Elyad Davidson

Hadassah-Hebrew University Medical Center, Israel

  • Attending physician, Department of Anesthesiology CCM and Pain management
  • Director, Pain Relief Unit, Hadassah-Hebrew University Medical Center
  • Professor, Hebrew University-Hadassah School of Medicine
  • Member, Board of Directors, Hebrew University Center for Research on Pain
  • Member, Board of Directors, Israel Pain Association
  • Chairman, Board of Directors, Acute Pain Section, Israel Society of Anesthesiology
  • Director, Jerusalem Pain Forum
  • Member, The multidisciplinary center on cannabinoid research- Hebrew University
  • Past Chairman of IPA (Israel Pain Association) during 2017-2019
  • Member , Board of IPA (Israel Pain Association)
  • Council- Israel representative, Board member EFIC ( European Pain Federation)

 

Research on Medical Cannabis

Cannabis and nociception

Cannabis has been used in medicine for centuries, for various indications, but substantial progress in biomedical research to better understand the exogenous and endogenous cannabinoids only began with discovery of the chemical structure of tetrahydrocannabinol (THC) and additional cannabinoids in the 1970s. The analgesic effect of cannabinoids has been demonstrated by extensive preclinical research, but in-depth human studies have been less consistent. Our initial experience with sublingual THC in patients with chronic nonmalignant pain demonstrated variable responses.1 However, in our more recent study examining the effect of long-term cannabis treatment on pain and functional outcomes, in one of the largest patient series in the literature, we found that cannabis treatment significantly improved pain control and sleep, as well as physical, social, and emotional quality-of-life (QOL) parameters. In addition, patients have reported reduced use of opioids. A manuscript reporting our findings has been published.2

Cannabis is consumed recreationally or for medical reasons in 5–15% of the Israeli population; however, the perioperative effects of cannabis use on anesthesia and surgery are poorly understood. We have received a grant and preliminary IRB approval to study the effects of a cannabis extract as anesthetic premedication on perioperative anxiety, anesthetic depth and on postoperative pain, nausea, and vomiting. Based on primary results of this study we have submitted our findings regarding effects of cannabis extract premedication on anesthetic depth in addition we presented our primary results in annual meeting of the Israel society of Anaesthesiology. This pilot study provides the first evidence that cannabinoids may affect bispectral index (BIS is a standard -anesthetic depth index monitor). We speculate that the cannabinoid-induced increase in BIS may be the result of changes in EEG activity rather than an indication of a shallower anesthetic state.3

 

 

Forms of cannabis administration

In collaboration with Prof A. Hoffman of the Hebrew University School of Pharmacy, we conducted studies examining the bioequivalence of oral administration vs oral spray of a cannabinoid combination. These trials in healthy human subjects were a PK-PD study using QST, cold pressure tests, and computerized task performance rapidity tests. We have analyzed the PK data and summarized them in two publications.4, 5 We are analyzing the pharmacodynamic data and notice primarily exciting findings to be published.  Based on our preliminary analysis, we are cautiously optimistic that we may be able to show benefit from a new form of cannabis administration compared with existing protocols.

 

Present & Future Projects

  1. We continue to collect data from about 600 patients who are managed with medical cannabis in the pain clinic using a combination of questionnaires and medical chart review to assess pain control, QOL, and medical outcome measures. We hope this research will provide a more complete and rigorous assessment of the effects of prolong use of cannabis in humans.
  2. Following our primary results obtained from the – Pilot study examining the effects of a cannabis extract as anesthetic premedication on perioperative anxiety, anesthetic depth and on postoperative pain, nausea, and vomiting (cannapremed study). We continuing to collect data in a larger group of patients (100) to confirm the results and examine the other endpoints .6
  3. We have approval from ethics comity and from Israel ministry of health to conduct a national study looking into disturbance of mental health in cannabis users. Currently there are more than 100,000 individuals with Ministry of Health approval for the use of medical cannabis in Israel. This study involves collaboration with psychiatrist’s, pharmacologist’s epidemiologist and health providers in Israel (kupot cholim).
  4. We have received ethics comity approval and have collected over 70 patients in a study, looking on the effect of cannabis extract on acute radicular pain and on analgesics requirement: a double-blinded, randomized, 24 hours follow-up study (100 patients). These patients, with neuropathic pain, will receive oral cannabis or placebo and will be able to administer morphine via a patient controlled analgesia pump (PCA). This project will be executed with scientific collaborators form Bazelet group.

 

  1. Cannabis is consumed recreationally or for medical reasons in 5–15% of the Israeli population. Since cannabis, use may have various effects on perioperative and anesthetic course; we designed a study examining these effects. We have received ethics comity approval and have already included 60 patients in this study. We aim to collect 300 patients.
  2. We have received ethics comity approval for a study, looking into the effect of cannabinoids on symptoms of neurogenic bladder.
  3. We have received ethics comity approval for a study, looking into the effect of addition of terpenes to chronic pain patients receiving medical cannabis. This project is planned and will be executed with scientific collaborators form Bazelet group.
  4. We have received ethics comity approval for a study looking into cardiovascular effects of cannabis exposure in patients treated with Anthracycline.
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