Cardiotoxic effects of common and emerging drugs: role of cannabinoid receptors.

Drug-induced cardiotoxicity has become one of the most common and detrimental health concerns, which causes significant loss to public health and drug resources. Cannabinoid receptors (CBRs) have recently achieved great attention for their vital roles in the regulation of heart health and disease, with mounting evidence linking CBRs with the pathogenesis and progression of drug-induced cardiotoxicity. This review aims to summarize fundamental characteristics of two well-documented CBRs (CB1R and CB2R) from aspects of molecular structure, signaling and their functions in cardiovascular physiology and pathophysiology. Moreover, we describe the roles of CB1R and CB2R in the occurrence of cardiotoxicity induced by common drugs such as antipsychotics, anti-cancer drugs, marijuana, and some emerging synthetic cannabinoids. We highlight the 'yin-yang' relationship between CB1R and CB2R in drug-induced cardiotoxicity and propose future perspectives for CBR-based translational medicine toward cardiotoxicity curation and clinical monitoring.

The Safety and Comparative Effectiveness of Non-Psychoactive Cannabinoid Formulations for the Improvement of Sleep: A Double-Blinded, Randomized Controlled Trial.

BACKGROUND: Clinical evidence on the use of cannabidiol (CBD) for sleep remains limited. Even fewer studies have tested the comparative effectiveness of cannabinoid formulations found within CBD products used for sleep or how they compare to other complementary therapies such as melatonin. METHODS: Participants (N = 1,793 adults experiencing symptoms of sleep disturbance) were randomly assigned to receive a 4-week supply of 1 of 6 products (all capsules) containing either 15 mg CBD or 5 mg melatonin, alone or in combination with minor cannabinoids. Sleep disturbance was assessed over a period of 5 weeks (baseline week and 4 weeks of product use) using Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A, administered via weekly online surveys. A linear mixed-effects regression model was used to assess the differences in the change in sleep disturbance through time between each active product arm and CBD isolate. RESULTS: All formulations exhibited a favorable safety profile (12% of participants reported a side effect and none were severe) and led to significant improvements in sleep disturbance (p < 0.001 in within-group comparisons). Most participants (56% to 75%) across all formulations experienced a clinically important improvement in their sleep quality. There were no significant differences in effect, however, between 15 mg CBD isolate and formulations containing 15 mg CBD and 15 mg cannabinol (CBN), alone or in combination with 5 mg cannabichromene (CBC). There were also no significant differences in effect between 15 mg CBD isolate and formulations containing 5 mg melatonin, alone or in combination with 15 mg CBD and 15 mg CBN. CONCLUSIONS: Our findings suggest that chronic use of a low dose of CBD is safe and could improve sleep quality, though these effects do not exceed that of 5 mg melatonin. Moreover, the addition of low doses of CBN and CBC may not improve the effect of formulations containing CBD or melatonin isolate.

Acute Treatment of Adolescent Cannabinoid Hyperemesis Syndrome With Haloperidol, Lorazepam, and/or Capsaicin: A Single Institution Case Series.

Cannabinoid hyperemesis syndrome (CHS), an under-recognized and seemingly paradoxical condition, arises in some adolescents and adults who chronically use cannabis. It presents acutely with intractable nausea, vomiting, and abdominal pain but standard antiemetic therapy leads to improvement for only a minority of patients. Randomized controlled trial evidence in adults indicates the superiority of haloperidol over ondansetron in alleviating the acute symptoms of CHS, but safe and effective treatment for adolescents with the disorder is currently unknown. The successful use of topical capsaicin has also been reported. We report a case series of 6 adolescent patients with CHS who presented to Johns Hopkins All Children's Hospital and were treated with haloperidol, lorazepam, and/or capsaicin. Four patients given 5 mg intravenous (IV) haloperidol and 2 mg IV lorazepam and 1 patient treated with 5 mg IV haloperidol and peri-umbilical topical capsaicin (0.025%) experienced full acute symptomatic relief. One patient, treated only with topical capsaicin, reported improvement of symptoms with some persistent nausea. Haloperidol/lorazepam, haloperidol/capsaicin, and topical capsaicin alone appear safe and effective in adolescents, but larger studies are required to confirm our findings.

