:5 (EPEA: C
22H
35NO
2; 20:5, ω-3) or Anandamide (20:5, n-3) and
docosahexaenoic acid (DHA: C
22H
32O
2; 22:6, ω-3) to NAE 22:6 (DHEA: C
24H
37NO
2; 22:6, ω-3), or Anandamide (22:6, n-3). This conversion to EPEA and DHEA decrease
IL-6 and
MCP-1 levels, and the combined incubations with
PPAR-gamma and
CB2 antagonists, suggest a role of these receptors in mediating the reduction of IL-6 by DHEA. These results are in line with the hypothesis, that in addition to other pathways, this formation of NAEs may contribute to the biological activity of n-3
PUFAs, and different targets, including the endocannabinoid system, may be involved in the
immune-modulating activity of
fish-oil derived NAEs.
The importance of a low ratio of omega-6 to omega-3 essential fatty acids
Studies have found, that humans
evolved on a
diet
Diet may refer to:
Food
* Diet (nutrition), the sum of the food consumed by an organism or group
* Dieting, the deliberate selection of food to control body weight or nutrient intake
** Diet food, foods that aid in creating a diet for weight loss ...
with a ratio of
omega-6
Omega-6 fatty acids (also referred to as ω-6 fatty acids or ''n''-6 fatty acids) are a family of polyunsaturated fatty acids that have in common a final carbon-carbon double bond in the ''n''-6 position, that is, the sixth bond, counting from ...
(n-6) to
omega-3
Omega−3 fatty acids, also called Omega-3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond, three atoms away from the terminal methyl group in their chem ...
(n-3)
essential fatty acids (EFA) of about 1:1, whereas in today's
Western diets the ratio is 15/1–16.7/1, or even more. The excessive amounts of n-6
polyunsaturated fatty acids (PUFA) and a very high n-6/n-3 ratio, promote the
pathogenesis of many diseases, including
cardiovascular
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, t ...
disease,
cancer, and
inflammatory and
autoimmune
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...
diseases, whereas a low n-6/n-3 ratio exert suppressive effects. However, it is found impotent, that this low ratio, should change a bit, depending on disease, as the ratio of 2.5/1 reduce
rectal
The rectum is the final straight portion of the large intestine in humans and some other mammals, and the gut in others. The adult human rectum is about long, and begins at the rectosigmoid junction (the end of the sigmoid colon) at the le ...
cell
proliferation in patients with
colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...
, and 2–3/1 suppress inflammation in patients with
rheumatoid arthritis, 4/1 is optimum for prevention of cardiovascular disease, showing a 70% decrease in total
mortality
Mortality is the state of being mortal, or susceptible to death; the opposite of immortality.
Mortality may also refer to:
* Fish mortality, a parameter used in fisheries population dynamics to account for the loss of fish in a fish stock throug ...
, and 5/1 have a beneficial effect on patients with
asthma
Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
, whereas 10/1 have adverse consequences, indicate, that the optimal ‘low ratio’, may vary with the specific disease.
The
World Health Organization (WHO) estimate
hemp, a culture
CO2 negative, - a crop that is capable in the
carbon cycle
The carbon cycle is the biogeochemical cycle by which carbon is exchanged among the biosphere, pedosphere, geosphere, hydrosphere, and atmosphere of the Earth. Carbon is the main component of biological compounds as well as a major componen ...
of removing more CO
2 from the ambient than it emits, where production of
biomass produce between 8 and 12 tons of CO
2, but seize between 10 and 15 tons per
hectare, with the possibility to sequester up to 22 tons of CO
2 from the increased dry matter of the stem, where 80% of atmospheric carbon is sequestered and stored, by a
nitrogen fertilization
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
between 0 and 120 kg per hectare,
as having what is considered to be an optimal 3:1 balance of omega 6 to omega 3 essential fatty acids, and where
hempseed oil
Hemp oil (hemp seed oil) is oil obtained by pressing hemp seeds. Cold pressed, unrefined hemp oil is dark to clear light green in color, with a nutty flavor. The darker the color, the grassier the flavour. It should not be confused with hash oi ...
is the only one that is in perfect balance according to what the human body needs – 3:1, and a
pound (454
gram
The gram (originally gramme; SI unit symbol g) is a unit of mass in the International System of Units (SI) equal to one one thousandth of a kilogram.
Originally defined as of 1795 as "the absolute weight of a volume of pure water equal to th ...
) of
hemp seed can provide all the
protein, essential fatty acids, and
dietary fiber necessary for human survival for two weeks, or 33 gram a day.
And their absence has been found responsible for the development of a wide range of diseases such as
metabolic disorders,
cardiovascular disorders
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
,
inflammatory processes,
viral infections, certain types of
cancer and
autoimmune disorders
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
.
Synthesis
Synthesis or synthesize may refer to:
Science Chemistry and biochemistry
* Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors
**Organic synthesis, the chemical synthesis of organ ...
of
LC-PUFAs in
humans
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
and many other
eukaryotes starts with:
* Linoleic acid
Linoleic acid (LA) is an organic compound with the formula COOH(CH2)7CH=CHCH2CH=CH(CH2)4CH3. Both alkene groups are ''cis''. It is a fatty acid sometimes denoted 18:2 (n-6) or 18:2 ''cis''-9,12. A linoleate is a salt or ester of this acid.
L ...
(LA:
C18 H32 O2; 18:
2-n6) →
Δ6-desaturation (removing two hydrogen atoms, creating a
double bond and a bend in the fatty acid) →
''γ''-linolenic acid (GLA: C
18H
30O
2; 18:3-n6) → Δ6-specific
elongase Elongase is a generic term for an enzyme that catalyzes carbon chain extension of an organic molecule, especially a fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid
In organic chemistry, a carboxyl ...
(introducing two carbons and four hydrogens) →
Dihomo-gamma-linolenic acid DGLA: C
20H
34O
2; 20:3-n6) →
Δ5-desaturase →
arachidonic acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...
(AA: C
20H
32O
2; 20:4-n6) → also endocannabinoids.
* α-Linolenic acid
''alpha''-Linolenic acid (ALA), also known as α-Linolenic acid (from Greek ''alpha'' meaning "first" and ''linon'' meaning flax), is an ''n''−3, or omega-3, essential fatty acid. ALA is found in many seeds and oils, including flaxseed, waln ...
(ALA: C
18H
30O
2; 18:3-n3) → Δ6-desaturation →
stearidonic acid
Stearidonic acid (SDA: C18 H28 O2; 18: 4, n-3) is an ω-3 fatty acid, sometimes called moroctic acid. It is biosynthesized from alpha-linolenic acid (ALA: C18H30O2; 18:3, n-3) by the enzyme delta-6-desaturase, that removes two hydrogen (H) ato ...
(SDA: C
18H
28O
2; 18:4-n3) and/or → Δ6-specific elongase →
eicosatetraenoic acid Eicosatetraenoic acid (ETA) designates any straight chain 20:4 fatty acid. Eicosatetraenoic acid belongs to the family of eicosanoids, molecules synthesized from oxidized polyunsaturated fatty acids (PUFAs) to mediate cell-cell communication. The e ...
(ETA: C
20H
32O
2; 20:4-n3) → Δ5-desaturase →
eicosapentaenoic acid (EPA: C
20H
30O
2; 20:5-n3).
By a Δ17-desaturase,
gamma-Linolenic acid (GLA: C
18H
30O
2; 18:3-n6) can be further converted to
stearidonic acid
Stearidonic acid (SDA: C18 H28 O2; 18: 4, n-3) is an ω-3 fatty acid, sometimes called moroctic acid. It is biosynthesized from alpha-linolenic acid (ALA: C18H30O2; 18:3, n-3) by the enzyme delta-6-desaturase, that removes two hydrogen (H) ato ...
(SDA: C
18H
28O
2; 18:4-n3),
dihomo-gamma-linolenic acid (DHGLA/DGLA: C
20H
34O
2; 20:3-n6) to
eicosatetraenoic acid Eicosatetraenoic acid (ETA) designates any straight chain 20:4 fatty acid. Eicosatetraenoic acid belongs to the family of eicosanoids, molecules synthesized from oxidized polyunsaturated fatty acids (PUFAs) to mediate cell-cell communication. The e ...
