Nir Treves1, Noa Yakirevic2, Tal Bergman-Levy3, Rinat Yoffe3, Paola Roska4, Elyad Davidson5, Omer Bonne2, Ilan Matok1
1Division of Clinical Pharmacy, School of Pharmacy, The Hebrew University, Israel
2Department of Psychiatry, Hadassah Hebrew University Medical Center, Israel
3Mental Health Division, Ministry of Health, Israel
4Department of Anesthesia, Hadassah Hebrew University Medical Center, Israel
5Israeli Ministry of Health Department for the Treatment of Substance Abuse, Ministry of Health, Israel
Background: Although most cannabis use is recreational, cannabis is already approved for various medical indications. One of most controversial safety concerns regarding the use of cannabis is its association with mental illness, in particular, induction or exacerbation of psychosis and schizophrenia, cognitive compromise in adolescents, suicidal attempts and depression. That said, current available data concerning mental illness outcomes with regards to cannabis exposure is based mostly upon cross-sectional studies of recreational users of cannabis and is therefore subject to inherent limitations and weaknesses. Therefore, benefits and risks of medical cannabis use should be evaluated by meticulously designed studies comparing large and well-matched populations. The proposed study will enable, for the first time, to explore favorable and deleterious effects of medical cannabis drawing on a large population registry. Findings from the study will provide crucially needed data that could be immediately implemented in clinical practice, will contribute to the ongoing debate about legalization of recreational cannabis and may lay the groundwork for additional research.
Study objectives: To study the association between exposure to medical cannabis and the risk for mental illness, including the risk for psychotic episodes, anxiety and suicidal behavior in previously mentally healthy subjects, as well as prompt a relapse of these conditions in individuals with psychiatric history.
Data acquisition and Study design:
Data will be retrieved from three databases. The first is the Israeli Medical Cannabis Agency at the Ministry of Health. This database contains the names of all patients who were granted a license to use medical cannabis, the indications and symptoms for cannabis usage and the monthly and total amount dispensed, Socioeconomic grade based on AGAS. This database will be linked with databases extracted from computerized records of Health Service Providers containing socio-demographic information, medical diagnoses, medication, and additional clinical data, and the Israel Ministry of health Psychiatric hospitalizations database, documenting psychiatric hospitalizations and key measurements related to these hospitalizations.
Subjects exposed to medical cannabis will be compared to a clinically matched unexposed control group (excluding Post Traumatic Stress Disorder [PTSD] patients) in a cohort study design. We will compare the incidence rate and hazard ratios in the exposed group to the unexposed control group, adjusting for potential confounders.
We will also perform subgroup analysis: a subgroup of patients treated with medical cannabis for the indication of PTSD and pain will be matched to a control group consisting of patients with PTSD treated with opioids for pain, by high dimensional propensity score.
Another subgroup analysis will be performed on medical cannabis exposed patients in a case-crossover design. The combined information will be analyzed after encryption for data privacy purposes to conclusively determine the relationship between exposure to medical cannabis and mental illness.
Importance to Medicine: Findings from the study will provide crucially needed data that could be immediately implemented in clinical practice, will contribute to the ongoing debate about legalization of recreational cannabis and may lay the groundwork for additional research.