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Clinical Endocannabinoid Deficiency CECD

34 Neuroendocrinology Letters Nos.1/2 Feb-Apr Vol.25, 2004 Copyright © Neuroendocrinology Letters ISSN 0172–780X www.nel.edu Fibromyalgia

Fibromyalgia, or myofascial pain syndrome, is an extremely common but controversial condition, whose very basis has been questioned, particularly among neurologists [65]. Even this author must admit to past prejudice in labeling it a “semi-mythical pseudo-disease.” Notwithstanding these opinions, the condition is the most frequent diagnosis in American rheumatology practices. Bennett has provided an excellent review [66], emphasizing new insights into fibromyalgia as a condition indicative of “central sensitization” and amplification of somatic nociception.

While no clear chemical or anatomical pathology has been clarified in tender muscle points, these present a self-sustaining and amplifying influence on pain perception in the brain over time, and lead to a concomitant disturbances in restful sleep, manifestations of dysautonomia, and prevalent secondary depression.

Interestingly, the application of standard antidepressant medication to the latter, and pharmacotherapy in general, provide disappointing results in fibromyalgia treatment. Has a promising therapeutic avenue been missed?
Returning to the work of Nicolodi and Sicuteri, the “secondary hyperalgesia” manifested by an increased response to noxious stimuli in areas adjacent to the pain is common to migraine and fibromyalgia (see below).

These authors suggested NMDA blockade as an approach to pain in defects of serotonergic analgesia in fibromyalgia [67].

Several studies of Richardson and her group provide key support for a relation of fibromyalgia and similar conditions to a clinical endocannanabinoid deficiency. An initial study [68] demonstrated that intrathecal injection of SR141716A, a powerful cannabinoid antagonist/inverse agonist, resulted in thermal hyperalgesia in mice. This suggests that the endocannabinoid system regulates nociceptive thresholds, and that absence of such regulation, or endocannabinoid hypofunction, underlies hyperalgesia and related chronic pain conditions. In a subsequent study [69], oligonucleotides directed against CB1 mRNA produced significant hyperalgesia. Additionally, the hyperalgesic effect of SR141716A was blocked in a dose-dependent manner by co-administration of two NMDA receptor antagonists, again supporting tonic activity of the endocannabinoid system under normal conditions. On this basis, it was suggested that cannabinoid agonists would be applicable to treatment of chronic pain conditions unresponsive to opioid analgesics.

Further investigation demonstrated that intrathecal AEA totally blocked carrageenan-induced spinal thermal hyperalgesia, while having no effect on normal thermal sensory and antinociceptive thresholds

[70]. Additionally, AEA inhibited K+ and capsaicinevoked calcitonin gene-related peptide (CGRP) release, and CB1 receptors were identified in rat sensory neurons and trigeminal ganglion. On this basis, the authors recommended cannabinoids for disorders driven by a primary afferent barrage (e.g., allodynia, visceral hyperalgesia, temporomandibular joint pain

(TMJ), and reflex sympathetic dystrophy (RSD)), and that such treatment could be effective a sub-psychoactive dosages.

Another study examined peripheral mechanisms [71], wherein AEA acted on CB1 to reduce hyperalgesia and inflammation via inhibition of CGRP neurosecretion in capsaicin activated nerve terminals. This is akin to mechanisms of “sterile inflammation” observed centrally in migraine, where CGRP is felt to be an important mediator [5]. Overall the results supported the notion that endocannabinoids modulate neurogenic inflammation through inhibition of peripheral terminal neurosecretion in capsaicin-sensitive fibers. AEA demonstrated anti-edema effects in addition to anti-hyperalgesia. Similar implications were provided by another study [72], in which WIN 55,212–2, a powerful CB1 agonist, blocked capsaicininduced hyperalgesia in rat paws. Once more, the benefit occurred at a dosage that did not produce analgesia or motor impairment, suggesting therapeutic benefit of cannabinoids without adverse effects. Similarly, local THC administration was evaluated in capsaicin-induced pain in rhesus monkeys [73], where, once more, pain was effectively reduced at low dosage, and was blocked by a CB1 antagonist. Another concept that is important to understanding of fibromyalgia is “wind-up,” a central sensitization of posterior horn neurons in pain pathways that occurs secondarily to tonic impulses form nociceptive afferent C fibers dependent on NMDA and substance P synaptic mechanisms in the spinal cord [74]. Similar mechanisms were implicated in TMJ dysfunction and RSD/CRP syndromes. The authors felt that some unknown peripheral tonic mechanism maintains allodynia, hyperalgesia, central sensitization and enhanced wind-up. Unfortunately, an obvious explanation was overlooked. In a previous publication [75], it was demonstrated that of wind-up was decreased in dose-dependent fashion by WIN 55,212 in spinal wide dynamic range and nociceptive-specific neurons. Thus, cannabinoids were able to suppress facilitation of spinal responses after repetitive noxious stimuli without impairment of non-nociceptive functions.

On a practical level, once more there have been no formal clinical trials of cannabis or THC in treatment of fibromyalgia. However, 21 California patients listed fibromyalgia and 11 myofascial pain (1.3% of a clinical population of 2480 subjects) as primary diagnoses leading to their usage of clinical cannabis [63]. Anecdotal reports to this author and other clinicians support unique efficacy of cannabis beyond conventional pharmacotherapy for alleviation of pain, dysphoria and sleep disturbances.

Irritable Bowel Syndrome (IBS) IBS is another difficult clinical syndrome for patients and their physicians. It is characterized by fluctuating symptoms of gastrointestinal pain, spasm, distention, and varying degrees of constipation or especially diarrhea. These may be triggered by infection,

Ethan B. Russo

Neuroendocrinology Letters Nos.1/2 Feb-Apr Vol.25, 2004 Copyright © Neuroendocrinology Letters ISSN 0172–780X www.nel.edu 35 but dietary indiscretions also figure prominently in discrete attacks. Although many clinicians regard it as a “diagnostic wastebasket,” irritable bowel syndrome represents the most frequent referral diagnosis for American gastroenterologists. Once more, a wide variety of treatments including atropinic agents, antidepressants and others affecting a myriad of neurotransmitter systems are prescribed, often with inadequate clinical benefits.
That endocannabinoids are important in GI function was powerfully underlined by the fact that 2- arachidonylglycerol (2-AG) was first isolated in canine gut [76].
In a recent review [77], the concept of “functional” bowel disorders as disturbances displaying “visceral hypersensitivity” was emphasized, involving a veritable symphony of neuroactive and pro-inflammatory modulators. In the susceptible subject, these lead to gastrointestinal allodynia and hyperalgesia to stimuli that would not discomfit the unaffected individual.

The role of vanilloid mechanisms in IBS was also explored, and it is worth emphasizing that Anandamide is an endogenous agonist at VR1 receptors, as is the phytocannabinoid cannabidiol (CBD) [78]. Repetitive VR1 stimulation rapidly produces a sensory neuron refractory state that would be a clinical advantage in treatment of visceral hypersensitivity. Pertwee has examined the relationship of cannabinoidsto gastrointestinal function in depth [79]. To summarize: The enteric nervous systems of mammals express CB1 and stimulation depresses gastrointestinal motility, especially through inhibition of contractile neurotransmitter release. Observed effects include delayed gastric emptying, some decrease in peptic acid production, and slowed enteric motility, inhibition of stimulated acetylcholine release, peristalsis, and both cholinergic and non-adrenergic non-cholinergic (NANC) contractions of smooth muscle, whether circular or longitudinal. These effects are mediated at the brain level as well as in the GI tract (This supports a chestnut frequently invoked by this author, ‘The brain and the gut speak the same language.”). These effects are opposed by CB1 antagonists (e.g., SR141716A).

This would strongly support the notion that GI motility is under tonic control of the endocannabinoid system.

The latter concept was reinforced by additional investigation from the same laboratory [80], in which it was demonstrated that the virtually all of the immunoreactive myenteric neurons in the ganglia of rat and guinea pig expressed CB1 receptors, and that there was a close correlation of such receptors to fibers labeled for synaptic protein, suggesting a fundamental role in neurotransmitter release. Additionally, it has been shown that chronic intestinal inflammation results in an up-regulation or sensitization of cannabinoid receptors

[81]. CBD has little effect on intestinal motility on its own, but synergizes the effect of THC in slowing transit of a charcoal meal when used in concert [82].

