Cannabis-based Medicines Research Articles

CORR Insights®: Does Cannabis-based Medicine Improve Pain and Sleep Quality in Patients With Traumatic Brachial Plexus Injuries? A Triple-blind, Crossover, Randomized Controlled Trial.

CORR Insights®: Does Cannabis-based Medicine Improve Pain and Sleep Quality in Patients With Traumatic Brachial Plexus Injuries? A Triple-blind, Crossover, Randomized Controlled Trial.

Comprehensive Review of Phytochemical Studies and Legalization of Cannabis in Morocco

Research on cannabis and its bioactive derivatives, including cannabinoids, non-cannabinoids, and extracts, has significantly increased in recent years due to their potential therapeutic applications as demonstrated by numerous published studies. Although there is evidence of the potential efficacy of cannabinoid and non-cannabinoid compounds from cannabis in the treatment of various diseases and syndromes, further research is required to mitigate the potential damage that could result from the excessive use of cannabinoid products, particularly tetrahydrocannabinol (THC), such as psychotropic effects, addiction, cognitive deficits, cardiovascular problems, and impacts on mental health. This review describes phytochemical and biological studies on cannabis grown in Morocco, utilizing databases such as SciFinder, ScienceDirect, Scopus, Google Scholar, and PubMed to provide updated data on cannabis in Morocco. The findings of this research aim to enable investors, economic operators, researchers, and policymakers to better understand the current state of cannabis in Morocco, thereby promoting industry growth and cannabis-related innovation. Additionally, this paper includes a brief discussion on the legalization of cannabis in Morocco, highlighting the new opportunities for investment in medical cannabis. This study also underscores that much remains to be explored regarding Moroccan cannabis, from the isolation of bioactive compounds and pre-clinical studies to clinical trials and the mass production of approved cannabis-based medicines. Furthermore, the findings are intended to inform key stakeholders about the current state of cannabis in Morocco, fostering industry growth and innovation.

Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits

AbstractThe legalization of cannabis for medical and recreational purposes has progressed internationally. Cannabis and cannabinoids are advocated for a plethora of medical indications. An increasing number of medical and nonmedical users regularly consume large doses of delta-9-Tetrahydrocannabinol (THC), the main active component of cannabis. Aim: to summarize the evidence on (1) risks of recreational cannabis use and (2) effectiveness and safety of medicinal cannabis. Findings on recreational use: Cannabis is mostly used to experience its acute rewarding effects. Regular use of high THC products can produce addiction (cannabis use disorder or CUD). Acute consumption of high THC doses (including unintentionally) can cause time-limited mental, gastrointestinal, and cardiovascular problems and motor vehicle accidents. Chronic patterns of cannabis use have been associated with multiple adverse outcomes that are of particular concern among adolescents and young adults, such as, disrupted learning, impaired cognitive performance, reduced educational attainment and an increased risk of CUD, psychosis/schizophrenia, mood and anxiety disorders and suicidal behaviors. There is debate about the extent to which cannabis use is a cause of these adverse outcomes. Physical health risks (e.g., respiratory and cardiovascular, prematurity and restricted fetal growth, hyperemesis syndrome among others) have also been linked with repeated consumption of cannabis with a high THC content. Findings on medical cannabis use: Herbal cannabis, medicines from extracted or synthetized cannabinoids—often used as adjuvants to standard medicines—may produce small to modest benefits. This is primarily the case in treating chronic pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and refractory epilepsy (in the case of cannabidiol, CBD). The evidence is inconclusive on their value in treating mental disorders and other medical conditions. Safety: Cannabis-based medicine is generally well tolerated. There is a risk of mild to moderate adverse effects and CUD.

Does Cannabis-based Medicine Improve Pain and Sleep Quality in Patients With Traumatic Brachial Plexus Injuries? A Triple-blind, Crossover, Randomized Controlled Trial.

