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PAGE | I TH 26 ANNUAL SYMPOSIUM OF THE INTERNATIONAL CANNABINOID RESEARCH SOCIETY BUKOVINA POLAND JUNE 26 – JULY 1, 2016 TH 26 ANNUAL SYMPOSIUM OF THE INTERNATIONAL CANNABINOID RESEARCH SOCIETY BUKOVINA POLAND JUNE 26 – JULY 1, 2016 Symposium Programming by Cortical Systematics LLC Copyright © 2016 International Cannabinoid Research Society Research Triangle Park, NC USA ISBN: 978-0-9892885-3-8 These abstracts may be cited in the scientific literature as follows: Author(s), Abstract Title (2016) 26th Annual Symposium on the Cannabinoids, International Cannabinoid Research Society, Research Triangle Park, NC, USA, Page #. Funding for this conference was made possible in part by grant 5R13DA016280 from the National Institute on Drug Abuse. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government. ICRS Sponsors Government Sponsors National Institute on Drug Abuse Non- Profit Organization Sponsors Kang Tsou Memorial Fund 2016 ICRS Board of Directors Executive Director Cecilia Hillard, Ph.D. President Michelle Glass, Ph.D. President- Elect Matt Hill, Ph.D. Past President Steve Alexander, Ph.D. Secretary Sachin Patel, M.D., Ph.D. Treasurer Steve Kinsey, Ph.D. International Secretary Roger Pertwee, M.a., D.Phil. , D.Sc. Student Representative Natalia Małek, M.Sc. Grant PI Jenny Wiley, Ph.D. Managing Director Jason Schechter, Ph.D. 2016 Symposium on the Cannabinoids Conference Coordinators Steve Alexander, Ph.D. Michelle Glass, Ph.D. Cecilia Hillard, Ph.D. Natalia Małek, M.Sc. Jason Schechter, Ph.D. Katarzyna Starowicz Ph.D. Programme Committee Mary Abood, Ph.D. Steve Alexander, Ph.D. John Ashton, Ph.D. Piray Atsak, Ph.D. Heather Bradshaw, Ph.D. Michelle Glass, Ph.D. Scott Graham, Ph.D. Natasha Grimsey, Ph.D. Matt Hill, Ph.D. Mel Kelly, Ph.D. Steve Kinsey, Ph.D. Mary Lynch, Ph.D. Saoirse O’Sullivan, Ph.D. Sachin Patel, M.D., Ph.D. Roger Pertwee, D.Phil., D.Sc. Kiran Vemuri, Ph.D. Jenny Wiley, Ph.D. Karen Wright, Ph.D. Committee on Awards Steve Kinsey, Ph.D., Chair Aron Lichtman, Ph.D. Sachin Patel, M.D., Ph.D. Student Awards Committee Steve Alexander, Ph.D., Chair Eliot Gardner, Ph.D. Mechoulam Award Committee Mary Abood, Ph.D. Francis Barth, Ph.D. Benjamin Cravatt, Ph.D. Vincenzo Di Marzo, Ph.D. Cecilia Hillard, Ph.D. Allyn Howlett, Ph.D. John Huffman, Ph.D. George Kunos, M.D., Ph.D. Gerard Le Fur, Ph.D. Aron Lichtman, Ph.D. Beat Lutz, Ph.D. Ken Mackie, M.D. Alex Makriyannis, Ph.D. Roger Pertwee, D.Phil. , D.Sc. Raj Razdan, Ph.D. Patti Reggio, Ph.D. Murielle Rinaldi- Carmona, Ph.D. 26TH Annual Symposium of the International Cannabinoid Research Society 26 June - 1 July, 2016 Bukovina, Poland S C H E D U L E O F E V E N T S Sunday, 26 June 16:00 – 18:00 REGISTRATION (Hotel Bukovina, Bukowina Tatrzanska) 18:30 – 20:00 WELCOME RECEPTION DAY 1: Monday, 27 June 08:15 - 08:30 WELCOME AND OPENING REMARKS (Hotel Bukovina) 08:30 – 10:00 ORAL SESSION 1: Medicinal Cannabis I 10:00 – 10:30 COFFEE BREAK 10:30 – 11:00 ICRS CAREER ACHIEVEMENT AWARD 11:00 – 12:15 ORAL SESSION 2: Endocannabinoid Transport / Dynamics 12:15 – 13:30 LUNCH/NIDA Trainee lunch 13:30 – 14:45 ORAL SESSION 3: Cardiovascular System 14:45 – 15:30 ORAL SESSION 4: Behavioural Neuroscience 1 – Pain and Sleep 