In the basis of available data, Di Carlo and Izzo recommended the application of cannabinoid drugs in treatment of IBS in humans [83]. To date, those studies have not eventuated, but cannabis has a long history in treating cholera, intestinal colic and related disorders (reviewed in [84]), and cannabis figures prominently in IBS treatment in testimonials on the Internet. Though anecdotal, reports suggest unique efficacy of symptomatic relief at cannabis dosages that do not impair activities of daily living. In comparison, recent trends in pharmacotherapy provide interesting contrasts. Alosetron, a 5-HT3 receptor antagonist marketed for females with diarrhea-predominant IBS produces only a 12–17% therapeutic gain [85], and was temporarily removed from the American market due to fatal cases of ischemic colitis with attendant obstipation. Tegaserod, a 5-HT4 receptor agonist marketed to women with constipation-predominant IBS, is reportedly well tolerated, but provides only a 5–15% improvement over placebo [85]. This “pushpull” dichotomy of serotonergic function in IBS is strongly suggestive that such efforts are barking up the wrong neurotransmitter tree. Rational analysis suggests that endocannabinoids may well be the more likely therapeutic neuromodulatory target, and that phytocannabinoid treatment might represent a more efficacious and safer therapeutic approach. In particularly severe IBS cases, the employment of a foaming rectal preparation of a whole cannabis extract might be considered.

Comorbidities of Migraine, Fibromyalgia and Irritable Bowel Syndrome

Further examination of pertinent literature supports that there are very interesting relationships between migraine, fibromyalgia and IBS. Recently, a syndrome of cutaneous allodynia associated with migraine has been reported [86], and experimentally, repetitive noxious stimulation of the skin in migraineurs between attacks facilitates pain perception [87]. Nicolodi, Sicuteri et al. similarly noted a decreased pain threshold in migraineurs tested with over-distension of upper extremity veins, but not mere pressure from a sphygmomanometer cuff [88], meriting a label for migraine as a “visceral systemic sensory disorder.” The same team noted a baseline fragility of serotonergic systems in migraine and fibromyalgia [89], plus the co-occurrence of primary headache in 97% of 201 fibromyalgia patients. In a later study [67], they supported the concept that both disorders represented a failure of serotonergic analgesia and NMDA-mediated neuronal plasticity. Other observations included the induction of fibromyalgic symptoms by the drug fenclonine in migraineurs but not others, and the production of migraine de novo in fibromyalgia patients without prior history after administration of nitroglycerine 0.6 mg sublingually. Similarly, an American group [90] examined 101 patients with the transformed migraine form of chronic daily headache, and were able to diagnose 35.6% as having comorbid fibromyalgia. Similarly, a high lifetime prevalence of migraine, IBS, depression and panic disorder were observed in 33 women meeting American College of Rheumatology criteria of fibromyalgia [91].

Clinical Endocannabinoid Deficiency (CECD)

36 Neuroendocrinology Letters Nos.1/2 Feb-Apr Vol.25, 2004 Copyright © Neuroendocrinology Letters ISSN 0172–780X www.nel.edu Sperber et al. examined separate groups of IBS and fibromyalgia patients [92]. Of the IBS cohort, 31.6% had fibromyalgia with significant numbers of tender muscle points compared to controls. Similarly, 32% of fibromyalgia patients met diagnostic criteria of IBS. In addition to these correlations, Bennett added irritable bladder syndrome to the comorbidities of fibromyalgia [66], supporting a concomitant visceral hyperalgesia

[93; 94] in a condition where cannabis extracts have already proven efficacious [95]. Most recently, in an experimental protocol, it was demonstrated that IBS patients displayed cutaneous hyperalgesia that was suppressed by temporary rectal anesthesia with lidocaine [96], indicating central sensitization.


Broadening the Concept of Clinical Endocannabinoid Deficiency

One may quickly see that certain patients display symptoms of all three disorders, or additional ones considered “functional.” With accrual of sufficient numbers of complaints lacking objective medical support, one assigns the label of somatization disorder.

Given the above data, however, one might reasonably ask three questions in such contexts: 1) Are there as yet unelucidated biochemical explanations for these disorders? 2) Might endocannabinoid deficiency explain their pathophysiology? 3) Are the symptoms alleviated by clinical cannabis? Globus hystericus and similar symptoms are frequently relegated to the psychogenic realm, but as a spasmodic disorder, it may well represent an endocannabinoid deficiency (CECD), as muscle tone (and tremor associated with demyelination) have been demonstrated to be under tonic endocannabinoid control in experimental animals [97]. Cannabis extracts have already proven efficacious in treatment of spasticity [98; 99].

Similarly, premature ejaculation in men is conventionally perceived as “psychological.” This seems less tenable, when anecdotes support that cannabis prolongs latency, and proof is apparent in the dose responsive delay in ejaculation in rats noted in experiments with HU 210, a powerful CB1 agonist [100].

A more obvious set of correlating conditions would be those of causalgia, allodynia and phantom limb pain, where application of cannabis based medicine extracts has already proven medically effective [99;

101]. Perhaps it will be demonstrable in the future that such conditions are associated with focal or spinal CECD states. It has long been known that cannabinoids lower intraocular pressure in glaucoma (reviewed [102]), but only recently noted that that the mechanism is under tonic endocannabinoid control. Glaucoma also represents a vascular retinopathy for which cannabis may be neuroprotective. Perhaps an endocannabinoid deficiency is operative here as well.

Cannabis has had numerous historical applications to obstetrics and gynecology (reviewed [103]). This suggests usage of cannabinoid treatment in spasmodic dysmenorrhea, hyperemesis gravidarum, and regulation of the uterine milieu in fertilization and unexplained fetal wastage, where endocannabinoid mechanisms have been demonstrated or implicated. Further investigation may shed light on whether dysregulation of the system underlies their pathophysiology.

In the pediatric realm, the entity of infantile colic has remained enigmatic. This disturbing anomaly is associated with apparent visceral sensitivity and distinct dysphoria, and is frequently medically recalcitrant to even desperate treatment measures with medications with serious adverse effect profiles. This author posits this to be another developmental endocannabinoid deficiency state that is likely amenable to phytocannabinoid treatment.

Endocannabinoid mechanisms also regulate bronchial function [104], and therapeutic efficacy in asthma treatment with cannabis preparations has been long known [105]. Based on similar analyses of the multi-organ involvement of cystic fibrosis [106], Fride has proposed endocannabinoid deficiencies as underlying the pathophysiology of that disorder, and its treatment with phytocannabinoids. In the psychiatric realm, bipolar disorder has been therapeutically recalcitrant to high dose antidepressants, but anecdotal data support cannabis efficacy [107]. Whether endocannabinoid tone is too low in the disorder would be conjectural at this time, but in the instance of post-traumatic stress disorder (PTSD), such a foundation seems likely, as endocannabinoids have been demonstrated as essential to the extinction of aversive memories in experimental animals [108].

Recent work by Wallace et al. has also demonstrated that convulsive thresholds are also under endocannabinoid control [109; 110], and that THC prevents 100% of subsequent seizures, far in excess of the capabilities of phenobarbital and phenytoin.

Affected rats demonstrated both acute increases in endocannabinoid production and a long-term up-regulation of CB1 production as apparent compensatory effects counteracting glutamate excitotoxicity. Based on this, one might conjecture that similar changes accrue when seizures are employed therapeutically as electroconvulsive therapy (ECT), in treatment of intractable depression. It seems that the resultant memory loss and prolonged improvement in mood may well be attributable to an increase in endocannabinoid levels rectifying their previous inadequacy.

Recent theory on depression suggests that mere deficiencies of serotonin and norepinephrine may be insufficient explanations of the disorder, but rather, innate neuroplasticity is inherently impaired and requires specific treatment [111]. Cannabinoids certainly seem to enhance that plasticity with their neuroprotective abilities [112; 113], and should be further explored therapeutically.

The apoptotic and anti-angiogenic properties of endo- and phytocannabinoids in various cancers (reviewed [114; 115]) raise the hypothesis that certain people who are especially susceptible to malignancy may be endocannabinoid deficient.

