Search

Purpose: Patient hesitancy to use MC due to the fear of negative social implications leads to intentional non-adherence and compromises therapeutic outcomes. Hence, we aimed to determine the rate of patient adherence to MC and explore factors influencing patient MC use., Methods: Demographic and quantitative data related to MC usage were extracted from medical records for patients prescribed MC at a single cancer centre in metropolitan Sydney. Qualitative data was generated from semi-structured interviews. Interview guides were developed based on the Theory of Planned Behaviour (TBP) domains (i.e. Attitudes, Subjective Norms, Behavioural Intention and Perceived Behavioural Control) to elucidate themes influencing MC use. A mixed method approach involving triangulation of quantitative and qualitative methods was used for data analysis., Results: Twenty patients were included in the study, and the majority of patients showed adherence (n = 14, 70%). The MC formulation used (p = .018), symptom relief (p = .001) and side effects experienced (p = .007) significantly influenced MC adherence. In addition to side effects experienced, findings for barriers to adherence were convergent or complementary for other medication-related factors, including the inconvenience of MC co-administration with food, cost and unpleasant taste., Conclusions: MC adherence is influenced by its effectiveness for symptom relief whereby appropriate MC formulation selection is crucial and should be determined by the indication (or symptom clusters). Social factors such as the views and experiences of close others had little bearing on MC adherence., Competing Interests: Declarations Ethics approval This study was performed in line with the principles of the National Health Medical Research Council Statement on Ethical Conduct in Human Research (2007). Approval was granted by the Sydney Local Health District Human Research Ethics Committee (Identifier 2022/ETH01119). Consent to participate Informed consent was obtained from all individual participants included in the study. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

U.S. adults increasingly report using cannabis to manage chronic pain and rural areas have inadequate comprehensive pain management. Using mixed methods, we aimed to understand how and why some rural adults use cannabis for pain, including within the context of co-use with opioids. Participants (N = 14, Oklahoma) were rural-dwelling adults who used tobacco and ≥1 other substance, including cannabis and opioids, ≥3 days per week. Participants completed 14 days of ecological momentary assessment (EMA) regarding substance use and subsequent in-depth interviews discussing maps of their substance use reports. Half (7/14) described cannabis use for chronic pain, and most of these (85%) reported use on ≥75% of EMA days. The most frequently reported cannabis use motive was therapeutic/medicinal (90% of use reports). Most reports were of combusted cannabis (88% of use reports) at home (99% of use reports). Same-day use of cannabis and opioids was relatively common (45% of daily surveys), but seemingly not within close temporal proximity. Interview narratives characterized cannabis as modifying pain-adjacent factors (eg, thoughts), not eliminating pain itself. They recounted using a repertoire of substances to manage different pain dimensions (eg, intensity, quality) and balance perceived trade-offs of different substances. Participants described high medical cannabis access, low pain specialist access, and most physicians as unwilling to discuss cannabis for pain. The findings suggest that rural-dwelling patients could benefit from increased access to comprehensive pain management, having cannabis addressed within pain management provider discussions, and that risks and benefits of cannabis use for pain must be better established. PERSPECTIVE: This study used a geographically explicit EMA mixed method to gather rich, intensive pilot data on cannabis use and co-use for chronic pain in rural Oklahoma. It provides unique insights to inform future research on cannabis use among a vulnerable and understudied subgroup of adults with pain-rural residents., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Cannabidiol (CBD) is a non-psychoactive substance that exerts numerous pharmacological benefits, including anti-inflammatory and antioxidant properties. It has received attention as a useful substance for the treatment of intractable pain, seizures, and anxiety, and related clinical trials have continued. However, the CBD pharmacokinetic results between reports are highly variable, making it difficult to clearly identify the pharmacokinetic properties of CBD. The main purpose of this study was to identify CBD clinical pharmacokinetic properties through meta-analysis. In particular, we sought to derive valid, interpretable independent variables and interpret their pharmacokinetic parameter correlations in relation to the large inter-individual and inter-study variability in CBD pharmacokinetics. For this study, CBD-related clinical trial reports were extensively screened and intercomparisons were performed between internal data sets through systematic classification and extraction of pharmacokinetic parameter values. The candidate independent variables associated with interpretation of CBD pharmacokinetic diversity established and explored in this study were as follows: diet, tetrahydrocannabinol (THC) combination, sample matrix type, liver and renal function, exposure route, dosage form, CBD exposure dose, cannabis smoking frequency, multiple exposure. The results of this study showed that CBD pharmacokinetics were influenced (increased plasma exposure by approximately 2-5 times) by diet immediately before or during CBD exposure, and that THC was not expected to have an antagonistic effect on the CBD absorption. The influence of changes in liver function would be significant in CBD pharmacokinetic diversity. Due to decreased liver function, the plasma exposure of CBD increased 2.57-5.15 times compared to healthy adults, and the half-life and clearance showed a 2.58-fold increase and a 5.15-fold decrease, respectively. CBD can be rapidly absorbed into the body (time to reach maximum concentration within 3.18 h) by oral, transdermal, and inhalation exposures, and lipid emulsification and nanoformulation of CBD will greatly improve CBD bioavailability (up to approximately 2 times). The pharmacokinetics of CBD generally follow linear kinetic characteristics. The importance of this study is that it suggests key factors that should be considered in terms of pharmacokinetics in further clinical trials and formulations of CBD in the future., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tea is a recommended way of administration of prescribed cannabis plant products in Denmark. We aimed to investigate the cannabinoid and terpene doses contained in different teas. We analysed tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), cannabidiolic acid (CBDA), and terpene concentrations in three repeated preparations of each type of tea, and in plant material. In standard tea, concentrations of THC were [median (min-max)] 9.5 (2.3-15), 19 (13-34), and 36 (26-57) μg/mL for products with a labelled content of 6.3%, 14%, and 22% total THC (THC + THCA), respectively. The CBD concentration in tea from a product labelled with 8% total CBD (CBD + CBDA) was 7.5 (1.9-10) μg/mL. Based on this, the recommended starting amount of 0.2 L of the different teas would contain between 0.46 and 11.3 mg THC, and 0.38 to 2.0 mg CBD. Adding creamer before, but not after boiling, increased the THC and CBD concentration 2.3-4.4 and 2.1-fold, respectively. Terpenes were detected in plant material, but not in tea. The study elucidates THC and CBD doses in different teas, which may assist the clinician's choice of cannabis product. Moreover, it underscores the need for caution as administration as tea can result in exposure to different doses, even when the same cannabis product is used., (© 2024 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background : Opioid therapy is critical for pain relief for most hospice patients but may be limited by adverse side effects. Combining medical cannabis with opioids may help mitigate adverse effects while maintaining effective pain relief. Aim : This single-arm study investigated the impact of combined medical cannabis/opioid therapy on pain relief, opioid dose, appetite, respiratory function, well-being, nausea, and adverse events in hospice inpatients. Design : Adult hospice inpatients using scheduled oral, parenteral, or transdermal opioids for pain were administered standardized oral medical cannabis, 40 mg CBD/1.5 mg THC or 80 mg CBD/3 mg THC. Descriptive statistics detailed demographic and clinical baseline characteristics, the Mann-Whitney test compared outcomes, and the longitudinal mixed effects regression model analyzed longitudinal effects of combined therapy. Setting/Participants : Sixty-six inpatients at The Connecticut Hospital, Inc. were assessed over 996 treatment days; average age was 68.2 ± 12.9 years, 90.9% were white. Cancer was the most common diagnosis. Results : The medical cannabis/opioid combination showed a significant longitudinal reduction in pain intensity ( P = .0029) and a non-significant trend toward lower opioid doses. Well-being, appetite, nausea, and respiratory function showed non-statistically significant changes. Three patients (4.5%) experienced minor, reversible adverse events potentially related to medical cannabis. No serious or life-threatening adverse events were seen. Conclusion : Combination medical cannabis/opioid therapy showed statistically significant pain relief and may have the potential for reducing opioid dose and mitigating opioid toxicity, offering a safe pain management alternative to opioids alone for patients in end-of-life care settings, and warrants further investigation in larger controlled trials., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Poor sleep is a common side effect of cancer. Cannabis is increasingly used to manage cancer treatment-related symptoms, including sleep. This study investigated factors related to cannabis use for sleep among Canadian cancer survivors., Method: Adult Canadian cancer survivors ( N  = 940) were recruited via the Angus Reid Institute and completed an online, cross-sectional survey. Univariate and multiple binomial logistic regression models identified factors associated with cannabis use for sleep., Results: Of the participants (M age  = 64.5 yrs; Women = 51.1%; White = 92.9%), 25.1% ( n  = 236) currently use cannabis for sleep. Participants were at greater odds of using cannabis for sleep if they identified as a gender other than man or woman (AOR = 11.132), were diagnosed with multiple medical conditions (2:AOR = 1.988; 3+:AOR = 1.902), two psychological conditions (AOR = 2.171), multiple sleep disorders (AOR = 2.338), insomnia (AOR = 1.942), bone (AOR = 6.535), gastrointestinal (AOR = 4.307), genitourinary (AOR = 2.586), hematological (AOR = 4.739), or an unlisted cancer (AOR = 3.470), received hormone therapy only (AOR = 3.054), drink heavily (AOR = 2.748), or had mild insomnia (AOR = 1.828). Older participants (AOR=.972) and those with sleep apnea were less likely to use cannabis for sleep (AOR=.560)., Conclusion: Given its prevalence, research is needed to understand how factors associated with cannabis use as a sleep aid among Canadian cancer survivors may influence its use and effectiveness and whether these factors are barriers to accessing evidence-based treatments.