History of Cannabis Regulation and Medicinal Therapeutics: It's Complicated.

The genus Cannabis has a complex history, with great variations in the genus itself, as well as in its current uses worldwide. Today, it is the most commonly used psychoactive substance, with 209 million users in 2020. The legalization of cannabis for medicinal or adult use is complex. From its origins as a therapeutic agent in 2800 bc China, to the current knowledge on cannabinoids and the cannabinoid system, to the complex status of cannabis regulation across continents-knowledge gained from the history of cannabis use can inform research on cannabis-based treatments for patients with medical conditions that remain challenging in 21st century medicine, warranting research and evidence-based policy options. Changes in cannabis-related policymaking, scientific advances, and perceptions may result in increasing patient inquiries about its medicinal usage, regardless of personal opinions, thus meriting education and training of clinicians. This commentary outlines the long history of cannabis use, its current therapeutic potential from a regulatory research perspective, and the continued challenges in research and regulation in the ever-changing era of modern cannabis use. It is crucial to understand the history and complexity of cannabis use as medicine to better understand its potential for clinical therapeutics and the effects of modern-day legalization on other health- and society-related issues.

Cannabis for the treatment of amyotrophic lateral sclerosis: What is the patients' view?

Cannabis may have therapeutic benefits to relieve symptoms of amyotrophic lateral sclerosis (ALS) thanks to its pleiotropic pharmacological activity. This study is the first to present a large questionnaire-based survey about the "real-life" situation regarding cannabis use in the medical context in ALS patients in France. There were 129 respondents and 28 reported the use of cannabis (21.7%) to relieve symptoms of ALS. Participants mostly reported the use of cannabidiol (CBD) oil and cannabis weed and declared benefits both on motor (rigidity, cramps, fasciculations) and non-motor (sleep quality, pain, emotional state, quality of life, depression) symptoms and only eight reported minor adverse reactions (drowsiness, euphoria and dry mouth). Even if cannabis is mostly used outside medical pathways and could expose patients to complications (street and uncontrolled drugs, drug-drug interactions, adverse effects…), most of the participants reported "rational" consumption (legal cannabinoids, with only few combustion and adverse reactions). Despite some limitations, this study highlights the need for further research on the potential benefits of cannabis use for the management of ALS motor and non-motor symptoms. Indeed, there is an urgent need and call for and from patients to know more about cannabis and secure its use in a medical context.

An outbreak of severe coagulopathy in northern Israel among users of illicit synthetic cannabinoids adulterated with brodifacoum.

INTRODUCTION: Adulteration of illicit drugs is a well-known phenomenon that may expose consumers to unexpected adverse effects. We report a large outbreak of severe coagulopathy in northern Israel during nine months in 2021-2022 among users of synthetic cannabinoids adulterated with a long-acting anticoagulant, brodifacoum. METHODS: We performed a retrospective cohort study based on data extracted from the Israeli National Poison Information Center database and from electronic medical patient records at three participating hospitals. Confiscated drug samples and blood samples obtained at admission in a subgroup of patients were tested for the presence of long-acting anticoagulants. RESULTS: We identified 98 patients affected by the outbreak. All patients had a prolonged international normalized ratio on admission, and in 69%, the blood was non-coagulating. For patients treated in the three participating centers (n = 72), the presenting complaint was overt bleeding in 79% of patients, most commonly in the urinary (53%) and gastrointestinal tracts (50%). The most severe complications were intracranial bleeding (4%), hemothorax (3%), pericardial bleeding (1%), and four patients died. Brodifacoum was detected in all available blood samples (median concentration 207 µg/L, interquartile range 112-349 µg/L, range 45-1,118 µg/L), and the drug samples contained both brodifacoum and the synthetic cannabinoid ADB-BUTINACA. All patients were treated with high-dose phytomenadione (vitamin K1) and additionally by packed red blood cell transfusions, fresh frozen plasma, and/or 4-factor prothrombin complex concentrate when indicated. The most frequent phytomenadione (vitamin K1) dose regimen was initially 20 mg intravenously every eight hours, and at discharge, 20 mg orally three times daily. CONCLUSIONS: Outbreaks of severe coagulopathies in users of synthetic cannabinoids adulterated with a long-acting anticoagulant continue to erupt in different regions of the world. Rapid recognition of an outbreak requires a high index of suspicion when confronting young, otherwise healthy subjects with otherwise unexplained severe coagulopathy.

