Experiences, patient interactions and knowledge regarding the use of cannabis as a medicine in a cohort of New Zealand doctors in an oncology setting.

PURPOSE OF STUDY: To explore the experiences, patient interactions and knowledge regarding the use of cannabis as a medicine in New Zealand doctors in an oncology setting. STUDY DESIGN: An observational cross-sectional survey undertaken between November 2019 and January 2020 across four secondary-care hospital oncology departments within New Zealand (Auckland, Wellington, Christchurch and Dunedin). Participants were a convenience sample of doctors; consultants, registrars, medical officers of special status and house surgeons working in oncology departments. Of 53 individuals approached, 45 participated (85% Response Rate). The primary outcome was reporteddoctor-patient interactions. Secondary outcomes included knowledge of cannabis-based products, their efficacy, prescribing regulations and educational access. RESULTS: Of 44 doctors, 37 (84%, 95% CI: 70 to 93) reported patient requests to prescribe cannabis-based products and 43 (98%, 95% CI: 88 to 100) reported patients using illicit cannabis for medical symptoms. Primary request reasons were pain, nausea/vomiting and cancer treatment. 33/45 (73%, 95% CI: 58 to 85) cited knowledge of at least one cannabis-based product and 27/45 (60%, 95% CI: 44 to 74) indicated at least one condition that had evidence of efficacy. 36/44 (82%, 95% CI: 67 to 92) expressed future prescribing concerns but all were willing to use a cannabis-based product developed with traditional medical provenance. CONCLUSION: In the oncology setting, patients are asking doctors about symptomatic and curative treatment with cannabis-based products. Doctors are not biased against the use of products showing medical provenance; however, NZ-specific clinical and regulatory guidelines are essential to support patient discussions and appropriate prescribing.

Cannabinoids in the Treatment of Insomnia Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND: Insomnia is associated with significant comorbidity, disability and impact on quality of life and, despite advances in pharmacotherapy and psychotherapy, remains a significant burden to society. Cannabinoids are gaining acceptance for use as medicines in the treatment of insomnia disorder. OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the efficacy of cannabinoids in the treatment of insomnia disorder. METHODS: We performed a systematic review of the PubMed, Cochrane Library, MEDLINE, and Cumulative Index to Nursing and Allied Health Literature Complete databases from inception to 5 December 2019, and again prior to data abstraction, for studies of cannabis-based products for the treatment of insomnia disorder in adults. Inclusion criteria were (1) clinical studies, (2) participants aged ≥ 18 years, (3) insomnia disorder either formally diagnosed against contemporaneous diagnostic criteria or quantified with validated instruments and (4) compared cannabis-based products with the standard of care, placebo or a sedative. No language restrictions were imposed. Non-primary research, animal studies and studies of cannabis-induced insomnia were excluded. Risk of bias was assessed using the RoB 2 tool for randomised controlled trials (RCTs) and Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) tool for non-randomized trials. Heterogeneity was assessed with the I2 statistic. RESULTS: A total of five studies (two RCTs and three non-randomised studies) with 219 study participants were included, of which three could be combined. The three non-randomised studies contributed data on the Pittsburgh Sleep Quality Index Questionnaire score, showing a favourable effect of cannabinoids at ≤ 4 weeks of follow-up (mean difference - 1.89 [95% confidence interval {CI} - 2.68 to - 1.10]; n = 176) and at 8 weeks of follow-up (mean difference - 2.41 [95% CI - 3.36 to - 1.46]; n = 166). One double-blind crossover RCT (n = 32) reported that, compared with amitriptyline, nabilone-a synthetic analogue to tetrahydrocannabinol (THC)-improved Insomnia Severity Index scores after 2 weeks of treatment (adjusted difference - 3.25 [95% CI - 5.26 to - 1.24]) and resulted in a more restful sleep as a sub-measure of the Leeds Sleep Evaluation Questionnaire (LSEQ) (difference 0.48 [95% CI 0.01-0.95]) but with no effect on overall sleep quality as measured by the LSEQ. In a single ascending-dose RCT (n = 9), THC reduced sleep-onset latency compared with placebo at 10 mg, 20 mg and 30 mg doses (mean difference - 43.00 min [95% CI - 82.76 to - 3.24], - 62.00 [95% CI - 103.60 to - 20.40] and - 54.00 [95% CI - 103.93 to - 4.07], respectively). All the included studies were assessed as poor quality, mainly due to small sample sizes, short treatment periods, uncertain clinical significance and high risk of bias. CONCLUSIONS: Few studies have examined the efficacy of cannabinoids in the treatment of insomnia disorder. Despite some possible signals for efficacy, the heterogeneity of participants, interventions, efficacy outcomes and results, and the high risk of bias across included trials, do not reliably inform evidence-based practice. This review highlights shortcomings in the existing literature, including lack of diagnostic clarity, poorly defined participant groups, non-standardised interventions and studies of inappropriate design, duration and power to detect clinically meaningful outcomes. Further research in the form of high-quality RCTs are required before drawing any conclusions about the efficacy of cannabinoids in the treatment of insomnia disorder. TRIAL REGISTRATION: PROSPERO registration number, CRD42020161043.

