Assessment of Clinical Outcomes in Patients With Osteoarthritis: Analysis From the UK Medical Cannabis Registry.

Osteoarthritis accounts for 0.6% of disability-adjusted life years globally. There is a paucity of research focused on cannabis-based medicinal products (CBMPs) for osteoarthritic chronic pain management. This study aims to assess changes in validated patient-reported outcome measures (PROMs) and CBMP clinical safety in patients with osteoarthritis. A prospective case series from the UK Medical Cannabis Registry was analyzed. Primary outcomes were changes in the Brief Pain Inventory (BPI), McGill Pain Questionnaire (MPQ2), EQ-5D-5L, Generalized Anxiety Disorder-7 (GAD-7) questionnaire, and Single-Item Sleep Quality Scale (SQS) at 1-, 3-, 6-, and 12-month follow-ups from baseline. Common Terminology Criteria for Adverse Events v.4.0 was used for adverse event (AE) analysis. Statistical significance was defined as p < 0.050. Seventy-seven patients met inclusion criteria. CBMP initiation correlated with BPI pain severity (p = 0.004), pain interference (p = 0.005), and MPQ2 (p = 0.017) improvements at all follow-ups compared to baseline. There were improvements in the EQ-5D-5L index (p = 0.026), SQS (p < 0.001), and GAD-7 (p = 0.038) up to 6 and 3 months, respectively. Seventeen participants (22.08%) recorded 76 mild AEs (34.86%), 104 moderate AEs (47.71%), and 38 severe AEs (17.43%). Though causality cannot be assumed in this observational study, results support development of randomized control trials for osteoarthritis pain management with CBMPs.

UK Medical Cannabis Registry: a case series analyzing clinical outcomes of medical cannabis therapy for generalized anxiety disorder patients.

This study aims to analyze changes in health-related quality of life (HRQoL) and safety in patients with generalized anxiety disorder (GAD) prescribed a homogenous selection of cannabis-based medicinal products (CBMPs). Patients prescribed Adven CBMPs (Curaleaf International, UK) for GAD were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in patient-reported outcome measures (PROMs) from baseline up to 12 months, including GAD-7, Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L. Adverse events were recorded using CTCAE version 4.0. A total of 120 patients were identified for inclusion, of which 38 (31.67%), 52 (43.33%), and 30 (25.00%) were prescribed oils, dried flower, and both formulations of CBMP. Associated improvements in GAD-7, SQS, and EQ-5D-5L at 1, 3, 6, and 12 months were observed compared to baseline (P < 0.010). There were 24 (20.00%) patients who reported 442 (368.33%) adverse events, most of which were mild (n = 184, 41.63%) and moderate (n = 197, 44.57%). This study reports an association between initiation of a homogeneous CBMP therapy and improvements in anxiety severity and HRQoL in individuals with GAD. Moreover, therapy was well-tolerated at 12 months follow-up. Further investigation through randomized controlled trials will ultimately be required to determine causation.

UK Medical Cannabis Registry: Assessment of clinical outcomes in patients with insomnia.

INTRODUCTION: The primary aim of this study was to assess changes in sleep-specific health-related quality of life (HRQoL) for those prescribed cannabis-based medicinal products (CBMPs) for insomnia. METHODS: A case series of UK patients with insomnia was analyzed. Primary outcomes were changes in the Single-Item Sleep-Quality Scale (SQS), Generalized Anxiety Disorder-7 (GAD-7), and EQ-5D-5L at up to 6 months from baseline. Statistical significance was identified as a p value < .050. RESULTS: 61 patients were included in the analysis. There was an improvement in the SQS from baseline at 1, 3, and 6 months (p < .001). There were also improvements in the EQ-5D-5L Index value and GAD-7 at 1, 3, and 6 months (p < .050). There were 28 (45.9%) adverse events recorded by 8 patients (13.1%). There were no life-threatening/disabling adverse events. CONCLUSION: Patients with insomnia experienced an improvement in sleep quality following the initiation of CBMPs in this medium-term analysis. Fewer than 15% of participants reported one or more adverse events. However, due to the limitations of the study design, further investigation is required before definitive conclusions can be drawn on the efficacy of CBMPs in treating insomnia.

Corrigendum: Cannabis use in the UK: a quantitative comparison of individual differences in medical and recreational cannabis users.

