[ROUTES OF MEDICAL CANNABIS ADMINISTRATION- IS SMOKING THE PREFERRED ROUTE?]

INTRODUCTION: The number of medical cannabis licenses in Israel is increasing persistently (over 120,000 approved licenses in October 2022), reaching about 1.5% of adult population. Medical cannabis products are available in two main forms: inflorescence (administered by smoking or evaporation) and cannabis oil (administered sub-lingually). Data from the Israel ministry of health, regarding the split between these forms, show a major preference for inflorescence products over cannabis oils. This preference is increasing over time. This article reviews the main differences between the administration of these forms and their effects on the quality of treatment. It's conclusion is that for the most common cases of cannabis treatment, sublingual oils should be preferred and that the medical community has an important role in driving this change.

Medicinal Cannabis (MedCan 3): a randomised, multicentre, double-blind, placebo-controlled trial to assess THC/CBD (1:20) to relieve symptom burden in patients with cancer-a study protocol for a randomised controlled trial.

BACKGROUND: Distressing symptoms are common in advanced cancer. Medicinal cannabinoids are commonly prescribed for a variety of symptoms. There is little evidence to support their use for most indications in palliative care. This study aims to assess a 1:20 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom distress in patients with advanced cancer undergoing palliative care. METHODS AND DESIGN: One hundred and fifty participants will be recruited across multiple sites in Queensland, Australia. A teletrial model will facilitate the recruitment of patients outside of major metropolitan areas. The study is a pragmatic, multicenter, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:20 THC/CBD medicinal cannabinoid preparation (10 mg THC:200 mg CBD/mL). It will compare the efficacy and safety outcomes of a titrated dose range of 2.5 mg THC/50mgCBD to 30 mg THC/600 mg CBD per day against a placebo. There is a 2-week patient-determined titration phase, to reach a dose that achieves symptom relief or intolerable side effects, with a further 2 weeks of assessment on the final dose. The primary objective is to assess the effect of escalating doses of a 1:20 THC/CBD medicinal cannabinoid preparation against placebo on change in total symptom distress score, with secondary objectives including establishing a patient-determined effective dose, the effect on sleep quality and overall quality of life. Some patients will be enrolled in a sub-study which will more rigorously evaluate the effect on sleep. DISCUSSION: MedCan-3 is a high-quality, adequately powered, placebo-controlled trial which will help demonstrate the utility of a THC:CBD 1:20 oral medicinal cannabis product in reducing total symptom distress in this population. Secondary outcomes may lead to new hypotheses regarding medicinal cannabis' role in particular symptoms or in particular cancers. The sleep sub-study will test the feasibility of using actigraphy and the Insomnia Severity Index (ISI) in this cohort. This will be the first large-scale palliative care randomised clinical trial to utilise the teletrial model in Australia. If successful, this will have significant implications for trial access for rural and remote patients in Australia and internationally. TRIAL REGISTRATION: ANZCTR ACTRN12622000083796 . Protocol number 001/20. Registered on 21 January 2022. Recruitment started on 8 August 2022.

Medical and Recreational Marijuana.

Information for nurses, patients, and the public.

Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials.

