An Updated Analysis of Clinical Outcome Measures Across Patients From the UK Medical Cannabis Registry.

Introduction: There is a growing body of literature supporting the efficacy of cannabis-based medicinal products (CBMPs). Despite an increase in prescribing globally, there is a paucity of high-quality clinical data on the efficacy of CBMPs for many conditions. This study aims to detail the changes in health-related quality of life (HRQoL) and associated clinical safety in patients prescribed CBMPs for any clinical indication from the UK Medical Cannabis Registry (UKMCR). Methods: An uncontrolled prospective case series of the UKMCR was analyzed. Primary outcomes included change from baseline in patient-reported outcome measures collected across all patients (the Generalized Anxiety Disorder Scale [GAD-7], EQ-5D-5L, and Sleep Quality Scale [SQS]) at 1, 3, and 6 months. Secondary outcomes included the self-reported incidence and severity of adverse events. Statistical significance was defined as p<0.050. Results: Three hundred twelve patients were included in the final analysis, with a mean age of 44.8. The most common primary diagnoses were chronic pain of undefined etiology (n=102, 32.7%), neuropathic pain (n=43, 13.8%), and fibromyalgia (n=31, 9.9%). Before enrolment, 112 (35.9%) patients consumed cannabis daily. The median cannabidiol and (-)-trans-Δ9-tetrahydrocannabinol doses prescribed at baseline were 20.0 mg (0.0-510.0 mg) and 3.0 mg (0.0-660.0 mg), respectively. Statistically significant improvements were observed in GAD-7, EQ-5D-5L Index, EQ-5D Visual Analog Scale and SQS scores at 1, 3, and 6 months (p<0.050). There were 94 (30.1%) reported adverse events, of which nausea (n=12, 3.8%), dry mouth (n=10, 3.2%), dizziness (n=7, 2.2%), and somnolence (n=7, 2.2%) were the most common. Conclusion: This study demonstrated CBMP treatment to be associated with a relatively low incidence of severe adverse events in the medium-term. Positive changes following treatment were observed in general, as well as anxiety and sleep-specific, HRQoL outcomes. Randomized controlled trials are still awaited to assess causation; however, real-world evidence can help inform current clinical practice, future trials, and is an important component of pharmacovigilance.

Real World Evidence in Medical Cannabis Research.

BACKGROUND: Whilst access to cannabis-based medicinal products (CBMPs) has increased globally subject to relaxation of scheduling laws globally, one of the main barriers to appropriate patient access remains a paucity of high-quality evidence surrounding their clinical effects. DISCUSSION: Whilst randomised controlled trials (RCTs) remain the gold-standard for clinical evaluation, there are notable barriers to their implementation. Development of CBMPs requires novel approaches of evidence collection to address these challenges. Real world evidence (RWE) presents a solution to not only both provide immediate impact on clinical care, but also inform well-conducted RCTs. RWE is defined as evidence derived from health data sourced from non-interventional studies, registries, electronic health records and insurance data. Currently it is used mostly to monitor post-approval safety requirements allowing for long-term pharmacovigilance. However, RWE has the potential to be used in conjunction or as an extension to RCTs to both broaden and streamline the process of evidence generation. CONCLUSION: Novel approaches of data collection and analysis will be integral to improving clinical evidence on CBMPs. RWE can be used in conjunction or as an extension to RCTs to increase the speed of evidence generation, as well as reduce costs. Currently, there is an abundance of potential data however, whilst a number of platforms now exist to capture real world data it is important the right tools and analysis are utilised to unlock potential insights from these.

UK Medical Cannabis Registry: an analysis of clinical outcomes of medicinal cannabis therapy for generalized anxiety disorder.