(ETA: C
20H
32O
2; 20:4-n3; omega-3 Arachidonic acid) and
arachidonic acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...
(AA: C
20H
32O
2; 20:4-n6) to
eicosapentaenoic acid (EPA: C
20H
30O
2; 20:5-n3), respectively.
*
Fatty acids with at least 20 carbons (C
20) and three double bonds (20:3) bind to
CB1 receptors.
*
Arachidonic acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...
(AA) is also the catalyst to the formation of the two main
endocannabinoids,
Anandamide
Anandamide (ANA), also known as ''N''-arachidonoylethanolamine (AEA), is a fatty acid neurotransmitter. Anandamide was the first endocannabinoid to be discovered: it participates in the body's endocannabinoid system by binding to cannabinoid rece ...
(AEA) and
2-arachidonoylglycerol
2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is present ...
(2-AG).
* Anandamide
Anandamide (ANA), also known as ''N''-arachidonoylethanolamine (AEA), is a fatty acid neurotransmitter. Anandamide was the first endocannabinoid to be discovered: it participates in the body's endocannabinoid system by binding to cannabinoid rece ...
(AEA: C
22H
37 NO2; 20:4,n-6) is an ''N''-acylethanolamine resulting from the formal
condensation
Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapor to ...
of the
carboxy
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
group of arachidonic acid (AA: C
20H
32O
2; 20:4-n6) with the
amino
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...
group of
ethanolamine (C
2H
7 NO), bind preferably to
CB1 receptors.
* 2-arachidonoylglycerol
2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is present ...
(2-AG: C
23H
38O
4; 20:4-n6) is an endogenous
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
of the
cannabinoid receptors
Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid recep ...
(CB1 and CB2), and the physiological
ligand for the cannabinoid
CB2 receptor
The cannabinoid receptor type 2, abbreviated as CB2, is a G protein-coupled receptor from the cannabinoid receptor family that in humans is encoded by the ''CNR2'' gene. It is closely related to the cannabinoid receptor type 1 (CB1), which is l ...
.
It is an
ester formed from omega-6-arachidonic acid (AA: C
20H
32O
2; 20:4-n6) and
glycerol (C
3H
8O
3).
Metabolic production of NAEs
Diets in mammals, containing 20:4,''n''−6 and 22:6'',n''−3, are found to increase several biologically active NAEs in brain
homogenates as
metabolic products, like 20:4'',n''−6 NAE (4-fold), 20:5'',n''−3 NAE (5-fold), and 22:5'',n''−3 and 22:6,''n''−3 NAE (9- to 10-fold). The increase in all of the metabolic NAEs is regarded biologically important, because NAEs having
fatty acids with at least 20 carbons and three double bonds bind to
CB1 receptors,
and endogenously released NAE 20:4 and
2-arachidonylglycerol
2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is present ...
(2-AG: C
23H
38O
4; 20:4,n-6), the ester metabolic formed from omega-6-
arachidonic acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...
(AA: C
20H
32O
2; 20:4, n-6) and glycerol (C
3H
8O
3), are also found to activate
CB2 receptors in addition,
where 2-AG is the physiological ligand.
The
hydrolysis of NAE to
free fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
(FFA) and ethanolamine (MEA) in animals, is catalyzed by
fatty acid amide hydrolase (FAAH) or by a ''N''-acylethanolamine-hydrolyzing acid amidase (NAAA), and the
polyunsaturated
In nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such compounds, most commonly those that occur in living beings or in food.
The term often refers specifically to triglycerides (triple est ...
NAEs such as NAE 18:2, NAE 18:3, or NAE 20:4 can also be oxygenated via
lipoxygenase
Lipoxygenases () are a family of (non-heme) iron-containing enzymes most of which catalyze the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene into cell signaling agents that serve diverse roles as a ...
(LOX) or
cyclooxygenase (COX), to produce ethanolamide
oxylipins, like
prostaglandin
The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are deri ...
ethanolamides (
prostamide) by
COX-2
Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (The HUGO official symbol is PTGS2; HGNC ID, HGNC:9605), also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the ''PTGS2'' gene ...
, with various potential
bioactivities that may have enhanced affinity with cannabinoid receptors in comparison to their respective non-oxygenated NAEs,
as well as to oxygenated
eicosanoid
Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a sub-c ...
ethanolamides, prostaglandins, and
leukotrienes, all believed to be important signaling compounds.
The major COX-2 derived prostanoid product from NAE 20:4 (AEA) are
prostaglandin E2 (PGE
2) ethanolamide (PGE
2-EA; prostamide E2) and
PGD2 ethanolamide (PGD
2-EA; prostamide D2), might have many important functions, as PGE
2 and PGD
2 are pro-inflammatory mediators responsible for the induction of
inflammation,
PGE
2-EA and PGD
2-EA are contrary both growth inhibitory and can induce
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes includ ...
, as well as that NAE 20:4 (AEA) and/or its prostamide metabolites in the
renal medulla
The renal medulla is the innermost part of the kidney. The renal medulla is split up into a number of sections, known as the renal pyramids. Blood enters into the kidney via the renal artery, which then splits up to form the segmental arteries whi ...
, may represent
medullipin Medullipin is a hormone created by the interstitial cells of renal papilla, which is converted to medullipin II in the liver. This, in turn, results in vasodilation and decreased blood pressure.
There are two kinds of medullipin, known as medulli ...
and function as a regulator of
body fluid
Body fluids, bodily fluids, or biofluids, sometimes body liquids, are liquids within the human body. In lean healthy adult men, the total body water is about 60% (60–67%) of the total body weight; it is usually slightly lower in women (52-55%). ...
and the
mean arterial pressure (MAP).
Fatty acid amide hydrolase (FAAH) is the main degrading enzyme of NAE 20:4 (AEA) and NAE 18:1 (OEA), which have opposite effects on food intake and
energy balance. AEA, an endogenous ligand of CB1 cannabinoid receptors, enhances food intake and energy storage, whereas OEA binds to
peroxisome proliferator-activated receptors-α to reduce food intake and promoting
lipolysis, thereby FAAH deficiency promotes
energy storage and enhances the
motivation for
food, through the enhancement of AEA levels rather than promoting the
anorexic
Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...
effects of OEA. Tetrahydrocannabinol (THC:
C21 H30 O2) is found to lower production of NAE 20:4 (AEA) and 2-AG, that is synthesized in an on-demand manner when needed for activation, by a
biphasic
Biphasic, meaning having two phases, may refer to:
* Phase (matter), in the physical sciences, a biphasic system, e.g. one involving liquid water and steam
* Biphasic sleep, a nap or siesta in addition to the usual sleep episode at night
* Phas ...
response after THC injection reaching maximal values at 30 min., where AEA increased slightly from 0.58 ± 0.21 ng/ml at baseline to 0.64 ± 0.24 ng/ml, and 2-AG from 7,60 ± 4,30 ng/ml to 9,50 ± 5,90 ng/ml, and after reaching maximal concentrations, EC plasma levels decreased markedly to a nadir of 300 min after THC administration to 0.32 ± 0.15 ng/ml for AEA, and 5,50 ± 3,01 ng/ml for 2-AG, and returned to near baseline levels until 48 hours after the experiment, in 25 healthy volunteers who received a large intravenous dose of THC (0.10 mg/kg).
Insulin medication and
intraoperative
The perioperative period is the time period of a patient's surgical procedure. It commonly includes ward admission, anesthesia, surgery, and recovery. Perioperative may refer to the three phases of surgery: preoperative, intraoperative, and posto ...
doses of
insulin is also found, but not recognized by companies
producing and selling medication to general public also as a slimming formula like
Wegovy, to get its
anorectic
An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. By contrast, an appetite stimulant is referred to as orexigenic.
The term is (from the Greek ''ἀν-'' (an-) = "without" and ...
effect by the increase of
FAAH
Fatty acid amide hydrolase or FAAH (, oleamide hydrolase, anandamide amidohydrolase) is a member of the serine hydrolase family of enzymes. It was first shown to break down anandamide in 1993. In humans, it is encoded by the gene ''FAAH''.;
Fun ...
activity, which, beside of other NAE's, degrade NAE 20:4 (AEA),
suggest that insulin may play a key role in the obesity-linked dysregulation of the adipose ECS at the
gene level.
