Friday, January 6, 2012

Cannabis and Cannabinoids, Cancer Antitumor Effects, Prion prevention, Pain management, Muscle relaxer, and Palliative Medicine

National Cancer Institute at the National Institutes of Health

Cannabis and Cannabinoids (PDQ®), Cancer Antitumor Effects, Prion prevention, Pain management, muscle relaxer, and Palliative Medicine

Cannabis and Cannabinoids (PDQ®)

Laboratory/Animal/Preclinical Studies

Antitumor Effects Appetite Stimulation Analgesia

Cannabinoids are a group of 21-carbon–containing terpenophenolic compounds produced uniquely by Cannabis sativa and Cannabis indica species.[1,2] These plant-derived compounds may be referred to as phytocannabinoids. Although delta-9-tetrahydrocannabinol (THC) is the primary psychoactive ingredient, other known compounds with biologic activity are cannabinol, cannabidiol (CBD), cannabichromene, cannabigerol, tetrahydrocannabivarin, and delta-8-THC. CBD, in particular, is thought to have significant analgesic and anti-inflammatory activity without the psychoactive effect (high) of delta-9-THC.

Antitumor Effects

One study in mice and rats suggested that cannabinoids may have a protective effect against the development of certain types of tumors.[3] During this 2-year study, groups of mice and rats were given various doses of THC by gavage. A dose-related decrease in the incidence of hepatic adenoma tumors and hepatocellular carcinoma was observed in the mice. Decreased incidences of benign tumors (polyps and adenomas) in other organs (mammary gland, uterus, pituitary, testis, and pancreas) were also noted in the rats. In another study, delta-9-THC, delta-8-THC, and cannabinol were found to inhibit the growth of Lewis lung adenocarcinoma cells in vitro and in vivo .[4] In addition, other tumors have been shown to be sensitive to cannabinoid-induced growth inhibition.[5-8]

Cannabinoids may cause antitumor effects by various mechanisms, including induction of cell death, inhibition of cell growth, and inhibition of tumor angiogenesis and metastasis.[9-11] Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death. These compounds have been shown to induce apoptosis in glioma cells in culture and induce regression of glioma tumors in mice and rats. Cannabinoids protect normal glial cells of astroglial and oligodendroglial lineages from apoptosis mediated by the CB1 receptor.[12]

The effects of delta-9-THC and a synthetic agonist of the CB2 receptor were investigated in hepatocellular carcinoma (HCC).[13] Both agents reduced the viability of hepatocellular carcinoma cells in vitro and demonstrated antitumor effects in hepatocellular carcinoma subcutaneous xenografts in nude mice. The investigations documented that the anti-HCC effects are mediated by way of the CB2 receptor. Similar to findings in glioma cells, the cannabinoids were shown to trigger cell death through stimulation of an endoplasmic reticulum stress pathway that activates autophagy and promotes apoptosis. Other investigations have confirmed that CB1 and CB2 receptors may be potential targets in non-small cell lung carcinoma[14] and breast cancer.[15]

In an in vivo model using severe combined immunodeficient mice, subcutaneous tumors were generated by inoculating the animals with cells from human non-small cell lung carcinoma cell lines.[16] Tumor growth was inhibited by 60% in THC-treated mice compared with vehicle-treated control mice. Tumor specimens revealed that THC had antiangiogenic and antiproliferative effects. However, research with immunocompetent murine tumor models has demonstrated immunosuppression and enhanced tumor growth in mice treated with THC.[17,18]

In addition, both plant-derived and endogenous cannabinoids have been studied for anti-inflammatory effects. A mouse study demonstrated that endogenous cannabinoid system signaling is likely to provide intrinsic protection against colonic inflammation.[19] As a result, a hypothesis that phytocannabinoids and endocannabinoids may be useful in the risk reduction and treatment of colorectal cancer has been developed.[20-23]

Appetite Stimulation
Many animal studies have previously demonstrated that delta-9-THC and other cannabinoids have a stimulatory effect on appetite and increase food intake. It is believed that the endogenous cannabinoid system may serve as a regulator of feeding behavior. The endogenous cannabinoid anandamide potently enhances appetite in mice.[24] Moreover, CB1 receptors in the hypothalamus may be involved in the motivational or reward aspects of eating.[25]

Understanding the mechanism of cannabinoid-induced analgesia has been increased through the study of cannabinoid receptors, endocannabinoids, and synthetic agonists and antagonists. The CB1 receptor is found in both the central nervous system (CNS) and in peripheral nerve terminals. Similar to opioid receptors, increased levels of the CB1 receptor are found in regions of the brain that regulate nociceptive processing.[26] CB2 receptors, located predominantly in peripheral tissue, exist at very low levels in the CNS. With the development of receptor-specific antagonists, additional information about the roles of the receptors and endogenous cannabinoids in the modulation of pain has been obtained.[27,28]

Cannabinoids may also contribute to pain modulation through an anti-inflammatory mechanism; a CB2 effect with cannabinoids acting on mast cell receptors to attenuate the release of inflammatory agents, such as histamine and serotonin, and on keratinocytes to enhance the release of analgesic opioids has been described.[29-31]


1.Adams IB, Martin BR: Cannabis: pharmacology and toxicology in animals and humans. Addiction 91 (11): 1585-614, 1996. [PUBMED Abstract]

2.Grotenhermen F, Russo E, eds.: Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. Binghamton, NY: The Haworth Press, 2002.

3. National Toxicology Program .: NTP toxicology and carcinogenesis studies of 1-trans-delta(9)-tetrahydrocannabinol (CAS No. 1972-08-3) in F344 rats and B6C3F1 mice (gavage studies). Natl Toxicol Program Tech Rep Ser 446 (): 1-317, 1996. [PUBMED Abstract]

4.Bifulco M, Laezza C, Pisanti S, et al.: Cannabinoids and cancer: pros and cons of an antitumour strategy. Br J Pharmacol 148 (2): 123-35, 2006. [PUBMED Abstract]

5.Sánchez C, de Ceballos ML, Gomez del Pulgar T, et al.: Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor. Cancer Res 61 (15): 5784-9, 2001. [PUBMED Abstract]

6.McKallip RJ, Lombard C, Fisher M, et al.: Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease. Blood 100 (2): 627-34, 2002. [PUBMED Abstract]

7.Casanova ML, Blázquez C, Martínez-Palacio J, et al.: Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. J Clin Invest 111 (1): 43-50, 2003. [PUBMED Abstract]

8.Blázquez C, González-Feria L, Alvarez L, et al.: Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas. Cancer Res 64 (16): 5617-23, 2004. [PUBMED Abstract]

9.Guzmán M: Cannabinoids: potential anticancer agents. Nat Rev Cancer 3 (10): 745-55, 2003. [PUBMED Abstract]

10.Blázquez C, Casanova ML, Planas A, et al.: Inhibition of tumor angiogenesis by cannabinoids. FASEB J 17 (3): 529-31, 2003. [PUBMED Abstract]

11.Vaccani A, Massi P, Colombo A, et al.: Cannabidiol inhibits human glioma cell migration through a cannabinoid receptor-independent mechanism. Br J Pharmacol 144 (8): 1032-6, 2005. [PUBMED Abstract]

12.Torres S, Lorente M, Rodríguez-Fornés F, et al.: A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol Cancer Ther 10 (1): 90-103, 2011. [PUBMED Abstract]

13.Vara D, Salazar M, Olea-Herrero N, et al.: Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy. Cell Death Differ 18 (7): 1099-111, 2011. [PUBMED Abstract]

14.Preet A, Qamri Z, Nasser MW, et al.: Cannabinoid receptors, CB1 and CB2, as novel targets for inhibition of non-small cell lung cancer growth and metastasis. Cancer Prev Res (Phila) 4 (1): 65-75, 2011. [PUBMED Abstract]

15.Nasser MW, Qamri Z, Deol YS, et al.: Crosstalk between chemokine receptor CXCR4 and cannabinoid receptor CB2 in modulating breast cancer growth and invasion. PLoS One 6 (9): e23901, 2011. [PUBMED Abstract]

16.Preet A, Ganju RK, Groopman JE: Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene 27 (3): 339-46, 2008. [PUBMED Abstract]

17.Zhu LX, Sharma S, Stolina M, et al.: Delta-9-tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway. J Immunol 165 (1): 373-80, 2000. [PUBMED Abstract]

18.McKallip RJ, Nagarkatti M, Nagarkatti PS: Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. J Immunol 174 (6): 3281-9, 2005. [PUBMED Abstract]

19.Massa F, Marsicano G, Hermann H, et al.: The endogenous cannabinoid system protects against colonic inflammation. J Clin Invest 113 (8): 1202-9, 2004. [PUBMED Abstract]

20.Patsos HA, Hicks DJ, Greenhough A, et al.: Cannabinoids and cancer: potential for colorectal cancer therapy. Biochem Soc Trans 33 (Pt 4): 712-4, 2005. [PUBMED Abstract]

21.Liu WM, Fowler DW, Dalgleish AG: Cannabis-derived substances in cancer therapy--an emerging anti-inflammatory role for the cannabinoids. Curr Clin Pharmacol 5 (4): 281-7, 2010. [PUBMED Abstract]

22.Malfitano AM, Ciaglia E, Gangemi G, et al.: Update on the endocannabinoid system as an anticancer target. Expert Opin Ther Targets 15 (3): 297-308, 2011. [PUBMED Abstract]

23.Sarfaraz S, Adhami VM, Syed DN, et al.: Cannabinoids for cancer treatment: progress and promise. Cancer Res 68 (2): 339-42, 2008. [PUBMED Abstract]

24.Mechoulam R, Berry EM, Avraham Y, et al.: Endocannabinoids, feeding and suckling--from our perspective. Int J Obes (Lond) 30 (Suppl 1): S24-8, 2006. [PUBMED Abstract]

25.Fride E, Bregman T, Kirkham TC: Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood. Exp Biol Med (Maywood) 230 (4): 225-34, 2005. [PUBMED Abstract]

26.Walker JM, Hohmann AG, Martin WJ, et al.: The neurobiology of cannabinoid analgesia. Life Sci 65 (6-7): 665-73, 1999. [PUBMED Abstract]

