Hemp oil and melatonin

Hello people. Have been lurking and absorbing for a while, and thought I'd finally join the conversation. The more minds cooperating with one another, the sooner I believe a final solution will be reached for all.

That said, I've been contemplating Rick Simpson hemp oil as a treatment. Here's an interesting piece of research I found-

"Research by Italian researchers discovered that when eight men smoked a cigarette containing the active ingredient in marijuana, THC (tetrahydrocannabinol), they had dramatically higher melatonin levels twenty minutes later. After two hours, their melatonin levels were 4,000 percent higher than at baseline!(11). Other research showing that melatonin is converted on a 25 hour cycle to seratonin and then back to melatonin is a clear indicator that those who smoke marijuana regularly are attempting to self medicate (i.e. perpetual prozac but without the same capacity to block the reuptake of seratonin thus more problems associated with the use of THC.).

(Russel J. Reiter, Ph.D., Jo Robinson)"

Well, according to this post here- https://immortalhair.forumotion.com/t3989-melatonin-increases-anagen-growth-cycles, melatonin increases anagen growth cycles in hair. There also seem to be other avenues, through which the oil could be of some benefit in one's hair care regimen. It would be interesting to see someone give it a fair trial.

Why not just supplement with melatonin? There is some evidence suggesting that excess seratonin activity is not good for hair and general well-being.

https://immortalhair.forumotion.com/t5948-cortisol-prolactin-estrogen-serotonin-reason-for-hair-loss

Hm.. so the conversion of the mass amounts of melatonin --> serotonin --> melatonin could in fact wind up being harmful you think? I wonder if all that extra melatonin is in fact actually converted back to serotonin? Will have to investigate all this further.

Would be nice to hear further commenting on this.

Hm.. just noticed something else about the oil- it stimulates ceramide production, which actually happens to be an important aspect of its antitumoral activity. Here are a couple of studies.

Cannabinoids and ceramide: two lipids acting hand-by-hand.
Velasco G, Galve-Roperh I, Sánchez C, Blázquez C, Haro A, Guzmán M.
Source
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain.
Abstract
Cannabinoids, the active components of Cannabis sativa (marijuana) and their endogenous counterparts, exert their effects by binding to specific G-protein-coupled receptors that modulate adenylyl cyclase and ion channels. Recent research has shown that the CB1 cannabinoid receptor is also coupled to the generation of the lipid second messenger ceramide via two different pathways: sphingomyelin hydrolysis and ceramide synthesis de novo. Sustained ceramide accumulation in tumor cells mediates cannabinoid-induced apoptosis, as evidenced by in vitro and in vivo studies. This effect seems to be due to the impact of ceramide on key cell signalling systems such as the extracellular signal-regulated kinase cascade and the Akt pathway. These findings provide a new conceptual view on how cannabinoids act, and raise interesting physiological and therapeutic questions.

Anti-tumoral action of cannabinoids: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation

Ismael Galve-Roperh1, 3, Cristina Sánchez1, 3, María Luisa Cortés2, Teresa Gómez del Pulgar1, Marta Izquierdo2 & Manuel Guzmán1
1 Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040-Madrid , Spain

2 Department of Molecular Biology, Severo Ochoa Molecular Biology Center, School of Sciences, Autónoma University, 28049-Madrid, Spain

3 I.G.-R. and C.S. contributed equally to this work

Correspondence should be addressed to Manuel Guzmán mgp @ solea.quim.ucm.es



9-Tetrahydrocannabinol, the main active component of marijuana, induces apoptosis of transformed neural cells in culture. Here, we show that intratumoral administration of 9-tetrahydrocannabinol and the synthetic cannabinoid agonist WIN-55,212-2 induced a considerable regression of malignant gliomas in Wistar rats and in mice deficient in recombination activating gene 2. Cannabinoid treatment did not produce any substantial neurotoxic effect in the conditions used. Experiments with two subclones of C6 glioma cells in culture showed that cannabinoids signal apoptosis by a pathway involving cannabinoid receptors, sustained ceramide accumulation and Raf1/extracellular signal-regulated kinase activation. These results may provide the basis for a new therapeutic approach for the treatment of malignant gliomas.