Knowledge and perspectives about the use of cannabis as a medicine: a mixed methods observational study in a cohort of New Zealand general practice patients.

AIM: To determine what patients presenting to general practice (GP) understand about the use of cannabis as a medicine, beliefs of how this may impact their medical conditions and interactions with doctors. METHOD: An in-person survey of 134 GP patients from four GP practices throughout the North Island of New Zealand undertaken from November 2018 to October 2019. RESULTS: Fifty-five percent of the sample were female, with 40% of all participants aged 60 years plus. Ninety-one percent of participants indicated they would use a prescribed medicinal cannabis product while 45% reported they believed it may be of some benefit to their medical condition. Of those who believed it beneficial, 71% indicated they thought it useful for pain relief. Participants indicated comfort discussing medicinal cannabis use with GPs and specialists (92% respectively); however, less than 10% had done this. CONCLUSIONS: Just under half of patients surveyed believe that medicinal cannabis products may be helpful to their condition, and while the majority report willingness, few have discussed this with their GP or specialist. There is need for accessible, accurate information regarding the use of cannabis-based medicine for patients and doctors alike to guide the patient-doctor consultation and decrease barriers to open discussion.

Cannabis-based medicinal products in arthritis, a painful conundrum.

AIMS: The changing medicolegal climate regarding the medicinal use of cannabinoids in New Zealand will increase the likelihood of patients consulting general practitioners (GPs) about these products. Arthritis is a common medical condition for which cannabis-based products are promoted and used; however, doctors' knowledge about the efficacy and safety of these products in the setting of arthritis may be limited. METHODS: We undertook a rapid review of the medical literature on cannabis-based medicinal products in arthritis. RESULTS: Animal studies have identified endocannabinoid pathways in arthritis that are potentially amenable to interventions. One randomised placebo-controlled trial of Sativex® in adults with rheumatoid arthritis has shown some improvements in pain but not in comparison with a standardised pharmacological treatment regimen. Systematic reviews of cannabis-based products in arthritis have determined that there is currently insufficient evidence to recommend cannabis-based medicines for routine clinical use. There were five ongoing registered clinical trials of cannabis-based products in arthritis, the results of which are yet to be reported. CONCLUSIONS: While animal models have identified possible endocannabinoid pathways in arthritis, there is no clear evidence of benefit in humans or comparative efficacy with current treatments. At this stage, there is little evidence to support GPs prescribing cannabis-based medicinal products for arthritis.

Medical cannabis: knowledge and expectations in a cohort of North Island New Zealand general practitioners.

