::::Cannabis Research::::

This is a collection of cannabis research. Please feel free to post cannabis related articles or other research....
Lets get some reading material together... Plenty of time to pass this winter....

A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae) -- Hillig and Mahlberg 91 (6): 966 -- American Journal of Botany

http://www.amjbot.org/cgi/content/full/91/6/966
--------------
Inheritance of Chemical Phenotype in Cannabis:

http://www.genetics.org/cgi/reprint/163/1/335.pdf
---------------------
Non-acute (residual) neurocognitive effects of cannabis
use: A meta-analytic study

http://www.hnrc.ucsd.edu/publication...348art2003.pdf

"The results of our meta-analytic study failed to reveal a
substantial, systematic effect of long-term, regular cannabis
consumption on the neurocognitive functioning of users
who were not acutely intoxicated."
--------------------
CANNABIS 2002 REPORT
Ministry of Public Health of Belgium
A joint international effort at the inititative of
the Ministers of Public Health of Belgium, France, Germany,
The Netherlands, Switzerland.
Technical Report of the International Scientific Conference
Brussels, Belgium, 25/2/2002

http://www.trimbos.nl/Downloads/Engl...002_Report.pdf
-------------------------
VAPORIZATION AS A SMOKELESS CANNABIS DELIVERY SYSTEM:
A PILOT STUDY

http://www.cmcr.ucsd.edu/geninfo/abrams_vap_abs_1.pdf
-------------------------
THC degredation:

https://www.icmag.com/ic/showthread.php?t=47174
---------------------------
NAIHC - North American Industrial Hemp Council
A Renewable Industrial Fiber & Oil Crop

Dr. Paul G. Mahlberg's Cannabis Research

http://www.naihc.org/MahlbergArticles.html
-----------------------

http://www.cannabis-med.org/studies/study.php
-------------------

http://www.unboundmedicine.com/medli...additional=thc
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PDF-- https://www.icmag.com/ic/attachment.php?attachmentid=1712&d=1234922382

great post! thank you
subbed

Thanks pipeline for starting this one.


Here is a HUGE reference list of studies; many on cananbis, all are in full text AFAIK, just click on the link, then on the next page click on the link "Resources - fulltext document - [view]"

Search for key words "cannabis" and "cannabinoid" to find the cannabis related papers:

• http://www.beckleyfoundation.org/librarycontents.html

this is a pretty good research link...haven't explored it though...gues i'd better get busy.

Cannabis Research
Alliance for Cannabis Therapeutics
California Cannabis Research Medical Group
Cannabis Freedom Activist Network
CannabisMD
CannabisMD Reports
Cannabis.net
Cannabis Research Institute
Center for Medicinal Cannabis Research
Coalition for Compassionate Access
Coalition for Rescheduling Cannabis
Contigo-Conmigo
Drug Policy Alliance Network
Drug Reform Coordination Network
DrugScience.org
Drugtext Foundation
ElectricEmperor.com
Erowid
International Cannabinoid Research Society
Lycaeum
Marijuana Policy Project
Multidisciplinary Association for Psychedelic Studies Inc
National Organization for the Reform of Marijuana Laws
New Scientist
North American Industrial Hemp Council
Olsen Marijuana Archive
OnlinePot
Oregon Medical Marijuana Guide
Partnership for Responsible Drug Information
RxMarijuana.com
Schaffer Library of Drug Policy
Science of Medical Marijuana
UK Cannabis Internet Activists
Web Station #19

Cannabis Researchers
Abrams, Donald I
Atkinson, J Hampston
Bakalar, James B
Cavanaugh, Jay R
Coates, Thomas J
Cohen, Sidney
Conrad, Chris
Corral, Mike
Corral, Valerie Leveroni
Dreher, Melanie C
Fride, Ester
Fry, Molly
Gampel, Joanne C
Gardner, Frederick H
Glick, Ed
Grant, Igopr
Grinspoon, Lester
Killian, Rob
Krumm, Bryan A
Kubby, Steve
Leveque, Phillip
Mahlberg, Paul G
Martinez, Martin
Mattison, Andrew (deceased)
McAllister, Sean
Mechoulam, Raphael
Meng, Ian D
Mikuriya, Tod Hiro
Morgan, John P
Musty, Richard E
Nahas, Gabriel G
Notcott, William
Peele, Stanton
Podrebarac, Francis
Raich, Angel McClary
Raich, Robert A
<A href="http://www.freedomactivist.net/personsr.html#billrosen">Rosen, Bill S
Rosenthal, Ed
Roth, Michael D
Russo, Ethan B
Slikker, William, Jr
Starks, Michael
Tashkin, Donald P
Terhune, Kenneth W
Ware, Mark
Zimmer, Lynn (deceased)

hey spurr. on the same quest?

To which quest do you refer?

A couple of more resources:


International Association of Cannabinoid Medicines
(science section; includes issues of cannabis growth, etc)
http://www.cannabis-med.org/index.php?tpl=page&id=37&lng=en



Center for Medical Cannabis Research
University of California
http://www.cmcr.ucsd.edu/

All on Cannabinoids 14 pages worth

Wiki Cannabinoids: http://en.wikipedia.org/wiki/Cannabinoid Plus a bunch of web surfing sites... Enjoy, but not all at once. lol

Types
At 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
Cannabigerol

Cannabigerol (CBG) is a non-psychoactive cannabinoid found in the Cannabis genus of plants. Cannabigerol is found in higher concentrations in hemp rather than in varieties of Cannabis with high THC content (the kind used as a drug).
Cannabigerol has been found to act as a high affinity α2-adrenergic receptor agonist, moderate affinity 5-HT1A receptor antagonist, and low affinity CB1 receptor antagonist.[1] It also binds to the CB2 receptor, but whether it acts as an agonist or antagonist at this site is unknown

Cannabichromene
Cannabichromene (abbreviated as CBC) is a cannabinoid found in the cannabis plant. It bears structural similarity to the other natural cannabinoids, including tetrahydrocannabinol, tetrahydrocannabivarin, cannabidiol, and cannabinol, among others. Evidence has suggested that it may play a role in the anti-inflammatory effects of cannabis, and may contribute to the overall analgesic effects of medical cannabis. However, more research into the compound may be needed before any definite medical effects can be verified.

