Predictors of Pain Reduction Among Fibromyalgia Patients Using Medical Cannabis: A Long-Term Prospective Cohort Study.

OBJECTIVE: Many patients with fibromyalgia (FM) report using cannabis as a strategy to improve pain. Given that pain often co-occurs with symptoms of anxiety and depression (i.e., negative affect) and sleep problems among patients with FM, improvements in these symptoms might indirectly contribute to reductions in pain intensity following cannabis use. The main objective of the study was to examine whether changes in pain intensity following initiation of medical cannabis among patients with FM could be attributed to concurrent changes (i.e., reductions) in negative affect and sleep problems. METHODS: This was a 12-month prospective cohort study among patients with FM (n = 323) initiating medical cannabis under the care of physicians. Patients were assessed at baseline, and follow-up assessment visits occurred every 3 months after initiation of medical cannabis. Patients' levels of pain intensity, negative affect, and sleep problems were assessed across all visits. RESULTS: Multilevel mediation analyses indicated that reductions in patients' levels of pain intensity were partly explained by concurrent reductions in sleep problems and negative affect (both P < 0.001). This remained significant even when accounting for patients' baseline characteristics or changes in medical cannabis directives over time (all P > 0.05). CONCLUSION: Our findings provide preliminary insight into the potential mechanisms of action underlying pain reductions among patients with FM who are using medical cannabis. Given the high attrition rate (i.e., 75%) observed in the present study at 12 months, our findings cannot be generalized to all patients with FM who are using medical cannabis.

Pharmacokinetics of Cannabidiol in Sprague-Dawley Rats After Oral and Pulmonary Administration.

Introduction: Cannabidiol (CBD) is primarily consumed through ingestion and inhalation. Little is known about how CBD pharmacokinetics differ between routes of administration, and duration of pulmonary exposure. Methods: Pharmacokinetics, brain distribution, and urinary elimination of CBD and its major metabolites (6-hydroxy-cannabidiol [6-OH-CBD], 7-hydroxy-cannabidiol [7-OH-CBD], 7-carboxy-cannabidiol [7-COOH-CBD], and CBD-glucuronide) were evaluated in adult Sprague-Dawley rats following a single oral CBD ingestion (10 mg/kg in medium chain triglyceride oil; 24 male animals), and 1 or 14 days of repeated inhalation (0.9-13.9 mg/kg in propylene glycol [41%/59% by weight]; 5 male and 5 female animals per dose). Blood and brain tissue were collected at a single time point from each animal. Collection times were staggered from 5 min to 24 h postoral gavage or first (blood only) and final inhalation. Urine was collected 24 h postoral gavage or final inhalation. Samples were analyzed through liquid chromatography-mass spectrometry (LC-MS/MS). Results: CBD was more rapidly absorbed following inhalation than ingestion (Tmax=5 min and 2 h, respectively). Inhalation resulted in a dose-responsive increase in CBD Cmax and AUClast. CBD Cmax was 24-fold higher following the highest pulmonary dose (13.9 mg/kg) versus an oral dose of comparable concentration (10 mg/kg). Cmax and AUClast (0-16 h) trended higher following repeated exposure. Elimination was notably faster with repeated CBD inhalation (t1/2=5.3 and 2.4 h on days 1 and 14, respectively). While metabolites were detectable in plasma, AUClast (0-2 h) was at least 10- (7-OH-CBD, 7-COOH-CBD) to 100- (6-OH-CBD) fold lower than the parent compound. Metabolite concentration trended higher following repeated inhalation (6.7 mg/kg CBD); AUClast (0-16 h) was ∼1.8-, ∼1.4-, and ∼2.4-fold higher following 14 days of exposure for 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, respectively. CBD was detectable in brain homogenate tissue 24-h after 14-day inhalation (>3.5 mg/kg deposited dose) or a single oral administration. CBD metabolites were only measurable in brain tissue following the highest inhaled dose (13.9 mg/kg CBD). CBD, but not metabolites, was detectable in urine for all dose groups following 2 weeks of CBD inhalation. Neither CBD nor metabolites were present in urine after oral administration. Conclusion: CBD pharmacokinetics differ across oral and pulmonary routes of administration and acute or repeated dosing.

