The Endocannabinoid System: A Fifty-Year Trip
The endocannabinoid system was discovered and we learned about its involvement in biological processes only over the last two decades – many years after the better known adrenergic, serotonergic or cholinergic systems. However, it has already been suggested that ” modulating endocannabinoid system activity may have therapeutic potential in almost all diseases affecting humans, including …neurodegenerative, inflammatory,…. pain, …psychiatric disorders, amongst many others ” – as stated in a recent review.
Dr. Mechoulam will discuss the development of the endocannabinoid system – from the isolation and structure elucidation of delta-9-tetrahydrocannabinol in 1964, through the identification of the CB1 and CB2 receptors and the specific agonists anandamide and 2-AG, to the involvement of endocannabinoids and structurally related endogenous molecules in a long list of biological processes.
Recent progress in several areas will be discussed:
Raphael Mechoulam is an Israeli organic chemist and professor of Medicinal Chemistry at the Hebrew University of Jerusalem in Israel. He is best known for his work (together with Y. Gaoni) in the isolation, structure elucidation and total synthesis of Δ9-tetrahydrocannabinol, the main active principle of cannabis and for the isolation and the identification of the endogenous cannabinoids anandamide from the brain and 2-arachidonoyl glycerol (2-AG) from peripheral organs together with his students, postdocs and collaborators.
Courtagen Life Sciences and Medicinal Genomics are proud to partner with Dr. Raphael Mechoulam and his lab team. A portion of the CannMed 2017 conference proceeds is designated to support the research projects in their laboratory. At present their focus covers chemistry of endogenous cannabinoids (isolation, structure elucidation, synthesis), as well as synthesis of novel compounds to be tested as drugs against pain, inflammation, high blood pressure and cancer. We truly value the work of this wonderful team and are honored to play a part in assisting them with these valuable studies. Learn more about Dr. Mechoulam’s research in the video below.
Would you like to join us and contribute to supporting Dr. Mechoulam’s lab at the Hebrew University of Jerusalem? Take a minute when paying your registration fee to make a contribution of your own. 100% of all contributions (minus credit card fees) will be given to the university for the purpose of funding the lab needs.
Israel, Leading a Process: From Illegal Substance to Potent Medication
The government of Israel is at the forefront of efforts to develop and expand the fast-growing medicinal marijuana industry. In a population of 8.5 million, the number of Israelis who hold permits to use medical marijuana to ease symptoms of cancer, epilepsy and other diseases. is 28,000 and growing, adding 100 new requests every day. That number is expected to grow rapidly with recent efforts to improve regulations within the industry that will pave the way to greater access and availability by prescription filled in pharmacies.
Michael Dor earned his medical degree at Tel Aviv University followed by his Diploma in Health Services and in Family Medicine through the Israeli Medical Association. Dr. Dor then completed his Masters in Public Administration at Harvard University – Kennedy School of Government. Dr. Dor’s commitment to providing quality healthcare for the people of Israel has led him to holding multiple leadership roles within his career, including Director of Emergency Walk-In Clinic – Jerusalem, Israel; Head of Community Medicine Division – Israeli Ministry of Health; and Deputy Director of All Medical Services – Israeli Ministry of Health. In 2014, he was honored with Presidential Award for volunteer work he did to establish a clinic for un-insurred illegal immigrant and victims of human trafficking. Today, Dr. Dor is active as a family physician and also serves as the Chief Medical Officer – Ministry of Foreign Affairs and the Medical Head Advisor of the Medical Cannabis Unit for the Israeli Ministry of Health.
How Patients Benefit from Medical Cannabis
Thousands of medical cannabis patients in Dr. Goldstein’s practice report benefits from using medical cannabis. In this talk, Dr. Goldstein will address the various ways that patients are successfully using cannabis and share the journey they are making from chronic illness to good health.
Bonni Goldstein, MD is the Medical Director of Canna-Centers, a California-based medical practice devoted to educating patients about the use of cannabis for serious and chronic medical conditions. After years of working in the specialty of Pediatric Emergency medicine, she developed an interest in the science of medical cannabis after witnessing its beneficial effects in an ill friend. Since then she has evaluated thousands of patients for use of medical cannabis. She has a special interest in treating children with intractable epilepsy, autism, and advanced cancers, as well as adults with chronic pain, autoimmune illnesses and other endocannabinoid deficiency disorders. Dr. Goldstein recently authored the book “Cannabis Revealed: How the world’s most misunderstood plant is treating everything from chronic pain to epilepsy.”
A native of New Jersey, Dr. Goldstein received her undergraduate education at Rutgers College and her medical degree at Robert Wood Johnson Medical School at the University of Medicine and Dentistry of New Jersey. Her post-doctoral education included internship and residency at Childrens Hospital Los Angeles. Dr. Goldstein also served as Chief Resident at Childrens Hospital Los Angeles. She was a Clinical Instructor in Pediatrics at USC School of Medicine in Los Angeles, Emergency Transport Attending Physician at Childrens Hospital Los Angeles and Emergency Medicine Attending Physician in the Pediatric Emergency Department at Los Angeles County-USC Medical Center. She is a member of the Society of Cannabis Clinicians, the International Association of Cannabis as Medicine, and the International Cannabinoid Research Society. Dr. Goldstein also serves on the Scientific Advisory Board for Courtagen Life Sciences, United Patients Group and United in Compassion Australia. She is the medical advisor to Weedmaps.com.
A Clinician’s Approach to Managing Uncertainty in Medically Refractory Patients
Dr. Gaitanis’s talk is intended for clinicians who treat patients with medically refractory epilepsy or autism with aggressive and self-injurious behaviors. The talk uses clinical vignettes to highlight real world challenges and emphasizes solutions that improve patient outcomes. It focuses on managing clinical uncertainty with medical options are limited. It also reviews ethical and legal considerations for caregivers recommending medicinal cannabis for their patients.
