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Homeostatic Cannabinoid Science ~ Publius’ World Cup Edition

7/6/2014

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PictureThe Cannabis Papers by Publius (2011)






The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius


A World (Cup) of Cannabinoids: Fielders Edition

Today’s science roundup looks at ten articles on how the cannabinoid system (CS) modulates our health and homeostasis; the line-up links to 2014 CS PubMed articles: four directly on homeostasis, two on the circulatory system, two on the central nervous system, and one each on our digestive and respiratory systems.

I. CNS (Pediatric Brain Injury) and the CS
“Paediatric traumatic brain injury (TBI) is a leading cause of death and disability. Previous studies showed neuroprotection after TBI by (endo)cannabinoid mechanisms, suggesting involvement of cannabinoid receptors (CBR). … The results may provide explanation for the neuroprotective properties of cannabinoid ligands and future therapeutic strategies of TBI.”
Early increase of cannabinoid receptor density after experimental traumatic brain injury in the newborn piglet.
Donat CK, Fischer F, Walter B, Deuther-Conrad W, Brodhun M, Bauer R, Brust P.
Acta Neurobiol Exp (Wars). 2014;74(2):197-210.
PMID: 24993629 [PubMed - in process]
Related citations

II. Digestive System (Irritable Bowel Syndrome) and the CS
“The activation of the ATP ion-gated channels, voltage-gated sodium (Nav) and calcium (Cav) channels, as well as the activation of protease-activated receptors (PAR2), transient receptor potential vanilloide-1, serotonin, cannabinoids and cholecystokinin are involved in the genesis of visceral hypersensitivity in IBS.”
Main ion channels and receptors associated with visceral hypersensitivity in irritable bowel syndrome.
de Carvalho Rocha HA, Dantas BP, Rolim TL, Costa BA, de Medeiros AC.
Ann Gastroenterol. 2014;27(3):200-206. Review.
PMID: 24976114 [PubMed - as supplied by publisher] Free PMC Article
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III. Respiratory System (Paraquat and Acute Lung Injury) and the CS
“Paraquat [PQ], a widely used herbicide, is well known to exhibit oxidative stress and lung injury. … The results suggested that activating CB2 receptor exerted protective activity against PQ-induced ALI [Acute Lung Injury], and it potentially contributed to the suppression of the activation of MAPKs and NF- κ B pathways.”
CB2 Receptor Activation Ameliorates the Proinflammatory Activity in Acute Lung Injury Induced by Paraquat.
Liu Z, Wang Y, Zhao H, Zheng Q, Xiao L, Zhao M.
Biomed Res Int. 2014;2014:971750. doi: 10.1155/2014/971750. Epub 2014 May 22.
PMID: 24963491 [PubMed - in process] Free PMC Article
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IV. Homeostasis (Indole Quinuclidine Analogs) and the CS
“Therefore, indole quinuclidines are a novel structural class of compounds exhibiting high affinity and a range of intrinsic activity at cannabinoid type-1 and type-2 receptors.”
Characterization of the intrinsic activity for a novel class of cannabinoid receptor ligands: Indole quinuclidine analogs.
Franks LN, Ford BM, Madadi NR, Penthala NR, Crooks PA, Prather PL.
Eur J Pharmacol. 2014 Aug 15;737:140-8. doi: 10.1016/j.ejphar.2014.05.007. Epub 2014 May 20.
PMID: 24858620 [PubMed - in process]
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V. Circulatory System (Ischemic Heart Disease) and the CS
“Ischemic heart disease is associated with inflammation, interstitial fibrosis and ventricular dysfunction prior to the development of heart failure. … Therefore, the endocannabinoid-CB2 receptor axis plays a key role in cardioprotection during the initial phase of ischemic cardiomyopathy development.”
The endocannabinoid-CB2 receptor axis protects the ischemic heart at the early stage of cardiomyopathy.
Duerr GD, Heinemann JC, Suchan G, Kolobara E, Wenzel D, Geisen C, Matthey M, Passe-Tietjen K, Mahmud W, Ghanem A, Tiemann K, Alferink J, Burgdorf S, Buchalla R, Zimmer A, Lutz B, Welz A, Fleischmann BK, Dewald O.
Basic Res Cardiol. 2014 Jul;109(4):425. doi: 10.1007/s00395-014-0425-x. Epub 2014 Jul 1.
PMID: 24980781 [PubMed - in process]
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VI. Homeostasis, Endocannabinoid Deficiencies and the CS
“Subsequent research has confirmed that underlying endocannabinoid deficiencies indeed play a role in migraine, fibromyalgia, irritable bowel syndrome and a growing list of other medical conditions. Clinical experience is bearing this out. Further research and especially, clinical trials will further demonstrate the usefulness of medical cannabis. As legal barriers fall and scientific bias fades this will become more apparent.”
Clinical endocannabinoid deficiency (CECD) revisited: Can this concept explain the therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?
Smith SC, Wagner MS.
Neuro Endocrinol Lett. 2014 Jun 30;35(3):198-201. [Epub ahead of print]
PMID: 24977967 [PubMed - as supplied by publisher]
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VII. Homeostasis (Epilepsy, Neuronal Plasticity) and the CS
“Synaptic communication requires constant adjustments of pre- and postsynaptic efficacies. In addition to synaptic long-term plasticity, the presynaptic machinery underlies homeostatic regulations which prevent out of range transmitter release. In this mini-review we will discuss the relevance of selected presynaptic mechanisms to epilepsy including voltage- and ligand-gated ion channels as well as cannabinoid and adenosine receptor signaling.”
Presynaptic mechanisms of neuronal plasticity and their role in epilepsy.
Meier J, Semtner M, Winkelmann A, Wolfart J.
Front Cell Neurosci. 2014 Jun 17;8:164. doi: 10.3389/fncel.2014.00164. eCollection 2014. Review.
PMID: 24987332 [PubMed]
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VIII. Homeostasis (Turning Agonists into Antagonists) and the CS
“However, we discovered that bivalency has an influence on the effect at both cannabinoid receptors. Moreover, we found out that the spacer length and the attachment position altered the efficacy of the bivalent ligands at the receptors by turning agonists into antagonists and inverse agonists.”
Synthesis and biological evaluation of bivalent cannabinoid receptor ligands based on hCB2R selective benzimidazoles reveal unexpected intrinsic properties.
Nimczick M, Pemp D, Darras FH, Chen X, Heilmann J, Decker M.
Bioorg Med Chem. 2014 Jun 13. pii: S0968-0896(14)00454-4. doi: 10.1016/j.bmc.2014.06.008. [Epub ahead of print]
PMID: 24984935 [PubMed - as supplied by publisher]
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IX. Circulatory System (Blood Vessels-Heart) and the CS
“2-Arachidonoylglycerol [2-AG] plays an important role in the regulation of the circulatory system via direct and/or indirect, through their metabolites, effects on blood vessels and/or heart. Accumulating evidence reveals that 2-AG is involved in the pathogenesis of various shocks and atherosclerosis.”
Role of endocannabinoid 2-arachidonoylglycerol in the physiology and pathophysiology of the cardiovascular system.
Karabowicz P, Grzęda E, Baranowska-Kuczko M, Malinowska B.
Postepy Hig Med Dosw (Online). 2014 Jun 12;68(0):814-27.
PMID: 24934539 [PubMed - in process]
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X. CNS (Brain Mitochondria) and the CS
“Our results show that the use of appropriate controls and quantifications allows detecting mtCB1 receptor with CB1 receptor antibodies, and that, if mitochondrial fractions are enriched and purified, CB1 receptor agonists reliably decrease respiration in brain mitochondria.”
Cannabinoid control of brain bioenergetics: Exploring the subcellular localization of the CB1 receptor.
Hebert-Chatelain E, Reguero L, Puente N, Lutz B, Chaouloff F, Rossignol R, Piazza PV, Benard G, Grandes P, Marsicano G.
Mol Metab. 2014 Apr 2;3(4):495-504. doi: 10.1016/j.molmet.2014.03.007. eCollection 2014 Jul.
PMID: 24944910 [PubMed] Free PMC Article
Related citations