27.Meng ID, Manning BH, Martin WJ, et al.: An analgesia circuit activated by cannabinoids. Nature 395 (6700): 381-3, 1998. [PUBMED Abstract]

28.Walker JM, Huang SM, Strangman NM, et al.: Pain modulation by release of the endogenous cannabinoid anandamide. Proc Natl Acad Sci U S A 96 (21): 12198-203, 1999. [PUBMED Abstract]
29.Facci L, Dal Toso R, Romanello S, et al.: Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc Natl Acad Sci U S A 92 (8): 3376-80, 1995. [PUBMED Abstract]

30.Ibrahim MM, Porreca F, Lai J, et al.: CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proc Natl Acad Sci U S A 102 (8): 3093-8, 2005. [PUBMED Abstract]

31.Richardson JD, Kilo S, Hargreaves KM: Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors. Pain 75 (1): 111-9, 1998. [PUBMED Abstract]

Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1
Robert Ramer*, Katharina Bublitz*, Nadine Freimuth*, Jutta Merkord*, Helga Rohde*, Maria Haustein*, Philipp Borchert*, Ellen Schmuhl*, Michael Linnebacher† and Burkhard Hinz*,1

+ Author Affiliations

*Institute of Toxicology and Pharmacology and

†Section of Molecular Oncology and Immunotherapy, Department of General Surgery, University of Rostock, Rostock, Germany

↵1Correspondence: Institute of Toxicology and Pharmacology, University of Rostock, Schillingallee 70, D-18057 Rostock, Germany. E-mail:


Cannabinoids inhibit cancer cell invasion via increasing tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). This study investigates the role of intercellular adhesion molecule-1 (ICAM-1) within this action. In the lung cancer cell lines A549, H358, and H460, cannabidiol (CBD; 0.001–3 μM) elicited concentration-dependent ICAM-1 up-regulation compared to vehicle via cannabinoid receptors, transient receptor potential vanilloid 1, and p42/44 mitogen-activated protein kinase. Up-regulation of ICAM-1 mRNA by CBD in A549 was 4-fold at 3 μM, with significant effects already evident at 0.01 μM. ICAM-1 induction became significant after 2 h, whereas significant TIMP-1 mRNA increases were observed only after 48 h. Inhibition of ICAM-1 by antibody or siRNA approaches reversed the anti-invasive and TIMP-1-upregulating action of CBD and the likewise ICAM-1-inducing cannabinoids Δ9-tetrahydrocannabinol and R(+)-methanandamide when compared to isotype or nonsilencing siRNA controls. ICAM-1-dependent anti-invasive cannabinoid effects were confirmed in primary tumor cells from a lung cancer patient. In athymic nude mice, CBD elicited a 2.6- and 3.0-fold increase of ICAM-1 and TIMP-1 protein in A549 xenografts, as compared to vehicle-treated animals, and an antimetastatic effect that was fully reversed by a neutralizing antibody against ICAM-1 [% metastatic lung nodules vs. isotype control (100%): 47.7% for CBD + isotype antibody and 106.6% for CBD + ICAM-1 antibody]. Overall, our data indicate that cannabinoids induce ICAM-1, thereby conferring TIMP-1 induction and subsequent decreased cancer cell invasiveness.

—Ramer, R., Bublitz, K., Freimuth, N., Merkord, J., Rohde, H., Haustein, M., Borchert, P., Schmuhl, E., Linnebacher, M., Hinz, B. Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1. cannabinoids tissue inhibitor of metalloproteinases-1 experimental metastasis ICAM-1 Received October 17, 2011. Accepted December 5, 2011.

Cannabis in Palliative Medicine: Improving Care and Reducing Opioid-Rel­ated Morbidity

Published online before print March 28, 2011, J HOSP PALLIAT CARE August 2011 vol. 28 no. 5 297-303

Cannabis in Palliative Medicine: Improving Care and Reducing Opioid-Related Morbidity

Gregory T. Carter, MD, MS Hospice Services, Providence Medical Group, Olympia, WA, USA, Aaron M. Flanagan, MD Providence Medical Group, Olympia, WA, USA Mitchell Earleywine, PhD Department of Psychology, University at Albany State University of New York, Albany, NY, USA Donald I. Abrams, MD University of California, San Francisco, CA, USA Sunil K. Aggarwal, MD, PhD Physical Medicine and Rehabilitation, The Rusk Institute of Rehabilitation Medicine, New York University, USA Lester Grinspoon, MD Department of Psychiatry, Harvard Medical School, USA, Massachusetts Mental Health Center, Boston, MA, USA


Unlike hospice, long-term drug safety is an important issue in palliative medicine. Opioids may produce significant morbidity. Cannabis is a safer alternative with broad applicability for palliative care. Yet the Drug Enforcement Agency (DEA) classifies cannabis as Schedule I (dangerous, without medical uses). Dronabinol, a Schedule III prescription drug, is 100% tetrahydrocannabinol (THC), the most psychoactive ingredient in cannabis. Cannabis contains 20% THC or less but has other therapeutic cannabinoids, all working together to produce therapeutic effects. As palliative medicine grows, so does the need to reclassify cannabis. This article provides an evidence-based overview and comparison of cannabis and opioids. Using this foundation, an argument is made for reclassifying cannabis in the context of improving palliative care and reducing opioid-related morbidity.
cannabis medical marijuana opioids hospice chronic pain palliative medicine

Published online ahead of print August 30, 2010 CMAJ 10.1503/cm­aj.091414

Smoked cannabis for chronic neuropathi­c pain: a randomized controlled trial


Background: Chronic neuropathic pain affects 1%–2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood.

Methods: Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events.

Results: We recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12 women [52%]), of whom 21 completed the trial. The average daily pain intensity, measured on the 11-point numeric rating scale, was lower on the prespecified primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02–1.4). Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief. Participants receiving 9.4% tetrahydrocannabinol reported improved ability to fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003) and improved quality of sleep (less wakefulness, p = 0.01) relative to 0% tetrahydrocannabinol. We found no differences in mood or quality of life. The most common drug-related adverse events during the period when participants received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in areas of neuropathic pain, dizziness, numbness and cough.

Conclusion­:: A single inhalation of 25 mg of 9.4% tetrahydro­cannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (Internati­onal Standard Randomised Controlled Trial Register no. ISRCTN6831­4063)

Our results support the claim that smoked cannabis reduces pain, improves mood and helps sleep. We believe that our trial provides a methodological approach that may be considered for further research. Clinical studies using inhaled delivery systems, such as vaporizers,32,33 are needed.

Cases J. 2009; 2: 7487.
Published online 2009 May 18

Standardiz­ed natural product cannabis in pain management and observatio­ns at a Canadian compassion society: a case report

Cases J. 2009; 2: 7487. Published online 2009 May 18. doi: 10.1186/1757-1626-2-7487 PMCID: PMC2740265

Copyright © 2009 Hornby et al.; licensee Cases Network Ltd.

Standardized natural product cannabis in pain management and observations at a Canadian compassion society: a case report

A Paul Hornby,1 Manju Sharma,2 and Bree Stegman3 1Department of Medial Cannabis Research, The Green Cross Society of BC, 2127 Kingsway, Vancouver, B.C., V5N 2T4, Canada 2Department of Pathology and Laboratory Medicine, Heather Pavilion, Vancouver General Hospital, Vancouver, B.C., Canada 3Canadian Registered Nurses Association of B.C., Vancouver Coastal Health Authority, 2755 Arbutus Street, Vancouver, B.C., Canada Corresponding author. A Paul Hornby: ; Manju Sharma: ; Bree Stegman:

Received November 5, 2008; Accepted February 13, 2009.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This article has been cited by other articles in PMC.


An adult Caucasian male with excruciating pains following multiple traumas was monitored, daily, over one year while managing chronic pain by self-administering quantifiable amounts of natural cannabis. Tetrahydrocannabinol, Cannabidiol, and Cannabinol were all measured in tinctures, capsules, smoke-able product plus some baked goods, prior to their administration. By allowing standardization, the subject was able to develop a daily regimen of pain management that was resistant to a battery of most patent analgesics.



The case reported here represents one of many observed at the Green Cross Society. With 70% of the members treating chronic pain the same phenomenon is observed over and over that people achieve a significant degree of pain management using standardized natural product cannabis. Often a better quality of life is attained with cannabis use only, or in conjunction with reduced opiate consumption. The subject in this study is nearly one year using only natural product cannabis plus supplements for his severe pain. He recently went through yet another two surgeries to back and hand using only cannabis for post-operative pain.

The roughly 4000 members of the Green Cross Society find similar benefit from standardized natural product cannabis medicine. To follow, will be publication of the Society's demographic data regarding use for various conditions such as arthritis, fybromyalgia, HIV/AIDS, and chronic pain, to name a few. A breakdown of the illnesses, what strains (cannabinoid profiles) is most effective, and at what dosages will be published at a later time.

Effect of D9-tetrahydrocannabinol, a cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans
H Beaumont1, J Jensen2, A Carlsson2, M Ruth3, A Lehmann2 and GE Boeckxstaens1,4 1Academic Medical Centre, Department of Gastroenterology and Hepatology, Amsterdam, the Netherlands, 2AstraZeneca R&D, Integrative Pharmacology, Mölndal, Sweden 3Discovery Medicine, Mölndal, Sweden, and 4University Hospital Leuven, Catholic University of Leuven, Department of Gastroenterology, Leuven, Belgium

Background and purpose: Transient lower oesophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastro-oesophageal reflux and are a potential pharmacological treatment target. We evaluated the effect of the CB1/CB2 receptor agonist D9-tetrahydrocannabinol (D9-THC) on TLESRs in dogs. Based on these findings, the effect of D9-THC was studied in healthy volunteers.

