Is omega 3 deficit linked with depression?
February 4th 2011 20:57
The link between deficits of omega-3 poly-unsaturated fatty acids (AGPO-3) and the onset of depressive disorders is not new in the medical field. However, what has not been known until now is the brain mechanism by which diet can condition mental health to a certain extent. Research undertaken by scientists in Bordeaux (France) and at the Faculty of Medicine and Odontology of the University of the Basque Country (UPV/EHU, Spain) and published in Nature Neuroscience, provides new clues to understanding this phenomenon.
The name of the research work, 'Omega-3 nutritional deficiencies annul the neuronal functions of the endocannabinoid system' describes the research findings, endocannabinoid system being linked to the onset of depressive disorders.
According to Doctor Susana Mato, researcher in the Ramón y Cajal programme, attached to the Neurosciences Department of the Faculty of Medicine and Odontology at the UPV/EHU and member of the Neurobiology Group, "we have observed that, in mice subjected to a diet low in omega-3 poly-unsaturated fatty acids, they have lower AGPO-3 brain levels, and this fact is associated with an alteration in the functioning of the endocannabinoid system". More concretely, the researcher points to the confirmation of "the existence of a deficit in the signalling of the CB1 cannabinoid receptor in the prefrontal cortex of the brain. This protein — the CB1 cannabinoid receptor — has been linked, over the last decade and in various studies, to depressive disorders."
Doctor Rafael Rodríguez-Puertas, research worker responsible for the Neurochemical and Neurodegeneration team at the Faculty of Medicine and Odontology at the UPV/EHU, points out that "certain forms of synaptic plasticity — a change in the efficiency of neuronal communication — measured by the brain's endocannabinoid system, disappear specifically from certain zones of the brains of mice with AGPO-3 deficit".
Despite several example in the scientific literature referring to the existence of a link between the low presence of AGPO-3 in the diet and depressive disorders, Susana Mato recognises that "little more is known about how modern Western diets, poor in AGPO-3, affect brain function and what might be the reason for a greater rate of depression associated with a deficit of these fatty acids".
As doctor Rodríguez-Puertas points out, "thanks to the results of this research new possibilities are opened up for undertaking deeper research, such as how diet modifies the functioning of the brain in general and the endocannabinoid system in particular, and how this is linked to mental disorders".
It also, "reinforces the idea that manipulating the endocannabinoid system can be useful for the treatment of depressive disorders, although the data we have up to now is very green for us to say what would be the ideal way to do so", pointed out Dr Mato.
The research work started with two French teams located in Bordeaux and led respectively by doctors Olivier J Manzoni and Sophie Layé. They have been working for a number of years with mice which show low levels of AGPO-3 in their brain, due to a low diet in these fatty acids.
"Dr Manzoni's team discovered that the synaptic plasticity of the neuronal connections, which is mediated by endocannabinoids, disappears in these animals", pointed out Dr S. Mato. To this end, in 2008, they made contact with researchers at the Faculty of Medicine at the UPV/EHU in order to obtain their collaboration in undertaking new research in order to identify possible change sin the expression and activity of the cannabinoid receptors.