See also: Alzheimer’s, Cancer and Homeostatic Cannabinoid Science

Bonus Video: Homeostasis

Posted by Bryan W. Brickner


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Alzheimer’s, Cancer and Homeostatic Cannabinoid Science

6/29/2014

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PictureThe Cannabis Papers by Publius (2011)








The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius

The CS World Cup: Goaltender Edition

Today, tending to the goals of mediating Alzheimer’s and preventing carcinogenesis, Publius spotlights two June abstracts from PubMed on the homeostatic cannabinoid system (CS). For Alzheimer’s disease it is CS
modulation of cognitive decline; for preventing carcinogenesis the findings unveil a previously unknown CS signaling platform: CB2-GPR55 receptor heteromers.



I. CS Mediates Cognitive Decline In Alzheimer's Disease

Set: “It has been widely reported that β-amyloid peptide (Aβ) blocks long-term potentiation (LTP) of hippocampal synapses. Here, we show evidence that Aβ more potently blocks the potentiation of excitatory postsynaptic potential (EPSP)-spike coupling (E-S potentiation). This occurs, not by direct effect on excitatory synapses or postsynaptic neurons, but rather through an indirect mechanism: reduction of endocannabinoid-mediated peritetanic disinhibition.”

Setting: “During high-frequency (tetanic) stimulation, somatic synaptic inhibition is suppressed by endocannabinoids. We find that Aβ prevents this endocannabinoid-mediated disinhibition, thus leaving synaptic inhibition more intact during tetanic stimulation.”

Science: “This intact inhibition opposes the normal depolarization of hippocampal pyramidal neurons that occurs during tetanus, thus opposing the induction of synaptic plasticity. Thus, a pathway through which Aβ can act to modulate neural activity is identified, relevant to learning and memory and how it may mediate aspects of the cognitive decline seen in Alzheimer's disease.”
β-Amyloid Inhibits E-S Potentiation through Suppression of Cannabinoid Receptor 1-Dependent Synaptic Disinhibition.
Orr AL, Hanson JE, Li D, Klotz A, Wright S, Schenk D, Seubert P, Madison DV.
Neuron. 2014 Jun 18;82(6):1334-45. doi: 10.1016/j.neuron.2014.04.039.
PMID: 24945775 [PubMed - in process]
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II. CS Oncology Signaling Unveiled: Evidence of Previously Unknown Platforms

Set: “The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. As a modulation of GPR55 activity by cannabinoids has been suggested, we analyzed whether this receptor participates in cannabinoid effects on cancer cells.”

Setting: “Here, we show that CB2R and GPR55 form heteromers in cancer cells, that these structures possess unique signaling properties, and that modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo.”