Serum Markers of Bone Turnover Following Controlled Administration of Two Medical Cannabis Products in Healthy Adults.

Introduction: Cannabidiol (CBD) has been shown to maintain bone integrity in pre-clinical models, but little is known about the effects of delta-9-tetrahydrocannabinol (THC) on bone turnover. In this study we explored the effects of two oral medical cannabis products on normal bone homeostasis through evaluation of markers of bone resorption (carboxyl-terminal collagen crosslinks, CTx) and bone formation (procollagen type 1 N-terminal propeptide, P1NP; alkaline phosphatase, ALP). Methods: This study is an analysis of secondary data from two Phase 1 double-blind, placebo-controlled trials of Spectrum Yellow (0.9 mg THC, 20 mg CBD/mL of oil) and Spectrum Red (2.5 mg THC, 0.3 mg CBD/softgel). Healthy participants (n=38 men, 45 women) were randomized to receive 5-20 mg THC (CBD levels varied as a function of administered product) or placebo daily (BID) for 7 days. Bone markers were assessed at baseline, upon completion of product administration (day 8), and after a 5-day washout (day 13). Results: All bone markers were significantly higher in men at baseline (p≤0.008). For CTx, there was a significant day×group interaction (F=3.23, p=0.04); CTx levels were significantly lower in participants treated with Spectrum Red (b=-164.28; 95% confidence interval [CI], -328 to -0.29; p=0.04) and marginally lower in participants treated with Spectrum Yellow (b=-157.31; 95% CI, -323 to 8.68; p=0.06) versus placebo on day 8. For P1NP and ALP, there were no significant differences between treatments across study days. Bone marker values outside the reference range (RR) were observed; CTx > RR (n=71) was predominantly (85.9%) observed in male participants, whereas P1NP > RR (n=100) was more evenly distributed between sexes (53.0% in men). These were not considered clinically significant and did not differ between treatment groups. Conclusions: These are the first interventional human data on the effect of cannabinoids on biomarkers of bone turnover. Short-term treatment with CBD- or THC-dominant medical cannabis products resulted in attenuation of a marker of bone resorption. Although the attenuation was not clinically significant, this finding may be indicative of protective properties of cannabinoids in bone. Further research over longer dosing durations in individuals exhibiting bone-specific conditions (e.g., osteoporosis) is warranted. ClinicalTrials.gov IDs: ACTRN12619001723178 and ACTRN12619001450101.

Longitudinal Relationship between the Introduction of Medicinal Cannabis and Polypharmacy: An Australian Real-World Evidence Study.

Background: Recent studies recommend medicinal cannabis (MC) as a potential treatment for chronic pain (CP) when conventional therapies are not successful; however, data from Australia is limited. This real-world evidence study explored how the introduction of MC related to concomitant medication use over time. Long-term safety also was examined. Methods: Data were collected by the Emerald Clinics (a network of seven clinics located across Australia) as part of routine practice from Jan 2020 toJan 2021. Medications were classified by group: antidepressants, benzodiazepines, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and total number of medications. Adverse events (AEs) were collected at each visit and subsequently coded using the Medical Dictionary for Regulatory Activities version 23 into the system organ class (SOC) and preferred term (PT). A total of 535 patients were analyzed. Results: The most common daily oral dose was 10 mg for delta-9-tetrahydrocannabinol (THC) and 15 mg for cannabidiol (CBD). With the introduction of MC, patients' total number of medications consumed decreased over the course of one year; significant reductions in NSAIDs, benzodiazepines, and antidepressants were observed (p < .001). However, the number of prescribed opioid medications did not differ from baseline to the end of one year (p = .49). Only 6% of patients discontinued MC treatment during the study. A total of 600 AEs were reported in 310 patients during the reporting period and 97% of them were classified as nonserious. Discussion. Though observational in nature, these findings suggest MC is generally well-tolerated, consistent with the previous literature, and may reduce concomitant use of some medications. Due to study limitations, concomitant medication reductions cannot be causally attributed to MC. Nevertheless, these data underscore early signals that warrant further exploration in randomized trials.

