Search

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., (© The Author(s) 2021. Published by Oxford University Press.)

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., (© The Author(s) 2021. Published by Oxford University Press.)

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.

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 Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Cannabis (marijuana) is undergoing extensive regulatory review in many global jurisdictions for medical and nonmedical access. Cannabis has potential impact on the health of athletes as well as on performance in both training and in competition. The aim of this general review is to identify and highlight the challenges in interpreting information with respect to elite athletic performance, and to point to important research areas that need to be addressed., Data Sources: A nonsystematic literature review was conducted using Medline and PubMed for articles related to cannabis/marijuana use and sports/athletic performance; abstracts were reviewed by lead author and key themes identified and explored., Main Results: Cannabis may be primarily inhaled or ingested orally for a range of medical and nonmedical reasons; evidence for efficacy is limited but promising for chronic pain management. Although evidence for serious harms from cannabis use on health of athletes is limited, one should be cognizant of the potential for abuse and mental health issues. Although the prevalence of cannabis use among elite athletes is not well-known, use is associated with certain high-risk sports. There is no evidence for cannabis use as a performance-enhancing drug., Conclusions: Medical and nonmedical cannabis use among athletes reflects changing societal and cultural norms and experiences. Although cannabis use is more prevalent in some athletes engaged in high-risk sports, there is no direct evidence of performance-enhancing effects in athletes. The potential beneficial effects of cannabis as part of a pain management protocol, including reducing concussion-related symptoms, deserve further attention.

Unlabelled: Chronic neuropathic pain, the most frequent condition affecting the peripheral nervous system, remains underdiagnosed and difficult to treat. Inhaled cannabis may alleviate chronic neuropathic pain. Our objective was to synthesize the evidence on the use of inhaled cannabis for chronic neuropathic pain. We performed a systematic review and a meta-analysis of individual patient data. We registered our protocol with PROSPERO CRD42011001182. We searched in Cochrane Central, PubMed, EMBASE, and AMED. We considered all randomized controlled trials investigating chronic painful neuropathy and comparing inhaled cannabis with placebo. We pooled treatment effects following a hierarchical random-effects Bayesian responder model for the population-averaged subject-specific effect. Our evidence synthesis of individual patient data from 178 participants with 405 observed responses in 5 randomized controlled trials following patients for days to weeks provides evidence that inhaled cannabis results in short-term reductions in chronic neuropathic pain for 1 in every 5 to 6 patients treated (number needed to treat = 5.6 with a Bayesian 95% credible interval ranging between 3.4 and 14). Our inferences were insensitive to model assumptions, priors, and parameter choices. We caution that the small number of studies and participants, the short follow-up, shortcomings in allocation concealment, and considerable attrition limit the conclusions that can be drawn from the review. The Bayes factor is 332, corresponding to a posterior probability of effect of 99.7%., Perspective: This novel Bayesian meta-analysis of individual patient data from 5 randomized trials suggests that inhaled cannabis may provide short-term relief for 1 in 5 to 6 patients with neuropathic pain. Pragmatic trials are needed to evaluate the long-term benefits and risks of this treatment., (Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Cannabinoids, including tetrahydrocannabinol and cannabidiol, are the most important active constituents of the cannabis plant. Over recent years, cannabinoid-based medicines (CBMs) have become increasingly available to patients in many countries, both as pharmaceutical products and as herbal cannabis (marijuana). While there seems to be a demand for multiple cannabinoid-based therapeutic products, specifically for symptomatic amelioration in chronic diseases, therapeutic effects of different CBMs have only been directly compared in a few clinical studies. The survey presented here was performed by the International Association for Cannabinoid Medicines (IACM), and is meant to contribute to the understanding of cannabinoid-based medicine by asking patients who used cannabis or cannabinoids detailed questions about their experiences with different methods of intake. The survey was completed by 953 participants from 31 countries, making this the largest international survey on a wide variety of users of cannabinoid-based medicine performed so far. In general, herbal non-pharmaceutical CBMs received higher appreciation scores by participants than pharmaceutical products containing cannabinoids. However, the number of patients who reported experience with pharmaceutical products was low, limiting conclusions on preferences. Nevertheless, the reported data may be useful for further development of safe and effective medications based on cannabis and single cannabinoids.