Science: “These findings unveil the existence of previously unknown signaling platforms that help explain the complex behavior of cannabinoids and may constitute new targets for therapeutic intervention in oncology.”
Targeting CB2-GPR55 Receptor Heteromers Modulates Cancer Cell Signaling.
Moreno E, Andradas C, Medrano M, Caffarel MM, Pérez-Gómez E, Blasco-Benito S, Gómez-Cañas M, Pazos MR, Irving AJ, Lluís C, Canela EI, Fernández-Ruiz J, Guzmán M, McCormick PJ, Sánchez C.
J Biol Chem. 2014 Jun 18. pii: jbc.M114.561761. [Epub ahead of print]
PMID: 24942731 [PubMed - as supplied by publisher] Free Article
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Video: Homeostasis 1, Physiological Principles ~ Dr. John Campbell

Posted by Bryan W. Brickner

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Solstice Serotonin (5HTP) Science Stories

6/20/2014

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PictureLife ~ circa 2014






Serotonin activation was our topic on 19 April 2014; it’s serotonin life sciences today with the precursor 5-HTP (5-hydroxytryptophan) in highlight. 

Below are four (brief) science stories from the National Institutes of Health (PubMed). Shortened titles should suffice to suggest the main themes: Therapeutic 5-HTP, Hot Flash and Breast Cancer Reduction, Irritable Bowels, and Morphine’s Efficacy. The links and quotes are from PubMed (1998-2014).

Healthy Solstice Everyone!
~.~
Therapeutic 5-HTP Has Been Shown … (1998)
“5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness. … Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.”
5-Hydroxytryptophan: a clinically-effective serotonin precursor.
Birdsall TC.
Altern Med Rev. 1998 Aug;3(4):271-80. Review.
PMID: 9727088 [PubMed - indexed for MEDLINE] Free Article
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Hot Flash (and Breast Cancer) Reduction: a hypothesis (2005)
“This would be particularly desirable for menopausal women with breast cancer or with risks of breast cancer. This article discusses the background information on hot flashes, SSRIs, tryptophan, and 5HTP, and possible clinical application of 5HTP for menopausal women with breast cancer risk.”
The potential of 5-hydryoxytryptophan for hot flash reduction: a hypothesis.
Curcio JJ, Kim LS, Wollner D, Pockaj BA.
Altern Med Rev. 2005 Sep;10(3):216-21.
PMID: 16164376 [PubMed - indexed for MEDLINE] Free Article
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A Serotonin-mediated Mechanism in Bowels (2014)
“Oral 5-HTP induced alterations in mucosal 5-HT metabolism. In healthy controls, a reinforcement of the intestinal barrier was seen whereas such reaction was absent in IBS [irritable bowel syndrome] patients. This could indicate the presence of a serotonin-mediated mechanism aimed to reinforce intestinal barrier function, which seems to dysfunction in IBS patients.”
Serotonergic reinforcement of intestinal barrier function is impaired in irritable bowel syndrome.
Keszthelyi D, Troost FJ, Jonkers DM, van Eijk HM, Lindsey PJ, Dekker J, Buurman WA, Masclee AA.
Aliment Pharmacol Ther. 2014 Jun 18. doi: 10.1111/apt.12842. [Epub ahead of print]
PMID: 24943480 [PubMed - as supplied by publisher]
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Serotonin and Morphine’s Efficacy (2014)
“Systemic administration of morphine increases 5-HT levels in the spinal cord, and the increase in 5-HT contributes to morphine-induced analgesia in the normal state but attenuates that in neuropathic pain through spinal 5-HT3 receptors. The plasticity of the descending serotonergic system may contribute to the reduced efficacy of systemic morphine in neuropathic pain.”
Peripheral Nerve Injury Reduces Analgesic Effects of Systemic Morphine via Spinal 5-Hydroxytryptamine 3 Receptors.
Kimura M, Obata H, Saito S.
Anesthesiology. 2014 Jun 2. [Epub ahead of print]
PMID: 24887968 [PubMed - as supplied by publisher]
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VIDEO:
5HTP benefit and side effects of 5htp, dosage, anxiety, weight loss, sleep

BONUS VIDEO: Serotonin/Binaural Beats
5-HTP secretion for happiness binaural beats, intensity WARNING

~ Posted by Bryan W. Brickner ~


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Preventing Carcinogenesis via One’s Cannabinoid System ~ Publius’ May 2014 Cancer Research Awareness

5/18/2014

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Picture
The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius

Cancer research awareness and the cannabinoid system (CS) are the focus of May’s health update from Publius and The Cannabis Papers: A citizen’s guide to cannabinoids (2011). This month: PubMed CS science on preventing skin and colon carcinogenesis, phototherapy, melanomas, eicosands, gliomas, mitochondria and the omega-3 fatty acids DHA and EPA.