Ethan B. Russo

Neuroendocrinology Letters Nos.1/2 Feb-Apr Vol.25, 2004 Copyright © Neuroendocrinology Letters ISSN 0172–780X www.nel.edu 37

Conclusions

Clinical Endocannabinoid Deficiency:

Is It a Provable Concept?

The preceding material has pertained to conjectural and experimental evidence of a conceptual alternative biochemical explanation for certain disease manifestations, but one must ask how these would obtain?

Baker et al. have described how endocannabinoids may demonstrate an impairment threshold if too high, and a range of normal function below which a deficit threshold may be crossed [112]. Syndromes of CECD may be congenital or acquired. In the former case, one could posit that genetically-susceptible individuals might produce inadequate endocannabinoids, or that their degradation is too rapid. The same conditions might be acquired in injury or infection. Unfortunately, the regulation of endocannabinoid synthesis and degradation are far from fully elucidated (reviewed [116]). While a single enzyme, Anandamide synthase, catalyzes AEA production, its degradation by fatty acid amidohydrolase (FAAH), is shared with many substrates. To complicate matters, an endocannabinoid with antagonistic properties at CB1 called virodhamine (virodha, Sanskrit for “opposition”) has recently been discovered [117]. Further research may shed light on these relationships.

In the meantime, a clinical agent that modifies endocannabinoid function will soon be clinically available in the form of cannabidiol. Recent research has demonstrated that although THC does not share VR1 agonistic activity with AEA, CBD does so to a similar degree as capsaicin [78]. What is more, CBD inhibits uptake of the endocannabinoid anandamide (AEA), and weakly inhibits its hydrolysis. The presence of this component in available cannabis based medicine extracts portends to vastly extend the clinical applications and therapeutic efficacy of this re-emerging modality [118–120].

It is highly likely that additional regulatory roles for endocannabinoids will be discovered for this neuroand immunomodulatory system. Some simple human experiments may be valuable, such as cerebrospinal fluid assay of AEA and 2-AG before and after ECT treatment. It is likely in the future that positron emission tomography (PET) or functional magnetic resonance imaging (fMRI) for cannabinoid ligands may clarify these concepts.

This article has examined the inter-relationships of three clinical syndromes and biochemical basis I endocannabinoid function, as well as reflecting on other conditions that may display similar correlations.

Only time and the scientific method will ascertain whether a new paradigm is applicable to human physiology and treatment of its derangements. Our insight into these possibilities is dependent on the contribution of one unique healing plant; for clinical cannabis has become a therapeutic compass to what modern medicine fails to cure.

REFERENCES

1 Freud S. Project for a scientific psychology. Trans. Strachey J. In: The standard edition of the complete psychological works of Sigmund Freud. Vol. 1, 24 vols. London: Hogarth Press.; 1966. p. 281–343.
2 Di Marzo V. ‘Endocannabinoids’ and other fatty acid derivatives with cannabimimetic properties: biochemistry and possible physiopathological relevance. Biochim Biophys Acta 1998; 1392:153–175.
3 Russo EB. Role of cannabis and cannabinoids in pain management. In: Weiner RS, editors. Pain management: A practical guide for clinicians. 6th edit., 2 vols. Boca Raton, FL: CRC Press; 2002. p. 357–375.
4 Pertwee RG. Cannabinoid receptors and pain. Prog Neurobiol 2001; 63:569–611.
5 Russo EB. Hemp for headache: An in-depth historical and scientific review of cannabis in migraine treatment. Journal of Cannabis Therapeutics 2001; 1:21–92.
6 Russo EB. Handbook of psychotropic herbs: A scientific analysis of herbal remedies for psychiatric conditions. 2001. Haworth Press,  Binghamton, NY.
7 Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992; 258:1946–1949.
8 Herkenham MA. Localization of cannabinoid receptors in brain: relationship to motor and reward systems. In: Korman SG, Barchas JD, editors. Biological Basis of Substance Abuse. London: OxfordUniversity; 1993. p. 187–200.
9 Fride E, Mechoulam R. Pharmacological activity of the cannabinoid receptor agonist, anandamide, a brain constituent. Eur J Pharmacol1993; 231:313–314.
10 Stewart WF, Lipton RB, Celentano DD, Reed ML. Prevalence of migraine headache in the United States. Relation to age, ncome, race, and other sociodemographic factors. Journal of the American Medical Association 1992; 267:64–69.
11 Lipton RB, Stewart WF. Migraine in the United States: A review of epidemiology and health care use. Neurology 1993; 43:S6–10.
12 Russo E. Cannabis for migraine treatment: The once and future prescription? An historical and scientific review. Pain 1998; 76:3–8.
13 Volfe Z, Dvilansky A, Nathan I. Cannabinoids block release of serotonin from platelets induced by plasma from migraine patients. Int J Clin Pharmacol Res 1985; 5:243–246.
14 Spadone C. Neurophysiologie du cannabis [Neurophysiology of cannabis]. Encephale 1991; 17:17–22.
15 Fan P. Cannabinoid agonists inhibit the activation of 5-HT3 receptors in rat nodose ganglion. Journal of Neurophysiology 1995; 73: 907–910.
16 Boger DL, Patterson JE, Jin Q. Structural requirements for 5-HT2A and 5-HT1A serotonin receptor potentiation by the biologically active lipid oleamide. Proc Natl Acad Sci U S A 1998; 95:4102–4107.
17 Hall B, Burnett A, Christians A, Halley C, Parker LA, Russo E, et al. (2004). Pharmacology of cannabidiol at serotonin receptors. Western Pharmacology Society, Honolulu, HI.
18 Russo EB, Macarah CM, Todd CL, Medora R, Parker K. (2000). Pharmacology of the essential oil of hemp at 5HT1A and 5HT2a receptors. 41st Annual Meeting of the American Society of Pharmacognosy, Seattle, WA.
19 Kimura T, Ohta T, Watanabe K, Yoshimura H, Yamamoto I. Anandamide, an endogenous cannabinoid receptor ligand, also interacts with 5-hydroxytryptamine (5-HT) receptor. Biol Pharm Bull 1998; 21:224–226.
20 Peroutka SJ. The pharmacology of current anti-migraine drugs. Headache 1990; 30:5–11; discussion 24–18.
21 Peroutka SJ. Dopamine and migraine. Neurology 1997; 49:650– 656.
22 Ferri S, Cavicchini E, Romualdi P, Speroni E, Murari G. Possible mediation of catecholaminergic pathways in the antinociceptive effect of an extract of Cannabis sativa L. Psychopharmacology 1986; 89: 244–247.
23 Stefano GB, Salzet B, Rialas CM, Pope M, Kustka A, Neenan K, et al. Morphine- and anandamide-stimulated nitric oxide production inhibits presynaptic dopamine release. Brain Res 1997; 763:63–68.
24 Muller-Vahl KR, Schneider U, Prevedel H, Theloe K, Kolbe H, Daldrup T, et al. Delta9-Tetrahydrocannabinol (THC) is Effective in the Treatment of Tics in Tourette Syndrome: a 6-Week Randomized Trial. J Clin Psychiatry 2003; 64:459–465.


