Medical Marijuana: Studying for Higher Purpose

      Marijuana was first comprehensively studied in Israel in the 1960s by Professor Raphael Mechoulam, considered “the father of medical marijuana.” Professor Mechoulam is with The Hebrew University of Jerusalem’s Department of Medicinal Chemistry and Natural Products at the Faculty of Medicine.

      Mechoulam’s research team isolated some of the major compounds in marijuana, many of which had been previously unknown, including THC (Tetrahydrocannabinol) and CBD (Cannabidiol). THC is the psychoactive compound in marijuana that causes the typical “high” effect, and CBD is non-psychoactive. Both compounds have medicinal properties.

      THC has proven valuable in helping to treat a multitude of issues such as pain, insomnia, depression, nausea and appetite loss. CBD has shown an ability to treat inflammation, nausea, diabetes, alcoholism, Posttraumatic stress disorder (PTSD), rheumatoid arthritis and cardiovascular disease. Hebrew University’s research on cannabinoids includes studying how different types and amounts of CBD treat various medical issues such as how it may help heal fractured bones, reduce or eliminate negative side effects from cancer treatment, anxiety, seizures, chronic pain and more.

      Israel boasts one of the most advanced medical marijuana programs in the world. More than 20,000 Israeli patients use medical marijuana to alleviate various ailments, such as Crohn’s disease, Tourette’s syndrome, pediatric epilepsy, cancer side effects and PTSD.

      In early 2015, Hebrew University ‘s technology transfer company, Yissum Research Development Co. Ltd., signed an exclusive licensing and collaboration agreement with PhytoTech Medical Ltd. for the development, manufacturing and marketing of a novel delivery system to enhance the bioavailability of cannabidiol (CBD) and/or THC. The novel formulations are based on oral and transbuccal delivery technologies developed by Professors Abraham Domb and Amnon Hoffman of The Hebrew University Faculty of Medicine, School of Pharmacy, Institute of Drug Research.

      Hebrew University’s efforts in medical marijuana research have been featured in The New York Times, BBC News, Washington Post, National Geographic, The New Yorker, Bloomberg and more.

      With more than 400 scientific papers and 35 patents to his name, Professor Mechoulam is so highly regarded that a documentary about him came out in 2015. Watch The Scientist below:


      Dr. Ofra Benny

      Dr. Ofra Benny was born and raised in Rishon Lezion. After her military service, she began her undergraduate studies in Biotechnology Engineering at the Technion. Upon completion of her engineering degree in 2001, Dr. Benny continued her education and earned a Ph.D. while working in the lab of Professor Marcelle Machluf. Her research focused on the development of polymeric drug delivery systems for the continuous release of inhibitors of blood vessel formation (anti-angiogenic factors) to treat glioblastoma brain tumors. She also developed an encapsulation procedure for peptides, specifically for PF4/CTF and PEX, in microspheres composed of the polymer PLGA. When injected intracranially in mice, these microspheres slowly release the peptides and inhibit vascular and tumor growth. Similarly, chemotherapy drugs released locally in the brain near the tumor site using this mechanism demonstrated improved anticancer activity with reduced systeic exposure. This research yielded a number of manuscripts in both the FASEB and Clinical Cancer Research Journals and, in 2006, she was awarded the Outstanding Pharmaceutical Paper Award by the Controlled Release Society for her work.

      Upon completion of the Ph.D. at the end of 2006, Dr. Benny began her postdoctoral studies at Harvard University, Boston Children’s Hospital in Boston, Massachusetts under the mentorship of Dr. Judah Folkman—a pioneer of the angiogenesis field who demonstrated the dependency of tumors on the formation of new blood vessels. Dr. Benny focused her research on improving a broad spectrum anti-angiogenic drug, named TNP 470, by reengineering the drug for cancer treatment. Her challenge was to maintain the drug’s activity while improving its pharmacological properties and eliminating the neurological side effects found during clinical trials. Dr. Benny chose to covalently conjugate the drug to a di-block polymer mPEG-PLA. Selecting the length and properties of the polymer enabled its self-assembly into nanomicelles in an aqueous environment. Compared to the original drug, the new formulation of TNP -470, named Lodamin (from the Hebrew “no blood in”), showed better stability, solubility and absorption in the intestine. Additionally, Lodamin’s penetration of the brain was prevented and the consequent neurological side effects attributed to the original drug were eliminated, as demonstrated in mice. Lodamin was able to inhibit various cancers including skin, lung, brain, liver, breast, ovarian and pancreatic cancers. Because the nanomicelles accumulated in the liver after oral administration, a dramatic inhibition of liver metastasis was seen in the mice. The results were published in Nature Biotechnology in 2008, in a paper that described the development of the drug and its anticancer activity.
      After the sudden death of Dr. Folkman, Ofra continued her research in the laboratory of Dr. Robert D’Amato. Her focus expanded to the vascular eye disease AMD (Age- related Macular Degeneration), one of the leading causes of blindness among elderly populations. Advanced stages of the disease are characterized by an accumulation of blood vessels in the retina (located at the back of the eye), which causes a rise in intraocular pressure and finally damage to the eye neurons. Ofra’s study demonstrated that Lodamin is highly active in the testing model of AMD (laser-induced choroidal neovascularisation) and exhibits advantages over the existing therapies by regressing neovascular lesions and not merely inhibiting their growth. Moreover, it can be administered in a less invasive manner, without intraocular injection as is required today.
      In 2010, Dr. Benny was promoted to the position of Instructor at Harvard University and Associate Scientist at Boston Children’s Hospital. Her research continued to focus on the dynamic field of tumor microenvironment, cancer and ocular vascular diseases. She joined the journal Frontiers in Bioscience as managing editor, and was a guest editor for the Journal of Ophthalmology, managing a special issue: Lymphatic and Blood Vessels in the Eye: Physiology, Health, and Disease.