2014 ~ Skin Carcinogenesis, Inflammation and the CS
“Cancer is an environmental disease and skin cancer (melanoma and non-melanoma) is the most common of all cancers.”
The role of inflammation in skin cancer.
Maru GB, Gandhi K, Ramchandani A, Kumar G.
Adv Exp Med Biol. 2014;816:437-69. doi: 10.1007/978-3-0348-0837-8_17.
PMID: 24818733 [PubMed - in process]
Related citations

2014 ~ CB2 and Antitumor (Phototherapy)
“Moreover, CB2R appears to have great potential as a phototherapeutic target for cancer treatment.”
Cannabinoid CB2 Receptor as a New Phototherapy Target for the Inhibition of Tumor Growth.
Jia N, Zhang S, Shao P, Bagia C, Janjic JM, Ding Y, Bai M.
Mol Pharm. 2014 May 8. [Epub ahead of print]
PMID: 24779700 [PubMed - as supplied by publisher]
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2014 ~ CB2 Receptor and Melanoma
“Extravasation of leukocytes through the BBB [blood-brain barrier] is decreased by the activation of type 2 cannabinoid receptors (CB2); therefore, in the present study we sought to investigate the role of CB2 receptors in the interaction of melanoma cells with the brain endothelium. … Our data identify CB2 as a potential target in reducing the number of brain metastastes originating from melanoma.”
CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier.
Haskó J, Fazakas C, Molnár J, Nyúl-Tóth A, Herman H, Hermenean A, Wilhelm I, Persidsky Y, Krizbai IA.
Int J Mol Sci. 2014 May 8;15(5):8063-74. doi: 10.3390/ijms15058063.
PMID: 24815068 [PubMed - in process] Free Article
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2014 ~ Colon Carcinogenesis and CBD ~ Botanical Drug Substance
“CBD BDS [botanical drug substance] attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation.”
Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol.
Romano B, Borrelli F, Pagano E, Cascio MG, Pertwee RG, Izzo AA.
Phytomedicine. 2014 Apr 15;21(5):631-9. doi: 10.1016/j.phymed.2013.11.006. Epub 2013 Dec 25.
PMID: 24373545 [PubMed - in process]
Related citations

2014 ~ Eicosands, 2-AG and Cancer
“While THC and its derivatives have garnered notoriety in the eyes of the public, the endocannabinoid system consists of two endogenous signaling lipids, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anandamide), which activate cannabinoid receptors CB1 and CB2 in the nervous system and peripheral tissues.”
Chemical approaches to therapeutically target the metabolism and signaling of the endocannabinoid 2-AG and eicosanoids.
Kohnz RA, Nomura DK.
Chem Soc Rev. 2014 Mar 28. [Epub ahead of print]
PMID: 24676249 [PubMed - as supplied by publisher]
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2014 ~ Antitumor (Gliomas) and the CS
“These findings indicate that cannabinoids are promising compounds for the treatment of gliomas.”
Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas.
Rocha FC, Dos Santos Júnior JG, Stefano SC, da Silveira DX.
J Neurooncol. 2014 Jan;116(1):11-24. doi: 10.1007/s11060-013-1277-1. Epub 2013 Oct 20.
PMID: 24142199 [PubMed - in process]
Related citations

2013 ~ Anticancer Effects of CBD
“Thus, VDAC1 [voltage-dependent anion channel 1] seems to serve as a novel mitochondrial target for CBD. The inhibition of VDAC1 by CBD may be responsible for the immunosuppressive and anticancer effects of CBD.”
Direct modulation of the outer mitochondrial membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: a novel mechanism for cannabinoid-induced cell death.
Rimmerman N, Ben-Hail D, Porat Z, Juknat A, Kozela E, Daniels MP, Connelly PS, Leishman E, Bradshaw HB, Shoshan-Barmatz V, Vogel Z.
Cell Death Dis. 2013 Dec 5;4:e949. doi: 10.1038/cddis.2013.471.
PMID: 24309936 [PubMed - in process] Free PMC Article
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2010 ~ Preventing Carcinogenesis and the CS
“Our findings suggest that the expression of cannabinoid receptors and of FAAH in some tumour cells could well influence the effectiveness of DHA and EPA or their ethanolamide derivatives as anticancer agents.”
Cannabinoid receptor-dependent and -independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor-positive and -negative prostate cancer cell lines.
Brown I, Cascio MG, Wahle KW, Smoum R, Mechoulam R, Ross RA, Pertwee RG, Heys SD.
Carcinogenesis. 2010 Sep;31(9):1584-91. doi: 10.1093/carcin/bgq151. Epub 2010 Jul 25.
PMID: 20660502 [PubMed - indexed for MEDLINE] Free PMC Article
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Posted by Bryan W. Brickner

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Indiscernible Cannabinoid Science ~ Publius’ March 2014 Roundup

3/30/2014

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Picture

The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius

Here are seven 2014 findings on how the cannabinoid system (CS) modulates homeostasis and other systems in our bodies: the roundup links to recent PubMed articles on the vanilloid, neurological, dopamine, visual, skeletal, and endocrine systems.