According to this post here - https://immortalhair.forumotion.com/t5872-ceramides-and-hair, ceramide production could perhaps be another very useful angle to approaching hair issues.

Hm.. hm indeed.. anyone else intrigued?

And another thing, supposedly arthritis treatments have been used quite successfully in overcoming baldness (https://immortalhair.forumotion.com/t3505-sulfasalazine-a-rheumatoid-arthritis-drug-provides-full-frontal-regrowth).

Guess what else suppresses an over-active immune system, is potently anti-inflammatory, inhibits MMPs, and is commonly known to work great on arthritis?

LightBringer - I take 6 milligrams of melatonin every night. It's one of the best antioxidants and anyone who is old enough to be taking it should consider it.

Oral distilled hemp oil has crossed my mind many times. Check out how ceramides affect hair.

https://immortalhair.forumotion.com/t5872-ceramides-and-hair

Yes, I did come across that thread CS. Very intriguing stuff indeed. In short, it certainly appears that ceramide serves a great variety of useful purposes for hair.

You're familiar with Rick Simpson, right? He actually does claim to have grown in a bald spot of his own using the oil. Now Rick's a credible guy. There's a lot of research to back much of what he says, but I couldn't just take him on his word alone. I had to go digging for information to show whether that may be possible, and so far it does seem to be.

I'm wondering about the 25 hour serotonin-->melatonin-->serotonin conversions though. The pineal gland is obviously responsible for performing those conversions, right? Is there any reason you can see why an extra amount of systemic melatonin would find itself being converted back to serotonin? I sort of wonder if the researchers mentioned in my first post were wrong to speculate that this would be the case. What do you think?

Hm.. another interesting piece..

Cannabidiol lowers incidence of diabetes in non-obese diabetic mice.
Weiss L, Zeira M, Reich S, Har-Noy M, Mechoulam R, Slavin S, Gallily R.
Source

Hadassah University Hospital, Department of Bone Marrow Transplantation & Cancer Immunotherapy, POB 12000, Jerusalem, 91120, Israel.
Abstract

Cannabidinoids are components of the Cannabis sativa (marijuana) plant that have been shown capable of suppressing inflammation and various aspects of cell-mediated immunity. Cannabidiol (CBD), a non-psychoactive cannabidinoid has been previously shown by us to suppress cell-mediated autoimmune joint destruction in an animal model of rheumatoid arthritis. We now report that CBD treatment significantly reduces the incidence of diabetes in NOD mice from an incidence of 86% in non-treated control mice to an incidence of 30% in CBD-treated mice. CBD treatment also resulted in the significant reduction of plasma levels of the pro-inflammatory cytokines, IFN-gamma and TNF-alpha. Th1-associated cytokine production of in vitro activated T-cells and peritoneal macrophages was also significantly reduced in CBD-treated mice, whereas production of the Th2-associated cytokines, IL-4 and IL-10, was increased when compared to untreated control mice. Histological examination of the pancreatic islets of CBD-treated mice revealed significantly reduced insulitis. Our results indicate that CBD can inhibit and delay destructive insulitis and inflammatory Th1-associated cytokine production in NOD mice resulting in a decreased incidence of diabetes possibly through an immunomodulatory mechanism shifting the immune response from Th1 to Th2 dominance.

So CBD alone cut the rate of diabetes incidences by more than half. This does fit quite well with Rick's numerous claims to have healed people with diabetes. Seems the oil is of great potential value in controlling blood sugar issues as well then.

And here we go again..

https://immortalhair.forumotion.com/t5438-il-1-tnf-alpha-destroy-hair-follicleshttps://immortalhair.forumotion.com/t5438-il-1-tnf-alpha-destroy-hair-follicles

The study mentioned in that post indicates that IL-1 and TNF-α are highly destructive to hair. Two more things that cannabinoids have been shown to suppress.

