Hemp Seed Oil Inhibits the Adipogenicity of the Differentiation-Induced Human Mesenchymal Stem Cells through Suppressing the Cannabinoid Type 1 (CB1).

Central and peripheral mechanisms of the endocannabinoid system (ECS) favor energy intake and storage. The ECS, especially cannabidiol (CBD) receptors, controls adipocyte differentiation (hyperplasia) and lipid accumulation (hypertrophy) in adipose tissue. In white adipose tissue, cannabidiol receptor 1 (CB1) stimulation increases lipogenesis and inhibits lipolysis; in brown adipose tissue, it decreases mitochondrial thermogenesis and biogenesis. This study compared the availability of phytocannabinoids [CBD and Δ9-tetrahydrocannabinol (THC)] and polyunsaturated fatty acids [omega 3 (ω3) and omega 6 (ω6)] in different hemp seed oils (HSO). The study also examined the effect of HSO on adipocyte lipid accumulation by suppressing cannabinoid receptors in adipogenesis-stimulated human mesenchymal stem cells (hMSCs). Most importantly, Oil-Red-O' and Nile red tests showed that HSO induced adipogenic hMSC differentiation without differentiation agents. Additionally, HSO-treated cells showed increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to controls (hMSC). HSO reduced PPARγ mRNA expression after differentiation media (DM) treatment. After treatment with HSO, DM-hMSCs had significantly lower CB1 mRNA and protein expressions than normal hMSCs. HSO treatment also decreased transient receptor potential vanilloid 1 (TRPV1), fatty acid amide hydrolase (FAAH), and monoacylglycerol lipase (MGL) mRNAs in hMSC and DM-hMSCs. HSO treatment significantly decreased CB1, CB2, TRPV1, and G-protein-coupled receptor 55 (GPCR55) protein levels in DM-hMSC compared to hMSC in western blot analysis. In this study, HSO initiated adipogenic differentiation in hMSC without DM, but it suppressed CB1 gene and protein expression, potentially decreasing adipocyte lipid accumulation and lipogenic enzymes.

Pharmacokinetic of two oral doses of a 1:20 THC:CBD cannabis herbal extract in cats.

Objective: To determine the pharmacokinetics (PK) of two oral doses of a Cannabis herbal extract (CHE) containing 1:20 THC:CBD in 12 healthy Domestic Shorthair cats. Methods: Single-dose PK were assessed after oral administration of CHE at low or high dose (2 mg CBD + 0.1 mg THC, or 5 mg CBD + 0.25 mg THC per kg bw, respectively; n = 6 per group) in fasting cats. Blood samples were drawn up to 48 h following CHE administration. Plasma samples were analyzed for CBD, THC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH using a previously validated LC-MS/MS method. Results: CBD and THC were quickly absorbed (mean Tmax of 2.4-2.9 h). Maximum plasma concentrations (Cmax) ranged from 36-511 ng/mL and 6.8-61 ng/mL for CBD and THC, respectively. Elimination was initially rapid for both CBD and THC, though a prolonged elimination phase was noted for CBD in some cats (T1/2 λ up to 26 h). Dose-adjusted Cmax and AUC0-last values were not statistically significantly different (p > 0.05) between dose groups indicating CBD and THC concentrations increased in a manner proportional (linear) to the dose. Dose-adjusted THC Cmax and AUC0-last were significantly higher than the corresponding dose-adjusted CBD parameters (p < 0.01). Low concentrations of the metabolite 6-OH-CBD were quantified but metabolites 7-OH-CBD, 11-OH-THC, and THC-COOH were not detected in any plasma samples. Inter-individual variance was notable. Salivation shortly after dosing was observed in two cats in the high dose group; these animals had substantially lower cannabinoid concentrations than other cats in this group. No adverse clinical signs (including vomiting, change in mentation or other neurological signs) were noted. Clinical significance: Although cats did not display adverse effects after administration of a single oral dose of 1:20 THC:CBD CHE formulation at 2 or 5 mg CBD/kg bw, observed plasma concentrations were highly variable but generally lower than in dogs receiving the same dose and formulation. Administration of CHE in the fasting state may not optimize CBD absorption, and oral dosing may be challenging when administering an oil-based CHE in some cats.