Experimental approach: In dogs, manometry was used to evaluate the effect of D9-THC in the presence and absence of the CB1 receptor antagonist SR141716A on TLESRs induced by gastric distension. Secondly, the effect of 10 and 20 mg D9-THC was studied in 18 healthy volunteers in a placebo-controlled study. Manometry was performed before and for 3 h after meal ingestion on three occasions.
Key results: In dogs, D9-THC dose-dependently inhibited TLESRs and reduced acid reflux rate. SR141716A significantly reversed the effects of D9-THC on TLESRs. Similarly, in healthy volunteers, D9-THC significantly reduced the number of TLESRs and caused a non-significant reduction of acid reflux episodes in the first postprandial hour. In addition, lower oesophageal sphincter pressure and swallowing were significantly reduced by D9-THC. After intake of 20 mg, half of the subjects experienced nausea and vomiting leading to premature termination of the study. Other side-effects were hypotension, tachycardia and central effects. Conclusions and implications: D9-THC significantly inhibited the increase in meal-induced TLESRs and reduced spontaneous swallowing in both dogs and humans. In humans, D9-THC significantly reduced basal lower oesophageal sphincter pressure. These findings confirm previous observations in dogs and indicate that cannabinoid receptors are also involved in the triggering of TLESRs in humans.

In conclusion, the present study demonstrates that D9-THC significantly inhibits the increase in TLESRs evoked by meal ingestion and reduces spontaneous swallowing in both dogs and humans. Furthermore, D9-THC reduces basal LES pressure in humans. These findings confirm previous findings in dogs and indicate that CB receptors are also involved in the triggering of TLESRs in humans.

British Journal of Pharmacology (2009) 156, 153–162; doi:10.1111/j.1476-5381.2008.00010.x; published online 5 December 2008

Keywords: gastro-oesophageal reflux disease; cannabinoid; transient lower oesophageal sphincter relaxation; D9-tetrahydrocannabinol

Abbreviations: GERD, gastro-oesophageal reflux disease; LES, lower oesophageal sphincter; TLESRs, transient lower oesophageal sphincter relaxations; CB, cannabinoid; D9-THC, D9-tetrahydrocannabinol; DMN, dorsal motor nucleus of the vagus; NTS, nucleus tractus solitarius; PPIs, proton pump inhibitors

J Neurosci. 2007 Sep 5;27(36):9­537-44.

Nonpsychoa­ctive cannabidio­l prevents prion accumulati­on and protects neurons against prion toxicity.
Dirikoc S, Priola SA, Marella M, Zsürger N, Chabry J.

Institut de Pharmacolo­gie Moléculair­e et Cellulaire­, Unité Mixte de Recherche 6097, Centre National de la Recherche Scientifiq­ue, 06560 Valbonne, France.


Prion diseases are transmissible neurodegenerative disorders characterized by the accumulation in the CNS of the protease-resistant prion protein (PrPres), a structurally misfolded isoform of its physiological counterpart PrPsen. Both neuropathogenesis and prion infectivity are related to PrPres formation. Here, we report that the nonpsychoactive cannabis constituent cannabidiol (CBD) inhibited PrPres accumulation in both mouse and sheep scrapie-infected cells, whereas other structurally related cannabinoid analogs were either weak inhibitors or noninhibitory. Moreover, after intraperitoneal infection with murine scrapie, peripheral injection of CBD limited cerebral accumulation of PrPres and significantly increased the survival time of infected mice. Mechanistically, CBD did not appear to inhibit PrPres accumulation via direct interactions with PrP, destabilization of PrPres aggregates, or alteration of the expression level or subcellular localization of PrPsen. However, CBD did inhibit the neurotoxic effects of PrPres and affected PrPres-induced microglial cell migration in a concentration-dependent manner. Our results suggest that CBD may protect neurons against the multiple molecular and cellular factors involved in the different steps of the neurodegenerative process, which takes place during prion infection. When combined with its ability to target the brain and its lack of toxic side effects, CBD may represent a promising new anti-prion drug.

Drugs: 9 July 2010 - Volume 70 - Issue 10 - pp 1245-1254 doi: 10.2165/11537930-000000000-00000 Review Articles Pharmacological Management of Pain in Patients with Multiple Sclerosis
Solaro, Claudio1; Messmer Uccelli, Michele2
Multiple sclerosis (MS) is an inflammatory, demyelinating, autoimmune disease of the CNS. There are currently a number of disease-modifying medications for MS that modulate or suppress the immune system; however, these medications do not directly relieve MS symptoms, which include visual deficits, gait problems, sensory deficits, weakness, tremor, spasticity and pain, among others.
Pain is a common symptom in MS which has recently been estimated to be experienced by more than 40% of patients. Nociceptive pain occurs as an appropriate physiological response transmitted to a conscious level when nociceptors in bone, muscle or any body tissue are activated, warning the organism of tissue damage. Neuropathic pain is initiated as a direct consequence of a lesion or disease affecting the somatosensory system, with no physiological advantage. Nociceptive and neuropathic pain in MS may be present concurrently and at different stages of the disease, and may be associated with other symptoms. Central neuropathic pain has been reported to be among the most common pain syndromes in MS. It is described as constant, often spontaneous, burning occurring more frequently in the lower limbs. Treatment typically includes tricyclic antidepressants and antiepileptic medications, although studies have been conducted in relatively small samples and optimal dosing has not been confirmed. Cannabinoids have been among the few treatments studied in well designed, randomized, placebo-controlled trials for central neuropathic pain. In the largest of these trials, which included 630 subjects, a 15-week comparison between Δ9-tetrahydrocannabinol and placebo was performed. More patients receiving active treatment perceived an improvement in pain than those receiving placebo, although approximately 20% of subjects reported worsening of pain while on active treatment.
Trigeminal neuralgia, while affecting less than 5% of patients with MS, is the most studied pain syndrome. The pain can be extreme and is typically treated with carbamazepine, although adverse effects can mimic an MS exacerbation. Painful topic spasms occur in approximately 11% of the MS population and are treated with antispasticity medications such as baclofen and benzodiazepines. Gabapentin has also demonstrated efficacy, but all studies have included small sample sizes.
In general, evidence for treating pain in MS is limited. Many clinical features of pain are often unrecognized by clinicians and are difficult for patients to describe. Treatment is often based on anecdotal reports and clinical experience. We present a review of treatment options for pain in MS, which should serve to update current knowledge, highlight shortcomings in clinical research and provide indications towards achieving evidence-based treatment of pain in MS.
Cannabinoids control spasticity and tremor in a multiple sclerosis model

David Baker1, Gareth Pryce1, J. Ludovic Croxford1, Peter Brown2, Roger G. Pertwee3, John W. Huffman4 & Lorna Layward
Neuroinflammation Group, Department of Neurochemistry, Institute of Neurology, University College London, 1 Wakefield Street, London WC1N 1PJ and the Institute of Ophthalmology, UCL, London EC1V 9EL, UK

The Medical Research Council Human Movement and Balance Unit, National Hospital for Neurology and Neurosurgery , Queen Square, London, WC1N 3BG, UK

Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill , Aberdeen AB25 2ZD, UK

Department of Chemistry, Clemson University, Clemson, South Carolina 29634-1905 , USA
Multiple Sclerosis Society of Great Britain and Northern Ireland , 25 Effie Road, London SW6 1EE, UK Correspondence to: Correspondence and requests for materials should be addressed to D.B. (e-mail: Email:
Chronic relapsing experimental allergic encephalomyelitis (CREAE) is an autoimmune model of multiple sclerosis1. Although both these diseases are typified by relapsing-remitting paralytic episodes, after CREAE induction by sensitization to myelin antigens1 Biozzi ABH mice also develop spasticity and tremor. These symptoms also occur during multiple sclerosis and are difficult to control. This has prompted some patients to find alternative medicines, and to perceive benefit from cannabis use2. Although this benefit has been backed up by small clinical studies, mainly with non-quantifiable outcomes3, 4, 5, 6, 7, the value of cannabis use in multiple sclerosis remains anecdotal. Here we show that cannabinoid (CB) receptor agonism using R(+)-WIN 55,212, 9-tetrahydrocannabinol, methanandamide and JWH-133 (ref. 8) quantitatively ameliorated both tremor and spasticity in diseased mice. The exacerbation of these signs after antagonism of the CB1 and CB2 receptors, notably the CB1 receptor, using SR141716A and SR144528 (ref. 8) indicate that the endogenous cannabinoid system may be tonically active in the control of tremor and spasticity. This provides a rationale for patients' indications of the therapeutic potential of cannabis in the control of the symptoms of multiple sclerosis2, and provides a means of evaluating more selective cannabinoids in the future.
Association Between Marijuana Exposure and Pulmonary Function Over 20 Years
Mark J. Pletcher, MD, MPH; Eric Vittinghoff, PhD; Ravi Kalhan, MD, MS; Joshua Richman, MD, PhD; Monika Safford, MD; Stephen Sidney, MD, MPH; Feng Lin, MS; Stefan Kertesz, MD
[+] Author Affiliations
Author Affiliations: Department of Epidemiology and Biostatistics (Drs Pletcher and Vittinghoff and Mr Lin) and Division of General Internal Medicine, Department of Medicine (Dr Pletcher), University of California, San Francisco; Asthma-COPD Program, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois (Dr Kalhan); Department of Surgery (Dr Richman) and Division of Preventive Medicine (Drs Safford and Kertesz), University of Alabama at Birmingham; Center for Surgical, Medical and Acute Care Research and Transitions, Veterans Affairs Medical Center, Birmingham (Drs Richman and Kertesz); and Division of Research, Kaiser Permanente of Northern California, Oakland (Dr Sidney). Abstract Context Marijuana smoke contains many of the same constituents as tobacco smoke, but whether it has similar adverse effects on pulmonary function is unclear.
Objective To analyze associations between marijuana (both current and lifetime exposure) and pulmonary function.
Design, Setting, and Participants The Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal study collecting repeated measurements of pulmonary function and smoking over 20 years (March 26, 1985-August 19, 2006) in a cohort of 5115 men and women in 4 US cities. Mixed linear modeling was used to account for individual age-based trajectories of pulmonary function and other covariates including tobacco use, which was analyzed in parallel as a positive control. Lifetime exposure to marijuana joints was expressed in joint-years, with 1 joint-year of exposure equivalent to smoking 365 joints or filled pipe bowls.
Main Outcome Measures Forced expiratory volume in the first second of expiration (FEV1) and forced vital capacity (FVC).
Results Marijuana exposure was nearly as common as tobacco exposure but was mostly light (median, 2-3 episodes per month). Tobacco exposure, both current and lifetime, was linearly associated with lower FEV1 and FVC. In contrast, the association between marijuana exposure and pulmonary function was nonlinear (P < .001): at low levels of exposure, FEV1 increased by 13 mL/joint-year (95% CI, 6.4 to 20; P < .001) and FVC by 20 mL/joint-year (95% CI, 12 to 27; P < .001), but at higher levels of exposure, these associations leveled or even reversed. The slope for FEV1 was −2.2 mL/joint-year (95% CI, −4.6 to 0.3; P = .08) at more than 10 joint-years and −3.2 mL per marijuana smoking episode/mo (95% CI, −5.8 to −0.6; P = .02) at more than 20 episodes/mo. With very heavy marijuana use, the net association with FEV1 was not significantly different from baseline, and the net association with FVC remained significantly greater than baseline (eg, at 20 joint-years, 76 mL [95% CI, 34 to 117]; P < .001).
Conclusion Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function.
bottom line, big brother and pharmaceutical companies i.e. $$$ i.e. Washington. ...