15:30 – 16:00 COFFEE BREAK 16:00 – 16:45 ORAL SESSION 4 (continued) 16:45 – 17:00 BREAK 17:00 – 19:30 ORAL SESSION 5: Focus on CBD 19:30 – DINNER DAY 2: Tuesday, 28 June 08:30 – 10:30 ORAL SESSION 6: Focus on CB2 10:30 – 11:00 COFFEE BREAK 11:00 – 12:00 ICRS PRESIDENTIAL ADDRESS: Moving from Mechanisms of GPCR Functionality to New Drugs 12:00 – 13:00 LUNCH 13:00 – 15:00 ORAL SESSION 7: Receptors, Probes and Signalling 15:00 – 17:15 COFFEE & POSTER SESSION 1 17:15 – 19:30 ORAL SESSION 8: Neuroprotection / Neuroinflammation / Neurogenesis 19:30 – DINNER DAY 3: Wednesday, 29 June 08:30 – 10:15 ORAL SESSION 9: Metabolism, Endocrine, Diabetes 10:15 – 10:45 COFFEE BREAK 10:45 – 12:15 ORAL SESSION 10: Cannabis, Medicinal 12:15 – 13:00 KANG TSOU MEMORIAL LECTURE: Human EXosome CompleX in Health and Disease 13:00 – 14:00 LUNCH 14:00 – OUTING DAY 4: Thursday, 30 June 08:30 – 09:30 ORAL SESSION 11: Addiction 09:30 – 10:00 YOUNG INVESTIGATOR AWARD PRESENTATION: Endocannabinoids as Homeostatic Signal Counteracting Adverse Effects of Stress 10:00 – 10:30 COFFEE BREAK 10:30 – 11:45 ORAL SESSION 12: Behavioural Neuroscience II – Anxiety, Stress 11:45 – 13:00 LUNCH 13:00 – 15:00 POSTER SESSION 2 15:00 – 16:15 ORAL SESSION 13: Endocannabinoid Metabolism 16:15 – 16:45 COFFEE BREAK 16:45 – 17:45 ORAL SESSION 13 (continued) 17:45 – 20:00 ICRS BUSINESS MEETING 20:00 – AWARDS CEREMONY & ICRS BANQUET Friday, 1 July DEPARTURE th Registration: June 26 , 2016, 16.00 – 18.00 Hotel Bukovina, Bukowina Tatrzanska Welcome Reception: 18.30 – 20.00 Day 1 Monday, June 27th Breakfast at your accommodations Welcome and Opening Remarks 8.15 Hotel Bukovina - Sala Kongresowa Oral Session 1. Medicinal Cannabis I CHAIRS: DROR ROBINSON AND MARK WARE Mark A. Ware, Julie Desroches, William PHARMACOVIGILANCE OF Barakett, Pierre MEDICAL CANNABIS: PRELIMINARY 8.30 1 Beaulieu, Andrée RESULTS FROM THE QUEBEC Néron, Yola Moride CANNABIS REGISTRY and Antonio Vigano EFFECT OF CANNABIS USE ON 8.45 Dror Robinson SEVERITY OF CHRONIC LOW 2 BACK PAIN AND SCIATICA SELF-REPORTED MEDICAL CANNABIS ACCESS, USE, Philippe Lucas AND SUBSTITUTION FOR 9.00 3 and Zach Walsh OTHER SUBSTANCES IN 301 CANADIAN MEDICAL CANNABIS PATIENTS Lihi Bar-Lev Schleider, Raphael Mechoulam, EPIDEMIOLOGICAL 9.15 Inbal Sikorin, Timna CHARACTERISTICS OF PATIENTS 4 Naftali, Zvi Bentwich TREATED WITH MEDICAL CANNABIS and Victor Novack TOWARDS A NATURALISTIC Lee Saynor, CHARACTERIZATION OF A MEDICAL 9.30 Kunal Sudan 5 CANNABIS POPULATION: and Henry J. Moller EMERGING CANADIAN DATA Mikael A. Kowal THE DEVELOPMENT OF 9.45 6 and Arno Hazekamp A CANNABIS PLACEBO 10.00 Coffee Break ICRS Career Achievement Award ANANDAMIDE UPTAKE, TRANSPORT AND INACTIVATION: STUDIES BRIDGING TWO CENTURIES 10.30 Dale Deutsch, Ph.D. Department of Biochemistry and Cell Biology Stony Brook University, Stony Brook, NY 11794, USA CHAIR: Allyn Howlett Oral Session 2. Endocannabinoid Transport / Dynamics CHAIRS : Martin Kaczocha and Matt Hill Jennifer Bialecki, Nicholas L. Weilinger, PANNEXIN-1 MODULATES Haley Vecchiarelli, GLUTAMATERGIC TRANSMISSION 11.00 7 Alexander W. Lohman, BY REGULATING SYNAPTIC Matthew N. Hill ANANDAMIDE CONCENTRATION and Roger J. Thompson Matthew W. Elmes, REGULATION OF CANNABINOID 11.15 Dale G. Deutsch ACTIVITY