Clinical Endocannabinoid Deficiency (CECD)

38 Neuroendocrinology Letters Nos.1/2 Feb-Apr Vol.25, 2004 Copyright © Neuroendocrinology Letters ISSN 0172–780X www.nel.edu 25 Müller-Vahl KR, Schneider U, Kolbe H, Emrich HM. Treatment of
Tourette’s syndrome with delta-9-tetrahydrocannabinol. Am J Psychiatry1999; 156:495. 26 Leweke FM, Giuffrida A, Wurster U, Emrich HM, Piomelli D. Elevated endogenous cannabinoids in schizophrenia. Neuroreport 1999; 10: 1665-1669.
27 Burstein S. Eicosanoids as mediators of cannabinoid action. In: Murphy L, Bartke A, editors. Marijuana/Cannabinoids: Neurobiologyand neurophysiology of drug abuse. Boca Raton: CRC Press; 1992. p. 73–91.
28 Evans AT, Formukong EA, Evans FJ. Actions of cannabis constituents on enzymes of arachidonate metabolism: anti-inflammatory potential. Biochem Pharmacol 1987; 36:2035–2037.
29 Formukong EA, Evans AT, Evans FJ. Analgesic and anti-inflammatory activity of constituents of Cannabis sativa L. Inflammation 1988; 12:361–371. 30 Formukong EA, Evans AT, Evans FJ. The inhibitory effects of cannabinoids, the active constituents of Cannabis sativa L. on human and rabbit platelet aggregation. J Pharm Pharmacol 1989; 41: 705–709.
31 McPartland J. Cannabis and eicosanoids: A review of molecular pharmacology. Journal of Cannabis Therapeutics 2001; 1:71–83. 32 Burstein S, Levin E, Varanelli C. Prostaglandins and cannabis. II. Inhibition of biosynthesis by the naturally occurring cannabinoids. Biochem Pharmacol 1973; 22:2905–2910.
33 Schaefer CF, Brackett DJ, Gunn CG, Dubowski KM. Decreased platelet aggregation following marihuana smoking in man. J Okla State Med Assoc 1979; 72:435–436.
34 Evans FJ. Cannabinoids: The separation of central from peripheral effects on a structural basis. Planta Med 1991; 57:S60–67.
35 Hampson AJ, Hill WA, Zan-Phillips M, Makriyannis A, Leung E, Eglen RM, et al. Anandamide hydroxylation by brain lipoxygenase:metabolite structures and potencies at the cannabinoid receptor. Biochim Biophys Acta 1995; 1259:173–179.
36 Fimiani C, Liberty T, Aquirre AJ, Amin I, Ali N, Stefano GB. Opiate, cannabinoid, and eicosanoid signaling converges on common intracellular pathways nitric oxide coupling. Prostaglandins Other Lipid Mediat 1999; 57:23–34.
37 Fettes I, Gawel M, Kuzniak S, Edmeads J. Endorphin levels in headache syndromes. Headache 1985; 25:37–39.
38 Wiegant VM, Sweep CG, Nir I. Effect of acute administration of delta 1-tetrahydrocannabinol on beta- endorphin levels in plasma and brain tissue of the rat. Experientia 1987; 43:413–415.
39 Mailleux P, Vanderhaeghen JJ. Delta-9-tetrahydrocannabinol regulates substance P and enkephalin mRNAs levels in the caudate-putamen. Eur J Pharmacol 1994; 267:R1–3.
40 Meng ID, Manning BH, Martin WJ, Fields HL. An analgesia circuit activated by cannabinoids. Nature 1998; 395:381–383.
41 Goadsby PJ, Gundlach AL. Localization of 3H-dihydroergotaminebinding sites in the cat central nervous system: relevance to migraine. Ann Neurol 1991; 29:91–94.
42 Lichtman AH, Martin BR. Spinal and supraspinal components of cannabinoid-induced antinociception. J Pharmacol Exp Ther 1991; 258:517–523.
43 Behbehani MM. Functional characteristics of the midbrain periaqueductal gray. Prog Neurobiol 1995; 46:575–605.
44 Castro ME, Pascual J, Romon T, del Arco C, del Olmo E, Pazos A. Differential distribution of [3H]sumatriptan binding sites (5-HT1B, 5- HT1D and 5-HT1F receptors) in human brain: focus on brainstem and spinal cord. Neuropharmacology 1997; 36:535–542.
45 Manzanares J, Corchero J, Romero J, Fernandez-Ruiz JJ, Ramos JA, Fuentes JA. Chronic administration of cannabinoids regulates proenkephalin mRNA levels in selected regions of the rat brain. Brain Res Mol Brain Res 1998; 55:126–132.
46 Walker JM, Huang SM, Strangman NM, Tsou K, Sanudo-Pena MC. Pain modulation by the release of the endogenous cannabinoid anandamide. Proceedings of the National Academy of Sciences 1999; 96: 12198–12203.
47 Hamann W, di Vadi PP. Analgesic effect of the cannabinoid analogue nabilone is not mediated by opioid receptors. Lancet 1999; 353: 560.
48 Nicolodi M. Painful and non-painful effects of low doses of morphine in migraine sufferers partly depend on excitatory amino acids and gamma- aminobutyric acid. Int J Clin Pharmacol Res 1998; 18: 79–85.
49 Storer RJ, Goadsby PJ. Trigeminovascular nociceptive transmission involves N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate receptors. Neuroscience 1999; 90:1371–1376. 50 Shen M, Piser TM, Seybold VS, Thayer SA. Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission in rat hippocampal cultures. J Neurosci 1996; 16:4322–4334.
51 Shen M, Thayer SA. Delta-9-tetrahydrocannabinol acts as a partial agonist to modulate glutamatergic synaptic transmission between rat hippocampal neurons in culture. Mol Pharmacol 1999; 55:8–13.
52 Nicolodi M, Sicuteri F. Exploration of NMDA receptors in migraine: Therapeutic and theoretic implications. Int J Clin Pharmacol Res 1995; 15:181–189.
53 Nicolodi M, Del Bianco PL, Sicuteri F. Modulation of excitatory amino acids pathway: a possible therapeutic approach to chronic daily headache associated with analgesic drugs abuse. Int J Clin Pharmacol Res 1997; 17:97–100.
54 Nicolodi M, Sicuteri F. Negative modultors [sic] of excitatory amino acids in episodic and chronic migraine: preventing and reverting chronic migraine. Special lecture 7th INWIN Congress. Int J Clin Pharmacol Res 1998; 18:93–100.
55 Hampson AJ, Grimaldi M, Axelrod J, Wink D. Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci U S A 1998; 95:8268–8273.
56 Main A, Dowson A, Gross M. Photophobia and phonophobia in migraineurs between attacks. Headache 1997; 37:492–495.
57 Mechoulam R, Ben-Shabat S. From gan-zi-gun-nu to Anandamide and 2-arachidonoylglycerol: The ongoing story of cannabis. Nat Prod Rep 1999; 16:131–143. than the sum of their parts? Journal of Cannabis Therapeutics 2001; 1:103–132.
59 Panikashvili D, Simeonidou C, Ben-Shabat S, Hanus L, Breuer A, Mechoulam R, et al. An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 2001; 413:527–531. 60 Mikuriya TH. 1997. Chronic migraine headache: Five cases successfully treated with marinol and/or illiciit cannabis.
61 Grinspoon L, Bakalar JB. Marihuana, the forbidden medicine. 1993. Yale University Press, New Haven. 62 el-Mallakh RS. Marijuana and migraine. Headache 1987; 27:442– 443.
63 Gieringer D. Medical use of cannabis: Experience in California. In: Grotenhermen F, Russo E, editors. Cannabis and cannabinoids: Pharmacology, toxicology, and therapeutic potential. Binghamton, NY: Haworth Press; 2001. p. 153–170.
64 Gieringer D. Medical cannabis potency testing project. Bulletin of the Multidisciplinary Association for Psychedelic Studies 1999; 9: 20–22.
65 Bohr T. Problems with myofascial pain syndrome and fibromyalgia syndrome. Neurology 1996; 46:593–597.
66 Bennett RM. Rational management of fibromyalgia. Rheum Dis Clin North Am 2002; 28:xiii–xv.
67 Nicolodi M, Volpe AR, Sicuteri F. Fibromyalgia and headache. Failure of serotonergic analgesia and N-methyl-D-aspartate-mediated neuronal plasticity: Their common clues. Cephalalgia 1998; 18 (Suppl 21):41–44.
68 Richardson JD, Aanonsen L, Hargreaves KM. SR 141716A, a cannabinoid receptor antagonist, produces hyperalgesia in untreated mice. Eur J Pharmacol 1997; 319:R3–4.
69 Richardson JD, Aanonsen L, Hargreaves KM. Hypoactivity of the spinal cannabinoid system results in NMDA-dependent hyperalgesia. J Neurosci 1998; 18:451–457.
70 Richardson JD, Aanonsen L, Hargreaves KM. Antihyperalgesic effects of spinal cannabinoids. Eur J Pharmacol 1998; 345:145–153.
71 Richardson JD, Kilo S, Hargreaves KM. Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors. Pain 1998; 75:111–119. 72 Li J, Daughters RS, Bullis C, Bengiamin R, Stucky MW, Brennan J, et the development of hyperalgesia produced by capsaicin in rats. Pain 1999; 81:25–33. 