Friday, December 16, 2011


FDA faulted over state inspections

(Ric Feld/ASSOCIATED PRESS) - A 2009 salmonella outbreak linked to a Georgia peanut plant occurred after several state inspections.

Published: December 14

The Food and Drug Administration is relying more often on states to inspect food plants but is failing to properly monitor those state inspections or follow through on their findings, the Department of Health and Human Services watchdog has concluded.

In a report released Wednesday, the department’s inspector general found that a lack of resources is forcing the FDA to lean more heavily on its counterparts at the state level to inspect plants responsible for everything from packing to processing foods.

More than half the agency’s inspections were done by state officials in fiscal 2009, up from 42 percent four years earlier, according to the report. If these inspections are not done properly, they can expose consumers to sometimes life-threatening illnesses.

A deadly salmonella outbreak linked to a Georgia peanut processing plant in 2009 occurred after the plant had been inspected several times by state officials working on the FDA’s behalf. The incident prompted Rep. Rosa DeLauro (D-Conn.) to ask Inspector General Daniel Levinson to examine the FDA’s oversight of its state partners.

Wednesday’s report confirms several weaknesses in that relationship, almost all of which the FDA acknowledged were indeed problems. “The report documents glitches we’re aware of. . . . These are things we are working on,” said Mike Taylor, the FDA’s deputy commissioner for foods.

The report found that the FDA has failed to ensure that the states have completed the number of inspections assigned to them. Of the 41 states the FDA was working with in 2009, eight did not complete 10 percent of the 2,170 inspections they were responsible for that year. The agency paid for 130 of the inspections that were not done.

The report did not specify how much was paid in those instances. But it did state that the FDA spent more than $8 million for state contract inspections in fiscal 2009.

The FDA also did not do its part in monitoring the inspections as required by law, according to the report.

Each year, the FDA has to audit at least 7 percent of a state’s inspections. That means that an FDA official must tag along to observe a state inspector’s performance and identify any systemic issues — such as problems that consistently emerge in multiple audits. But the agency failed to complete the required audits in 14 states, and therefore can’t determine the effectiveness of those state inspections, the report said.

“FDA officials generally attributed their inability to complete the required number of audits to a lack of resources,” the report said. An official in one of the FDA’s 14 districts said his district ran out of travel funds. Another said his district lacked trained auditors.

Even in cases where recurring problems were identified, the problems were not always addressed. Corrective action was taken in only four of the 10 states where systemic problems were found, the report said.

When audits were conducted, the most common problem cited had to do with the state inspectors’ inability to identify violations. At least 32 percent of the 419 inspectors audited had at least one deficiency. The report cited instances in which inspectors failed to note evidence of rodents or a leaky roof above exposed food.

Even when inspectors noted food safety violations, FDA officials who reviewed the inspectors’ reports did not properfly classify all of them, the report said. Officials responsible for 11 states said they did not classify some incidents as serious and in need of official action because they thought they were not allowed to, the report said.

Officials in another 11 states said that FDA was not always notified when actions were taken and therefore could not determine if the violations were properly addressed.

“Taken together, these findings demonstrate that more needs to be done to protect public health and to ensure that contract inspections are effective,” the report concluded.

Aside from the resource issues, FDA officials told investigators that the agency relies heavily on the states in part because states have more enforcement power than the federal government. For instance, state officials can sometimes instantly shut down a plant or seize unsafe food, whereas FDA cannot achieve the same instant results.

DeLauro, the congresswoman who requested the report, said that it “illustrates a vicious cycle of woefully inadequate oversight. It is clear to me that more must be done to ensure that federal inspection and oversight of food facilities best protects the public health.”

The Food Safety Modernization Act, adopted by the previous Congress, would grant the FDA more authority. But it would also demand that the agency take on more inspections and work more with the states to keep the food supply safe.

Department of Health and Human Services



Daniel R. Levinson Inspector General December 2011 OEI-02-09-00430



1. To determine the extent to which the Food and Drug Administration (FDA) enters into contracts with States to inspect food facilities.

2. To determine the extent to which FDA ensures that States complete the inspections required by their contracts.

3. To determine whether FDA ensures that State inspections are properly classified and violations are remedied.

4. To determine the extent to which FDA audits State inspections and addresses deficiencies identified by audits.


Each year, 128,000 Americans are hospitalized and 3,000 die after consuming contaminated foods and beverages. FDA is responsible for safeguarding the Nation’s food supply and for routinely inspecting food facilities. In addition to conducting its own inspections, FDA relies on State agencies to conduct inspections on its behalf; however, in recent years, concerns have been raised about the rigor of these State inspections. For example, the peanut processing plant responsible for a 2009 salmonella outbreak was inspected multiple times by a State agency working on behalf of FDA. This outbreak resulted in one of the largest food recalls in U.S. history and has led to serious questions about the effectiveness of State food facility inspections. Because of concerns about food facility inspections conducted by State agencies, this review was requested by the House Committee on Appropriations, Subcommittee on Agriculture, Rural Development, Food and Drug Administration, and Related Agencies.

FDA often enters into contracts with State agencies responsible for ensuring food safety. Each contract includes the number of food facility inspections the State will conduct for FDA and the amount the State will be paid for each inspection. During the 2009 contract year, FDA held contracts with 41 States to conduct FDA’s inspections.

FDA oversees State inspections though its Contract Inspection Audit Program. The audit program is designed to verify that States conduct inspections that satisfy the requirements of their contracts. FDA requires that a minimum of 7 percent of a State’s contract inspections be audited each year. This minimum percentage—which is known as the minimum audit rate—ensures that States are conducting adequate inspections that meet the conditions of the contract.

We based this study on several sources of data: (1) FDA’s inspection data, (2) FDA’s documentation of contract inspections and payment data, (3) audit and corrective action documentation, and (4) structured interviews with FDA officials.


FDA has increasingly relied on States to inspect food facilities. Although the number of food facilties inspected by FDA has decreased since 2004, the number of facilities inspected by States under contract to FDA has increased significantly. In fiscal year (FY) 2009, 59 percent of FDA’s food inspections were conducted by State inspectors, compared to only 42 percent in FY 2004.

In eight States, FDA failed to ensure that the required number of inspections was completed; FDA paid for many inspections that were incomplete. These 8 States were responsible for completing a total of 2,170 inspections; however, these States failed to complete 10 percent of these inspections during the contract year. When States fail to complete the inspections required in their contracts, FDA’s ability to identify facilities with potentially serious food safety violations is diminished. Also, FDA paid for 130 of the 221 inspections that were not completed. In four additional States, FDA paid for inspection visits, even though payment for such visits was not specified in the States’ contracts. FDA did not ensure that all State inspections were properly classified and that all violations were remedied. FDA officials responsible for 11 of 41 States were unclear about how to properly classify contract inspections. In these 11 States, FDA officials reported that they would not assign official action indicated classifications to State inspections under any circumstances, contrary to FDA guidance. If FDA does not correctly classify inspections that reveal serious violations, its ability to assess facilities’ relative risk is impaired. Additionally, FDA officials responsible for another 11 States reported that when States were responsible for correcting violations, FDA was not always informed about actions taken by the States. As a result, FDA was unable to ensure that serious violations had been adequately addressed.

FDA failed to complete the required number of audits for one-third of the States and did not always follow up on systemic problems identified. For 14 of 41 States with contracts, FDA did not complete the required number of audits and therefore failed to meet its minimum audit rate. Additionally, the audits in 10 States revealed systemic problems that needed to be corrected; however, FDA initiated corrective action in only 4 of the 10 States. If FDA does not follow its guidance and complete the required number of audits and address systemic problems, it cannot verify that States are conducting suitable inspections that satisfy the requirements of the contracts.


Our report identified significant weaknesses in FDA’s oversight of food facility inspections conducted by States. Taken together, the findings demonstrate that more needs to be done to protect public health and to ensure that contract inspections are effective and prevent outbreaks of foodborne illness. Therefore, we recommend that FDA:

Ensure that all contract inspections are completed, properly documented, and appropriately paid for.

Ensure that contract inspections are properly classified in accordance with FDA guidance.

Ensure that all inspection violations are remedied by routinely tracking all actions taken to correct violations.

Ensure that the minimum audit rate is met in all States.

Address any systemic problems identified by audits.


FDA concurred with four of our recommendations and agreed in part with the fifth.

In response to our first recommendation, to ensure that all contract inspections are completed, properly documented, and appropriately paid for, FDA concurred, stating that it is conducting a systematic review of the State contracting program.

In response to our second recommendation, to ensure that contract inspections are properly classified, FDA concurred and noted that it is revising its directive to emphasize more clearly that classifications must be accurate, timely, and uniform.

In response to our third recommendation, to ensure that all inspection violations are remedied by routinely tracking all actions taken to correct violations, FDA agreed to track most violative inspections and the remedies taken by industry. However, FDA noted that certain violations may not be suitable for inspection followup and that other approaches may be used to track such violations. While we appreciate FDA’s commitment to track certain violations, we encourage it to track all violations, even those that do not warrant followup inspections. FDA can use violation information to help establish the relative risk of facilities and determine how often they should be inspected. In response to our fourth recommendation, to ensure that the minimum audit rate is met in all States, FDA concurred, noting that it is reviewing the current reporting requirements to ensure that audits are completed and tracked to verify compliance with FDA requirements.

