Cannibinoid Curiosity

cantweight · Nov 28, 2014

Introduced cannabis oil a few weeks ago, no THC. I am having some very good response...increased energy and weight loss. I am using in conjunction with CT at least 3 times a week.

I have had to back my drops down to 12 daily, due to too much energy...over caffeinated type feeling while my son and husband are up to 15 drops feeling nothing.

I simply dont understand cannibinoid receptors enough to understand such a discrepancy...thought y'all might be able to enlighten me...or try to anyway

Jack Kruse · Nov 28, 2014

Eventually I will hit them...........LDN and cannabis are signs of a cell membrane issue.......Dec webinar will cover this.........

Josh · Nov 28, 2014

http://www.nature.com/cddis/journal/v5/n9/full/cddis2014364a.html

Spinal cord injury (SCI) is a devastating condition of CNS that often results in severe functional impairments for which there are no restorative therapies. As in other CNS injuries, in addition to the effects that are related to the primary site of damage, these impairments are caused by degeneration of distal regions that are connected functionally to the primary lesion site. Modulation of the endocannabinoid system (ECS) counteracts this neurodegeneration, and pharmacological modulation of type-2 cannabinoid receptor (CB2R) is a promising therapeutic target for several CNS pathologies, including SCI. This study examined the effects of CB2R modulation on the fate of axotomized rubrospinal neurons (RSNs) and functional recovery in a model of spinal cord dorsal hemisection (SCH) at the cervical level in rats. SCH induced CB2R expression, severe atrophy, and cell death in contralateral RSNs. Furthermore, SCH affected molecular changes in the apoptotic cascade in RSNs – increased cytochrome crelease, apoptosome formation, and caspase-3 activity. CB2R stimulation by its selective agonist JWH-015 significantly increased the bcl-2/bax ratio, reduced cytochrome c release, delayed atrophy and degeneration, and improved spontaneous functional recovery through ERK1/2 inactivation. These findings implicate the ECS, particularly CB2R, as part of the endogenous neuroprotective response that is triggered after SCI. Thus, CB2R modulation might represent a promising therapeutic target that lacks psychotropic effects and can be used to exploit ECS-based approaches to counteract neuronal degeneration.
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http://www.nature.com/neuro/journal/v15/n4/full/nn.3053.html

The mammalian brain is one of the organs with the highest energy demands, and mitochondria are key determinants of its functions. Here we show that the type-1 cannabinoid receptor (CB1) is present at the membranes of mouse neuronal mitochondria (mtCB1), where it directly controls cellular respiration and energy production. Through activation of mtCB1 receptors, exogenous cannabinoids and in situ endocannabinoids decreased cyclic AMP concentration, protein kinase A activity, complex I enzymatic activity and respiration in neuronal mitochondria. In addition, intracellular CB1 receptors and mitochondrial mechanisms contributed to endocannabinoid-dependent depolarization-induced suppression of inhibition in the hippocampus. Thus, mtCB1receptors directly modulate neuronal energy metabolism, revealing a new mechanism of action of G protein–coupled receptor signaling in the brain.
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Josh · Nov 28, 2014

http://www.hindawi.com/journals/sci/2013/796715/

Abstract
Significant loss of bone due to trauma, underlying metabolic disease, or lack of repair due to old age surpasses the body’s endogenous bone repair mechanisms. Mesenchymal stem cells (MSCs) are adult stem cells which may represent an ideal cell type for use in cell-based tissue engineered bone regeneration strategies. The body’s endocannabinoid system has been identified as a central regulator of bone metabolism. The aim of the study was to elucidate the role of the cannabinoid receptor type 1 in the differentiation and survival of MSCs. We show that the cannabinoid receptor type 1 has a prosurvival function during acute cell stress. Additionally, we show that the phytocannabinoid, -Tetrahydrocannabinol, has a negative impact on MSC survival and osteogenesis. Overall, these results show the potential for the modulation of the cannabinoid system in cell-based tissue engineered bone regeneration strategies whilst highlighting cannabis use as a potential cause for concern in the management of orthopaedic patients.
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http://www.medicinalgenomics.com/wp...nges-in-respiration-of-brain-mitochondria.pdf