Cannabinoids in Treating Parkinson's Disease Symptoms: A Systematic Review of Clinical Studies.

Background: Parkinson's disease (PD) is a serious neurodegenerative condition impacting many individuals worldwide. There is a need for new non-invasive treatments of PD. Cannabinoids in the form of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) may offer utility as treatment, and our objective was hence to conduct a systematic review regarding the clinical evidence for the efficacy and safety of cannabinoids in treating PD. Methods: Screening, data extraction, and quality assessments were all conducted by multiple reviewers, with discrepancies resolved by consensus. Results: After conducting searches in 4 different databases, 673 articles were screened. Thirteen articles were deemed eligible for inclusion in this review. It was shown that cannabis, CBD, and nabilone (a synthetic form of THC) were capable of consistently improving motor symptoms more than a placebo. All treatments improved various non-motor symptoms, particularly with cannabis improving pain intensity, and CBD improving psychiatric symptoms in a dose-dependent manner. Adverse effects were usually minor, and, in the case of CBD, rare (except at very high doses). Conclusion: Cannabinoids have been shown to safely offer important potential in treating motor symptoms in PD and some non-motor symptoms. More large-scale randomized control trials for specific forms of cannabinoid treatments are required to determine their overall efficacy.

Effectiveness and Safety of Cannabinoids as an Add-On Therapy in the Treatment of Resistant Spasticity in Multiple Sclerosis: A Systematic Review.

Background: Spasticity continues to be a very prevalent, highly invalidating, and difficult-to-manage symptom in patients with multiple sclerosis (MS). The aim of this systematic review is to evaluate the effectiveness of the use of cannabis and cannabinoids in these patients, evaluating its use as an additional therapy. Methods: We performed a systematic review of the literature searching in the major scientific databases (PubMed, Scopus, EMBASE, WOS, and Cochrane Library) for articles from January 2017 to May 2022 containing information about the effectiveness of cannabis and cannabinoids in patients with insufficient response to first-line oral antispastic treatment. Results: A total of five medium high-quality articles were selected to be part of the study and all evaluated the effectiveness of the tetrahydrocannabinol (THC) and cannabidiol (CBD) spray. The effectiveness of this drug and the significant improvements are produced on the patient-related spasticity assessment scales, obtaining improvement up to 45%; and on quality of life, producing a decrease in the appearance of symptoms related to spasticity, as well as an increase in the development of basic activities of daily living. The average dose is 5-7 sprays/day. The discontinuation rate for these treatments is around 40% due to lack of effectiveness and adverse events. All reported adverse effects are mild to moderate in severity and their incidence is ∼17%, although this figure tends to decrease with drug use. Conclusions: Adding the THC:CBD sprays have been shown to be more effective in treating MS spasticity than optimizing the dose of first-line antispastic drugs in selected responders patients. The safety and tolerability profiles remain in line with those obtained in other trials. More patients would benefit from treatment if the initial response search period was extended.

Therapeutic and Supportive Effects of Cannabinoids in Patients with Brain Tumors (CBD Oil and Cannabis).

OPINION STATEMENT: The potential medicinal properties of Cannabis continue to garner attention, especially in the brain tumor domain. This attention is centered on quality of life and symptom management; however, it is amplified by a significant lack of therapeutic choices for this specific patient population. While the literature on this matter is young, published and anecdotal evidence imply that cannabis could be useful in treating chemotherapy-induced nausea and vomiting, stimulating appetite, reducing pain, and managing seizures. It may also decrease inflammation and cancer cell proliferation and survival, resulting in a benefit in overall patient survival. Current literature poses the challenge that it does not provide standardized guidance on dosing for the above potential indications and cannabis use is dominated by recreational purposes. Furthermore, integrated and longitudinal studies are needed but these are a challenge due to arcane laws surrounding the legality of such substances. The increasing need for evidence-based arguments about potential harms and benefits of cannabis, not only in cancer patients but for other medical use and recreational purposes, is desperately needed.