Finally, in response to our fifth recommendation, to address any systemic problems identified by audits, FDA concurred and noted that it will continue to develop processes and procedures to ensure that systemic problems are identified and that corrective action plans are implemented.

We support FDA’s efforts to strengthen State contract inspections and address the issues identified in the report. With the implementation of the Manufactured Food Regulatory Program Standards, FDA’s oversight of State inspections is even more critical. As States adopt the standards, it is essential that FDA strengthen not only States’ oversight but also its own oversight to ensure that States conduct high-quality food facility inspections.


Identifying Inspection Violations

During an inspection, State inspectors may identify potential violations of food safety laws and regulations. These violations are recorded in the inspection report. Based on the inspection report, FDA generally assigns one of three classifications: official action indicated (OAI), voluntary action indicated (VAI), or no action indicated (NAI).10 An OAI classification signifies that the inspector found objectionable conditions in the food facility and that these violations potentially “warrant regulatory action.”11 This type of violation is the most significant identified by inspectors. A VAI classification signifies that the inspector found violations that are serious enough to record but do not cross “the threshold for regulatory action.”12 An NAI classification signifies that the inspector found either no violations of law and regulations or violations that were so insignificant that no action is warranted.13


PLEASE NOTE, FDA LAST BSE MAD COW FEED REPORT WAS ALMOST A YEAR AGO (they use to come out weekly, then monthly, then quarterly, now I guess only yearly) ;


January 13, 2011 January 2011 Update on Feed Enforcement Activities to Limit the Spread of BSE

Monday, January 17, 2011

MAD COW Update on Feed Enforcement Activities to Limit the Spread of BSE January 13, 2011


Subject: BSE FEED VIOLATIONS UPDATE From 01/01/2009 To 06/10/2009

FDA BSE/Ruminant Feed Inspections Firms Inventory Report

Data reported as of: 06/06/2009 Search by: Last BSE Insp Date From 01/01/2009 To 06/10/2009 Sort by: FDA District, State, Firm Name

FDA District Firm Id (FEI) Firm Name Street Address City State Zip Code Opr. Status Firm Type(s) Prgm Risk Last BSE Insp Date Last BSE Dist. Dcsn** Handles Feed for Rum. Animals?

ATL-DO 3007582627 Hoffner Brothers Dairy 610 Ketchie Rd Mount Ulla NC 28125-9685 OPR FR, OF, OT NP 02/03/2009 VAI Y

CIN-DO 3002766655 Lester J Stutzman Feed Mill 2811 Mt Zion Rd Marion KY 42064 OPR DR, FR, NL, OF DP 01/05/2009 VAI Y

CIN-DO 3003407434 Direct Action Co Inc 6668 Old SR 39 NW Dover OH 44622 OPR DR, NL, OT HP 05/04/2009 VAI Y

KAN-DO 1000050408 Mid-South Milling Co Inc 213 Central Ave Kansas City KS 66118-1117 OPR OT, PB, TH HP 01/14/2009 VAI N

KAN-DO 3007495971 Midwest Bulk Inc 3404 N Emporia St Wichita KS 67219-3615 OPR TH DP 02/26/2009 VAI Y

KAN-DO 3007458821 Murray Grain Co Inc 900 E 21st St N Ste 201 Wichita KS 67214-1406 OPR TH DP 02/26/2009 VAI Y

KAN-DO 3006292356 Orscheln Farm & Home 1702 W 11th St Coffeyville KS 67337-3115 OPR DR DP 02/02/2009 VAI Y

LOS-DO 2027094 Nestle, USA/ Nestle Prepared Foods Company 9601 Canoga Ave Chatsworth CA 91311-4115 OPR HF HP 05/26/2009 VAI N

NYK-DO 1310558 Birkett Mills 1 Main St Penn Yan NY 14527-1615 OPR DR, HF, NL NP 01/11/2009 RTS Y

Data reported as of: 06/06/2009 Search by: Last BSE Insp Date From 01/01/2003 To 06/10/2009 and Last BSE District Decision = OAI Sort by: FDA District, State, Firm Name

FDA District Firm Id (FEI) Firm Name Street Address City State Zip Code Opr. Status Firm Type(s) Prgm Risk Last BSE Insp Date Last BSE Dist. Dcsn** Handles Feed for Rum. Animals?

KAN-DO 1927975 Hahn & Phillips Grease Co Inc 913 N Odell, PO Box 130 Marshall MO 65340 OPR NL, PB, TH HP 12/22/2008 OAI Y

Legend - Opr.Status:OPR=Operational, SEA=Seasonal, PRP=Pre-Production, Firm Type: AF=Animal Feed/Pet Food Salvager, DR=Distributor/Retailer, FL=Feed Mill (FDA Licensed), FR=Feeder of Ruminants, HF=Human Food Processor, NL=Feed Mill (not FDA Licensed), OF=On-farm Feed Mixer, OT=Other, PB=Protein Blender, PF=Pet Food Manufacturer, RE=Renderer, RO=Feeder of Ruminants and Other Species, TH=Transporter (Hauler), Prgm Risk:DP=Only Distributes Prohib.Mat.(DP), HP=Handles Prohibited Materials(HP), NP=Does not handle Prohib.Mat.(NP), Dist Dcsn:OAI=Official Action Indicated (OAI), VAI=Voluntary Action Indicated (VAI), NAI=No Action Indicated (NAI), RTS=Referred to State (RTS),

February 6, 2004

To help prevent the establishment and amplification of BSE through feed in the United States, FDA implemented a final rule that prohibits the use of most mammalian protein in feeds for ruminant animals. This rule, Title 21 Part 589.2000 of the Code of Federal Regulations, became effective on August 4, 1997.

This is an update on FDA enforcement activities regarding the ruminant feed (BSE) regulation. FDA's CVM has assembled data from the inspections that have been conducted AND whose final inspection report has been recorded in the FDA's inspection database as of January 23, 2004. As of January 23, 2004, FDA had received over 26,000 inspection reports. The majority of these inspections (around 70%) were conducted by State officials under contract to FDA, with the remainder conducted by FDA officials.

Inspections conducted by FDA or State investigators are classified to reflect the compliance status at the time of the inspection based upon the objectionable conditions documented. These inspection conclusions are reported as Official Action Indicated (OAI), Voluntary Action Indicated (VAI), or No Action Indicated (NAI).

An OAI inspection classification occurs when significant objectionable conditions or practices were found and regulatory sanctions are warranted in order to address the establishment's lack of compliance with the regulation. An example of an OAI inspection classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspections classified with OAI violations will be promptly re-inspected following the regulatory sanctions to determine whether adequate corrective actions have been implemented

A VAI inspection classification occurs when objectionable conditions or practices were found that do not meet the threshold of regulatory significance, but do warrant advisory actions to inform the establishment of findings that should be voluntarily corrected. Inspections classified with VAI violations are more technical violations of Title 21 Part 589.2000 of the Code of Federal Regulations, (here called the Ruminant Feed Ban) became effective on August 4, 1997. Ruminant Feed Ban provisions such as minor recordkeeping lapses and conditions involving non-ruminant feeds.

A NAI inspection classification occurs when no objectionable conditions or practices were found during the inspection or the significance of the documented objectionable conditions found does not justify further actions.

The results to date are reported here both by “segment of industry” and “in total”. NOTE – A single firm can operate as more than one firm type. As a result, the categories of the different industry segments are not mutually exclusive.


THERE were 100s of NAI's, but you get the just. also, please note ;

“A VAI inspection classification occurs when objectionable conditions or practices were found that do not meet the threshold of regulatory significance, but do warrant advisory actions to inform the establishment of findings that should be voluntarily corrected. Inspections classified with VAI violations are more technical violations of Title 21 Part 589.2000 of the Code of Federal Regulations, (here called the Ruminant Feed Ban) became effective on August 4, 1997. Ruminant Feed Ban provisions such as minor recordkeeping lapses and conditions involving non-ruminant feeds. “

PLEASE note, most of the VAIs DID handle feed for ruminant animals. sure would be nice to be able to read the complete report, on a single page, for each violation, on a single day, given once a week, at a simple url, like it use to be. here is an example ;


please see my full report here ;

Monday, January 17, 2011

MAD COW Update on Feed Enforcement Activities to Limit the Spread of BSE January 13, 2011

Saturday, August 14, 2010

BSE Case Associated with Prion Protein Gene Mutation

(g-h-BSEalabama) and VPSPr PRIONPATHY

(see mad cow feed in COMMERCE IN ALABAMA...TSS)


Molecular characterization of BSE in Canada

Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada

Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.

Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.

Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. *** It also suggests a similar cause or source for atypical BSE in these countries.

North Dakota Firm Recalls Whole Beef Head Products That Contain Prohibited Materials


Congressional and Public Affairs (202) 720-9113 Catherine Cochran

WASHINGTON, April 5, 2010 - North American Bison Co-Op, a New Rockford, N.D., establishment is recalling approximately 25,000 pounds of whole beef heads containing tongues that may not have had the tonsils completely removed, which is not compliant with regulations that require the removal of tonsils from cattle of all ages, the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS) announced today.

Tonsils are considered a specified risk material (SRM) and must be removed from cattle of all ages in accordance with FSIS regulations. SRMs are tissues that are known to contain the infective agent in cattle infected with Bovine Spongiform Encephalopathy (BSE), as well as materials that are closely associated with these potentially infective tissues. Therefore, FSIS prohibits SRMs from use as human food to minimize potential human exposure to the BSE agent.

The product subject to recall includes: Various weight cases of "Beef Heads KEEP FROZEN." Each case bears the establishment number "EST. 18859" inside the USDA mark of inspection and a case code number "16999." "North Dakota Natural Beef" is printed in the bottom left-hand corner of each label.

The recalled products were produced between June 25, 2009, and February 19, 2010. These products were shipped to distribution centers in Md., Mich., and Minn. for further sale.

The problem was discovered during FSIS inspection activities at the establishment. FSIS routinely conducts recall effectiveness checks to verify recalling firms notify their customers of the recall and that steps are taken to make certain that the product is no longer available to consumers.

Media with questions about the recall should contact Philip Wicke, Vice President of Operations, at (701) 356-7723. Consumers with questions about the recall should contact Jeremy Anderson, Director of Customer Service, at (952) 545-2495.