OBJECTIVES: Anxiety disorders are one of the most common reasons for seeking treatment with cannabis-based medicinal products (CBMPs). Current pharmacological treatments are variable in efficacy and the endocannabinoid system has been identified as a potential therapeutic target. This study aims to detail the changes in health-related quality-of-life (HRQoL) and clinical safety following CBMP therapy for generalized anxiety disorder. METHODS: A case series from the UK Medical Cannabis Registry was performed. Primary outcomes included changes from baseline in patient-reported outcome measures (the General Anxiety Disorder Scale (GAD-7), EQ-5D-5L (a measure of health-related quality of life), and Sleep Quality Scale (SQS)) at 1, 3 and 6 months. Statistical significance was defined as p<0.050. RESULTS: Sixty-seven patients were treated for generalized anxiety disorder. Statistically significant improvements were observed in GAD-7, EQ-5D-5L Index Value, EQ5D Visual Analog Scale, and SQS scores at 1, 3 and 6 months (p<0.050). Twenty-five (39.1%) patients reported adverse events during the follow-up period. CONCLUSION: This study suggests that CBMPs may be associated with improvements in HRQoL outcomes when used as a treatment for generalized anxiety disorder. These findings must be treated with caution considering limitations of study design; however this data may help inform future clinical studies and practice.Plain Language SummaryAnxiety disorders are the most prevalent psychiatric illness type in the United Kingdom, with 8.2 million cases reported in 2010. Generalized anxiety disorder (GAD), the most common anxiety disorder, debilitates, and so reduces the quality of life of those who suffer from the condition.The efficacy of current treatments for GAD varies greatly from person-to-person. The endocannabinoid system in the human body is currently attracting a lot of attention in the scientific community as it can be targeted by chemicals in the cannabis plant to produce therapeutic effects in order to treat GAD. There is, however, a lack of studies investigating the effects of medicinal cannabis in GAD, and so this study aims to explore the drug's effect on quality of life in patients suffering from GAD.Sixty-seven patients who attended the Sapphire Clinics for medicinal cannabis treatment for GAD were included in the study. The results from this study highlight that medicinal cannabis may improve generalized anxiety disorder, general health-related quality of life, and sleep-specific outcomes at 1, 3, and 6 months after starting treatment. There was also a low number of severe, disabling, and life-threatening adverse events experienced by patients. Although this study explores the effects of medicinal cannabis in a real clinical setting, the results were not compared to other types of treatment. Future studies with a comparator are therefore needed before concluding the true effects of medicinal cannabis in patients with GAD.

UK Medical Cannabis registry: an analysis of clinical outcomes of medicinal cannabis therapy for chronic pain conditions.

OBJECTIVES: To explore pain-specific, general health-related quality of life (HRQoL), and safety outcomes of chronic pain patients prescribed cannabis-based medicinal products (CBMPs). METHODS: A case series was performed using patients with chronic pain from the UK Medical Cannabis Registry. Primary outcomes were changes in Brief Pain Inventory short-form (BPI), Short-form McGill Pain Questionnaire-2 (SF-MPQ-2), Visual Analogue Scale-Pain (VAS), General Anxiety Disorder-7 (GAD-7), Sleep Quality Scale (SQS), and EQ-5D-5L, at 1, 3, and 6 months from baseline. Statistical significance was defined at p-value<0.050. RESULTS: 190 patients were included. Median initial Δ9-tetrahydrocannabinol and cannabidiol daily doses were 2.0mg (range:0.0-442.0mg) and 20.0mg (range:0.0-188.0mg) respectively. Significant improvements were observed within BPI, SF-MPQ-2, GAD-7, SQS, EQ-5D-5 L index, and VAS measures at all timepoints (p<0.050). Seventy-five adverse events (39.47%) were reported, of which 37 (19.47%) were rated as mild, 23 (12.11%) as moderate, and 14 (7.37%) as severe. Nausea (n=11; 5.8%) was the most frequent adverse event. CONCLUSION: An association was identified between patients with chronic pain prescribed CBMPs and improvements in pain-specific and general HRQoL outcomes. Most adverse events were mild to moderate in severity, indicating CBMPs were well tolerated. Inherent limitations of study design limit its overall applicability.

UK Medical Cannabis Registry palliative care patients cohort: initial experience and outcomes.

INTRODUCTION: Palliative care aims to improve quality of life through optimal symptom control and pain management. Cannabis-based medicinal products (CBMPs) have a proven role in the treatment of chemotherapy-induced nausea and vomiting. However, there is a paucity of high-quality evidence with regards to the optimal therapeutic regimen, safety, and effectiveness of CBMPs in palliative care, as existing clinical trials are limited by methodological heterogeneity. The aim of this study is to summarise the outcomes of the initial subgroup of patients from the UK Medical Cannabis Registry who were prescribed CBMPs for a primary indication of palliative care, cancer pain and chemotherapy-induced nausea and vomiting, including effects on health-related quality of life and clinical safety. METHODS: A case series from the UK Medical Cannabis Registry of patients, who were receiving CBMPs for the indication of palliative care was undertaken. The primary outcome consisted of changes in patient-reported outcome measures including EQ-5D-5L, General Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), Pain Visual Analog Scale (VAS) and the Australia-Modified Karnofsky Performance Scale at 1 and 3 months compared to baseline. Secondary outcomes included the incidence and characteristics of adverse events. Statistical significance was defined by p-value< 0.050. RESULTS: Sixteen patients were included in the analysis, with a mean age of 63.25 years. Patients were predominantly prescribed CBMPs for cancer-related palliative care (n = 15, 94%). The median initial CBD and THC daily doses were 32.0 mg (Range: 20.0-384.0 mg) and 1.3 mg (Range: 1.0-16.0 mg) respectively. Improvements in patient reported health outcomes were observed according to SQS, EQ-5D-5L mobility, pain and discomfort, and anxiety and depression subdomains, EQ-5D-5L index, EQ-VAS and Pain VAS validated scales at both 1-month and 3-months, however, the changes were not statistically significant. Three adverse events (18.75%) were reported, all of which were either mild or moderate in severity. CONCLUSION: This small study provides an exploratory analysis of the role of CBMPs in palliative care in the first cohort of patients since CBMPs legalisation in the UK. CBMPs were tolerated with few adverse events, all of which were mild or moderate and resolved spontaneously. Further long-term safety and efficacy studies involving larger cohorts are needed to establish CBMPs role in palliative care, including comparisons with standard treatments.