In fact, in order to draw conclusions from the study, it has been necessary to employ a large number of research techniques, amongst which were "the analysis of the brain's fatty acids, electrophysiology, autoradiography of receptors, the western blot (for quantification of proteins), the determination of levels of endocannabinoids and behaviour tests", listed Doctor Rodríguez-Puertas. "In fact", continued the researcher, "in our research team we are experts in the autoradiography of receptors technique and in anatomically identifying the activation of the receptors of the endocannabinoid system
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Cannabinoids are a class of chemical compounds which include the phytocannabinoids (oxygen-containing C21 aromatic hydrocarbon compounds found in the cannabis), and chemical compounds which mimic the actions of phytocannabinoids or have a similar structure (e.g. endocannabinoids, found in the nervous and immune systems of animals and that activate cannabinoid receptors). The most notable of the cannabinoids is ∆9-tetrahydrocannabinol (∆9-THC—the primary psychoactive compound of cannabis).[1][2]
Synthetic cannabinoids encompass a variety of distinct chemical classes: the classical cannabinoids structurally related to THC, the nonclassical cannabinoids including the aminoalkylindoles, 1,5-diarylpyrazoles, quinolines and arylsulphonamides, as well as eicosanoids related to the endocannabinoids.[1]
Contents [hide]
1 Cannabinoid receptors
1.1 Cannabinoid receptor type 1
1.2 Cannabinoid receptor type 2
2 Phytocannabinoids
2.1 Types
2.1.1 Tetrahydrocannabinol
2.1.2 Cannabidiol
2.1.3 Cannabinol
2.1.4 Cannabigerol
2.1.5 Tetrahydrocannabivarin
2.1.6 Cannabichromene
2.1.7 Double bond position
2.1.8 Length
2.1.9 Plant profile
2.2 Pharmacology
2.2.1 Plant synthesis
2.2.2 Separation
2.3 History
3 Endocannabinoids
3.1 Types of endocannabinoid ligands
3.2 Function
3.2.1 Retrograde signal
3.2.2 Range
3.3 Other thoughts
3.4 U.S. Patent # 6630507
4 Synthetic and patented cannabinoids
5 Table of natural cannabinoids
6 See also
7 References
8 Further reading
9 External links
[edit] Cannabinoid receptorsBefore the 1980s, it was often speculated that cannabinoids produced their physiological and behavioral effects via nonspecific interaction with cell membranes, instead of interacting with specific membrane-bound receptors. The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate. These receptors are common in animals, and have been found in mammals, birds, fish, and reptiles. At present, there are two known types of cannabinoid receptors, termed CB1 and CB2, with mounting evidence of more.[3] In recent study it has been found that humans have these receptors as well.
[edit] Cannabinoid receptor type 1Main article: Cannabinoid receptor type 1
CB1 receptors are found primarily in the brain, to be specific in the basal ganglia and in the limbic system, including the hippocampus. They are also found in the cerebellum and in both male and female reproductive systems. CB1 receptors are absent in the medulla oblongata, the part of the brain stem responsible for respiratory and cardiovascular functions. Thus, there is not the risk of respiratory or cardiovascular failure that can be produced by some drugs. CB1 receptors appear to be responsible for the euphoric and anticonvulsive effects of cannabis.
[edit] Cannabinoid receptor type 2Main article: Cannabinoid receptor type 2
CB2 receptors are almost exclusively found in the immune system, with the greatest density in the spleen. While found only in the peripheral nervous system, a report does indicate that CB2 is expressed by a subpopulation of microglia in the human cerebellum .[4] CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis.
[edit] PhytocannabinoidsType Skeleton Cyclization
Cannabigerol-type
CBG
Cannabichromene-type
CBC
Cannabidiol-type
CBD
Tetrahydrocannabinol-
and
Cannabinol-type
THC, CBN
Cannabielsoin-type
CBE
iso-
Tetrahydrocannabinol-
type
iso-THC
Cannabicyclol-type
CBL
Cannabicitran-type
CBT
Main classes of natural cannabinoids
Phytocannabinoids, also called natural cannabinoids, herbal cannabinoids, and classical cannabinoids, are only known to occur naturally in significant quantity in the cannabis plant, and are concentrated in a viscous resin that is produced in glandular structures known as trichomes. In addition to cannabinoids, the resin is rich in terpenes, which are largely responsible for the odour of the cannabis plant.
Phytocannabinoids are nearly insoluble in water but are soluble in lipids, alcohols, and other non-polar organic solvents. However, as phenols, they form more water-soluble phenolate salts under strongly alkaline conditions.
All-natural cannabinoids are derived from their respective 2-carboxylic acids (2-COOH) by decarboxylation (catalyzed by heat, light, or alkaline conditions).