Consumers with food safety questions can "Ask Karen," the FSIS virtual representative available 24 hours a day at The toll-free USDA Meat and Poultry Hotline 1-888-MPHotline (1-888-674-6854) is available in English and Spanish and can be reached from l0 a.m. to 4 p.m. (Eastern Time) Monday through Friday. Recorded food safety messages are available 24 hours a day. #

Thursday, June 26, 2008

Texas Firm Recalls Cattle Heads That Contain Prohibited Materials

Tuesday, July 1, 2008

Missouri Firm Recalls Cattle Heads That Contain Prohibited Materials SRMs

Friday, August 8, 2008

Texas Firm Recalls Cattle Heads That Contain Prohibited Materials SRMs 941,271 pounds with tonsils not completely removed

Saturday, April 5, 2008


Wednesday, April 30, 2008

Consumption of beef tongue: Human BSE risk associated with exposure to lymphoid tissue in bovine tongue in consideration of new research findings

Sunday, October 18, 2009

Wisconsin Firm Recalls Beef Tongues That Contain Prohibited Materials SRM WASHINGTON, October 17, 2009

Thursday, October 15, 2009

Nebraska Firm Recalls Beef Tongues That Contain Prohibited Materials SRM WASHINGTON, Oct 15, 2009


Date: March 21, 2007 at 2:27 pm PST




Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007


Cattle feed delivered between 01/12/2007 and 01/26/2007


Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

Firm initiated recall is ongoing.


Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.


42,090 lbs.







The firm does not utilize a code - only shipping documentation with commodity and weights identified.


Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.


Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.


9,997,976 lbs.


ID and NV



Thursday, March 19, 2009


Friday, September 4, 2009

FOIA REQUEST ON FEED RECALL PRODUCT 429,128 lbs. feed for ruminant animals may have been contaminated with prohibited material Recall # V-258-2009

and all this was confirmed here ;


----- Original Message -----

From: "Terry S. Singeltary Sr."


Sent: Thursday, November 05, 2009 9:25 PM

Subject: [BSE-L] re-FOIA REQUEST ON FEED RECALL PRODUCT contaminated with prohibited material Recall # V-258-2009 and Recall # V-256-2009

Thursday, November 12, 2009

BSE FEED RECALL Misbranding of product by partial label removal to hide original source of materials 2009

Tuesday, March 2, 2010

Animal Proteins Prohibited in Ruminant Feed/Adulterated/Misbranded Rangen Inc 2/11/10 USA

Monday, March 1, 2010


Monday, April 5, 2010

Update on Feed Enforcement Activities to Limit the Spread of BSE April 5, 2010

Saturday, July 23, 2011


Saturday, November 6, 2010

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS


Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR> Prion disease update 2010 (11)


Monday, October 10, 2011

EFSA Journal 2011 The European Response to BSE: A Success Story


EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.


see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans.

Transmissible Spongiform Encephalopathy (TSE) Prion Disease, aka mad cow disease, are emerging in more ways than one, and the risk factors there from are very disturbing. The TSE Prion disease has morphed into many different strains, and in some cases, with Co-occurrence of multiple Prion Protein Types in one recipient. There are now many more strains of BSE aka Mad Cow Disease, what are termed 'atypical' BSE. atypical BSE is more virulent than the typical UK c-BSE. L-BSE, H-BSE, along with the U.K. C-BSE, have all been documented in North America (IBNC prion disease in cattle has not been documented in North America to date), along with two different strains of Chronic Wasting Disease (CWD) in deer and elk (documented to date), and many typical strains of Scrapie in sheep and goat, with the atypical Nor-98 Scrapie documented and spreading in North America. Over time, all these different TSE prion disease have been rendered and fed back to food producing animals here in the USA. The August 4, 1997 partial and voluntary mad cow feed ban in the USA was nothing more than ink on paper. The Bovine Spongiform Encephalopathy (BSE) aka mad cow disease surveillance program of the USA was terrible flawed (see GAO, OIG reports), and the BSE testing program was just as flawed, and this all a proven fact. With the mad cow feed ban having not been enforceable, 100s and 100s of TONS of banned MBM went on to be fed to USA cattle a decade after the August 4, 1997 partial and voluntary feed ban for BSE was inked on paper. Today, the USA has no idea (in my opinion), just how bad the BSE aka mad cow disease really is. However, the USA has more documented TSE prion disease in different species in the wild, than any other country, all rendered and fed back to food producing animals for man and animal. sporadic Creutzfeldt Jakob Disease in humans, with unknown pathology is rising in the USA and Canada. I urge Science to move forward, leaving the politics behind $$$

Monday, October 10, 2011 EFSA Journal 2011

The European Response to BSE: A Success Story

Monday, September 26, 2011

L-BSE BASE prion and atypical sporadic CJD

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.


The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...

Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque


Saturday, December 3, 2011

Isolation of Prion with BSE Properties from Farmed Goat

Volume 17, Number 12—December 2011

Saturday, November 19, 2011

Novel Prion Protein in BSE-affected Cattle, Switzerland

Friday, October 28, 2011

CVM Issues Animal Feed Safety System (AFSS) (BSE) Overview October 28 2011

CVM Issues Animal Feed Safety System (AFSS) Overview

Document -


Historically, FDA’s feed program has focused on specific safety issues, such as unsafe tissue residues resulting from feeding of medicated feeds, Bovine Spongiform Encephalopathy (BSE), and Salmonella, but has not addressed feed safety in a comprehensive manner. A comprehensive feed safety program is intended to help identify feed hazards and their potential sources and to enable establishments and FDA to prevent or eliminate the occurrence of unacceptable feed risks from those hazards.


i about choked when i read about the _historically_ part. in truth, FDA historically failed in the BSE mad cow protein feed ban and SRM removal, along with the BSE surveillance program.

strange, i wrote and sent this off earlier today. ...tss

----- Original Message -----

From: Terry S. Singeltary Sr.


Sent: Friday, October 28, 2011 1:35 PM


Hello Ms. Yao Ma'am and FDA et al,

A kind and warm greetings from Bacliff, Texas.

I have been following the mad cow saga here in the USA, pretty much since it started here in the USA. I lost my mother to the Heidenhain Variant of Creutzfeldt Jakob Disease, an exceedingly rare strain of the sporadic CJD's. as a layperson, i never accepted the myth that 85%+ of all human TSE i.e. the sporadic CJD was just a happenstance of bad luck, a spontaneous happening, no source, no route. just bad luck. i am sorry, i just could never accept that.

anyway Ma'am, I am wondering why there have been NO reports on the Enforcement Activities to Limit the Spread of BSE since January 12, 2011 ?



Monday, April 12, 2010

Senator Kay Bailey Hutchison says NO to safer food and S. 510 FDA Food Safety Modernization Act of 2009


Tuesday, May 10, 2011

Food safety for whom? Corporate wealth versus people's health

Food safety for whom? Corporate wealth versus people's health

GRAIN, May 2011


School children in the US were served 200,000 kilos of meat contaminated with a deadly antibiotic-resistant bacteria before the nation's second largest meat packer issued a recall in 2009. A year earlier, six babies died and 300,000 others got horribly sick with kidney problems in China when one of the country's top dairy producers knowingly allowed an industrial chemical into its milk supply. Across the world, people are getting sick and dying from food like never before. Governments and corporations are responding with all kinds of rules and regulations, but few have anything to do with public health. The trade agreements, laws and private standards used to impose their version of "food safety" only entrench corporate food systems that make us sick and devastate those that truly feed and care for people, those based on biodiversity, traditional knowledge, and local markets. People are resisting, whether its movements against GMOs in Benin and "mad cow" beef in Korea or campaigns to defend street hawkers in India and raw milk in Colombia. The question of who defines "food safety" is increasingly central to the struggle over the future of food and agriculture.

The growing global menace

Food should be a source of health, not harm. But food can maim, cripple, and kill. The leading cause of food poisoning in the United Kingdom today is Campylobacter, a tiny bacterium, rife throughout the country's chicken supply, that causes in humans diarrhoea, fever, abdominal pain and cramping, and in some cases chronic, even life-threatening, conditions. People get it from touching raw poultry or eating undercooked birds. Some 85% of the chicken population in the UK may be infected. In the United States, the top culprits these days are Norovirus, mostly transmitted from dirty hands, and Salmonella, contracted from eating food with faeces on it. Norovirus will give you acute vomiting and diarrhoea, while Salmonella causes vomiting, fever and cramps


Graph: Data compiled by GRAIN from government and UN sources, 2008-2010 (except Australia=2005)

Among the more notorious food safety incidents in recent years was the melamine scandal in China in 2008. Six babies died and 300,000 others got horribly sick with kidney problems when the industrial chemical melamine got into the commercial milk distribution circuit. There was also a dioxin scandal in Germany in January 2011, where the German authorities shut down more than 4,000 farms after it was discovered that a German company had sold 200,000 tonnes of dioxin-tainted animal feed, which had subsequently entered the food chain. Dioxins are cancer-causing poisons formed in the burning of waste and other industrial processes. 1

How bad is the problem globally? Believe it or not, there are no global statistics or tracking mechanisms on food safety incidents worldwide; reliable data on their frequency and impact are grossly inadequate. Nevertheless, the available data do show that food poisoning is quite common in most countries (see Graph 1). 2 According to the Singaporean authorities, who run a pretty tight food hygiene system, roughly 1.5 billion people worldwide are affected by food-borne disease outbreaks each year, resulting in 3 million deaths. 3

The price of this food safety mess is huge. The UK puts the annual costs to the British economy at US$1.92 billion, which its Food Standards Agency bluntly calls "too much". Australia's annual bill is US$1.23 billion. The World Health Organisation says that the annual cost to Vietnam is US$210 million. In the US, the Centers for Disease Control (CDC) has long given the figure of US$35 million per year, but a new study released by the Pew Charitable Trusts at Georgetown University in 2010 puts the figure astronomically higher, at US$152 billion. 4

Food safety in the Fast Food Nation

Does US-style production represent the future of global food? Possibly. Certainly, elite Western opinion shapers and policymakers – the editors of The Economist, the directors of the Bill and Melinda Gates Foundation, certain key elements in the Obama administration – think it should. So it is worthwhile to consider how the US food safety regime has responded to the dilemmas of scale in recent years.