A B S T R A C T
Cannabinoids exert various biological effects that are either receptor-mediated or independent of receptor
signaling. Mitochondrial effects of cannabinoids were interpreted either as non-receptor-mediated
alterationofmitochondrialmembranes, or as indirect consequences of activation ofplasmamembrane type
1 cannabinoid receptors (CB1). Recently, CB1 receptors were confirmed to be localized to the membranes of
neuronal mitochondria, where their activation directly regulates respiration and energy production. Here,
we performed in-depth analysis of cannabinoid-induced changes of mitochondrial respiration using both
an antagonist/inverse agonist of CB1 receptors, AM251 and the cannabinoid receptor agonists,
D9-tetrahydrocannabinol (THC), cannabidiol, anandamide, and WIN 55,212-2. Relationships were
determined between cannabinoid concentration and respiratory rate driven by substrates of complex I,
II or IV in pig brain mitochondria. Either full or partial inhibition of respiratory rate was found for the tested
drugs, with an IC50 in the micromolar range, which verified the significant role of non-receptor-mediated
mechanism in inhibiting mitochondrial respiration. Effect of stepwise application of THC and
AM251 evidenced protective role of AM251 and corroborated the participation of CB1 receptor activation
inthe inhibitionofmitochondrial respiration.Weproposed amodel,which includesboth receptor- andnonreceptor-mediated
mechanisms of cannabinoid action on mitochondrial respiration. This model explains
both the inhibitory effect of cannabinoids and the protective effect of the CB1 receptor inverse agonist.
ã 2014 Published by Elsevier Ireland Ltd.
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Josh · Nov 28, 2014

Figure 1. Then, because of these widespread properties of cannabinoid
compounds, targeting the ECS could represent a unique and
reliable opportunity to advance toward an effective therapy against
the AD. Moreover, cannabinoids might represent a safe low-cost
therapy, with their natural origin and low side effects profile. From
our point of view, the success of cannabinoid-based therapy in
AD could be increased taking into account two important aspects:
(i) the use of a combination of compounds that cover the whole
spectrum of therapeutic properties described for cannabinoids,
i.e., combination of CB1 and CB2 receptors agonists plus CBD,
which presents interesting neuroprotective properties spite of its
mechanism of action remaining poorly understood, and (ii) the
early initiation of the treatment in the neurodegenerative process,
which ensures the integrity of the ECS target components and
increases the possibility of curbing the exponential degenerative
progression toward dementia.
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Abstract
The limited effectiveness of current therapies against Alzheimer's disease (AD) highlights the need for intensifying research efforts devoted to developing new agents for preventing or retarding the disease process. During the last few years, targeting the endogenous cannabinoid system has emerged as a potential therapeutic approach to treat Alzheimer. The endocannabinoid system is composed by a number of cannabinoid receptors, including the well-characterized CB1 and CB2 receptors, with their endogenous ligands and the enzymes related to the synthesis and degradation of these endocannabinoid compounds. Several findings indicate that the activation of both CB1 and CB2 receptors by natural or synthetic agonists, at non-psychoactive doses, have beneficial effects in Alzheimer experimental models by reducing the harmful β-amyloid peptide action and tau phosphorylation, as well as by promoting the brain's intrinsic repair mechanisms. Moreover, endocannabinoid signaling has been demonstrated to modulate numerous concomitant pathological processes, including neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress. The present paper summarizes the main experimental studies demonstrating the polyvalent properties of cannabinoid compounds for the treatment of AD, which together encourage progress toward a clinical trial.
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http://www.ncbi.nlm.nih.gov/pubmed/24634659

Josh · Nov 28, 2014

https://www.google.com/url?sa=i&rct...X-NPz5T3evEcUKZzglEAdoDg&ust=1417316100768119

Josh · Nov 28, 2014

Looking into a bit, I am guessing that the response to cannabanoids, endogenous and exogenous, will be an issue without reliable fatty acid metabolism for both formation and degradation.A positive response might be indicative of issues related to handling Omega 6 and Arachidonic Acid precursors and or the production of the enzymes for degradation.