This is in line with a study that find low-
carbohydrate and high-fat diet, called Low Carb High Fat-diet (
LCHF), a possible treatment strategy for
type 2 diabetes mellitus (T2DM) and
nonalcoholic fatty liver disease (NAFLD), as they find lower
blood sugar
Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the bl ...
and insulin intake, and a better
mood and
energy of the 165 participants with T2DM, that replaced
rye bread,
flour and
pasta products with
fleawort seed shells,
hemp seeds
Hemp, or industrial hemp, is a botanical class of ''Cannabis sativa'' cultivars grown specifically for industrial or medicinal use. It can be used to make a wide range of products. Along with bamboo, hemp is among the fastest growing plants o ...
and pofiber (potato fiber),
butter
Butter is a dairy product made from the fat and protein components of churned cream. It is a semi-solid emulsion at room temperature, consisting of approximately 80% butterfat. It is used at room temperature as a spread, melted as a condiment ...
, oil, meat and fat, some has cut insulin consumption by half. However, the greater improvements in
glycemic control
The term ''diabetes'' includes several different metabolic disorders that all, if left untreated, result in abnormally high concentration of a sugar called glucose in the blood. Diabetes mellitus type 1 results when the pancreas no longer produces ...
and reduced weight, were not sustained 9 months after start, could show a
homeostatic reaction.
A FAAH 385A
mutant alleles have been found to have a direct effect on elevated plasma levels of NAE 20:4 (AEA) and related NAEs in humans, and biomarkers that may indicate risk for severe
obesity that suggest novel
ECS obesity treatment strategies, as
leptin increases the FAAH activity and reduces NAE 20:4 (AEA) signaling, particularly within the
hypothalamus, to promote a suppression of
food intake
Eating (also known as consuming) is the ingestion of food, typically to provide a heterotrophic organism with energy and to allow for growth. Animals and other heterotrophs must eat in order to survive — carnivores eat other animals, herbi ...
, a mechanism that is lost in diet-induced obesity and modulated by a human genetic variant (C385A) of the ''FAAH''
gene. The cannabinoid type 1 receptors (CB1) and their endogenous ligands, the endocannabinoids, present in peripheral organs, such as
liver,
white adipose tissue
White adipose tissue or white fat is one of the two types of adipose tissue found in mammals. The other kind is brown adipose tissue. White adipose tissue is composed of monolocular adipocytes.
In humans, the healthy amount of white adipose ti ...
,
muscle, and
pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an ...
, where it regulate
lipid and
glucose homeostasis
In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and i ...
, and dysregulation of it, has been associated with the development of obesity, characterized by chronic mild
inflammation, and its sequelae, such as
dyslipidemia
Dyslipidemia is an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular disease ( ASCVD). ASCVD includes coronary ar ...
and
diabetes, are involved in modulating food intake and the motivation to consume
palatable Palatability (or palatableness) is the hedonic reward (i.e., pleasure) provided by foods or fluids that are agreeable to the "palate", which often varies relative to the homeostatic satisfaction of nutritional, water, or energy needs. The palatabil ...
food.
NAE 20:4 related THC treatment have shown to increase culture protein content and reduced methyl-(3)H-thymidine incorporation, and cells treated with THC underwent
adipogenesis Adipogenesis is the formation of adipocytes (fat cells) from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as preadipoc ...
shown by the expression of
PPARγ
Peroxisome proliferator- activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance
receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a tran ...
and had increased
lipid accumulation Adipogenesis is the formation of adipocytes (fat cells) from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as preadipocy ...
. Basal and IP-stimulated
lipolyses were also inhibited by THC, and the effects on methyl-(3)H-thymidine incorporation and lipolysis seem to be mediated through CB1- and CB2-dependent pathways. THC did also decrease NAPE-PLD, the
enzyme that catalyzes and converts ordinary
lipids into chemical signals like NAE 20:4 (AEA) and NAE 18:1 (OEA), in preadipocytes and increased
adiponectin
Adiponectin (also referred to as GBP-28, apM1, AdipoQ and Acrp30) is a protein hormone and adipokine, which is involved in regulating glucose levels as well as fatty acid breakdown. In humans it is encoded by the ''ADIPOQ'' gene and it is produced ...
and
TGFβ
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sig ...
transcription in
adipocyte
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. ...
s, results that show the ECS interferes with adipocyte biology and may contribute to adipose
tissue (AT) remodeling. And this stimulation of adiponectin production and inhibition of lipolysis from THC may be in favor of improved
insulin sensitivity under cannabinoid influence.
A
full agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the a ...
at the
CB1 receptor is found able to up-regulate
PPARy, and increased (+50%)
glucose uptake, the
translocation of
glucose transporter 4, and intracellular
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...
in
fat cells, that indicate a role for the local endocannabinoids in the regulation of
glucose metabolism
Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation, breakdown, and interconversion of carbohydrates in living organisms.
Carbohydrates are central to many essential metabolic pathways. P ...
in human adipocytes and suggest a role in channelling excess
energy fuels to
adipose tissue
Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular e ...
in obese humans. This is consistent with the decreased prevalence of diabetes seen in marijuana users, and significantly reduced body mass index (
BMI) and rates of obesity in ''Cannabis'' users, as endocannabinoids modulate
pancreatic β-cells function,
proliferation, and survival, as well as
insulin production,
secretion, and
resistance, where animal and human research suggest that increased activity of the endocannabinoid system, may lead to
insulin resistance
Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin.
Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood sugar ...
,
glucose intolerance and obesity.
Consistent with the associated reduced prevalence of
non-alcoholic fatty liver disease (NAFLD) among cannabis users, that find significantly lower NAFLD prevalence compared to non-users, i.e. 15% lower in non-dependent users and 52% lower in dependent users, and dependent patients had 43% significantly lower prevalence of NAFLD compared to non-dependent patients.
In addition to metabolism by FAAH, COX-2 and LOXs, NAE 20:4 (AEA) can also undergo oxidation by several of human
cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various comp ...
(CYPs) enzymes, resulting in various oxidized lipid species, some of which have biological relevance as CYP-derived
epoxides, that can act as a potent agonist of CB2 receptors.
NAE 20:4 (AEA: C
22H
37NO
2) which is similar in structure to
N-arachidonoyl glycine
''N''-Arachidonylglycine (NAGly) is a carboxylic metabolite of the endocannabinoid anandamide (AEA). Since it was first synthesized in 1996, NAGly has been a primary focus of the relatively contemporary field of lipidomics due to its wide range o ...
(Nagly: C
22H
35NO
3 - a
carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
COOH) are metabolically interconnected, as
oxidation of the
hydroxyl group of NAE 20:4 (AEA) leads to NAgly, prefering
G-protein coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
(GPR)
118 118 may refer to:
*118 (number)
*AD 118
*118 BC
*118 (TV series)
*118 (film)
*118 (Tees) Corps Engineer Regiment
*118 (Tees) Field Squadron, Royal Engineers
See also
*11/8 (disambiguation)
*Oganesson
Oganesson is a synthetic chemical element wi ...
, with a molecular structure, that are found of pharmacological interest, as region one confers a high degree of specificity of action, as
polyunsaturated
In nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such compounds, most commonly those that occur in living beings or in food.
The term often refers specifically to triglycerides (triple est ...
residues produce molecules with
analgesic
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It i ...
and
anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as op ...
action, of which
saturated
Saturation, saturated, unsaturation or unsaturated may refer to:
Chemistry
* Saturation, a property of organic compounds referring to carbon-carbon bonds
**Saturated and unsaturated compounds
**Degree of unsaturation
**Saturated fat or fatty acid ...
structures, are inactive. Region two is related to metabolic stability as NAgly is degraded by FAAH activity. And last, region 3, the
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
residue, can have an effect on the analgesic and anti-inflammatory activities depending on
steric factors and the
chiral
Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object.
An object or a system is ''chiral'' if it is distinguishable from i ...
nature of the amino acid.