Safety issues are a major barrier to the use of cannabis and cannabinoid medications for clinical purposes. Information on the safety of herbal cannabis may be derived from studies of recreational cannabis use, but cannabis exposure and effects may differ widely between medical and recreational cannabis users. Standardized, quality-controlled cannabinoid products are available in Canada, and safety profiles of approved medications are available through the Canadian formulary. In the present article, the evidence behind major safety issues related to cannabis use is summarized, with the aim of promoting informed dialogue between physicians and patients in whom cannabinoid therapy is being considered. Caution is advised in interpreting these data, because clinical experience with cannabinoid use is in the early stages. There is a need for long-term safety monitoring of patients using cannabinoids for a wide variety of conditions, to further guide therapeutic decisions and public policy.

There has been a surge in interest in medicinal cannabis in Canada. We conducted a questionnaire survey to determine the current prevalence of medicinal cannabis use among patients with chronic non-cancer pain, to estimate the dose size and frequency of cannabis use, and to describe the main symptoms for which relief was being sought. Over a 6-week period in mid-2001, 209 chronic non-cancer pain patients were recruited in an anonymous cross-sectional survey. Seventy-two (35%) subjects reported ever having used cannabis. Thirty-two (15%) subjects reported having used cannabis for pain relief (pain users), and 20 (10%) subjects were currently using cannabis for pain relief. Thirty-eight subjects denied using cannabis for pain relief (recreational users). Compared to never users, pain users were significantly younger (P=0.001) and were more likely to be tobacco users (P=0.0001). The largest group of patients using cannabis had pain caused by trauma and/or surgery (51%), and the site of pain was predominantly neck/upper body and myofascial (68% and 65%, respectively). The median duration of pain was similar in both pain users and recreational users (8 vs. 7 years; P=0.7). There was a wide range of amounts and frequency of cannabis use. Of the 32 subjects who used cannabis for pain, 17 (53%) used four puffs or less at each dosing interval, eight (25%) smoked a whole cannabis cigarette (joint) and four (12%) smoked more than one joint. Seven (22%) of these subjects used cannabis more than once daily, five (16%) used it daily, eight (25%) used it weekly and nine (28%) used it rarely. Pain, sleep and mood were most frequently reported as improving with cannabis use, and 'high' and dry mouth were the most commonly reported side effects. We conclude that cannabis use is prevalent among the chronic non-cancer pain population, for a wide range of symptoms, with considerable variability in the amounts used. Discussions between patients and health care providers concerning cannabis use may facilitate education and follow up, and would allow side effects and potential interactions with other medications to be monitored. Clinical trials of cannabis for chronic non-cancer pain are warranted.

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.

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. [ABSTRACT FROM AUTHOR]

Unlabelled: Cannabinoids show promise as therapeutic agents, particularly as analgesics, but their development and clinical use has been complicated by recognition of their botanical source, cannabis, as a substance of misuse. Although research into endogenous cannabinoid systems and potential cannabinoid pharmaceuticals is slowly increasing, there has been intense societal interest in making herbal (plant) cannabis available for medicinal use; 23 U.S. States and all Canadian provinces currently permit use in some clinical contexts. Whether or not individual professionals support the clinical use of herbal cannabis, all clinicians will encounter patients who elect to use it and therefore need to be prepared to advise them on cannabis-related clinical issues despite limited evidence to guide care. Expanded research on cannabis is needed to better determine the individual and public health effects of increasing use of herbal cannabis and to advance understanding of the pharmaceutical potential of cannabinoids as medications. This article reviews clinical, research, and policy issues related to herbal cannabis to support clinicians in thoughtfully advising and caring for patients who use cannabis, and it examines obstacles and opportunities to expand research on the health effects of herbal cannabis and cannabinoids.Perspective: Herbal cannabis is increasingly available for clinical use in the United States despite continuing controversies over its efficacy and safety. This article explores important considerations in the use of plant Cannabis to better prepare clinicians to care for patients who use it, and identifies needed directions for research. [ABSTRACT FROM AUTHOR]