I. Vanilloid System and the CS
“These data indicate that the eCB system can modulate inflammatory activation of the endothelium and may have important implications for a variety of acute inflammatory disorders that are characterized by EC [Endothelial Cell] activation.”
The endocannabinoid/endovanilloid N-arachidonoyl dopamine (NADA) and synthetic cannabinoid WIN55,212-2 abate the inflammatory activation of human endothelial cells.
Wilhelmsen K, Khakpour S, Tran A, Sheehan K, Schumacher M, Xu F, Hellman J.
J Biol Chem. 2014 Mar 18. [Epub ahead of print]
PMID: 24644287 [PubMed - as supplied by publisher] Free Article
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II. Neurological System (Migraines) and the CS
“These findings suggest that the pharmacological manipulation of the CB2 receptor may represent a potential therapeutic tool for the treatment of migraine.”
Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model.
Greco R, Mangione AS, Sandrini G, Nappi G, Tassorelli C.
J Headache Pain. 2014 Mar 17;15(1):14. doi: 10.1186/1129-2377-15-14.
PMID: 24636539 [PubMed - in process] Free Article
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III. Dopamine System and the CS
“The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system.”
Involvement of the Cannabinoid CB1 Receptor in Modulation of Dopamine Output in the Prefrontal Cortex Associated with Food Restriction in Rats.
Dazzi L, Talani G, Biggio F, Utzeri C, Lallai V, Licheri V, Lutzu S, Mostallino MC, Secci PP, Biggio G, Sanna E.
PLoS One. 2014 Mar 14;9(3):e92224. doi: 10.1371/journal.pone.0092224. eCollection 2014.
PMID: 24632810 [PubMed - in process] Free PMC Article
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IV. Neurological System (Alzheimer’s disease) and the CS
“Moreover, endocannabinoid signaling has been demonstrated to modulate numerous concomitant pathological processes, including neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress.”
Cannabinoids for treatment of Alzheimer's disease: moving toward the clinic.
Aso E, Ferrer I.
Front Pharmacol. 2014 Mar 5;5:37. eCollection 2014. Review.
PMID: 24634659 [PubMed - as supplied by publisher] Free PMC Article
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V. Visual System and the CS
“Our findings provide neurophysiologic evidence for a link between cannabinoid-signaling, network dynamics and the function of a canonical cortical circuit.”
Cannabinoid neuromodulation in the adult early visual cortex.
Ohiorhenuan IE, Mechler F, Purpura KP, Schmid AM, Hu Q, Victor JD.
PLoS One. 2014 Feb 19;9(2):e87362. doi: 10.1371/journal.pone.0087362. eCollection 2014.
PMID: 24586271 [PubMed - in process] Free PMC Article
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VI. Skeletal System (Osteoarthritis) and the CS
“The ubiquitous distribution of cannabinoid receptors, together with the physiological role of the endocannabinoid system in the regulation of pain, inflammation and even joint function further support the therapeutic interest of cannabinoids for osteoarthritis.”
Involvement of the endocannabinoid system in osteoarthritis pain.
La Porta C, Bura SA, Negrete R, Maldonado R.
Eur J Neurosci. 2014 Feb;39(3):485-500. doi: 10.1111/ejn.12468.
PMID: 24494687 [PubMed - in process]
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VII. Endocrine System (HP-axis) and the CS
“Since the endocannabinoid system components are present at sites involved in the hypothalamic-pituitary axis regulation, several studies were performed in order to investigate the endocannabinoid-mediated neurotransmitters and hormones secretion under physiological and pathological conditions.”
Role of the Endocannabinoid System in the Neuroendocrine Responses to Inflammation.
De Laurentiis A, Araujo HA, Rettori V.
Curr Pharm Des. 2014 Jan 30. [Epub ahead of print]
PMID: 24588819 [PubMed - as supplied by publisher]
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~’~
posted by bwb

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Preventing Carcinogenesis Via One’s Cannabinoid System ~ Publius’ March 2014 Colorectal Cancer Awareness

3/29/2014

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Picture

The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius

Colorectal (colon) cancer awareness and the cannabinoid system (CS) are the focus of March’s health update from Publius and The Cannabis Papers: A citizen’s guide to cannabinoids (2011). This month: PubMed CS science on preventing carcinogenesis, inducing apoptosis, attenuating cancer’s damage, and an estrogen-responsive connection to controlling colon cancer proliferation.