Dr. Gaitanis, a graduate of Brown Medical School, completed his neurology training at Children’s Hospital Boston. He went on to finish an epilepsy fellowship at Beth Israel Deaconess Medical Center before returning to Children’s Hospital Boston to join their epilepsy staff. In 2004, Dr. Gaitanis returned to Brown Medical School and Hasbro Children’s Hospital where he served as the director of pediatric epilepsy. He aided in the development of ketogenic diet and epilepsy surgery programs at Brown, providing comprehensive epilepsy care for children in Rhode Island. He now serves as the Director of Child Neurology at Tufts Medical Center/Floating Hospital for Children. Apart from his clinical duties, Dr. Gaitanis serves as the Chairperson of the Matthew Siravo Memorial Foundation’s Scientific Advisory Board, a non-profit organization dedicated to improving epilepsy advocacy and education. Dr. Gaitanis’ research is aimed at improving the sensitivity of EEG through digital signal processing and advancements in lead design.
Cannabidiol (Epidiolex) in Dravet and Lennox-Gastaut Syndromes: Preliminary Clinical Trial Results
The talk will summarize ‘top-line’ results of the first 3 randomized placebo-controlled trials for Dravet Syndrome and Lennox-Gastaut Syndrome, as well as an update on the open-label studies and pharmacokinetic studies.
Orrin Devinsky is Professor of Neurology, Neurosurgery, and Psychiatry at the NYU School of Medicine, where he directs the Epilepsy Center. His epilepsy research includes SUDEP, cannabidiol, ataluren, phenome-genome correlations, healthful behavioral changes, autism, therapeutic electrical stimulation, quality-of- life, cognitive and behavioral issues, and surgical therapy. He is the Principal Investigator for the North American SUDEP Registry and for the SUDC Registry and Research Collaborative. He is on the Executive Committee of the SUDEP Institute and Scientific Advisory Boards of the Epilepsy Foundation, Dup15q Alliance, Tuberous Sclerosis Association, KCNQ2 Cure Alliance Foundation, and UPenn/Loulou Foundation CDKL5 Program of Excellence. He serves as the lead investigator for the Epidiolex Dravet and Lennox Gastaut studies. He founded Finding A Cure for Epilepsy and Seizures (FACES) and co-founded the Epilepsy Therapy Project and epilepsy.com. Outside interests include behavioral neurology, evolutionary biology, and history of neuroscience.
Cannabis Therapeutic Use in the Elderly
There has been an increase in medical marijuana use in the senior population in recent years, especially since the advent of more preparations including cannabidiol (CBD). Dr. Malka shares the results of a small observational study of cannabis use in a group of patients at an Assisted Living Center in the central coast of California. She will review delivery, dosage, the effects of CBD, THC and their combination, and the most common conditions for which they are helpful in elderly patients.
Deborah Malka MD, Ph.D is a holistic physician specializing in cannabis medical consultations. Her private practice, CANNABIS PLUS, provides medical marijuana evaluations and natural health consulting with offices in Monterey and Santa Cruz, California. Prior to clinical practice, Dr. Malka completed her doctorate in Human Genetics from Columbia University, and studied both natural and traditional medicine, with degrees from the University of New Mexico School of Medicine and the Santa Fe College of Natural Medicine. The field of cannabis medicine allows her to integrate her expertise in allopathic medicine, herbal medicine, research, and patient care.
She is both a clinician and an educator in this specialty. She has previously served as the medical director for MediCann Inc., a group of clinics providing medical marijuana evaluations in California, serving over 300,000 patients. She was the faculty director of the first comprehensive online course in Clinical Cannabinoid Medicine, offered at www.themedicalcannabisinstitute.org. She continues to provide quality medical education about cannabis to multiple audiences including physicians, patients, and dispensaries.
Is Cannabis a Solution to the Opioid Epidemic?
Opioid overuse and abuse is a major public health challenge without an effective solution. Dr. Sulak will review the latest preclinical and clinical data examining the potential of cannabinoids to replace opioids, enhance the safety of co-administered opioids, improve opioid efficacy, improve adherence to other opioid-abuse treatments, and reduce the symptoms of opioid withdrawal. Learn the clinical pearls and treatment guidelines from Dr. Sulak’s clinics in their experience using cannabis to help over 400 patients decrease or discontinue opioid drugs.
Dr. Dustin Sulak is an integrative medicine physician with an emphasis in osteopathy, mind-body medicine, and medical cannabis. His clinical practice focuses on treating refractory conditions in adults and children. Dr. Sulak is the founder of Integr8 Health, a medical practice with 3 locations in New England that treat over 18,000 patients with medical cannabis, Tested Labs, a cannabis analytic laboratory, and Healer.com, a medical cannabis patient education resource. His sits on the board of directors of the Society of Cannabis Clinicians and has lectured to healthcare providers internationally on the clinical applications of cannabis.
Cannabis for Pain Management and Opioid Use Reduction
Pain, from various sources, is the number one complaint of patients in the United States. It is also the number problem that patients state is poorly addressed by their clinicians. This has lead, in recent years, to the over-prescription of opioid pain medications, resultant over-use or misuse of these medications, addiction, increased use of illegal opiates like heroin, and overdose related deaths. The federal government, having only lately caught on to this trend, has called it an “epidemic” and released multiple documents describing ways to reduce opioid prescription, none of which truly address the underlying problem: patients’ pain.
Further, a secondary issue of what to do about patients who have already become dependent on opiates has been met with plans that leave much to be desired, and often do not adequately address patients’ pain.
Cannabis has been shown to effectively address pain from multiple sources, and has a much better safety profile than opiates. It has also been shown that Cannabis use concomitantly with opioids can reduce the amount of opioids needed, presumably increasing patient safety. In many instances, Cannabis can treat pain sufficiently that all opiates can be discontinued. There is some preliminary data on using Cannabis to detox patients from opiates.
In this session, I will present a synopsis of the evidence mentioned above and address clinical approaches to real-world treatment of patients with chronic pain who are either using, or not yet using, opioids medications.
Dr. Tishler is a leading expert in the field of Medical Cannabis therapeutics. As an Emergency Physician, he has treated countless alcoholics and drug users. His observation that he had never seen a Cannabis overdose lead Dr. Tishler to delve deeply into the science of Cannabis safety and treatment. After years of research and learning, Dr. Tishler brings his knowledge, reason, and caring to patients at Inhale Medical Consulting and through his advocacy work at the local and national levels.
Dr. Tishler graduated from both Harvard College and then Harvard Medical School (affectionately known together as Preparation H), trained in Internal Medicine at the esteemed Brigham and Women’s Hospital, and has spent many years working with the underserved, particularly our Veterans.