Cannabicyclol
Cannabicyclol (CBL) is a non-psychotomimetic cannabinoid found in the Cannabis species. CBL is a degradative product like cannabinol. Light converts cannabichromene to CBL.

Cannabivarin
Cannabivarin, also known as cannabivarol or CBV, is a non-psychoactive cannabinoid found in minor amounts in the hemp plant Cannabis sativa. It is an analog of cannabinol (CBN) with the sidechain shortened by two CH2 groups. CBV is an oxidation product of tetrahydrocannabivarin (THCV, THV).

Tetrahydrocannabivarin
Natural occurrence
THCV is found in largest quantities in Cannabis sativa subsp. sativa strains. Some varieties that produce propyl cannabinoids in significant amounts, over five percent of total cannabinoids, have been found in plants from South Africa, Nigeria, Afghanistan, India, Pakistan and Nepal with THCV as high as 53.69% of total cannabinoids.[1] They usually have moderate to high levels of both THC and Cannabidiol (CBD) and hence have a complex cannabinoid chemistry representing some of the world's most exotic cannabis varieties.[2]
Pharmaceutical properties

It has been shown to be a CB1 receptor antagonist, i.e. blocks the effects of THC.[3] In 2007 GW Pharmaceuticals announced that THCV is safe in humans in a clinical trial and it will continue to develop THCV as a potential cannabinoid treatment for type 2 diabetes and related metabolic disorders, similar to the CB1 receptor antagonist rimonabant.[4]

Cannabidivarin
Cannabidivarine (CBDV), also known as cannabidivarol, is a non-psychoactive cannabinoid found in low amounts in Cannabis sativa. It is an analog of cannabidiol (CBD), with the side-chain shortened by two CH2 groups. Under acidic conditions it isomerizes into the psychoactive cannabinoid tetrahydrocannabivarin (THCV). CBDV is the Biosynthetic precursor of THCV in the plant.
Cannabinoids, oh Cannabinoids! Even more interesting are Endocannabinoids, which are cannabinoids that are naturally occurring in the human body. Their existence is basically brand new knowledge, only having been discovered about 10 years or so ago.

In brief, endocannabinoids help regulate the amount of information that our brains get bombarded with. If you stop and consider all the stimuli out there in the world that is happening every freakin second of our waking consciousness, it is obvious that our brains wouldn't be able to handle every bit of it and still allow us to function socially. Endocannabinoids are instrumental in this regulation.

Here is the introduction from a website that explains what's goin on. Google the term endocannabinoids to find a bunch of other stuff, maybe better than this site, and less technical too:

Cannabis sativa is one of the most widely used psychoactives and has a documented history of use going back thousands of years; however, the mechanisms of its actions are only just being elucidated. Until relatively recently, the intoxicating effect of cannabis was thought to act in a way similar to ethanol. The active principle, Δ9-tetrahydrocannabinol (THC), a highly lipophilic molecule, was thought to insert itself into the lipid cell membrane of nerve cells. However, it is now known that a specific receptor in the brain selectively binds this ligand. The characteristic effects of cannabis intoxication are thus generated by intracellular changes and altered signalling of the neurons.

Different subtypes of this receptor are known to be present in the body. When these receptors were first discovered, there were no naturally-occurring molecules in the body that were known to bind them. Early fringe speculation suggested that the receptor system might have co-evolved with the ancient use of cannabis, but its natural function is not to mediate the effects of the most widely distributed and used drug of plant origin, but to interact with naturally occurring, or endogenous, cannabinoids. These cannabinoids, their receptors, and their possible roles in the normal functioning of the body are the focus of intensive research. Present evidence suggests that the endocannabinoids and their receptors constitute a widespread modulatory system that fine tunes bodily responses to a number of stimuli.



The full article can be found here: http://www.erowid.org/plants/cannabi...y2.shtml#intro
From Wiggs Dannyboy's link:
1.0 Introduction #


Cannabis sativa is one of the most widely used psychoactives and has a documented history of use going back thousands of years; however, the mechanisms of its actions are only just being elucidated. Until relatively recently, the intoxicating effect of cannabis was thought to act in a way similar to ethanol. The active principle, Δ9-tetrahydrocannabinol (THC), a highly lipophilic molecule, was thought to insert itself into the lipid cell membrane of nerve cells. However, it is now known that a specific receptor in the brain selectively binds this ligand. The characteristic effects of cannabis intoxication are thus generated by intracellular changes and altered signalling of the neurons.

Different subtypes of this receptor are known to be present in the body. When these receptors were first discovered, there were no naturally-occurring molecules in the body that were known to bind them. Early fringe speculation suggested that the receptor system might have co-evolved with the ancient use of cannabis, but its natural function is not to mediate the effects of the most widely distributed and used drug of plant origin, but to interact with naturally occurring, or endogenous, cannabinoids. These cannabinoids, their receptors, and their possible roles in the normal functioning of the body are the focus of intensive research. Present evidence suggests that the endocannabinoids and their receptors constitute a widespread modulatory system that fine tunes bodily responses to a number of stimuli.

This short review article outlines what is currently known about this system from experiments undertaken by scientists in a range of fields. The purpose of this article is not to provide a comprehensive review of all research and knowledge in the field of endocannabinoid research, but to give an overview of the system as it is currently known and to highlight several interesting areas. First, the cannabinoid receptors shall be discussed, followed by the molecules thought to selectively bind them (their ligands) under normal physiological conditions. The final section of this review focuses on some of the possible functions this recently discovered system could perform and the individual roles that the endocannabinoids and their receptors could play. An outline of the optimistic outlook for cannabinoid therapies is then given.