Therapeutic Effects of Medicinal Cannabinoids on the Gastrointestinal System in Pediatric Patients: A Systematic Review.

Changes in cannabis legalization have generated interest in medicinal cannabinoids for therapeutic uses, including those that target the gastrointestinal (GI) tract. These effects are mediated through interactions with the endocannabinoid system. Given the increasing societal awareness of the therapeutic potential of cannabinoids, it is important to ensure pediatric representation in clinical studies investigating cannabinoid use. This systematic review aims to assess the efficacy of medicinal cannabinoids in treating GI symptoms in pediatric patients. A literature search of Medline, Embase, CINAHL, Web of Science, and the Cochrane Library was performed from inception until June 23, 2020. Study design, patient characteristics, type, dose and duration of medicinal cannabinoid therapy, and GI outcomes were extracted. From 7303 records identified, 5 studies met all inclusion criteria. Included studies focused on chemotherapy-induced nausea, inflammatory bowel disease, and GI symptoms associated with severe complex motor disorders. Results varied based on the symptom being treated, the type of cannabinoid, and the patient population. Medicinal cannabinoids may have a potential role in treating specific GI symptoms in specific patient populations. The limited number and heterogenicity of included studies highlight the demand for future research to distinguish effects among different cannabinoid types and patient populations and to examine drug interactions. As interest increases, higher quality studies are needed to understand the efficacy of cannabinoids as a pediatric GI treatment and whether these benefits outweigh the associated risks (Registration Number: PROSPERO CRD42020202486).

Cannabinoid hyperemesis syndrome in North America: evaluation of health burden and treatment prevalence.

BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is a poorly understood vomiting disorder associated with chronic cannabis use. AIMS: To characterise patients experiencing CHS in North America and to obtain a population-based estimate of CHS treatment prevalence in Canada before and during the Covid-19 pandemic METHODS: Internet survey of 157 CHS sufferers in Canada and the United States. Administrative health databases for the province of Alberta (population 5 million) were accessed to measure emergency department (ED) visits for vomiting, with a concurrent diagnostic code for cannabis use. Three time periods of 1 year were assessed: prior to recreational cannabis legalisation (2017-2018), after recreational legalisation (2018-2019) and during the first year of the Covid-19 pandemic (2020-2021). RESULTS: Problematic cannabis use (defined as a CUDIT-R score ≥8) was universal among the survey cohort, and 59% and 68% screening for moderate or worse anxiety or depression, respectively. The overall treatment prevalence of CHS across all ages increased from 15 ED visits per 100,000 population (95% CI, 14-17) prior to legalisation, to 21 (95% CI, 20-23) after legalisation, to 32 (95% CI, 31-35) during the beginning of the Covid-19 pandemic (p < 0.001). Treatment prevalence among chronic cannabis users was as high as 6 per 1000 in the 16-24 age group. CONCLUSION: Survey data suggest patients with CHS almost universally suffer from a cannabis use disorder, which has significant treatment implications. Treatment prevalence in the ED has increased substantially over a very short time period, with the highest rates seen during the Covid-19 pandemic.

A cannabinoid Hairy-Tale: Hair loss or hair gain?