BY HEPATIC FATTY 8 and Martin Kaczocha ACID BINDING PROTEINS Martin Kaczocha, Matthew W. Elmes, Keith Studholme, FATTY ACID BINDING PROTEINS Jeremy T. Miyauchi, 11.30 MEDIATE RETROGRADE 9 Stella E. Tsirka, ENDOCANNABINOID SIGNALING Dale G. Deutsch, Panayotis K. Thanos, and Samir Haj-Dahmane Yao Chen, Xiaojie Liu, Casey R. Vickstrom, NEURONAL AND ASTROCYTIC Michelle J. Liu, MONOACYLGLYCEROL LIPASE LIMIT 11.45 10 Andreu Viader, THE SPREAD OF ENDOCANNABINOID Benjamin F. Cravatt SIGNALING IN THE CEREBELLUM and Qing-song Liu STEROL CARRIER PROTEIN 2 Cecilia J. Hillard DELETION ENHANCES FEAR 12.00 and Elizabeth EXTINCTION THROUGH 11 Sabens Liedhegner MODULATION OF THE ENDOCANNABINOID SYSTEM Lunch 12.15 NIDA LUNCH & MENTORING Oral Session 3. Cardiovascular System CHAIRS: SAOIRSE O’SULLIVAN AND VANESSA HO Eugen Brailoiu, NOVEL EFFECTS OF CANNABIDIOL 13.30 G. Cristina Brailoiu 12 ON NUCLEUS AMBIGUUS NEURONS and Mary E. Abood Barbara Malinowska, DIFFERENT EFFECTS OF CHRONIC Anna Pędzińska-Betiuk, ADMINISTRATION OF THE FATTY Jolanta Weresa, ACID AMIDE HYDROLAZE INHIBITOR Michał Biernacki, 13.45 URB597 ON CARDIAC PERFORMANCE 13 Marek Toczek, AND OXIDATIVE STRESS IN Marta Baranowska- NORMOTENSIVE AND Kuczko and Elżbieta HYPERTENSIVE RATS Skrzydlewska Catherine T. Choy, PROTECTIVE EFFECTS OF FAAH 14.00 Stephen P Alexander SUBSTRATES ON AGE-RELATED 14 and W.S. Vanessa Ho ENDOTHELIAL DYSFUNCTION CANNABINOID RECEPTOR 2 Rajesh Mohanraj, Partha ACTIVATION ALLEVIATES Mukhopadhyay, Sandor 14.15 DIABETES-INDUCED CARDIAC 15 Batkai, Zoltan Varga DYSFUNCTION, INFLAMMATION, and Pal Pacher OXIDATIVE STRESS AND FIBROSIS Eilidh E McNaughton, ROLE OF GPR55 AND GPR18 Catherine T. Choy, RECEPTORS IN THE VASCULAR 14.30 16 Charles E Sudlow ACTIONS OF ENDOCANNABINOIDS and W.S. Vanessa Ho AND RELATED LIPIDS Oral Session 4. Behavioural Neuroscience I - Pain and Sleep CHAIRS: Aron Lichtman and Sara Jane Ward ROLE OF HYPOTHALAMIC WAKE Xiaolong Sun, Ning Gu 14.45 CIRCUITRY IN CANNABINOID 17 and Xia Zhang MODULATION OF SLEEP Daniel J. Morgan, Matthew B. Yuill, MECHANISMS OF TOLERANCE TO 15.00 Michael L. Zee, Δ9-THC IN RODENT MODELS OF 18 Rebecca LaFleur PATHOLOGICAL PAIN and Josée Guindon Jenny Wilkerson, Travis Grim, Rehab Abdullah, DIACYLGLYCEROL LIPASE ALPHA: 15.15 Daisuke Ogasawara, INFLAMMATORY AND 19 Benjamin F. Cravatt NEUROPATHIC PAIN RELIEF IN MICE and Aron H. Lichtman 15.30 Coffee Break Alyssa M Myers, SINGLE AND COMBINATION Kirsten King, Ariele EFFECTS OF CANNABINOIDS 16.00 Soroka-Monzo, Ronald 20 ON NEUROPATHIC PAIN Tuma, Ellen A Walker AND COGNITION and Sara Jane Ward Christopher R. McCurdy, SIGMA RECEPTOR BLOCKADE Lisa L. Wilson, 16.15 POTENTIATES THE ANALGESIC 21 Jacqueline Morris, EFFECTS OF CANNABINOIDS Jennifer M. Miller and Stephen J. Cutler Lawrence M. Carey, A PRO-NOCICEPTIVE PHENOTYPE Richard A. Slivicki, REVEALED IN MICE LACKING THE Emma Leishman, Ben 16.30 ANANDAMIDE HYDROLYZING 22 Cornett, Ken Mackie, ENZYME FATTY-ACID AMIDE Heather Bradshaw and HYDROLASE Andrea G. Hohmann 16.45 Break Oral Session 5. Focus on CBD CHAIRS: JOHN ASHTON AND ALESSIA LIGRESTI Ronald Tuma, Hongbo Li, Weimin Kong, TARGETING SPINAL CORD INJURY- 17.00 Christina Chambers, ASSOCIATED NEUROPATHIC PAIN 23 Doina Ganea WITH CANNABIDIOL and Sara Jane Ward James T.