OBJECTIVE: To determine the benefits and harms of medical cannabis and cannabinoids for chronic pain. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, AMED, PsycInfo, CENTRAL, CINAHL, PubMed, Web of Science, Cannabis-Med, Epistemonikos, and trial registries up to January 2021. STUDY SELECTION: Randomised clinical trials of medical cannabis or cannabinoids versus any non-cannabis control for chronic pain at ≥1 month follow-up. DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently assessed risk of bias and extracted data. We performed random-effects models meta-analyses and used GRADE to assess the certainty of evidence. RESULTS: A total of 32 trials with 5174 adult patients were included, 29 of which compared medical cannabis or cannabinoids with placebo. Medical cannabis was administered orally (n=30) or topically (n=2). Clinical populations included chronic non-cancer pain (n=28) and cancer related pain (n=4). Length of follow-up ranged from 1 to 5.5 months. Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of -0.50 cm (95% CI -0.75 to -0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of -0.35 cm (-0.55 to -0.14 cm, high certainty)). Medical cannabis taken orally does not improve emotional, role, or social functioning (high certainty). Moderate certainty evidence shows that medical cannabis taken orally probably results in a small increased risk of transient cognitive impairment (RD 2% (0.1% to 6%)), vomiting (RD 3% (0.4% to 6%)), drowsiness (RD 5% (2% to 8%)), impaired attention (RD 3% (1% to 8%)), and nausea (RD 5% (2% to 8%)), but not diarrhoea; while high certainty evidence shows greater increased risk of dizziness (RD 9% (5% to 14%)) for trials with <3 months follow-up versus RD 28% (18% to 43%) for trials with ≥3 months follow-up; interaction test P=0.003; moderate credibility of subgroup effect). CONCLUSIONS: Moderate to high certainty evidence shows that non-inhaled medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning, and sleep quality among patients with chronic pain, along with several transient adverse side effects, compared with placebo. The accompanying BMJ Rapid Recommendation provides contextualised guidance based on this body of evidence. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/3pwn2.

Medical cannabis or cannabinoids for chronic pain: a clinical practice guideline.

CLINICAL QUESTION: What is the role of medical cannabis or cannabinoids for people living with chronic pain due to cancer or non-cancer causes? CURRENT PRACTICE: Chronic pain is common and distressing and associated with considerable socioeconomic burden globally. Medical cannabis is increasingly used to manage chronic pain, particularly in jurisdictions that have enacted policies to reduce use of opioids; however, existing guideline recommendations are inconsistent, and cannabis remains illegal for therapeutic use in many countries. RECOMMENDATION: The guideline expert panel issued a weak recommendation to offer a trial of non-inhaled medical cannabis or cannabinoids, in addition to standard care and management (if not sufficient), for people living with chronic cancer or non-cancer pain. HOW THIS GUIDELINE WAS CREATED: An international guideline development panel including patients, clinicians with content expertise, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. The panel applied an individual patient perspective. THE EVIDENCE: This recommendation is informed by a linked series of four systematic reviews summarising the current body of evidence for benefits and harms, as well as patient values and preferences, regarding medical cannabis or cannabinoids for chronic pain. UNDERSTANDING THE RECOMMENDATION: The recommendation is weak because of the close balance between benefits and harms of medical cannabis for chronic pain. It reflects a high value placed on small to very small improvements in self reported pain intensity, physical functioning, and sleep quality, and willingness to accept a small to modest risk of mostly self limited and transient harms. Shared decision making is required to ensure patients make choices that reflect their values and personal context. Further research is warranted and may alter this recommendation.

High quantities: Evaluating the association between cannabis use and propofol anesthesia during endoscopy.

BACKGROUND: Endoscopy under propofol sedation has become a routine procedure. Given the number of Canadians undergoing an endoscopy annually, as well as the pervasive use of cannabis by many patients, understanding the effect of cannabis use on the propofol dose at endoscopy is highly relevant. We aimed to evaluate the association between cannabis exposure and the propofol dose needed to achieve adequate sedation at endoscopy. METHODS: A case-control study of individuals undergoing endoscopy was conducted at a single outpatient endoscopy clinic in London, Ontario between 2014 and 2017. Cases included all individuals with any self-reported cannabis exposure, while controls included all individuals without any self-reported history of cannabis use. Dose of propofol administered by a single anesthetist was collected on each subject as well as additional demographic and procedure-related covariates. RESULTS: Three hundred and eighteen participants were included (cases, n = 151; controls, n = 167). Cannabis exposure was associated with an increase in propofol dose (cases 0.33 mg/kg/minute ±0.24; controls, 0.18 mg/kg/minute ±0.11; p<0.0001). Cannabis exposure remained an independent predictor of propofol dose on multivariate linear regression accounting for other important covariates (p<0.0001). Daily cannabis users required a higher propofol dose than weekly or monthly users. Three procedural sedation-related complications occurred in the cannabis-exposed group, while none occurred in the unexposed group. CONCLUSION: Our data suggest that cannabis use is significantly associated with the quantity of propofol needed for sedation at endoscopy. Further study is needed to better understand the molecular basis for this possible drug-drug interaction.