It is found that
long-chain fatty acid conjugates from the metabolic hydroxyl oxidation product of the phytocannabinoid, THC (
C21 H30 O2), 11-
hydroxy-THC (
11-OH-THC: C
21H
30O
3) are proposed to be a form in which THC may be stored within
tissues. And the last cytochrome P450 oxidation product of THC afford the non-psychoactive and long-living 11-nor-9-
carboxy
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
-THC (
THC-COOH: C
21H
28O
4) as main metabolite, that in some authors’ opinion, are insufficiently characterized, as an
acid
In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...
metabolite seen as a final product in both
cannabis-plants and
mammals, with there main unanswered questions, "Could any of the pharmacological effects observed for THC be attributed to
THCA (C
22H
30O
4) and/or THC-COOH, and could THC also be a potential
pro-drug
A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...
to another pharmacological entity?".
NSAIDs that
inhibit COX2, may find its
medical
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care practic ...
influence from the cannabinoid system, either by inhibiting the break down of NAE 20:4 (AEA) by
FAAH
Fatty acid amide hydrolase or FAAH (, oleamide hydrolase, anandamide amidohydrolase) is a member of the serine hydrolase family of enzymes. It was first shown to break down anandamide in 1993. In humans, it is encoded by the gene ''FAAH''.;
Fun ...
(i.e.
ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arte ...
,
indomethacin,
flurbiprofen
Flurbiprofen is a member of the phenylalkanoic acid derivative family of nonsteroidal anti-inflammatory drugs (NSAIDs). It is primarily indicated as a pre-operative anti-miotic (in an ophthalmic solution) as well as orally for arthritis or dent ...
, ibu–am5), or by inhibiting a possible
intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
transporter of endocannabinoids (i.e.
acetaminophen
Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol.
At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
).
The phytocannabinoid THC is found to have twenty times the anti-inflammatory potency of
aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat in ...
and twice that of
hydrocortisone
Hydrocortisone is the name for the hormone cortisol when supplied as a medication. Uses include conditions such as adrenocortical insufficiency, adrenogenital syndrome, high blood calcium, thyroiditis, rheumatoid arthritis, dermatitis, asthma, ...
, but in contrast to NSAIDs, it demonstrates no COX inhibition at physiological concentrations.
Another of the main phytocannabinoids,
cannabidiol
Cannabidiol (CBD) is a phytocannabinoid discovered in 1940. It is one of 113 identified cannabinoids in cannabis plants, along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. , clinical research on CBD incl ...
(CBD:
C21 H30 O2) is found to produce a significant increase in serum NAE 20:4 (AEA) levels, by inhibiting the
intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
degradation catalyzed by FAAH, suggest the inhibition of NAE 20:4 (AEA) deactivation may contribute to the
antipsychotic
Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...
effects of CBD, potentially representing a mechanism in the treatment of
schizophrenia, with a markedly superior
side-effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
profile, compare to
amisulpride
Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold und ...
, a potent
antipsychotic
Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...
. CBD were also seen to elevate serum levels of the non-cannabimimetic lipid mediators, NAE 16:0 (PEA) and NAE 18:1 (OEA), but amisulpride did not.
FAAH inhibitors are seen to both increase
alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
consumption (NAE 20:4; AEA) and prevent against
oxidative stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal r ...
caused by
binge
Binge or Binges may refer to:
Behavior
Binge, a behavior engaged in excessively over a short period of time, such as:
* Binge drinking
* Binge eating
* Binge-watching
Arts, entertainment, and media
* ''Binge'' (EP), a 2018 EP by Machine Gun Kell ...
ethanol consumption, and as NAE 16:0 (PEA) and NAE 18:1 (OEA), through the endocannabinoidome-related peroxisome proliferator-activated receptor-α (
PPAR-α) is involved in the actions of NAEs with no endocannabinoid activity, have been reported to exhibit
neuroprotective
Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal los ...
effects, suggest a strengthening of the
ECS may reflect a
homeostatic mechanism to prevent the
neurotoxic effects induced by
alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
with a relevant role of other non-cannabinoid
congeners in the alcohol exposure, and the further activation in response to the negative
affective state, like the
anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
,
associated to alcohol
withdrawal. Or poorer
recall
Recall may refer to:
* Recall (bugle call), a signal to stop
* Recall (information retrieval), a statistical measure
* ''ReCALL'' (journal), an academic journal about computer-assisted language learning
* Recall (memory)
* ''Recall'' (Overwatc ...
of
verbal and nonverbal information, as well as reduced
visuospatial skills related to alcohol
hangover and withdrawal symptoms in youth, a relationship not seen in
adolescents
Adolescence () is a transitional stage of physical and psychological development that generally occurs during the period from puberty to adulthood (typically corresponding to the age of majority). Adolescence is usually associated with the ...
with similar levels of alcohol involvement if they are heavy users of marijuana.
The cannabinoid
CB1 receptor
Cannabinoid receptor type 1 (CB1), also known as cannabinoid receptor 1, is a G protein-coupled cannabinoid receptor that in humans is encoded by the ''CNR1'' gene. The human CB1 receptor is expressed in the peripheral nervous system and cent ...
play a critical role in mediating the
adolescent behavior, because enhanced CB1 density and endocannabinoid (eCB) signaling occur transiently during the periode from
childhood
A child ( : children) is a human being between the stages of birth and puberty, or between the developmental period of infancy and puberty. The legal definition of ''child'' generally refers to a minor, otherwise known as a person younger ...
to adolescence and reverse when
adult
An adult is a human or other animal that has reached full growth. In human context, the term ''adult'' has meanings associated with social and legal concepts. In contrast to a " minor", a legal adult is a person who has attained the age of major ...
and mature in normal phenotypes. Reports on enhanced adolescent CB1 signaling, suggest a pivotal role for the CB1 in an adolescent brain as an important molecular mediator of adolescent behavior, as adult CB1 mutant rats exhibit an adolescent-like phenotype with typical high
risk seeking,
impulsivity, and augmented
drug and nondrug
reward
Reward may refer to:
Places
* Reward (Shelltown, Maryland), a historic home in Shelltown Maryland
* Reward, California (disambiguation)
* Reward-Tilden's Farm, a historic home in Chestertown Maryland
Arts, entertainment, and media
* "Rewa ...
sensitivity, by an
instinctive need or call for activation, and
partial
Partial may refer to:
Mathematics
*Partial derivative, derivative with respect to one of several variables of a function, with the other variables held constant
** ∂, a symbol that can denote a partial derivative, sometimes pronounced "partial d ...
inhibition of CB1 activity normalized behavior and led to an adult phenotype, is why it is concluded that the activity state and functionality of the CB1 is critical for mediating adolescent behavior and further turn to an adult phenotype, by normal CB1 downscaling. This is also do to the cannabinoid system and its neurotransmitter NAE 20:4 (AEA), that highly participate in the modulation of human states and appropriate human
emotional responses by activation of the CB1 receptor,
also found in frontal
neocortical
The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, s ...
areas, subserving higher
cognitive
Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, though ...
and
executive functions, and in the
posterior cingulate
The posterior cingulate cortex (PCC) is the caudal part of the cingulate cortex, located posterior to the anterior cingulate cortex. This is the upper part of the "limbic lobe". The cingulate cortex is made up of an area around the midline of the ...
, a region pivotal for
consciousness
Consciousness, at its simplest, is sentience and awareness of internal and external existence. However, the lack of definitions has led to millennia of analyses, explanations and debates by philosophers, theologians, linguisticians, and scien ...
and higher cognitive processing.
Alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
(
EtOH) is seen to increase levels of NAE 20:4 (AEA), and its precursor ''N''‐arachidonoylphosphatidylethanolamine (N‐ArPE), a glycero-phospho-ethanolamine, significantly, that may be a mechanism for
neuronal adaptation and serve as a compensatory mechanism to counteract a continuous presence of EtOH, that together with previous results indicate the involvement of the endocannabinoid system in mediating some of the
pharmacological
Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemic ...
actions alleged of EtOH, also seen in
red wine components
Circuit Component may refer to:
•Are devices that perform functions when they are connected in a circuit.
In engineering, science, and technology Generic systems
*System components, an entity with discrete structure, such as an assemb ...
,
and in
Humulus lupulus
''Humulus lupulus'', the common hop or hops, is a species of flowering plant in the hemp family Cannabinaceae, native to Europe, western Asia and North America. It is a perennial, herbaceous climbing plant which sends up new shoots in early ...
to preserve and flavor
beer, widely cultivated for use by the
brewing industry
Beer is one of the oldest and the most widely consumed type of alcoholic drink in the world, and the third most popular drink overall after water and tea. It is produced by the brewing and fermentation of starches, mainly derived from cerea ...