2.0 Cannabinoid receptors #

The first cannabinoid receptor to be discovered was characterized and cloned in 1990 from the mammalian brain1. Its structure and function resembles that of other known hormone receptors2. As of May 2003, two subtypes of the cannabinoid receptor, CB1 and CB2, have been distinguished and are expressed both in the nervous system and peripheral tissues and organs. Both subtypes belong to the seven transmembrane spanning receptor family with seven a-helices spanning the cell membrane. The intracellular loops of the receptor protein are involved with G-proteins responsible for the transduction of the intercellular signal. This G-protein-coupled receptor causes the inhibition of the enzymatic activity of adenylate cyclase responsible for the production of cyclic adenosine monophosphate (cAMP) in the cell. A large number of hormones act through G-protein-coupled receptors and so cAMP has been termed a 'second messenger' because it transmits signals originating at the surface of cells from a variety of 'first messengers' to the interior of cells.


2.1 The CB1 receptor #
The CB1 receptor is present in both the nervous system and other tissues and organs of the body. By using the imaging technique called quantitative radiography, researchers have determined that this receptor is responsible for the psychotropic actions of THC and other cannabinoids3. The primary regions where cannabinoids bind in the human brain are the basal ganglia, which control unconscious muscle movements, and the limbic system, including the hippocampus, which is involved in integrating memory. It is this last distribution that points to the reason why the most consistent effect of THC on performance is the disruption of selective aspects of short-term memory tasks, similar to patients with damage to the limbic cortical areas4.

The CB1 receptor is also present in the cerebellum, throughout the cerebral cortex and also in many parts of the body including both the male and female reproductive systems. The scarcity of receptors in the medulla oblongata, responsible for controlling respiratory and cardiovascular functions, explains the virtual absence of reports of fatal cannabis overdose in humans5.


2.2 The CB2 receptor #
Three years after the discovery of CB1, a second human cannabinoid receptor, CB2, was identified in the marginal zone of the spleen6. The CB2 receptor is homologous to the CB1 receptor, sharing an overall 44% homology with CB17. It is confined to the immune system with its greatest density in the region where it was first discovered8. It is this form of the receptor that is expressed on T-cells of the immune system9 but is not expressed in the central nervous system (CNS) or, like the CB1 receptor, in the liver, lungs or kidneys.

The existence of two homologous receptor subtypes, with moderate to low sequence identity, allowed for the development of both agonists and antagonists selective for either type. THC is known to act as a weak, but functional, agonist of the CB2 receptor10. Exciting research is being undertaken into the possibility of developing therapeutically useful compounds that selectively bind the CB2 receptor. These compounds could perform their beneficial function without their potentially unwanted, psychotropic side effects.


2.3 The possibility of CBn receptors #
Although no further subtypes have been discovered, it is possible that other cannabinoid receptors may exist. Advances in molecular biology, including the possibility of in silico screening of complete gene libraries, may uncover CBn (that is, neither CB1, nor CB2) receptors with low amino acid sequence homology to the cloned receptors. Indirect evidence also supports the existence of as yet undiscovered receptors both in the periphery and the brain. It has been shown that certain compounds exert typical cannabimimetic actions, such as the down-regulation of mast cells, but this cannot be reproduced in cells transfected with either the CB1 or CB2 receptors11.

Although there has been no progress in finding CBn receptors, a functionally active short isoform has been characterized called CB1A12. The distribution of mRNA for both the CB1 and CB1A receptor has been found throughout the brain and in all peripheral tissues examined. The putative CB1A receptor is present in amounts of up to 20% that of CB1 and has been shown to exhibit all the known properties of CB1 to a slightly attenuated extent13.



3.0 Endocannabinoids #

We have seen that receptors for cannabinoids exist in the body. The presence of these receptors that selectively bind THC and other cannabinoids could only be explained by the presence of endogenous ligands that can bind them. Otherwise, it would indeed be strange that receptors exist in the body, having as their only function the binding of molecules of plant origin. Researchers thus looked for molecules in the body that utilized these orphan receptors and thereby discovered their natural functions.


3.1 Anandamide #
In 1992, Devane et al., identified the first putative endocannabinoid from porcine brain14. This ligand was later called anandamide, which is derived from the Sanskrit word for bliss (ananda) due to its possible cannabimimetic, psychotropic properties. Anandamide, or N-arachidonylethanolamine, is a modified form of arachidonic acid. It is a polyunsaturated fatty acid that serves as a common precursor for many biologically active metabolites. Although the structure of anandamide is quite different from THC, experiments have shown that it binds to cannabinoid receptors. It has also been shown to share with THC, and other cannabinoids, most of the pharmacological properties exerted both in the CNS and peripheral system. These include the basic characteristic actions in behavioral tests on rodents15. Cross-tolerance to THC also substantiates the evidence that anandamide works through the same mechanism as THC and, like THC, anandamide also increases both the affinity and number of rat cerebellum and hippocampal receptors after chronic and acute exposure16.


3.2 2-arachidonoyl-glycerol #
Because anandamide, like THC, behaves as a weak agonist at CB2 receptors, the question arose whether there may be other endogenous cannabinoids more selective for the CB2 receptor and produced in the peripheral tissues. Investigations led to the discovery of 2-arachidonoyl-glycerol from the canine gut17. This derivative of arachidonic acid was shown to bind to both CB1 and CB2 receptors.

This putative endocannabinoid caused the typical behavioral reactions in mice, affected levels of cAMP17 and had similar effects to some actions of THC in the periphery18. It has also been shown to be present in the brain of rats, at levels higher than those of anandamide19 and also in dog spleen and pancreas20.


3.3 Palmitoyl-ethanolamide #
Palmitoyl-ethanolamide, or N-(2-Hydroxyethyl)hexadecamide, is an N-acyl-ethanolamide. It is co-synthesized with anandamide in all tissues so far examined and possibly acts as an endogenous CB2 ligand. Its proposed role is that of an autocoid, or 'local hormone', capable of negatively regulating mast cell activation and inflammation [21]. It has also been reported that palmitoyl-ethanolamide can down-regulate IgE-triggered activation of cultured mast cells through the CB2 receptor present on these cells21.