Medical cannabis authorization patterns, safety, and associated effects in older adults.

BACKGROUND: Use of medical cannabis is increasing among older adults. However, few investigations have examined cannabis use in this population. METHODS: We assessed the authorization patterns, safety, and effects of medical cannabis in a sub-analysis of 201 older adults (aged ≥ 65 years) who completed a 3-month follow-up during this observational study of patients who were legally authorized a medical cannabis product (N = 67). Cannabis authorization patterns, adverse events (AEs), Edmonton Symptom Assessment Scale-revised (ESAS-r), and Brief Pain Inventory Short Form (BPI-SF) data were collected. RESULTS: The most common symptoms for which medical cannabis was authorized were pain (159, 85.0%) and insomnia (9, 4.8%). At baseline and at the 3-month follow-up, cannabidiol (CBD)-dominant products were authorized most frequently (99, 54%), followed by balanced products (76, 42%), and then delta-9-tetrahydrocannabinol (THC)-dominant products (8, 4.4%). The most frequent AEs were dizziness (18.2%), nausea (9.1%), dry mouth (9.1%), and tinnitus (9.1%). Significant reductions in ESAS-r scores were observed over time in the domains of drowsiness (p = .013) and tiredness (p = .031), but not pain (p = .106) or well-being (p = .274). Significant reductions in BPI-SF scores over time were observed for worst pain (p = .010), average pain (p = .012), and overall pain severity (p = 0.009), but not pain right now (p = .052) or least pain (p = .141). CONCLUSIONS: Overall, results suggest medical cannabis was safe, well-tolerated, and associated with clinically meaningful reductions in pain in this sample of older adults. However, the potential bias introduced by the high subject attrition rate means that all findings should be interpreted cautiously and confirmed by more rigorous studies.

Effectiveness and Tolerability of Dronabinol Use in Patients with Chronic Pain: A Retrospective Analysis of 12-Week Open-Label Real-World Data Provided by the German Pain e-Registry.

OBJECTIVE: To evaluate the effectiveness of Δ9-tetrahydrocannabinol (dronabinol [DRO]) as an add-on treatment in patients with refractory chronic pain (CP). METHODS: An exploratory retrospective analysis of 12-week data provided by the German Pain e-Registry on adult patients with treatment refractory CP who received DRO. RESULTS: Between March 10, 2017, and June 30, 2019, the German Pain e-Registry collected information on 89,095 patients with pain, of whom 1,145 patients (1.3%) received DRO (53.8% female, mean ± standard deviation age: 56.9 ± 10.6 years), and 70.0% documented use for the entire 12-week evaluation period. The average DRO daily dose was 15.8 ± 7.5 mg, typically in three divided doses (average DRO dose of 5.3 ± 2.1 mg). Average 24-hour pain intensity decreased from 46.3 ± 16.1 to 26.8 ± 18.7 mm on a visual analog scale (absolute visual analog scale difference: -19.5 ± 17.3; P < 0.001). Among patients who completed follow-up, an improvement from baseline of at least 50% was documented for pain (46.5%), activities of daily living (39%), quality of life (31.4%), and sleep (35.3%). A total of 536 patients (46.8%) reported at least one of 1,617 drug-related adverse events, none of which were serious, and 248 patients (21.7%) stopped treatment. Over the 12-week period, 59.0% of patients reported a reduction of other pain treatments, and 7.8% reported a complete cessation of any other pharmacological pain treatments. CONCLUSION: Add-on treatment with DRO in patients with refractory CP was well tolerated and associated with a significant improvement.