Here-

The synthetic cannabinoid R(+)WIN 55,212-2 inhibits the interleukin-1 signaling pathway in human astrocytes in a cannabinoid receptor-independent manner.
Curran NM, Griffin BD, O'Toole D, Brady KJ, Fitzgerald SN, Moynagh PN.
Source

UCD School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Abstract

R(+)WIN 55,212-2 is a synthetic cannabinoid that controls disease progression in models of multiple sclerosis. This is associated with its ability to reduce migration of leukocytes into the central nervous system. Because leukocyte migration is dependent on induction of adhesion molecules and chemokines by pro-inflammatory cytokines, we examined the effects of R(+)WIN 55,212-2 on their expression. Using 1321N1 astrocytoma and A-172 glioblastoma as cell models we show that R(+)WIN 55,212-2, but not its inactive chiral form S(-)WIN 55,212-2, strongly inhibits the interleukin-1 (IL-1) induction of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the chemokine IL-8. This inhibition is not mediated via the CB1 or CB2 cannabinoid receptors, because their selective antagonists and pertussis toxin failed to affect the inhibitory effects of R(+)WIN 55,212-2. Furthermore reverse transcription-PCR analysis did not detect the expression of either receptor in 1321N1 cells. R(+)WIN 55,212-2 was shown to inhibit adhesion molecule and chemokine expression at the level of transcription, because it strongly inhibited the IL-1 induction of ICAM-1, VCAM-1, and IL-8 mRNAs and blocked the IL-1 activation of their promoters. The NFkappaB pathway was then assessed as a lead target for R(+)WIN 55,212-2. NFkappaB was measured by expression of a transfected NFkappaB-regulated reporter gene. Using this assay, R(+)WIN 55,212-2 strongly inhibited IL-1 activation of NFkappaB. Furthermore R(+)WIN 55,212-2 inhibited the ability of overexpressed Myd88, Tak-1, and IKK-2 to induce the reporter gene suggesting that R(+)WIN 55,212-2 acts at or downstream of IKK-2 in the IL-1 pathway. However R(+)WIN 55,212-2 failed to inhibit IL-1-induced degradation of IkappaBalpha, excluding IKK-2 as a direct target. In addition electrophoretic mobility shift and chromatin immunoprecipitation assays showed that R(+)WIN 55,212-2 does not regulate the IL-1-induced nuclear translocation of NFkappaB or the ability of the latter to bind to promoters regulating expression of ICAM-1 and IL-8. These data suggest that R(+)WIN 55,212-2 blocks IL-1 signaling by inhibiting the transactivation potential of NFkappaB.

^Granted, the study involved a synthetic cannabinoid.

But there's also this-

Marijuana components stimulate human peripheral blood mononuclear cell secretion of interferon-gamma and suppress interleukin-1 alpha in vitro.
Watzl B, Scuderi P, Watson RR.
Source

Department of Family and Community Medicine, Arizona Health Sciences Center, Tucson.
Abstract

We investigated the in vitro effects of both psychoactive and nonpsychoactive marijuana components on leukocyte secretion of the immunoregulatory cytokines interleukin-1 alpha (IL-1), tumor necrosis factor alpha (TNF), interferon-gamma (IFN) and interleukin-2 (IL-2). Psychoactive delta-9-tetrahydrocannabinol (THC) and nonpsychoactive cannabidiol (CBD) were added to cultures of mitogen-activated human peripheral blood mononuclear cells (PBMC) and the concentrations of IL-1, TNF, IFN and IL-2 in culture supernatants were measured by ELISA systems. Concentrations of THC and CBD, comparable to plasma levels found after smoking marijuana (10-100 ng/ml), increased the concentration of measurable IFN (139 and 68%), while high concentrations of both cannabinoids (5-20 micrograms/ml) completely blocked synthesis and/or release of this cytokine. CBD was also shown to decrease the measurable quantity of both IL-1 and TNF. In contrast to the effects on IFN, IL-1 and TNF, both cannabinoids, had no effect on IL-2 secretion. This report suggests that both psychoactive and nonpsychoactive components of marijuana are immunomodulating and can potentially alter cytokine secretion of human PBMC.