In an industrialised, highly consolidated food system geared to maximising profit by selling vast volumes of cheap food, pressure exists at every phase of the production chain to cut costs by cutting corners, including safe food practices. Moreover, the very scale of modern food production means that seemingly isolated lapses can become quite grave, subjecting millions of people to danger based on the actions of a single production facility.

The case of Peanut Corp. of America demonstrates the perils of scale. Until recently, the company ran two plants: one in Texas, one in Georgia. These two facilities processed 2.5% of the peanuts produced in the United States, and sold "peanut paste" to the entire US processed food industry. By late 2007, the company had evidently given up trying to maintain hygienic conditions at its facilities. In late 2008, people started coming down with salmonella from a dizzying array of products containing Peanut Corp.'s paste, prompting the FDA to initiate a "voluntary recall". By the time all was said and done, the recall affected no fewer than 1,800 supermarket brands. The tainted products killed nine people and officially sickened around 700 – half of them children – in 46 US states. The Centers for Disease Control (CDC) reckons that for every reported case of salmonella, another 38 cases go unreported – so the real number of people made ill from the output of just two facilities may be up to 26,000. In the wake of the fiasco, US journalists showed that the FDA had "outsourced" inspection of the Georgia plant to state authorities, and then ignored the state inspectors' findings of atrocious hygiene practices. Moreover, it turned out that the company's own testing had found salmonella in huge batches of peanut paste, which it proceeded to send out anyway. i

In another incident in 2009, a company called Beef Packers, owned by transnational agribusiness giant Cargill, had to declare two "voluntary recalls" involving over 500 tonnes of ground beef infected with antibiotic-resistant salmonella. ii The USDA announced that consuming the suspect meat could cause "treatment failure" iii – that is, death – because of its ability to withstand drugs. At least 39 people in 11 states reported getting sick, and more than 200,000 thousand kilos of the tainted meat was served to school children through the National School Lunch program. iv

The official response to such incidents has been minimal. In January 2011, a hotly debated piece of legislation called the Food Safety Modernisation Act was signed into being. The intention of the original Bill was to update and inject some resources into the US food safety system. It basically called for more inspections, gave the government authority to mandate food recalls, and provided some traceability to an otherwise fairly unregulated industrial sector. Who would oppose such a move? The fat cats from the food industry, you might think – the Cargills and the Tysons, who don't want to be controlled. But you would be wrong. The new rules would hardly affect them.

According to an analysis by the US NGO Food & Water Watch, nothing in the Act would have prevented the Peanut Company of America from sending out its tainted paste. Worse, the rules would not even touch the meat sector, the biggest source of food-borne illness in the United States. v The main opponents of the bill throughout the debate were small family farm activists who, because of the way the bill was framed, saw themselves falling under these controls when they are not the problem. So instead of instigating real food safety reform in a country where one out of four people gets sick and 5,000 people die from eating contaminated food each year, the law might do next to nothing.

In the absence of stricter public action around food safety, corporations have moved to fill the void -- sometimes to tragicomic effect. A case in point: in the mid-2000s, a company called Beef Products Inc. had an ingenious idea: it would buy slaughterhouse scraps – which are extremely likely to be infected by bacterial pathogens – from large-scale beef processors at cut-rate prices. It would purée those parts into a paste, which it would then mix with ammonia to kill bacterial pathogens. It would sell the product back the the beef industry as a cheap filler for ground beef, with the added feature that the ammonia in the paste would sterilise the ground beef it was mixed with. The beef industry had found a "solution" to the problem of bacterial pathogens in ground beef! The product, known in the industry as "pink slime" for its distinctive look, could be found in 70% of hamburgers consumed in the United States by the end of the decade. The USDA's Food Safety Inspection Service, which oversees meat safety, applauded -- it recognised "pink slime" as safe without requiring testing, on the grounds that it had been sterilised by ammonia. But in 2009, a New York Times exposé found that pink slime in fact tended to be ridden with pathogens -- and was actively adding to the pathogen load of the ground beef it was mixed with. Beef Products Inc. responded by merely upping the ammonia dose for its mix. To this day, the product remains widely used in the vast US ground beef market, including at fast-food chains nationwide. vi

If the official US response to highly visible manifestations of food poisoning, like Salmonella-tainted meat and peanut butter, has been underwhelming and industry-friendly, then the response to low-level exposure to pathogens that cause cumulative damage has been virtually non-existent. The first kind causes spectacular, impossible-to-ignore symptoms like vomiting and diarrhoea; the second entails subtle, easy-to-ignore ones that can cause significant long-term damage. Corporate-led food safety regimes like the one in the United States have to at least gesture at the first kind; the second kind, not so much.

It turns out that the USDA's Food Safety Inspection Service (FSIS), which oversees the safety of the US meat supply, routinely endorses meat that it knows to be tainted with residues of "veterinary drugs, pesticides, and heavy metals", the USDA Inspector General revealed in a 2010 report. vii The damning report was met with silence by the US media – probably because small amounts of substances like heavy metals don't cause dramatic immediate symptoms, but rather hard-to-trace, slow-to-develop conditions like cancer. As the report puts it, the "effects of residue are generally chronic as opposed to acute, which means that they will occur over time, as an individual consumes small traces of the residue". In its report, the USDA Inspector General's office expressed confidence that the FSIS would redouble efforts to keep heavy metals and antibiotic traces out of the meat supply going forward. Yet it had expressed the same thing, after exposing the same problem, in its report two years earlier. viii

Another example is the US Food and Drug Administration's refusal to act on mounting evidence that Bisphenol A, an industrial compound found in many food containers, is an endocrine disrupter. If the food safety regime for spectacular pathogens could be described as porous, that for the second, more subtle, kind barely exists at all.

Written with contributions from Tom Philpott, senior writer on food and agriculture for Grist magazine.

i "Peanut Corp. Shipped Product After Finding Salmonella", Bloomberg News, 27 January 2009,;
 and "Peanut Plant Had History of Health Lapses", New York Times, 26 January 2009,

ii "Antibiotic-resistant salmonella, school lunches, and Cargill's dodgy California beef plant", Grist, 10 December 2010,

iii "California Firm Recalls Ground Beef Products Due to Possible Salmonella Contamination", USDA Food Safety and Inspection Service, 9 December 2009,

iv "Why a recall of tainted beef didn't include school lunches", USA Today, 2 December 2009,

v Responsibility for food safety in the US is divided between two agencies. The US Department of Agriculture is responsible for meat, poultry and egg products, which accounts for 20% of the US food supply. The Food and Drug Administration, within the US Department of Health, takes care of the rest. The Food Safety Modernisation Act addresses only the work of the FDA. The top sources of food poisoning in the United States are, however, poultry, beef and leafy vegetables (in that order, 2007). See: "Can Congress make a food-safety omelette without breaking the wrong eggs? ", Grist, 25 October 2010.

vi "Safety of Beef Processing Method Is Questioned", New York Times, 30 December 2009,
; See also, "Lessons on the food system from the ammonia-hamburger fiasco", Grist, 5 January 2010,

vii "FSIS National Residue Program for Cattle", Office of the Inspector General, US Department of Agriculture,

viii "USDA Inspector General: meat supply routinely tainted with harmful residues", Grist, 15 April 2010:

This is "food safety"?

Government and industry action on food safety gives little indication that they recognise any fundamental problem with industrial food production. Rarely do their regulations or standards hinder corporate practices in any significant way. On the contrary, they tend to reinforce the power of large industry while undermining, or even criminalising, small-scale production and local food cultures. Colombia, for instance, is in the process of implementing legislation to prevent the sale of raw milk in urban areas. Well over two million farmers and vendors depend for their livelihoods on these sales of raw milk, and around 20 million Colombians, most of them poor, depend on raw milk as an affordable and essential source of nutrition, easily made safe by boiling it at home. Hard pressed to justify its moves on public health grounds, the government says that the legislation is part of its commitment to the WTO, and that it will help to "modernise" the dairy sector, making it better able to compete with imports when a looming free trade agreement with the EU kicks in. 5

These days, in Colombia and elsewhere, "food safety" policy has little to do with public health or consumers. It has become a battleground among contesting interests, the site of power struggles for control over food and agriculture, with decisions being increasingly taken far from producers and consumers, in the obscure world of trade negotiations and multilateral agencies, where politics and commerce, not science and public health, are what drive things.

Consider the case of bovine spongiform encephalopathy (BSE), the fatal brain-wasting condition popularly known as mad cow disease. People get the human strain of it by eating the meat of cows that have been fed diseased animals as a cheap source of protein – a practice common in industrial feedlots since the 1970s. The US and Canada lost Japan, Korea and several other major export markets for beef when BSE was found in their herds in 2003, and have had a tough time regaining those markets because risks remain from their industries' feeding practices. 6 Indeed, in March 2011, a new case of BSE was identified in a Canadian cow. 7 But through constant pressure, particularly at the trade negotiating table, both countries have secured some concessions to allow certain parts of the cow, or the meat of younger animals, to cross borders freely. Both countries also went to the Organisation for Animal Health (OIE) in Paris, which has a similar role to Codex Alimentarius Commission in Rome but for the animal kingdom, to get their beef declared generally safe for consumption. Where does that leave Japan? Unmoved. It says that its standards are higher than those of the OIE or the US, and have to be given priority.