BACKGROUND: Few studies have reported on the use of cannabinoid products to treat hair loss. AIM: This article aims to reconcile cannabinoids' impact on hair growth. METHOD: A comprehensive and structured search was conducted in PubMed and Google Scholar on June 23, 2022. RESULT: While cannabidiol (CBD), a phytocannabinoid, may cause hair growth, several other phytocannabinoids may lead to hair loss. Additionally, the effect of CBD on hair growth may be concentration-dependent. CBD may cause hair loss at high concentrations (≥10 µM). Therefore, the concentration of CBD needs to be adjusted so that it is optimal for hair growth. One trial found that once-daily application of CBD-rich topical cannabis extract for 6 months increased nonvellus hair count by approximately 93.5% in 35 Caucasian AGA patients: 28 males aged 28-72 years [average 43 years] and 7 females aged 46-76 years [average 61 years]. Each application contained 3-4 mg of CBD. The CBD-rich topical cannabis extract was prepared by ultra-pulverizing Cannabis sativa [hemp] flower into a green chalk-like powder [10.78% CBD and 0.21% tetrahydrocannabinol] and then infusing the powder into a lanolin paste and Emu oil carrier. CONCLUSION: Topical CBD preparations require further studies to establish their safety and efficacy profile. An ideal topical cannabinoid preparation should contain CBD at the right concentration and lack other phytocannabinoid adulterants.

Cannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis.

BACKGROUND: Spasticity and chronic neuropathic pain are common and serious symptoms in people with multiple sclerosis (MS). These symptoms increase with disease progression and lead to worsening disability, impaired activities of daily living and quality of life. Anti-spasticity medications and analgesics are of limited benefit or poorly tolerated. Cannabinoids may reduce spasticity and pain in people with MS. Demand for symptomatic treatment with cannabinoids is high. A thorough understanding of the current body of evidence regarding benefits and harms of these drugs is required. OBJECTIVES: To assess benefit and harms of cannabinoids, including synthetic, or herbal and plant-derived cannabinoids, for reducing symptoms for adults with MS. SEARCH METHODS: We searched the following databases from inception to December 2021: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), CINAHL (EBSCO host), LILACS, the Physiotherapy Evidence Database (PEDro), the World Health Organisation International Clinical Trials Registry Platform, the US National Institutes of Health clinical trial register, the European Union Clinical Trials Register, the International Association for Cannabinoid Medicines databank. We hand searched citation lists of included studies and relevant reviews. SELECTION CRITERIA: We included randomised parallel or cross-over trials (RCTs) evaluating any cannabinoid (including herbal Cannabis, Cannabis flowers, plant-based cannabinoids, or synthetic cannabinoids) irrespective of dose, route, frequency, or duration of use for adults with MS. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane Risk of bias 2 tool for parallel RCTs and crossover trials. We rated the certainty of evidence using the GRADE approach for the following outcomes: reduction of 30% in the spasticity Numeric Rating Scale, pain relief of 50% or greater in the Numeric Rating Scale-Pain Intensity, much or very much improvement in the Patient Global Impression of Change (PGIC), Health-Related Quality of Life (HRQoL), withdrawals due to adverse events (AEs) (tolerability), serious adverse events (SAEs), nervous system disorders, psychiatric disorders, physical dependence. MAIN RESULTS: We included 25 RCTs with 3763 participants of whom 2290 received cannabinoids. Age ranged from 18 to 60 years, and between 50% and 88% participants across the studies were female.  The included studies were 3 to 48 weeks long and compared nabiximols, an oromucosal spray with a plant derived equal (1:1) combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (13 studies), synthetic cannabinoids mimicking THC (7 studies), an oral THC extract of Cannabis sativa (2 studies), inhaled herbal Cannabis (1 study) against placebo. One study compared dronabinol, THC extract of Cannabis sativa and placebo, one compared inhaled herbal Cannabis, dronabinol and placebo. We identified eight ongoing studies. Critical outcomes • Spasticity: nabiximols probably increases the number of people who report an important reduction of perceived severity of spasticity compared with placebo (odds ratio (OR) 2.51, 95% confidence interval (CI) 1.56 to 4.04; 5 RCTs, 1143 participants; I2 = 67%; moderate-certainty evidence). The absolute effect was 216 more people (95% CI 99 more to 332 more) per 1000 reporting benefit with cannabinoids than with placebo. • Chronic neuropathic pain: we found only one small trial that measured the number of participants reporting substantial pain relief with a synthetic cannabinoid compared with placebo (OR 4.23, 95% CI 1.11 to 16.17; 1 study, 48 participants; very low-certainty evidence). We are uncertain whether cannabinoids reduce chronic neuropathic pain intensity. • Treatment discontinuation due to AEs: cannabinoids may increase slightly the number of participants who discontinue treatment compared with placebo (OR 2.41, 95% CI 1.51 to 3.84; 21 studies, 3110 participants; I² = 17%; low-certainty evidence); the absolute effect is 39 more people (95% CI 15 more to 76 more) per 1000 people. Important outcomes • PGIC: cannabinoids probably increase the number of people who report 'very much' or 'much' improvement in health status compared with placebo (OR 1.80, 95% CI 1.37 to 2.36; 8 studies, 1215 participants; I² = 0%; moderate-certainty evidence). The absolute effect is 113 more people (95% CI 57 more to 175 more) per 1000 people reporting improvement. • HRQoL: cannabinoids may have little to no effect on HRQoL (SMD -0.08, 95% CI -0.17 to 0.02; 8 studies, 1942 participants; I2 = 0%; low-certainty evidence); • SAEs: cannabinoids may result in little to no difference in the number of participants who have SAEs compared with placebo (OR 1.38, 95% CI 0.96 to 1.99; 20 studies, 3124 participants; I² = 0%; low-certainty evidence); • AEs of the nervous system: cannabinoids may increase nervous system disorders compared with placebo (OR 2.61, 95% CI 1.53 to 4.44; 7 studies, 1154 participants; I² = 63%; low-certainty evidence); • Psychiatric disorders: cannabinoids may increase psychiatric disorders compared with placebo (OR 1.94, 95% CI 1.31 to 2.88; 6 studies, 1122 participants; I² = 0%; low-certainty evidence); • Drug tolerance: the evidence is very uncertain about the effect of cannabinoids on drug tolerance (OR 3.07, 95% CI 0.12 to 75.95; 2 studies, 458 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: Compared with placebo, nabiximols probably reduces the severity of spasticity in the short-term in people with MS. We are uncertain about the effect on chronic neurological pain and health-related quality of life. Cannabinoids may increase slightly treatment discontinuation due to AEs, nervous system and psychiatric disorders compared with placebo. We are uncertain about the effect on drug tolerance. The overall certainty of evidence is limited by short-term duration of the included studies.