, through
caryophyllene
Caryophyllene (), more formally (−)-β-caryophyllene, (BCP), is a natural bicyclic sesquiterpene that is a constituent of many essential oils, especially clove oil, the oil from the stems and flowers of '' Syzygium aromaticum'' (cloves), the ess ...
that is a selective
full agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the a ...
at
CB2, and may constitute part of a common brain pathway mediating
reinforcement
In behavioral psychology, reinforcement is a consequence applied that will strengthen an organism's future behavior whenever that behavior is preceded by a specific antecedent stimulus. This strengthening effect may be measured as a higher freq ...
of
drugs of abuse including EtOH,
by elevated CB1. As, CB1 receptor binding is 20-30% lower in patients with
alcohol dependence
Alcohol dependence is a previous (DSM-IV and ICD-10) psychiatric diagnosis in which an individual is physically or psychologically dependent upon alcohol (also chemically known as ethanol).
In 2013, it was reclassified as alcohol use disorder ...
than in control subjects in all brain regions and is negatively correlated with years of alcohol abuse, and the CB1 receptor binding remain similarly reduced after 2–4 weeks of abstinence, suggests an involvement of CB1 receptors in alcohol dependence in humans.
Similar pathways of hydrolysis or oxidation of NAEs are also found in plant cells.
NAE system in plants
N-acylethanolamines (NAEs), constitute a class of lipid compounds naturally present in both animal and
plant membranes
A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...
, as constituents of the
membrane-bound
phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
,
N-acylphosphatidylethanolamine (NAPE). NAPE is composed of a third fatty acid moiety linked to the
amino
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...
head group of the commonly occurring membrane
phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
,
phosphatidylethanolamine.
A study in 2000 find, that
higher plants
Vascular plants (), also called tracheophytes () or collectively Tracheophyta (), form a large group of land plants ( accepted known species) that have lignified tissues (the xylem) for conducting water and minerals throughout the plant. They al ...
use defense signaling, to combat
cellular stressful situations (
homeostasis
In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and i ...
), like in
osmotic stress
Osmotic shock or osmotic stress is physiologic dysfunction caused by a sudden change in the solute concentration around a cell, which causes a rapid change in the movement of water across its cell membrane. Under hypertonic conditions - conditions ...
, where high levels of NAEs after a periode of
dehydration, are
metabolized
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
fast during the first few hours of
imbibition, and in response to
pathogen elicitors, that lead to
signal transduction and
membrane protection, in the same way as several
mammalian
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur o ...
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
types, coupled to
endocannabinoid signaling, do, by releasing saturated and unsaturated long-chain NAEs, and saturated medium-chain NAEs, that can act as lipid mediators to modulate
ion
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conv ...
flux and activate defense
gene expression.
The levels of NAEs increases 10- to 50-fold in tobacco (''
Nicotiana tabacum'')
leaves
A leaf ( : leaves) is any of the principal appendages of a vascular plant stem, usually borne laterally aboveground and specialized for photosynthesis. Leaves are collectively called foliage, as in "autumn foliage", while the leaves, ste ...
treated with
fungal elicitors, as a
protection
Protection is any measure taken to guard a thing against damage caused by outside forces. Protection can be provided to physical objects, including organisms, to systems, and to intangible things like civil and political rights. Although th ...
against it, by producing the ''N-''myristoylethanolamine (''Myristamide''-MEA: C
16H
33NO
2; NAE 14:0), that specific binds to a
protein in tobacco membranes with
biochemical
Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
properties appropriate for the
physiological
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...
responses, and it do not show identical binding properties to NAE-
binding protein A binding protein is any protein that acts as an agent to bind two or more molecules together.
Examples include:
*DNA-binding protein
**Single-strand binding protein
** Telomere-binding protein
*RNA-binding protein
**Poly(A)-binding protein
** N ...
s in intact tobacco
microsome
In cell biology, microsomes are heterogeneous vesicle-like artifacts (~20-200 nm diameter) re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, li ...
s, compared to non-intact microsomes. In addition to this,
antagonists
An antagonist is a character in a story who is presented as the chief foe of the protagonist.
Etymology
The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...
of mammalian CB receptors was seen to block both of the biological activities previously attributed to NAE 14:0, this endogenous NAE that is accumulated in tobacco
cell suspension
A cell suspension or suspension culture is a type of cell culture in which single cells or small aggregates of cells are allowed to function and multiply in an agitated growth medium, thus forming a suspension. Suspension culture is one of the two ...
s and leaves after
pathogen elicitor perception
Perception () is the organization, identification, and interpretation of sensory information in order to represent and understand the presented information or environment. All perception involves signals that go through the nervous system ...
, is why it is proposed, that plants possess an NAE-
signaling pathway with functional similarities to the “endocannabinoid” pathway of animal systems, and this pathway, in part, participates in
xylanase
Endo-1,4-β-xylanase (EC 3.2.1.8, systematic name 4-β-D-xylan xylanohydrolase) is any of a class of enzymes that degrade the linear polysaccharide xylan into xylose, thus breaking down hemicellulose, one of the major components of plant cel ...
elicitor
perception
Perception () is the organization, identification, and interpretation of sensory information in order to represent and understand the presented information or environment. All perception involves signals that go through the nervous system ...
in the tobacco plant, as well as in the
Arabidopsis
''Arabidopsis'' (rockcress) is a genus in the family Brassicaceae. They are small flowering plants related to cabbage and mustard. This genus is of great interest since it contains thale cress (''Arabidopsis thaliana''), one of the model organis ...
and ''
Medicago truncatula
''Medicago truncatula'', the barrelclover, strong-spined medick, barrel medic, or barrel medick, is a small annual legume native to the Mediterranean region that is used in genomic research. It is a low-growing, clover-like plant tall with trifol ...
'' plant
tissues.
Medical values
N-acylethanolamines (NAEs), with its
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
-protective and
stress-
combating action-response of organisms, also produced in
neurons, together with
N-acyl-phosphatidylethanolamine
''N''-Acylphosphatidylethanolamines (NAPEs) are hormones released by the small intestine into the bloodstream when it processes fat. NAPEs travel to the hypothalamus in the brain and suppress appetite. This mechanism could be relevant for treating ...
(NAPE), in response to the high
intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
Ca2+ concentrations that occur in injured neurons, have showed promise as therapeutic potential in treating
bacterial
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
,
fungal, and
viral infections, as NAEs also exhibit
anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as op ...
,
antibacterial
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
, and
antiviral properties, which have considerable application potential.
In
pediatric medicine for conditions including “non-organic
failure-to-thrive” and
cystic fibrosis.
A dysfunction of the endocannabinoid system is researched for a possible determining factor for causing
infertility in cystic fibrosis (CF), as the
illness is associated with an imbalance of
fatty acids, show that mild stimulation of the endocannabinoid system (CB1 and CB2) in
infancy and
adolescence
Adolescence () is a transitional stage of physical and psychological development that generally occurs during the period from puberty to adulthood (typically corresponding to the age of majority). Adolescence is usually associated with t ...
, appears to normalize many reproductive processes and prevent infertility in CF males. The mild stimulated, were fully fertile, producing offspring comparable by the number of litters and the number of pups as the wild-type mice, and there counterparts, not treated, were shown completely infertile.
As NAE related Cannabis has an
ancient
Ancient history is a time period from the beginning of writing and recorded human history to as far as late antiquity. The span of recorded history is roughly 5,000 years, beginning with the Sumerian cuneiform script. Ancient history cove ...
tradition of usage as a medicine in
obstetrics and gynecology, its extracts, may represent an efficacious and safe alternative for treatment of a wide range of conditions in
women including
dysmenorrhea
Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in the ...
,
dysuria,
hyperemesis gravidarum
Hyperemesis gravidarum (HG) is a pregnancy complication that is characterized by severe nausea, vomiting, weight loss, and possibly dehydration. Feeling faint may also occur. It is considered more severe than morning sickness. Symptoms often get ...
, and
menopausal symptoms.