3.4 Docosatetraenylethanolamide and Homo-γ-linoenylethanolamide #
Researchers looking for further endocannabinoids reasoned that other classes of chemical mediators originating from the precursor arachidonic acid, such as prostaglandins and leukotrienes, do not exist as single entities but as large families of chemically-related substances. They therefore expected that anandamide was only the first identified representative of a class of unsaturated fatty acid-derived ethanolamides that bind to the cannabinoid receptor22. Within a short period of anandamide being identified, two analogues of anandamide -- docosatetraenylethanolamide (DTEA) and homo-g-linoenylethanolamide (HLEA) were also isolated and identified. They were found to exert similar effects to both anandamide and THC in behavioral tests on rodents and also inhibited the action of adenylate cyclase through G-proteins, the action of which could be blocked by the highly specific CB1 antagonist SR 141716A 23, 24. It was therefore proposed that these substances might function as endogenous agonists at the neuronal CB1 receptor.


3.5 Oleamide #
Another putative endogenous cannabinoid, oleamide, or cis-9-octadecenoamide, has also been isolated and shown to have similar actions to anandamide in the behavioral rodent tests. This molecule is a long-chain fatty acid derivative that was first isolated from the cerebrospinal fluid of cats and humans deprived of sleep. This extract had a sleep-inducing action in mammals25, which has often been suggested for anandamide and THC because of their sedative and motor inhibitory properties.

The cannabimimetic actions of oleamide, however, cannot have been mediated though any of the known cannabinoid receptor types. Oleamide can only bind CB1 or CB2 receptors at very high concentrations never present under physiological conditions26. [This statement on oleamide binding has been disputed, see Comments.] An indirect way that oleamide could exert its cannabimimetic action could be through the competitive inhibition of the enzyme responsible for the degradation of anandamide27. This action would thus raise the concentration of the latter cannabinoid, causing its actions to be recorded. Other long-chain fatty acid ethanolamides, co-synthesized with anandamide in neurons, are also thought to have a similar function28.



4.0 Proposed roles of the endogenous cannabinoid system #

Although the distribution of receptors in the body is becoming clearer and their putative ligands becoming more fully characterized, the correlation between pathophysiological responses and the production and activation of these ligands is by no means certain. Nevertheless, from the existing data, it is possible to suggest a widespread modulatory role for the cannabinoid system, responsible for regulating a number of tasks. This system is not limited to the central nervous system but is also concerned with peripheral processes and could act to modulate neurotransmitter release and action from autonomic and sensory nerve fibers. Functions within the control of immunological, gastrointestinal, reproductive and cardiovascular performance are also indicated.


4.1 Learning and synaptic plasticity #
It has been shown that, in the brain, the CB1 receptor is one of the most abundant G-protein coupled receptors present29. Activation of these CB1 receptors suppresses the release of a number of nerotransmitters including acetylcholine, noradrenaline, dopamine, serotonin, GABA, glutamate and aspartate30, 31, 32, 33 and cannabimimetic drugs are known to produce a number of behavioral effects including the impairment of memory34, 35, 36. This could be due to CB1 receptors modulating cAMP-dependent synaptic plasticity and thereby preventing the recruitment of new synapses by inhibiting the formation of cAMP37. Due to both functional and anatomical evidence suggesting that CB1 receptors are present pre-synaptically30, 38, 39, cannabinoids may therefore act at this site to inhibit new synapse formation. This is further suggested by the observation that hippocampal presynaptic boutons assemble before the postsynaptic assembly40. Synaptic plasticity is an important property involved in a number of processes and the possibility therefore exists that endocannabinoids act to modulate changes in neuronal communication associated with brain development, learning, and also pain41.

It has recently been shown that the endogenous cannabinoid system has a central function in the extinction of aversive memories42. Aversive memories are important for the survival of an organism. These memories are kept by reinforcement but if reinforcement does not occur, the resulting behavioral response to the noxious stimuli will diminish until it no longer exists. This extinction process is also important but its mechanism is not fully known. Endocannabinoids acting through the CB1 receptor in the amygdala of the limbic system (which is known to be involved in this process43) are now thought to facilitate the memory loss through an inhibitory effect on local inhibitory networks (possibly GABA-using neurons).

The actions of endocannabinoids may be mediated by cannabinoid receptors located both pre- and post- synaptically. The activation of pre-synaptic receptors could lead to such intracellular changes that modulate the release and/or actions of other neurotransmitters, such as dopamine, acetylcholine and glutamate44, 45, 46, 47 and thereby have even further-reaching effects. In such a way, THC has been found to facilitate the release of dynorphins (endogenous opiate-like molecules), which act at opioid receptors. This action may have a role to play in the pain-reducing, or analgesic, properties of both THC and anandamide.


4.2 Pain #
Pain is initiated when a variety of physical stimuli activate specific pain receptors. The endogenous cannabinoid, anandamide, can inhibit the stimulation of one such pain receptor, the vanilloid receptor (VR1), which results in an analgesic effect. Anandamide and structurally-related lipids may also act as vanilloid receptor modulators in the regulation of various afferent stimuli such as pain reception and visceral reflexes and also efferent actions such as vasodilation and inflammation arising from the nervous signals. However, this research is currently in the preliminary stages and the natural occurrence in vivo has yet to be determined48.

Recent research has tentatively shown that THC does not affect the VR1 receptor. In other studies, when the CB1 receptor of mice was genetically eliminated, the CB1 knockout mice did not exhibit significant alterations of pain indicators49. These results, however, appear to contradict other studies that demonstrate anti-nociceptive activity produced by marijuana or THC. One possibility that may explain these apparently contradictive data may lie in the fact that THC has a high affinity for the CB1 receptor. Exogenously applied THC, such as when a subject smokes marijuana, may compete with other agonists of the CB1 receptor thus competing with anandamide for binding to the CB1 receptor. This would free endogenous anandamide and increase the concentration available to bind to the VR1 receptor and therefore provide the reported pain relief. Some anecdotal evidence suggests that users of medical marijuana become insensitive to the euphoric effects of marijuana after sustained use while still benefiting from its pain relieving properties. The mechanism proposed above may underlie this action, although the question will have to await further research before being fully clarified.


4.3 Vision #
A large amount of anecdotal evidence and several published scientific reports describe numerous effects of cannabinoids on visual perception. This includes altered thresholds of light detection and recovery from glare. The possible positions within the brain and/or retina of the eye responsible for these changes in perception are, as yet, unknown, although research has found that CB1 receptors are found in the retina of many vertebrate species50. This report also presents strong evidence for an endogenous cannabinoid signalling system in the vertebrate retina utilizing 2-arachidonoyl-glycerol and palmitoyl-ethanolamide which may act pre-synaptically to regulate the release of the neurotransmitter glutamate across synapses.