In Vitro and In Vivo Anti-Inflammatory Effects of Cannabis sativa Stem Extract.

With growing scientific interest in cannabinoids, a number of studies have focused on biological activities of cannabidiol and its major source, inflorescence and leaf of Cannabis sativa plant. However, recent analytical chemistry studies have reported the pharmacological significance of non-cannabinoid phytochemicals that are rich in other parts of the plant. Thus, the objective of this study was to investigate the anti-inflammatory effects of Cannabis extracts from plant parts of shelled seeds, roots, and stems containing no or trace amounts of cannabinoids. Among water and ethanol extracts from three plant parts, Cannabis stem ethanol extract (CSE) had the most potent free radical scavenging activities and suppressive effects on the production of nitric oxide from macrophages. In further studies using macrophages, CSE effectively inhibited lipopolysaccharide (LPS)-induced inflammatory responses by suppressing proinflammatory cytokines, nuclear factor-κB and mitogen-activated protein kinase phosphorylations, and cellular accumulation of reactive oxygen species. Moreover, in mice exposed to LPS, CSE reduced tumor necrosis factor-α production and normalized activations of proapoptotic proteins in the liver, kidney, and spleen. Gas chromatography/mass spectrometry analyses of CSE showed several active compounds that might be associated with its antioxidant and anti-inflammatory effects. Collectively, these findings indicate that CSE counteracts LPS-induced acute inflammation and apoptosis, suggesting pharmaceutical applications for the stem part of C. sativa.

A critical review of cannabis in medicine and dentistry: A look back and the path forward.