The characterization of CB1 and CB2 receptors permitted the discovered of endocannabinoids or cannabinoids produced and released by nerve cells. Endocannabinoids are lipid compounds of the eicosanoid family derived from the degradation of membrane phospholipids (Piomelli, 2003). The most representative are arachidonoylethanolamine (AEA), also named anandamide, and 2-arachidonoylglycerol (2-AG), although several others have also been identified, such as 2-arachidonylglyceryl ether (2-AGE), virodhamine, and N-arachidonyldopamine (Piomelli, 2003). Endocannabinoids act as neurotransmitters since they are synthesized and released by neurons, are able to bind and activate membrane receptors, and are inactivated by reuptake and enzymatic degradation within the cell. However, endocannabinoids have two fundamental characteristics that differentiate them from other neurotransmitters: they act as retrograde messengers and they do not accumulate in the interior of synaptic vesicles (Wilson and Nicoll, 2002). For several years, endocannabinoid compounds have been supposed to be exclusively synthesized on demand to act on cells located near their site of synthesis, and then to be rapidly inactivated by the action of specific degradation enzymes. However, recent studies have shown intracellular stores of anandamide in places other than synaptic vesicles as in adiposomes where it is sequestered and concentrated to higher levels than in the extracellular space (Hillard and Jarrahian, 2000; Maccarrone et al., 2010). Moreover, an active intracellular binding of anandamide to TRPV1 and PPARs suggest an additional role of anandamide as a second messenger in intracellular signaling (Maccarrone et al., 2010). This new scenario contemplates the possibility that anandamide may act as an autocrine/paracrine ligand of CB receptors but also as an intracellular ligand to TRPV1 and PPARs; moreover, the presence of extracellular anandamide transporters would point anandamide as an endocrine messenger (Maccarrone et al., 2010).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942876/

The PPAR binding catches my eye as well...

Josh · Nov 28, 2014

I recall Dr. Kruse mentioning that Cannabanoids might be useful when redox is poor...