After traumatic brachial plexus injuries, despite treatment with appropriate medications, some patients experience uncontrollable pain, which can be devastating. Cannabis-based medicine is considered to have pain-relieving benefits in this situation, but the evidence is limited. Is cannabis-based medicine effective compared with the placebo in (1) reducing pain (measured by the VAS for pain) and neuropathic pain (measured by the DN4 questionnaire), and (2) improving sleep quality (measured by the VAS for sleep quality) in patients with traumatic brachial plexus injury? This prospective, triple-blinded (the researcher administering the substance, the patients, and the evaluator were all blinded to the substance used), two-period crossover, placebo-controlled, randomized controlled trial was conducted at a single center. Between January 2020 and January 2022, we treated 147 patients for neuropathic pain related to a traumatic brachial plexus injury. Our inclusion criteria were age between 20 and 60 years and moderate-to-severe pain (VAS for pain equal to or greater than 4 of 10 for more than 6 months), even with the use of appropriate medications. Based on these criteria, 20% (30) of patients were eligible. They were randomly allocated to receive either cannabis-based medicine followed by the placebo or vice versa. Fifteen patients received cannabis-based medicine first, and 15 patients received the placebo first. The groups did not differ at baseline in terms of demographic parameters. Participants received both the cannabis-based medicine and the placebo; they started with 10 days of the initial intervention, followed by a 14-day washout period, and then a 10-day period with the second intervention. The dosage regimen adhered strictly to the protocol. The outcomes were the (1) VAS for pain, which ranges from 0 to 10 and where 0 represents no pain and 10 signifies the worst pain; (2) the DN4 questionnaire which ranges from 1 to 10 and where a score of 4 or higher indicates a positive result for neuropathic pain; and (3) VAS for sleep quality, from 0 (worst) to 10 (best). The minimum clinically important difference of VAS for pain was defined as a 2-point improvement. After enrollment, 7% (2 of 30) of patients (one patient received the cannabis-based medicine first and another received the placebo first) were lost before the minimum study follow-up, leaving 93% (28 of 30) for analysis. With 28 patients in each group, the study was powered a priori at 90% to detect a clinically important difference of 2 points in the VAS for pain. No carryover or period effects were observed in the study. Four patients experienced mild dizziness during the cannabis-based medicine period but were able to continue the intervention. When comparing the use of cannabis-based medicine alongside pain control medications with the combination of placebo and pain control medications, the reduction in pain VAS from the preintervention resulted in a mean difference of 1 (99% CI -0.03 to 2.1; p = 0.01). Neuropathic pain was reported by 75% (21 of 28) of patients in both interventions (OR 1 [99% CI 0.07 to 14.1]; p > 0.99). The VAS for sleep quality favored cannabis-based medicine with a mean difference of 1.5 (99% CI 0.7 to 2.4; p < 0.001). Our study findings indicate that cannabis-based medicine did not improve pain by a clinically important margin. Consequently, our study advises against the addition of cannabis-based medicine to the standard medication treatment for pain in patients with traumatic brachial plexus injury. Level 1, therapeutic study.

The Therapeutic Potential and Molecular Mechanisms Underlying the Neuroprotective Effects of Sativex® - A Cannabis-derived Spray.

Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants. Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders. The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.

Efficacy of cannabinoids compared to the current standard treatments on symptom relief in persons with multiple sclerosis (CANSEP trial): study protocol for a randomized clinical trial.

Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system. More than 90,000 Canadians are affected; a cure is yet to be found. Available treatments to manage the disease course are only partially effective. For many years, persons with MS (PwMS) have used cannabis to relax, to reduce pain and spasticity, or to improve sleep and daily functioning, despite the lack of scientific evidence on the efficacy of specific cannabinoids [i.e., tetrahydrocannabinol (THC) and cannabidiol (CBD)] on these MS symptoms. The purpose of this clinical trial is to assess the effectiveness of different doses of these cannabinoids, alone or combined, on spasticity relief, compared to placebo. Moreover, we aim to determine which treatment is best effective to address other key MS conditions. A double-blinded, randomized, factorial, placebo-controlled trial will be performed. We intend to include up to 250 PwMS aged over 21 recruited from the Centre hospitalier de l'Université de Montréal MS Clinic. PwMS will be randomly assigned on a 1:1:1:1 ratio to one of the trial arms: THC alone, CBD alone, THC/CBD combination, or placebo, using stratified blocked randomization, with random blocks within each stratum. The primary outcome is a self-assessment of spasticity using the mean Numeric Rating Scale score over 7 days. The main outcome will be the difference in this score at 4 weeks compared to baseline. Secondary outcomes include assessments of spasticity as measured by a clinician, pain, fatigue, sleep, bowel, bladder, and sexual dysfunction, restless legs syndrome, mental health, quality of life, mobility, cognitive functioning, and adverse events. Treatment responders are eligible for a 12-week extension phase, using the same treatment allocation and assessments. Previous clinical studies examined the efficacy of cannabis-based medicines in PwMS, mostly using products with 1:1 THC/CBD ratio. The major barrier to effectively use cannabis in real-world clinical settings is the lack of evidence on benefits of specific cannabinoids and information on possible related risks. The CANSEP study will contribute to overcome these limitations and identify the risks and benefits of cannabis-based treatments in PwMS. ClinicalTrials.Gov, NCT05092191.

Nanocarriers for Cannabinoid Delivery: Enhancing Therapeutic Potential.

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.

Feasibility of a Randomized, Interventional Pilot Clinical Study of Oral Cannabinoids in People with HIV on Antiretroviral Therapy: CTNPT 028.

Cannabis-based medicines (CBMs) could help reduce systemic inflammation in people with HIV (PWH). In a prospective, randomized pilot study we enrolled participants from August 2021-April 2022 with HIV, aged ≥18 and on antiretroviral therapy and randomly assigned them to cannabidiol (CBD) ± Δ9-tetrahydrocannabinol (THC) capsules for 12 weeks with the primary objective being to assess safety and tolerability. Here we report on timeliness to study initiation, enrolment, compliance and retention rates. The target sample size was not reached. Two hundred and five individuals were approached, and 10 consented and were randomized; the rest refused (reasons: cannabis-related stigma/discomfort; too many study visits/insufficient time; unwillingness to undergo a "washout period" for three weeks) or were not eligible. The age of those randomized was 58 years (IQR 55-62); 80% were male. Only three met all criteria (30% enrolment compliance); seven were enrolled with minor protocol deviations. Compliance was excellent (100%). Eight (80%) participants completed the study; two (20%) were withdrawn for safety reasons (transaminitis and aggravation of pre-existing anemia). Time to study initiation and recruitment were the most challenging aspects. Ongoing work is required to reduce stigma related to CBMs. Future studies should find a balance between the requirements for safety monitoring and frequency of study visits.

Overview of global monitoring systems for the side effects and adverse events associated with medicinal cannabis use: a scoping review using a systematic approach

ObjectivesThe use of cannabis-based medicine (CBM) as a therapeutic has surged in Australia over the past 5 years. Historically, the United Nations Single Convention on Narcotic Drugs (1961) prohibited cannabis...

Evidence for the use of cannabis-based medicines in osteoarthritis: a scoping review.

The purpose of this study was to conduct a scoping review to describe the evidence on the efficacy and safety of using cannabis-based medicines for osteoarthritis. The review was conducted following the framework proposed by Arksey and O'Malley and reported following PRISMA extension for scoping reviews guidelines. We conducted a comprehensive search across various databases including MEDLINE, Embase, Cochrane Library, CINAHL, Scopus, and Proquest, spanning from inception of each database to March 2023. We retrieved 2533 citations, and after deduplication, title and abstract screening, and full-text screening, 10 articles were included for analysis. These studies were composed of randomized-controlled trials (n = 4/10), cross-sectional surveys (n = 3/10), case studies (n = 2/10), and a cohort study (n = 1/10). Evidence for using cannabis-based medicines was mixed, with just 60% (n = 6/10) of included studies reporting statistically significant improvements in pain. Studies with larger samples sizes and longer durations of exposure did not find significant benefits for pain. The few adverse effects reported were generally mild and affected a minority of participants. Several studies also discovered that cannabis-based medicines were associated with a reduction in opioid use. Currently available data on the use of cannabis-based medicines in osteoarthritis is insufficient to make recommendations. Future research should address concerns regarding small sample sizes and short treatment durations to provide a more robust evidence base. Key Points • Current evidence remains mixed; studies that found a positive benefit with using cannabis-based medicines had limitations with small sample sizes and short durations of exposure • The use of cannabis-based medicines in osteoarthritis appears to be generally well tolerated, adverse effects are mild and experienced by a minority of participants • Cannabis-based medicines may decrease the use of opioids in patients with osteoarthritis • Future research should address the gaps in long-term efficacy and safety data.