[edit] TypesAt least 85 cannabinoids have been isolated from the cannabis plant[5] To the right the main classes of natural cannabinoids are shown. All classes derive from cannabigerol-type compounds and differ mainly in the way this precursor is cyclized.
Tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) are the most prevalent natural cannabinoids and have received the most study. Other common cannabinoids are listed below:
CBG Cannabigerol
CBC Cannabichromene
CBL Cannabicyclol
CBV Cannabivarin
THCV Tetrahydrocannabivarin
CBDV Cannabidivarin
CBCV Cannabichromevarin
CBGV Cannabigerovarin
CBGM Cannabigerol Monoethyl Ether
[edit] TetrahydrocannabinolMain article: Tetrahydrocannabinol
Tetrahydrocannabinol (THC) is the primary psychoactive component of the plant. It appears to ease moderate pain (analgetic) and to be neuroprotective. THC has approximately equal affinity for the CB1 and CB2 receptors.[6]
Delta-9-Tetrahydrocannabinol (Δ9-THC, THC) and delta-8-tetrahydrocannabinol (Δ8-THC), mimic the action of anandamide, a neurotransmitter produced naturally in the body. The THCs produce the high associated with cannabis by binding to the CB1 cannabinoid receptors in the brain.
[edit] CannabidiolMain article: Cannabidiol
Cannabidiol (CBD) is not particularly psychoactive in and of itself, and was thought not to affect the psychoactivity of THC.[7] However, recent evidence shows that smokers of cannabis with a higher CBD/THC ratio were less likely to experience schizophrenia-like symptoms.[8] This is supported by psychological tests, in which participants experience less intense psychotic-like effects when intravenous THC was co-administered with CBD (as measured with a PANSS test).[9] Cannabidiol has no affinity for CB1 and CB2 receptors but acts as an indirect antagonist of cannabinoid agonists.[10] Recently it was found to be an antagonist at the putative new cannabinoid receptor, GPR55, a GPCR expressed in the caudate nucleus and putamen.[11] Cannabidiol has also been shown to act as a 5-HT1A receptor agonist,[12] an action which is involved in its antidepressant,[13][14] anxiolytic,[14][15] and neuroprotective[16][17] effects.
It appears to relieve convulsion, inflammation, anxiety, and nausea.[18] CBD has a greater affinity for the CB2 receptor than for the CB1 receptor.[18]
CBD shares a precursor with THC and is the main cannabinoid in low-THC Cannabis strains. CBD apparently plays a role in preventing the short-term memory loss associated with THC in mammals.
[edit] CannabinolMain article: Cannabinol
Cannabinol (CBN) is the primary product of THC degradation, and there is usually little of it in a fresh plant. CBN content increases as THC degrades in storage, and with exposure to light and air. It is only mildly psychoactive. Its affinity to the CB2 receptor is higher than for the CB1 receptor.[19]
[edit] CannabigerolMain article: Cannabigerol
Cannabigerol (CBG) is non-psychotomimetic but still affects the overall effects of Cannabis. It acts as an α2-adrenergic receptor agonist, 5-HT1A receptor antagonist, and CB1 receptor antagonist.[20] It also binds to the CB2 receptor.[20]
[edit] TetrahydrocannabivarinMain article: Tetrahydrocannabivarin
Tetrahydrocannabivarin (THCV) is prevalent in certain South African and Southeast Asian strains of Cannabis. It is an antagonist of THC at CB1 receptors and attenuates the psychoactive effects of THC.[21]
[edit] CannabichromeneMain article: Cannabichromene
Cannabichromene (CBC) is non-psychoactive and does not affect the psychoactivity of THC .[7]
[edit] Double bond positionIn addition, each of the compounds above may be in different forms depending on the position of the double bond in the alicyclic carbon ring. There is potential for confusion because there are different numbering systems used to describe the position of this double bond. Under the dibenzopyran numbering system widely used today, the major form of THC is called Δ9-THC, while the minor form is called Δ8-THC. Under the alternate terpene numbering system, these same compounds are called Δ1-THC and Δ6-THC, respectively.
