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The Medical Marijuana Series

A Dive Into The History & Practical Medical Application of Cannabis in Medicine

by Dr. Michael Rothman, a Board Certified Physician in Emergency & Internal Medicine

Introduction of Cannabis and its History of Use in Medicine

Marijuana, its legalization, its legitimacy as medicine, and its surrounding controversies are constantly in the news.  While the medical marijuana conversation seems current, cannabis or marijuana has been used medicinally in the United States since the mid-1800’s until 1937. The depth of use of cannabis for symptom relief was so common that cannabis was listed […]


The Role of Cannabis, Cannabinoids and the Endocannabinoid System in Disorders of your Immune System – such as Cancer and Autoimmune Diseases

A dysfunctional, impaired immune system is a contributing factor to all chronic inflammatory diseases. Therefore, one of the most effective ways to reduce inflammation in your body is by improving the functioning of your immune system. The endocannabinoid system has myriad effects on how your immune system functions. There are two main parts of your immune system, the innate immune […]


The Role of Cannabis, Cannabinoids and the Endocannabinoid System in Anxiety Disorders

Anxiety is a very common complaint amongst chronically ill patients and can have devastating effects on your quality of life.  Anxiety can negatively impact appetite, sleep, work, relations, and over  time contribute to worsening states of health. What are the Different Forms of Anxiety? Anxiety is defined as the emotional state characterized by maladaptive and excessive emotional responsiveness to potentially dangerous […]


Pharmaceutically derived Cannabis Extracts Now FDA Approved – Good News or Bad News for Medical Marijuana Patients?

Cannabis (Medical Marijuana) has been used for medicinal purposes for millennia. (Please read our previous blog: Introduction to Cannabis and its history of use in medicine.) However, legal use of marijuana ended in 1937 with the passage of the Marijuana Tax Act of 1937. Subsequently, marijuana was classified as a class I drug with no medical benefits. […]


A Full List of References for Medical Marijuana Series:

Turning Over a New Leaf: Cannabinoid and Endocannabinoid Modulation of Immune Function.

Cabral GA, Rogers TJ, Lichtman AH.

J Neuroimmune Pharmacol. 2015 Jun;10(2):193-203. doi: 10.1007/s11481-015-9615-z. Epub 2015 Jun 9.

The endocannabinoid system and pain.

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CNS Neurol Disord Drug Targets. 2009 Dec;8(6):403-21. Review.

Endocannabinoid binding to the cannabinoid receptors: what is known and what remains unknown.

Reggio PH.

Curr Med Chem. 2010;17(14):1468-86. Review.

Endocannabinoid chemical biology: a tool for the development of novel therapies.

Petrosino S, Ligresti A, Di Marzo V.

Curr Opin Chem Biol. 2009 Jun;13(3):309-20. doi: 10.1016/j.cbpa.2009.04.616. Epub 2009 May 18. Review.

Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration.

Basavarajappa BS, Nixon RA, Arancio O.

Mini Rev Med Chem. 2009 Apr;9(4):448-62. Review.

From endocannabinoid profiling to ‘endocannabinoid therapeutics’.

Ligresti A, Petrosino S, Di Marzo V.

Curr Opin Chem Biol. 2009 Jun;13(3):321-31. doi: 10.1016/j.cbpa.2009.04.615. Epub 2009 Jun 3. Review.

Immunomodulatory lipids in plants: plant fatty acid amides and the human endocannabinoid system.

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Planta Med. 2008 May;74(6):638-50. doi: 10.1055/s-2008-1034302. Epub 2008 Feb 14. Review.

The emerging role of the endocannabinoid system in the sleep-wake cycle modulation.

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Cent Nerv Syst Agents Med Chem. 2011 Sep 1;11(3):189-96. Review.

Endocannabinoid system in neurodegenerative disorders.

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J Neurochem. 2017 Sep;142(5):624-648. doi: 10.1111/jnc.14098. Epub 2017 Jul 5. Review.

Endocannabinoid mechanisms of pain modulation.

Hohmann AG, Suplita RL 2nd.