4.4 Neuroprotection #
A neuroprotective role may also exist for the acyl-ethanolamides in general and palmitoyl-ethanolamide in particular, due to their production at the sites of neuronal damage and cell death51, 52, 53, 54, 55. It is also becoming clear that CB1 receptors are present in the hypothalamus and may be responsible for the fine-tuning of pituitary hormone secretion56, 57, 58. Injection of anandamide into the ventricles of the brain led to the release of the hypothalamic hormone, corticotrophin-releasing factor-4156. This hormone ultimately leads to the production of corticosterone, a regulator of carbohydrate and protein metabolism, from the adrenal gland. Anandamide working at the hypothalamus may also inhibit the release of other hormones, such as prolactin and the luteinising, follicle stimulating and growth hormones57, 58.


4.5 Allergy and regulation of inflammation #
In addition to modulating the release of neurotransmitters and hormones, it is becoming increasingly clear that the endocannabinoid system is intimately linked to other processes in the periphery. A system may exist where endocannabinoids mediate chemical communication between different types of immune cells and between sensory fibers and blood cells. They have also been found to play an important role in acute inflammatory reactions. The standard picture of inflammatory reactions is that binding of an allergen to IgE receptors on immune cells leads to the activation of basophil and mast cells. These cells then release histamine, serotonin and leukotrienes. Within this mixture of inflammatory mediators, palmitoyl-ethanolamide and anandamide have also been discovered59. Palmitoyl-ethanolamide is thought to act as an autocoid on the same, or neighboring, basophilic or mast cells and thereby inhibits the further release of mediators60, thereby keeping the inflammatory reaction in check.

Anandamide from basophils might also increase the production of prostaglandin E2 from macrophages, which suppresses the activity and proliferation of both lymphocytes and macrophages. Anandamide could also directly inhibit the recruitment of lymphocytes during the late phase of the allergic response and induce their cell death61. It would thus appear that both palmitoyl-ethanolamide and anandamide could help to prevent the excessive propagation of the inflammatory response. This would reduce the risk of subsequent hypersensitivity to the initial stimulus and prevent the development of allergic disease54, 62. Further research is needed to determine which receptor types are expressed in the different sub-populations of each immune cell-type. It is, at present, unclear which of the immunological actions of the endocannabinoids are mediated by which cannabinoid receptor. Research directed into giving a clearer picture of receptor expression would certainly help clarify their immunomodulatory role.


4.6 Reproduction #
There are a number of other ideas for possible roles for the endocannabinoid system based on the expression of the ligands, and/or their receptors in the body. These include the very interesting observation that tissues of the reproductive system also contain receptors and are able to synthesize and degrade endocannabinoids.

It is conceivable that endocannabinoids in the reproductive system act as local hormones and evidence exists for an anandaminergic system in the rat testes and mouse vas deferens that controls spermatogenesis and male fertility63, 64, 65. THC and anandamide are also both thought to inhibit the acrosome reaction through cannabinoid receptors on the sperm cell membrane66, 67, 68. These receptors have been found on the sperm cell of the sea urchin, and the ovaries from the same species are known to synthesize and degrade both anandamide and palmitoyl-ethanolamide69. It is therefore conceivable that the sea urchin synthesizes anandamide during the acrosome reaction in order to prevent fertilization by more than one sperm. It is not yet known whether an analogous system also occurs in mammals although some evidence does point towards an increased infertility among chronic cannabis users.

Anandamide may also play another interesting role in the female reproductive system. CB1 and CB2 receptors are present in the embryos of mice from the very early stages of their development and also in the adult uterus70. Due to the inhibitory effect of anandamide on embryonic cell division, anandamide might act as a negative signal for embryonic development and implantation71. High levels of the synthesizing enzyme, and low levels of the degrading enzyme exist at the time when the uterus is the least receptive for embryo implantation. The uterus may therefore utilize anandamide in order to direct both the location and timing of embryo implantation.



5.0 Concluding remarks #

In just over one decade, the abundance of quality research has changed our basic views of the mechanism of cannabis intoxication. It has also unveiled a new and extensive regulatory system within the body. Further multidisciplinary research must be undertaken to improve our understanding of these functions and provide more data on the expression and inactivation of the components of this system. It will then be possible to exploit this knowledge in order to make therapeutic compounds for the treatment of symptoms, and possible prevention, of a number of disorders.


5.1 Therapeutic possibilities #
Such therapies could act through the agonistic/antagonistic properties of the novel compounds acting at cannabinoid receptors, or by targeting the synthesizing, or degrading, enzymes responsible for endocannabinoids. As cannabinoids are effective at countering muscle spasms, this property could be exploited to provide relief for sufferers of multiple sclerosis and patients who suffer from chronic tremors, or other involuntary movements. Ongoing research is presently determining whether cannabinoid ligands are effective agents in the treatment of chronic pain, glaucoma, spasms, and the wasting and emesis associated with AIDS and cancer chemotherapy72, 73. This latter property is currently being exploited and a cannabinoid called Nabilone is on the market, indicated for the suppression of nausea and vomiting during cytotoxic chemotherapy. The potential therapeutic application of cannabinoids is, however, controversial and constitutes a widely debated issue with relevance in both scientific and social circles.

One of the most interesting potential therapeutic actions of cannabinoids reported to date is the ability of cannabinoids to inhibit the growth of cancerous, or transformed, cells in culture. Anandamide can inhibit breast cancer cell proliferation74 and THC can cause the programmed cell death, or apoptosis, of transformed neural cells in vitro75. In vivo research has also begun to elucidate the biochemical mechanisms involved in the anti-tumoral actions of CB1 agonists, including THC76. These experiments have shown that it is possible to completely eradicate malignant brain tumors in rats by THC administration.