[edit] LengthMost herbal cannabinoid compounds are 21-carbon compounds. However, some do not follow this rule, primarily because of variation in the length of the side-chain attached to the aromatic ring. In THC, CBD, and CBN, this side-chain is a pentyl (5-carbon) chain. In the most common homologue, the pentyl chain is replaced with a propyl (3-carbon) chain. Cannabinoids with the propyl side-chain are named using the suffix varin, and are designated, for example, THCV, CBDV, or CBNV.
[edit] Plant profileCannabis plants can exhibit wide variation in the quantity and type of cannabinoids they produce. The mixture of cannabinoids produced by a plant is known as the plant's cannabinoid profile. Selective breeding has been used to control the genetics of plants and modify the cannabinoid profile. For example, strains that are used as fiber (commonly called hemp) are bred such that they are low in psychoactive chemicals like THC. Strains used in medicine are often bred for high CBD content, and strains used for recreational purposes are usually bred for high THC content or for a specific chemical balance.
Quantitative analysis of a plant's cannabinoid profile is usually determined by gas chromatography (GC), or more reliably by gas chromatography combined with mass spectrometry (GC/MS). Liquid chromatography (LC) techniques are also possible, although these are often only semi-quantitative or qualitative. There have been systematic attempts to monitor the cannabinoid profile of cannabis over time, but their accuracy is impeded by the illegal status of the plant in many countries.
[edit] PharmacologyCannabinoids can be administered by smoking, vaporizing, oral ingestion, transdermal patch, intravenous injection, sublingual absorption, or rectal suppository. Once in the body, most cannabinoids are metabolized in the liver, especially by cytochrome P450 mixed-function oxidases, mainly CYP 2C9. Thus supplementing with CYP 2C9 inhibitors leads to extended intoxication.
Some is also stored in fat in addition to being metabolized in liver. Δ9-THC is metabolized to 11-hydroxy-Δ9-THC, which is then metabolized to 9-carboxy-THC. Some cannabis metabolites can be detected in the body several weeks after administration. These metabolites are the chemicals recognized by common antibody-based "drug tests"; in the case of THC et al., these loads do not represent intoxication (compare to ethanol breath tests which measure instantaneous blood alcohol levels) but an integration of past consumption over an approximately month-long window.
[edit] Plant synthesisCannabinoid production starts when an enzyme causes geranyl pyrophosphate and olivetolic acid to combine and form CBG. Next, CBG is independently converted to either CBD or CBC by two separate synthase enzymes. CBD is then enzymatically cyclized to THC. For the propyl homologues (THCV, CBDV and CBNV), there is a similar pathway that is based on CBGV.
[edit] SeparationCannabinoids can be separated from the plant by extraction with organic solvents. Hydrocarbons and alcohols are often used as solvents. However, these solvents are flammable and many are toxic. Butane may be used, which evaporates extremely quickly. Supercritical solvent extraction with carbon dioxide is an alternative technique. Although this process requires high pressures (73 atmospheres or more), there is minimal risk of fire or toxicity, solvent removal is simple and efficient, and extract quality can be well-controlled. Once extracted, cannabinoid blends can be separated into individual components using wiped film vacuum distillation or other distillation techniques. However, to produce high purity cannabinoids, chemical synthesis or semisynthesis is generally required.
[edit] HistoryCannabinoids were first discovered in the 1940s, when CBD and CBN were identified. The structure of THC was first determined in 1964.
Due to molecular similarity and ease of synthetic conversion, CBD was originally believed to be a natural precursor to THC. However, it is now known that CBD and THC are produced independently in the cannabis plant.
[edit]
And there's more, so there is a connection, but not one that the lay person should endeavour to derive much substance from. It is not a recommendation for the general use of cannabis