[This corrects the article DOI: 10.3389/fpsyg.2023.1279123.].

A cohort study comparing the effects of medical cannabis for anxiety patients with and without comorbid sleep disturbance.

BACKGROUND: Research on cannabis-based medicinal products (CBMPs) in anxiety remains inconclusive due to a paucity of high-quality evidence. Studies indicate a bidirectional relationship between generalized anxiety disorder (GAD) and sleep disruption, but it is unclear how this affects CBMP treatment outcomes. This study aims to compare the patient-reported outcome measures (PROMs) of patients prescribed CBMPs for GAD, with and without impaired sleep. METHODS: Changes in PROMs were recorded from baseline to 1, 3, 6, and 12 months between those with impaired or unimpaired sleep. Multivariate logistic regression was applied to compare factors associated with a clinically significant improvement in GAD-7 at 12 months. Secondary outcomes included adverse event incidence and frequency. RESULTS: Of the 302 patients that fit the inclusion criteria, mean GAD-7, single-item sleep quality, and EQ-5D-5L index values improved at all time points (p < 0.001). A relationship between sleep impairment and clinically significant changes in GAD-7 at 1 and 3 months was identified (p ≤ 0.01). On multivariate regression, only baseline GAD severity was associated with an increased likelihood of observing a clinically significant improvement in anxiety (p < 0.001). Seven hundred and seven (234%) adverse events were reported by 55 (18.21%) participants. CONCLUSIONS: This study observed an association between CBMP treatment and improvements in anxiety in patients with GAD. While patients with comorbid sleep disruption had greater improvements in anxiety, the differences were not maintained in a multivariate analysis. Baseline anxiety severity may be a predictor for CBMP treatment outcomes.

UK Medical Cannabis Registry: An analysis of clinical outcomes of medicinal cannabis therapy for attention-deficit/hyperactivity disorder.

AIM: This study aims to analyze the health-related quality of life (HRQoL) and safety outcomes in attention-deficit/hyperactivity disorder (ADHD) patients treated with cannabis-based medicinal products (CBMPs). METHODS: Patients were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in the following patient-reported outcome measures (PROMs) at 1, 3, 6, and 12 months from baseline: EQ-5D-5L index value, generalized anxiety disorder-7 (GAD-7) questionnaire, and the single-item sleep quality score (SQS). Secondary outcomes assessed the incidence of adverse events. Statistical significance was defined as p < 0.050. RESULTS: Sixty-eight patients met the inclusion criteria. Significant improvements were identified in general HRQoL assessed by EQ-5D-5L index value at 1, 3, and 6 months (p < 0.050). Improvements were also identified in GAD-7 and SQS scores at 1, 3, 6, and 12 months (p < 0.010). 61 (89.71%) adverse events were recorded by 11 (16.18%) participants, of which most were moderate (n = 26, 38.24%). CONCLUSION: An association between CBMP treatment and improvements in anxiety, sleep quality, and general HRQoL was observed in patients with ADHD. Treatment was well tolerated at 12 months. Results must be interpreted with caution as a causative effect cannot be proven. These results, however, do provide additional support for future evaluation within randomized controlled trials.

An observational study of clinical outcome measures in patients treated with cannabis-based medicinal products on the UK Medical Cannabis Registry.

INTRODUCTION: While there is increasing evidence of the effects of cannabis-based medicinal products (CBMPs) on health-related quality of life (HRQoL), a major limitation of the current literature is the heterogeneity of studied CBMPs. This study aims to analyze changes in HRQoL in patients prescribed a homogenous selection of CBMPs. METHODS: Primary outcomes were changes in patient-reported outcomes (PROMs) at 1, 3, 6, and 12 months from baseline. The secondary outcome was an adverse events analysis. Statistical significance was defined as p < 0.050. RESULTS: 1378 patients prescribed Adven® CBMPs (Curaleaf International, Guernsey, UK) were included in the final analysis. 581 (42.16%) participants were current users of cannabis at baseline. 641 (46.51%), 235 (17.05%), and 502 (36.43%) patients were treated with oils, dried flowers, or a combination of the two, respectively. Improvements were found in all PROMs in each route of administration at 1, 3, 6, and 12 months from baseline (p < 0.010). Those prescribed dried flower only or both oils and dried flower experienced greater improvements in GAD-7, SQS, and EQ-5D-5L index values at 12 months (p < 0.050). There was no difference in outcomes between those prescribed dried flower only or dried flower with oils (p > 0.050). 3663 (265.82%) adverse events were reported by 297 (21.55%) patients. CONCLUSION: There was an associated improvement in self-reported anxiety, sleep quality, and HRQoL in patients treated with the CBMPs. Those prescribed treatment formulations including dried flower were most likely to show a clinical improvement. However, these results must be interpreted with caution given the limitations of study design.