Medical Cannabis in Oncology: a Valuable Unappreciated Remedy or an Undesirable Risk?

OPINION STATEMENT: The use of the cannabis plant by cancer patients has been rising significantly in the past few years worldwide, primarily driven by public demand. There is an obvious need for more reliable scientific data, pharmacology information, a better understanding of its mode of action, and available clinical evidence supporting its robust use. Physicians must complete a thorough medical assessment, screening for potential drugs, or treatment contraindications before allowing its consumption. In light of the growing popularity of cannabis usage, it is highly essential that, in the near future, the medical community will be able to provide practical recommendations and explicit guidelines, including doses, and that cannabinoid concentrations in the used products are defined regarding its prescription before any medical procedure involving its usage is authorized. Here, we review and describe the favorable outcomes demonstrating the benefits of cannabis as an adjunctive treatment to conventional medicines for chemotherapy-induced nausea, vomiting, and cancer-related pain (primarily refractory chronic or neuropathic pain). Although not yet substantial enough, the treatment of anorexia, insomnia, depression, and anxiety is also seemingly favorable. To date, reports regarding its anti-neoplastic effects or its potent immunosuppressive properties influencing response to immunotherapy are still very conflicting and controversial. Thus, with the current state of evidence, cannabis use is not advisable as initial treatment, as an adjunct or an advanced line of care. In the coming years, we expect that preclinical data and animal models will shift to the clinical arena, and more patients will be recruited for clinical trials, and their reports will advance the field. Thus, physicians should prescribe cannabis only if careful clarification and consideration is provided together with a follow-up response evaluation.

Cannabis: An Emerging Treatment for Common Symptoms in Older Adults.

BACKGROUND/OBJECTIVES: Use of cannabis is increasing in a variety of populations in the United States; however, few investigations about how and for what reasons cannabis is used in older populations exist. DESIGN: Anonymous survey. SETTING: Geriatrics clinic. PARTICIPANTS: A total of 568 adults 65 years and older. INTERVENTION: Not applicable. MEASUREMENTS: Survey assessing characteristics of cannabis use. RESULTS: Approximately 15% (N = 83) of survey responders reported using cannabis within the past 3 years. Half (53%) reported using cannabis regularly on a daily or weekly basis, and reported using cannabidiol-only products (46%). The majority (78%) used cannabis for medical purposes only, with the most common targeted conditions/symptoms being pain/arthritis (73%), sleep disturbance (29%), anxiety (24%), and depression (17%). Just over three-quarters reported cannabis "somewhat" or "extremely" helpful in managing one of these conditions, with few adverse effects. Just over half obtained cannabis via a dispensary, and lotions (35%), tinctures (35%), and smoking (30%) were the most common administration forms. Most indicated family members (94%) knew about their cannabis use, about half reported their friends knew, and 41% reported their healthcare provider knowing. Sixty-one percent used cannabis for the first time as older adults (aged ≥61 years), and these users overall engaged in less risky use patterns (e.g., more likely to use for medical purposes, less likely to consume via smoking). CONCLUSION: Most older adults in the sample initiated cannabis use after the age of 60 years and used it primarily for medical purposes to treat pain, sleep disturbance, anxiety, and/or depression. Cannabis use by older adults is likely to increase due to medical need, favorable legalization, and attitudes.

Exploring the Use of State Medical Cannabis Legislation as a Proxy for Medical Cannabis Use Among Patients Receiving Chemotherapy.