AIM: To investigate GP knowledge of the use of cannabis as a medicine and its regulation in New Zealand. METHOD: A convenience sample of GPs completed a questionnaire during continuing medical education sessions. Key domains investigated were: patient interactions around use of cannabis as a medicine; prescription facilitation and impediments; knowledge of evidence for and against the use of cannabis as a medicine; knowledge of the New Zealand regulatory processes and knowledge of pharmaceutical grade products. Questionnaires were administered between June and October 2018. RESULTS: There were 42/76 (55%) GPs who stated at least one patient had asked for a cannabis prescription for medical use in the last 12 months and 43/76 (57%) were aware of pharmaceutical grade preparations, the majority Sativex. There were 59/75 (79%) who expressed concerns about future prescribing; however, 63/75 (84%) indicated they would be 'somewhat' or 'very' likely to prescribe a PHARMAC-funded product with good evidence in specific conditions. CONCLUSION: Some GPs have concerns about prescribing medicinal cannabis. Due to regulatory restrictions, including no currently funded products, and uncertain scientific evidence of efficacy and safety, education programmes will be required to inform the medico-legal, evidential and practical elements of prescribing cannabis as a medicine.

Protocol for a randomised, single-blind, two-arm, parallel-group controlled trial of the efficacy of rhinothermy delivered by nasal high flow therapy in the treatment of the common cold.

INTRODUCTION: The common cold is the most common infectious disease affecting humans. It is usually a self-limiting disease; however, the common cold can cause significant morbidity and has a substantial economic impact on society. Human rhinoviruses (HRVs), which cause up to two-thirds of colds, have temperature-dependent replication and most HRV strains replicate optimally at 33°C. Delivery of heated, humidified air to the upper airways has the potential to reduce viral replication, but evidence of the effectiveness of this treatment of the common cold is inconclusive. We plan to test the hypothesis that delivery of humidified air heated to 41°C at high flow, nasal high flow rhinothermy (rNHF), for 2 hours daily for five days is more effective in reducing common cold symptom severity and duration than five days of 'sham' rhinothermy. METHODS AND ANALYSIS: This is a randomised, single-blind, parallel-group trial comparing rNHF to 'sham' rhinothermy in the treatment of common cold. We plan to recruit 170 participants within 48 hours of the onset of symptoms of common cold and randomise them 1:1 to receive one of the two treatments for five days. The study duration is 14 days, which includes clinic visits on the first day of randomisation and four days post-randomisation, and a phone call on the 14th day. Participants will complete daily symptom diaries which include a symptom score, the Modified Jackson Score (MJS). The primary outcome is the MJS after four days. ETHICS AND DISSEMINATION: New Zealand Ethics Registration: 17/STH/174. Results will be published in a peer-reviewed medical journal, presented at academic meetings, and reported to participants. TRIAL REGISTRATION NUMBER: U1111-1194-4345 and ACTRN12617001340325; Pre-results.

Kanuka honey versus aciclovir for the topical treatment of herpes simplex labialis: a randomised controlled trial.

OBJECTIVE: To compare New Zealand medical grade kanuka honey with topical aciclovir for the treatment of herpes simplex labialis. DESIGN: Prospective parallel randomised controlled open-label superiority trial. SETTING: 76 community pharmacies across New Zealand between 10 September 2015 and 13 December 2017. PARTICIPANTS: 952 adults randomised within the first 72 hours of a herpes simplex labialis episode. INTERVENTIONS: Random assignment 1:1 to either 5% aciclovir cream or medical grade kanuka honey (90%)/glycerine (10%) cream, both applied five times daily. OUTCOME MEASURES: The primary outcome was time from randomisation to return to normal skin (stage 7). Secondary outcomes included time from randomisation to stage 4 (open wound), time from stage 4 to 7, maximal pain, time to pain resolution and treatment acceptability. RESULTS: Primary outcome variable: Kaplan-Meier-based estimates (95% CI) for the median time in days for return to normal skin were 8 (8 to 9) days for aciclovir and 9 (8 to 9) for honey; HR (95% CI) 1.06 (0.92 to 1.22), p=0.56. There were no statistically significant differences between treatments for all secondary outcome variables. No related serious adverse events were reported. CONCLUSION: There was no evidence of a difference in efficacy between topical medical grade kanuka honey and 5% aciclovir in the pharmacy-based treatment of herpes simplex labialis. TRIAL REGISTRATION NUMBER: ACTRN12615000648527;Post-results.