Vasoactive and Antifibrotic Properties of Cannabinoids and Applications to Vasospastic/Vaso-Occlusive Disorders

Background Management of vasospastic and vaso-occlusive disorders is a complex challenge, with current treatments showing varied success. Cannabinoids have demonstrated both vasodilatory and antifibrotic properties, which present potential mechanisms for therapeutic relief. No existing review examines these effects in peripheral circulation in relation to vasospastic and vaso-occlusive disorders. This study aims to investigate vasodilatory and antifibrotic properties of cannabinoids in peripheral vasculature for application in vasospastic and vaso-occlusive disorders affecting the hand. Methods A systematic search was conducted by 2 independent reviewers across PubMed, Cochrane, Ovid MEDLINE, and CINAHL to identify studies in accordance with the determined inclusion/exclusion criteria. Information regarding study design, medication, dosage, and hemodynamic or antifibrotic effects were extracted. Descriptive statistics were used to summarize study findings as appropriate. Results A total of 584 articles were identified, and 32 were selected for inclusion. Studies were grouped by effect type: hemodynamic (n = 17, 53%) and antifibrotic (n = 15, 47%). Vasodilatory effects including reduced perfusion pressure, increased functional capillary density, inhibition of vessel contraction, and increased blood flow were reported in 82% of studies. Antifibrotic effects including reduced dermal thickening, reduced collagen synthesis, and reduced fibroblast migration were reported in 100% of studies. Conclusion Overall, cannabinoids were found to have vasodilatory and antifibrotic effects on peripheral circulation via both endothelium-dependent and independent mechanisms. Our review suggests the applicability of cannabis-based medicines for vasospastic and vaso-occlusive disorders affecting the hand (eg, Raynaud disease, Buerger disease). Future research should aim to assess the effectiveness of cannabis-based medicines for these conditions.

Assessing the preparedness and future-readiness of Malaysian community pharmacists in Klang Valley regarding the use of medical marijuana

BackgroundThis study investigated community pharmacists' level of knowledge and attitude towards medical marijuana and its association with sociodemographic characteristics.MethodsA cross-sectional study was conducted from 21 February 2022 to 15 November 2022. Community pharmacists working in Klang Valley were given a self-administered questionnaire. This survey instrument facilitated the collection of information about their sociodemographic attributes, training background, and knowledge and attitude concerning medical marijuana. Through rigorous analysis of the accumulated data, discernible factors correlating with the levels of knowledge and attitudes surrounding medical marijuana were identified.ResultsThe majority (n=149, 53.8%) of participants had low knowledge of medical marijuana. Participants with lower knowledge of medical marijuana tend to have a negative attitude toward medical marijuana. Besides that, male participants showed higher knowledge of medical marijuana than female participants. Furthermore, it was found that atheists had the most negative attitude among other religions toward medical marijuana.ConclusionMost community pharmacists in Malaysia lack sufficient knowledge about medical marijuana. This indicates that Malaysian pharmacists are not future-ready and need to equip themselves with adequate knowledge of the indications and adverse effects of medical marijuana if it is to be legalised one day. Thus, there is a need for improved training and education of pharmacists around cannabis-based medicines.