Dr. Tishler is also a parallel entrepreneur working for patients’ well being in the corporate space, helping to elevate dosing and safety profiles of medication, and helping to establish best practice for bringing new Cannabis products to market.
Dr. Tishler is a frequent speaker and author on a variety of topics related to the medical applications of cannabis. He is also a Massachusetts spokesperson for Doctors for Cannabis Regulation (DFCR). He sits on the advisory board of CannaKorp, makers of a medical Cannabis inhaler, and the Massachusetts Patient Advocacy Alliance.
The Role of Cannabidiol in the Treatment of Refractory Pediatric Epilepsy
Approximately one in three individuals with epilepsy develop medically refractory epilepsy. In spite of the available anticonvulsant medications, there continues to be a significant unmet need for safe and effective therapies. There is increasing experience with cannabidiol (GW Pharma Epidiolex) in the treatment of refractory pediatric epilepsy, including a large expanded access program as well as three randomized controlled trials in Dravet Syndrome and Lennox Gastaut Syndrome which have been completed. The results from these studies, including efficacy, safety and tolerability will be discussed.
Elizabeth A. Thiele is Director of the Pediatric Epilepsy Program and Director of the Herscot Center for Tuberous Sclerosis Complex at Massachusetts General Hospital. Dr. Thiele is also Professor of Neurology at Harvard Medical School.
Dr. Thiele directs clinical research efforts in the neurologic aspects of Tuberous Sclerosis Complex including epilepsy, autism and mental health issues. She also works on improved dietary therapies for epilepsy, including Low Glycemic Index Treatment. Dr. Thiele has received awards for teaching in residency programs at Massachusetts General Hospital and the Longwood Neurology Program, and for research mentoring from the Harvard MIT Health Sciences and Technology program. She also received the Manuel R. Gomez Award from the Tuberous Sclerosis Alliance in 2008, the inaugural John M Freeman Award in 2014 and the Infantile Spasms Award from the Child Neurology Foundation in 2014.
Dr. Thiele received her A.B., scl from Washington University, St. Louis in 1983 and her M.D. and Ph.D. from The Johns Hopkins University School of Medicine in 1990. She completed a residency in pediatrics at The Johns Hopkins Hospital in Baltimore and a residency in child neurology with the Longwood Program and Children’s Hospital in Boston. In addition, she completed a neuroscience fellowship at Children’s Hospital in Boston. Dr. Thiele is board certified in neurology with a special qualification in child neurology, and in clinical neurophysiology.
Assertions v. Evidence, Kindly Check Your Assertions at the Door
With the continued classification of cannabis as a Schedule 1 drug, studies of the safety and efficacy of cannabis are nearly nonexistent. Federally supported studies asserting harm from cannabis continue to perpetuate fear among physicians in questioning the use of cannabis as medicine.
A critical review of the assertions of harm and the evidence surrounding these topics lead to the understanding that the cannabis prohibition is eroding. Cannabis clinicians shackled by misinformation and the embargo on clinical cannabis studies must rely on basic cannabinoid science, limited clinical studies, and clinical observations as their sources of evidence to guide their treatment plans.
Dr. Jeffrey Hergenrather is a cannabis consultation physician who practices in Northern California. He is also President of the Society of Cannabis Clinicians, and a member of the International Cannabinoid Research Society and the American Academy of Cannabinoid Medicine (AACM). Formerly, Dr. Hergenrather worked as a general practitioner. He received his MD from Brown University in 1975 and believes that cannabis is an alternative/complementary medicine with trivial negative impacts.
Kevin is currently the CSO of Courtagen Life Sciences, Inc. Prior to joining Courtagen, Kevin was the founder and CEO of Medicinal Genomics Corporation. Medicinal Genomics made world-wide news in 2011 when it publically released the first genome sequence for Cannabis Sativa L. As a result of this work, Medicinal Genomics (MGC) launched a suite of qPCR tools for the detection of microbial contamination on Cannabis. In 2015, MGC is the largest provider of microbiological testing equipment in the cannabis space and has been selected to present on its genome sequencing, cannabis sex determination and microbiome work at ICRS 2014 and 2015. In December of 2011, Medicinal Genomics Corporation was acquired by Courtagen Life Sciences Inc. (CLS). As a CLIA and CAP regulated clinical next-gen sequencing company, CLS sequences the genomes of over 700 patients a month believed to have Epilepsy, Autism, Mitochondrial disease, and various diseases thought to be governed by the Endocannabinoid system. Courtagen’s expertise on the genetics of drug-drug interactions with cannabinoids and the genomics of neurological disease has proven to be a valuable physician tool experiencing over 100% year over year growth. Together, Courtagen and MGC are pioneering personalized medicine in the cannabinoid space concurrently with a strong “picks and shovel” position in the cannabis safety testing markets.
Previously, Kevin held the position of Vice President and Director of R&D of Life Technologies where he managed the development of Life Technologies next generation SOLiD sequencing technology. Integral to the SOLiD R&D process, Kevin oversaw over 100 research collaborations exploring the new biological frontiers with next generation sequencing and saw particular excitement and traction in human tumor sequencing. Kevin initiated an R&D project to investigate chemFET semiconductor based DNA sequencing and spearheaded a process to acquire the DNA sequencing company, Ion Torrent, for $350M. These collaborations resulted in hundreds of publications and seven journal covers from Science Translational Medicine to Nature.
Kevin was the President and CSO of Agencourt Personal Genomics, a startup company he co-founded in 2005 to invent revolutionary sequencing technologies that dropped the cost of sequencing a human genome from $300M to $3,000; a 100,000-fold improvement in sequencing speed and cost in a few years. Kevin oversaw the growth and research for APG which was acquired by ABI in 2006. In 2000, Kevin co-founded Agencourt Biosciences Corporation and acted as the CSO until 2005 when it was acquired by Beckman Coulter who had an expressed interest in nucleic acid testing and blood diagnostics. From 1996 to 2000, Kevin managed the Research and Development Team for the Human Genome Project at Whitehead Institute/MIT which resulted in several patents for nucleic acid purification. Kevin holds a B.S. in Biology from Emory University with a focus on cloning and expressing Norepinephrine Transporters.