Protocol for a randomised controlled trial of 90% kanuka honey versus 5% aciclovir for the treatment of herpes simplex labialis in the community setting.

INTRODUCTION: Worldwide, about 90% of people are infected with the herpes simplex virus, 30% of whom will experience recurrent herpes simplex labialis, commonly referred to as 'cold sores', which can last up to 10 days. The most common treatment is aciclovir cream which reduces healing time by just half a day compared with no specific treatment. This is a protocol for a randomised controlled trial (RCT) to determine the efficacy of medical grade kanuka honey-based topical treatment (Honevo) in reducing the healing time and pain of cold sores, compared with topical aciclovir treatment (Viraban). METHODS AND ANALYSIS: This open-label, parallel-group, active comparator superiority RCT will compare the efficacy of medical grade kanuka honey with 5% aciclovir cream in the treatment of cold sores in the setting of a pharmacy research network of 60 sites throughout New Zealand. Adults presenting with a cold sore (N=950) will be randomised by pharmacy-based investigators. The pharmacy-based investigators will dispense the investigational product to randomised participants and both study groups apply the treatment five times daily until their skin returns to normal or for 14 days, whichever occurs first. In response to a daily SMS message, participants complete an assessment of their cold sore healing, with reference to a visual guide, and transmit it to the investigators by a smartphone eDiary in real time. The primary outcome variable is time (in days) from randomisation to return to normal skin. Secondary endpoints include total healing time stratified by stage of the lesion at onset of treatment, highest pain severity and time to pain resolution. ETHICS AND DISSEMINATION: New Zealand Ethics Registration 15/NTB/93. Results will be published in a peer-reviewed medical journal, presented at academic meetings and reported to participants. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trials Registry: ACTRN12615000648527, pre-results.SCOTT Registration: 15/SCOTT/14 PROTOCOL VERSION: 4.0 (12 June 2017).

RCT of the effect of berryfruit polyphenolic cultivar extract in mild steroid-naive asthma: a cross-over, placebo-controlled study.

OBJECTIVE: There is preclinical evidence that consumption of berryfruit extract may reduce chronic airways inflammation and modify airway remodelling in allergen-induced models of lung inflammation. We investigated the effect of berryfruit extract on the fractional expired nitric oxide (FeNO), a biomarker of eosinophilic airways inflammation, in adults with steroid-naïve asthma. DESIGN: Randomised placebo-controlled cross-over double-blind trial. SETTING: Single-centre community-based trial. PARTICIPANTS: 28 steroid-naïve mild asthmatics with Feno >40 ppb, of whom 25 completed both study interventions. INTERVENTIONS: Participants were randomised to receive, according to the cross-over design, 100 mg berryfruit polyphenolic extract (BFPE) or placebo for 4 weeks, with a 4-week washout period between the interventions. PRIMARY OUTCOME MEASURE: The primary outcome variable was FeNO at 4 weeks, analysed by a mixed linear model, with a random effect for participant and baseline FeNo as a covariate. RESULTS: The mean (SD) natural logarithm transformed (ln) FeNO after 4 weeks of treatment for the BFPE and placebo groups was 4.28 (0.47) and 4.22 (0.47), respectively. The paired change from baseline mean (SD) BFPE minus placebo ln FeNO was -0.03 (0.39), N=25. The mixed linear model estimate, with baseline covariate adjustment, difference in ln FeNO, was -0.002 (95% CI -0.15 to 0.14), p=0.98. This is equivalent to a ratio of geometric mean FeNO of 1.0 (95% CI 0.86 to 1.15). CONCLUSIONS: In steroid-naïve participants with mild asthma and elevated FeNO, there was no effect of BFPE on FeNO, a biomarker of eosinophilic airways inflammation. Caution is required in the extrapolation of apparent benefit in murine models of lung eosinophilia to clinical efficacy in patients with asthma. TRIAL REGISTRATION NUMBER: ANZCTR: 12613000451707; Results.