Cannabis and its major constituents, Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), are being widely used to treat sleep disturbances. However, THC can cause acute cognitive and psychomotor impairment and there are concerns that driving and workplace safety might be compromised the day after evening use. Here, we examined possible 'next day' impairment following evening administration of a typical medicinal cannabis oil in adults with insomnia disorder, compared to matched placebo. This paper describes the secondary outcomes of a larger study investigating the effects of THC/CBD on insomnia disorder. Twenty adults [16 female; mean (SD) age, 46.1 (8.6) y] with physician-diagnosed insomnia who infrequently use cannabis completed two 24 h in-laboratory visits involving acute oral administration of combined 10 mg THC and 200 mg CBD ('THC/CBD') or placebo in a randomised, double-blind, crossover trial design. Outcome measures included 'next day' (≥9 h post-treatment) performance on cognitive and psychomotor function tasks, simulated driving performance, subjective drug effects, and mood. We found no differences in 'next day' performance on 27 out of 28 tests of cognitive and psychomotor function and simulated driving performance relative to placebo. THC/CBD produced a small decrease (-1.4%, p=.016, d=-0.6) in accuracy on the Stroop-Colour Task (easy/congruent) but not the Stroop-Word Task (hard/incongruent). THC/CBD also produced a small increase (+8.6, p=.042, d=0.3) in self-ratings of Sedated at 10 h post-treatment, but with no accompanying changes in subjective ratings of Alert or Sleepy (p's>0.05). In conclusion, we found a lack of notable 'next day' impairment to cognitive and psychomotor function and simulated driving performance following evening use of 10 mg oral THC, in combination with 200 mg CBD, in an insomnia population who infrequently use cannabis., (© 2024. The Author(s).)

Family physicians are fielding questions about cannabis --particularly for the use of cannabis for treatment of pain. Like about every substance ingested to treat medical conditions, cannabis has risks and benefits. But regarding evidence-based practice and practice-based recommendations for patients about cannabis use, the cart is in front of the horse. Cannabis use is still illegal at a federal level and a Schedule 1 drug, but most states have challenged federal law by decriminalizing or legalizing cannabis for a variety of uses. Research is difficult due to this federal status as a Schedule 1 drug since federal funding is not readily available to support research. As a result, physicians have little to no guidance about the clinical usefulness of the product. This article explores what we know and what we are learning about cannabis, and the authors provide clinical guidance for patient care based on this evidence., Competing Interests: Conflict of interest: None., (© Copyright by the American Board of Family Medicine.)