Terpenes in Cannabis sativa Inhibit Capsaicin Responses in Rat DRG Neurons via Na+/K+ ATPase Activation.

Terpenes in Cannabis sativa exert analgesic effects, but the mechanisms are uncertain. We examined the effects of 10 terpenes on capsaicin responses in an established model of neuronal hypersensitivity. Adult rat DRG neurons cultured with neurotrophic factors NGF and GDNF were loaded with Fura2AM for calcium imaging, and treated with individual terpenes or vehicle for 5 min, followed by 1 µMol capsaicin. In vehicle treated control experiments, capsaicin elicited immediate and sustained calcium influx. Most neurons treated with terpenes responded to capsaicin after 6-8 min. Few neurons showed immediate capsaicin responses that were transient or normal. The delayed responses were found to be due to calcium released from the endoplasmic reticulum, as they were maintained in calcium/magnesium free media, but not after thapsigargin pre-treatment. Terpene inhibition of calcium influx was reversed after washout of medium, in the absence of terpenes, and in the presence of the Na+/K+ ATPase inhibitor ouabain, but not CB1 or CB2 receptor antagonists. Thus, terpenes inhibit capsaicin evoked calcium influx by Na+/K+ ATPase activation. Immunofluorescence showed TRPV1 co-expression with α1ß1 Na+/K+ ATPase in most neurons while others were either TRPV1 or α1ß1 Na+/K+ ATPase positive.

Clinical outcome data of anxiety patients treated with cannabis-based medicinal products in the United Kingdom: a cohort study from the UK Medical Cannabis Registry.

RATIONALE: Cannabis-based medicinal products (CBMPs) have been identified as novel therapeutics for generalised anxiety disorder (GAD) based on pre-clinical models; however, there is a paucity of high-quality evidence on their effectiveness and safety. OBJECTIVES: This study aimed to evaluate the clinical outcomes of patients with GAD treated with dried flower, oil-based preparations, or a combination of both CBMPs. METHODS: A prospective cohort study of patients with GAD (n = 302) enrolled in the UK Medical Cannabis Registry prescribed oil or flower-based CBMPs was performed. Primary outcomes were changes in generalised anxiety disorder-7 (GAD-7) questionnaires at 1, 3, and 6 months compared to baseline. Secondary outcomes were single-item sleep quality scale (SQS) and health-related quality of life index (EQ-5D-5L) questionnaires at the same time points. These changes were assessed by paired t-tests. Adverse events were assessed in line with CTCAE (Common Terminology Criteria for Adverse Events) v4.0. RESULTS: Improvements in anxiety, sleep quality and quality of life were observed at each time point (p < 0.001). Patients receiving CBMPs had improvements in GAD-7 at all time points (1 month: difference -5.3 (95% CI -4.6 to -6.1), 3 months: difference -5.5 (95% CI -4.7 to -6.4), 6 months: difference -4.5 (95% CI -3.2 to -5.7)). Thirty-nine participants (12.9%) reported 269 adverse events in the follow-up period. CONCLUSIONS: Prescription of CBMPs in those with GAD is associated with clinically significant improvements in anxiety with an acceptable safety profile in a real-world setting. Randomised trials are required as a next step to investigate the efficacy of CBMPs.

Characterization of the biochemical and behavioral effects of cannabidiol: implications for migraine.