It has been found that
social contact increases, whereas
isolation decreases, the production of the
endogenous marijuanna-like
neurotransmitter, NAE 20:4 (AEA), in
nucleus accumbens
The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for "nucleus adjacent to the septum") is a region in the basal forebrain rostral to the preoptic area of the hypotha ...
(NAc), which regulate
motivated behavior, and this NAE 20:4 (AEA) production is via
oxytocin
Oxytocin (Oxt or OT) is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. It plays a role in social bonding, reproduction, childbirth, and the period after childbirth. Oxytocin ...
, the
neuropeptide
Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like t ...
reinforcing
parental and social
bonding. Activation of CB1
cannabinoid receptor
Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid recept ...
s in NAc, are necessary and sufficient to express the
rewarding
The reward system (the mesocorticolimbic circuit) is a group of neural structures responsible for incentive salience (i.e., "wanting"; desire or craving for a reward and motivation), associative learning (primarily positive reinforcement and class ...
properties of social interactions, i.e.
social contact reward. In addition, CB1 activation also suppresses release of
serotonin,
dopamine,
acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts ...
and
noradrenaline, which are mediating the characteristic
cognitive
Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, though ...
and
antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, heada ...
effects. As well as
norepinephrine release,
as it is suggested that a major function of the ECS also lies in buffering the
symphatico-
adrenergic
Adrenergic means "working on adrenaline (epinephrine) or noradrenaline (norepinephrine)" (or on their receptors). When not further qualified, it is usually used in the sense of enhancing or mimicking the effects of epinephrine and norepinephrine in ...
response to stress.
To use in expected
global heating
Global means of or referring to a globe and may also refer to:
Entertainment
* ''Global'' (Paul van Dyk album), 2003
* ''Global'' (Bunji Garlin album), 2007
* ''Global'' (Humanoid album), 1989
* ''Global'' (Todd Rundgren album), 2015
* Bruno ...
scenario, in a catastrophic “hothouse Earth,” possible well beyond the control of
humans
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
, where "
wet bulb temperatures," taken by a thermometer wrapped in a wet cloth, show temperatures of 35C or higher, and considered the limit to human survival and heighten
humidity makes it harder for people to cool down via
sweating,
coursed by the
pollution of the
troposphere, that tight holds 99% of human made solid
particle pollution, and keeps
CO2 in it for more than 100 years, for citizens who cant afford an
air-condition unit, to
cool down
Cooling down (also known as limbering down or warming down) is an important transition, done after intense activity, to allow the body to gradually return to resting or near-resting state. Depending on the intensity of the exercise, cooling down a ...
and prevent
heatstroke
Heat stroke or heatstroke, also known as sun stroke, is a severe heat illness that results in a body temperature greater than , along with red skin, headache, dizziness, and confusion. Sweating is generally present in exertional heatstroke, b ...
with an elevated core
body temperature
Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...
above 40℃ with
neurologic
Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal c ...
dysfunctions, that can lead to a syndrome of multiple
organ defect, and
cell stress, as it is found, that the CB1 receptor activation, here by a phytocannabinoid Δ9-THC administration, induces profound
hypothermia, that is rapid in onset, persistent for 3–4 hours, dose-dependent and is accompanied by a reduction in
oxygen (O)
consumption
Consumption may refer to:
*Resource consumption
*Tuberculosis, an infectious disease, historically
* Consumption (ecology), receipt of energy by consuming other organisms
* Consumption (economics), the purchasing of newly produced goods for curren ...
, which indicate reduced
heat production, as opposed to increased
heat loss
Heat transfer is a discipline of thermal engineering that concerns the generation, use, conversion, and exchange of thermal energy (heat) between physical systems. Heat transfer is classified into various mechanisms, such as thermal conduction, ...
.
* → THCA:
COOH: C
22H
30O
4 (heating/storage) → THC:
C21 H30 O2 → THC-OH: C
21H
30O
3 → THC:COOH: C
21H
28O
4 → profound hypothermia accompanied by a reduction in oxygen consumption
In metabolism of THCA from fresh plant
material
Material is a substance or mixture of substances that constitutes an object. Materials can be pure or impure, living or non-living matter. Materials can be classified on the basis of their physical and chemical properties, or on their geologica ...
used
orally, is conversion to Delta9-THC not observed:
THCA:
COOH: C
22H
30O
4 →
THC
Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC'' ...
-
OH: C
21H
30O
3 →
THC
Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC'' ...
:COOH: C
21H
28O
4
To be protected where
head injury
A head injury is any injury that results in trauma to the skull or brain. The terms ''traumatic brain injury'' and ''head injury'' are often used interchangeably in the medical literature. Because head injuries cover such a broad scope of inju ...
is a possibility, as a positive THC screen is associated with significant decreased
mortality
Mortality is the state of being mortal, or susceptible to death; the opposite of immortality.
Mortality may also refer to:
* Fish mortality, a parameter used in fisheries population dynamics to account for the loss of fish in a fish stock throug ...
in adult patients sustaining
traumatic brain injury (TBI), as research work, by a 3-year retrospective review of registry data at a
Level I center of patients sustaining TBI, find mortality in the THC(+) group (2.4%
patients significantly decreased compared with the THC(-) group (11.5%
2 in 446 cases meeting all inclusion criteria.
And further have shorter hospital
length of stay (LOS) and shorter
ventilator
A ventilator is a piece of medical technology that provides mechanical ventilation by moving breathable air into and out of the lungs, to deliver breaths to a patient who is physically unable to breathe, or breathing insufficiently. Ventilators ...
days, than THC(-) patients sustaining TBI. For severely injured trauma patients with
Injury Severity Score ≥16, a THC(+) screen show significantly lower
intensive care unit LOS and mortality (19.3% versus 25.0%) than THC(-) patients, shown by 4849 patients included at two large regional trauma centers between 2014 and 2018.
As the fatty acid amide hydrolase (FAAH) have showed significant decreased in
bhang
Bhang (IAST: ''Bhāṅg'') is an edible preparation made from the leaves of the cannabis plant originating from the Indian subcontinent. It has been used in food and drink as early as 1000 BC in ancient India. Bhang is traditionally distribu ...
users as compared to controls, and indicating that the decrease in FAAH protein level is closely related to the duration of bhang use, and further revealed that the bhang–induced
immunotoxicity, could be attributed to decrease in FAAH protein, bhang could also be a healthy drink/preparation to suppress an overactive
immune response.
A
molecular mechanism through which NAE 20:4 (AEA) plant competitive substitute THC cannabinoid molecules can affect the development of
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As ...
, the leading cause of
dementia, or its impact:
THC:
C21 H30 O2 → THC-OH: C
21H
30O
3 → THC:COOH: C
21H
28O
4 → a significantly superior inhibitor of
Amyloid beta
Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is ...
(Aβ) aggregation compared to
approved drugs prescribed for the treatment of Alzheimer's disease in 2008, through which these molecules directly can affect the development by inhibiting the enzyme
acetylcholinesterase
Acetylcholinesterase ( HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acet ...
(AChE), which prevent AChE-induced amyloid β-
peptide (Aβ) aggregation, as they are able to bind to the
anionic
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...
site of AChE, a region involved in and critical for
amyloid
Amyloids are aggregates of proteins characterised by a fibrillar morphology of 7–13 nm in diameter, a beta sheet (β-sheet) secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the hum ...
formation.
Evidence indicates that several classes of
pharmaceuticals
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and r ...
upregulate the endocannabinoidome, including
analgesic
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It i ...
s (
acetaminophen
Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol.
At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
,
non-steroidal anti-inflammatory drugs (NSAIDs),
opioids,
glucocorticoids),
antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, heada ...
s,
antipsychotic
Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...
s,
anxiolytic
An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxi ...
s, and
anticonvulsant
Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment o ...
s. Clinical interventions characterized as “
complementary and alternative medicine
Alternative medicine is any practice that aims to achieve the healing effects of medicine despite lacking biological plausibility, testability, repeatability, or evidence from clinical trials. Complementary medicine (CM), complementary and al ...