Cannabinoids have also been found to protect neurons in culture from glutamate-induced excitotoxicity77, 78 and from ischaemic death (lack of oxygen)79. These ligands are currently under test as therapeutic agents in the treatment of neurodegenerative diseases such as multiple sclerosis and Parkinson's Disease. Research is also being directed into the possibility of using cannabinoids as drugs that could stop the growth and spread of cancer cells, based on the research mentioned above.

A prominent researcher in the field described the discovery of anandamide as a 'new dawn for cannabinoid pharmacology'7. Although a lot of work has been conducted, we can expect far more research in the near future that could revolutionize the way we view our bodies and the treatments we use to prevent their malfunction.
http://www.suite101.com/article.cfm/...atments/104300



Cannabinoids for Cancer Treatment
Oct 31, 2003 - © David Olle


Research into the value of marijuana or its active components for use in medicine is severely limited due to federal laws that restrict its availability. Marijuana is classified as a Schedule I drug by the Drug Enforcement Administration, meaning that it has no medical use and a high potential for abuse. However, many would dispute this classification, since it has proven benefits in palliative care (treatment of symptoms of medical conditions) and holds promise of other benefits as well. This article focuses on the potential of the cannabinoids as anticancer drugs.
What are cannabinoids and how do they function?

Marijuana is a hemp plant with the scientific name Cannabis sativa. When chemists isolated the primary psychoactive compound in marijuana they named it tetrahydrocannibinol, abbreviated as THC. They subsequently found a related active compound called cannabidiol. Compounds that are structurally similar to these compounds, or have a similar effect in the body are called cannabinoids. Interestingly, cannabinoids are found naturally in the body as well, known as endocannabinoids. Examples are arandamide and arachidonolyglycerol. Researchers have found that endocannabinoids have important roles in pain, in memory, in nerve degeneration, and in inflammation.

In order carry out their effects in the body, the cannabinoids must first bind to specific receptors in the body. Receptors are protein molecules found on the cell membranes. There are two types of cannabinoid receptors, CB1 and CB2. CB1 receptors are associated with the nervous system and are found in abundance in the brain as well as other parts of the body. The psychoactive effects of cannabinoids are dependent on binding to the CB1 receptor. CB2 receptors are associated with cells and tissues related to the immune system, whose function is still not well understood. The binding of cannabinoid to its receptor results in the transmission of signals that effect changes in physiological functions.

Palliative effects

Advocates of the use of medical marijuana have long sought its use to alleviate the suffering of patients with severely debilitating and terminal diseases such as AIDS and cancer. Although many patients would prefer to smoke marijuana in order to achieve a more rapid response, physicians are not inclined to approve of this method due to its history of abuse and the known dangers of smoking. Instead, the physician administers the pure cannabinoids.

1. Pain inhibition- Cancer pain originates from inflammation, mechanical pressure from growing tumors, and nerve damage. Cannabinoids reduce pain by inhibiting neurotransmission, and may act locally by inhibiting the release of mediators of pain and inflammation.

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Oct 31, 2003 - © David Olle


2. Inhibition of nausea and vomiting - These symptoms regularly accompany the administration of chemotherapeutic drugs. Cannabinoids apparently act on the CB1 receptors located in the stomach, duodenum, and colon to reduce motility (movement) due to the release of acetylcholine. They may also act on the portion of the brainstem that controls the vomiting reflex. Although cannabinoids are quite effective for this purpose, modern drugs have been developed that are more effective than previously.
3. Appetite stimulation - More than half of the patients with advanced cancer experience lack of appetite and weight loss. Cannabinoids apparently act upon the CB1 receptors in the hypothalamus of the brain that controls food intake, and may act on receptors in nerve terminals and fat cells.

4. Psychological effects - Marijuana is taken for its psychological effects, and cannabinoids properly administered may aid in reduction of anxiety and depression and improved sleep for cancer patients. However, information about these effects is still largely anecdotal.

In 1985, the Food and Drug Administration approved the marketing of dronabinol, trade name Marinol. This product is THC, synthesized commercially rather than extracted from marijuana. It is approved for use in the treatment of nausea and vomiting associated with cancer chemotherapy, and for the treatment of loss of appetite associated with weight loss in patients with AIDS. It is classified as Schedule II (of medical benefit, but with high potential for abuse). It remains the only cannabinoid approved for medical treatment.

Antitumor effects

All evidence to date on the antitumor effects of cannabinoids is based on laboratory studies. Mouse studies have shown that lung carcinoma, glioma (brain tumors), thyroid epithelioma, lymphoma, leukemia, and skin carcinoma are sensitive to cannabinoids. In vitro (tissue culture) studies have shown effectiveness against uterine, breast, and prostate carcinomas, as well as neurocarcinoma.

How do cannabinoids exert their effect? The binding of cannabinoids to their receptors stimulates biochemical-signaling processes that result in the inhibition of tumor cell growth. The processes include increases apoptosis (programmed cell death), cell-cycle arrest (required for multiplication of cells), inhibition of angiogenesis (blood vessel growth within the tumors), and inhibition of metastasis (spread of cancer to other parts of the body).

Why should clinical trials be initiated with cannabinoids?

Cannabinoids have a favorable drug safety profile, and do not produce the generalized toxic effects of most conventional chemotherapeutic drugs. Limited studies have shown that cannabinoid treatment does not result in marked alteration of a wide array of physiological, neurological,

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Oct 31, 2003 - © David Olle


neurological, and blood tests.
The major limiting factor in cannabinoid use is their psychoactive effects. Researchers are synthesizing new cannabinoids that could circumvent this problem. Cannabinoids that bind to CB2 or other receptors have already been developed. Clinical trials are taking place in other countries on the use of cannabidiol, since this cannabinoid is less psychoactive. Another possibility would be the development of cannabinoids that do not cross the blood-brain barrier, and thus operate only in the peripheral tissues. Finally, the effectiveness of endocannabinoids could be prolonged if inhibitors of its breakdown could be developed.