Influence of short-term chronic oral cannabidiol application on muscle recovery and performance after an intensive training protocol - a randomized double-blind crossover study.

BACKGROUND: Rapid regeneration after intense exercise is essential for competitive athletes. Based on this assumption, supplementation strategies, focusing on food supplements, are increasing to improve the recovery processes. One such supplement is cannabidiol (CBD) which is gaining more attention in competitive sports. However, the evidence is still lacking and there are no data available about the effect of a short-term chronic application. METHODS: A three-arm double-blind cross-over study was conducted to determine the effects of two different CBD products on performance, muscle damage and inflammatory processes in well-trained athletes. In total 17 subjects took successfully part in this study. Each subject underwent the six-day, high-intensity training protocol three times. After each training session, each subject took either a placebo or a CBD product (60 mg of oil or solubilisate). Between the intervention phases, at least four weeks of washout period was conducted. Before and after the training protocols the performance capacity in countermovement jump (CMJ), back squat (BS), bench press (BP) and 1-mile run were measured and biomarkers for muscle damage (creatine kinase, myoglobin), inflammatory processes (interleukin 6 and 10) and immune cell activity (ratios of neutrophil granulocytes, lymphocytes and, platelets) were analyzed. For statistical analyses, the current version of R and a linear mixed model was used. RESULTS: It could identify different effects of the training protocol depending on performance level (advanced or highly advanced athletes) (p < .05). Regardless of the performance level, muscle damage and a reduction in performance could be induced by the training protocol. Only CBD oil was associated with a reduction in myoglobin concentration (p < .05) in advanced athletes. Concerning immune activity, a significant decrease in platelets lymphocyte ratios was observed in advanced athletes after placebo treatment (p < .05). CBD oil application showed a slight inhibitory effect (p < .10). Moreover, the reduction in performance differs between the performance levels. A significant decrease in CMJ was observed in advanced athletes and a decreasing trend in BS was observed in highly advanced athletes after placebo treatment (p < 0.10). Both CBD products do not affect performance parameters. For inflammatory parameters, no effects were observed. CONCLUSION: It was found that the performance level of the subjects was a decisive factor and that they responded differently to the training protocol and the CBD application. However, no clear effects of either CBD product were found and further research is needed to identify the long-term effects of CBD application.

A narrative review of the therapeutic and remedial prospects of cannabidiol with emphasis on neurological and neuropsychiatric disorders.

BACKGROUND: The treatment of diverse diseases using plant-derived products is actively encouraged. In the past few years, cannabidiol (CBD) has emerged as a potent cannabis-derived drug capable of managing various debilitating neurological infections, diseases, and their associated complications. CBD has demonstrated anti-inflammatory and curative effects in neuropathological conditions, and it exhibits therapeutic, apoptotic, anxiolytic, and neuroprotective properties. However, more information on the reactions and ability of CBD to alleviate brain-related disorders and the neuroinflammation that accompanies them is needed. MAIN BODY: This narrative review deliberates on the therapeutic and remedial prospects of CBD with an emphasis on neurological and neuropsychiatric disorders. An extensive literature search followed several scoping searches on available online databases such as PubMed, Web of Science, and Scopus with the main keywords: CBD, pro-inflammatory cytokines, and cannabinoids. After a purposive screening of the retrieved papers, 170 (41%) of the articles (published in English) aligned with the objective of this study and retained for inclusion. CONCLUSION: CBD is an antagonist against pro-inflammatory cytokines and the cytokine storm associated with neurological infections/disorders. CBD regulates adenosine/oxidative stress and aids the downregulation of TNF-α, restoration of BDNF mRNA expression, and recovery of serotonin levels. Thus, CBD is involved in immune suppression and anti-inflammation. Understanding the metabolites associated with response to CBD is imperative to understand the phenotype. We propose that metabolomics will be the next scientific frontier that will reveal novel information on CBD's therapeutic tendencies in neurological/neuropsychiatric disorders.