Pharmacokinetics of cannabichromene in a medical cannabis product also containing cannabidiol and Δ9-tetrahydrocannabinol: a pilot study.

PURPOSE: Cannabichromene (CBC) is a phytocannabinoid commonly found in cannabis, yet its acute post-dose pharmacokinetics (PK) have not been examined in humans. This is a secondary data analysis from a trial investigating Spectrum Yellow oil, an oral cannabis product used for medical purposes that contained 20 mg cannabidiol (CBD), 0.9 mg Δ9-tetrahydrocannabinol (THC), and 1.1 mg CBC, per 1 mL of oil. METHODS: Participants (N = 43) were randomized to one of 5 groups: 120 mg CBD, 5.4 mg THC, and 6.6 mg CBC daily; 240 mg CBD, 10.8 mg THC, and 13.2 mg CBC daily; 360 mg CBD, 16.2 mg THC, and 19.8 mg CBC daily; 480 mg CBD, 21.6 mg THC, and 26.4 mg CBC daily; or placebo. Study medication was administered every 12 h for 7 days. Plasma CBC concentrations were analyzed by a validated two-dimensional high-performance liquid chromatography-tandem mass spectrometry assay. RESULTS: After a single dose and after the final dose, the Cmax of CBC increased by 1.3-1.8-fold for each twofold increase in dose; the tmax range was 1.6-4.3 h. Based on the ratio of administered CBD, THC, and CBC to the plasma concentration, the dose of CBD was 18 times higher than the dose of CBC, yet the AUC0-t of CBD was only 6.6-9.8-fold higher than the AUC0-t of CBC; the dose of THC was similar to the dose of CBC, yet THC was quantifiable in fewer plasma samples than was CBC. CONCLUSIONS: CBC may have preferential absorption over CBD and THC when administered together. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry #ACTRN12619001450101, registered 18 October 2019.

Cannabinoid Profiles in Medical Cannabis Users: Effects of Age, Gender, Symptoms, and Duration of Use.

Introduction: Clinical trials remain the gold standard for evaluating efficacy, but there is increasing interest in using real-world evidence (RWE) to inform health care decision making. The aims of this observational study were to describe patterns of medical cannabis use, associated changes in symptom severity over time, and to evaluate change in cannabis dose over time for pain-related symptoms. Methods: Data were collected by Strainprint™, an application that is HIPAA, PIPEDA, and PHIPA compliant. A total of 629 participants recorded data between May 2017 and August 2019. A total of 65 symptoms were grouped as Pain, Mental Health, Physical Symptoms, Seizures, Headaches/Migraines, and Other. Descriptive statistics and mixed-effects modeling were applied. Results: THC-dominant products were more frequently consumed for symptoms of pain and sleep, while CBD-dominant products were more frequently consumed for anxiety and depression. Male and female participants demonstrated significant differences in the type of cannabis they consumed. Females more frequently consumed CBD-dominant products, and males more frequently consumed balanced (THC:CBD) products. Oil use was more prominent among females, while vaping was more common among males. Product use also varied by age tertiles (<31; 31-39; >40 years). CBD-dominant products were more common among younger participants, <31 years, THC-dominant products were more common among the 31-39 years category and balanced (THC:CBD) products were common among older participants >41 years. Dosages of CBD-dominant and balanced (THC:CBD) products increased over time irrespective of symptom response. THC-dominant products demonstrated a significant relationship between dose and symptom reduction over time. Conclusions: Recognizing that RWE has important methodological limitations, we observed cannabis product preferences based on demographic characteristics, such as gender and age and the primary symptom treated such as pain and anxiety. Our study offers real-world insights into how participants use and respond to cannabis products and suggests important avenues and methodologies for future research.

Safety, Pharmacokinetics and Pharmacodynamics of Spectrum Yellow Oil in Healthy Participants.