2013 ~ Attenuating Damage and the CS
“These findings support a discrete role for CB2 receptors in the attenuation of detrimental pro-inflammatory cytokine-mediated mucosal damage in the human colon without directly affecting mucosal epithelial barrier function.”
Cannabinoid CB2 receptor activation attenuates cytokine-evoked mucosal damage in a human colonic explant model without changing epithelial permeability.
Harvey BS, Nicotra LL, Vu M, Smid SD.
Cytokine. 2013 Aug;63(2):209-17. doi: 10.1016/j.cyto.2013.04.032. Epub 2013 May 22.
PMID: 23706402 [PubMed - indexed for MEDLINE]
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2013 ~ Immunoreactivity (Immune Reaction) and the CS
“The high immunoreactivity of the cannabinoid type 1 receptor is a significant prognostic factor following surgery in stage IV CRC [colorectal cancer].”
Expression of the cannabinoid type I receptor and prognosis following surgery in colorectal cancer.
Jung CK, Kang WK, Park JM, Ahn HJ, Kim SW, Taek Oh S, Choi KY.
Oncol Lett. 2013 Mar;5(3):870-876. Epub 2012 Dec 18.
PMID: 23426698 [PubMed] Free PMC Article
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2012 ~ Preventing Carcinogenesis and the CS
“Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis.”
Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer.
Aviello G, Romano B, Borrelli F, Capasso R, Gallo L, Piscitelli F, Di Marzo V, Izzo AA.
J Mol Med (Berl). 2012 Aug;90(8):925-34. doi: 10.1007/s00109-011-0856-x. Epub 2012 Jan 10.
PMID: 22231745 [PubMed - indexed for MEDLINE]
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2011 ~ Inducing Apoptosis and the CS
“Cannabinoid receptor agonists induce phosphatases and phosphatase-dependent apoptosis in cancer cell lines; however, the role of the CB receptor in mediating this response is ligand-dependent.”
Induction of apoptosis by cannabinoids in prostate and colon cancer cells is phosphatase dependent.
Sreevalsan S, Joseph S, Jutooru I, Chadalapaka G, Safe SH.
Anticancer Res. 2011 Nov;31(11):3799-807.
PMID: 22110202 [PubMed - indexed for MEDLINE] Free PMC Article
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2008 ~ Silencing Cancer and the CS
“Here we show that CB1 expression was silenced in human colorectal cancer due to methylation of the CB1 promoter.”
Loss of cannabinoid receptor 1 accelerates intestinal tumor growth.
Wang D, Wang H, Ning W, Backlund MG, Dey SK, DuBois RN.
Cancer Res. 2008 Aug 1;68(15):6468-76. doi: 10.1158/0008-5472.CAN-08-0896.
PMID: 18676872 [PubMed - indexed for MEDLINE] Free PMC Article
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2008 ~ Estrogen-Responsive Genes and the CS
“The CB1 receptor can be considered an estrogen-responsive gene in DLD-1, HT-29 and SW620 cells. Up-regulation of CB1 expression by 17beta-estradiol is a further mechanism of estrogens to control colon cancer proliferation.”
Estrogenic induction of cannabinoid CB1 receptor in human colon cancer cell lines.
Notarnicola M, Messa C, Orlando A, Bifulco M, Laezza C, Gazzerro P, Caruso MG.
Scand J Gastroenterol. 2008 Jan;43(1):66-72.
PMID: 18938775 [PubMed - indexed for MEDLINE]
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2004 ~ Preventing Metastasis and the CS
“Therefore, specific inhibition of tumor cell migration via CB1-R engagement might be a selective tool to prevent metastasis formation without depreciatory effects on the immune system of cancer patients.”
Anandamide is an endogenous inhibitor for the migration of tumor cells and T lymphocytes.
Joseph J, Niggemann B, Zaenker KS, Entschladen F.
Cancer Immunol Immunother. 2004 Aug;53(8):723-8. Epub 2004 Mar 18.
PMID: 15034673 [PubMed - indexed for MEDLINE]
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2003 ~ Inhibiting Cancer and the CS
“The endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) inhibit cancer cell proliferation by acting at cannabinoid receptors (CBRs).”
Possible endocannabinoid control of colorectal cancer growth.
Ligresti A, Bisogno T, Matias I, De Petrocellis L, Cascio MG, Cosenza V, D'argenio G, Scaglione G, Bifulco M, Sorrentini I, Di Marzo V.
Gastroenterology. 2003 Sep;125(3):677-87.
PMID: 12949714 [PubMed - indexed for MEDLINE]
Related citations

~ posted by bryan w. brickner
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Indiscernible Cannabinoid System Science ~ Publius’ February 2014 Roundup

2/27/2014

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Picture
The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius 


This roundup links to seven 2014 PubMed articles on cannabinoids modulating other systems in our bodies, such as: the olfactory, endocrine, vanilloid, serotonin, opioid, dopamine, and nervous systems. There’s also a bit of systemic science ~ getting a good night’s sleep.


I. Olfactory System and CS
“Thus, CB1 receptor-dependent control of cortical feedback projections in olfactory circuits couples internal states to perception and behavior.”

The endocannabinoid system controls food intake via olfactory processes.
  Soria-Gómez E, Bellocchio L, Reguero L, Lepousez G, Martin C, Bendahmane M, Ruehle S, Remmers F, Desprez T, Matias I,
  Wiesner T, Cannich A, Nissant A, Wadleigh A, Pape HC, Chiarlone AP, Quarta C, Verrier D, Vincent P, Massa F, Lutz B,
  Guzmán M, Gurden H, Ferreira G, Lledo PM, Grandes P, Marsicano G.
  Nat Neurosci. 2014 Mar;17(3):407-15. doi: 10.1038/nn.3647. Epub 2014 Feb 9.
  PMID: 24509429 [PubMed - in process]

II. Endocrine System (Hypothalamus-pituitary axis) and CS
“Whereas the effect on 3β-HSD was counteracted by SR141716A (Rimonabant) - a selective antagonist of CB1, thus indicating a CB1 dependent modulation - the effect on cyp17 was not, suggesting a possible involvement of receptors other than CB1, probably the type-1 vanilloid receptor (TRPV1), since AEA works as an endocannabinoid and an endovanilloid as well.”

Hypothalamus-pituitary axis: an obligatory target for endocannabinoids to inhibit steroidogenesis in frog testis.
  Chianese R, Ciaramella V, Fasano S, Pierantoni R, Meccariello R.
  Gen Comp Endocrinol. 2014 Feb 21. pii: S0016-6480(14)00053-7. doi: 10.1016/j.ygcen.2014.02.010. [Epub ahead of print]
  PMID: 24566122 [PubMed - as supplied by publisher]

III. Vanilloid System (Schizophrenia) and CS
“Our results indicate that the schizophrenia-like behaviors displayed by SHR [Spontaneously Hypertensive Rats]  are differently altered by cannabinoid and vanilloid drugs when compared to control animals and suggest the endocannabinoid and the vanilloid systems as a potential target for the treatment of schizophrenia.”