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

As cannabinoid-based medications gain popularity in the treatment of refractory medical conditions, it is crucial to examine the neurocognitive effects of commonly prescribed products to ensure associated safety profiles. The present study aims to investigate the acute effects of a standard 1 mL sublingual dose of CannEpil®, a medicinal cannabis oil containing 100 mg cannabidiol (CBD) and 5 mg Δ9-tetrahydrocannabinol (THC) on neurocognition, attention, and mood. A randomised, double-blind, placebo-controlled, within-subjects design assessed 31 healthy participants (16 female, 15 male), aged between 21 and 58 years, over a two-week experimental protocol. Neurocognitive performance outcomes were assessed using the Cambridge Neuropsychological Test Automated Battery, with the Profile of Mood States questionnaire, and the Bond-Lader Visual Analogue Scale used to assess subjective state and mood. CannEpil increased Total Errors in Spatial Span and Correct Latency (median) in Pattern Recognition Memory, while also increasing Efficiency Score (lower score indicates greater efficiency) relative to placebo (all p < .05). Subjective Contentedness (p < .01) and Amicability (p < .05) were also increased at around 2.5 h post dosing, relative to placebo. Drowsiness or sedative effect was reported by 23 % of participants between three to six hours post CannEpil administration. Plasma concentrations of CBD, THC, and their metabolites were not significantly correlated with any observed alterations in neurocognition, subjective state, or adverse event occurrence. An acute dose of CannEpil impairs select aspects of visuospatial working memory and delayed pattern recognition, while largely preserving mood states among healthy individuals. Intermittent reports of drowsiness and sedation underscore the inter-individual variability of medicinal cannabis effects on subjective state. (ANZCTR; ACTRN12619000932167; https://www.anzctr.org.au)., Competing Interests: Declaration of competing interest AH is supported by a Rebecca L Cooper Al and Val Rosenstrauss Fellowship (GNT: F2021894). BM, SC, CS, BS, and LD have no conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Distressing symptoms are common in advanced cancer. Medicinal cannabinoids are commonly prescribed for a variety of symptoms. There is little evidence to support their use for most indications in palliative care. This study aims to assess a 1:20 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom distress in patients with advanced cancer undergoing palliative care., Methods and Design: One hundred and fifty participants will be recruited across multiple sites in Queensland, Australia. A teletrial model will facilitate the recruitment of patients outside of major metropolitan areas. The study is a pragmatic, multicenter, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:20 THC/CBD medicinal cannabinoid preparation (10 mg THC:200 mg CBD/mL). It will compare the efficacy and safety outcomes of a titrated dose range of 2.5 mg THC/50mgCBD to 30 mg THC/600 mg CBD per day against a placebo. There is a 2-week patient-determined titration phase, to reach a dose that achieves symptom relief or intolerable side effects, with a further 2 weeks of assessment on the final dose. The primary objective is to assess the effect of escalating doses of a 1:20 THC/CBD medicinal cannabinoid preparation against placebo on change in total symptom distress score, with secondary objectives including establishing a patient-determined effective dose, the effect on sleep quality and overall quality of life. Some patients will be enrolled in a sub-study which will more rigorously evaluate the effect on sleep., Discussion: MedCan-3 is a high-quality, adequately powered, placebo-controlled trial which will help demonstrate the utility of a THC:CBD 1:20 oral medicinal cannabis product in reducing total symptom distress in this population. Secondary outcomes may lead to new hypotheses regarding medicinal cannabis' role in particular symptoms or in particular cancers. The sleep sub-study will test the feasibility of using actigraphy and the Insomnia Severity Index (ISI) in this cohort. This will be the first large-scale palliative care randomised clinical trial to utilise the teletrial model in Australia. If successful, this will have significant implications for trial access for rural and remote patients in Australia and internationally., Trial Registration: ANZCTR ACTRN12622000083796 . Protocol number 001/20. Registered on 21 January 2022. Recruitment started on 8 August 2022., (© 2024. The Author(s).)

Objective: To relate the topical use of cannabis as an analgesic therapeutic alternative in patients with some inflammatory diseases in Salud Social I.P.S during May to July 2023., Methods: An analytical, retrospective study was carried out. The population from which the sample was obtained corresponds to patients diagnosed with Arthrosis, Unspecified, Non-Toxic Multinodular Goiter, Epilepsy, Unspecified Type Venous Insufficiency (Chronic) (Peripheral), Unspecified Lumbago, Secondary Gonarthrosis, Rotator Cuff Syndrome, Carpal Tunnel Syndrome, in Salud Social I.P.S of Barranquilla, Atlántico. A sample of 23 patients diagnosed with these pathologies was obtained by non-probabilistic convenience sampling., Results: All patients showed pain relief after two months of follow-up, two experienced adverse effects. Some studies suggest that cannabinoids present in cannabis, such as CBD and THC, may have analgesic and anti-inflammatory properties that could alleviate pain and inflammation associated with these conditions. This is consistent with the present study., Conclusion: Topical cannabis is presented as a therapeutic alternative in inflammatory diseases, however, it is important to highlight that research on the use of cannabis in these diseases is limited and more studies are needed to fully understand its effects and potential benefits.

Background: How cannabis products are being used by cancer patients and survivors in the United States is poorly understood. This study reviewed observational data to understand the modes, patterns, reasons, discontinuation, and adverse experiences of cannabis use., Methods: PubMed and PsycINFO database searches were conducted between May 2022 and November 2022. Of the 1162 studies identified, 27 studies met the inclusion criteria. The intercoder agreement was strong (0.81)., Results: The majority (74%) of the studies were cross-sectional in design. Study samples were approximately equal proportions of men and women and majority White participants. The prevalence of cannabis use based on national samples ranged between 4.8% and 22%. The most common modes of cannabis intake were topical application (80%), smoking (73%), vaping (12%), and ingestion of edible products (10%). Younger age, male gender, being a current or former smoker, and higher socioeconomic status were associated with greater likelihood of cannabis use. The main motive for cannabis use was management of symptoms due to cancer or cancer treatment such as pain, nausea, lack of sleep, and anxiety. A majority of the participants across studies reported that cannabis helped reduce these symptoms. Lack of symptom improvement, side effects such as fatigue and paranoia, cost, and social stigma were identified as some of the reasons for discontinuing cannabis use., Conclusions: It appears that cannabis may help cancer patients and survivors manage symptoms. However, more longitudinal studies are needed to determine whether positive experiences of cannabis use outweigh adverse experiences over time in this vulnerable population., (© The Author(s) 2024. Published by Oxford University Press.)