INTRODUCTION: In the last two decades, our understanding of the therapeutic utility and medicinal properties of cannabis has greatly changed. This change has been accompanied by widespread cannabis use in various communities and different age groups, especially within the United States. With this increase, we should consider the potential effects of cannabis-hemp on general public health and how they could alter therapeutic outcomes. MATERIAL AND METHODS: The present investigation examined cannabis use for recreational and therapeutic use and a review of pertinent indexed literature was performed. The focused question evaluates "how cannabis or hemp products impact health parameters and do they provide potential therapeutic value in dentistry, and how do they interact with conventional medicines (drugs)." Indexed databases (PubMed/Medline, EMBASE) were searched without any time restrictions but language was restricted to English. RESULTS: The review highlights dental concerns of cannabis usage, the need to understand the endocannabinoid system (ECS), cannabinoid receptor system, its endogenous ligands, pharmacology, metabolism, current oral health, and medical dilemma to ascertain the detrimental or beneficial effects of using cannabis-hemp products. The pharmacological effects of pure cannabidiol (CBD) have been studied extensively while cannabis extracts can vary significantly and lack empirical studies. Several metabolic pathways are affected by cannabis use and could pose a potential drug interaction. The chronic use of cannabis is associated with health issues, but the therapeutic potential is multifold since there is a regulatory role of ECS in many pathologies. CONCLUSION: Current shortcomings in understanding the benefits of cannabis or hemp products are limited due to pharmacological and clinical effects not being predictable, while marketed products vary greatly in phytocompounds warrant further empirical investigation. Given the healthcare challenges to manage acute and chronic pain, this review highlights both cannabis and CBD-hemp extracts to help identify the therapeutic application for patient populations suffering from anxiety, inflammation, and dental pain.

Cannabinoids in rheumatology: Friend, foe or a bystander?

OBJECTIVES: Cannabinoids have gained popularity recently with special emphasis on their use for chronic pain. Although NICE guidelines advise against their usage for management of chronic pain, almost all rheumatologists encounter a few patients in their daily practice who either use them or are curious about them. We reviewed the mechanism of action of cannabinoids, current knowledge about their role in rheumatology and potential drug interactions with common drugs used in Rheumatology. We attempted to answer the question "If cannabinoids are friend, foe or just a mere bystander?" METHODS: We adhered to a search strategy for writing narrative reviews as per available guidelines. We searched PubMed with the search terms "Cannabinoids", "Rheumatology" and "Chronic pain" for published articles and retrieved 613 articles. The abstracts and titles of these articles were screened to identify relevant studies focusing on mechanism of actions, adverse effects and drug interactions. We also availed the services of a musculoskeletal librarian. RESULTS: Despite the NHS guidelines against the usage of cannabinoids and associated significant stigma, cannabinoids are increasingly used for the management of pain in rheumatology without prescription. Cannabinoids act through two major receptors CB1 and CB2, which are important modulators of the stress response with potential analgesic effects. Their role in various rheumatological diseases including Rheumatoid arthritis, Osteoarthritis and Fibromyalgia have been explored with some benefits. However, in addition to the adverse effects, cannabinoids also have some potential interactions with common drugs used in rheumatology, which many users are unaware of. CONCLUSION: While the current studies and patient reported outcomes suggest cannabinoids to be a "friend" of rheumatology, their adverse events and drug interactions prove to be a "Foe". We were unable to arrive at a definite answer for our question posed, however on the balance of probabilities we can conclude cannabinoids to be a "foe". Under these circumstances, a disease and drug focussed research is need of the hour to answer the unresolved question.

Cannabinoids: Therapeutic Use in Clinical Practice.

Medical case reports suggest that cannabinoids extracted from Cannabis sativa have therapeutic effects; however, the therapeutic employment is limited due to the psychotropic effect of its major component, Δ9-tetrahydrocannabinol (THC). The new scientific discoveries related to the endocannabinoid system, including new receptors, ligands, and mediators, allowed the development of new therapeutic targets for the treatment of several pathological disorders minimizing the undesirable psychotropic effects of some constituents of this plant. Today, FDA-approved drugs, such as nabiximols (a mixture of THC and non-psychoactive cannabidiol (CBD)), are employed in alleviating pain and spasticity in multiple sclerosis. Dronabinol and nabilone are used for the treatment of chemotherapy-induced nausea and vomiting in cancer patients. Dronabinol was approved for the treatment of anorexia in patients with AIDS (acquired immune deficiency syndrome). In this review, we highlighted the potential therapeutic efficacy of natural and synthetic cannabinoids and their clinical relevance in cancer, neurodegenerative and dermatological diseases, and viral infections.