Effects of cannabinoid and vanilloid drugs on positive and negative-like symptoms on an animal model of schizophrenia: The SHR strain.
  Almeida V, Peres FF, Levin R, Suiama MA, Calzavara MB, Zuardi AW, Hallak JE, Crippa JA, Abílio VC.
  Schizophr Res. 2014 Feb 17. pii: S0920-9964(14)00062-0. doi: 10.1016/j.schres.2014.01.039. [Epub ahead of print]
  PMID: 24556469 [PubMed - as supplied by publisher]

IV. Serotonin, Opioid, and Dopamine Systems and CS
“In this review we highlight the evidence for the physiological role of such constitutive GPCR [G protein-coupled receptor]   activity (in particular for cannabinoid 1, serotonin 2C and mu-opioid receptors) in the ventral tegmental area and in its output regions like the nucleus accumbens. We also address the behavioral relevance of constitutive GPCR signaling and discuss the repercussions of its abolition in dopamine-related psychiatric diseases.”

The vital role of constitutive GPCR activity in the mesolimbic dopamine system.
  Meye FJ, Ramakers GM, Adan RA.
  Transl Psychiatry. 2014 Feb 11;4:e361. doi: 10.1038/tp.2013.130.
  PMID: 24518399 [PubMed - in process]

V. Sleep, Systems and CS
“Overall, these findings demonstrate that the EC [Endo-Cannabinoid] system actively regulates cortical up-states and important features of NREM sleep such as its duration and low frequency cortical oscillations.”

Endocannabinoid Modulation of Cortical Up-States and NREM Sleep.
  Pava MJ, den Hartog CR, Blanco-Centurion C, Shiromani PJ, Woodward JJ.
  PLoS One. 2014 Feb 10;9(2):e88672. doi: 10.1371/journal.pone.0088672. eCollection 2014.
  PMID: 24520411 [PubMed - in process] Free PMC Article

VI. Central Nervous System and CS
“In the present study, we discovered that 2-AG significantly protects CN neurons in culture against lipopolysaccharide (LPS)-induced inflammatory response.”

Endocannabinoid 2-Arachidonylglycerol Protects Primary Cultured Neurons Against LPS-Induced Impairments in Rat Caudate Nucleus.
  Lu Y, Peng F, Dong M, Yang H.
  J Mol Neurosci. 2014 Feb 9. [Epub ahead of print]
  PMID: 24510751 [PubMed - as supplied by publisher]

VII. Nervous System (Alzheimer’s/Dementia) and CS
“The altered CB1 levels appear, rather, to be age-and/or pathology-dependent, indicating an involvement of the endocannabinoid system in AD pathology and supporting the ECS as a potential novel therapeutic target for treatment of AD.”

Altered Expression of the CB1 Cannabinoid Receptor in the Triple Transgenic Mouse Model of Alzheimer's Disease.
  Bedse G, Romano A, Cianci S, Lavecchia AM, Lorenzo P, Elphick MR, Laferla FM, Vendemiale G, Grillo C, Altieri F, Cassano
  T, Gaetani S.
  J Alzheimers Dis. 2014 Feb 4. [Epub ahead of print]
  PMID: 24496074 [PubMed - as supplied by publisher]

~.~
February's Video
What if Cannabinoids in Cannabis Cured Cancer & Other Diseases?

  Posted by bwb.

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Cannabinoid System Stops Cancer ~ Publius’ February 2014 Prevention Awareness

2/26/2014

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Picture
The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius

Cancer prevention awareness and the cannabinoid system are the focus of February’s health update from Publius and The Cannabis Papers: A citizen’s guide to cannabinoids (2011). This month: PubMed science on inflammation, a unique receptor, GPR55, and the ability of one’s cannabinoid system to induce apoptosis, programmed cancer cell death.

2014 ~ Inflammation (HIV-1) and CS/GPR55
“Receptors for THC, CB1, CB2, and GPR55, are differentially expressed on multiple cell types including monocytes and macrophages, which are important modulators of inflammation in vivo and target cells for HIV-1 infection.”

Δ9-Tetrahydrocannabinol Treatment During Human Monocyte Differentiation Reduces Macrophage Susceptibility to HIV-1 Infection.
Williams JC, Appelberg S, Goldberger BA, Klein TW, Sleasman JW, Goodenow MM.
J Neuroimmune Pharmacol. 2014 Feb 23. [Epub ahead of print]
PMID: 24562630 [PubMed - as supplied by publisher]


2013 ~ Alcohol, Dentric Cells and CS/GPR55
"Our results provide insights into alcohol mechanisms of DC [dentric cell] regulation and show, for the first time, that alcohol is inducing CNR2 [CB2] and GPR55 in human DCs."

Differential expression and functional role of cannabinoid genes in alcohol users.
Agudelo M, Yndart A, Morrison M, Figueroa G, Muñoz K, Samikkannu T, Nair MP.
Drug Alcohol Depend. 2013 Dec 1;133(2):789-93. doi: 10.1016/j.drugalcdep.2013.08.023. Epub 2013 Sep 5.
PMID: 24060590 [PubMed - in process]


2013 ~ Inflammation (Cancer) and CS/GPR55
“GPR55 has been shown to have a role in cancer and gastrointestinal inflammation, as well as in obesity and type 2 diabetes mellitus (T2DM).”

A potential role for GPR55 in the regulation of energy homeostasis.
Simcocks AC, O'Keefe L, Jenkin KA, Mathai ML, Hryciw DH, McAinch AJ.
Drug Discov Today. 2013 Dec 24. pii: S1359-6446(13)00423-6. doi: 10.1016/j.drudis.2013.12.005. [Epub ahead of print] Review.
PMID: 24370891 [PubMed - as supplied by publisher]


2013 ~ CS Synergistic Against Cancer
“The observed synergistic effect with cannabinoid agonists implicates an involvement of the cannabinoid system.”