Phytotherapeutic recommendations in medical guidelines for the treatment of gastroenterological diseases - a systematic review

Phytotherapeutics are gaining influence in the treatment of gastroenterological diseases. Their popularity and growing evidence of efficacy contribute to their integration into medical guidelines. A systematic screening identified recommended phytotherapeutic approaches. Based on current scientific data, some recommendations for the use of phytotherapeutic agents are given. For irritable bowel syndrome the use of peppermint oil is "strongly recommended", especially for pain and flatulence. Other phytotherapeutics such as STW-5, Tibetan Padma Lax or warm caraway oil pads have proven effective in alleviating symptoms. It is "recommended" to integrate them into the treatment concept. For chronic constipation, 30g of fiber per day is recommended. Best data exists for plantago psyllium with moderate evidence and chicory inulin. In case of ulcerative colitis, plantago psyllium as well as the combination of myrrh, chamomile flower extract, and coffee charcoal can be used as a complementary treatment in maintaining remission. There is also an "open recommendation" for curcumin for both, remission induction and maintenance. Some phytotherapeutic treatments (e.g., Artemisia absintium, Boswellia serata) show evidence of effectiveness for the treatment of Crohn's disease, but data are not yet sufficient for recommendations. Cannabis-based medicines can be considered for abdominal pain and clinically relevant appetite loss if standard therapy is ineffective or contraindicated, but they should not be used for acute inflammation in active Crohn's disease. Further recommendations for other gastroenterological diseases are discussed. The safety and tolerability of the phytotherapeutics were rated as predominantly "very good" to "acceptable". Some clear recommendations for the use of phytotherapeutics to treat gastroenterological diseases show their great potential. Due to their wide range of effects, phytotherapeutics can be used very well as a complement to conventional medicines in case of complex regulatory disorders. However, further methodologically well-conducted impact studies would be helpful in order to be able to make further recommendations.

Cannabinoids in the Treatment of Selected Mental Illnesses: Practical Approach and Overview of the Literature.

Although an increasing number of patients suffering from mental illnesses self-medicate with cannabis, current knowledge about the efficacy and safety of cannabis-based medicine in psychiatry is still extremely limited. So far, no cannabis-based finished product has been approved for the treatment of a mental illness. There is increasing evidence that cannabinoids may improve symptoms in autism spectrum disorder (ASD), Tourette syndrome (TS), anxiety disorders, and post-traumatic stress disorder (PTSD). According to surveys, patients often use cannabinoids to improve mood, sleep, and symptoms of attention deficit/hyperactivity disorder (ADHD). There is evidence suggesting that tetrahydrocannabinol (THC) and THC-containing cannabis extracts, such as nabiximols, can be used as substitutes in patients with cannabis use disorder.Preliminary evidence also suggests an involvement of the endocannabinoid system (ECS) in the pathophysiology of TS, ADHD, and PTSD. Since the ECS is the most important neuromodulatory system in the brain, it possibly induces beneficial effects of cannabinoids by alterations in other neurotransmitter systems. Finally, the ECS is an important stress management system. Thus, cannabinoids may improve symptoms in patients with mental illnesses by reducing stress.Practically, cannabis-based treatment in patients with psychiatric disorders does not differ from other indications. The starting dose of THC-containing products should be low (1-2.5 mg THC/day), and the dose should be up-titrated slowly (by 1-2.5 mg every 3-5 days). The average daily dose is 10-20 mg THC. In contrast, cannabidiol (CBD) is mainly used in high doses>400 mg/day.