AAPS J. 2006 Nov 17;8(4):E693-708. Review.

In vivo pharmacology of endocannabinoids and their metabolic inhibitors: therapeutic implications in Parkinson’s disease and abuse liability.

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Prostaglandins Other Lipid Mediat. 2010 Apr;91(3-4):90-103. doi: 10.1016/j.prostaglandins.2009.05.004. Epub 2009 Jun 10. Review.

Endocannabinoid system and mood disorders: priming a target for new therapies.

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Pharmacol Ther. 2013 Apr;138(1):18-37. doi: 10.1016/j.pharmthera.2012.12.002. Epub 2012 Dec 20. Review.

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Alcohol Alcohol. 2005 Jan-Feb;40(1):2-14. Epub 2004 Nov 18. Review.

Cannabinoids and Pain: Sites and Mechanisms of Action.

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Adv Pharmacol. 2017;80:437-475. doi: 10.1016/bs.apha.2017.05.003. Epub 2017 Jun 20. Review.

The endocannabinoid system: its general strategy of action, tools for its pharmacological manipulation and potential therapeutic exploitation.

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Pharmacol Res. 2009 Aug;60(2):77-84. doi: 10.1016/j.phrs.2009.02.010. Epub 2009 Mar 4. Review.

Endocannabinoids and endocannabinoid-related mediators: Targets, metabolism and role in neurological disorders.

Iannotti FA, Di Marzo V, Petrosino S.

Prog Lipid Res. 2016 Apr;62:107-28. doi: 10.1016/j.plipres.2016.02.002. Epub 2016 Mar 7. Review.

Psychopharmacology of the endocannabinoids: far beyond anandamide.

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J Psychopharmacol. 2012 Jan;26(1):7-22. doi: 10.1177/0269881111405357. Epub 2011 Jun 7. Review.

Changes in endocannabinoid receptors and enzymes in the spinal cord of SOD1(G93A) transgenic mice and evaluation of a Sativex(®)

-like combination of phytocannabinoids: interest for future therapies in amyotrophic lateral sclerosis.

Moreno-Martet M, Espejo-Porras F, Fernández-Ruiz J, de Lago E.

CNS Neurosci Ther. 2014 Sep;20(9):809-15. doi: 10.1111/cns.12262. Epub 2014 Apr 7.

Endogenous cannabinoids in the brain and peripheral tissues: regulation of their levels and control of food intake.

Matias I, Bisogno T, Di Marzo V.

Int J Obes (Lond). 2006 Apr;30 Suppl 1:S7-S12. Review.

Why do cannabinoid receptors have more than one endogenous ligand?

Di Marzo V, De Petrocellis L.

Philos Trans R Soc Lond B Biol Sci. 2012 Dec 5;367(1607):3216-28. doi: 10.1098/rstb.2011.0382. Review.

Endocannabinoid tone versus constitutive activity of cannabinoid receptors.

Howlett AC, Reggio PH, Childers SR, Hampson RE, Ulloa NM, Deutsch DG.

Br J Pharmacol. 2011 Aug;163(7):1329-43. doi: 10.1111/j.1476-5381.2011.01364.x. Review.

Endocannabinoid signaling in neurotoxicity and neuroprotection.

Pope C, Mechoulam R, Parsons L.

Neurotoxicology. 2010 Sep;31(5):562-71. doi: 10.1016/j.neuro.2009.12.002. Epub 2009 Dec 5.

The endocannabinoid system in neurodegeneration.

Battista N, Fezza F, Finazzi-Agrò A, Maccarrone M.

Ital J Biochem. 2006 Sep-Dec;55(3-4):283-9. Review.

The endocannabinoid system: a general view and latest additions.

De Petrocellis L, Cascio MG, Di Marzo V.

Br J Pharmacol. 2004 Mar;141(5):765-74. Epub 2004 Jan 26. Review.

Cannabinoids and the gut: new developments and emerging concepts.

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Pharmacol Ther. 2010 Apr;126(1):21-38. doi: 10.1016/j.pharmthera.2009.12.005. Epub 2010 Feb 1. Review.