Cannabidiol (CBD) is the main pharmacologically active phytocannabinoid. CBD exerts an analgesic effect in several pain models, does not have side effects and has low toxicity. The data about CBD mechanisms of action in pain and its therapeutic potential in this area are limited. Here, we tested CBD effects in animal models specific for migraine. We assayed CBD distribution in plasma and in cranial areas related to migraine pain in male Sprague Dawley rats treated chronically (5 days). Successively, we tested CBD activity on the behavioral and biochemical effects induced in the acute and the chronic migraine animal models by nitroglycerin (NTG) administration. In the acute migraine model, rats received CBD (15 mg or 30 mg/kg, i.p) 3 h after NTG (10 mg/kg i.p.) or vehicle injection. In the chronic migraine model, rats were treated with CBD and NTG every other day over nine days with the following doses: CBD 30 mg/kg i.p., NTG 10 mg/kg i.p. We evaluated behavioral parameters with the open field and the orofacial formalin tests. We explored the fatty acid amide hydrolase gene expression, cytokines mRNA and protein levels in selected brain areas and CGRP serum level. CBD levels in the meninges, trigeminal ganglia, cervical spinal cord, medulla pons, and plasma were higher 1 h after the last treatment than after 24 h, suggesting that CBD penetrates but does not accumulate in these tissues. In the acute model, CBD significantly reduced NTG-induced trigeminal hyperalgesia and CGRP and cytokine mRNA levels in peripheral and central sites. In the chronic model, CBD caused a significant decrease in NTG-induced IL-6 protein levels in the medulla-pons, and trigeminal ganglion. It also reduced CGRP serum levels. By contrast, CBD did not modulate TNF-alpha protein levels and fatty acid amide hydrolase (FAAH) gene expression in any of investigated areas. In both experimental conditions, there was no modulation of anxiety, motor/exploratory behavior, or grooming. These findings show that CBD reaches brain areas involved in migraine pain after systemic administration. They also show for the first time that CBD modulates migraine-related nociceptive transmission, likely via a complex signaling mechanism involving different pathways.

Assessment of clinical outcomes in patients with fibromyalgia: Analysis from the UK Medical Cannabis Registry.

INTRODUCTION: There are limited therapeutic options for individuals with fibromyalgia. The aim of this study is to analyze changes in health-related quality of life and incidence of adverse events of those prescribed cannabis-based medicinal products (CBMPs) for fibromyalgia. METHODS: Patients treated with CBMPs for a minimum of 1 month were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in validated patient-reported outcome measures (PROMs). A p-value of <.050 was deemed statistically significant. RESULTS: In total, 306 patients with fibromyalgia were included for analysis. There were improvements in global health-related quality of life at 1, 3, 6, and 12 months (p < .0001). The most frequent adverse events were fatigue (n = 75; 24.51%), dry mouth (n = 69; 22.55%), concentration impairment (n = 66; 21.57%), and lethargy (n = 65; 21.24%). CONCLUSION: CBMP treatment was associated with improvements in fibromyalgia-specific symptoms, in addition to sleep, anxiety, and health-related quality of life. Those who reported prior cannabis use appeared to have a greater response. CBMPs were generally well-tolerated. These results must be interpreted within the limitations of study design.

Clinical outcome data of chronic pain patients treated with cannabis-based oils and dried flower from the UK Medical Cannabis Registry.

BACKGROUND: The following study evaluated the clinical outcomes of patients enrolled in the UK Medical Cannabis Registry, who were treated with inhaled dried flower (Adven® EMT2, Curaleaf International, Guernsey), and sublingual/oral medium-chain triglyceride-based oils (Adven, Curaleaf International, Guernsey) for chronic pain. METHODS: In this cohort study, the primary outcomes were changes in validated patient reported outcome measures (PROMs) at 1, 3, and 6 months compared to baseline, and adverse event analysis. Statistical significance was defined as p < 0.050. RESULTS: Three hundred and forty-eight (45.7%), 36 (4.7%), and 377 (49.5%) patients were treated with oils, dried flower, or both, respectively. Patients treated with oils or combination therapy recorded improvements within health-related quality of life, pain, and sleep-specific PROMs at 1, 3, and 6 months (p < 0.050). Patients treated with combination therapy recorded improvements in anxiety-specific PROMs at 1, 3, and 6 months (p < 0.050). 1,273 (167.3%) adverse events were recorded, with previously cannabis naïve users, ex-cannabis users, and females more likely to experience adverse events (p < 0.050). CONCLUSIONS: This study observed an association between initiation of CBMP treatment and improved outcomes for chronic pain patients. Prior cannabis use and gender were associated with adverse event incidence. Placebo-controlled trials are still necessary to establish the efficacy and safety of CBMPs for chronic pain.