Medical cannabis has potential therapeutic benefits in managing pain, anxiety, depression, and neurological and movement disorders. Phytocannabinoids derived from the cannabis plant are responsible for their pharmacological and therapeutic properties. However, the complexity of cannabis components, especially cannabinoids, poses a challenge to effective medicinal administration. Even with the increasing acceptance of cannabis-based medicines, achieving consistent bioavailability and targeted distribution remains difficult. Conventional administration methods are plagued by solubility and absorption problems requiring innovative solutions. After conducting a thorough review of research papers and patents, it has become evident that nanotechnology holds great promise as a solution. The comprehensive review of 36 research papers has yielded valuable insights, with 7 papers reporting enhanced bioavailability, while others have focused on improvements in release, solubility, and stability. Additionally, 19 patents have been analyzed, of which 7 specifically claim enhanced bioavailability, while the remaining patents describe various formulation methods. These patents outline effective techniques for encapsulating cannabis using nanocarriers, effectively addressing solubility and controlled release. Studies on the delivery of cannabis using nanocarriers focus on improving bioavailability, prolonging release, and targeting specific areas. This synthesis highlights the potential of nanotechnology to enhance cannabis therapies and pave the way for innovative interventions and precision medicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cannabis (in all the varied methods of delivery) continues to garner significant attention as a potential therapeutic intervention for neurodegenerative disorders, including Parkinson's disease (PD). The recent legalization of personal use of cannabis products in some parts of the world has increased this interest and with it, potential availability to many more people. However, such access has led to more questions than answers for both patients and health care professionals. These include what symptom(s) of PD will cannabis products treat; what dose; what type of cannabis product to use and what are the side effects?

Cannabis usage has steadily increased as acceptance is growing for both medical and recreational reasons. Medical cannabis is administered for treatment of chronic pain based on the premise that the endocannabinoid system signals desensitize pain sensor neurons and produce anti-inflammatory effects. The major psychoactive ingredient of cannabis is Δ9-tetrahydrocannabinol (THC) that signals mainly through cannabinoid receptor-1 (CBr), which is also present on nonneuron cells including blood platelets of the circulatory system. In vitro, CBr-mediated signaling has been shown to acutely inhibit platelet activation downstream of the platelet collagen receptor glycoprotein (GP)VI. The systemic effects of chronic THC administration on platelet activity and function remain unclear. This study investigates the effects of chronic THC administration on platelet function using a nonhuman primate (NHP) model. Our results show that female and male NHPs consuming a daily THC edible had reduced platelet adhesion, aggregation, and granule secretion in response to select platelet agonists. Furthermore, a change in bioactive lipids (oxylipins) was observed in the female cohort after THC administration. These results indicate that chronic THC edible administration desensitized platelet activity and function in response to GPVI- and G-protein coupled receptor-based activation by interfering with primary and secondary feedback signaling pathways. These observations may have important clinical implications for patients who use medical marijuana and for providers caring for these patients.

Neuropathic pain represents a broad category of pain syndromes that include a wide variety of peripheral and central disorders. The overall prevalence of neuropathic pain in the general population is reported to be between 7 and 10%. Management of neuropathic pain presents an unmet clinical need, with less than 50% of patients achieving substantial pain relief with medications currently recommended such as pregabalin, gabapentin, duloxetine and various tricyclic antidepressants. It has been suggested that cannabis-based medicines (CbMs) and medical cannabis (MC) may be a treatment option for those with chronic neuropathic pain. CbMs/MC are available in different forms: licensed medications or medical products (plant-derived and/or synthetic products such as tetrahydrocannabinol or cannabidiol); magistral preparations of cannabis plant derivatives with defined molecular content such as dronabinol (tetrahydrocannabinol); and herbal cannabis with a defined content of tetrahydrocannabinol and/or cannabidiol, together with other active ingredients (phytocannabinoids other than cannabidiol/tetrahydrocannabinol, terpenes and flavonoids). The availability of different types of CbMs/MC varies between countries worldwide. Systematic reviews of available randomised controlled trials have stated low-quality evidence for CbMs and MC for chronic neuropathic pain. Depending on the studies included in the various quantitative syntheses, authors have reached divergent conclusions on the efficacy of CbMs/MC for chronic neuropathic pain (from not effective to a clinically meaningful benefit). Clinically relevant side effects of CbMs/MC, especially for central nervous system and psychiatric disorders, have been reported by some systematic reviews. Recommendations for the use of CbMs/MC for chronic neuropathic pain by various medical associations also differ, from negative recommendations, no recommendation possible, recommended as third-line therapy, or recommended as an alternative in selected cases failing standard therapies within a multimodal concept. After reading this paper, readers are invited to formulate their own conclusions regarding the potential benefits and harms of CbMs/MC for the treatment of chronic neuropathic pain., (© 2021. The Author(s).)