Therapeutic potential of the endocannabinoid system in the brain.

Ramos JA, González S, Sagredo O, Gómez-Ruiz M, Fernández-Ruiz J.

Mini Rev Med Chem. 2005 Jul;5(7):609-17. Review.

Lipid rafts control signaling of type-1 cannabinoid receptors in neuronal cells. Implications for anandamide-induced apoptosis.

Bari M, Battista N, Fezza F, Finazzi-Agrò A, Maccarrone M.

J Biol Chem. 2005 Apr 1;280(13):12212-20. Epub 2005 Jan 18.

Cannabinoid/Endocannabinoid signaling impact on early pregnancy events.

Sun X, Dey SK.

Curr Top Behav Neurosci. 2009;1:255-73. doi: 10.1007/978-3-540-88955-7_10. Review.

Basic neuroanatomy and neuropharmacology of cannabinoids.

Breivogel CS, Sim-Selley LJ.

Int Rev Psychiatry. 2009 Apr;21(2):113-21. doi: 10.1080/09540260902782760. Review.

The potent emetogenic effects of the endocannabinoid, 2-AG (2-arachidonoylglycerol) are blocked by delta(9)-tetrahydrocannabinol and other cannnabinoids.

Darmani NA.

J Pharmacol Exp Ther. 2002 Jan;300(1):34-42.

The endocannabinoids anandamide and 2-arachidonoylglycerol inhibit cholinergic contractility in the human colon.

Smid SD, Bjorklund CK, Svensson KM, Heigis S, Revesz A.

Eur J Pharmacol. 2007 Dec 1;575(1-3):168-76. Epub 2007 Jul 26.

Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain.

Mitrirattanakul S, Ramakul N, Guerrero AV, Matsuka Y, Ono T, Iwase H, Mackie K, Faull KF, Spigelman I.

Pain. 2006 Dec 15;126(1-3):102-14. Epub 2006 Jul 14.

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 May 9;289(19):13079-100. doi: 10.1074/jbc.M113.536953. Epub 2014 Mar 18.

Type 1 cannabinoid receptor ligands display functional selectivity in a cell culture model of striatal medium spiny projection neurons.

Laprairie RB, Bagher AM, Kelly ME, Dupré DJ, Denovan-Wright EM.

J Biol Chem. 2014 Sep 5;289(36):24845-62. doi: 10.1074/jbc.M114.557025. Epub 2014 Jul 18.

Role of lipids and lipid signaling in the development of cannabinoid tolerance.

Martin BR.

Life Sci. 2005 Aug 19;77(14):1543-58. Review.

Endocannabinoids and Their Pharmacological Actions.

Pertwee RG.

Handb Exp Pharmacol. 2015;231:1-37. doi: 10.1007/978-3-319-20825-1_1. Review.

The endocannabinoid system in ageing: a new target for drug development.

Paradisi A, Oddi S, Maccarrone M.

Curr Drug Targets. 2006 Nov;7(11):1539-52. Review.

Endocannabinoid 2-arachidonoylglycerol protects neurons against β-amyloid insults.

Chen X, Zhang J, Chen C.

Neuroscience. 2011 Mar 31;178:159-68. doi: 10.1016/j.neuroscience.2011.01.024. Epub 2011 Jan 19.

The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis.

Maccarrone M, Finazzi-Agró A.

Cell Death Differ. 2003 Sep;10(9):946-55. Review.

Discriminative Stimulus Properties of Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids.

Wiley JL, Owens RA, Lichtman AH.

Curr Top Behav Neurosci. 2016 Jun 9. [Epub ahead of print]

Molecular Pharmacology of Phytocannabinoids.

Turner SE, Williams CM, Iversen L, Whalley BJ.

Prog Chem Org Nat Prod. 2017;103:61-101. doi: 10.1007/978-3-319-45541-9_3. Rev

Enhanced endocannabinoid tone as a potential target of pharmacotherapy.

Toczek M, Malinowska B.