Toward Precision Medicine for Cannabidiol Treatment in Epilepsy, and the Impact of Rare Variation in Endocannabinoid System Genes
Dr. Smith and his team have been collaborating with several investigators involved in clinical trials to evaluate the efficacy of Cannabidiol as an anti-seizure medication in patients with treatment-refractory epilepsy. Their hypothesis is that the magnitude of CBD-mediated seizure reduction is influenced by the nature of the epilepsy-causing mutations that occur in individual patients, as well as by the combined effects of common variants in regulatory sequences that modulate the expression of genes in pathways linked to the pharmacological action of the drug.
Preliminary analysis based on the sequencing results from 75 patients using the epiSEEK Comprehensive gene panel (471 genes) indicated possible enrichment of rare mutations affecting one epilepsy-associated gene in patients with increased seizure frequency. In addition, using a statistical genetics approach based on SNP genotyping and linear regression, they identified two linked SNPs in a regulatory region of another gene that may be positively associated with response to CBD.
In a separate study, the team analyzed clinical genetic test results from over 6,500 patients with neurological and functional disorders to identify rare genetic variants in the core ECS genes that encode the CB1 and CB2 receptors, diacylglycerol lipase alpha (which synthesizes 2-AG), monoglyceride lipase (which breaks down 2-AG), and fatty acid amide hydrolase (which breaks down AEA). Heterozygous rare variants in CNR1 were found to be significantly associated with headache/migraine, headache/migraine with anxiety, and sleep disorders. Heterozygous rare variants in DAGLA were found to be significantly associated with seizures, developmental disorders and abnormalities of brain morphology. Rare variants in MGLL, FAAH and CNR2 were not found to be significantly associated with neurological phenotypes.
Dr. Douglas R. Smith is a Senior Research Director with over 30 years of experience in genetic analysis, large-scale genome sequencing, bioinformatics, and technology development. His research experience encompasses numerous federally funded technology development and sequencing projects, including the human genome project. Additional experience encompasses development of commercial genomics applications at Genome Therapeutics Corp., Agencourt Bioscience Corp., Beckman Coulter Genomics and Courtagen Life Sciences. His current research interests include the molecular genetics of neurological disorders, pharmacogenetics and precision medicine, cannabis genetics and metagenomics, and the advancement of next generation sequencing based molecular diagnostics.
It’s Not Easy Being Green: Assessing the Impact of Medical Marijuana on Cognition, Mood, Brain Function and Related Measures
Dr. Gruber will discuss the newly launched MIND (Marijuana Investigations for Neuroscientific Discovery) Program, the first of its kind to assess individuals using medical marijuana (MMJ) before they begin their regimen and follow them over the course of a year. She will present data related to indications for MMJ use: clinical state, cognitive performance, sleep, medication use, as well as multimodal neuroimaging findings. She will also discuss the second, treatment-based phase of the program.
Dr. Staci Gruber is the Director of the Cognitive and Clinical Neuroimaging Core at McLean Hospital’s Brain Imaging Center and an Associate Professor of Psychiatry at Harvard Medical School. Dr. Gruber’s clinical research focuses on applying neurocognitive models and brain imaging to better characterize risk factors for substance abuse and psychiatric conditions. In recent work, her lab has examined the effects of chronic recreational marijuana use on cognitive performance, brain structure and function in adolescents and adults. This work has underscored the importance of delaying adolescent onset of marijuana use, and has been the basis of national and international symposia, press conferences, and news pieces, including CNN’s documentary series “WEED” with Dr. Sanjay Gupta. Dr. Gruber also directs the newly launched MIND (Marijuana Investigations for Neuroscientific Discovery) Program, designed to clarify the effects of medical marijuana on brain structure, function, and quality of life, as she is invested in exploring the therapeutic potential of specific cannabinoids, including cannabidiol, for a range of indications. Findings from Dr. Gruber’s recreational and medical marijuana research have informed public policy and helped to educate the public regarding the potential risks and benefits of marijuana use.
Cannabinoids as Medicine: Pain and CNS Injury
Pain is a major symptom in many medical conditions, significantly interfering with quality of life and functioning. Inadequate treatment of chronic pain in particular is widespread. The gold standard opioid analgesics are not sufficiently effective for the management of chronic inflammatory or neuropathic pain, and available non-opioid alternatives suffer from limited efficacy and adverse effects. A history of analgesic properties of Cannabis goes back centuries, and analgesic effects of its main psychoactive constituent THC have been reported in humans. However, THC is associated with adverse psychoactive effects that limit acceptance and compliance. A recent advance in Cannabis-based pharmaceuticals is the buccal spray Sativex, a 1:1 formulation of THC and the non-psychoactive phytocannabinoid cannabidiol (CBD). Among its uses are treatment of spasticity and pain in multiple sclerosis and cancer respectively.
Dr. Ward and her colleagues were the first to report anti-neuropathic effects of CBD alone in a preclinical model of neuropathic pain, and more recently they have demonstrated synergistic anti-neuropathic pain effects with combinations of THC+CBD. Other research programs in their laboratory focus on the neuroprotective effects of CBD, as well as synthetic non-psychoactive cannabinoid compounds, in other injury models including stroke, spinal cord injury, and traumatic brain injury. Taken together, the work of Dr. Ward’s laboratory and others points to great therapeutic potential of non-psychoactive cannabinoid-based therapies alone and in combination with THC.
Dr. Sara Jane Ward is an Assistant Professor in the Center for Substance Abuse Research and Department of Pharmacology. She earned her Ph.D in neuroscience at Wake Forest University in Winston-Salem NC. She conducted her own NIH-funded research under a postdoctoral fellowship at the University of North Carolina at Chapel Hill and Temple University where she began to study the role of cannabinoids in learning and memory and reward processing. Dr. Ward is currently working on several projects to elucidate the therapeutic potential of non-psychoactive cannabinoids, including studies supported by the National Institutes of Health and Department of Defense investigating the efficacy of Cannabidiol for the treatment of peripheral and central neuropathic pain. Other projects in collaboration with TUSM faculty investigate the efficacy of Cannabidiol and synthetic cannabinoids on a range of nervous system targets including stroke, traumatic brain injury, and addiction. Dr. Ward has been a member of the International Cannabinoid Research Society since 2005.
