'The wild west of medicine': A qualitative investigation of the factors influencing Australian health-care practitioners' delivery of medicinal cannabis.

INTRODUCTION: Strong patient interest in the use of medicinal cannabis to treat various clinical indications has sparked global legislative changes. Practitioners are vital in implementing regulatory changes and facilitating patient access to medicinal cannabis, however, little is currently known about the factors influencing practitioners' uptake. Recent rapid increases in practitioner applications to prescribe medicinal cannabis in Australia provides a unique backdrop to examine the current factors influencing prescribing behaviours. This qualitative study examined Australian practitioners' perspectives on prescribing medicinal cannabis to provide a comprehensive exploration of the potential factors influencing uptake in clinical practice. METHODS: Seventeen semi-structured interviews were conducted with Australian health-care practitioners. Transcripts were analysed using the Framework approach to thematic analysis and cross-mapped to appropriate domains of the Theoretical Domains Framework. RESULTS: We identified four themes related to the barriers and facilitators to prescribing medicinal cannabis: (i) clinical capabilities needed to prescribe; (ii) prescribing an unapproved therapeutic good; (iii) negative attitudes towards prescribers in the medical community; and (iv) divergent beliefs about clinical utility. DISCUSSION AND CONCLUSIONS: Practitioners face multiple pervasive barriers to prescribing medicinal cannabis. Beliefs about clinical utility appear to be highly influential in shaping prescribing behaviours. Moreover, our findings suggest that a medicinal cannabis 'specialisation' has emerged within the Australian medical community. Findings demonstrate that a range of complex and multifaceted factors influence practitioners' medicinal cannabis prescribing behaviours. We highlight several considerations for policy and practice to support safe and appropriate patient access to medicinal cannabis in this emerging area of clinical practice.

A provisional evaluation of Australia's medical cannabis program.

In 2016, the Australian Government legislated to allow cannabis to be prescribed to patients as an unapproved medicine under the special access provisions of the Therapeutic Goods Act. This paper compares the Australian regulatory approach with other national approaches, outlines the main provisions of the Special Access Scheme for medical cannabis, describes how the program has evolved since 2017, includes an analysis of adverse events reported to the Therapeutic Goods Administration, and discusses the barriers that remain for patients who wish to access medical cannabis. It assesses how well the Australian program has addressed the challenges of providing patients with easier access to medical cannabis while ensuring that high-quality products are used safely and effectively under medical guidance.

Medicinal Cannabis Guidance and Resources for Health Professionals to Inform Clinical Decision Making.

PURPOSE: Interest in the use of cannabis as a medicine has markedly increased during the last decade, with an unprecedented number of patients now seeking advice or prescriptions for medicinal cannabis. Unlike other medicines prescribed by physicians, many medicinal cannabis products have not undergone standard clinical trial development required by regulatory authorities. Different formulations with varying strengths and ratios of tetrahydrocannabinol and cannabidiol are available, and this diversity of medicinal cannabis products available for a myriad of therapeutic indications adds to the complexity. Physicians face challenges and barriers in their clinical decision making with medicinal cannabis because of current evidence limitations. Research efforts to address evidence limitations are ongoing; in the interim, educational resources and clinical guidance are being developed to address the gap in clinical information and support the needs of health professionals. METHODS: This article provides an overview of various resources that health professionals may use when seeking information about medicinal cannabis in the absence of high-quality evidence and clinical guidelines. It also identifies examples of international evidence-based resources that support clinical decision making with medicinal cannabis. FINDINGS: Similarities and differences between international examples of guidance and guideline documents are identified and summarized. IMPLICATIONS: Guidance can help guide physicians in the individualized choice and dose of medicinal cannabis. Before quality clinical trials and regulator-approved products with risk management programs, safety data require clinical and academic collaborative pharmacovigilance.

From growers to patients: Multi-stakeholder views on the use of, and access to medicinal cannabis in Australia.