Cannabis-based medicinal products (CBMPs) are an emerging therapeutic option in the management of primary chronic pain, using the role of the endocannabinoid system in modulating central and peripheral pain processes. Despite promising preclinical data, there is a paucity of high-quality evidence to support the use of CBMPs for chronic pain. This study aimed to investigate the health-related quality-of-life outcomes of patients with chronic pain who were prescribed CBMP oil preparations (Adven, Curaleaf International, Guernsey, UK). This study is a case series of patients from the UK Medical Cannabis Registry, who were treated with CBMP oils for an indication of chronic pain. The primary outcomes were the changes in Brief Pain Inventory short form, Short-Form McGill Pain Questionnaire-2, Visual Analog Scale Pain, General Anxiety Disorder-7, Sleep Quality Scale, and EQ-5D-5L, at 1, 3, and 6 months. One hundred ten patients were included. Significant improvements in Sleep Quality Scale, EQ-5D-5L pain and discomfort subscale, and Brief Pain Inventory Interference Subscale (P < .05) at 1, 3, and 6 months were demonstrated. There were no notable differences between cannabis-naïve and previous cannabis users in quality-of-life outcomes. The adverse event incidence was 30.0%, with most (n = 58; 92.1%) adverse events being mild or moderate in intensity. Treatment of chronic pain with Adven CBMP oils was associated with an improvement in pain-specific outcomes, health-related quality of life, and self-reported sleep quality. Relative safety was demonstrated over medium-term prescribed use. While these findings must be treated with caution considering the limitations of study design, they can inform future clinical trials., (© 2021 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Information for nurses, patients, and the public., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The use of cannabis for symptoms of endometriosis was investigated utilising retrospective archival data from Strainprint Technologies Ltd., a Canadian data technology company with a mobile phone application that tracks a range of data including dose, mode of administration, chemovar and their effects on various self-reported outcomes, including pelvic pain., Methods: A retrospective, electronic record-based cohort study of StrainprintTM users with self-reported endometriosis was conducted. Self-rated cannabis efficacy, defined as a function of initial and final symptom ratings, was investigated across the included symptom clusters of cramps, pelvic pain, gastrointestinal pain, nausea, depression, and low libido. Cannabis dosage form, dose and cannabinoid ratio information was also recorded., Results: A total number of 252 participants identifying as suffering endometriosis recorded 16193 sessions using cannabis between April 2017 and February 2020. The most common method of ingestion was inhalation (n = 10914, 67.4%), with pain as the most common reported symptom being treated by cannabis (n = 9281, 57.3%). Gastrointestinal symptoms, though a less common reason for cannabis usage (15.2%), had the greatest self-reported improvement after use. Inhaled forms had higher efficacy for pain, while oral forms were superior for mood and gastrointestinal symptoms. Dosage varied across ingestion methods, with a median dose of 9 inhalations (IQR 5 to 11) for inhaled dosage forms and 1 mg/mL (IQR 0.5 to 2) for other ingested dosage forms. The ratio of THC to CBD had a statistically significant, yet clinically small, differential effect on efficacy, depending on method of ingestion., Conclusions: Cannabis appears to be effective for pelvic pain, gastrointestinal issues and mood, with effectiveness differing based on method of ingestion. The greater propensity for use of an inhaled dosage delivery may be due to the rapid onset of pain-relieving effects versus the slower onset of oral products. Oral forms appeared to be superior compared to inhaled forms in the less commonly reported mood or gastrointestinal categories. Clinical trials investigating the tolerability and effectiveness of cannabis for endometriosis pain and associated symptoms are urgently required., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: As a medical research institute, NICM Health Research Institute receives research grants and donations from foundations, universities, government agencies, individuals and industry. Sponsors and donors also provide untied funding for work to advance the vision and mission of the Institute. The authors declare no competing financial interests. JS is the recipient of a Western Sydney University Postgraduate Research Scholarship. J.Sarris has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments from: Australian Natural Therapeutics Group (being a scientific advisor to Australian Natural Therapeutics Group: a cannabis grower and manufacturer), Integria Healthcare & MediHerb, Pfizer, Scius Health, Key Pharmaceuticals, Taki Mai, Fiji Kava, FIT-BioCeuticals, Blackmores, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Kantar Consulting, Angelini Pharmaceuticals, Grunbiotics, Polistudium, Research Reviews, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, SPRIM, Terry White Chemists, ANS, Society for Medicinal Plant and Natural Product Research, Sanofi-Aventis, Omega-3 Centre, the National Health and Medical Research Council, CR Roper Fellowship. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Clinical Question: What is the role of medical cannabis or cannabinoids for people living with chronic pain due to cancer or non-cancer causes?, Current Practice: Chronic pain is common and distressing and associated with considerable socioeconomic burden globally. Medical cannabis is increasingly used to manage chronic pain, particularly in jurisdictions that have enacted policies to reduce use of opioids; however, existing guideline recommendations are inconsistent, and cannabis remains illegal for therapeutic use in many countries., Recommendation: The guideline expert panel issued a weak recommendation to offer a trial of non-inhaled medical cannabis or cannabinoids, in addition to standard care and management (if not sufficient), for people living with chronic cancer or non-cancer pain., How This Guideline Was Created: An international guideline development panel including patients, clinicians with content expertise, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. The panel applied an individual patient perspective., The Evidence: This recommendation is informed by a linked series of four systematic reviews summarising the current body of evidence for benefits and harms, as well as patient values and preferences, regarding medical cannabis or cannabinoids for chronic pain., Understanding the Recommendation: The recommendation is weak because of the close balance between benefits and harms of medical cannabis for chronic pain. It reflects a high value placed on small to very small improvements in self reported pain intensity, physical functioning, and sleep quality, and willingness to accept a small to modest risk of mostly self limited and transient harms. Shared decision making is required to ensure patients make choices that reflect their values and personal context. Further research is warranted and may alter this recommendation., Competing Interests: Competing interests: All authors have completed the BMJ Rapid Recommendations interests disclosure form and a detailed, contextualised description of all disclosures is reported in appendix 2. As with all BMJ Rapid Recommendations, the executive team and The BMJ judged that no panel member had any financial conflict of interest. Personal, professional, and academic interests were minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form www.icmje.org/disclosure-of-interest/ and declare: no financial support from any industry for the submitted work; IP and SU have received research funds from Northern Green Canada; IP has been a paid consultant for Northern Green Science, Northern Green Canada, Monk-E psychedelics, and Evergreen Pacific Insurance Corporation; SU and IP received honoraria from Spectrum Therapeutics and Tilray Inc. for educational presentations; MAW is the chief medical officer for Canopy Growth Corporation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The field of Cannabis sativa L. research for medical purposes has been rapidly advancing in recent decades and a growing body of evidence suggests that phytocannabinoids are beneficial for a range of conditions. At the same time impressing development has been observed for formulations and delivery systems expanding the potential use of cannabinoids as an effective medical therapy. The objective of this review is to present the most recent results from pharmaceutical companies and research groups investigating methods to improve cannabinoid bioavailability and to clearly establish its therapeutic efficacy, dose ranges, safety and also improve the patient compliance. Particular focus is the application of cannabinoids in pain treatment, describing the principal cannabinoids employed, the most promising delivery systems for each administration routes and updating the clinical evaluations. To offer the reader a wider view, this review discusses the formulation starting from galenic preparation up to nanotechnology approaches, showing advantages, limits, requirements needed. Furthermore, the most recent clinical data and meta-analysis for cannabinoids used in different pain management are summarized, evaluating their real effectiveness, in order also to spare opioids and improve patients' quality of life. Promising evidence for pain treatments and for other important pathologies are also reviewed as likely future directions for cannabinoids formulations., (© 2021. The Author(s).)