Also, other cannabinoids have been shown to inhibit/suppress many other forms of IL as well.

One more for now..

Inhibition by delta-9-tetrahydrocannabinol of tumor necrosis factor alpha production by mouse and human macrophages.
by Z M Zheng, S Specter, H Friedman

International Journal of Immunopharmacology (1992)
Volume: 14, Issue: 8, Pages: 1445-1452

PubMed: 1334476

Abstract

Suppression by delta-9-tetrahydrocannabinol (THC) of tumor necrosis factor (TNF) production by macrophages has not been reported previously. The present study evaluated the effect in vitro of THC on soluble TNF-alpha production by cultured murine peritoneal macrophages. THC at 5 or 10 micrograms/ml added to medium RPMI 1640 containing 10 ng LPS/ml, mouse IFN-gamma (100 u/ml), and 0.5% bovine serum albumin (BSA) used to induce TNF significantly decreased TNF-alpha production by BALB/c mouse macrophages. Macrophages pretreated with THC at 0.1, 0.5, or 1.0 micrograms/ml in protein-free medium for 3 h at 37 degrees C, prior to TNF induction, also showed a decreased ability to produce TNF-alpha in a dose-dependent manner. Increasing the protein concentration from 0.5 to 5% BSA in the medium which was used to induce TNF prevented the inhibitory activity of THC. Human peripheral blood adherent cells treated with THC-containing medium produced less TNF-alpha than controls that were not exposed to THC. Thus, our data provide evidence that THC can inhibit TNF production by mouse and human macrophages. The drug's activity is concentration dependent and is related to the amount of serum protein in the medium used to induce this cytokine.

I'll just keep adding whatever I find to the thread. Anyone else feel free to add relevant info, good or bad.

EDIT: Since this thread has evolved quite a way since the first post, I wonder if a mod could perhaps edit the title to something that would be more fitting. Perhaps something like 'Hemp for Hair'?

Nice studies, LightBringer.

Thanks imprisonedradical.

Here's some more-

MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis.
Hiratsuka S, Nakamura K, Iwai S, Murakami M, Itoh T, Kijima H, Shipley JM, Senior RM, Shibuya M.
Source

Department of Genetics, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Abstract

The molecular mechanism of tissue-specific metastasis in tumors endogenously expressing members of the vascular endothelial growth factor (VEGF) family is not yet clear. Here we demonstrate that MMP9 is specifically induced in premetastatic lung endothelial cells and macrophages by distant primary tumors via VEGFR-1/Flt-1 tyrosine kinase (TK) and that it significantly promotes lung metastasis. In a genetic approach using mice, suppression of MMP9 induction by deletion of either VEGFR-1TK or MMP9 markedly reduced lung metastasis. Furthermore, the MMP9 levels in endothelial cells of normal lung lobes from patients carrying distant tumors were significantly elevated as compared with those from patients without tumors. Thus, a block of MMP9 induction via VEGFR-1 inhibition could be useful for the prevention of tumor metastasis in lung.

Okay, so inhibition of VEGFR-1 means less MMP9. MMP9 as we know, is horrible for hair. See here-

Identification of clustered cells in human hair follicle responsible for MMP-9 gelatinolytic activity: consequences for the regulation of hair growth.
Jarrousse F, Boisnic S, Branchet MC, Beranger JY, Godeau G, Breton L, Bernard BA, Mahé YF.
Source

Hair Biology Research Group and Cutaneous Physiology Department, L' OREAL, Clichy Cedex, GREDECO, Paris, France.
Abstract
BACKGROUND:

The control of human hair follicle growth and differentiation is dependent upon several well-identified factors, including androgens, cytokines, and growth factors. In humans, alopecia androgenetica is a common aging process thought to be regulated through complex genetic imbalances, which also involve several of these crucial identified factors (and probably others not yet characterized), alone or in combination. Among these factors, epidermal growth factor (EGF), as well as pro-inflammatory cytokines, play a pivotal role, as evidenced by their direct inhibitory effects on hair growth both in vitro and in vivo. Following such treatments, the in vitro growth of hair follicles was rapidly arrested and deleterious modifications of hair morphology were also observed.
AIM:

Because these cytokines act, at least partly, through the induction of matrix metalloproteinases (MMP), and because tissue remodeling occurs during the hair cycle, we attempted to identify and localize MMP in the human pilosebaceous unit.
METHOD:

We used zymography to observe human hair follicles in culture in vitro.
RESULTS:

We observed that human hair follicles in culture in vitro mainly and almost exclusively produce MMP-2 and MMP-9 gelatinolytic activities. Furthermore, after stimulation with EGF, tumor necrosis factor-alpha (TNF-alpha), or interleukin-1alpha (IL-1alpha), MMP-9 production was strongly increased. Using immunohistochemistry, we then precisely localized MMP-9 in the lower part of the inner root sheath (Henle's layer) of control human anagen hair follicles.
CONCLUSIONS:

Cytokine- and EGF-induced upregulation of MMP-9 in the lower epithelial compartment of the human hair bulb is a major mechanism through which hair follicle involution, observed in alopecia, may occur.

So where am I going with this? Take a guess..

Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in Gliomas

Cristina Blázquez 1 ,
Luis González-Feria 4 ,
Luis Álvarez 2 ,
Amador Haro 1 ,
M. Llanos Casanova 3 , and
Manuel Guzmán 1

+ Author Affiliations

1Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University; 2 Research Unit, La Paz University Hospital; 3 Project on Cellular and Molecular Biology and Gene Therapy, CIEMAT, Madrid, Spain; and 4 Department of Neurosurgery, University Hospital, Tenerife, Spain

Abstract

Cannabinoids inhibit tumor angiogenesis in mice, but the mechanism of their antiangiogenic action is still unknown. Because the vascular endothelial growth factor (VEGF) pathway plays a critical role in tumor angiogenesis, here we studied whether cannabinoids affect it. As a first approach, cDNA array analysis showed that cannabinoid administration to mice bearing s.c. gliomas lowered the expression of various VEGF pathway-related genes. The use of other methods (ELISA, Western blotting, and confocal microscopy) provided additional evidence that cannabinoids depressed the VEGF pathway by decreasing the production of VEGF and the activation of VEGF receptor (VEGFR)-2, the most prominent VEGF receptor, in cultured glioma cells and in mouse gliomas. Cannabinoid-induced inhibition of VEGF production and VEGFR-2 activation was abrogated both in vitro and in vivo by pharmacological blockade of ceramide biosynthesis. These changes in the VEGF pathway were paralleled by changes in tumor size. Moreover, intratumoral administration of the cannabinoid Δ9-tetrahydrocannabinol to two patients with glioblastoma multiforme (grade IV astrocytoma) decreased VEGF levels and VEGFR-2 activation in the tumors. Because blockade of the VEGF pathway constitutes one of the most promising antitumoral approaches currently available, the present findings provide a novel pharmacological target for cannabinoid-based therapies.

Okay then. So cannabinoids down-regulate VEGF, which promotes MMP9 production, which is involved in the whole pro-inflammatory process involving cytokines, etc which destroys hair follicles. In other words, that entire deletorious cascade of events could apparently be completely abated with the use of cannabinoids. And this isn't just theory- it's obvious that hemp oil does down-regulate VEGF effectively, hence its potent anti-tumoral action.

Also note that in that last study, that it was actually ceramide biosynthesis brought on by the cannabinoids that caused the down-regulation of VEGF. Remember how important ceramides are for hair? It's all connected. What up-regulates healthy cellular processes down-regulates the destructive ones, and vice versa- what's good for cancers and inflammations is bad news for us.