CANNABINOID ACTIONS ON MITOCHONDRIA ACTIVITY: OXIDATIVE
STRESS AND ENERGY METABOLISM
Mitochondria are vital cellular components essential for ATP
production and calcium homeostasis. The relevance of these
organelles in neurons is even greater than in other cell types
because neurons are highly demanding energy cells mainly dependent
on aerobic oxidative phosphorylation, due to their limited
capacity for glycolysis. Long axons require energy transport
over long distances, and synaptic transmission depends on calcium
signals. Mitochondria are abundant in presynaptic nerve
terminals where they provide energy for sustained neurotransmitter
release. Therefore, defects in mitochondrial activity can
have severe consequences for the cell, including energetic failure
associated with decreased ATP production and apoptosis
resulting from the release of death factors and impaired calciumbuffering
capacity. Moreover, alterations in the protein complexes
of the respiratory chain located in the inner mitochondrial
membrane lead to electron transport leakage that enables the
production of ROS, which may overwhelm the capacity of the
anti-oxidant systems existing in cells to counteract free radical
damage, with the subsequent oxidative damage produced to
proteins, DNA, RNA, and lipids. Numerous studies have linked
mitochondrial dysfunction to neurodegenerative diseases, including
AD (Ferrer, 2009; Ankarcrona et al., 2010; Burchell et al.,
2010). Altered mitochondrial function appears early in time
in AD, even preceding the characteristic Alzheimer pathology
in mouse models, and ultimately leads to exhausted neurons
as a result of the convergence of reduced energy production,
increased energy demand, and excessive oxidative stress (Ferrer,
2009).
The anti-oxidant properties of cannabis derivatives, notably
CBD, were demonstrated early in cell cultures exposed to toxic
glutamate levels (Hampson et al., 1998, 2000). In line with these
findings, CBD prevented ROS production and lipid peroxidation
in PC12 neuronal cells exposed to Aβ, as well as reduced
apoptosis from reduced caspase 3 levels, and in counteracting
the Aβ-induced increase in intracellular calcium concentration
(Iuvone et al., 2004). CBD also reduced, in similar conditions,
the levels of nitrite (NO), a potent oxidant reactive molecule, as
well as the expression of iNOS, one of the enzymes responsible
for the synthesis of NO (Esposito et al., 2006b, 2011). Moreover,
other cannabinoid compounds exhibited anti-oxidant properties
in animal models of AD. Thus, the selective CB2 receptor agonist
JWH-133 reduced hydroxynonenal adducts, derived from lipid
peroxidation, and enhanced the levels of the superoxide dismutases
SOD1 and SOD2 in the vicinity of plaques in APP/PS1 mice,
indicating the role of CB2 receptors in reducing oxidative stress
damage and to promote responses against such damage (Aso et al.,
2013). A reduction of free radicals and mitochondrial activity
was also suggested in a mouse model of tauopathy exposed to
www.frontiersin.org March 2014 | Volume 5 | Article 37 | 5Aso and Ferrer Cannabinoids in Alzheimer
chronic treatment with the Sativex® mixture of 9-THC and CBD
(Casarejos et al., 2013).
An additional topic deserving attention is the putative role
of cannabinoid receptors in the regulation of neuronal energy
metabolism. The little information available to date supports the
direct control of CB1 over neuronal respiration and energy production.
One study, using anti-CB1 receptor antibodies, revealed
CB1 receptor protein localization in approximately 30% of neuronal
mitochondria, which when activated by exogenous or
endogenous cannabinoids reduces the respiratory chain complex I
activity and oxygen consumption, likely through cyclic adenosine
monophosphate (cAMP) and protein kinase A (PKA) signaling
(Bénard et al., 2012). These findings are in agreement with previous
observations showing that AEA, 9-THC, and HU-210, all
of them partial CB1 agonists, significantly decreased oxygen consumption
and mitochondrial membrane potential (Athanasiou
et al., 2007). However, these data must be interpreted with caution
as commercial anti-CB1 receptor antibodies also recognize
the mitochondrial protein stomatin-like protein 2 and that the formerly
described effect of WIN 55,212-2 on mitochondrial complex
III is in fact not detectable in isolated mitochondrial preparations
(Morozov et al., 2013).
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http://www.ncbi.nlm.nih.gov/pubmed/24634659

cantweight · Nov 28, 2014

Josh said: ↑

View attachment 1122

http://www.ncbi.nlm.nih.gov/pubmed/24634659
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I'm having the opposite reaction. Increase in agitation and aggressiveness...total lack of appetite.....lots of thirst.

cantweight · Nov 28, 2014

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209357/

Josh · Dec 27, 2014

https://www.nabp.net/events/assets/Carter_Aggarwal.pdf

Josh · Jan 15, 2015

Cannabinoid and Pregnenolone curiosity....I ask myself why at a quantum level is this so? I imagine it will force me to go many places?? Interesting that Pregnenolone affects the Cannabinoid receptors in the brain???

http://www.eurekalert.org/pub_releases/2014-01/ind-mdt010214.php

Two INSERM research teams led by Pier Vincenzo Piazza and Giovanni Marsicano (INSERM Unit 862 "Neurocentre Magendie" in Bordeaux) recently discovered that pregnenolone, a molecule produced by the brain, acts as a natural defence mechanism against the harmful effects of cannabis in animals. Pregnenolone prevents THC, the main active principle in cannabis, from fully activating its brain receptor, the CB1 receptor, that when overstimulated by THC causes the intoxicating effects of cannabis. By identifying this mechanism, the INSERM teams are already developing new approaches for the treatment of cannabis addiction.
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Shijin13 · Jan 15, 2015

Josh said: ↑

Cannabinoid and Pregnenolone curiosity....I ask myself why at a quantum level is this so? I imagine it will force me to go many places?? Interesting that Pregnenolone affects the Cannabinoid receptors in the brain???

http://www.eurekalert.org/pub_releases/2014-01/ind-mdt010214.php
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Interesting find @Josh I wonder how this works with cannabinoids that have THC removed?