73 Ko MC, Woods JH. Local administration of delta9-tetrahydrocannabinol attenuates capsaicin-induced thermal nociception in rhesus monkeys: a peripheral cannabinoid action. Psychopharmacology (Berl) 1999; 143:322–326.
74 Staud R, Vierck CJ, Cannon RL, Mauderli AP, Price DD. Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome. Pain 2001; 91:165–175.
75 Strangman NM, Walker JM. Cannabinoid WIN 55,212–2 inhibits the activity-dependent facilitation of spinal nociceptive responses. J Ethan B. Russo Neuroendocrinology Letters Nos.1/2 Feb-Apr Vol.25, 2004 Copyright © Neuroendocrinology Letters ISSN 0172–780X www.nel.edu 39 Neurophysiol 1999; 82:472–477.
76 Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, et al. Identification of an endogenous 2 monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995; 50:83–90.
77 Holzer P. Gastrointestinal afferents as targets of novel drugs for the treatment of functional bowel disorders and visceral pain. Eur J Pharmacol 2001; 429:177–193.
78 Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol 2001; 134:845–852.
79 Pertwee RG. Cannabinoids and the gastrointestinal tract. Gut 2001; 48:859–867.
80 Coutts AA, Irving AJ, Mackie K, Pertwee RG, Anavi-Goffer S. Localisation of cannabinoid CB(1) receptor immunoreactivity in the guinea pig and rat myenteric plexus. J Comp Neurol 2002; 448: 410–422.
81 Izzo AA, Fezza F, Capasso R, Bisogno T, Pinto L, Iuvone T, et al. Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation. Br J Pharmacol 2001; 134:563–570.
82 Anderson PF, Jackson DM, Chesher GB. Interaction of delta-9-tetrahydrocannabinol and cannabidiol on intestinal motility in mice. J Pharm Pharmacol 1974; 26:136–137.
83 Di Carlo G, Izzo AA. Cannabinoids for gastrointestinal diseases: potential therapeutic applications. Expert Opin Investig Drugs 2003; 12:39–49.
84 Russo E. Cannabinoids in pain management. Study was bound to conclude that cannabinoids had limited efficacy. Brit Med J 2001; 323:1249–1250; discussion 1250–1241. 85 Talley NJ. Evaluation of drug treatment in irritable bowel syndrome. Br J Clin Pharmacol 2003; 56:362–369. 86 Burstein R, Yarnitsky D, Goor-Aryeh I, Ransil BJ, Bajwa ZH. An association between migraine and cutaneous allodynia. Ann Neurol 2000; 47:614–624.
87 Weissman-Fogel I, Sprecher E, Granovsky Y, Yarnitsky D. Repeated noxious stimulation of the skin enhances cutaneous pain perception of migraine patients in-between attacks: clinical evidence for continuous sub-threshold increase in membrane excitability of central trigeminovascular neurons. Pain 2003; 104:693–700.
88 Nicolodi M, Sicuteri R, Coppola G, Greco E, Pietrini U, Sicuteri F. Visceral pain threshold is deeply lowered far from the head in migraine. Headache 1994; 34:12–19.
89 Nicolodi M, Sicuteri F. Fibromyalgia and migraine, two faces of the same mechanism. In: Filippini GA, editors. Recent advances in tryptophan research. New York: Plenum Press; 1996. p. 373–379.
90 Peres MF, Young WB, Kaup AO, Zukerman E, Silberstein SD. Fibromyalgia is common in patients with transformed migraine. Neurology 2001; 57:1326–1328.
91 Hudson JI, Goldenberg DL, Pope HG, Jr., Keck PE, Jr., Schlesinger L. Comorbidity of fibromyalgia with medical and psychiatric disorders. Am J Med 1992; 92:363–367.
92 Sperber AD, Atzmon Y, Neumann L, Weisberg I, Shalit Y, Abu- Shakrah M, et al. Fibromyalgia in the irritable bowel syndrome: studies of prevalence and clinical implications. Am J Gastroenterol 1999; 94:3541–3546.
93 Jaggar SI, Hasnie FS, Sellaturay S, Rice AS. The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain. Pain 1998; 76:189–199.
94 Jaggar SI, Sellaturay S, Rice AS. The endogenous cannabinoid anandamide, but not the CB2 ligand palmitoylethanolamide, prevents the viscero-visceral hyper-reflexia associated with inflammation of the rat urinary bladder. Neurosci Lett 1998; 253:123–126.
95 Brady CM, DasGupta R, Wiseman OJ, Berkley KJ, Fowler CJ. (2001). Congress of the International Association for Cannabis as Medicine, Berlin, Germany. 96 Verne GN, Robinson ME, Vase L, Price DD. Reversal of visceral and cutaneous hyperalgesia by local rectal anesthesia in irritable bowel
97 Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Huffman JW, et al. Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature 2000; 404:84–87.
98 Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomized placebo-controlled trial. Lancet 2003; 362:1517–1526.
99 Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clinical Rehabilitation 2003; 17:18–26.
100 Ferrari F, Ottani A, Giuliani D. Inhibitory effects of the cannabinoid agonist HU 210 on rat sexual behaviour. Physiol Behav 2000; 69: 547–554.
101 Notcutt W, Price M, Miller R, Newport S, Phillips C, Simmonds S, et al. Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 “N of 1” studies. Anaesthesia 2004; 59:440-452.
102 Jarvinen T, Pate D, Laine K. Cannabinoids in the treatment of glaucoma. Pharmacol Ther 2002; 95:203.
103 Russo E. Cannabis treatments in obstetrics and gynecology: A historical review. Journal of Cannabis Therapeutics 2002; 2:5–35.
104 Pertwee RG, Ross RA. Cannabinoid receptors and their ligands. Prostaglandins Leukot Essent Fatty Acids 2002; 66:101–121.
105 Williams SJ, Hartley JP, Graham JD. Bronchodilator effect of delta1-tetrahydrocannabinol administered by aerosol of asthmatic patients. Thorax 1976; 31:720–723.
106 Fride E. Cannabinoids and cystic fibrosis: A novel approach. Journal of Cannabis Therapeutics 2002; 2:59–71.
107 Grinspoon L, Bakalar JB. The use of cannabis as a mood stabilizer in bipolar disorder: anecdotal evidence and the need for clinical research. J Psychoactive Drugs 1998; 30:171–177.
108 Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, et al. The endogenous cannabinoid system controls extinction of aversive memories. Nature 2002; 418:530–534.
109 Wallace MJ, Martin BR, DeLorenzo RJ. Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity. Eur J Pharmacol 2002; 452:295–301.
110 Wallace MJ, Blair RE, Falenski KW, Martin BR, DeLorenzo RJ. The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther 2003; 307:129–137.
111 Delgado P, Moreno F. Antidepressants and the brain. Int Clin Psychopharmacol 1999; 14 Suppl 1:S9–16.
112 Baker D, Pryce G, Giovannoni G, Thompson AJ. The therapeutic potential of cannabis. Lancet Neurology 2003; 2:291–298.
113 Mechoulam R, Panikashvili D, Shohami E. Cannabinoids and brain injury: therapeutic implications. Trends Mol Med 2002; 8:58–61.
114 Guzman M. Cannabinoids: potential anticancer agents. Nat Rev Cancer 2003; 3:745–755.
115 Maccarrone M, Finazzi-Agro A. The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis. Cell Death Differ 2003; 10:946–955.
116 Hillard CJ, Jarrahian A. Cellular accumulation of anandamide: consensus and controversy. Br J Pharmacol 2003; 140:802–808.
117 Porter AC, Sauer JM, Knierman MD, Becker GW, Berna MJ, Bao J, et al. Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther 2002; 301:1020–1024.
118 Russo EB. Cannabis-From pariah to prescription. Journal of Cannabis Therapeutics 2003; 3(3):1–29.
119 Whittle BA, Guy GW, Robson P. Prospects for new cannabis-based prescription medicines. Journal of Cannabis Therapeutics 2001; 1: 183–205.
120 Whittle BA, Guy GW, Robson P. Cannabis and cannabinoids as medicines. 2003. Pharmaceutical Press, London. Clinical Endocannabinoid Deficiency (CECD)
Read More... Clinical Endocannabinoid Deficiency (CECD)

Moon with a View

Moon with a View: Or, What Did Arthur Know … and When Did He Know it?
By Richard C. Hoagland



Read More... Moon with a View

Richard Feynman - Elementary Particles and the Laws of Physics

Elementary Particles and the Laws of Physics
1:14:24 - 3 years




The 1986 Dirac Memorial Lecture presented by Richard Feynman. Paul Dirac predicted the existence of antiparticles, and Richard Feynman explains now why there must be antiparticles. He lectures about particles, quantum theory, and relativity. A special pleasure is watching Feynman’s personal style of lecturing: his humor, his showmanship, and his brilliance.