ATR-FTIR spectroscopy and LDA: a rapid, non-destructive and cost effective strategy to trace the geographical origin of Cannabis sativa L

Abstract Cannabis recreational and/or medicinal use have been legalized in the past years in many states and countries. As a consequence, many Cannabis growers and product developers have emerged in a new market throughout the world; at the same time, issues regarding questionable quality control have also risen, as several reports on Cannabis users’ health-related problems caused by inaccurate labeling content in Cannabis-based medicines, edibles or other derivatives are being published and brought out to the public’s attention. These facts make traceability methodologies crucial whether for forensic use, such as drug trafficking eradication, or for quality control purposes of legal Cannabis and of products derived from it. Hence, the objective of this study was to analyze Cannabis by means of Attenuated Total Reflection Spectroscopy (ATR-FTIR) in order to assess the capability of this technique to trace the geographical origin of Cannabis cultivated in Brazil and in Colorado, United States of America. Forty-seven samples from Brazil and 18 samples from Colorado were analyzed by ATR-FTIR. Linear Discriminant Analysis (LDA) was employed to source the samples. The combination of ATR-FTIR and LDA achieved up to 95.23% accuracy in assigning Cannabis samples to their geographical locations of origin in Brazil and up to 100% in Colorado.

Cannabis-based medicines and medical fitness-to-drive: current legal issues in Switzerland.

Interest in cannabis-based medicines has risen importantly in recent years due to the wide range of potential uses. On the other hand, delta-9-tetrahydrocannabinol (THC) impairs driving performance and other safety-sensitive tasks. Under the Swiss law, use of cannabis with a THC content of at least 1% is generally prohibited. However, the Swiss Parliament has decided to lift the ban on cannabis-based medicines from 1 August 2022. Hence, exceptional authorisation from the Federal Office of Public Health is no longer required for cannabis-based medicine prescription. Accordingly, general practitioners may prescribe these medicines (e.g. 'magistral preparations', i.e. a medicinal preparation prepared on prescription by a pharmacist). On the other hand, prescribing physicians must inform their patients that cannabis-based medicines may affect momentary ability to drive and general fitness-to-drive. The positioning of cannabis as a legitimate medical treatment produces some tensions with other regulatory frameworks. A notable example of this is the so-called 'zero tolerance' drug driving legal frameworks, which criminalise the presence of THC in a driver's bodily fluids irrespective of impairment. On the other hand, it has been observed that there is little evidence to justify the differential treatment of patients taking cannabis-based medicines compared with those taking other medications potentially impairing driving performances. The aim of this paper is to briefly discuss current Swiss legal issues concerning drivers who are prescribed medicines containing cannabis, as well as to update prescribing physicians on relevant issues and the best guidance to offer their patients.

DIsCOvER: A multicenter, randomized, double-blind, placebo-controlled, phase III clinical trial to investigate the efficacy and safety of dronabinol in the improvement of chemotherapy-induced and tumor-related symptoms in patients with locally advanced or metastatic pancreas cancer during first-line chemotherapy.

TPS711 Background: Patients (pts) with pancreatic cancer suffer from multiple symptoms related to the tumor itself or induced by chemotherapy (ctx). The available supportive therapy is still not able to relief all symptoms caused by the cancer itself or by the antineoplastic therapy. Additionally, anorexia and weight loss often result in increased morbidity and mortality in this population as well as in psycho-social burden and suffering. These are unmet needs in pancreatic cancer pts. Dronabinol has shown beneficial effects observed in cancer pts. However, evidence from randomized, placebo controlled trials in the use of cannabinoids for the treatment of cancer related anorexia-cachexia syndrome are lacking. Aim of this phase III trial is to investigate the efficacy and safety of dronabinol (orally administered tetrahydrocannabinol (THC)) as adjuvant, individually titrated therapy to first-line standard chemotherapy in pts with metastatic pancreas cancer for improvement of ctx- and tumor-related symptoms. Methods: Locally advanced or metastatic pancreas cancer pts from Austria and Germany with age of ≥18 yrs tolerating FOLFIRINOX or gemcitabine/nab-paclitaxel based ctx are eligible for enrolment. Exclusion criteria are use of dronabinol, cannabis-based medicine with THC or marihuana or relevant psychiatric disorders. The study duration for each patient will be a maximum of 18 wks treatment. Eligible pts are randomized 1:1 for treatment with dronabinol oral solution (2.5%) or placebo oral solution stratified by underlying ctx. The primary endpoint variable is the standardized area under the curve of the EORTC QLQ-C30 symptom summary score over the on-treatment period. Secondary endpoints include: other quality of life parameters, changes in Glasgow Prognostic Score, mean time to critical weight-loss (5%), ctx dose intensity over the treatment of 18 wks, adverse events/reactions, PFS and OS. Changes from baseline for bioelectrical impedance analysis parameters (e.g. fat-free mass, total body water, fat mass and phase angle) and handgrip strength will be evaluated. Estimating a difference of 20% in the primary endpoint between the treatment groups with a power of 80% and an expected standard deviation of 30 a total sample size of 74 assuming a balanced design is required. A total sample size of 104 pts is needed with expected drop-out rate of 30 pts. Enrolment started in 2019 and continues until 2024. The DIsCOvER trial is the first randomized, placebo-controlled phase III trial that investigates the impact of individually dosed dronabinol in cancer pts (Registration: NCT03984214). Clinical trial information: NCT03984214 .