Beijing, for its part, has so far refused to budge. But that doesn't mean that Chinese consumers are getting ractopamine-free pork. The same government fighting off ractopamine-laced US pork, is aggressively pushing, in the name of "food safety", a consolidation and modernisation of the country's pig production based on the US factory farm model. China's two largest, vertically-integrated pork producers, Yurun and Shineway, both of whom have been heavily funded by the US bank Goldman Sachs, were implicated in recent food safety incidents involving ractopamine and clenbuterol (another banned drug added to pig feed for the same purposes). 8 In March 2011, Chinese consumers were shocked when a CCTV television report uncovered how ractopamine and clenbuterol are widely used in the farms supplying Shineway in Henan Province. 9 The report found that Shineway was actually offering farmers higher prices for pigs fed ractopamine. 10

Superbugs and megafarms

"Superbug" is a term used to describe bacteria that have acquired the ability to resist commonly used antibiotics. One of the most notorious is Methicillin-resistant Staphylococcus aureus (MRSA), which emerged in the 1960s in the UK and has since spread around the world, with deadly consequences. In the US alone, 17,000 people died from MRSA infection in 2005. i

MRSA is typically associated with hospitals, where the superbug has a tendency to get into open wounds and cause difficult-to-heal infections. But in recent years these superbugs have found another place to thrive: industrial pig farms. ii

In 2004, Dutch researchers identified a new strain of MRSA, later labelled ST398 or "pig MRSA", which they found in people in close contact with Dutch pig farms. Within two years ST398 become a leading source of human MRSA infection in the country, accounting for more than one in five human MRSA cases. Studies showed that these cases were closely related with pigs, and further research revealed that ST398 was running rampant in pigs on Dutch farms. A 2007 survey found ST398 in 39% of pigs and 81% of local piggeries. iii

New surveys of farms outside of the Netherlands have turned up similar numbers. iv The first ever EU-wide survey for MRSA on pig farms in 2009, using a method that "largely underestimates MRSA prevalence", found ST398 in more than two-thirds of EU member states. Spain and Germany had the highest incidence, with over 40% of pig holdings testing positive for MRSA. v Not surprisingly, given the European pig industry's heavy exports overseas, ST398 is turning up in pigs beyond Europe's borders, too. A study of pigs in the Canadian province of Ontario, for instance, found ST398 in a quarter of local pigs, as well as in one-fifth of the pig farmers tested. vi Only one study has been conducted in the US so far: it was a pilot study of two large hog operations in the midwest that found ST398 in 49% of the pigs and 45% of the workers. vii

MRSA has the potential to evolve in very dangerous ways in its new home on pig farms. The density of animals in factory farms allows the bacteria to evolve rapidly and in diverse ways. Also, the use of antibiotics on factory farms is ubiquitous. Pigs are routinely fed antibiotics in their feed and water, often as a preventive measure against disease outbreaks and even simply to increase growth rates.

In the US, 80% of all antibiotics consumed annually are consumed by livestock. viii In China, the figure is nearly 50%. ix Even in the EU, where the non-therapeutic use of antibiotics for animals is banned and where the types of antibiotics allowed for livestock are controlled, the use of antibiotics for animals still exceeds their use for humans. In Germany, for example, three times as many antibiotics are given to animals as to humans. x Such widespread use of antibiotics in factory farms speeds up the development of antibiotic resistance among bacteria. Unlike other strains of MRSA, ST398 can already withstand tetracyclines, a group of antibiotics that is given heavily and regularly to pigs in factory farms. The medical profession is getting increasingly worried about what this will mean for the future of human health care, as antibiotics may become useless. The WHO now calls it "the greatest threat to human health". xi

The good news, however, is that ST398 still hasn't shown much virulence in humans, nor is it easily transmitted between people. Not yet, at least.

In 2010, a 14-year-old girl in France, recovering in hospital from pneumonia, was infected with a superbug. She soon began having serious respiratory problems, her lungs started bleeding, and within six days she died. The superbug that killed her was a clone of MRSA ST398 that is known to circulate in humans. The most alarming issue for the French doctors studying the case was that this was the first incident on record in which this strain of MRSA had acquired the capacity to produce a lethal toxin in humans, something that certain other strains of superbugs are able to do. They reasoned that if the clone of MRSA ST398 could do it, then surely "pig MRSA" has the same capacity. xii

It is not much of a stretch to imagine a situation where "pig MRSA" passes from a pig to a farm worker carrying another MRSA strain with virulence to humans, mixes with that strain, and acquires its capacity for virulence. The new virulent strain of ST398 could then easily pass back into the pigs, where it would rapidly amplify and spread. ST398 is transmitted to humans not only through contact with live pigs: the bacteria is also present on meat sold in supermarkets and can be carried over large distances by the insects that pass in and out of farms. xiii

The EU is slowly starting to take action to defend against such a possibility. It has implemented several measures to restrict the use of antibiotics in livestock production and, at national and at EU level, some surveillance of farms is being carried out. In 2009, a panel of the European Food Safety Authority recommended that the EU move towards "systematic surveillance and monitoring of MRSA in intensively reared animals". South Korea, for its part, banned the use of seven antibiotics in animal feed in 2008, and implemented a national programme to reduce the use of antibiotics on livestock farms. But such restrictions on the use of antibiotics for livestock hardly exist in the US, although proposed legislation restricting the non-therapeutic use of certain antibiotics in feed is currently before Congress. As for surveillance, the US National Antimicrobial Resistance Monitoring System doesn't even test for MRSA. xiv Outside the industrialised countries, where the meat industry is expanding most rapidly, there is an almost complete absence of controls on the use of antibiotics in agriculture and of surveillance for pathogens such as MRSA.

Enhancing surveillance and cutting back on the use of antibiotics in factory farms are important measures. But they aren't enough to deal effectively with the threat posed by MRSA and the myriad other pathogens that thrive in factory farms. A staggering 61% of all human pathogens, and 75% of new human pathogens, are transmitted by animals, with many of the most dangerous – such as bird flu, BSE, swine flu and the Nypah virus – having emerged from intensive livestock farms. xv It is the way that animals are farmed that is fundamentally at issue. xvi

i E. Klein, D.L. Smith, R. Laxminarayan, "Hospitalizations and Deaths Caused by Methicillin-Resistant Staphylococcus aureus, United States, 1999–2005", Emerg. Infect. Dis. Vol. 13, No. 12, 2007, pp. 1840–46.

ii Ed Yong, "MRSA in pigs and pig farmers", 23 January 2009,

iii X.W. Huijsdens et al., "Community-acquired MRSA and pig-farming", Ann. Clin. Microbiol. Antimicrob., Vol. 5, No. 26, 2006; A.J. de Neeling et al., "High prevalence of methicillin resistant Staphylococcus aureus in pigs", Vet. Microbiol., Vol. 122, No. 3–4, 21 June 2007, pp. 366–72; I. van Loo et al., "Emergence of methicillin-resistant Staphylococcus aureus of animal origin in humans", Emerg. Infect. Dis., Vol. 13, No. 12, 2007, pp. 1834–9.

iv Danish Integrated Antimicrobial Resistance Monitoring and Research Programme,

v "Pig MRSA widespread in Europe", Ecologist, 25 November 2009; Broens et al., "Diagnostic validity of pooling environmental samples to determine the status of sow-herds for the presence of methicillin-resistant Staphylococcus aureus (MRSA)", Poster presented at the ASM–ESCMID Conference on Methicillin-resistant Staphylococci, in Animals: Veterinary and Public Health Implications, London, 2009.

vi "Guelph Researchers Find MRSA in Pigs", University of Guelph, 8 November 2007,

vii T.C. Smith, M.J. Male, A.L. Harper, J.S. Kroeger, G.P. Tinkler et al., (2009) "Methicillin-Resistant Staphylococcus aureus (MRSA) Strain ST398 Is Present in Midwestern US Swine and Swine Workers", PLoS ONE, Vol. 4, No. 1, 2009.

viii See "New FDA Numbers Reveal Food Animals Consume Lion's Share of Antibiotics", Center for a Liveable Future, Johns Hopkins University, 23 December 2010,.
 See also Margaret Mellon, Charles Benbrook, Karen Lutz Benbrook, "Hogging it!: Estimates of antimicrobial abuse in Livestock", Union of Concerned Scientists, 2001,

ix "Half of China's antibiotics fed to animals: expert", Xinhua, 26 November 2010.

x Kristen Kerksiek, "Farming out Antibiotics: The fast track to the post-antibiotic era", Infection Research, Germany, 22 March 2010,

xi AAP, "Greatest threat to human health", Sydney Morning Herald, 16 February 2011,

xii Frédéric Laurent, "Les souches de staphylococcus aureus ST398 sont-elles virulents", Bull. Acad. Vét. France, Vol. 163, No. 3, May 2010.

xiii See Aqeel Ahmad et al., "Insects in confined swine operations carry a large antibiotic resistant and potentially virulent enterococcal community", BMC Microbiology, 2011,

xiv Maryn McKenna, "Alarm over 'pig MRSA' – but not in the US", Wired, 30 October 2010,

xv John McDermott and Delia Grace, "Agriculture-Associated diseases: Adapting Agriculture to improve Human Health", ILRI, February 2011.

xvi GRAIN, "Germ warfare: Livestock disease, public health and the military-industrial complex", Seedling, January 2008,

Food safety and global trade: Europe and the US impose their standards


Read the synopsis of this report here.

Approximately 50.3 million pounds of the beef recalled by HallmarkWestland went to federal nutrition programs, including the National School Lunch Program, and of those 50.3 million pounds, about 19.6 million pounds had already been consumed at the time the recall was issued. Release No. 0054.08, USDA, Transcript of Technical Briefing - HallmarkWestland Meat Packing Company (Feb. 21, 2008).

9. HSUS members that consume meat products, including beef products, are concerned about eating adulterated meat products and the health risks associated with such adulterated meat. Specifically, they are concerned that downed cattle are at an increased risk for harboring and transmitting BSE prions and other pathogens. The consumption of meat products derived from BSE-infected cattle is believed to cause a human neurological disease known as variant Creutzfeldt-Jakob disease ("vCJD"). The disease is progressive, invariably fatal, and there is no known effective treatment or cure. Downed cattle may also be at higher risk for harboring other foodborne transmissible pathogens, including E. coli 0157:H7, Salmonella, and anthrax. By allowing downed cattle to enter the food supply, USDA's regulatory loophole injures members of The HSUS by placing them at an increased risk of contracting these food-borne illnesses each time they eat beef.

10. Members of The HSUS are also concerned about the meat products provided to their children through the National School Lunch Program. More than 31 million school children receive lunches through the program each school day. To assist states in providing healthful, low-cost or free meals, USDA provides states with various commodities including ground beef.

As evidenced by the HallmarkWestland investigation and recall, the potential for downed animals to make their way into the National School Lunch Program is neither speculative nor hypothetical.

Sunday, May 01, 2011

STUDY OF ATYPICAL BSE 2010 Annual Report May 2011

Monday, April 18, 2011

Multidrug-Resistant Staphylococcus aureus in US Meat and Poultry