Josh · Jan 15, 2015

THC is a cannabinoid, I imagine it has some affect on the others that use CB1, a lot more to figure out here for me....

sulfated pregnenolone must be an inverse agonist...

Josh · Jan 15, 2015

http://cbdcrew.org/assets/circle-of-cannabinoids.jpg

Note the range of cannabinoid activity in this diagram that I posted above. It appears that THC is the dominant player at CB1 with CBD also having some activity there....

Shijin13 · Jan 15, 2015

Josh said: ↑

THC is a cannabinoid, I imagine it has some affect on the others that use CB1, a lot more to figure out here for me....

sulfated pregnenolone must be an inverse agonist...
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We're back to sulfated hormones. again....

cantweight · Jan 15, 2015

Does this explain craving sulfur foods when using CBD?

From what I have read there is significant overlap in effects of CBD and THC. Hemp, while lower in CBD has almost no THC just requires larger amounts of plants to extract like amts. of CBD.

kovita · Jan 15, 2015

Josh said: ↑

Cannabinoid and Pregnenolone curiosity....I ask myself why at a quantum level is this so? I imagine it will force me to go many places?? Interesting that Pregnenolone affects the Cannabinoid receptors in the brain???

http://www.eurekalert.org/pub_releases/2014-01/ind-mdt010214.php
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this is intersting, I never liked cannabis, should I read it is always low pregnenolone?!

kovita · Jan 16, 2015

Christi, I forgot to say...sometimes you just randomly discover something that at that exact moment of your life does you extremaly well. Maybe in the summer you would see different effect...to me it looks like the things are chnaging continuously and unless we observe and listen well to our own chnaging needs we can not keep up witht this rhythm well in the modern world. I just discovered propolis makes me probably so well, I have my mouth opened. I found out while on the bee farm, wher I just could not resist to put it in my mouth. I tried it in the past however the quality was much worse that this time. Or maybe (most llikely) right now propolis just is the right thing. I wish I was as smart to be able to understand why and how...but one of the things I learnt as well (very valuable btw) is that we do not have to understamd everyhting as long as we are sensitive enough to listen, observe and follow the speach of own our bodies. I will never stop studying and reading and asking, but this very old aproach brought a lot of suscess to traditional medicinal systems, so ther is "something about ir" ;-)

cantweight · Jan 16, 2015

kovita said: ↑

Christi, I forgot to say...sometimes you just randomly discover something that at that exact moment of your life does you extremaly well. Maybe in the summer you would see different effect...to me it looks like the things are chnaging continuously and unless we observe and listen well to our own chnaging needs we can not keep up witht this rhythm well in the modern world. I just discovered propolis makes me probably so well, I have my mouth opened. I found out while on the bee farm, wher I just could not resist to put it in my mouth. I tried it in the past however the quality was much worse that this time. Or maybe (most llikely) right now propolis just is the right thing. I wish I was as smart to be able to understand why and how...but one of the things I learnt as well (very valuable btw) is that we do not have to understamd everyhting as long as we are sensitive enough to listen, observe and follow the speach of own our bodies. I will never stop studying and reading and asking, but this very old aproach brought a lot of suscess to traditional medicinal systems, so ther is "something about ir" ;-)
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So true! I have noticed more and more following my instincts and body's inclinations have been leading me down a great path when I listen. I used to listen well, then I stopped and began pushing agendas that made sense but did not match with my body. I don't understand so much of the why's and sometimes I am frustrated by that...especially when people want help and ask me how did I do something...but in the end I am grateful.

The Dr that suggested the CBD oil caused me to discover pine pollen and it seems it may have some similarity to propolis...I was much more drawn to the pine pollen. I ordered it but am second guessing its use and wonder if it is more suited for spring time since that is when the pollen would be in the air....Im rambling....but yes there is definitely "something about it all'

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