4th International Medical Cannabis Conference (CannX 2019)
Tel Aviv, Israel, September 9–10, 2019
Dr. Adi Aran
Director of the Neuro-Pediatric Unit, Shaare Zedek Medical Center, Israel
Prof. Gil Bar-Sela
Head, Cancer Center, Emek Medical Center Afula, Israel
Dr. Nirit Bernstein
Principle Research Scientist, Plant Physiology and Nutrition Institute of Soil Water and
Environmental Sciences, Volcani Center, Israel
Prof. Lumir Hanus
Chief Scientist, Lumir Lab, Associate Professor, Palacký University, Jerusalem
Biotechnology Park, Hebrew University, Ein Kerem Campus, Senior Fellow, IEHP, Thomas
Jefferson University, Philadelphia, USA, Professor Chaver and Research Fellow, Hebrew
University (Ret.) Institute for Drug Research, School of Pharmacy, Faculty of Medicine,
Hebrew University, Israel
Dr. Shaul Lev-Ran, MHA
Deputy Director, Lev Hasharon Medical Center and Director of Addiction Medicine and
Dual Disorders Clinic, Lev Hasharon Medical Center, Sackler Faculty of Medicine, Tel Aviv
Cannabis Consulted Breeder, Israel
Dr. David (Dedi) Meiri
Head of Scientific Advisory Committee Assistant Professor, Heads the “Laboratory of
Cancer Biology and Cannabinoid Research” Technion, Institute of Technology, Israel
Dr. Yossi (Joseph) Tam
Head, Obesity and Metabolism Laboratory, The Institute for Drug Research, Faculty of
Medicine, Director, Multidisciplinary Center on Cannabinoid Research, The Hebrew
University of Jerusalem, Israel
Medical Cannabis & Cannabinoids Published online: September 3, 2019
Doi : 10.1159/000502323
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Science – Innovations in Science and Medicine
Kinematic Signatures of Cannabinoids in 3D Motion Capture in Mice
B. Ignatowska-Jankowska1, A. Kuck1, M.Y. Uusisaari1
1Okinawa Institute of Science and Technology, Neuronal Rhythms in Movement Unit, Okinawa, Japan
One of most pronounced behavioral effects of cannabinoid CB1 receptor activation is inhibitory effect on locomotor activity. However, effects of cannabinoids on subtle motor behavior have not been extensively studied. We hypothesize that at low doses that do not produce significant somatic effects but are known to evoke interoceptive effects, cannabinoids will cause changes in body kinematics during natural behavior.
We utilized marker-based, high-speed, high-resolution 3D motion capture system (Qualisys) to track movement trajectories of mice with high spatiotemporal precision. The adult male C57BL6 mice (n = 4–10 per group, within-subject design) were administered CP55,940 (0.03, 0.1, 0.3 mg/kg) or vehicle (ethanol, Kolliphor® EL, saline, at 1:1:18 ratio) and behaviorally assessed: a) in a familiar open field, b) in a novel open field, c) on a vertical wire mesh (climbing task) d) on a horizontal wire. Parameters measured included gait analysis (step height, length, width, velocity, duration etc.), 3D trajectories of markers, assessment of speed, distance and activity index (average velocity of all markers).
With this approach we observed changes in locomotor activity and gait characteristics with low doses of CP55,940. Preliminary data indicate that mice took shorter steps at doses that did not lead to catalepsy, hypothermia, analgesia or decrease in total distance traveled. Low-level catalepsy, hypothermia, analgesia or significant reduction in distance traveled were observed only at 0.3 mg/ kg. Interestingly, while marked reduction in distance traveled was observed following dose of 0.3 mg/kg in the open field, no reduction in locomotor activity was seen in the climbing task. Also, the effects of CP55,940 in climbing and open field tasks differed. At 0.1 mg/kg locomotion was enhanced (as measured by increased activity index and distance traveled) during climbing but such effect was not observed in the open field.
The results indicate that step characteristics is a sensitive indicator of kinematic alternation following CP55,940 and that cannabinoid signaling affects locomotor activity in a task-dependent fashion. Precise movement analysis as described here could be useful in development of cannabinoid-based treatments for neurological and pain-related disorders both to assess therapeutic effects and untoward effects on fine motor control.
An Approach to Dosing: The Cannabis Oil in Pain Effectiveness (COPE) Trial
M. Slaven1, M. Levine1, S. Parpia1, E. Shaw1
1McMaster University, Oncology, Hamilton, Canada
Background: During the cancer journey, 80–90% of people experience moderate to severe pain. Narcotics are the main stay of pharmacologic pain management. However, they are often associated with significant side effects and their safety profile is of concern. Although, the Canadian Government has legalized cannabis, there is a lack of information on dosing for pain management.
Objective: The overall goal of our research is to develop a dosing regimen for oral cannabis.
Methods: Cancer patients whose pain is poorly controlled by low to moderate doses of narcotics are eligible for this phase I/II trial. Compliance is assessed by a one-week run-in phase. Then cannabis oil capsules (containing both THC and CBD) are taken. Response is assessed based on either a 2-point decrease in worst average pain on the Brief Pain Inventory (BPI) 10-point scale or 25% decrease in narcotic use. Patients start at 1 capsule daily and then the number of capsules is titrated weekly (maximum, 6 per day) until patients achieve a sustained response which is defined by two consecutive weeks with a pain response. Patients with a sustained response can continue on that dose of cannabis for up to three months. The target sample size is 40 patients.
Results: The study began enrolling patients in August 2018 and is ongoing. Baseline data on the first 16 patients include: 5 men; mean age = 53; cancer sites (8 breast and 8 gastro-intestinal); mean Milligram Morphine Equivalent = 46 (range 15–114). To date, there have been 8 sustained responses on doses ranging from 2 capsules per day to 6 capsules per day. There were 2 non-responders at maximum study dose of 6 capsules. Three subjects discontinued the study agent early; two of whom because of side effects. There have been no serious adverse events.
Conclusion: Early results of our trial are promising. To our knowledge, our trial is the first of its kind, using plant-based medicinal cannabis oil. The results, although preliminary suggest an approach to guide clinicians and patients in evidence-based dosing and titrating cannabinoids.