LightBringer,

Here's a topic that CS started a while ago about the potential negative effects of an overactive endocannabinoid system:
https://immortalhair.forumotion.com/t1250-the-endocannabinoid-system-of-the-skin-in-health-and-disease

Activation of the cannabinoid receptors in hair follicles actually inhibits hair growth.

Recent studies strongly suggest that the cannabinoid system is a key player in cell growth control. Since the organ-culture of human hair follicles (HF) offers an excellent, clinically relevant model for complex tissue interaction systems, we have asked whether the cannabinoid system plays a role in hair growth control. Here, we show that human scalp HF, intriguingly, are both targets and sources of endocannabinoids. Namely, the endocannabinoid N-arachidonoylethanolamide (anandamide, AEA) as well as the exocannabinnoid (9) -tetrahydrocannabinol dose-dependently inhibited hair shaft elongation and the proliferation of hair matrix keratinocytes, and induced intraepithelial apoptosis and premature HF regression (catagen). These effects were inhibited by a selective antagonist of cannabinoid receptor-1 (CB1). In contrast to CB2, CB1 was expressed in a hair cycle-dependent manner in the human HF epithelium. Since we successfully identified the presence of endocannabinoids in human HF, our data strongly suggest that human HF exploit a CB1-mediated endocannabinoid signaling system for negatively regulating their own growth. Clinically, CB1 agonists may therefore help to manage unwanted hair growth,while CB1 antagonists might counteract hair loss. Finally, human HF organ culture offers an instructive, physiologically relevant new research tool for dissecting "nonclassical" effects of endocannabinoids and their receptor-mediated signaling in general.—Telek, A., Bíró, T., Bodó, E., Tóth, B. I., Borbíró, I. Cayenne Pepper is the only natural CB1 blocker known and this mechanism may account for its apparent hair growth stimulation effects, especially when orally consumed with Soy Isoflavone extracts. Cayenne pepper has profoundly beneficial effects for certain types of heart disease and is considered curative for certain types of cancer.

The curcumin/resveratrol combination is supposed to inhibit cannabinoid signaling in the skin. I haven't actually seen any studies showing this, however.

Yes, I've read that before about CB1 agonists being counter-productive. THC though, is actually only a partial CB1 agonist, which also has some affinity for CB2 (however, according to the study it does seem to still be capable of down-regulating hair growth when used on its own). Here's the thing though, the oil is quite a bit more diverse in its effects than simple CB1 agonism, and its interactions with the cannabinoid system are vastly more complex than that, given that it contains not just one, but at least 85 different cannabinoids all working synergistically with one another. For instance, another main cannabinoid in the plant which actually predominates THC in many indica strains, is called CBD. CBD has a greater affinity for CB2 than CB1 (although its affinity for either is somewhat limited), and it's been said before that CB2 could actually be quite a useful gateway for promoting hair growth. Here's a post about it:

https://immortalhair.forumotion.com/t853-the-cannabinoid-receptor-cb2-exerts-antifibrotic-effects-in-experimental-dermal-fibrosis

It's obvious that hemp oil does achieve the powerful anti-fibrotic effects he's describing there, hence the vast number of fibrotic illnesses it is known to relieve. Thus, with 85 different cannabinoids in ratios such as the plant contains, it's clear that there's a lot more being done here than simple CB1 agonism. The oil is working the entire cannabinoid system, and it seems that virtually any time it's ever been tested out, the result of that is to push the body towards a more healthful state of cellular activity. Many of the cannabinoids in the plant aren't agonists of either receptor, and actually act as antagonists instead. And if one is still worried about it, you've always got curcumin and resveratrol in your arsenal. Well, that's my analysis so far.

Here's another example- it's been found that meditation seems to raise prolactin levels, and of course prolactin is counter-productive to hair. But is anybody going to suggest that meditation makes your hair fall out? I personally would find that a bit absurd, as in my experience it's the very opposite of meditation that makes hair fall out (ie; sitting around worrying about what meditation might do to you would obviously be far more damaging and stressful than the meditation itself could ever be). Meditation, like anything in nature, goes along with a vastly more complex hormonal chemistry than a rise of one particular molecule over all the rest. Nature works in orchestrations, rather than single notes. Sometimes we dwell too heavily on a single detail and lose sight of the greater image.