Using marijuana has become popular and is allowed for medical purposes in some countries. The effect of marijuana on Parkinson's disease is controversial and Medical marijuana may benefit for motor and non-motor symptoms of patients with Parkinson's disease. No research has been conducted to fully prove the benefits, risks, and uses of marijuana as a treatment for patients with Parkinson's disease. In the present study, several different approaches, including behavioral measures and the western blot method for protein level assay, were used to investigate whether exposure to marijuana affects the motor and synaptic plasticity impairment induced by 6-OHDA. Marijuana consumption significantly decreased apomorphine-induced contralateral rotation, beam travel time, beam freeze time, and catalepsy time, but significantly increased latency to fall in the rotarod test, balance time, and protein level of PSD-95 and dopamine receptor D1 in the 6-OHDA + marijuana group. These results suggest that marijuana may be helpful for motor disorders and synaptic changes in patients with Parkinson's disease., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Pediatric-onset multiple sclerosis (POMS), representing approximately 5% of all MS cases, affects the central nervous system during its ongoing development. POMS is most commonly diagnosed during adolescence but can occur in younger children as well. For pediatric patients with MS, it is critical to manage the full impact of the disease and monitor for any effects on school and social functioning. Disease management includes not only disease-modifying therapies but also strategies to optimize wellbeing. We review the interventions with the highest evidence of ability to improve the disease course and quality of life in POMS. High levels of vitamin D and a diet low in saturated fat are associated with lower relapse rates. Exercise ameliorates fatigue and sleep. Behavioral strategies for sleep hygiene and mood regulation can also improve fatigue and perceived health. POMS management should be addressed holistically, including assessing overall symptom burden as well as the psychological and functional impact of the disease., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Cannabis has been legalised for medical use in an ever-increasing number of countries. A growing body of scientific evidence supports the use of medical cannabis for a range of therapeutic indications. In parallel with these developments, concerns have been expressed by many prescribers that increased use will lead to patients developing cannabis use disorder. Cannabis use disorder has been widely studied in recreational users, and these findings have often been projected onto patients using medical cannabis. However, studies exploring medical cannabis dependence are scarce and the appropriate methodology to measure this construct is uncertain. This article provides a narrative review of the current research to discern if, how and to what extent, concerns about problems of dependence in recreational cannabis users apply to prescribed medical users. We focus on the main issues related to medical cannabis and dependence, including the importance of dose, potency, cannabinoid content, pharmacokinetics and route of administration, frequency of use, as well as set and setting. Medical and recreational cannabis use differs in significant ways, highlighting the challenges of extrapolating findings from the recreational cannabis literature. There are many questions about the potential for medical cannabis use to lead to dependence. It is therefore imperative to address these questions in order to be able to minimise harms of medical cannabis use. We draw out seven recommendations for increasing the safety of medical cannabis prescribing. We hope that the present review contributes to answering some of the key questions surrounding medical cannabis dependence.

Previous studies have demonstrated improvements in pain following short-term medical cannabis (MC) use, suggesting long-term MC treatment may alleviate symptoms associated with chronic pain. The goal of this observational and longitudinal study was to examine patients using MC to treat chronic pain pre versus post MC treatment. These interim analyses included 37 patients with chronic pain evaluated prior to initiation of MC treatment and following 3 and 6 months of MC use; pain, clinical state, sleep, quality of life, and conventional medication use were assessed. Correlation analyses examined the relationship between changes in pain and other clinical measures, assessed the impact of cannabinoid exposure on pain and clinical ratings, and assessed whether baseline cannabis expectancies influenced outcome variables. Additionally, a pilot group of treatment-as-usual patients (n = 9) who did not use MC were examined at baseline and 3 months later. Relative to baseline, following 3 and 6 months of treatment, MC patients exhibited improvements in pain which were accompanied by improved sleep, mood, anxiety, and quality of life, and stable conventional medication use. Reduced pain was associated with improvements in aspects of mood and anxiety. The results generally suggest increased THC exposure was related to pain-related improvement, while increased CBD exposure was related to improved mood. Cannabis expectancies were not related to observed improvements. Pilot analyses revealed that treatment-as-usual patients do not demonstrate the same pattern of improvement. Findings highlight the potential efficacy of MC treatment for pain and underscore the unique impact of individual cannabinoids on specific aspects of pain and comorbid symptoms. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Endoscopy under propofol sedation has become a routine procedure. Given the number of Canadians undergoing an endoscopy annually, as well as the pervasive use of cannabis by many patients, understanding the effect of cannabis use on the propofol dose at endoscopy is highly relevant. We aimed to evaluate the association between cannabis exposure and the propofol dose needed to achieve adequate sedation at endoscopy., Methods: A case-control study of individuals undergoing endoscopy was conducted at a single outpatient endoscopy clinic in London, Ontario between 2014 and 2017. Cases included all individuals with any self-reported cannabis exposure, while controls included all individuals without any self-reported history of cannabis use. Dose of propofol administered by a single anesthetist was collected on each subject as well as additional demographic and procedure-related covariates., Results: Three hundred and eighteen participants were included (cases, n = 151; controls, n = 167). Cannabis exposure was associated with an increase in propofol dose (cases 0.33 mg/kg/minute ±0.24; controls, 0.18 mg/kg/minute ±0.11; p<0.0001). Cannabis exposure remained an independent predictor of propofol dose on multivariate linear regression accounting for other important covariates (p<0.0001). Daily cannabis users required a higher propofol dose than weekly or monthly users. Three procedural sedation-related complications occurred in the cannabis-exposed group, while none occurred in the unexposed group., Conclusion: Our data suggest that cannabis use is significantly associated with the quantity of propofol needed for sedation at endoscopy. Further study is needed to better understand the molecular basis for this possible drug-drug interaction., Competing Interests: The authors have declared that no competing interests exist.

Purpose of Review: The use of cannabis for the treatment of migraine has become an area of interest with the legalization of medical cannabis in the USA. Understanding the mechanisms of cannabinoids, available studies, and best clinical recommendations is crucial for headache providers to best serve patients., Recent Findings: Patients utilizing medical cannabis for migraine have reported improvement in migraine profile and common comorbidities. Reduction in prescription medication is also common, especially opioids. Side effects exist, with the majority being mild. Not enough data is available for specific dose recommendations, but THC and CBD appear to mediate these observed effects. The purpose of this article is twofold: review the limited research surrounding cannabis for migraine disease and reflect on clinical management experiences to provide recommendations that best capture the potential use of cannabis for migraine.

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

Background: Little is known about the patients' view on treatment with medical cannabis (MC) for Parkinson's disease (PD)., Objective: To assess the PD community's perception of MC and patients' experience with MC., Methods: Applying a questionnaire-based survey, we evaluated general knowledge and interest in MC as well as the frequency, modalities, efficacy, and tolerability of application. Questionnaires were distributed nationwide via the membership journal of the German Parkinson Association and locally in our clinic to control for report bias., Results: Overall, 1.348 questionnaires (1.123 nationwide, 225 local) were analysed. 51% of participants were aware of the legality of MC application, 28% of various routes of administration (ROA) and 9% of the difference between delta9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). PD-related cannabis use was reported by 8.4% of patients and associated with younger age, living in large cities and better knowledge about the legal and clinical aspects of MC. Reduction of pain and muscle cramps was reported by more than 40% of cannabis users. Stiffness/akinesia, freezing, tremor, depression, anxiety and restless legs syndrome subjectively improved for more than 20% and overall tolerability was good. Improvement of symptoms was reported by 54% of users applying oral CBD and 68% inhaling THC-containing cannabis. Compared to CBD intake, inhalation of THC was more frequently reported to reduce akinesia and stiffness (50.0% vs. 35.4%; p < 0.05). Interest in using MC was reported by 65% of non-users., Conclusion: MC is considered as a therapeutic option by many PD patients. Nevertheless, efficacy and different ROA should further be investigated.