Due to a lack of published pharmacokinetic (PK) and/or pharmacodynamic (PD) data, decision-making surrounding appropriate dosing of cannabis used for medical purposes is limited. This multiple-dose study evaluated the safety, tolerability, PK and PD of Spectrum Yellow oil [20 mg/mL cannabidiol (CBD)/<1 mg/mL ∆9-tetrahydrocannabinol (THC)]. Participants (n = 43) were randomized to one of five groups: 120 mg CBD and 5.4 mg THC daily, 240 mg CBD and 10.8 mg THC daily, 360 mg CBD and 16.2 mg THC daily, 480 mg CBD and 21.6 mg THC daily or placebo. Study medication was administered every 12 h for 7 consecutive days. Treatment-emergent adverse events (TEAEs); plasma and urine concentrations of THC, CBD and metabolites; and self-reported subjective effects were collected. Nearly all TEAEs (44/45) were of mild or moderate severity; none was serious. The highest incidence of TEAEs (67%) was in the two higher-dose treatment groups. The highest number of TEAEs (17/45) occurred on the first treatment day. Steady-state plasma CBD concentrations were reached by Day 7. On Day 7, CBD exposure showed dose proportionality (AUC0-t slope = 1.03 [0.70, 1.36], Cmax slope = 0.92 [0.53, 1.31]). Most plasma THC concentrations were below the limit of quantification. Across Days 1 and 7, there were no consistent differences in subjective effects between placebo and active study medication. A prudent approach to improve tolerability with Spectrum Yellow oil might involve initial doses no higher than 240 mg total CBD and 10.8 mg total THC daily in divided doses, with titration upward over time as needed based on tolerability.

Safety, Pharmacokinetics and Pharmacodynamics of Spectrum Red Softgels in Healthy Participants.

Due to a lack of published pharmacokinetic (PK) and/or pharmacodynamic (PD) data, informed physician and patient decision-making surrounding appropriate dosing of cannabis for medical purposes is limited. This Phase 1, multiple-dose study evaluated the safety, tolerability, PK and PD of Spectrum Red softgels (2.5 mg Δ9-tetrahydrocannabinol (THC) and <0.25 mg cannabidiol (CBD)). Participants (n = 41) were randomized to one of five groups: 5 mg THC and 0.06 mg CBD daily (Treatment A), 10 mg THC and 0.12 mg CBD daily (Treatment B), 15 mg THC and 0.18 mg CBD daily (Treatment C), 20 mg THC and 0.24 mg CBD daily (Treatment D) or placebo. Study medication was administered in divided doses, every 12 h, ∼60 min after a standardized meal, for 7 consecutive days. All treatment-emergent adverse events (TEAEs) (65/65) were of mild-to-moderate severity; none was serious. The highest number of TEAEs (30/65) occurred on the first day of treatment. The most common TEAEs included somnolence, lethargy and headache (reported by eight, seven and five participants, respectively). On Day 7, maximum observed plasma concentration of 11-carboxy-THC increased by 2.0- and 2.5-fold as the dose doubled between Treatments A and B and between Treatments B and D, respectively. Mean peak post-treatment ratings of self-reported subjective effects of 'feel any effect' and 'dazed' differed between Treatment D and placebo on Days 1, 3 and 7. Over a week of twice-daily dosing of Spectrum Red softgels, daily doses of THC up to 20 mg and of CBD up to 0.24 mg were generally safe and became better tolerated after the first day of treatment. A prudent approach to improve tolerability with Spectrum Red softgels might involve initial daily doses no higher than 10 mg THC and 0.12 mg CBD in divided doses, with titration upward over time as needed based on tolerability.

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.

Authorization Patterns, Safety, and Effectiveness of Medical Cannabis in Quebec.