Cannabinoids as Antitumor Agents: Moving Toward the Clinic
Dr. McAllister’s group has an active research program focusing on the antitumor activity of both synthetic and plant-based cannabinoid compounds with the goal of developing therapeutic interventions for aggressive cancers. The presentation will briefly review cannabinoid-based compounds that have been advanced to the clinic or are moving toward the clinic. The well-known palliative effects of cannabinoids in cancer patients will also be discussed. The majority of the presentation will focus on the potential of cannabinoids to directly target cancer and enhance the activity of first-line antitumor agents.
A growing body of research suggests that non-psychotropic cannabinoid compounds, found in the Cannabis plant, are effective antitumor agents in multiple pre-clinical models of aggressive cancers.
Senior Scientist Sean McAllister, Ph.D, and colleague Pierre Desprez, Ph.D, discovered that the cannabinoid, cannabidiol (CBD), inhibits breast cancer metastasis—and more recent research suggests a role in treating the most common and aggressive form of brain cancer, glioblastoma.
Because of the promising preclinical trial research led by Dr. McAllister and colleagues at CPMCRI, the U.S. Food and Drug Administration granted orphan drug designation to CBD for the treatment of GBM. The approval significantly advances development of the compound and moves the research one step further toward phase 2 and 3 clinical trials to test the drug in human patients with the disease.
His knowledge of novel cancer chemotherapies for pre-clinical testing is instrumental to CPMCRI’s Cancer Avatar Project, for which Dr. McAllister developed a sophisticated drug screening model to test new cancer drugs and combination therapies. The project will give oncologists key information about how well a patient’s tumor might respond to a particular drug regimen.
Dr. McAllister earned his Bachelor’s Degree in Biology and his doctoral degree in Pharmacology and Toxicology from the Medical College of Virginia Commonwealth University. His doctoral research focused on the interactions of cannabinoids with their endogenous receptors. He completed postdoctoral training at the Forbes Norris Amyotrophic Lateral Sclerosis Research Center, before joining CPMCRI in 1999.
Use of CB2 Receptor Inverse Agonists in the Treatment of Traumatic Brain Injury
Dr. Reiner and his team have tested the benefit of a CB2 receptor inverse agonist in a closed-head mouse model of mild TBI in which a high-pressure air blast is delivered to the left side of the cranium overlying the forebrain, because microglia are thought to exacerbate the effects of TBI and because microglia are especially enriched in CB2 receptors. They tested CB2 receptor inverse agonist benefit because they have shown that CB2 receptor inverse agonists bias microglia from a harmful pro-inflammatory M1 state to a beneficial M2 state. The team specifically tested a CB2 receptor inverse agonist developed at UTHSC termed SMM189. Two weeks of daily SMM189 decreased functional deficits and associated axonal degeneration and neuron loss. Their studies suggest that neuronal injury and functional deficits resulting from mild TBI are worsened by the actions of M1 state microglia, and that SMM189 provides benefit by reducing M1-related harm and boosting M2-related protection.
Dr. Anton Reiner is a Full Professor in the Department of Anatomy & Neurobiology at The University of Tennessee Health Science Center. He earned his Ph.D in Experimental Psychology at Bryn Mawr College in Bryn Mawr PA in 1977, and subsequently carried out postdoctoral training with Dr. Harvey Karten at the State University of New York at Stony Brook. He became an adjunct Assistant Professor at the State University of New York at Stony Brook in 1980, and then moved to the Department of Anatomy & Cell Biology at the University of Michigan in 1982, again as an adjunct Assistant Professor. In 1987, he joined the Department of Anatomy & Neurobiology at The University of Tennessee Health Science Center as an Associate Professor, and was promoted to Full Professor in 1992. His research has focused on the pathogenesis and treatment of neurodegenerative diseases of the eye and brain, with a particular recent interest in the pathophysiology and treatment of mild traumatic brain injury. In these latter studies, he has been studying the therapeutic potential in mild traumatic brain injury of targeting microglia with CB2 receptor inverse agonists that bias them away from the harmful M1 state toward the beneficial M2 state.
The Endocannabinoid System – A Source for Drug Discovery
Among the lipid modulators endocannabinoids play a key role. Our current knowledge of the endocannabinoid system includes CB1 and CB2, two Gi/o GPCRs involved in a number of signaling mechanisms. The endogenous molecules that modulate this biochemical system, which include ethanolamides as well as 2-glycerol esters of long fatty acids are represented by arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG). The levels of these endocannabinoids are modulated by a number of membrane associated enzymes, including the amidase, fatty acid amide hydrolase (FAAH) and the esterase, monoacylglycerol lipase (MGL), as well as by a transporter system that remains to be fully characterized.
Regulation of the levels of endocannabinoids and related lipids in different organs can provide significant nutritional or therapeutic opportunities. Modulation of the endocannabinoid system either directly (through CB1/CB2) or indirectly (through enzymatic or transport inhibition) provides opportunities for the design and development of small ligands capable of effecting physiological changes and, thus, serve as potential drug candidates. This target-based drug design utilizes a combination of computational and biophysical methods.
The biochemistry of the endocannabinoid system and approaches involving its modulation for nutritional or therapeutic opportunities will be discussed.
Research Supported by grants from NIH: DA009158, DA003801, and DA023142
Alex Makriyannis is the George Behrakis Chair of Pharmaceutical Biotechnology at Northeastern University, Boston, MA, and is the Founder and Director of the Center for Drug Discovery. He is a highly successful medicinal chemist and is well recognized nationally and internationally for his important contributions in endocannabinoid research. Inventor of over 50 issued U.S. patents, Makriyannis played an important role in the discovery of this relatively newly characterized biochemical system that regulates many physiological functions including pain, neuroprotection, addiction, immunomodulation and cognition.
Over the past four decades, his laboratory has designed and synthesized some of the key pharmacological endocannabinoid probes that are widely used and serve as leads for the development of new medications. He has also made important contributions aimed at understanding the molecular basis of cannabinoid activity. Very recently, working with an international team, Alex participated in obtaining the crystal structure of the CB1 cannabinoid receptor.
He has been a creative pioneer in the field of chemical biology where he combined the use of medicinal chemistry, biochemistry, molecular biology and biophysics. His work is recognized for its high level of originality. Some of his compounds are in advanced preclinical trials for the treatment of metabolic disorders and liver function, neuropathic pain, addiction and neurodegenerative diseases.