Randomised controlled trial of topical kanuka honey for the treatment of acne.

OBJECTIVE: To investigate the efficacy of Honevo, a topical 90% medical-grade kanuka honey, and 10% glycerine (honey product) as a treatment for facial acne. DESIGN: Randomised controlled trial with single blind assessment of primary outcome variable. SETTING: Outpatient primary care from 3 New Zealand localities. PARTICIPANTS: Of 136 participants aged between 16 and 40 years with a diagnosis of acne and baseline Investigator's Global Assessment (IGA) for acne score of ≥ 2.68, participants were randomised to each treatment arm. INTERVENTIONS: All participants applied Protex, a triclocarban-based antibacterial soap twice daily for 12 weeks. Participants randomised to the honey product treatment arm applied this directly after washing off the antibacterial soap, twice daily for 12 weeks. OUTCOME MEASURES: The primary outcome was ≥ 2 point decrease in IGA score from baseline at 12 weeks. Secondary outcomes included mean lesion counts and changes in subject-rated acne improvement and severity at weeks 4 and 12, and withdrawals for worsening acne. RESULTS: 4/53 (7.6%) participants in the honey product group and 1/53 (1.9%) of participants in the control group had a ≥ 2 improvement in IGA score at week 12, compared with baseline, OR (95% CI) for improvement 4.2 (0.5 to 39.3), p=0.17. There were 15 and 14 participants who withdrew from the honey product group and control group, respectively. CONCLUSIONS: This randomised controlled trial did not find evidence that addition of medical-grade kanuka honey in combination with 10% glycerine to standard antibacterial soap treatment is more effective than the use of antibacterial soap alone in the treatment of acne. TRIAL REGISTRATION NUMBER: ACTRN12614000003673; Results.

Randomised controlled trial of topical kanuka honey for the treatment of rosacea.

OBJECTIVE: To investigate the efficacy of topical 90% medical-grade kanuka honey and 10% glycerine (Honevo) as a treatment for rosacea. DESIGN: Randomised controlled trial with blinded assessment of primary outcome variable. SETTING: Outpatient primary healthcare population from 5 New Zealand sites. PARTICIPANTS: 138 adults aged ≥ 16, with a diagnosis of rosacea, and a baseline blinded Investigator Global Assessment of Rosacea Severity Score (IGA-RSS) of ≥ 2. 69 participants were randomised to each treatment arm. 1 participant was excluded from the Honevo group, and 7 and 15 participants withdrew from the Honevo and control groups, respectively. INTERVENTIONS: Participants were randomly allocated 1:1 to Honevo or control cream (Cetomacrogol), applied twice daily for 8 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of participants who had a ≥ 2 improvement in the 7-point IGA-RSS at week 8 compared to baseline. Secondary outcomes included change in IGA-RSS and subject-rated visual analogue score of change in severity (VAS-CS) on a 100 mm scale (0 mm 'much worse', 100 mm 'much improved') at weeks 2 and 8. RESULTS: 24/68 (34.3%) in the Honevo group and 12/69 (17.4%) in the control group had a ≥ 2 improvement in IGA-RSS at week 8 compared to baseline (relative risk 2.03; 95% CI 1.11 to 3.72, p=0.020). The change in IGA-RSS for Honevo compared to control at week 2 minus baseline was -1 (Hodges-Lehman estimate, 95% CI -1 to 0, p=0.03), and at week 8 minus baseline was -1 (Hodges-Lehman estimate, 95% CI -1 to 0, p=0.005). The VAS-CS at week 2 was 9.1 (95% CI 3.5 to 14.7), p=0.002, and at week 8 was 12.3 (95% CI 5.7 to 18.9)¸ p<0.001 for Honevo compared to control. CONCLUSIONS: Honevo is an effective treatment for rosacea. TRIAL REGISTRATION NUMBER: This trial was registered in the Australian and New Zealand Clinical Trials Registry ACTRN12614000004662.