OPINION STATEMENT: The use of medical cannabis is expanding in the USA. Due to conflicting, low-quality evidence, many oncologists may not feel confident to recommend it to patients. Given the potential for legal and financial risks when conducting clinical trials with medical cannabis, the use of observational data should be explored. Observational data that directly capture medical cannabis use in relation to prescription medications and track the prevalence and patterns of cannabis use is sparse. To gain insights into the role medical cannabis plays in the pharmaceutical landscape, proxies such as cannabis legislation need to be explored. In the context of recommendation-nonadherent antiemetic prescribing among patients experiencing chemotherapy-induced nausea and vomiting, medical cannabis may be a suitable alternative to an antiemetic in states that allow medical cannabis. Findings suggest that legislation may impact the use of certain antiemetics in states with cannabis legislation in place. The presence or absence of legislation regarding medical cannabis use may serve as an early, observable surrogate marker of medical cannabis use in the community. In light of the paucity of clinical trials and observational datasets that capture cannabis use, there remains a tremendous need for the development of methodologies or standardized datasets that appropriately and reliably capture the use of medical cannabis to facilitate research into its clinical application and effect on prescription medication use. Standardizing the reporting and destigmatizing use could eliminate the dependence upon proxy measures as a substitute for more extensive data and go a long way in improving data capture, thus allowing us to generate knowledge and hypotheses from observational data until research conditions improve and allow for expanded clinical trials involving medical cannabis.

Cannabis and cannabidiol (CBD) for the treatment of fibromyalgia.

Fibromyalgia is a complex disease process that is as prevalent as it is poorly understood. Research into the pathophysiology is ongoing, and findings will likely assist in identifying new therapeutic options to augment those in existence today that are still insufficient for the care of a large population of patients. Recent evidence describes the use of cannabinoids in the treatment of fibromyalgia. This study provides a systematic, thorough review of the evidence alongside a review of the seminal data regarding the pathophysiology, diagnosis, and current treatment options. Fibromyalgia is characterized by widespread chronic pain, fatigue, and depressive episodes without an organic diagnosis, which may be prevalent in up to 10% of the population and carries a significant cost in healthcare utilization, morbidity, a reduced quality of life, and productivity. It is frequently associated with psychiatric comorbidities. The diagnosis is clinical and usually prolonged, and diagnostic criteria continue to evolve. Some therapies have been previously described, including neuropathic medications, milnacipran, and antidepressants. Despite some level of efficacy, only physical exercise has strong evidence to support it. Cannabis has been used historically to treat different pain conditions since ancient times. Recent advances allowed for the isolation of the active substances in cannabis and the production of cannabinoid products that are nearly devoid of psychoactive influence and provide pain relief and alleviation of other symptoms. Many of these, as well as cannabis itself, are approved for use in chronic pain conditions. Evidence supporting cannabis in chronic pain conditions is plentiful; however, in fibromyalgia, they are mostly limited. Only a handful of randomized trials exists, and their objectivity has been questioned. However, many retrospective trials and patient surveys suggest the significant alleviation of pain, improvement in sleep, and abatement of associated symptoms. Evidence supporting the use of cannabis in chronic pain and specifically in fibromyalgia is being gathered as the use of cannabis increases with current global trends. While the current evidence is still limited, emerging data do suggest a positive effect of cannabis in fibromyalgia. Cannabis use is not without risks, including psychiatric, cognitive, and developmental as well as the risks of addiction. As such, clinical judgment is warranted to weigh these risks and prescribe to patients who are more likely to benefit from this treatment. Further research is required to define appropriate patient selection and treatment regimens.

Clinical Data for the Use of Cannabis-Based Treatments: A Comprehensive Review of the Literature.