References

1. Guzman, M. Cannabinoids: Potential Anticancer Agents. Nature Reviews Cancer, Vol. 3, No. 10, pp. 745-755 (October 2003)

2. Mandavilli, A. Marijuana Researchers Reach for Pot of Gold. Nature Medicine, Vol. 9, No. 10, p. 1227 (October 2003)

3. Marijuana and Medicine. Institute of Medicine, National Academy of Sciences, 1999.
endogenous cannabinoid system
From the following article:
Cannabinoids: potential anticancer agents

Manuel Guzmán

Nature Reviews Cancer 3, 745-755 (October 2003)

doi:10.1038/nrc1188

Back to article | Next Box
Plant-derived cannabinoids such as 9-tetrahydrocannabinol (THC), as well as their synthetic analogues, act in the organism by activating specific cell-surface receptors that are normally engaged by a family of endogenous ligands — the endocannabinoids (see figure). The first endocannabinoid discovered was named anandamide (AEA), from the sanscrit ananda, 'internal bliss', and with reference to its chemical structure — arachidonoylethanolamide, the amide of arachidonic acid (AA) and ethanolamine (Et)100. A second arachidonic-acid derivative (2-arachidonoylglycerol (2-AG)) that binds to cannabinoid receptors was subsequently described101, 102. These endocannabinoid ligands, together with their receptors103, 104 and specific processes of synthesis105, 106, uptake107 and degradation108, constitute the endogenous cannabinoid system.



A well-established function of the endogenous cannabinoid system is its role in brain neuromodulation. Postsynaptic neurons synthesize membrane-bound endocannabinoid precursors and cleave them to release active endocannabinoids following an increase of cytosolic free Ca2+ concentrations: for example, after binding of neurotransmitters (NTs) to their IONOTROPIC (iR) or METABOTROPIC (mR) receptors109. Endocannabinoids subsequently act as retrograde messengers by binding to presynaptic CB1 cannabinoid receptors, which are coupled to the inhibition of voltage-sensitive Ca2+ channels and the activation of K+ channels110. This blunts membrane depolarization and exocytosis, thereby inhibiting the release of NTs such as glutamate, dopamine and -aminobutyric acid (GABA) and affecting, in turn, processes such as learning, movement and memory, respectively111. Endocannabinoid neuromodulatory signalling is terminated by an unidentified membrane-transport system107 (T) and a family of intracellular degradative enzymes, the best characterized of which is fatty acid amide hydrolase (FAAH), which degrades AEA to AA and Et108. The endogenous cannabinoid system might also exert modulatory functions outside the brain, both in the peripheral nervous system and in extraneural sites, controlling processes such as peripheral pain, vascular tone, INTRAOCULAR PRESSURE and immune function.
The administration of cannabinoids to humans and laboratory animals exerts psychoactive effects7, 81, 82. In humans, cannabinoids induce a unique mixture of depressing and stimulatory effects in the central nervous system that can be divided into four groups: affective (euphoria and easy laughter), sensory (alterations in temporal and spatial perception and disorientation), somatic (drowsiness, dizziness and motor discoordination) and cognitive (confusion, memory lapses and difficulties in concentration). Owing to the ubiquitous distribution of cannabinoid receptors, cannabinoids might affect not only the brain, but also almost every body system; for example, the cardiovascular (tachycardia), respiratory (bronchodilatation), musculoskeletal (muscle relaxation) and gastrointestinal (decreased motility) systems7, 81, 82.
The central and peripheral effects of cannabinoids are variable and sometimes pronounced in those smoking cannabis for recreational purposes, but are not necessarily apparent in a controlled clinical setting. In fact, dronabinol (Marinol) and nabilone (Cesamet) are usually innocuous when administered as antiemetics to patients with cancer10, 82. Moreover, tolerance to the unwanted effects of cannabinoids develops rapidly in humans and laboratory animals81, 82. For example, the most frequently reported adverse psychoactive effects of dronabinol during clinical trials occurred in 33% of patients. This value decreased to 25% reporting minor psychoactivity after 2 weeks and 4% after 6 weeks of treatment. The possibility that tolerance also develops to therapeutically sought effects has not been substantiated. Cannabinoid tolerance is mainly attributed to PHARMACODYNAMIC changes, such as a decrease in the number of total and functionally coupled cannabinoid receptors on the cell surface, with a possible minor PHARMACOKINETIC component caused by increased cannabinoid biotransformation and excretion7, 81, 82.
Some people consider cannabinoids as addictive drugs. A withdrawal syndrome, which consists of irritability, insomnia, restlessness and a sudden, temporary sensation of heat — 'hot flashes' — has been occasionally observed in chronic cannabis smokers after abrupt cessation of drug use. However, this occurs rarely, and symptoms are mild and usually dissipate after a few days7, 81, 82. Similarly, after chronic tetrahydrocannabinol (THC) treatment, no somatic signs of spontaneous withdrawal appear in different animal species, even at extremely high doses112. Animal models of cannabinoid dependence have been obtained only after administration of an antagonist of cannabinoid receptor CB1 together with the cessation of chronic administration of high doses of THC to precipitate somatic manifestations of withdrawal112. In the clinical context, long-term surveys of dronabinol administration at prescription doses have shown no sign of dependence82, 113. The low-addictive capacity of THC is usually ascribed to its pharmacokinetic properties (Box 3) as, unlike commonly used drugs, cannabinoids are stored in adipose tissue and excreted at a low rate. So, cessation of THC intake is not accompanied by rapid decreases in drug plasma concentration82.
The route of administration affects the time course and intensity of the drug effects. At present, clinical use of cannabinoids is limited to oral administration of dronabinol and nabilone. However, absorption by this route is slow and erratic; cannabinoids might be degraded by the acid of the stomach; rates of FIRST-PASS METABOLISM in the liver vary greatly between individuals; and patients sometimes have more than one plasma peak, which makes it more difficult to control the drug effects82.
Anecdotal reports indicate that in certain patients cannabis is more effective and might have fewer psychological effects when smoked than when taken orally. However, cannabis smoke contains the same chemical carcinogens that are found in tobacco, making it potentially harmful in long-term use and difficult to investigate in clinical trials80. A safer alternative for inhaled administration of cannabinoids has been recently produced by GW Pharmaceuticals and Bayer AG. This is a medicinal cannabis extract known as Sativex, which contains tetrahydrocannabinol (THC) and cannabidiol, that is administered by spraying into the mouth and is now in clinical trials for pain and the debilitating symptoms of multiple sclerosis.
Other routes of cannabinoid administration tested so far in humans include intravenous (THC and dexanabinol in saline/ethanol/adjuvant), rectal (THC-hemisuccinate suppositories) and sublingual administration (THC- and cannabidiol-rich cannabis extracts)82. These three routes circumvent the aforementioned problems of oral administration by producing single, rapid and high drug-plasma peaks.
Owing to its high hydrophobicity, absorbed THC binds to lipoproteins and albumin in plasma and is mainly retained in adipose tissue — the main long-term THC storage site. THC is only slowly released back into the bloodstream and other body tissues, so that full elimination from the body is slow (half-life 1–3 days). THC metabolism occurs mainly by hepatic cytochrome P450 isoenzymes. The process yields 11-hydroxy-THC and many other metabolites resulting from hydroxylation, oxidation, conjugation and other chemical modifications that are cleared from the body by excretion.