” also upregulate this system:
massage
Massage is the manipulation of the body's soft tissues. Massage techniques are commonly applied with hands, fingers, elbows, knees, forearms, feet or a device. The purpose of massage is generally for the treatment of body stress or pain. In Eu ...
and
chiropractic
Chiropractic is a form of alternative medicine concerned with the diagnosis, treatment and prevention of mechanical disorders of the musculoskeletal system, especially of the spine. It has esoteric origins and is based on several pseudosc ...
,
acupuncture
Acupuncture is a form of alternative medicine and a component of traditional Chinese medicine (TCM) in which thin needles are inserted into the body. Acupuncture is a pseudoscience; the theories and practices of TCM are not based on scientifi ...
,
dietary supplements, and
herbal medicines. Lifestyle modification, like
diet
Diet may refer to:
Food
* Diet (nutrition), the sum of the food consumed by an organism or group
* Dieting, the deliberate selection of food to control body weight or nutrient intake
** Diet food, foods that aid in creating a diet for weight loss ...
,
weight control,
exercise,
mindfulness like
yoga and
meditation, and the use of
psychoactive substances
A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior.
Th ...
, like
alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
,
tobacco
Tobacco is the common name of several plants in the genus ''Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the chie ...
,
coffee, and
cannabis
''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: ''Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternativel ...
, beside
general anaesthesia
General anaesthesia (UK) or general anesthesia (US) is a medically induced loss of consciousness that renders the patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general ...
regimens (i.e.
propofol,
etomidate
Etomidate (USAN, INN, BAN; marketed as Amidate) is a short-acting intravenous anaesthetic agent used for the induction of general anaesthesia and sedation for short procedures such as reduction of dislocated joints, tracheal intubation, cardiove ...
,
sevoflurane,
isoflurane
Isoflurane, sold under the brand name Forane among others, is a general anesthetic. It can be used to start or maintain anesthesia; however, other medications are often used to start anesthesia rather than isoflurane, due to airway irritation wi ...
,
sufentanil
Sufentanil, sold under the brand names Dsuvia and Sufenta, is a synthetic opioid analgesic drug approximately 5 to 10 times as potent as its parent drug, fentanyl, and 500 times as potent as morphine. Structurally, sufentanil differs from fe ...
), and
Insulin medication and
intraoperative
The perioperative period is the time period of a patient's surgical procedure. It commonly includes ward admission, anesthesia, surgery, and recovery. Perioperative may refer to the three phases of surgery: preoperative, intraoperative, and posto ...
doses of
insulin,
do also modulate it, either by being a FAAH inhibitor, that blocks the breakdown of NAE 20:4 (AEA), and/or enhance or lowering its production, and/or by activate or inactivate the receptors connected, as
arachidonic acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...
(C
20H
32 O2; 20:4, ω-6), the precursor of NAE 20:4 (AEA) and other eCBs, is present in every
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
membrane of the body, and their on demand
synthesis
Synthesis or synthesize may refer to:
Science Chemistry and biochemistry
* Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors
**Organic synthesis, the chemical synthesis of organ ...
is regulated by
electrical
Electricity is the set of physical phenomena associated with the presence and motion of matter that has a property of electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as described ...
activity and
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...
(
Ca2+) shifts.
The evolutionary harm reduction program
The central
thesis
A thesis ( : theses), or dissertation (abbreviated diss.), is a document submitted in support of candidature for an academic degree or professional qualification presenting the author's research and findings.International Standard ISO 7144: ...
is, that
harm reduction
Harm reduction, or harm minimization, refers to a range of public health policies designed to lessen the negative social and/or physical consequences associated with various human behaviors, both legal and illegal. Harm reduction is used to de ...
is not only a
social concept, but also a
biological
Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary in ...
one. More specifically,
evolution does not make
moral distinctions in the selection process, but utilizes a cannabis-based approach, seen from the oldest
pollen, where ''
Cannabis
''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: ''Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternativel ...
'' and ''
Humulus''
diverged between 18.23 mya and 27.8 mya ago, and consistent with Cannabis dated to 19.6 ago (
Ma), in
northwestern China, and converge on the northeastern
Tibetan Plateau, in the general vicinity of
Qinghai Lake, which is deduced as the Cannabis centre of origin, and co-localizes with the first
steppe community that evolved in
Asia
Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an area ...
, or
Yunnan, in
the southwest of
China, also identified as "the birthplace of
tea
Tea is an aromatic beverage prepared by pouring hot or boiling water over cured or fresh leaves of ''Camellia sinensis'', an evergreen shrub native to East Asia which probably originated in the borderlands of southwestern China and norther ...
... the first area where humans
figured out that eating tea leaves or brewing a cup could be
pleasant", and helpful, by its cannabimimetic bioactivity of
catechin
Catechin is a flavan-3-ol, a type of secondary metabolite providing antioxidant roles in plants. It belongs to the subgroup of polyphenols called flavonoids.
The name of the catechin chemical family derives from '' catechu'', which is the tanni ...
derivatives occurring in tea leaves, as the region of origin, to harm reduction in order to promote
survival of the fittest
"Survival of the fittest" is a phrase that originated from Darwinian evolutionary theory as a way of describing the mechanism of natural selection. The biological concept of fitness is defined as reproductive success. In Darwinian terms, th ...
. Evidence provided from peer-reviewed scientific literature supports the hypothesis, that humans, and all
animal
Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...
s, since the primordial
CB receptor evolved at least 600 million years ago; a date that broadly consistent with the
Cambrian
The Cambrian Period ( ; sometimes symbolized Ꞓ) was the first geological period of the Paleozoic Era, and of the Phanerozoic Eon. The Cambrian lasted 53.4 million years from the end of the preceding Ediacaran Period 538.8 million years ago ( ...
explosion, make and use internally produced cannabis-like products (endocannabinoids) as part of the evolutionary harm reduction program. More specifically, endocannabinoids
homeostatically regulate all
body systems (
cardiovascular
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, t ...
,
digestive,
endocrine
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neur ...
,
excretory
Excretion is a process in which metabolic waste
is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after le ...
,
immune,
nervous,
musculo-skeletal,
reproductive
The reproductive system of an organism, also known as the genital system, is the biological system made up of all the anatomical organs involved in sexual reproduction. Many non-living substances such as fluids, hormones, and pheromones are al ...
),
and modulating endocannabinoid activity have therapeutic potential in almost all diseases affecting humans.
Therefore, the health of each individual is dependent on this system are working appropriately,
and imagine what could be achieved if signaling through these receptors could be controlled:
happy,
slim
Slim or SLIM may refer to:
Arts and entertainment Fictional characters
* Slim Goodbody, a fictional character who teaches about anatomy
* Slim, one of the alien antagonists of the 1988 film '' Killer Klowns from Outer Space''
* Slim, the Pixl fro ...
, and
healthy people who remember that they're pain-free,
by
forgetting
Forgetting or disremembering is the apparent loss or modification of information already encoded and stored in an individual's short or long-term memory. It is a spontaneous or gradual process in which old memories are unable to be recalled from ...
, and ignore it, achieved though cannabis, the evolutionary byproduct of a plant that evolved to affect the
ECS and to become its natural
key
Key or The Key may refer to:
Common meanings
* Key (cryptography), a piece of information that controls the operation of a cryptography algorithm
* Key (lock), device used to control access to places or facilities restricted by a lock
* Key (ma ...
, stemming back to aquatic species 400 million years before the arrival of plants and trees.
Cosmic birth of NAE elements by star death
NAE 20:4 (AEA:
C22 H37 NO2; 20:
4,
ω-6) is the amide of
arachidonic acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...
(C
20H
32 O2; 20:4, ω-6) and
ethanolamine (MEA: C
2H
7NO).
NAE 20:5 (EPEA: C
22H
35NO
2; 20:5, ω-3) or Anandamide (20:5, n-3). It is the amide of
eicosapentaenoic acid (EPA: C
20H
30O
2; 20:5, ω-3)
NAE 22:6 (DHEA: C
24H
37NO
2; 22:6, ω-3), or Anandamide (22:6, n-3) "synaptamide", is the amide of
docosahexaenoic acid (DHA: C
22H
32O
2; 22:6,
ω-3) and ethanolamine (MEA: C
2H
7NO)
In the heart of a heavy
star
A star is an astronomical object comprising a luminous spheroid of plasma held together by its gravity. The nearest star to Earth is the Sun. Many other stars are visible to the naked eye at night, but their immense distances from Earth ma ...
