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.

¹Division of Clinical Pharmacy, School of Pharmacy, The Hebrew University

²Department of Psychiatry, Hadassah Hebrew University Medical Center

³Hebrew University-Hadassah Braun School of Public Health and Community Medicine, Jerusalem   

⁴Department of Anesthesia, Hadassah Hebrew University Medical Center

⁵MoreBetter LTD

Although cannabis products are marketed for mental-related conditions, one of the main concerns of cannabis use is its adverse mental effects. Studies suggest an association between cannabis use and the risk for mental diseases or exacerbation of existing mental conditions. This database study characterizes users who experienced negative mental emotions after cannabis exposure.

Methods: We used a self-report database of the ReleafApp by MoreBetter LTD, which enables users to track real-time cannabis user experience. From a list of 42 possible emotions and symptoms  on which the user may report, we focused on a group of negative mental emotions as an outcome that may indicate mental deterioration. Multivariable logistic regression models with mixed effects analyses were performed to study the association between user’s traits, cannabis products, and reporting negative mental emotions.

Results: 144,954 sessions of cannabis consumption were reported by 6,191 users. Females and non-binary gender were associated with an increased risk for negative mental emotions than males (OR=1.16, 95%CI: 1.05-1.28, OR=1.48, 95%CI: 1.26-1.34). Older age was associated with less negative mental emotions than young age (OR=0.88, 95%CI: 0.78-0.99, OR=0.71, 95%CI: 0.62-0.81, in 30-40 and 40-50, respectively compared to the age group of 18-30 years). New users were associated with an increased risk for negative mental emotions compared to experts (OR=1.35, 95%CI: [1.12-1.64]). Oral cannabis products were associated with negative mental emotions compared to flowers. Nevertheless, the experience of negative mental emotions was not associated with a change in the response to the cause for which the cannabis was used. In a cluster analysis, negative mental emotions were more correlated with one other than with other emotions. 

Conclusions: Cannabis use in females and non-binary users was associated with negative mental emotions. Oral cannabis products are also associated with negative mental emotions, compared to flowers products. Older age and previous experience with cannabis were associated with fewer negative mental emotions. Further studies should examine the abovementioned traits in the context of cannabis use and mental illness.

Division of Clinical Pharmacy, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.

Department of Development and Regeneration, KU Leuven, Leuven, Belgium 

Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium 

Department of Hospital Pharmacy, Erasmus MC University Medical Center, Rotterdam, the Netherlands 

Clinical Pharmacology Unit, Shamir Medical Center (Assaf Harofeh), Zerifin, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

The Autism Center, Alut, Shamir Medical Center (Assaf Harofeh), Zerifin

Despite the increased use of medical cannabinoids, the efficacy and safety of the treatment among children remain uncertain. The objective was to study the efficacy and safety of medical cannabinoids in children. The search included studies through 11-May-2020. Selection criteria included studies evaluating efficacy and safety outcomes of medical cannabinoids (tetrahydrocannabinol, cannabidiol and other cannabis derivatives) versus control in children, independently assessed by two reviewers. Eight studies were included, all of which are randomized controlled trials. Cannabidiol is associated with 50% reduction in seizures rate (Relative Risk (RR) = 1.69, 95% CI [1.20–2.36]) and caregiver global impression of change (Median Estimated difference = (− 1), 95%CI [− 1.39–(− 0.60)]) in Dravet syndrome, compared to placebo. While cannabidiol was associated with a reduction in reported seizure events (RR = 0.59, 95% CI [0.36–0.97]), no association was found in products contained also tetrahydrocannabinol (RR = 1.35, 95% CI [0.46–4.03]). Higher dose of cannabidiol was associated with decreased appetite (RR = 2.40, 95% CI [1.39–4.15]). A qualitative assessment suggests that medical cannabinoids might be associated with adverse mental events. In conclusion, cannabidiol is associated with clinical improvement in Dravet syndrome. However, cannabidiol is also associated with decreased appetite. Adverse mental events were reported as well, however, more research should be performed to assess well this outcome.