Unlabelled: Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic non-cancer pain. The safety of cannabis use for medical purposes has not been systematically evaluated. We conducted a prospective cohort study to describe safety issues among individuals with chronic non-cancer pain. A standardized herbal cannabis product (12.5% tetrahydrocannabinol) was dispensed to eligible individuals for a 1-year period; controls were individuals with chronic pain from the same clinics who were not cannabis users. The primary outcome consisted of serious adverse events and non-serious adverse events. Secondary safety outcomes included pulmonary and neurocognitive function and standard hematology, biochemistry, renal, liver, and endocrine function. Secondary efficacy parameters included pain and other symptoms, mood, and quality of life. Two hundred and fifteen individuals with chronic pain were recruited to the cannabis group (141 current users and 58 ex-users) and 216 controls (chronic pain but no current cannabis use) from 7 clinics across Canada. The median daily cannabis dose was 2.5 g/d. There was no difference in risk of serious adverse events (adjusted incidence rate ratio = 1.08, 95% confidence interval = .57-2.04) between groups. Medical cannabis users were at increased risk of non-serious adverse events (adjusted incidence rate ratio = 1.73, 95% confidence interval = 1.41-2.13); most were mild to moderate. There were no differences in secondary safety assessments. Quality-controlled herbal cannabis, when used by patients with experience of cannabis use as part of a monitored treatment program over 1 year, appears to have a reasonable safety profile. Longer-term monitoring for functional outcomes is needed.Study Registration: The study was registered with www.controlled-trials.com (ISRCTN19449752).Perspective: This study evaluated the safety of cannabis use by patients with chronic pain over 1 year. The study found that there was a higher rate of adverse events among cannabis users compared with controls but not for serious adverse events at an average dose of 2.5 g herbal cannabis per day. [ABSTRACT FROM AUTHOR]

Background: There is increasing global awareness and interest in the use of cannabis for therapeutic purposes (CTP). It is clear that health care professionals need to be involved in these decisions, but often lack the education needed to engage in informed discussions with patients. This study was conducted to determine the educational needs of Canadian physicians regarding CTP. Methods: A national needs assessment survey was developed based on previous survey tools. The survey was approved by the Research Ethics Board of the McGill University Health Centre Research Institute and was provided online using LimeSurvey®. Several national physician organizations and medical education organizations informed their members of the survey. The target audience was Canadian physicians. We sought to identify and rank using 5-point Likert scales the most common factors involved in decision making about using CTP in the following categories: knowledge, experience, attitudes, and barriers. Preferred educational approaches and physician demographics were collected. Gap analysis was conducted to determine the magnitude and importance of differences between perceived and desired knowledge on all decision factors. Results: Four hundred and twenty six responses were received, and physician responses were distributed across Canada consistent with national physician distribution. The most desired knowledge concerned "potential risks of using CTP" and "safety, warning signs and precautions for patients using CTP". The largest gap between perceived current and desired knowledge levels was "dosing" and "the development of treatment plans". Conclusions: We have identified several key educational needs among Canadian physicians regarding CTP. These data can be used to develop resources and educational programs to support clinicians in this area, as well as to guide further research to inform these gaps. [ABSTRACT FROM AUTHOR]

This study was undertaken to determine the prevalence of use, reasons for use, amounts and methods used, and perceived effectiveness of cannabis and dronabinol among persons living with HIV/AIDS in Canada. Cross-sectional anonymous self-administered questionnaire study. Four hundred patients were consecutively recruited from 3 primary care HIV clinics in Toronto, Ottawa and Montreal, and 50 questionnaires were distributed to PHAs (persons having AIDS) at one “cannabis compassion club.” Responses were received from 160 clinic patients and 19 compassion club patients (40% response rate). Of 160 PHAs attending the HIV clinics, 59 patients (37.3%, 95% CI 29.5-45.1%) reported current use of cannabis. Of 19 compassion club clients, all reported current use of cannabis. Cannabis was most commonly used for stress relief and loss of appetite in both populations, in addition to relief of stress and nausea. Side effects included “high” and dry mouth. Dronabinol and cannabis were also reported to relieve adverse effects of antiretroviral therapy. Dronabinol is less widely used, cannabis being preferred. Cannabis is commonly used among PHAs for a wide range of symptom relief. Clinical trials using standardized material are required to assess the magnitude of the effects of cannabis, to explore the role of the placebo effect, and to define dose exposures for risk-benefit assessment. [ABSTRACT FROM PUBLISHER]