Introduction: Despite increasing demand for data, little is known about the authorization patterns, safety, and effectiveness of medical cannabis products. Materials and Methods: We conducted a 2 year observational study of adult patients who were legally authorized a medical cannabis product from a single licensed producer; we captured and analyzed authorized cannabis use patterns by cannabinoid profile (tetrahydrocannabinol [THC]-dominant; cannabidiol [CBD]-dominant; and balanced (THC:CBD) and clinical outcomes using standardized outcome measures every 3 months for 12 months at a network of medical cannabis clinics in Quebec, Canada. Results: We recruited 585 patients (average age 56.5 years), of whom 61% identified as female and 85% reported pain as their primary complaint. Over 12 months, there was a significant increase in the number of products authorized (Z=2.59, p=0.01). The proportion of authorizations for a THC-dominant or CBD-dominant product increased relative to the proportion of authorizations for a balanced (THC:CBD) product (all p<0.01). Symptom improvement over time was observed for pain, tiredness, drowsiness, anxiety, and well-being. Patients authorized THC-dominant products exhibited less symptom improvement for anxiety and well-being relative to those authorized CBD-dominant or balanced (THC:CBD) products. Medical cannabis was well tolerated across all product profiles. Conclusion: These real-world data reveal changes in medical cannabis authorization patterns and suggest that symptom improvement may vary by cannabinoid profile over 12 months of follow-up.

Clinical Profiles of Concurrent Cannabis Use in Chronic Pain: A CHOIR Study.

OBJECTIVE: Despite evidence of the analgesic benefits of cannabis, there remains a relative scarcity of research on the short- and long-term effects of cannabis use in individuals with chronic pain. DESIGN: The current study is a secondary analysis of clinical data from the Collaborative Health Outcomes Information Registry (CHOIR). SETTING: Data were drawn from a cohort of patients of a multidisciplinary tertiary care pain clinic. SUBJECTS: The study sample consisted of data from 7,026 new patient visits from CHOIR; of these, 1,668 patients with a follow-up time point within 180 days were included in a longitudinal analysis. METHODS: Clinical data were analyzed to characterize cross-sectional differences in pain and indicators of psychological and physical function according to self-reported, concurrent cannabis use. Additionally, a propensity score-weighted longitudinal analysis was conducted, examining cannabis use as a predictor of changes in clinical variables across time. RESULTS: Cross-sectional analyses suggested significantly poorer sleep and significantly higher intensities of pain, emotional distress, and physical and social dysfunction in patients reporting ongoing cannabis use; however, these differences were relatively small in magnitude. However, no differences between cannabis users and nonusers in terms of longitudinal changes in clinical variables were noted. DISCUSSION: Our results are among the first to examine concurrent cannabis use as a prognostic variable regarding trajectories of pain-related variables in tertiary care. Future studies may benefit from examining the effect of cannabis initiation, concurrent medication use, and specific aspects of cannabis use (dose, duration of use, or cannabis type) on clinical outcomes.

The Quebec Low Back Pain Study: a protocol for an innovative 2-tier provincial cohort.

INTRODUCTION: The neurobiological mechanisms underlying recovery from or persistence of low back pain (LBP) remain misunderstood, limiting progress toward effective management. We have developed an innovative two-tier design to study the transition from acute to chronic LBP. The objective of the first tier is to create a provincial web-based infrastructure to recruit and monitor the trajectory of individuals with acute LBP. The objective of the second tier is to fuel hypothesis-driven satellite data collection centers with specialized expertise to study the role of biomechanical, epigenetic, genetic, neuroanatomical, ontological, physiological, psychological, and socioeconomic factors in LBP chronicity. METHODS: This article describes the first tier of the protocol: establishment of the Core Dataset and Cohort. Adults with acute LBP will be recruited through networks, media, and health care settings. A web-based interface will be used to collect self-reported variables at baseline and at 3, 6, 12, and 24 months. Acute LBP will be defined according to the Dionne 2008 consensus. Measurements will include the Canadian minimum data set for chronic LBP research, DN4 for neuropathic pain, comorbidities, EQ-5D-5L for quality of life, and linkage with provincial medico-administrative databases. The primary outcome will be the transition to chronic LBP, as defined by Deyo 2014. Secondary outcomes include health care resource utilization, disability, sick leave, mood, and quality of life. PERSPECTIVE: This study brings together diverse research expertise to investigate the transition from acute to chronic LBP, characterize the progression to recovery or chronicity, and identify patterns associated with that progression.