Background/objectives: Use of cannabis is increasing in a variety of populations in the United States; however, few investigations about how and for what reasons cannabis is used in older populations exist., Design: Anonymous survey., Setting: Geriatrics clinic., Participants: A total of 568 adults 65 years and older., Intervention: Not applicable., Measurements: Survey assessing characteristics of cannabis use., Results: Approximately 15% (N = 83) of survey responders reported using cannabis within the past 3 years. Half (53%) reported using cannabis regularly on a daily or weekly basis, and reported using cannabidiol-only products (46%). The majority (78%) used cannabis for medical purposes only, with the most common targeted conditions/symptoms being pain/arthritis (73%), sleep disturbance (29%), anxiety (24%), and depression (17%). Just over three-quarters reported cannabis "somewhat" or "extremely" helpful in managing one of these conditions, with few adverse effects. Just over half obtained cannabis via a dispensary, and lotions (35%), tinctures (35%), and smoking (30%) were the most common administration forms. Most indicated family members (94%) knew about their cannabis use, about half reported their friends knew, and 41% reported their healthcare provider knowing. Sixty-one percent used cannabis for the first time as older adults (aged ≥61 years), and these users overall engaged in less risky use patterns (e.g., more likely to use for medical purposes, less likely to consume via smoking)., Conclusion: Most older adults in the sample initiated cannabis use after the age of 60 years and used it primarily for medical purposes to treat pain, sleep disturbance, anxiety, and/or depression. Cannabis use by older adults is likely to increase due to medical need, favorable legalization, and attitudes., (© 2020 The American Geriatrics Society.)

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

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

Introduction: The opioid epidemic has resulted in the deaths of millions of Americans and was declared a public health emergency in 2017. In response, many states have enacted policies and analyzed various interventions for harm reduction and overdose prevention, which have embraced limited success. With more states legalizing medical marijuana, another intervention of interest in pain management, much research has since focused on the potential for medical marijuana laws (MMLs) to curb the opioid epidemic. Nonetheless, marijuana legalization and its use for medical purposes has been a polarizing debate from ethical, social, and clinical perspectives., Areas Covered: We examine evidence on the merits of medical marijuana to address its potential as a diversion from prescription painkillers. Additionally, we review the impact of MMLs on opioid-related outcomes. Furthermore, we provide multi-layered recommendations for future directions in the evaluation of medical marijuana and MMLs as potential mitigators of the opioid epidemic., Expert Opinion: Despite limited and mixed evidence of efficacy, medical marijuana may still play an important role in addressing the opioid epidemic in the United States. Furthermore, we believe coordinated responses among the federal government, states, researchers, and patients are crucial in producing more robust evaluations of medical marijuana and MMLs.

Cannabidiol (CBD) is an alkaloid present in Cannabis sativa , along with tetrahydrocannabinol (THC) and more than 100 other substances belonging to a group of compounds called cannabinoids. Whereas the legal status and medical use of Cannabis is a controversial issue in many countries, inconsistent legislation makes CBD status even more complicated. Some CBD products are legal in some countries, while banned in other countries, further compounding the confusion. In 2018, the Food and Drug Administration (FDA) approved the first CBD containing medical product, Epidiolex ® , for the treatment of paediatric seizures. Currently, several clinical trials are in progress for the potential treatment of neurologic and behavioural disorders. CBD's current legal and regulatory status is a continuously evolving issue; the current review is presenting historical and present information regarding the use of CBD products worldwide.

Fibromyalgia is a complex disease process that is as prevalent as it is poorly understood. Research into the pathophysiology is ongoing, and findings will likely assist in identifying new therapeutic options to augment those in existence today that are still insufficient for the care of a large population of patients. Recent evidence describes the use of cannabinoids in the treatment of fibromyalgia. This study provides a systematic, thorough review of the evidence alongside a review of the seminal data regarding the pathophysiology, diagnosis, and current treatment options. Fibromyalgia is characterized by widespread chronic pain, fatigue, and depressive episodes without an organic diagnosis, which may be prevalent in up to 10% of the population and carries a significant cost in healthcare utilization, morbidity, a reduced quality of life, and productivity. It is frequently associated with psychiatric comorbidities. The diagnosis is clinical and usually prolonged, and diagnostic criteria continue to evolve. Some therapies have been previously described, including neuropathic medications, milnacipran, and antidepressants. Despite some level of efficacy, only physical exercise has strong evidence to support it. Cannabis has been used historically to treat different pain conditions since ancient times. Recent advances allowed for the isolation of the active substances in cannabis and the production of cannabinoid products that are nearly devoid of psychoactive influence and provide pain relief and alleviation of other symptoms. Many of these, as well as cannabis itself, are approved for use in chronic pain conditions. Evidence supporting cannabis in chronic pain conditions is plentiful; however, in fibromyalgia, they are mostly limited. Only a handful of randomized trials exists, and their objectivity has been questioned. However, many retrospective trials and patient surveys suggest the significant alleviation of pain, improvement in sleep, and abatement of associated symptoms. Evidence supporting the use of cannabis in chronic pain and specifically in fibromyalgia is being gathered as the use of cannabis increases with current global trends. While the current evidence is still limited, emerging data do suggest a positive effect of cannabis in fibromyalgia. Cannabis use is not without risks, including psychiatric, cognitive, and developmental as well as the risks of addiction. As such, clinical judgment is warranted to weigh these risks and prescribe to patients who are more likely to benefit from this treatment. Further research is required to define appropriate patient selection and treatment regimens., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: This study estimated the percentage of age 35 and 55 adults reporting using medical marijuana intended for someone else (diverted use) and compared demographics and health status of such users with respondents reporting recommended use (i.e., individuals with a medical marijuana recommendation for their own health conditions) and to respondents using marijuana not intended for medical use (nonmedical marijuana [NMM] use)., Method: Cross-sectional analyses were conducted using complex sample survey data collected from 2013 to 2018 from 12,138 adults (6,998 women) at modal ages 35 or 55 participating in the U.S. national Monitoring the Future study., Results: Diverted use was reported by 72.9% [95% CI, 66.4, 79.4] and 64.3% [56.0, 72.7] of age 35 and 55 past-12-month medical marijuana users, respectively. Age 35 diverted users were more likely than recommended users to not work full time and have no postsecondary education. Age 55 recommended users were more likely than NMM users to be retired. Age 35 diverted users were less likely than recommended users to report poor physical health (odds ratio [OR] = 0.40 [0.17, 0.94]). Age 55 diverted users were less likely than recommended users to report three or more poor health conditions (OR = 0.22 [0.09, 0.55]) and any qualifying conditions (OR = 0.21 [0.08, 0.58]). Prevalence of these conditions was similar between diverted and NMM users., Conclusions: Results indicated a substantial degree of nonmedical (i.e., recreational) marijuana use. Diverted and NMM users reported generally similar levels of health conditions, whereas diverted users had fewer indicators of poor health than recommended users.