Cannabis, Cannabinoids and Cannabis-Based Medicines in Cancer Care.

As medical cannabis becomes legal in more states, cancer patients are increasingly interested in the potential utility of the ancient botanical in their treatment regimen. Although eager to discuss cannabis use with their oncologist, patients often find that their provider reports that they do not have adequate information to be helpful. Oncologists, so dependent on evidence-based data to guide their treatment plans, are dismayed by the lack of published literature on the benefits of medical cannabis. This results largely from the significant barriers that have existed to effectively thwart the ability to conduct trials investigating the potential therapeutic efficacy of the plant. This is a narrative review aimed at clinicians, summarizing cannabis phytochemistry, trials in the areas of nausea and vomiting, appetite, pain and anticancer activity, including assessment of case reports of antitumor use, with reflective assessments of the quality and quantity of evidence. Despite preclinical evidence and social media claims, the utility of cannabis, cannabinoids or cannabis-based medicines in the treatment of cancer remains to be convincingly demonstrated. With an acceptable safety profile, cannabis and its congeners may be useful in managing symptoms related to cancer or its treatment. Further clinical trials should be conducted to evaluate whether the preclinical antitumor effects translate into benefit for cancer patients. Oncologists should familiarize themselves with the available database to be able to better advise their patients on the potential uses of this complementary botanical therapy.

Are Cannabis, Cannabis-Derived Products, and Synthetic Cannabinoids a Therapeutic Tool for Rheumatoid Arthritis? A Friendly Summary of the Body of Evidence.

BACKGROUND: Symptom management in rheumatoid arthritis (RA) remains a complex challenge. Widespread use of cannabis-based medicines for a myriad of symptoms has fostered rheumatology patients' interest. However, their safety and efficacy in RA remain unclear. OBJECTIVE: The aim of this study was to perform a structured summary of the body of evidence in order to determine whether cannabis, cannabis-derived products, and synthetic cannabinoids are an effective treatment for rheumatoid arthritis. METHODS: An electronic search in Epistemonikos database was performed to identify systematic reviews and their primary studies that addressed our clinical question. The body of evidence was collected in a pivot table in Epistemonikos. Information and data from the primary studies were extracted from the identified reviews. Finally, extracted data were reanalyzed, and a summary of findings table was generated using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Twenty-six systematic reviews were identified which included in total only 1 randomized trial assessing our clinical question. CONCLUSIONS: Cannabis, cannabis-derived products and synthetic cannabinoids may slightly reduce disease activity in patients with RA. Its use may result in little to no difference in pain reduction and may slightly increase nervous system adverse events. The evidence is very uncertain about the effect of cannabis, cannabis-derived products, and synthetic cannabinoids on serious adverse events risk.

Cannabis hyperemesis syndrome: Incidence and treatment with topical capsaicin. / Síndrome de hiperémesis por cannabis: incidencia y tratamiento con capsaicina tópica.

There are few studies in Spain on cannabinoid hyperemesis syndrome (CHS), as well as on the use of topical capsaicin as a treatment. METHODS: Retrospective study of patients over 14 years of age seen in a hospital emergency department during 2018 and 2019 with a diagnosis of CHS based on the following criteria: compatible clinical picture, cannabis use less than 48h and positive urine cannabis test. Epidemiological and clinical variables, attendance times and treatment (including use of topical capsaicin 0.075%) were collected. RESULTS: Fifty-nine attendances were studied, from 29 patients (4.4 cases/10,000 visits, 95% CI 2.8-4.7). Fifty per cent returned for CHS, differing only in more tobacco (P=.01) and cocaine (P=.031) use. Capsaicin was used in 74.6% of visits. The mean time to resolution of vomiting after application was 17.87min. CONCLUSIONS: Although probably underdiagnosed, CHS has a low incidence in the emergency department in Spain, with high patient recurrence. The use of capsaicin ointment is efficient and safe.