An interesting paper...

But the authors left out the most important data, the 'hows' because they are douche bags and didn't want the public to have the info! LOL, like there isn't a mountain of 'how to' info for growing cannabis in the public domain already...

It's funny to read about how the scientists, who had never grown cannabis before, screwed up the crop a few times. It kind of invalids much of the data they present because they are shitty growers. But the pics and info is wroth reading.

I am trying to get their other paper that does list the 'how', such as PPFD, etc. I for one would never move to New Zealand due to their shitty laws about publishing cannabis info:

trichrider said:

this is a pretty good research link...haven't explored it though...gues i'd better get busy.

Click to expand...

Nice post man, I liked the colors and formatting

here are several more i been into lately...mostly medical and therapeutic studies...



Center for Medicinal Cannabis Research, University of California American College of Physicians Institute of Medicine
Pharmacology Biochemistry and Behavior
Annals of Internal Medicine
Cancer
Neurologist
Journal of Acquired Immune Deficiency Syndrome
Psychopharmacology
Canadian Medical Association Journal
Clinical Toxicology
Neuropsychology Review
Lancet
Current Psychiatry Reports
Current Opinion in Psychiatry
Cancer Epidemiology, Biomarkers & Prevention
http://cannabis-science.com/

although it appears that divergent catagories are competeing for space in this thread, i defer my entries to the OP with an apology for diluting or polluting your botany thread with medical links.
i shoulda read the title, got to admit i messed myself.

Some research is more botany oriented, and some is more medically oriented... Either way, I was just making a place to get everything together so users can have the info accessable, if they have a hunch they're chasing, or a specific question... Thanks for the cannabis and cancer article.... My cousin has a progressed stomach cancer and he's needing all the help he can get from cannabis....I'll forward the info...

Thanks Carl, I had not seen this yet!

I'm going to add the link to the hemp plant tissue analysis research.... Another important piece to the puzzle!

PDF
https://www.icmag.com/ic/attachment.php?attachmentid=68399&d=1279061516

Well I think I've done it..(no thanks to yall) but I think I overloaded my brain with info..But seriously thanks for the reading material, will keep me busy for a while.

pipeline said:

I'm going to add the link to the hemp plant tissue analysis research.... Another important piece to the puzzle!

Click to expand...

that's cool, I sent a message to the moderator of this forum, asking them to move it over.

spurr said:

An interesting paper...

But the authors left out the most important data, the 'hows' because they are douche bags and didn't want the public to have the info! LOL, like there isn't a mountain of 'how to' info for growing cannabis in the public domain already...

It's funny to read about how the scientists, who had never grown cannabis before, screwed up the crop a few times. It kind of invalids much of the data they present because they are shitty growers. But the pics and info is wroth reading.

"The results of an experimental indoor hydroponic Cannabis growing study, using the ‘Screen of Green’ (ScrOG) method—Yield, tetrahydrocannabinol (THC) and DNA analysis"
Glenys Knight, Sean Hansen, Mark Connor, Helen Poulsen, Catherine McGovern, Janet Stacey
Forensic Sci. Int. (2010)​

Click to expand...

Entertaining read for sure. I did some numbers for my own curiosity, figured might as well post them.

If they followed general guidelines for HID used by most cultivators here, based on the size of their room (4.32m x 3.48m) it looks like they used 6kw of light, probably 1 KW over each plant. Based on this assumption their first and best grow pulled almost .9g/w! Assuming a 9 week flowering strain, this would have put their veg time at about 8 weeks. Their 2nd and 3rd grow were .7g/w and .4g/w, the former being nuteburned, the latter being infested with "two-spotted red spider mite". Never heard of this type before, probably an accidental conflation of the two common types, red and two spotted. Or maybe some killer kiwi hybrid mite?

My favorite part of this study was that after harvest and drying and determination of yield, the cannabis was "packaged in one-ounce quantities in zip-lock plastic bags, a common quantity and packaging found to be used by indoor growers."

I fail to see the scientific merit in this step but am completely tickled by the imagery of some phd scaling zones into baggies.

edit: numbers above are for 40w/sqft (~6kw). Assuming 50 w/sqft (8kw) would reduce their efficiency to .7g/w , .6g/w and .3g/w for grows 1,2 and 3 respectively. Realistically, their canopy size was less than their room size so... pointless exercise in division I guess.

Here is another paper I thought is on topic to this thread, it deals in part with cananbis genotype and DNA testing, etc., useful info for some of us:


"Application of new DNA markers for forensic examination of Cannabis sativa seizures – Developmental validation of protocols and a genetic database"
Christopher Howard, PhD, Simon Gilmore, PhD, James Robertson, PhD, Rod Peakall, PhD
National Drug Law Enforcement Research Fund (NDLERF); (2008) Monograph Series No. 29

• I uploaded this file to an offshore (from the US) file host, it's too big to upload here. Turn off JavaScript to prevent ads from loading (or just use NoScript in Firefox), the passphrase is "ilovecanna" (without quotes): http://www.file-upload.net/download-3072098/29.zip.html

Thanks for taking the time to compile such info guys.
i found this an interesting read,,sorry if already been posted....remain in harmony

http://jxb.oxfordjournals.org/content/59/15/4171.full