BACKGROUND: Patient interest in the use of cannabis-based medicines (CBMs) has increased in Australia. While recent policy and legislative changes have enabled health practitioners to prescribe CBMs for their patients, many patients still struggle to access CBMs. This paper employed a thematic analysis to submissions made to a 2019 Australian government inquiry into current barriers of patient access to medical cannabis. METHODS: We identified 121 submissions from patients or family members (n = 63), government bodies (n = 5), non-government organisations (i.e., professional health bodies, charities, consumer organisations or advocacy groups; n = 25), medical cannabis and pharmaceutical industry (n = 16), and individual health professionals, academics, or research centres (n = 12). Data were coded using NVivo 12 software and thematically analysed. The findings were presented narratively using a modified Levesque's patient-centred access to care framework which includes: i) appropriateness; ii) availability and geographic accessibility; iii) acceptability; and iv) affordability. RESULTS: Submissions from government agencies and professional health bodies consistently supported maintaining the current regulatory frameworks and access pathways, whereas an overwhelming majority of patients, advocacy groups and the medical cannabis industry described the current regulatory and access models as 'not fit for purpose'. These differing views seem to arise from divergent persepctives on (i) what and how much evidence is needed for policy and practice, and (ii) how patients should be given access to medical cannabis products amidst empirical uncertainty. Notwithstanding these differences, there were commonalities among some stakeholders regarding the various supply, regulatory, legislative, financial, and dispensing challenges that hindered timely access to CBMs. CONCLUSIONS: Progress in addressing the fundamental barriers that determine if and how a patient accesses and uses CBMs needs i) a 'system-level' reform that gives due consideration to the geographic disparity in access to prescribers and medical cannabis, and ii) reframing societal and health professional's views of CBMs by decoupling recreational vs medical cannabis.

Cannabidiol drug interaction considerations for prescribers and pharmacists.

INTRODUCTION: In light of the widespread use of non-prescribed and prescribed cannabidiol, the use of cannabidiol with other medications is likely, and this may result in drug interactions. AREAS COVERED: We aimed to ascertain if clinical guidance could be provided on the dose range at which cannabidiol drug interactions are likely to occur with concurrently prescribed medicines. Literature searches were conducted in Embase, MEDLINE, and PubMed from database inception to January 2022 using Emtree and MeSH terms. Reference list screening yielded further studies. Using currently available data, likely drug interactions of which prescribers of cannabidiol need to be aware, at the doses likely to cause clinically significant interactions, and drug dosing changes that may be needed are highlighted. EXPERT OPINION: We have provided an overview of evidence-based pharmacokinetic predictions and general guidance about the dose range at which clinically relevant cannabidiol drug interactions are likely. For an individual patient, there are inherent limitations in providing clinical guidance due to gaps in specific drug dose-response data and knowledge of individual pharmacokinetic profiles, including different co-morbidities, and concurrent medicines. Clinician awareness of cannabinoid pharmacology, along with clinical and therapeutic drug monitoring, are current best practice approaches to manage cannabinoid drug interactions.

Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies.

Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED50) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED50 of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer experimental pain studies, two found increased pain, two found decreased pain and one found reduced pain bothersomeness with cannabinoid administration; three demonstrated that cannabinoid co-administration may increase opioid abuse liability. Three randomized controlled trials (RCTs) found no evidence of opioid-sparing effects of cannabinoids in acute pain. Meta-analysis of four RCTs in patients with cancer pain found no effect of cannabinoid administration on opioid dose (mean difference -3.8 mg, 95% CI -10.97, 3.37) or percentage change in pain scores (mean difference 1.84, 95% CI -2.05, 5.72); five studies found more adverse events with cannabinoids compared with placebo (risk ratio 1.13, 95% CI 1.03, 1.24). Of five controlled chronic non-cancer pain trials; one low-quality study with no control arm, and one single-dose study reported reduced pain scores with cannabinoids. Three RCTs found no treatment effect of dronabinol. Meta-analyses of observational studies found 39% reported opioid cessation (95% CI 0.15, 0.64, I2 95.5%, eight studies), and 85% reported reduction (95% CI 0.64, 0.99, I2 92.8%, seven studies). In summary, preclinical and observational studies demonstrate the potential opioid-sparing effects of cannabinoids in the context of analgesia, in contrast to higher-quality RCTs that did not provide evidence of opioid-sparing effects.

Expert advice for prescribing cannabis medicines for patients with epilepsy-drawn from the Australian clinical experience.