, like
Betelgeuse
Betelgeuse is a red supergiant of spectral type M1-2 and one of the largest stars visible to the naked eye. It is usually the tenth-brightest star in the night sky and, after Rigel, the second-brightest in the constellation of Orio ...
, and in its
core
Core or cores may refer to:
Science and technology
* Core (anatomy), everything except the appendages
* Core (manufacturing), used in casting and molding
* Core (optical fiber), the signal-carrying portion of an optical fiber
* Core, the central ...
, is where all the ingredients of
life (and elements of NAEs) are found made. Deep in its core, the star will fight a futile battle against its own
gravity, as it tries to stop itself collapsing under its own weight, is where new
elements are made in a sequence of separate stages.
Stage one, is while there is still a supply of
hydrogen (H) to
burn
A burn is an injury to skin, or other tissues, caused by heat, cold, electricity, chemicals, friction, or ultraviolet radiation (like sunburn). Most burns are due to heat from hot liquids (called scalding), solids, or fire. Burns occur mainl ...
. As the star burn in hydrogen to
helium (He) in the core, are vast amounts of
energy released and that energy escapes and thereby creating an outward
pressure, which balances the force of gravity, and holds the star off and keeps it stable. But the hydrogen (H) in the core will eventually run out, and the
fusion reaction
Nuclear fusion is a reaction in which two or more atomic nuclei are combined to form one or more different atomic nuclei and subatomic particles (neutrons or protons). The difference in mass between the reactants and products is manifest ...
s will stop and no energy will be released, and the outward pressure will disappear, and the core will start to collapse and very rapidly leaving a
shell
Shell may refer to:
Architecture and design
* Shell (structure), a thin structure
** Concrete shell, a thin shell of concrete, usually with no interior columns or exterior buttresses
** Thin-shell structure
Science Biology
* Seashell, a hard o ...
of hydrogen (H) and helium (He) behind.
Beneath this shell, as the core collapses, the temperature rises again until at a hundred million
degrees, the stage two stars and
helium nuclear begin to fuse together.
Helium fusion does two things. First, it releases more energy so the collapse is halted, and secondly it produce two more elements in that process.
Carbon (C) and
oxygen (O), two elements vital for
life (and molecules in the NAE structure), with further collapses until it eventually form
iron (Fe). And when that happens, the star collapses around itself. And, through a
nebula
A nebula ('cloud' or 'fog' in Latin; pl. nebulae, nebulæ or nebulas) is a distinct luminescent part of interstellar medium, which can consist of ionized, neutral or molecular hydrogen and also cosmic dust. Nebulae are often star-forming region ...
,
meteorites and
comet impact, this is where all the carbon, hydrogen, oxygen etc. in the NAE molecular structure come from, and every
atom particle
In the physical sciences, a particle (or corpuscule in older texts) is a small localized object which can be described by several physical or chemical properties, such as volume, density, or mass.
They vary greatly in size or quantity, from s ...
in every living thing on the
planet earth, was probably produced in and carried from the elements of a
dying star.
And due to the chemical ability to build
chains and
rings, carbon (C) forms with quite a few other elements, like hydrogen (H), oxygen (O), nitrogen (N),
phosphorus (P) and
sulfur (S) the basis of the myriad of the chemical compounds,
proteins,
DNA,
carbohydrates,
lipids, etc. of living organisms.
NASA-funded
scientists have evidenced, that some building blocks of DNA, a nucleic acid, and the molecule that carry Genetic code, genetic instructions for life, found in meteorites, were likely created in Universe, space. The research supports the theory, that a "kit" of finished parts created in space and delivered to Earth by Meteorite fall, meteorite and Impact event, comet impact, has aided the Abiogenesis, origin of life.
A simulated Comet impact on the surface of the
earth, as it probably would look like 3.8 billion years ago at the Late Heavy Bombardment, late heavy bombardment, show that
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s (i.e. Organic compound, organic compounds arisen from
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent suc ...
(-NH2) and
carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
(-COOH) functional groups, producing
proteins) in
water is able to make peptide bonds (i.e. bonds from the carboxyl group of one amino acid to the amino group of the other amino acid), and
peptides from the heat of the impact through Earth's atmosphere, and this could be a spark to early life on earth.
Using the samples returned by the spacecraft Stardust (spacecraft), Stardust, other scientists discovered the amino acid glycine (C
2H
5NO
2) fully formed in a comet tail, but this glycine was not like this on Earth; it was built with some subtle differences - traces of
COOH's important presence and Interstellar medium, interstellar heritage, as well as strengthened the theory of panspermia, which claims that these "seeds" of life are widespread throughout the universe, and among the most widespread and versatile signaling molecules ever discovered.
Further other scientists have used the radio telescope (Green Bank Telescope, GBT) in West Virginia to study a giant Interstellar cloud, cloud of gas about 25,000 light-years from Earth, near the center of our Milky Way. The chemicals found in the cloud include one molecule that is thought to be a precursor to a key element in DNA and another that may have a role in the formation of the
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
, alanine (Ala: C
3H
7NO
2).
Cyanomethanimine (C
2H
2N
2), is a step in the process that is believed to produce adenine (C
5H
5N
5), one of the four nucleobases that make up the "step" of the ladder-like structure of
DNA. The second molecule, called ethanamine (C
5H
5N), is thought to play a role in the formation of alanine (Ala - C
3H
7NO
2), one of the twenty
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s in the genetic code.
Big Bang, * → An
atom consists of a nucleus, the atom nucleus, and a shell. The atom's Electric charge, positively charged Particle physics, particles, Proton, protons, lie in the nucleus and consist of the smallest building blocks we know of in the universe, called Quark, quarks, which are held together by Gluon, gluons, are everywhere. Along with the protons are Neutron, neutrons, which are neutral. Outside the nucleus is the mantle, where the atom's negatively charged particles, Electron, electrons, interact (in the form of standing waves), and is the absolute smallest part of an element, that can exist independently, but is most often bound to other atoms that can either belong to the same element or other elements, thereby forming a molecule.
With a spike on a graph, an entourage effect and
retrograde signaling
Retrograde signaling in biology is the process where a signal travels backwards from a target source to its original source. For example, the nucleus of a cell is the original source for creating signaling proteins. During retrograde signaling, ins ...
, by the motto “Science for Peace", and, also in the spirit of Niels Bohr, the Danish physicist with the first relatively correct model of how an atom looks like, - an international group of about 6000 researchers connected at CERN, by a particle accelerator located 100 meters underground, called LHC Large Hadron Collider, Large Hadron Collider 1, which consists of a 27 km long tube in a circle, that can accelerate protons to near the speed of light and smash them together, demonstrated on 4 July 2012 the existence of the Higgs boson, Higgs particle, a manifestation of the existence of the Higgs field - an Invisibility, invisible field in the entire Universe (symmetry breaking), believed to have emerge at about 1 picosecond (10
−12 s) after the Big Bang, and required for Atom, atoms and other structures to form, as well as for Nuclear reaction, nuclear reactions in stars, such as our Sun and
Betelgeuse
Betelgeuse is a red supergiant of spectral type M1-2 and one of the largest stars visible to the naked eye. It is usually the tenth-brightest star in the night sky and, after Rigel, the second-brightest in the constellation of Orio ...
. As so, the Higgs field is responsible for this symmetry breaking, and which all particles pass through, and which provide them their mass and thereby, weight, and without this field, all particles and elements in the NAE-structure, would be moving around at the speed of light, because they didn't have a mass, and they and living nature, wouldn't be able to exist.
See also
* Fatty acid desaturase
*Retrograde signaling
*Endocannabinoid system
*Cannabis in pregnancy
*Evolutionary history of life
*Evolutionary history of plants
*Hemp oil, Hemp seed oil
*Hemp#Nutrition, Hemp seed protein
*COX-2 inhibitors
References
External links
N-Acylphosphatidylethanolamines (NAPEs), N-acylethanolamines (NAEs) and Other Acylamides: Metabolism, Occurrence and Functions in Plants Center for Plant Lipid Research, Department of Biological Sciences, University of North Texas, Denton, TX, USA
{{DEFAULTSORT:Acylethanolamine, N-
Fatty acid amides
Lipids