Narrative bias ("spin") is common in randomised trials and systematic reviews of cannabinoids for pain.

We define narrative bias as a tendency to interpret information as part of a larger story or pattern, regardless of whether the facts support the full narrative. Narrative bias in title and abstract means that results reported in the title and abstract of an article are done so in a way that could distort their interpretation and mislead readers who had not read the whole article. Narrative bias is often referred to as "spin." It is prevalent in abstracts of scientific papers and is impactful because abstracts are often the only part of an article read. We found no extant narrative bias instrument suitable for exploring both efficacy and safety statements in randomized trials and systematic reviews of pain. We constructed a 6-point instrument with clear instructions and tested it on randomised trials and systematic reviews of cannabinoids and cannabis-based medicines for pain, with updated searches to April 2021. The instrument detected moderate or severe narrative bias in the title and abstract of 24% (8 of 34) of randomised controlled trials and 17% (11 of 64) of systematic reviews; narrative bias for efficacy and safety occurred equally. There was no significant or meaningful association between narrative bias and study characteristics in correlation or cluster analyses. Bias was always in favour of the experimental cannabinoid or cannabis-based medicine. Put simply, reading title and abstract only could give an incorrect impression of efficacy or safety in about 1 in 5 papers reporting on these products.

Overview: Chronic Pain and Cannabis-Based Medicines.

Chronic pain is primarily conceptualized as a disease in its own right when it is associated with emotional distress and functional impairment. Pathophysiologically, dysfunction of the cortico-mesolimbic connectome is of major importance, with overlapping signals in the nociceptive and stress systems. The endocannabinoid system plays an important role in the central processing of nociceptive signals and regulates the central stress response. Clinically, there is moderate evidence that cannabis-based medicines (CBM) can contribute to a significant reduction in pain, especially the associated pain affect, and improvement in physical function and sleep quality in a proportion of patients with chronic pain. The analgesic effect appears to be largely independent of the cause of pain. In this context, CBM preferentially regulates stress-associated pain processing.

Traceability and control as levers to prevent leakage from legal circulation when legalizing medical cannabis.

Aim: To reveal traceability and control as levers to prevent leakage from legal circulation when legalizing medical cannabis. Materials and Methods: The methodological basis of this research work is based on a systematic approach. Methods of structural and logical analysis, bibliosemantic, abstraction and generalization were used in this article. Results: The analysis of the regulatory framework and regulatory initiatives in the field of circulation of narcotic drugs, in particular, cannabis (in total 56 documents) demonstrated repeated attempts to reform it in Ukraine in order to increase the availability and efficiency of medical and pharmaceutical services. Recently adopted law on the legalization of medical cannabis pays special attention to the traceability of the circulation of medical cannabis and cannabis-based medicines (CbMs) by digitalization and creation of the appropriate electronic information system. Conclusions: With the adoption of the law on the legalization of medical cannabis Ukraine became the 57th country in the world to legalize such cannabis. The study and analysis of the regulatory framework of Ukraine, taking into account the best world practices, showed that the legalization of medical cannabis will allow for providing more effective care to many patients including wounded defenders.