Determinants Of Patient Experience With Low Back Pain Interdisciplinary Care: A Pre-Post Interventional Study.

BACKGROUND AND PURPOSE: Measuring patients' experiences of health services has become an essential part of quality of care reporting and a means for identifying opportunities for improvement. This study aimed to evaluate change in patient experience in an interdisciplinary primary care program and to estimate the impact on patient experience of sociodemographic, function, pain and general health status, resource utilization, and process variables. PATIENTS AND METHODS: A 6-month interdisciplinary care program for individuals with low back pain (LBP) was implemented at four primary care settings and evaluated using an observational pre/post study design. The change in patient experience was evaluated using the Patient Assessment of Chronic Illness Care questionnaire (PACIC) completed at baseline and 6 months post-intervention (n=132). Descriptive and multivariable analyses were performed using SAS version 9.3. RESULTS: The average patient age was 57 (SD: 14) years of age and the majority were female (53%). The mean overall PACIC score was 2.6 (SD: 1.1) at baseline and 3.6 (SD: 0.9) at 6 months. The experience of care improved for 62% of the participants based on the minimal clinically important difference (MCID). No significant determinants of overall PACIC change score were identified in the multivariable regression models. CONCLUSION: The lack of association of hypothesized determinants requires further examination of the properties of the PACIC and with a larger sample. Future investigation is needed on the relationship between improved patient experience and outcomes.

Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis.

BACKGROUND: Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management. However, there is a lack of research using individual-level data to explore this question. We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain. METHODS AND FINDINGS: This study included data from people in 2 prospective cohorts of PWUD in Vancouver, Canada, who reported major or persistent pain from June 1, 2014, to December 1, 2017 (n = 1,152). We used descriptive statistics to examine reasons for cannabis use and a multivariable generalized linear mixed-effects model to estimate the relationship between daily (once or more per day) cannabis use and daily illicit opioid use. There were 424 (36.8%) women in the study, and the median age at baseline was 49.3 years (IQR 42.3-54.9). In total, 455 (40%) reported daily illicit opioid use, and 410 (36%) reported daily cannabis use during at least one 6-month follow-up period. The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34-0.74, p < 0.001). Limitations of the study included self-reported measures of substance use and chronic pain, and a lack of data for cannabis preparations, dosages, and modes of administration. CONCLUSIONS: We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain.

Guidelines for public health and safety metrics to evaluate the potential harms and benefits of cannabis regulation in Canada.

ISSUES: Canada recently introduced a public health-based regulatory framework for non-medical cannabis. This review sought to identify a comprehensive set of indicators to evaluate the public health and safety impact of cannabis regulation in Canada, and to explore the ways in which these indicators may be expected to change in the era of legal non-medical cannabis. APPROACH: Five scientific databases were searched to compile a list of cannabis-related issues of interest to public health and safety. A set of indicators was developed based on topics and themes that emerged. Preliminary evidence from other jurisdictions in the USA and Canada that have legalised medical and/or non-medical cannabis (e.g. Colorado, Washington) was summarised for each indicator, wherever possible. KEY FINDINGS: In total, 28 indicators were identified under five broad themes: public safety; cannabis use trends; other substance use trends; cardiovascular and respiratory health; and mental health and cognition. Preliminary trends from other legalised jurisdictions reveal little consensus regarding the effect of cannabis legalisation on public health and safety harms and an emerging body of evidence to support potential benefits (e.g. reductions in opioid use and overdose). IMPLICATIONS: In addition to indicators of commonly discussed challenges (e.g. cannabis-related hospitalisations, cannabis-impaired driving), this review led to the recommendation of several indicators to monitor for possible public health and safety improvements. CONCLUSION: In preparing a comprehensive public health and safety monitoring and evaluation system for cannabis regulation, this review underscores the importance of not only measuring the possible risks but also the potential benefits.

