A large Australian longitudinal cohort registry demonstrates sustained safety and efficacy of oral medicinal cannabis for at least two years.

INTRODUCTION: Oral medicinal cannabis (MC) has been increasingly prescribed for a wide range of clinical conditions since 2016. Despite an exponential rise in prescriptions and publications, high quality clinical efficacy and safety studies are lacking. The outcomes of a large Australian clinical electronic registry cohort are presented. METHODS: A prospective cannabis-naïve patient cohort prescribed oral MC participated in an ongoing longitudinal registry at a network of specialised clinics. Patient MC dose, safety and validated outcome data were collected regularly over two years and analysed. RESULTS: 3,961 patients (mean age 56.07 years [SD 19.08], 51.0% female) with multimorbidity (mean diagnoses 5.14 [SD 4.08]) and polypharmacy (mean 6.26 medications [SD 4.61]) were included in this analysis. Clinical indications were for: chronic pain (71.9%), psychiatric (15.4%), neurological (2.1%), and other diagnoses (10.7%). Median total oral daily dose was 10mg for Δ9-tetrahydrocannabinol (THC) and 22.5mg for cannabidiol (CBD). A stable dose was observed for over two years. 37.3% experienced treatment related adverse events. These were graded mild (67%), moderate (31%), severe (<2%, n = 23) and two (0.1%) serious adverse events. Statistically significant improvements at a p value of <0.001 across all outcomes were sustained for over two years, including: clinical global impression (CGI-E, +39%: CGI-I, +52%; p<0.001), pain interference and severity (BPI, 26.1% and 22.2%; p<0.001), mental health (DASS-21, depression 24.5%, anxiety 25.5%, stress 27.7%; p<0.001), insomnia (ISI, 35.0%; p<0.001), and health status (RAND SF36: physical function, 34.4%: emotional well-being, 37.3%; p<0.001). Mean number of concomitant medications did not significantly change over 2 years (p = 0.481). CONCLUSIONS: Oral MC was demonstrated to be safe and well-tolerated for a sustained period in a large complex cohort of cannabis-naïve, multimorbid patients with polypharmacy. There was significant improvement (p<0.001) across all measured clinical outcomes over two years. Results are subject to limitations of Real World Data (RWD) for causation and generalisability. Future high quality randomised controlled trials are awaited.

Longitudinal Relationship between the Introduction of Medicinal Cannabis and Polypharmacy: An Australian Real-World Evidence Study.

Background: Recent studies recommend medicinal cannabis (MC) as a potential treatment for chronic pain (CP) when conventional therapies are not successful; however, data from Australia is limited. This real-world evidence study explored how the introduction of MC related to concomitant medication use over time. Long-term safety also was examined. Methods: Data were collected by the Emerald Clinics (a network of seven clinics located across Australia) as part of routine practice from Jan 2020 toJan 2021. Medications were classified by group: antidepressants, benzodiazepines, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and total number of medications. Adverse events (AEs) were collected at each visit and subsequently coded using the Medical Dictionary for Regulatory Activities version 23 into the system organ class (SOC) and preferred term (PT). A total of 535 patients were analyzed. Results: The most common daily oral dose was 10 mg for delta-9-tetrahydrocannabinol (THC) and 15 mg for cannabidiol (CBD). With the introduction of MC, patients' total number of medications consumed decreased over the course of one year; significant reductions in NSAIDs, benzodiazepines, and antidepressants were observed (p < .001). However, the number of prescribed opioid medications did not differ from baseline to the end of one year (p = .49). Only 6% of patients discontinued MC treatment during the study. A total of 600 AEs were reported in 310 patients during the reporting period and 97% of them were classified as nonserious. Discussion. Though observational in nature, these findings suggest MC is generally well-tolerated, consistent with the previous literature, and may reduce concomitant use of some medications. Due to study limitations, concomitant medication reductions cannot be causally attributed to MC. Nevertheless, these data underscore early signals that warrant further exploration in randomized trials.

Efficacy of scalp cooling in reducing alopecia in early breast cancer patients receiving contemporary chemotherapy regimens.

INTRODUCTION: Hair loss as a result of chemotherapy for early breast cancer (EBC) is a frequent and distressing side effect. Minimising hair loss may improve mood and body image. Our aim was to determine scalp cooling (SC) efficacy in EBC patients receiving contemporary chemotherapy regimen, to inform future patients choice to use SC or not. METHODS AND RESULTS: Prospective cohort study of 60 stage 1-3 EBC patients recommended to receive taxane or anthracycline-taxane chemotherapy regimens. The primary outcome was incidence of minimal hair-loss (MHL - defined as 60% Dean grade 1 or 2). Patients were categorised by chemotherapy (3 groups) and randomised 1:1 within each group to two scalp cooling temperature settings using the Dignitana Dignicap machine (secondary endpoint). Patients reported degree of hair loss using the Dean score on day 1 of each cycle and following the last chemotherapy. RESULTS: On an intention-to-treat basis, 33% of patients reported MHL, thus our primary endpoint was not achieved. Patients receiving taxane-only chemotherapy had the highest rate of MHL (45%). No other factors (including hair type, age, body weight, temperature setting) predicted for MHL. Patient-reported anxiety reduced significantly in all patients, but no difference was observed for depression or body image irrespective of degree of hair loss. SC-related adverse events were uniformly of low grade and all resolved. We would recommend the use of SC for all patients receiving taxane-based chemotherapy, with its use for those patients recommended for anthracycline-taxane regimens being made on an individual basis. Trial Registration anztr.org.au ACTRN12615001106527.