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  • Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System

    Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System

    International Journal of Molecular Sciences Review Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System Ana Lago-Fernandez , Sara Zarzo-Arias, Nadine Jagerovic * and Paula Morales * Medicinal Chemistry Institute, Spanish Research Council, Juan de la Cierva 3, 28006 Madrid, Spain; [email protected] (A.L.-F.); [email protected] (S.Z.-A.) * Correspondence: [email protected] (N.J.); [email protected] (P.M.); Tel.: +34-91-562-2900 (P.M.) Abstract: Cannabinoids have shown to exert their therapeutic actions through a variety of targets. These include not only the canonical cannabinoid receptors CB1R and CB2R but also related orphan G protein-coupled receptors (GPCRs), ligand-gated ion channels, transient receptor potential (TRP) channels, metabolic enzymes, and nuclear receptors. In this review, we aim to summarize reported compounds exhibiting their therapeutic effects upon the modulation of CB1R and/or CB2R and the nuclear peroxisome proliferator-activated receptors (PPARs). Concomitant actions at CBRs and PPARα or PPARγ subtypes have shown to mediate antiobesity, analgesic, antitumoral, or neuroprotective properties of a variety of phytogenic, endogenous, and synthetic cannabinoids. The relevance of this multitargeting mechanism of action has been analyzed in the context of diverse pathologies. Synergistic effects triggered by combinatorial treatment with ligands that modulate the aforementioned targets have also been considered. This literature overview provides structural and pharmacological insights for the further development of dual cannabinoids for specific disorders. Citation: Lago-Fernandez, A.; Zarzo-Arias, S.; Jagerovic, N.; Keywords: PPAR; cannabinoids; CB1R; CB2R; FAAH; multitarget; endocannabinoid system Morales, P. Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System.
  • Cyproterone Acetate in the Management of Polycystic Ovary Syndrome

    Cyproterone Acetate in the Management of Polycystic Ovary Syndrome

    CORE Metadata, citation and similar papers at core.ac.uk Provided by Journal of Rawalpindi Medical College Journal of Rawalpindi Medical College (JRMC); 2018;22(3): 262-265 Original Article Comparison of Metformin and Ethinyl Estradiol- Cyproterone Acetate in the Management of Polycystic Ovary Syndrome Sadaf Ajaib, Maimoona Ali Department of Gyanecology and Obstetrics, Military Hospital, Rawalpindi Abstract predisposition. The rudimentary quandary is in the hypothalamic pituitary axis leading to incremented Background: To compare ethinyl estradiol- LH/FSH ratio1. The cumulation of anovulation and cyproterone acetate and metformin for polycystic hyperandrogenism denotes the classic form of PCOS ovarian syndrome in terms of mean hirsutism score which exhibits the adverse metabolic phenotype of the and waist hip ratio (WHR). syndrome. Clinical and biochemical features of these Methods: A total of 120 patients (60 patients in patients may vary well-according to race, ethnicity and each group) were included in the study. Group-A the diagnostic criteria used. 2 Hyper-androgenism received metformin 500mg and group-B was given may result in acne and hirsutism. Hirsutism afflicts 5- ethinyl estradiol 35 mg as treatment of polycystic 15% of females and is a paramount denouement of ovary disease (PCOD), mean hirsuitism and waist to background hyper-androgenemia. The manifestations hip ratio was measured at 6months. Hirsuitism was of polycystic ovary syndrome depends largely on measured according to Ferriman Gallway score. obesity, which exacerbates the reproductive and Circumferences were measured with an metabolic aberrations in women tormented by PCOs. anthropometric tape over light clothing. Waist girth Further studies conclude that obesity might promote was measured at the minimum circumference the phenotypic expression of PCOS in a population at between the iliac crest and the rib cage and hip girth risk of this disease.1,2 at the maximum width and their ratio was calculated Well known risk determinants for cardiovascular as baseline and after 6 months of treatment.