Anyway, it is sometimes aggravating that all so many of these stupid studies focus on is this molecule, or that molecule (thanks to the patent interests that usually motivate them, no doubt). In an ideal world where most of the people paying for research to be done on health issues actually cared about healing people, a lot more of these studies would show us what the overall mix of chemicals from the actual plant is doing instead of one or two select and often synthetic cannabinoids.

Just adding to the thread:

The dietary polyphenols trans-resveratrol and curcumin selectively bind human CB1 cannabinoid receptors with nanomolar affinities and function as antagonists/inverse agonists.
Seely KA, Levi MS, Prather PL.
Source

Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72205, USA.
Retraction in

* Prather PL, Seely KA, Levi MS. J Pharmacol Exp Ther. 2009 Dec;331(3):1147.

Abstract

The dietary polyphenols trans-resveratrol [5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-1,3-benzenediol; found in red wine] and curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1E,6E-heptadiene-3,5-dione] (found in curry powders) exert anti-inflammatory and antioxidant effects via poorly defined mechanisms. It is interesting that cannabinoids, derived from the marijuana plant (Cannabis sativa), produce similar protective effects via CB1 and CB2 receptors. We examined whether trans-resveratrol, curcumin, and ASC-J9 [1,7-bis(3,4-dimethoxyphenyl)-5-hydroxy-1E,4E,6E-heptatriene-3-one] (a curcumin analog) act as ligands at cannabinoid receptors. All three bind to human (h) CB1 and mouse CB1 receptors with nanomolar affinities, displaying only micromolar affinities for hCB2 receptors. Characteristic of inverse agonists, the polyphenols inhibit basal G-protein activity in membranes prepared from Chinese hamster ovary (CHO)-hCB1 cells or mouse brain that is reversed by a neutral CB1 antagonist. Furthermore, they competitively antagonize G-protein activation produced by a CB1 agonist. In intact CHO-hCB1 cells, the polyphenols act as neutral antagonists, producing no effect when tested alone, whereas competitively antagonizing CB1 agonist mediated inhibition of adenylyl cyclase activity. Confirming their neutral antagonist profile in cells, the polyphenols similarly attenuate stimulation of adenylyl cyclase activity produced by a CB1 inverse agonist. In mice, the polyphenols dose-dependently reverse acute hypothermia produced by a CB1 agonist. Upon repeated administration, the polyphenols also reduce body weight in mice similar to that produced by a CB1 antagonist/inverse agonist. Finally, trans-resveratrol and curcumin share common structural motifs with other known cannabinoid receptor ligands. Collectively, we suggest that trans-resveratrol and curcumin act as antagonists/inverse agonists at CB1 receptors at dietary relevant concentrations. Therefore, these polyphenols and their derivatives might be developed as novel, nontoxic CB1 therapeutics for obesity and/or drug dependence.

So it seems that cannabinoids from the actual marijuana plant can have effects similar to those of curcumin and resveratrol (ie., antagonism).

This abstract is also interesting because it confirms that curcumin/resveratrol modulate the CB system even at physiologically relevant concentrations.

I've been taking the curcumin/resveratrol combo on almost a daily basis since December of 2010. I can say certainly that I have minimal dandruff now compared to one year ago. But since I've made so many other modifications to my diet/regimen/lifestyle it's almost impossible to say that the curcumin/resveratrol are responsible.

Thanks for adding to the thread imprisoned. Yes, there is a lot to think about here.. more than I'll ever get through it seems..

But what's clear is that curcumin/resveratrol do behave in at least a roughly analogous manner to the cannabis cannabinoids, in that they produce the same kinds of effects (ie; anti-oxidation, anti-inflammation, etc).