OBJECTIVE: To compile and synthesize the available literature describing medical cannabis use across various disease states. DATA SOURCES: PubMed, EBSCO, and Google Scholar searches were conducted using MeSH and/or keywords. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they described the use of cannabis-based products and medications in the treatment of a predefined list of disease states in humans and were published in English. The extraction period had no historical limit and spanned through April 2019. DATA SYNTHESIS: Evidence was compiled and summarized for the following medical conditions: Alzheimer disease, amyotrophic lateral sclerosis, autism, cancer and cancer-associated adverse effects, seizure disorders, human immunodeficiency virus, inflammatory bowel disease, multiple sclerosis (MS), nausea, pain, posttraumatic stress disorder, and hospice care. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Based on identified data, the most robust evidence suggests that medical cannabis may be effective in the treatment of chemotherapy-induced nausea and vomiting, seizure disorders, MS-related spasticity, and pain (excluding diabetic neuropathy). Overall, the evidence is inconsistent and generally limited by poor quality. The large variation in cannabis-based products evaluated in studies limits the ability to make direct comparisons. Regardless of the product, a gradual dose titration was utilized in most studies. Cannabis-based therapies were typically well tolerated, with the most common adverse effects being dizziness, somnolence, dry mouth, nausea, and euphoria. CONCLUSIONS: As more states authorize medical cannabis use, there is an increasing need for high-quality clinical evidence describing its efficacy and safety. This review is intended to serve as a reference for clinicians, so that the risks and realistic benefits of medical cannabis are better understood.

Cannabis and cannabinoids in cancer pain management.

PURPOSE OF REVIEW: An increasing number of patients are turning to cannabis and cannabinoids for management of their palliative and nonpalliative cancer pain and other cancer-related symptoms. Canadians have a legal framework for access to medical cannabis, which provides a unique perspective in a setting lacking robust clinical evidence. This review seeks to delineate the role of cannabis and cannabinoids in cancer pain management and offers insight into the Canadian practice. RECENT FINDINGS: A cohort study using nabiximols on advanced cancer pain in patients already optimized on opioids, over 3 weeks, demonstrated improved average pain score. A large observational study of cancer patients using cannabis over 6 months demonstrated a decreased number of patients with severe pain and decreased opioid use, whereas the number of patients reporting good quality of life increased. SUMMARY: Good preclinical animal data and a large body of observational evidence point to the potential efficacy of cannabinoids for cancer pain management. However, there are relatively weak data pointing to clinical efficacy from clinical trial data to date. In Canada, the burgeoning cannabis industry has driven the population to embrace a medicine before clinical evidence. There remains a need for high-quality randomized controlled trials to properly assess the effectiveness and safety of medical cannabis, compared with placebo and standard treatments for cancer-related symptoms.

Medical cannabis in supportive cancer care: lessons from Canada.

Medical cannabis, or cannabinoid-based products, continues to grow in popularity globally, driving the evolution of regulatory access frameworks; cancer patients and caregivers often rely on guidance from their physicians regarding cannabinoid-based treatments. But the majority of healthcare practitioners still feel unprepared and insufficiently informed to make reasonable, evidence-based recommendations about medical cannabis. More than 30 countries worldwide have now legalized access to medical cannabis; yet various nations still face arduous regulatory challenges to fulfill the needs of patients, healthcare practitioners, and other medical stakeholders. This has affected the deployment of comprehensive medical cannabis access programs adapted to cultural and social realities. With a 20-year history of legal medical cannabis access and nearly 400,000 registered patients under its federal access program, Canada serves as a model for countries which are developing their regulatory frameworks. The Canadian clinical experience in cannabinoid-based treatments is also a valuable source of lessons for healthcare professionals who wish to better understand the current evidence examining medical cannabis for oncology patients.

Cannabis Enthusiasts' Knowledge of Medical Treatment Effectiveness and Increased Risks From Cannabis Use.