      Since the beginning of 2013, Dr. Benny has been a faculty member at Hebrew University’s Institute of Drug Research, Faculty of Medicine, School of Pharmacy. Her team is currently investigating the mechanisms involved in angiogenesis and factors causing resistance to anti-angiogenic therapies. Their goal is to understand the mechanisms responsible for drug resistance in order to develop innovative treatments with improved activity for prolonged treatment without tumor escape. Treatment optimization is being investigated at the molecular level by searching for new drug targets, and at the formulations level by developing nanoparticles with improved cancer-targeting abilities and enhanced uptake.

      Additional studies focus on understanding the tissue microenvironment in neovascular pathologies, including the lymphatic system. By better understanding this specific niche, Dr. Benny and her team will be able to develop innovative tools to deliver drugs more efficiently. To achieve these goals, the lab employs several different techniques, including drug encapsulation, polymer conjugation, molecular biology, tissue culture, cellular models of angiogenesis, vascular permeability, and cancer. The studies are performed in primary cultures of endothelial, lymphatic, and various cancer cell lines. In addition, the laboratory uses research models for angiogenesis, cancer, and metastasis.

      Hebrew University Looks for High Impact with New Cannabinoid Multidisciplinary Center

      The Hebrew University announced the launch of a Multidisciplinary Center on Cannabinoid Research. The new Center will serve as one of the world’s leading institutes for conducting and coordinating research about cannabinoids, endocannabinoids, and medical Cannabis. In addition, it will promote collaboration and disseminate information. 

      Staffed by some of the world’s leading scientists and medical doctors from the Hebrew University and its affiliated Hadassah Medical Center, the Multidisciplinary Center is already supporting exciting new research. In February 2017, the Center awarded funding to three research projects:

      —The effects of CBD on traumatic brain injury (Professor Rami Yaka & Professor Oren Ostresetzer)

      —The anti-angiogenic and anti-cancer activity of cannabinoid receptor 2 (CB2) agonists (Dr. Ofra Benny)

      —Effect of a Cannabis extract on acute radicular pain and on analgesics (Professor Elyad Davidson)

      “The establishment in Israel of the Multidisciplinary Center on Cannabinoid Research is of great relevance at this time since both academic institutions and pharmaceutical companies worldwide are channeling enormous efforts to basic and clinical research in this field,” said Dr. Joseph (Yossi) Tam, Director of the Hebrew University’s Multidisciplinary Center on Cannabinoid Research, and Head of the Obesity and Metabolism Laboratory at the Hebrew University’s Institute for Drug Research in the Faculty of Medicine.

      The Center’s research will focus on the following areas: CancerPainInflammation & Stress ManagementImmunityMetabolismDrug Delivery & NanotechnologyPharmaceutical ChemistryNeuroscience; and Plant Science & Genetics.

      Dr. Yossi Tam

      Along with integrating the research activities of multiple Hebrew University research laboratories into interdisciplinary networks, the Center, which relies on the infrastructure of the Institute for Drug Research at the School of Pharmacy in the Faculty of Medicine, will also foster collaborations between its participating laboratories and other well-established research groups around the globe.

      “We feel incredibly fortunate to team up with a vast number of scientists working together on this expanding field of medicine with the significant potential to discover new therapies based on cannabinoids,” said Dr. Tam.

      Until very recently, the Cannabis plant and its extracts (popularly called marijuana, hashish, weed, and grass) were mostly frowned upon as purely recreational drugs. However, over the last 50 years, Professor Raphael Mechoulam at the Hebrew University has spearheaded a new scientific era of Cannabis research. Professor Mechoulam, along with his colleagues, isolated the active constituent of the Cannabis plant, tetrahydrocannabinol, elucidated its structure and synthesized it. Later he identified the endogenous cannabinoids (formed in the mammalian body) and thus pioneered the field of cannabinoid research.

      “It has been shown that modulating endocannabinoid activity has therapeutic potential in a large number of human diseases, hence research on cannabinoids may lead to very significant advances, not only in basic science but also in therapeutics. Our Multidisciplinary Center addresses many aspects in this promising area, such as cancer, head injury, addiction, bone formation, obesity and others,” said Professor Raphael Mechoulam, Head of the Academic Committee of the Multidisciplinary Center, and the Lionel Jacobson Professor Emeritus of Medicinal Chemistry in the Hebrew University’s Faculty of Medicine.

      The Center’s teams of highly qualified researchers comprise Heads of Labs and Research Groups ranging through Nano-Medicine & Nano Delivery Systems, Tumor Micro-environment, Neurobiology, Pain Relief & Plasticity, Molecular Modeling & Drug Design, Immuno-pharmacology, Free Radicals, Stress, and Plant Pathogen Interactions.

      The Center’s informational resources include a World Calendar of Cannabinoids, featuring information about major upcoming events in the field of cannabinoid research.

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