Examination of the Course of Low Back Pain Intensity Based on Baseline Predictors and Health Care Utilization Among Patients Treated in Multidisciplinary Pain Clinics: A Quebec Pain Registry Study.

OBJECTIVES: The study objectives were to identify baseline predictors of low back pain severity changes over a one-year period among patients attending multidisciplinary tertiary clinics and determine whether health care utilization impacts this outcome. METHODS: This is a retrospective cohort study using the Quebec Pain Registry (QPR). A total of 686 low back pain (LBP) patients (55.8% females, mean age = 56.51 ± 14.5 years) from the QPR were selected for this study. Patients completed self-report questionnaires and nurse-administered questionnaires before their first appointment at a multidisciplinary pain treatment center. Analysis was conducted using a linear growth model. RESULTS: There was a modest (10%) improvement in pain severity scores over a 12-month period. Pain catastrophizing and depressive symptoms predicted higher baseline levels of pain severity (P < 0.001). Having used self-management approaches over the past six months was associated with higher levels of pain severity at 12 months (P < 0.001). DISCUSSION: Results from this study showed no clear pattern of association between the use of different treatment disciplines and pain severiy over the first year after multidisciplinary treatment intervention. These results raise an important question as to the best way of utilizing scarce multidisciplinary resources to optimize cost-effectiveness and improve outcomes among complex, chronic LBP patients.

Cannabis use and driving-related performance in young recreational users: a within-subject randomized clinical trial.

BACKGROUND: With the legalization of cannabis in Canada, young adults, who are already at risk of automobile crashes, may increase their use of cannabis, which may further increase the risk of crashes. We examined the effects of inhaled cannabis on driving-related performance in healthy 18- to 24-year-old recreational cannabis users. METHODS: In this within-subject randomized study, participants completed tests in the no-cannabis state and at 1, 3 and 5 hours after inhalation of a standard 100-mg dose of cannabis. We then measured performance (in useful-field-of-view and driving-simulation tests) and self-reported perceptions (driving ability and safety, cannabis effects). Repeated-measures analysis of variance (for cannabis effects on continuous performance measures), Cochran Q tests (for performance-related crash risk and binary complex simulator task scores) and correlational analyses (for self-reported perceptions relative to performance) were employed. RESULTS: Forty-five participants completed all 180 testing sessions. Significant effects of cannabis (relative to no cannabis) were noted on complex useful-field-of-view tasks at 3 hours (complex divided-attention task: 70 ± 24 ms v. 37 ± 12 ms, 95% confidence intervals [CIs] 28-114 ms v. 29-45 ms, t = -2.98, df = 41, p = 0.005; complex selective-attention task: 102 ± 66 ms v. 64 ± 18 ms, 95% CIs 60-144 ms v. 53-75 ms, t = -2.42, df = 41, p = 0.02) and 5 hours (complex selective-attention task: 82 ± 29 ms v. 61 ± 19 ms, 95% CIs 62-100 ms v. 48-75 ms, t = -2.32, df = 41, p = 0.03) after cannabis use when the tasks were novel (performed in a cannabis state at the first session). Participants were significantly more likely to be classified as having a high crash risk (on the basis of simulator tasks) after cannabis use (χ 2 = 13.23, df = 1, p < 0.001, odds ratio 4.31, 95% CI 0.41-45.2) and reported significantly lower perceived driving ability and safety after cannabis use relative to non-use. INTERPRETATION: Among young recreational cannabis users, a 100-mg dose of cannabis by inhalation had no effect on simple driving-related tasks, but there was significant impairment on complex tasks, especially when these were novel. These effects, along with lower self-perceived driving ability and safety, lasted up to 5 hours after use. TRIAL REGISTRATION: The trial was registered with Health Canada (NOL [No Objection Letter] no. 215101).