Comparing the effects of medical cannabis for chronic pain patients with and without co-morbid anxiety: A cohort study.

INTRODUCTION: There is growing evidence on the efficacy of cannabis-based medicinal products (CBMPs) for chronic pain (CP). Due to the interaction between CP and anxiety, and the potential impact of CBMPs on both anxiety and CP, this article aimed to compare the outcomes of CP patients with and without co-morbid anxiety following CBMP treatment. METHODS: Participants were prospectively enrolled and categorized by baseline General Anxiety Disorder-7(GAD-7) scores, into 'no anxiety'(GAD-7 < 5) and 'anxiety'(GAD-7 ≥ 5) cohorts. Primary outcomes were changes in Brief Pain Inventory Short-Form, Short-form McGill Pain Questionnaire-2, Pain Visual Analogue Scale, Sleep Quality Scale (SQS), GAD-7 and EQ-5D-5L index values at 1, 3 and 6 months. RESULTS: 1254 patients (anxiety = 711; no anxiety = 543) met inclusion criteria. Significant improvements in all primary outcomes were observed at all timepoints (p < 0.050), except GAD-7 in the no anxiety group(p > 0.050). The anxiety cohort reported greater improvements in EQ-5D-5L index values, SQS and GAD-7(p < 0.050), but there were no consistent differences in pain outcomes. CONCLUSION: A potential association between CBMPs and improvements in pain and health-related quality of life (HRQoL) in CP patients was identified. Those with co-morbid anxiety reported greater improvements in HRQoL.

UK medical cannabis registry: assessment of clinical outcomes in patients with headache disorders.

OBJECTIVES: Headache disorders are a common cause of disability and reduced health-related quality of life globally. Growing evidence supports the use of cannabis-based medicinal products (CBMPs) for chronic pain; however, a paucity of research specifically focuses on CBMPs' efficacy and safety in headache disorders. This study aims to assess changes in validated patient-reported outcome measures (PROMs) in patients with headaches prescribed CBMPs and investigate the clinical safety in this population. METHODS: A case series of the UK Medical Cannabis Registry was conducted. Primary outcomes were changes from baseline in PROMs (Headache Impact Test-6 (HIT-6), Migraine Disability Assessment (MIDAS), EQ-5D-5L, Generalized Anxiety Disorder-7 (GAD-7) questionnaire and Single-Item Sleep Quality Scale (SQS)) at 1-, 3-, and 6-months follow-up. P-values <0.050 were deemed statistically significant. RESULTS: Ninety-seven patients were identified for inclusion. Improvements in HIT-6, MIDAS, EQ-5D-5L and SQS were observed at 1-, 3-, and 6-months (p < 0.005) follow-up. GAD-7 improved at 1- and 3-months (p < 0.050). Seventeen (17.5%) patients experienced a total of 113 (116.5%) adverse events. CONCLUSION: Improvements in headache/migraine-specific PROMs and general health-related quality of life were associated with the initiation of CBMPs in patients with headache disorders. Cautious interpretation of results is necessary, and randomized control trials are required to ascertain causality.

UK Medical Cannabis Registry: A Patient Evaluation.

The UK Medical Cannabis Registry is the largest real world data platform for medical cannabis outcomes in the UK, providing insight into clinical outcomes and monitoring safety of this novel therapy. This study aims to assess the functionality and accessibility of the online data collection platform and patient priorities for future research. Descriptive statistics were used to analyze quantitative data. For open-ended questions an inductive thematic analysis was performed. 600 responses were recorded. 554 (92.3%) patients had used the platform. 272 (90.4%) patients believed it was easy to input medications. 52 (8.67%) patients recorded an adverse event with 38 (73.1%) finding it easy to record. 535 (96.6%) patients had completed health questionnaires with 490 (91.6%) patients finding this easy to do. 553 (92.2%) patients agreed that contributing to the registry would impact the medical care of future patients. "Assessing the impact of medical cannabis on quality of life generally" was the top research priority for 357 (59.3%) patients. This study demonstrates that most enrolled patients found the platform easy to use and believed they were positively impacting future medical cannabis patient care. Future patient research priorities included assessment of quality of life and condition-specific outcomes.