Elucidating Cannabinoid Biosynthesis Using Trichome Targeted Genomics
The presentation will focus on the production of cannabinoids and terpenes in the glandular trichomes of cannabis. The use of trichome targeted genomics, together with biochemical characterization, has led to the successful discovery of many of the enzymes involved in cannabinoid biosynthesis.
Jonathan is the founder of Anandia Labs, a cannabis testing and genetics company based in Vancouver, and an Adjunct Professor in the Botany Department at the University of British Columbia. He has spent his scientific career deciphering the genetic and biochemical secrets of medicinal plants, including the production of THC and other cannabinoids in cannabis. He received his PhD from The University of British Columbia (1998), undertook postdoctoral training in Germany (1998-2003) and directed a lab at the National Research Council’s Plant Biotechnology Institute (2003-2013). Jonathan co-led the Canadian team that published the first cannabis genome and he continues to work on the genomic analysis of cannabis. His work has helped elucidate the biochemical pathway leading to the major cannabinoids. His passions are building a strong science foundation for cannabis, and turning Anandia Labs into a world leader in cannabis genetics.
Cannabis Used in Research Does Not Reflect Legal Markets
The National Institute on Drug Abuse (NIDA) is designated as the sole legal producer of Cannabis for use in US research studies. We compared the chemical profiles of Cannabis varieties that are available to consumers in states that have state-legalized use versus what is available to researchers interested in studying the plant and its effects. Our results demonstrate that the federally-produced Cannabis has significantly less variety and lower concentrations of cannabinoids than are observed in state-legal U.S. dispensaries. Most dramatically, NIDA’s varieties contain only 27% of the THC levels and as much as 11-23 times the Cannabinol (CBN) content compared to what is available in the state-legal markets. Research restricted to using the current range of federally-produced Cannabis thus may yield limited insights into the chemical, biological and pharmacological properties, and medical potential of material that is available in the state markets.
Dr. Nolan Kane has been a professor for only 3 years, but already has over 70 publications, including important discoveries about the biology, evolution, and genetics of Cannabis. His Ph.D research examined the genetics of adaptation and speciation in several species of wild sunflowers, at Indiana University. His post-doctoral research involved assembling the genome of the domesticated sunflower, Helianthus annuus at the University of British Columbia. Ongoing research projects include research on lichen, sunflowers, mustard andCannabis. A common tie among all of these projects is to understand the origins of new lineages. In many cases hybridization between divergent taxa can lead to varieties or species with entirely new properties.
Amir Golan is a young enthusiastic Medical Student currently studying in the Hebrew University Class of 2020. He works as a Research Associate at the Hebrew University’s Cannabinoids Research Center and has authored “Medical Marijuana- A Source for a New Treatment of Autoimmune Diseases?”, Harefuah. 2016 Feb;155(2):74-8 133. In addition, Amir currently serves as a dedicated Volunteer at the Open Clinic of “PHR” Jaffa and has also given his time and talent to the “Push” Foundation, as a privet teacher for straggling elementary school students.
Case Presentations of Cancer Patients Treated with Low Dose Cannabis Oil Alone or in Combination with Conventional Therapy
Case Presentations of cancer patients treated with low dose cannabis oil alone or in combination with conventional therapy. Dr. Kimless will present four examples of cancer patients treated with low dose cannabis oil either as a sole treatment or in conjunction with conventional cancer therapies.
Cannabis has been shown to play an important role in cancer treatment from mitigating treatment side effects to causing cancer cell apoptosis. Dosing is always a question, and these cases present successful treatments based on individual metrics using very lose doses of cannabinoids.
Debra Kimless, M.D. graduated magna cum laude from Muhlenberg College with a double major in Natural Sciences and Biology. She was selected to be part of Phi Beta Kappa honor society. She went on to medical school at Rutgers and residency at Temple University Hospital where she studied and became a clinical practitioner for over 15 years as a boarded Anesthesiologist with a subspecialty certification in Pain Medicine.
Motivated by her mother who suffered horribly with intractable pain at the end of her life and who had always responded paradoxically to opiates, Dr. Kimless became a passionate champion for medical cannabis.
Dr. Kimless dedicated the last several years to immersing herself in all aspects of medical cannabis, including scientific and medical applications for the treatment of patients. She has traveled the world studying under the most respected experts in cannabis medicine and science, most notably, in both the Netherlands and in Israel (two countries regarded as best practice models in the use of medical cannabis).
She shares her knowledge by speaking with physicians to educate them about the endocannabinoid system and to help them understand how medical cannabis can be an effective tool to help patients. She also consults with patients pro bono to introduce cannabis medicine as a treatment option. She has first-hand experience in successfully treating patients with a variety of medical conditions using an individualized treatment plan. She collects patient data and has presented the case studies at national and international conferences and seminars.
Her passion is to educate physicians, patients, and the public to de-stigmatize cannabis, so they understand that is a real and effective medical therapeutic choice.
Matching an effective cannabis strain extract for a specific subtype of cancer
In the last year we established novel ability to metabolomics analyzing all the chemical content of the cannabis plants (e.g. all the phytocannabinoids and the terpenes).
In our work, we intend to identify the effects of different cannabinoids and terpenes combinations, on various cancer pathways. In order to demonstrate differential antitumor effects of different cannabis extracts, we established a method for screening antitumor effects of cannabinoids compounds on various cancer subtypes in-vitro. Our preliminary data shows that cannabis extracts are very potent in killing tumor cells. We found that different strains (with a distinct cannabinoid composition) have different effects on various tumor cell lines. We suggest that specific pathways have been activated or inhibited by Cannabis extracts according to the cancer driving mutations.
David (Dedi) Meiri, Ph.D., is an Assistant Professor at the Faculty of Biology at the Technion Israel Institute of Technology and a member of the Technion Integrated Cancer Center (TICC). Dr. Meiri’s scientific background is highly diverse. He holds a M.Sc. in biochemistry and a Ph.D. in plant biotechnology from Tel Aviv University. Dr. Meiri conducted his post-doctoral fellowship at the Ontario Cancer Institute where he focused on the role of the GEF-H1 protein in tumor invasion and metastasis. During his post-doctoral studies, he expanded his knowledge in human biology and cancer pathogenesis and succeeded within a very short time frame to receive worldwide recognition as an expert in the fields of G-protein coupled receptors (GPCRs) and small GTPases. Upon completion of his post-doctoral fellowship, Dr. Meiri took a position at the Technion Israel Institute of Technology, where he heads the “Laboratory of Cancer Biology and Cannabinoid Research”.