WIKI SEZ!
IMDB SEZ!
BBC Clip Archive Feynman
Read More... Richard Feynman - Elementary Particles and the Laws of Physics

Richard P Feynman - The Last Journey Of A Genius

The Last Journey Of A Genius 
(The Quest For Tannu Tuva) 1988 54:37 - 2 years ago


I love Feynman a true genius, he has written many books. They are extremely interesting and hilarious, despite some of the serious subject matter disguised in them. I will be posting all the Feynman I can possibly find.

NOVA looks at the bongo-playing scientist, adventurer, safecracker and yarn-spinner Richard Feynman, most recently famous for his role as gadfly of the Presidential Commission investigating the explosion of the space shuttle Challenger.

WIKI SEZ Tannu Tuva
Word IQ SEZ
WIKI SEZ!
IMDB SEZ!
BBC Clip Archive Feynman
Read More... Richard P Feynman - The Last Journey Of A Genius

Richard Feynman - The Pleasure of Finding Things Out

The Pleasure of Finding Things Out 49:37 - 3 years ago
BBC Horizon/PBS Nova



I love Feynman a true genius, he has also written many books. They are extremely interesting and hilarious, despite some of the serious subject matter disguised in them. I will be posting all the Feynman I can possibly find.

This is the original Horizon Nova interview - essential for any Feynman fan... and for everyone else too! "I'm an explorer, OK I like to find out!" Richard Feynman, physicist and adventurer extraordinary, was filmed in 1981 will delight and inspire anyone who would like to share something of the joys of scientific discovery. Feynman is a master storyteller, and his tales about childhood, Los Alamos, or how he won a Nobel Prize. A vivid and entertaining insight into the mind of a great scientist at work and play. 
"The 1981 Feynman Horizon is the best science program I have ever seen. This is not just my opinion - it is also the opinion of many of the best scientists that I know who have seen the program... It should be mandatory viewing for all students whether they be science or arts students." - Professor Sir Harry Kroto, Nobel Prize for Chemistry


WIKI SEZ!
IMDB SEZ!
BBC Clip Archive Feynman  
Read More... Richard Feynman - The Pleasure of Finding Things Out

A request to my internet family!! please take the time and read this

NON Profit Organization for Medical Marijuana in Israel

A request to my internet family,

I am looking for people around the world with experience and talent to help with the various issues connected to the web presence for the NON Profit Organization for Medical Marijuana in Israel. The charity is to help the sick and needy and not for personal gain, be assured it is for a good cause.
We need artists, designers, web geeks an others to help get the new charity's web presence up and running. If you are an artist, free thinker or any of the above we can use your help with graphics, code and other issues associated with the over all internet presence that I may not be aware of or have overlooked. If you want to help, mail my Facebook account with your personal talents and what you think you can do to help the cause.

Where you live and what language you speak or what god you pray to has nothing to do with the cause or issue of medical marijuana for the sick.

This is your chance to make a difference in some ones life, take a stand for what is correct!

All suggestions and all forms of help are welcome,

mazanga
Read More... A request to my internet family!! please take the time and read this

The Association Method - Carl G. Jung

The Association Method - Carl G. Jung (1910)
First published in American Journal of Psychology, 31, 219-269.



LECTURE I

Ladies and Gentlemen: When I was honored with the invitation from Clark University to lecture before this esteemed assemblage, a wish was at the same time expressed that I should speak about my methods of work, and especially about the psychology of childhood. I hope to accomplish this task in the following manner:

In my first lecture I shall try to present to you the view points of my association methods; in my second lecture I shall discuss the significance of the familiar constellations; while in my third lecture I shall enter more fully into the psychology of the child. I might easily confine myself exclusively to my theoretical views, but I believe that it will be better to illustrate my lectures with as many practical examples as possible. We shall therefore occupy ourselves first with the method of association, a method which has been of valuable assistance to me both practically and theoretically. The association method in vogue in psychology, as well as its history, is of course, so familiar to you that there is no need to speak of it.
Read More... The Association Method - Carl G. Jung

ISIS UNVEILED: By H. P. Blavatsky

ISIS UNVEILED:
A MASTER-KEY TO THE MYSTERIES OF ANCIENT AND MODERN SCIENCE AND THEOLOGY.
BY H. P. BLAVATSKY,
CORRESPONDING SECRETARY OF THE THEOSOPHICAL SOCIETY.
"Cecy est un livre de bonne Foy." -- MONTAIGNE.



Blavatsky's first major work on theosophy, examining religion and science in the light of Western and Oriental ancient wisdom and occult and spiritualistic phenomena. 
Anciently known as Brachmanes, mistaken sometimes for Brahmans.* They are all magicians, or rather sensitives or mediums artificially developed. At present those who act as priests among the Tartars are generally very ignorant, and far below the fakirs in knowledge and education. Both men and women may be Shamans.

Forget any anything you have EVER heard about Helena Blavatsky!!!
LEARN FOR YOURSELF WHY SO MANY PEOPLE DONT WANT YOU READING THESES BOOKS!!!
We just have to point out how intelligent and incredible this person was!!!

(WARNING) THIS MAY SHOW YOU THINGS YOU DONT WANT TO KNOW!!! (WARNING)

Would you like to know where so MANY researchers, authors, movie producers, governments
And secret societies learned so many of the basics of the GAME??? Well HERE it IS!!!


* Orpheus is said to have ascribed to the grand cycle 120,000 years of duration, and Cassandrus 136,000. See Censorinus: "de Natal. Die"; "Chronological and Astronomical Fragments."

Have you ever wondered where the moon came from?
Have you ever contemplated how the asteroid belt Came to be?
These are basic things to WONDER about!! We need everyoneÆs help!! Do your part!!

When the student is ready, the teacher will present oneÆs self.
Come help us figure this mystery OUT!!!!
No matter what your color or belief, Sex or age, YOU can be a scientist!!
Challenge yourself, your peers, your teachers. Participate in a revolution in science!!
Read More... ISIS UNVEILED: By H. P. Blavatsky

Letter #3 to POS lawyer #4

A year ago approximately I appointed you to take care of my interests in all   matters and proceedings concerning my disease. You were highly recommended by Dorit my lawyer who then persuaded me that you were the most able to succeed. You asked $$$$$ +blood money XXX in fees.
      I was reluctant having giving my trust to a previous lawyer who took fees without giving services...
       My situation then: a crippling condition which left me unable to work, to walk, to tend my house, but despite of it, was not fully recognized.
I have no other income except the minimal help from the xxxxx xxxx, I used all the money I had, to pay your fees and those of xxxxx. A year later nothing changed except, that after paying a years rent I will have nothing left and my physical condition continues to degrade.
        You accomplished nothing, you haven’t even shown the slightest evidence of progress, I have doubts that you even sent letters to any administration and a phone conversation that I had with you showed me that you didn't even care to read any of the kg of papers I sent to your office. I still wait for their return after a year.
You don't return my calls or messages, what did you do for $$$$$$ + blood money?
I say all u did is collect it, I have seen nothing else. And your secretary has the nerve to demand $$ for paperwork.
          I remind you again what you were paid to act on my behalf on.
xxxxxxxxxx: Getting me a hearing for my disability along with a parking permit, a house helper, subsidized vehicle, specialized care, the additional money for my disability allowance and all other benefits that they offer for disabled moneyless suffering people like me.
I.D.F: Getting the injuries I had received during my military service recognized along with their health consequences, settling the various issues related to the military disability. I have received from your office 3 papers that state nothing.

