Cannabis-Induced Anxiety Disorder in the Emergency Department.

BACKGROUND: In December 2018, Michigan became the 10th state to legalize marijuana for adults. Since this law took effect, increased availability and use of cannabis in Michigan have led to increased emergency department (ED) visits associated with the drug's psychiatric effects. OBJECTIVES: To describe cannabis-induced anxiety disorder's prevalence, clinical features, and disposition in a community-based study. METHODS: This was a retrospective cohort analysis of consecutive patients diagnosed with acute toxicity related to cannabis use (ICD-10 code F12). Patients were seen at seven EDs over a 24-month study period. Data collected included demographics, clinical features, and treatment outcomes in ED patients who met the criteria for cannabis-induced anxiety disorder. This group was compared to a cohort experiencing other forms of acute cannabis toxicity. Chi-squared and t-tests were used to compare these two groups across key demographic and outcome variables. RESULTS: During the study period, 1135 patients were evaluated for acute cannabis toxicity. A total of 196 patients (17.3%) had a chief complaint of anxiety, and 939 (82.7%) experienced other forms of acute cannabis toxicity, predominantly symptoms of intoxication or cannabis hyperemesis syndrome. Patients with anxiety symptoms had panic attacks (11.7%), aggression or manic behavior (9.2%), and hallucinations (6.1%). Compared to patients presenting with other forms of cannabis toxicity, those with anxiety were likelier to be younger, ingested edible cannabis, had psychiatric comorbidities, or had a history of polysubstance abuse. CONCLUSIONS: Cannabis-induced anxiety occurred in 17.3% of ED patients in this community-based study. Clinicians must be adept in recognizing, evaluating, managing, and counseling these patients following cannabis exposure.

Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status.

Poly (ADP-ribose) polymerase inhibitors (PARPi) have proven to be beneficial to patients with metastatic breast cancer with BRCA1/2 (BReast CAncer type 1 and type 2 genes) mutations. However, certain PARPi in pre-clinical studies have been shown to inhibit cell growth and promote the death of breast cancer cells lacking mutations in BRCA1/2. Here, we examined the inhibitory potency of 13 different PARPi in 12 breast cancer cell lines with and without BRCA-mutations using cell viability assays. The results showed that 5 of the 8 triple-negative breast cancer (TNBC) cell lines were susceptible to PARPi regardless of the BRCA-status. The estrogen receptor (ER) negative/ human epidermal growth factor receptor 2 (HER2) positive (ER-/HER2+) cells, SKBR3 and JIMT1, showed high sensitivity to Talazoparib. Especially JIMT1, which is known to be resistant to trastuzumab, was responsive to Talazoparib at 0.002 µM. Niraparib, Olaparib, and Rucaparib also demonstrated effective inhibitory potency in both advanced TNBC and ER-/HER2+ cells with and without BRCA-mutations. In contrast, a BRCA-mutant TNBC line, HCC1937, was less sensitive to Talazoparib, Niraparib, Rucaparib, and not responsive to Olaparib. Other PARPi such as UPF1069, NU1025, AZD2461, and PJ34HCl also showed potent inhibitory activity in specific breast cancer cells. Our data suggest that the benefit of PARPi therapy in breast cancer is beyond the BRCA-mutations, and equally effective on metastatic TNBC and ER-/HER2+ breast cancers.

PARP Inhibitors as a Therapeutic Agent for Homologous Recombination Deficiency in Breast Cancers.

Poly (ADP-ribose) polymerases (PARPs) play an important role in various cellular processes, such as replication, recombination, chromatin remodeling, and DNA repair. Emphasizing PARP's role in facilitating DNA repair, the PARP pathway has been a target for cancer researchers in developing compounds which selectively target cancer cells and increase sensitivity of cancer cells to other anticancer agents, but which also leave normal cells unaffected. Since certain tumors (BRCA1/2 mutants) have deficient homologous recombination repair pathways, they depend on PARP-mediated base excision repair for survival. Thus, inhibition of PARP is a promising strategy to selectively kill cancer cells by inactivating complementary DNA repair pathways. Although PARP inhibitor therapy has predominantly targeted BRCA-mutated cancers, this review also highlights the growing conversation around PARP inhibitor treatment for non-BRCA-mutant tumors, those which exhibit BRCAness and homologous recombination deficiency. We provide an update on the field's progress by considering PARP inhibitor mechanisms, predictive biomarkers, and clinical trials of PARP inhibitors in development. Bringing light to these findings would provide a basis for expanding the use of PARP inhibitors beyond BRCA-mutant breast tumors.