Presently, his lab investigates the therapeutic potential of phytocannabinoids, the unique active compounds of the Cannabis sativa plant. On top of other research being conducted in the lab, the main focus of his research is to determine the antitumor effects of cannabinoids, including the anti-metastatic and pro-apoptotic effects of phytocannabinoids.
In addition to the laboratory cannabis research performed on-site, Dr. Meiri collaborates with cannabis growers, clinicians, major manufacturers and distributors of medical cannabis for the purpose of revolutionizing cannabis treatment. He is operating the “Cannabis Database Project” and his lab is currently involved in eight clinical trials covering diverse aspects of cannabis treatment such as colon disease, pain prevention, cancer treatment and epilepsy.
Dr. Meiri is also highly involved in governmental regulations and is a residing member in several Israeli Ministry of Health committees which seek to advance the fundamental understanding of optimal cannabis usage and minimization of adverse side effects.
Hydrogenated Cannabis Oil
Hydrogenation represents a simple, scalable chemical transformation that has be employed to chemically modify plant extracts. In cannabis extracts, hydrogenation converts the tetrahydrocannabinoids and terpenes into their saturated analogs. We found that hydrogenation shows a slight improvement in reducing glioblastoma tumor size in mice vs. the non-hydrogenated starting materials. Implications of the enrichment of hexahydro-cannabinoids in cannabis extracts will be discussed.
Dr. Scialdone is a recognized expert in the field of organic chemistry specializing in natural product chemistry including plant oil extraction, analysis and chemical modification. He is an inventor of 33 issued US patents and has authored 15 publications in the scientific literature during more than two decades of both basic fundamental and product development research. He has given invited lectures at more than 30 different academic institutions and international symposia.
Dr. Scialdone holds a Bachelor of Science and a Master’s of Science in Chemistry from Michigan Technological University, a Doctor of Philosophy in Chemistry from Wayne State University and was a Postdoctoral Research Associate at Colorado State University.
Dr. Scialdone was employed as a principal investigator at DuPont Central Research from 1994 to 2013. He then founded BetterChem Consulting Inc. to provide chemistry consulting services to clients worldwide in the chemical, plant essential oil and cannabis industries.
Automated Workflows for the Cannabis Analytical Lab: Increasing Sample Throughput and Data Reliability
With the increasing public support of cannabis and the momentum of state legislative action, it seems nearly inevitable that the demand for cannabis and cannabis-infused products is going to grow tremendously, and concomitant with the demand growth will come more regulatory requirements. Analytical laboratories will therefore look to automation to increase throughput while maintaining consistent and reliable results. Hamilton Company has collaborated with other industry partners to provide solutions to meet these emerging needs. Ryan will present data collected on a high throughput method for pesticide screening in 96 well plate format and also introduce other options like in-tip chemistry. Additionally, he will discuss how automation can benefit other analytical processes within the cannabis testing laboratory.
Ryan M. Ravenelle graduated with a BS in Chemical Engineering from the University of Nevada and obtained his PhD in Chemical and Biomolecular Engineering from the Georgia Institute of Technology. After multiple research and technical roles in industry, Ryan joined the Hamilton Robotics team in 2015 for the role of Scientific Leader of Applied Sciences. At Hamilton, Ryan’s role is to ultimately introduce and market Hamilton’s technology to industries outside of the traditional biology and life sciences customer base, as well as provide technical sales assistance and support new product development. One of his key interests is in promoting and developing automation solutions for the cannabis industry.
Impact of Standardized Cannabis Therapy in Chronic Noncancer Pain with or without Opiate Use
By a wide margin, chronic pain is the number one indication for the use of cannabis across all States with legal medical cannabis. Opiate abuse is currently a nationwide problem and many patients are seeking alternatives to opiate therapy to deal with their chronic pain. Our presentation will look at the results of an observational, longitudinal study of clinic patients with the diagnosis of chronic noncancer pain and the impact cannabis has on their pain, quality of life, and opioid use. Treatment protocols used at the clinic will be discussed as well as the importance of standardized, cannabis-based formulations.
Kent Crowley, Pharm.D., is a board-certified Pharm.D. through the American Academy of Anti-Aging Medicine. He received his Doctor of Pharmacy from University of California, San Francisco and completed his residency with Kaiser Permanente in Los Angeles, CA. He completed his Fellowship in Metabolic and Nutritional Medicine in 2011. During his 34 years in practice, he has worked in primary research at UCI, Dept. of Pediatrics, Division of Child Development, involved in the development of several drugs; holds two patents in neuropathic pain and a patent-pending buccal delivery system incorporating cannabis.
Dr. Crowley currently is the Director of R&D at Silver State Trading in Sparks, NV, a 40,000 sq.ft. permitted cannabis cultivation and production facility. He serves as the CMO for the Palliative Care Corporation in Huntington Beach, CA, where he works with patients and physicians incorporating cannabis to disease state treatment and symptoms management, whether as a primary treatment or complementary to traditional and/or other modalities.
Potential clinical benefits of CBD-enriched extracts over purified CBD in treatment-resistant epilepsy
Different therapies including cannabinoid compounds have become popular for treatment-resistant epilepsy in the recent years. This was the beginning of a rush of small-scale enterprises to produce “Cannabis oils”, followed by independent initiatives of patients and patient associations, which decided to produce the “oils” by themselves. This meta-analysis study evaluated all the observational clinical data available in the scientific literature for cannabinoid treatment in treatment-resistant epilepsy in children. The aim is to shine some light on the currently controversial question of whether “Cannabis-based extracts” or “purified/synthetic compounds” would be a preferential therapeutic approach. The meta-analysis study with clinical observational data from 442 patients suggests that treatments using CBD-enriched extracts have higher potency and a better side effects profile (but not higher efficacy) than purified CBD, at least for this group of treatment-resistant epilepsy patients.