Life Sci. 2018 Jul 1;204:20-45. doi: 10.1016/j.lfs.2018.04.054. Epub 2018 May 2. Review.

The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease.

Hasenoehrl C, Taschler U, Storr M, Schicho R.

Neurogastroenterol Motil. 2016 Dec;28(12):1765-1780. doi: 10.1111/nmo.12931. Epub 2016 Aug 26. Review.

Plant, synthetic, and endogenous cannabinoids in medicine.

Di Marzo V, Petrocellis LD.

Annu Rev Med. 2006;57:553-74. Review.

Endocannabinoid metabolic pathways and enzymes.

Ligresti A, Cascio MG, Di Marzo V.

Curr Drug Targets CNS Neurol Disord. 2005 Dec;4(6):615-23. Review.

Therapeutic potential of cannabinoids in schizophrenia.

Kucerova J, Tabiova K, Drago F, Micale V.

Recent Pat CNS Drug Discov. 2014 Apr;9(1):13-25. Review.

[Endogenous cannabinoid receptor ligands–anandamide and 2-arachidonoylglycerol].

Waku K.

Yakugaku Zasshi. 2006 Feb;126(2):67-81. Review. Japanese.

TRP Channels as Novel Targets for Endogenous Ligands: Focus on Endocannabinoids and Nociceptive Signalling.

Storozhuk MV, Zholos AV.

Curr Neuropharmacol. 2018 Jan 30;16(2):137-150. doi: 10.2174/1570159X15666170424120802.

Cannabinoids biology: the search for new therapeutic targets.

Felder CC, Dickason-Chesterfield AK, Moore SA.

Mol Interv. 2006 Jun;6(3):149-61. Review.

Phytocannabinoids and Cannabimimetic Drugs: Recent Patents in Central Nervous System Disorders.

Ranieri R, Marasco D, Bifulco M, Malfitano AM.

Recent Pat CNS Drug Discov. 2016;10(2):157-177. Review.

Anandamide, but not 2-arachidonoylglycerol, accumulates during in vivo neurodegeneration.

Hansen HH, Schmid PC, Bittigau P, Lastres-Becker I, Berrendero F, Manzanares J, Ikonomidou C, Schmid HH, Fernández-Ruiz JJ, Hansen HS.

J Neurochem. 2001 Sep;78(6):1415-27.

Cannabinoids, endocannabinoids, and related analogs in inflammation.

Burstein SH, Zurier RB.

AAPS J. 2009 Mar;11(1):109-19. doi: 10.1208/s12248-009-9084-5. Epub 2009 Feb 6. Review.

New insights into endocannabinoid degradation and its therapeutic potential.

Bari M, Battista N, Fezza F, Gasperi V, Maccarrone M.

Mini Rev Med Chem. 2006 Mar;6(3):257-68. Review.

The future of cannabinoids as analgesic agents: a pharmacologic, pharmacokinetic, and pharmacodynamic overview.

McCarberg BH, Barkin RL.

Am J Ther. 2007 Sep-Oct;14(5):475-83. Review.

Human adipose tissue binds and metabolizes the endocannabinoids anandamide and 2-arachidonoylglycerol.

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Biochimie. 2006 Dec;88(12):1889-97. Epub 2006 Aug 22.

Endocannabinoids as regulators of transient receptor potential (TRP) channels: A further opportunity to develop new endocannabinoid-based therapeutic drugs.

Di Marzo V, De Petrocellis L.

Curr Med Chem. 2010;17(14):1430-49. Review.

Endocannabinoids: synthesis and degradation.

Di Marzo V.

Rev Physiol Biochem Pharmacol. 2008;160:1-24. doi: 10.1007/112_0505. Review.

Cannabinoid drugs and enhancement of endocannabinoid responses: strategies for a wide array of disease states.

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Curr Mol Med. 2006 Sep;6(6):677-84. Review.

Endocannabinoids in appetite control and the treatment of obesity.

Kirkham TC, Tucci SA.

CNS Neurol Disord Drug Targets. 2006 Jun;5(3):272-92. Review.

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