  • Mitochondrial ADP/ATP Exchange Inhibition

    Mitochondrial ADP/ATP Exchange Inhibition

    www.nature.com/scientificreports OPEN Mitochondrial ADP/ATP exchange inhibition: a novel off-target mechanism underlying ibipinabant- Received: 27 March 2015 Accepted: 27 August 2015 induced myotoxicity Published: 29 September 2015 Tom J. J. Schirris1,2, Tina Ritschel3, G. Herma Renkema2,4, Peter H. G. M. Willems2,5, Jan A. M. Smeitink2,4 & Frans G. M. Russel1,2 Cannabinoid receptor 1 (CB1R) antagonists appear to be promising drugs for the treatment of obesity, however, serious side effects have hampered their clinical application. Rimonabant, the first in class CB1R antagonist, was withdrawn from the market because of psychiatric side effects. This has led to the search for more peripherally restricted CB1R antagonists, one of which is ibipinabant. However, this 3,4-diarylpyrazoline derivative showed muscle toxicity in a pre-clinical dog study with mitochondrial dysfunction. Here, we studied the molecular mechanism by which ibipinabant induces mitochondrial toxicity. We observed a strong cytotoxic potency of ibipinabant in C2C12 myoblasts. Functional characterization of mitochondria revealed increased cellular reactive oxygen species generation and a decreased ATP production capacity, without effects on the catalytic activities of mitochondrial enzyme complexes I–V or the complex specific-driven oxygen consumption. Using in silico off-target prediction modelling, combined with in vitro validation in isolated mitochondria and mitoplasts, we identified adenine nucleotide translocase (ANT)-dependent mitochondrial ADP/ATP exchange as a novel molecular mechanism underlying ibipinabant-induced toxicity. Minor structural modification of ibipinabant could abolish ANT inhibition leading to a decreased cytotoxic potency, as observed with the ibipinabant derivative CB23. Our results will be instrumental in the development of new types of safer CB1R antagonists.
  • Potential Cannabis Antagonists for Marijuana Intoxication

    Potential Cannabis Antagonists for Marijuana Intoxication

    Central Journal of Pharmacology & Clinical Toxicology Bringing Excellence in Open Access Review Article *Corresponding author Matthew Kagan, M.D., Cedars-Sinai Medical Center, 8730 Alden Drive, Los Angeles, CA 90048, USA, Tel: 310- Potential Cannabis Antagonists 423-3465; Fax: 310.423.8397; Email: Matthew.Kagan@ cshs.org Submitted: 11 October 2018 for Marijuana Intoxication Accepted: 23 October 2018 William W. Ishak, Jonathan Dang, Steven Clevenger, Shaina Published: 25 October 2018 Ganjian, Samantha Cohen, and Matthew Kagan* ISSN: 2333-7079 Cedars-Sinai Medical Center, USA Copyright © 2018 Kagan et al. Abstract OPEN ACCESS Keywords Cannabis use is on the rise leading to the need to address the medical, psychosocial, • Cannabis and economic effects of cannabis intoxication. While effective agents have not yet been • Cannabinoids implemented for the treatment of acute marijuana intoxication, a number of compounds • Antagonist continue to hold promise for treatment of cannabinoid intoxication. Potential therapeutic • Marijuana agents are reviewed with advantages and side effects. Three agents appear to merit • Intoxication further inquiry; most notably Cannabidiol with some evidence of antipsychotic activity • THC and in addition Virodhamine and Tetrahydrocannabivarin with a similar mixed receptor profile. Given the results of this research, continued development of agents acting on cannabinoid receptors with and without peripheral selectivity may lead to an effective treatment for acute cannabinoid intoxication. Much work still remains to develop strategies that will interrupt and reverse the effects of acute marijuana intoxication. ABBREVIATIONS Therapeutic uses of cannabis include chronic pain, loss of appetite, spasticity, and chemotherapy-associated nausea and CBD: Cannabidiol; CBG: Cannabigerol; THCV: vomiting [8]. Recreational cannabis use is on the rise with more Tetrahydrocannabivarin; THC: Tetrahydrocannabinol states approving its use and it is viewed as no different from INTRODUCTION recreational use of alcohol or tobacco [9].