An initial analysis of the UK Medical Cannabis Registry: Outcomes analysis of first 129 patients.

AIM: Cannabis-based medicinal products (CBMPs) are prescribed with increased frequency, despite a paucity of high-quality randomized controlled trials. The aim of this study is to analyze the early outcomes of the first series of patients prescribed CBMPs in the UK with respect to effects on health-related quality of life and clinical safety. METHODS: A prospective case series was performed using the UK Medical Cannabis Registry. Primary outcomes were change in patient-reported outcomes measures (EQ-5D-5L, General Anxiety Disorder-7 (GAD-7) and Single-Item Sleep Quality Scale (SQS)) at 1 and 3 months from baseline. The secondary outcome was the incidence of adverse events. Statistical significance was defined by a P-value <.050. RESULTS: There were 129 patients included in the final analysis with a mean age of 46.23 (±14.51) years. The most common indication was chronic pain of undefined etiology (n = 48; 37.2%). The median initial cannabidiol and (-)-trans-Δ9-tetrahydrocannabinol daily dose was 20.0 mg (Range: 0.0-768.0 mg) and 3.9 mg (Range: 0.0-660.0 mg), respectively. Statistically significant improvements in health-related quality of life were demonstrated at 1 and 3 months in GAD-7, SQS, EQ-5D-5L pain and discomfort subscale, EQ-5D-5L anxiety and depression subscale, EQ-VAS and EQ-5D-5L index values(P < .050). There were 31 (24.03%) total reported adverse events. CONCLUSION: This study suggests that CBMP therapy may be associated with an improvement in health-related quality-of-life outcomes as self-reported by patients. CBMPs are also demonstrated to be relatively safe in the short to medium-term. These findings must be treated with caution given the limited scope of this initial analysis, with no placebo or an active comparator, with further research required.

Cannflavins - From plant to patient: A scoping review.

INTRODUCTION: Cannflavins are a group of prenylflavonoids derived from Cannabis sativa L.. Cannflavin A (CFL-A), B (CFL-B) and C (CFL-C) have been heralded for their anti-inflammatory properties in pre-clinical evaluations. This scoping review aims to synthesise the evidence base on cannflavins to provide an overview of the current research landscape to inform research strategies to aid clinical translation. METHODS: A scoping review was conducted of EMBASE, MEDLINE, Pubmed, CENTRAL and Google Scholar databases up to 26th February 2020. All studies describing original research on cannflavins and their isomers were included for review. RESULTS: 26 full text articles were included. CFL-A and CFL-B demonstrated potent anti-inflammatory activity via inhibition of 12-o-tetradecanoylphorbol 13-acetate induced PGE2 release (CFL-A half maximal inhibitory concentration (IC50): 0.7 µM; CFL-B IC50: 0.7 µM) and microsomal prostaglandin E synthase-1 (CFL-A IC50: 1.8 µM; CFL-B IC50: 3.7 µM). Outcomes were also described in preclinical models of anti-oxidation (CFL-A), anti-parasitic activity (CFL-A, CFL-C), neuroprotection (CFL-A) and cancer (Isocannflavin B, a CFL-B isomer). In-silico screening identified that CFL-A has binding affinity with viral proteins that warrant further investigation. CONCLUSIONS: Cannflavins demonstrate a number of promising therapeutic properties, most notably as an anti-inflammatory agent. Low yields of extraction however have previously limited research to small pre-clinical investigations. Identification of cannflavin-rich chemovars, novel extraction techniques and recent identification of a biosynthetic pathway will hopefully allow research to be scaled appropriately. In order to fully evaluate the therapeutic properties of cannflavins focused research now needs to be embedded within institutions with a track-record of clinical translation.