Insurance matters: All issues related to my disability, getting the insurance claim that the insurance company has not paid me in 14 + years. My questions on stopping payment of the premiums that I have been paying and can no longer afford remain unanswered.
In a year you were not even able to get me an appointment with XXXXX XXXXX board for the additional  benefits and conditions offered to me for my disability. People without the “help” of a lawyer get it generally in six months. Dumb I was to think that you'll speed up the procedure, just like the last lawyer that did nothing he was paid for.
   A week ago I was forced to ask for urgent help from the town social services for food, (I have reached the point where I need help to buy food because my lawyers have all my money, not that they even care. I am sure you are eating well, and taking flights out of Israel and enjoying yourself with my money but as of yet I have seen nothing)

The social worker asked for the following documents:
         -protocol of the XXXXX XXXX
         -proof that I receive an allowance from XXXXX XXXX
         -proof that I didn't work since my last accident (1996)
         -proof that I'm disabled.
The social worker also made me sign a document for disclosure of personal medical information which I didn’t like the idea of, but she assured me that she could retrieve the protocol quickly, that seems to be better than my over priced lawyer who I see has done nothing so far.
In addition, you were supposed to give me back all my medical documents that I need for doctors visits after making copies of them. That was eight+ months ago, I am still waiting.



You told me that that you were not able to find any contact information for my former lawyer (the one I told you stole my money and did nothing, he was supposed to be different to you) it took me all of 30 min on the internet and a few telephone calls to find him.
As you see I'm more disappointed and disgusted by your “services” or the absence of, or is it up to the client to ride and remind his “lawyer” what he was appointed and paid to do?
What made me deserve your lack of professional standards?
Didn't I pay your fee in full and in cash?
Would you have felt different if I argued with you about it all?
What makes other clients worth your efforts?
I'm sure they exist otherwise XXXXX wouldn't have recommend you, but even of that I am not sure. Or do you ignore them all as you seem not to have the time for me, even though I am paid in full. You are the one that owes me at this point, and I will remind you again that you are accountable for your service and for the third time you owe me.

I demand that you send me a list of all the proceedings in progress and where they stand; I believe and trust no one especially so called lawyers any more.

Totally disgusted and disappointed,

XXXXXX
Read More... Letter #3 to POS lawyer #4

The Secret Rulers of the World #5 The Bilderberg Group

The Bilderberg Group 48:11 - 1 year ago
Aired date: Sun, May 27, 2001

Plot: Ronson teams up with reporter James P. Tucker, Jr., who has been investigating the Bilderberg Group, an annual invitation-only conference, for over thirty years. According to Tucker, around 130 guests, most of whom are persons of influence in business, academic, or political circles, meet annually in secret. The duo encounter unwelcoming suited security men and a car chase. Ronson also interviews Group founder Denis Healey.






Read More... The Secret Rulers of the World #5 The Bilderberg Group

The Secret Rulers of The World #2 David Icke The Lizards and The Jews

David Icke, The Lizards and The Jews 48:54 - 4 years ago
Aired date: Sun, May 6, 2001

Plot: Jon Ronson follows David Icke as he promotes his theory that "the elite are genetically descended from a race of 12 foot, blood drinking, shape shifting lizards". During the film Icke is accused in Canada of antisemitism. Ronson questions whether Icke literally means lizards, as he steadfastly maintains, or whether the reptilians are a coded reference to Jews, which Icke denies adamantly. At the end of the documentary, it is shown that one of the members of the Anarchist organization who is used as a main presenter of the idea that David Icke is an anti-Semite finally reads the book written by David and admits himself that David Icke obviously means Reptiles and can't justly be claimed as an anti-Semite.

Read More... The Secret Rulers of The World #2 David Icke The Lizards and The Jews

The Secret Rulers Of The World #4 The Satanic Shadowy Elite?

The Satanic Shadowy Elite 48:57 - 2 years ago 
Aired date: Sun, May 20, 2001

Plot: Jon Ronson follows conspiracy theorist and radio host Alex Jones as he attempts to infiltrate the annual gathering of dignitaries and business leaders (reportedly including George Bush and Henry Kissinger) at Bohemian Grove, California. The film includes footage of attendees dressed in robes and burning an effigy at the foot of a giant stone owl. Jones believes that the ceremony is related to occult secret societies. After the event, Ronson meets comedy actor and fellow attendee Harry Shearer who describes the event as a glorified fraternity party. Shearer largely dismisses Jones's dramatic retelling of the gathering and notes that the music is supplied by The Symphony Orchestra of San Francisco

Read More... The Secret Rulers Of The World #4 The Satanic Shadowy Elite?

BitTorrent Admins Charged in $1.25bn Movie Piracy Case

BitTorrent Admins Charged in $1.25bn Movie Piracy Case

Written by enigmax on July 13, 2010 
Following the country’s first ever raid on a BitTorrent site in 2009, Russian authorities have now begun a criminal investigation into the operators of Interfilm.ru. Run by a married couple, the site is now at the center of copyright infringement claim which runs to a staggering $1.25 billion. Reports suggest that the investigation has also traced some of the site’s top users.
mvdClaiming that the site was a major source of pre-release cammed movies with links to piracy groups outside the country, on May 26th 2009 the Russian Federation Ministry of Internal Affairs Investigation Committee under the Ministry of Internal Affairs carried out a raid on the the Russian BitTorrent tracker, Interfilm.ru.
The action followed complaints from anti-piracy group RAPO, a founding member of the MPA which represents the interests of Universal, Paramount, Sony, Warner Bros and 20th Century Fox in Russia.
At Interfilm’s Moscow base the police arrested several staff and also the main targets, husband and wife team Ivan and Irina Podorozhnikovymi.
Just over a year later the Interior Ministry Investigation Committee has now filed criminal charges against the pair, known online as ‘Ripper’ and ‘Nadezhda’. The scope of the accusations are quite incredible. Domestic and foreign film companies claim that the tracker caused 38.7 billion rubles in damages – a mind-blowing $1.253 billion.
interfilmAlthough it has not been revealed how this astronomical figure was reached, if convicted the founders – who the authorities say moved house and took technical measures to keep the site up during the investigation – could be facing up to six years in jail under Part 3 of Article 146 of the Criminal Code.
In addition to action against the site’s founders, there is an ongoing investigation into some of the top users of the site. However, in order to prove that regular users committed any crimes, under Russian law it would be necessary to prove they profited from their actions on a large scale.
There are claims that some individuals downloaded fresh movie releases from Interfilm and then uploaded them to their own sites. Police are considering whether to launch criminal investigations in these cases.
Although Interfilm went down after the initial raid, it reappeared at LeaseWeb in The Netherlands. The site remains operational today with a Malaysian host but is perhaps preparing for trouble. In addition to using the Interfilm.ru domain, the site is also in operation from BitHouse.org. Russia’s biggest torrent site, Torrents.ru, recently had to change its name to RUTracker.org after its domain was seized by Russian authorities.

http://torrentfreak.com/bittorrent-admins-charged-in-1-25bn-movie-piracy-100713/?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+Torrentfreak+%28Torrentfreak%29
Read More... BitTorrent Admins Charged in $1.25bn Movie Piracy Case

The Theory of Psychoanalysis BY DR. C. G. JUNG



Carl Gustav Jung
The Theory of Psychoanalysis
In these lectures I have attempted to reconcile my practical experiences in psychoanalysis with the existing theory, or rather, with the approaches to such a theory. Here is my attitude towards those principles which my honored teacher Sigmund Freud has evolved from the experience of many decades. Since I have long been closely connected with psychoanalysis, it will perhaps be asked with astonishment how it is that I am now for the first time defining my theoretical position. When, some ten years ago, it came home to me what a vast distance Freud had already traveled beyond the bounds of contemporary knowledge of psycho-pathological phenomena, especially the psychology of the complex mental processes, I no longer felt myself in a position to exercise any real criticism. I did not possess the sorry mandarin courage of those people who upon a basis of ignorance and incapacity consider themselves justified in "critical "rejections. I thought one must first work modestly for years in such a field before one might dare to criticize. The evil results of premature and superficial criticism have certainly not been lacking. A preponderating number of critics have attacked with as much anger as ignorance. Psychoanalysis has flourished undisturbed and has not troubled itself one jot or tittle about the unscientific chatter that has buzzed around it.
Read More... The Theory of Psychoanalysis BY DR. C. G. JUNG

The Secret Rulers of The World #3 April 19th The Oklahoma Bomb

The Secret Rulers Of The World S1E3
Aired date: Sun, May 13, 2001
April 19th: The Oklahoma Bomb
THIS VIDEO IS EXTREMELY HARD TO FIND, I have cut the documentary in to 5 pieces and posted it on YouTube and on this blog. Enjoy and learn!
Plot: Before his involvement in the Oklahoma City bombing, Timothy McVeigh believed that a shadowy elite secretly controlled the governments of the world, conspiring to establish a genocidal New World Order. He believed that the Alfred P. Murrah building was local New World Order headquarters. But many other theorists are convinced that the world only knows part of an apparent complex conspiracy story behind the bombing. Ronson meets a number of theorists whilst investigating the story, and concludes his film in Elohim City, a survivalist compound in Oklahoma.