There is international interest for consensus advice for prescribers working in the field of drug resistant epilepsy intending to trial potential therapies that are nonregistered or off-label. Cannabinoids are one such therapy. In 2017, the New South Wales State Government (Australia) set up a cannabinoid prescribing guidance service for a wide variety of indications, based on known pharmacology together with the relevant new literature as it became available. Increasing interest in cannabis medicines use outside this State over the following 5 years together with a paucity of registration-standard clinical trials, lack of information around dosing issues, drug interactions and biological plausibility meant there remained a large unmet need for such advice. To address the unmet need in epilepsy, and until medicines were registered or regulator quality data were available, it was agreed to bring together a working group comprising paediatric and adult epilepsy specialists, clinical pharmacists., clinical pharmacologists and cannabis researchers from across Australia to develop interim consensus advice for prescribers. Although interim, this consensus advice addresses much of the current practice gap by providing an informed overview of the different cannabis medicines currently available for use in the treatment of epilepsy in paediatric and adult settings, with information on dose, drug interactions, toxicity, type of seizure and frequency of symptom relief. As such it supplements the limited evidence currently available from clinical trials with experience from front-line practice. It is expected that this consensus advice will be updated as new evidence emerges and will provide guidance for a subsequent Guideline.

Over the counter low-dose cannabidiol: A viewpoint from the ACRE Capacity Building Group.

Amidst growing global acceptance of medicinal cannabinoids as a potential therapeutic interest in cannabidiol (CBD) is increasing. In Australia in 2020, a government inquiry examined the barriers that the public are experiencing in accessing medicinal cannabis. A number of recommendations to improve access were made. In response to these recommendations, the Australian therapeutics regulatory authority down-scheduled CBD from Prescription Only (Schedule 4) to Pharmacist Only (Schedule 3). As a group of early to mid-career researchers of the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), we propose some considerations in relation to over-the-counter availability of CBD and opportunities to improve knowledge about its potential therapeutic benefits alongside its increased uptake.

NSW Cannabis Medicines Advisory Service preliminary survey results: enquirer perceptions and patient outcomes.

BACKGROUND: In 2018, an innovative, State government-funded cannabis medicines drug information service was established for health professionals in New South Wales (NSW). The NSW Cannabis Medicines Advisory Service (CMAS) provides expert clinical guidance and support to medical practitioners considering prescribing a cannabis medicine to their patient(s). AIMS: This research examines quality assurance and patient outcomes related to enquirers' experience with NSW CMAS. METHODS: Data collection involved an online, anonymous survey with two components. Following a health professional enquiry, quality assurance data were collected about the enquirers' experience with NSW CMAS. The second survey focussed on patient outcomes and provides real-world observational data about cannabis medicines safety and effectiveness across a wide range of indications. RESULTS: Data collection occurred between January 2020 and June 2021. Preliminary analyses were based on 68 quality assurance and 50 patient outcomes survey responses. General practitioners represented the highest proportion of survey responses (n = 33; 49%). The most common enquiry involved 'patient-specific advice' (n = 50; 74%). Patient-specific information provided by the service was mainly used for prescribing decision support (n = 45; 90%). CONCLUSIONS: Preliminary findings highlight the impact of an innovative cannabis medicines drug information service in supporting health professional clinical practice in an area of rapid knowledge translation. Quality assurance data indicate that the service is perceived well by the majority of enquirers. Patient outcomes data across a wide range of indications suggest some effectiveness and a reasonable safety profile for prescribed cannabis medicines for most patients.

Translational hurdles with cannabis medicines.

PURPOSE: Internationally, there has been widespread medical use of cannabis medicines before rigorous evaluations in randomised controlled trials (RCTs). Some advocates of medicinal use of cannabis argue that real-world evidence (RWE) can be a substitute for or at least supplement evidence from RCTs. We explore the utility, limitations and impact of RWE in the translation of cannabis medicines research into clinical practice using the established literature. METHODS: A literature search was performed via Embase and Medline using a diverse range of cannabinoid and RWE search terms. The review provides a snapshot of cannabis medicine RWE initiatives from around the world. RESULTS: Diverse and novel sources of real-world data and RWE include international cannabis registries, surveys, post-marketing data collection and use of electronic or digital health records. The strengths and limitations of using RWE in translational research are highlighted, along with the identification of barriers to RCTs involving cannabis medicines. CONCLUSIONS: RWE promises to play a significant role in the evaluation of cannabis medicines around the world. When used appropriately RWE may complement RCT data by providing valuable insights into cannabis medicine safety and effectiveness. TAKE HOME MESSAGES: It is important that real-world evidence (RWE) is used to complement rather than replace randomised controlled trial (RCT) evidence on cannabis medicines. Technological advances have created the opportunity to explore diverse and novel sources of cannabis medicine RWE. Although RWE may be more reflective of real-world clinical practice, it cannot provide conclusive evidence of the safety and efficacy of cannabis medicines. While acknowledging its limitations, RWE may nonetheless provide some guidance on safety and adverse events of cannabis medicines. RWE has already had a significant impact on the regulation of cannabis medicines.