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

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

Cannabis-based medications are being increasingly used for the treatment of different clinical conditions. Among all galenic formulations, olive oil extracts from medical Cannabis are the most prescribed ones for their easy preparation and usage. A great variety of methods have been described so far for the extraction of medical Cannabis oils to reach a high yield of Δ 9 -tetrahydrocannabinol (Δ 9 -THC), but poor attention has been paid to the preservation of the terpene fraction from the plant, which may contribute to the overall bioactivity of the extracts. In this context, the present study was aimed at the chemical characterization of different medical Cannabis oils prepared by following both innovative and existing extraction protocols, with particular attention to cannabinoids and terpenes, in order to set up a suitable method to obtain an extract rich in these chemical classes. In particular, six different extraction procedures were followed, based on different techniques, of which all but one included a decarboxylation of the plant material. The profile of cannabinoids was studied in detail by means of HPLC-ESI-MS/MS, while terpenes were characterized by means both GC-MS and GC-FID techniques coupled with solid-phase microextraction operated in the head-space mode (HS-SPME). An innovative method that is based on the extraction of the oil by dynamic maceration at room temperature from plant inflorescences, which were partially decarboxylated in a closed system at a moderate temperature and partially pre-extracted with ethanol, produced similar yields of bioactive compounds as that obtained by using a microwave-assisted distillation of the essential oil from the plant material, in combination with a maceration extraction of the oil from the residue. Both these new methods provided a higher efficiency over already existing extraction procedures of medical Cannabis oils and they can be applied to obtain a product with a high therapeutic value., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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

Posttraumatic stress disorder (PTSD) is an often chronic condition for which currently available medications have limited efficacy. Medical cannabis is increasingly used to treat patients with PTSD; however, evidence for the efficacy and safety of cannabinoids is scarce. To learn more about patients' opinions on and experiences with medical cannabis, we organized a focus group discussion among military veterans (N = 7) with chronic PTSD who were treated with medical cannabis. Afterwards, some of their partners (N = 4) joined the group for an evaluation, during which they shared their perspective on their partner's use of medical cannabis. Both sessions were audio-recorded, transcribed verbatim, and analyzed by means of qualitative content analysis. Five overarching themes were identified. The first four themes related to the different phases of medical cannabis use - namely, 1) Consideration; 2) Initiation; 3) Usage; and 4) Discontinuation. The fifth theme related to several general aspects of medical cannabis use. Patients used medical cannabis to manage their symptoms and did not experience an urge to "get high." They used a variety of different cannabis strains and dosages and reported several therapeutic effects, including an increased quality of sleep. Furthermore, discussions about the experienced stigma surrounding cannabis generated insights with implications for the initiation of medical cannabis use. These results underscore the value of qualitative research in this field and are relevant for the design of future clinical trials on the use of medical cannabis for the treatment of PTSD., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Objective : Scientific research on how consumption of whole, natural Cannabis flower affects low mood and behavioral motivations more generally is largely nonexistent, and few studies to date have measured how common and commercially available Cannabis flower used in vivo may affect the experience of "depression" in real-time. Methods : We observed 1,819 people who completed 5,876 cannabis self-administration sessions using the ReleafApp™ between 06/07/2016 and 07/08/2019, with the goal of measuring real-time effects of consuming Cannabis flower for treating symptoms of depression. Results: On average, 95.8% of users experienced symptom relief following consumption with an average symptom intensity reduction of -3.76 points on a 0-10 visual analogue scale (SD = 2.64, d = 1.71, p <.001). Symptom relief did not differ by labeled plant phenotypes (" C. indica ," "C. sativa ," or "hybrid") or combustion method. Across cannabinoid levels, tetrahydrocannabinol (THC) levels were the strongest independent predictors of symptom relief, while cannabidiol (CBD) levels, instead, were generally unrelated to real-time changes in symptom intensity levels. Cannabis use was associated with some negative side effects that correspond to increased depression ( e.g. feeling unmotivated) in up to 20% of users, as well as positive side effects that correspond to decreased depression ( e.g. feeling happy, optimistic, peaceful, or relaxed) in up to 64% of users. Conclusions : The findings suggest that, at least in the short term, the vast majority of patients that use cannabis experience antidepressant effects, although the magnitude of the effect and extent of side effect experiences vary with chemotypic properties of the plant., (Copyright ©2020, Yale Journal of Biology and Medicine.)

Objectives: To evaluate safety and pharmacokinetic parameters (PK) of medical cannabis in add-on for children and young adults with drug-resistant epilepsy., Design, Setting: Ten patients (4 females, 6 males, age 2.5-23.2 years) were enrolled in a prospective open trial with a galenic preparation (decoction) of Italian cannabis (FM2, ratio THC:CBD = 3:5, range THC 5.2-7.2 %; CBD 8.2-11.1 %). Patients received the first dose in Hospital, progressively augmented by CBD dose titration (from 1 to 4 mg/kg/day)., Outcome Measures: In order to assess safety, blood parameters, heart rates and electrocardiograms (ECGs) were evaluated before the enrollment and during the follow up. The PK study was performed measuring THC and CBD concentrations by UHPLC-MS/MS in plasma samples collected during the first administration and at each follow-up visit., Results: Two out of ten patients stopped the treatment for adverse events (detected in 6/10: gastroenteric, sleep or behavioral disorders) and difficulties in drug supply. We observed minor ECG alterations in two patients and asymptomatic transient reductions of fibrinogen after 6 months of therapy. The PK study during follow-up revealed statistically significant correlations between THC-CBD blood concentrations and: volumes of decoction, FM2 and THC-CBD daily dosages., Conclusions: The present study, although with some limitations, shows a good safety profile of medical cannabis in children and young patients with drug-resistant epilepsy and encourages the possibility of further studies with oral cannabis-based drugs. The correlations between THC-CBD plasma concentrations and their administered dosages underline the need of a therapeutic drug monitoring for cannabinoids therapy., Competing Interests: Declaration of Competing Interest All the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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