#1

#2

#3

#4

#5


http://www.imdb.com/title/tt1130470/http://en.wikipedia.org/wiki/The_Secret_Rulers_of_the_World
http://www.ovguide.com/tv/the_secret_rulers_of_the_world.htm



The Secret Rulers of The World #1 The Legend of Ruby Ridge
The Secret Rulers of The World #2 David Icke, The Lizards and The Jews
The Secret Rulers of The World #3 April 19th The Oklahoma Bomb
The Secret Rulers of The World #4 The Satanic Shadowy Elite?
The Secret Rulers of The World #5 The Bilderberg Group
Read More... The Secret Rulers of The World #3 April 19th The Oklahoma Bomb

Your balls r hanging out of your shorts.avi

Bondi Beach life guard saves mans balls from burning!!
Read More... Your balls r hanging out of your shorts.avi

Mazanga Von Badman - powered by FeedBurner

Read More... Mazanga Von Badman - powered by FeedBurner

Contractor for BOEING has decided to Warn People.2010



The anomaly is confirmed. The object is artificial. Now we have confirmation...What is it??
StarViewerTeam Internacional 2010. StarViewerTeam International 2010.

I.-Summary.
Between 10:05:39 pm on March 19 and 11:42 pm, an anomaly is detected in LASCO C3 (One of the nodes Telescope SOHO).. The anomaly can be seen in the trace of an object, whose trajectory can be determined with the help of the Hubble STEREO Behind COR Node 1. For latrayectoria, displacement and object positions, we can determine that its size is similar to the size of Earth, and its speed, trajectory and relative positions are incompatible with any natural object. The object has been photographed from several different geographical locations, New Zealand, USA, Australia. AEO1 Bright Objects near the Sun. Bright Objects AEO1 near the Sun. AEO2 Starlike Objects with Anomalous Motions.AEX1 Objects Crossing the Face of the Sun. Objects with AEO2 Starlike Anomalous Objects Motions.AEX1 Crossing the Face of the Sun.
_________________
The turning of the stars bring a time when my secrets can give you immortality.
but when that time has passed, those fleeting minutes gone, the secret is worthless.
until once again the stars unlock its power.

Last edited by 01000001 on Mon Mar 22, 2010 11:23 am, edited 1 time in total.

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Post subject: Re: 2012 - Planet X, Geologically how much damage can we expect?
PostPosted: Mon Mar 22, 2010 11:17 am
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Image
NASA Images Earth Sized Spherical Objects Inside Corona of SUN

BINGO!!!!!
What you are seeing here is a "SOLID OBJECT" It's not compression artifacts, pixels or dust, who says so? NASA! on their official web site read on below

Important Update, a new video from Sandi and some new pictures

Below is the official NASA website Astronomy Picture of the Day, on the picture below you can see spheres passing by the Sun, the sphere is Mercury and it has an uncanny resemblance to the spheres Mr. Joseph Gurman of NASA dismissed as "Compression artifacts, highly magnified". It would suggest all the photo's below are images of solid objects and not, Compression artifacts, pixels or dust!

Astronomy Picture of the Day
Discover the cosmos! Each day a different image or photograph of our fascinating universe is featured, along with a brief explanation written by a professional astronomer.

2004 June 6
Click on image to enlarge
Mercury Spotting
Credit: SOHO - EIT Consortium, ESA, NASA
Explanation: Can you spot the planet? The diminutive disk of Mercury, the solar system's innermost planet, spent about five hours crossing in front of the enormous solar disk on 2003 May 7, as viewed from the general vicinity of planet Earth. The Sun was above the horizon during the entire transit for observers in Europe, Africa, Asia, or Australia, and the horizon was certainly no problem for the sun-staring SOHO spacecraft. Seen as a dark spot, Mercury progresses from left to right (top panel to bottom) in these four images from SOHO's extreme ultraviolet camera. The panels' false-colors correspond to different wavelengths in the extreme ultraviolet which highlight regions above the Sun's visible surface. This was the first of 14 transits of Mercury which will occur during the 21st century, but the next similar event will be a much more rare transit of Venus this coming Tuesday. Need help spotting Mercury? Just click on the picture.
Astronomy Picture of the day

Who are NASA trying to kid? Here are two NASA SOHO images of the Sun taken yesterday, one at 23:24 and one at 23:44, did the sun suddenly flip over?

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Letter #2 to Lawyer!

A bit more than a year ago I appointed you to take care of my interests in the various legal cases opposing me to my ex wife, the important points were:
                -the definitive custody of my son **** (my only child who has not been alienated from me by his mother and who is still balanced and well adjusted despite all what he went through).
                 -the rights of visit over my two daughters (I still have no contacts whatsoever with Dana and Lilach has discontinued hers when I have refused to participate in her lies and manipulations )
                 -the supervision of the education of my daughter Lilach (I'm very concerned by the degradation of her behavior (truancy, petty larceny, alcoholism, auto mutilation, etc
                 -the financial settlement after the selling of the family house.
                 -the question of the unfair child support granted to my ex.

To carry through these action you asked me X for fees, and I paid in full, in cash!
Since then the custody of **** have been granted to me TEMPORARILY not so much because of your proceedings but because of the defection of his mother (she has been out of the country for months and will be going again very soon) and entrusting my son to his aunt was clearly unrealistic. During this time in my custody **** has regained his balance, he is living a regular life, has social interactions with his fellow pupils, and with the families of my circle of friends, has improved his school grades, sleeps and eat better and in a word is happier.

Now my ex wife is carrying another offensive:

She came back from the Philippines ago after living there in luxury hotels on the account of public charity. To maintain her life standards (new car, new clothes etc) she is scraping what she can, she is asking for half of my sum left after the selling of our house.
And she's again using **** as a bargaining chip to have more; she has told me many times “You better accept otherwise... I will sue you in court again and force **** to come back) **** is also still made to hear nasty remarks from all connected to my ex wifes house hold (....”bastard”, “jackass”, “we will never talk to him again” and endless other chains of garbage which do him NO good!).
I phoned and smsed you several times to report the recent developments you don’t return my calls, I see no actions taking place on my behalf whats so ever. Meanwhile I'm sure that my ex wife is not losing time looking for more ways to make my life a living hell.
 I'm greatly disappointed about the way you are dealing with me and my problems. I never discussed your fees despite my financial situation and you have been far from volunteering, I find myself asking again, am I stupid to give you my trust, I think that I deserved more responsible and thorough treatment and notifications. But in a year almost nothing has been done and I fear for my son: what would happen to him if he was returning to this atmosphere of hysteria and emotional blackmail and total alienation and denial of the true fact.

And for me if nothing is being done I'm going to be dispossessed of the last remnant of my money. How am I going to live?  I remind you again that I have only a pension for disability ****. To add to the situation the lawyer YOU advised me to employ for taking care of my insurance matters isn't doing anything either. He even didn't take accurately the in formations I gave him and funny enough doesnt return calls either.
I wouldn't like to qualify these behaviors as unethical, immoral, how else would you call a so called professional who is collecting very comfortable fees but deliver no service or drags it out to the point of hopelessness?
I seriously hope that it is a misunderstanding, or an undervaluation of the situation, my SOS having not been properly reported.

Nonetheless I keep asking myself what make some other clients deserving of attention I'm deprived of, I have paid in full but get no service or replies to my calls or faxes.

In conclusion I ask you to send me an accurate report of the accomplished proceedings and of the ones which are in progress and where they all stand. That includes all the faxes I have sent to you in the past and that are still unanswered.


Read More... Letter #2 to Lawyer!

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