Cytotoxic effect of efavirenz is selective against cancer cells and associated with the cannabinoid system.
Hecht M, Harrer T, Büttner M, Schwegler M, Erber S, Fietkau R, Distel LV.
AIDS. 2013 Aug 24;27(13):2031-40. doi: 10.1097/QAD.0b013e3283625444.
PMID: 23612009 [PubMed - in process]


2011 ~ GPR55 Driving Cancer Cell Migration
“It has now been revealed that LPI [L-α-lysophosphatidylinositol] activates GPR55, a G protein-coupled receptor that couples to G(12/13) and G(q) proteins, which direct oncogenic signalling. New evidence indicates that LPI and GPR55 are key partners in driving cancer cell proliferation and migration.”

L-α-lysophosphatidylinositol meets GPR55: a deadly relationship.
Ross RA.
Trends Pharmacol Sci. 2011 May;32(5):265-9. doi: 10.1016/j.tips.2011.01.005. Epub 2011 Mar 1.
PMID: 21367464 [PubMed - indexed for MEDLINE]


2010 ~ Breast Cancer and CS/GPR55
“LPI and GPR55 play a role in the modulation of migration, orientation and polarization of breast cancer cells in response to the tumour microenvironment.”

A role for L-alpha-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells.
Ford LA, Roelofs AJ, Anavi-Goffer S, Mowat L, Simpson DG, Irving AJ, Rogers MJ, Rajnicek AM, Ross RA.
Br J Pharmacol. 2010 Jun;160(3):762-71. doi: 10.1111/j.1476-5381.2010.00743.x.
PMID: 20590578 [PubMed - indexed for MEDLINE] Free PMC Article


2006 ~ Evolution and CS/GPR55
“Within this limited number of twelve organisms, the endocannabinoid genes exhibited heterogeneous evolutionary trajectories, with functional orthologs limited to mammals (TRPV1 and GPR55), or vertebrates (CB2 and DAGLbeta), or chordates (MAGL and COX2), or animals (DAGLalpha and CB1-like receptors), or opisthokonta (animals and fungi, NAPE-PLD), or eukaryotes (FAAH).”

Evolutionary origins of the endocannabinoid system.
McPartland JM, Matias I, Di Marzo V, Glass M.
Gene. 2006 Mar 29;370:64-74. Epub 2006 Jan 23.
PMID: 16434153 [PubMed - indexed for MEDLINE]

~ posted by bwb

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Cancer and One’s Cannabinoid System ~ Publius’ January Awareness

1/26/2014

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Picture
The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius

Cervical cancer awareness and one’s cannabinoid system are the focus of this month’s health update from Publius of The Cannabis Papers: A citizen’s guide to cannabinoids (2011). January's highlighted message is the ability of one’s cannabinoid system, using the endocannabinoid anandamide, to induce apoptosis ~ programmed cancer cell death.

2004
The endocannabinoid Anandamide (arachidonyl ethanolamide) inducing apoptosis of uterine cervix cancer cells via another type of receptor ~ the vanilloid receptor-1.


Arachidonyl ethanolamide [Anandamide] induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1.
Contassot E, Tenan M, Schnüriger V, Pelte MF, Dietrich PY.
Gynecol Oncol. 2004 Apr;93(1):182-8.
 

2009
The stable analogue of the endocannabinoid Anandamide, R(+)-methanandamide, inducing apoptosis in human cervical carcinoma cells.


R(+)-methanandamide-induced apoptosis of human cervical carcinoma cells involves a cyclooxygenase-2-dependent pathway.
Eichele K, Ramer R, Hinz B.
Pharm Res. 2009 Feb;26(2):346-55. doi: 10.1007/s11095-008-9748-3. Epub 2008 Oct 28.


2012
The ability of the endocannabinoid Anandamide to induce apoptosis is enhanced by blocking fatty acid amide hydrolase (FAAH).


Arachidonoyl ethanolamide [Anandamide] (AEA)-induced apoptosis is mediated by J-series prostaglandins and is enhanced by fatty acid amide hydrolase (FAAH) blockade.
Kuc C, Jenkins A, Van Dross RT.
Mol Carcinog. 2012 Feb;51(2):139-49. doi: 10.1002/mc.20770. Epub 2011 Mar 22.


2013
The cannabinoid system and omega-3/6 endocannabinoids noted for their anticancer modulation.


Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators.
Brown I, Cascio MG, Rotondo D, Pertwee RG, Heys SD, Wahle KW.
Prog Lipid Res. 2013 Jan;52(1):80-109. doi: 10.1016/j.plipres.2012.10.001. Epub 2012 Oct 26.


2013
The cannabinoid system and cannabidiol inhibiting colon carcinogenesis.


Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol.
Romano B, Borrelli F, Pagano E, Cascio MG, Pertwee RG, Izzo AA.
Phytomedicine. 2013 Dec 24. pii: S0944-7113(13)00472-8. doi: 10.1016/j.phymed.2013.11.006. [Epub ahead of print]

Posted by Bryan W. Brickner

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    Author

    Brickner has a 1997 political science doctorate from Purdue University, cofounded Illinois NORML in 2001, and was a 2007 National NORML Cannabis Advocate Awardee. He is also publisher and coauthor of the 2011 book banned by the Illinois Department of Corrections – The Cannabis Papers: A Citizen’s Guide to Cannabinoids.

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