PURPOSE: To compare cannabis enthusiasts' knowledge about cannabis risks and effectiveness in treating medical conditions with existing empirical evidence. DESIGN: A brief survey assessed cannabis use, information sources, and knowledge about risks and effectiveness. SETTING: A cannabis advocacy event in April 2019 in a state with legal medical and recreational cannabis. PARTICIPANTS: Demographically diverse adults (N = 472) who frequently used cannabis; 85% used cannabis for health or medical purposes. MEASURES: Participants reported the sources of their cannabis information, health conditions they thought cannabis was effective in treating (n = 10), and health risks increased by cannabis (n = 6). Conditions and risks were based on ratings of evidence (ie, from substantial to insufficient) for therapeutic effects and risks identified in a review by The National Academies of Sciences, Engineering, and Medicine (NASEM, 2017). ANALYSES: Chi-square tests examined the correspondence between participants' knowledge and NASEM conclusions. RESULTS: Most participants' (95% confidence interval [CI]: 74%-81%) knowledge of cannabis was from their own experiences; 18% (95% CI: 14%-21%) received information from primary care providers. On average, participants' beliefs matched NASEM conclusions for half of effectiveness (95% CI: 50%-53%) and risk items (95% CI: 55%-57%). Many (95% CI: 38%-42%) thought that cannabis use did not increase any risk. Contrary to NASEM conclusions, many thought cannabis was effective in treating cancer (76%), depressive symptoms (72%), and epilepsy (68%). Those who received cannabis information from their primary care providers had better knowledge of medical effectiveness. Medicinal cannabis use frequency inversely predicted knowledge of medical effectiveness and increased risks of adverse events. CONCLUSION: There were considerable discrepancies between cannabis users' knowledge and available evidence, highlighting the need for more research and education (by physicians, caregivers, and dispensaries) on effectiveness and health risks, especially for users with specific health issues such as pregnant women and people with depression.

Cannabis use in pediatric cancer patients: what are they reading? A review of the online literature.

BACKGROUND: Recent changes to the legal status of marijuana in Canada warrant a review of the information that patients and families are accessing online regarding the role of cannabis in cancer. The aims of the current research were to identify the quality of literature available online as well as the themes, and opinion (i.e., pro-, neutral, or anti-cannabis) of online articles. METHODS: Searches were conducted using three primary search engines: Google, Yahoo, and DuckDuckGo. Articles were assessed for quality based on a modified scale for evaluating online sources. Content of all unique articles was coded using a qualitative thematic methodology in a line-by-line fashion. Codes were clustered to determine themes within articles. Finally, opinions were determined by examining all articles in a line-by-line fashion. Each statement was coded as either pro-cannabis (positive) or anti-cannabis (negative). RESULTS: We found most articles were authored by journalists (39.4%) and MDs (14.1%) and published as news (35.2%) or web articles (28.2%). The content of articles focused on four themes: the reasons for and against cannabis use; the opinions of health care providers; the restrictions placed by governing bodies and the need for additional research, education, and standardization. Article opinions were neutral-pro-cannabis. CONCLUSIONS: Health care providers should be aware that the overall quality of information found online is considered "satisfactory." The majority of articles present a pro-cannabis opinion.

Tetrahydrocannabinol and Cannabidiol Use in an Outpatient Palliative Medicine Population.

BACKGROUND: Palliative medicine physicians are challenged by lack of guidance regarding effectiveness and dosing of cannabis products in the setting of their emerging popularity. OBJECTIVE: The aim of this study was to describe early patterns of tetrahydrocannabinol (THC) and cannabidiol (CBD) use in Florida following passage of the state's first medical marijuana law. We describe here the perceived benefits, side effects, and beliefs expressed by patients in a single outpatient academic palliative medicine practice. METHODS: A cross-sectional survey was performed of a sequential convenience sample of patients who presented to an outpatient academic palliative medicine clinic over a 3-month period. RESULTS: In all, 24% (14/58) of respondents reported THC use, with half using THC on a daily basis. Patients reported improvements in pain, appetite, and nausea. In all, 71% (10/14) began using THC after the diagnosis of their chronic illness, and the most common form of usage was vaping. In all, 24% (14/58) of patients reported CBD use. Patients reported improvements in pain, and the most common form of usage was topical application. None of the patients had used CBD prior to the onset of their chronic illness. In all, 21% (3/14) of THC users and 21% (3/14) of CBD users thought that their substance was helping to cure their illness. Individual reported side effects in both groups were minimal. CONCLUSIONS: Approximately a quarter of outpatient palliative care patients use THC or CBD, often on a daily basis. Palliative care providers should be aware of the frequency, diverse usage, and beliefs behind cannabis product use in this patient population.