Fabricio Pamplona is a Brazilian psychopharmacologist with broad experience in cannabinoid research. His major discovery, so far, was the description of the first endogenous allosteric modulator of the endocannabinoid system, with important implications to understand how different molecules interact at the CB1 cannabinoid receptors. He is currently Scientific Director of Entourage Phytolab, a pharmaceutical R&D company dedicated to the development of Cannabis-based medicines for unmet medical needs.
Cannabis Contaminants: Practical Considerations vs. Regulatory Requirements
The cannabis industry is currently one of the fastest-growing industries in the United States, with 28 states permitting medicinal use, as well as 8 states that permit adult-use. This growth is fueled by recent revelations of the benefits of cannabinoid therapies for many health conditions. One challenge that has emerged is the ability to ensure consumer safety, providing accurate dosing and products that are free from potential contaminants. Analytical testing is a necessary component to ensure patient/consumer safety for products that are being consumed both medicinally as well as recreationally. Yet, many states have minimal or no regulations in place to require analytical testing. For the states that do mandate testing, there is little synchronicity between requirements from state to state. In an effort to address this, several organizations have begun to develop and validate methods that can be used as a basis for this testing. These methods not only encompass testing for the active phytochemical constituents (cannabinoids and terpenes), but also for potential contaminants including heavy metals, residual solvents (VOCs), pesticides, mycotoxins, and microbiological contaminants. Many of these contaminants are the simple result of human handling and processing of the products. The methodologies that are being used to address these testing requirements include a wide variety of chromatographic techniques in addition to mass spectrometry and a variety of approaches to address microbiological contaminants. Standardization of these methods for the industry will give regulators the resources they need to include sensible requirements for regulation and legislation that is being crafted to monitor and control the use of cannabis within the US medical and adult-use markets.
Dr. Hudalla is a Ph.D. analytical chemist with more than 25 years of research experience in analytical chemistry, spectroscopy and chromatographic method development. He is recognized worldwide as an expert in the field of traditional Reverse Phase Liquid, Supercritical Fluid and Convergence Chromatography and an active leader in the development and implementation of the UltraPerformance Convergence Chromatography instrumentation. Dr. Hudalla is a founder and Chief Scientific Officer of ProVerde Laboratories, Inc., a premier analytical testing, CO 2 extraction and derivative product formulation consultancy for the regulated medical cannabis and hemp industries. ProVerde is one of few laboratories in the U.S. to receive an ISO 17025 accreditation that specifically governs medical cannabis testing. ProVerde Laboratories operates at the cutting edge of medical cannabis extraction, purification and product formulation techniques, supported by expert analytical testing, with expertise that will move research into cannabis and its effects on various medical conditions forward as the medical cannabis industry progresses. Dr. Hudalla plays an integral part in providing clients operating in the Medical Marijuana and hemp industries the ability to deliver new products and product formulations that meet the highest standards for quality, consistency, safety and labeling. Dr. Hudalla received his M.S. and Ph.D. from the University of California at Santa Barbara and was a Postdoctoral Fellow at the Eppley Institute for Cancer Research within the University of Nebraska Medical Center. Dr. Hudalla has delivered presentations all over the world in his areas of expertise, including analytical testing specific to medical cannabis.
Comparison of the Anti-Tumor Efficacy of a Whole-Plant Extract vs. Pure THC in Preclinical Models of HER2-Positive Breast Cancer
Comparison of the anti-tumor efficacy of a whole-plant extract vs. pure THC in preclinical models of HER2-positive breast cancer.
Mara Gordon is Founder, Aunt Zelda’s, Calla Spring Wellness, and Zelda Therapeutics. Mara specializes in the development of treatment protocols utilizing Bio Pharmaceutical grade cannabis extracts for seriously ill patients in California. She co-founded Aunt Zelda’s, Calla Spring Wellness, and Zelda Therapeutics in order to provide real outcomes for patients with serious diseases.
Prior to Aunt Zelda’s, Mara worked as a process engineer, helping Fortune 500 companies create intelligent software by utilizing the Rational Unified Process. This experience has enabled her to take a detailed and scientific approach to utilizing cannabis as a Biopharmaceutical-grade treatment.
Gordon sits on the boards of Zelda Therapeutics, Daya Foundation, Leaf of Life Holdings International, and Hmbldt. She has presented at multiple CME-accredited medical conferences, including Patients Out of Time 2014, 2016, delivered 3.5 hour courses along with Drs. Cristina Sanchez, Manuel Guzman, Donald Abrams, and Joe D. Goldstrich. Gordon has spoken at medical cannabis conferences in Australia, Costa Rica, Chile, Colombia, the Czech Republic, Israel, as well as numerous events throughout the USA and worldwide. These include CannMed 2016, CannaTech in Israel, and Medical Marijuana for Professionals 2014 and 2016 in CO. Her work is featured in the upcoming documentaries, “Weed the People”, “Mary Janes: Women of Weed”, and in Joe Dolce’s book, “Brave New Weed”. Mara resides in California.
A Mother’s Story: What is the Drug War, Really?
As a nation, our war on drugs isn’t really about drugs. Rather, it’s about our government’s expansion and intrusion into our lives. Learn about the devastation the drug war wreaks and how it assaults our freedoms and protections while feeding the United States prison industry. Learn more at FreeRoss.org
Lyn Ulbricht is the mother of Ross Ulbricht, who was given a double life sentence without parole for all non-violent charges for his role in the Silk Road website. At sentencing the judge made it clear that this sentence was to be a warning to others as regards the government’s drug war. Ross is appealing this excessive sentence as well as his conviction and trial violations, including precluded evidence, blocked defense witnesses and important constitutional issues.
Since Ross’ arrest Lyn has strived to direct awareness beyond the sensationalism of the case to the important precedents and issues at stake. She has become known as an advocate for constitutional protections, individual freedom and has spoken out against the failed war on drugs. Lyn has spoken at numerous events, both in the US and internationally; appeared on a range of TV, radio and podcast shows, including Reason TV, CNN, HuffPost Live and Fox; and conducted many interviews with both major and alternative media, including the New York Times, Wall Street Journal, Forbes and The Guardian. She is also prominently featured in the documentary Deep Web.
When not working to raise awareness, Lyn focuses on raising funds for Ross’s appeal through www.freeross.org.