A phase III multisite randomised controlled trial to compare the efficacy of cannabidiol to placebo in the treatment of cannabis use disorder: the CBD-CUD study protocol.

BACKGROUND: Cannabis use disorder (CUD) is increasingly common and contributes to a range of health and social problems. Cannabidiol (CBD) is a non-intoxicating cannabinoid recognised for its anticonvulsant, anxiolytic and antipsychotic effects with no habit-forming qualities. Results from a Phase IIa randomised clinical trial suggest that treatment with CBD for four weeks reduced non-prescribed cannabis use in people with CUD. This study examines the efficacy, safety and quality of life of longer-term CBD treatment for patients with moderate-to-severe CUD. METHODS/DESIGN: A phase III multi-site, randomised, double-blinded, placebo controlled parallel design of a 12-week course of CBD to placebo, with follow-up at 24 weeks after enrolment. Two hundred and fifty adults with moderate-to-severe CUD (target 20% Aboriginal), with no significant medical, psychiatric or other substance use disorders from seven drug and alcohol clinics across NSW and VIC, Australia will be enrolled. Participants will be administered a daily dose of either 4 mL (100 mg/mL) of CBD or a placebo dispensed every 3-weeks. All participants will receive four-sessions of Cognitive Behavioural Therapy (CBT) based counselling. Primary endpoints are self-reported cannabis use days and analysis of cannabis metabolites in urine. Secondary endpoints include severity of CUD, withdrawal severity, cravings, quantity of use, motivation to stop and abstinence, medication safety, quality of life, physical/mental health, cognitive functioning, and patient treatment satisfaction. Qualitative research interviews will be conducted with Aboriginal participants to explore their perspectives on treatment. DISCUSSION: Current psychosocial and behavioural treatments for CUD indicate that over 80% of patients relapse within 1-6 months of treatment. Pharmacological treatments are highly effective with other substance use disorders but there are no approved pharmacological treatments for CUD. CBD is a promising candidate for CUD treatment due to its potential efficacy for this indication and excellent safety profile. The anxiolytic, antipsychotic and neuroprotective effects of CBD may have added benefits by reducing many of the mental health and cognitive impairments reported in people with regular cannabis use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12623000526673 (Registered 19 May 2023).

[Patient-reported outcomes in chronic diseases under treatment with cannabis medicines : Analysis of the results of the Copeia survey]. / "Patient-reported outcomes" bei chronischen Erkrankungen unter Therapie mit Cannabisarzneimitteln : Analyse der Ergebnisse der Befragung von Copeia.

BACKGROUND: The survey of Copeia captured early 2022 patient-reported outcomes (PRO) in Germany under cannabis medicinal product (CAM) therapy, with particular attention to symptoms, symptom changes, indications, side effects, dosages, and cost bearers. GOAL: This study investigated the question of whether associations emerge from the results that could play a role in the indication and treatment monitoring of CAM in chronically ill patients. MATERIALS AND METHODS: A standardized questionnaire was administered online nationwide in dialogue form over a 15-week period to collect itemized symptoms and PRO. Recruitment was supported by pharmacies, prescribing physicians, and patient associations. Inclusion criteria included physician-prescribed CAM therapy. RESULTS AND DISCUSSION: Of 1582 participants, 1030 data sets (65%) could be completely analyzed. There was a heterogeneous patient population, whose common feature was disease chronicity. The frequency distribution of symptoms showed a homogeneous pattern for the respective indications, in which the most frequent six (pain 71%, sleep disturbance 64%, stress/tension 52%, inner restlessness 52%, depressive mood 44% and muscle tension 43%) seem to have a special significance. According to subjective assessment, quality of life improved significantly in 84% of all participating patients. CONCLUSION: A symptom matrix (SMX) composed of different symptoms seems to play a special role in CAM therapy to improve the quality of life of chronically ill patients, regardless of the underlying disease. The SMX could contribute to the identification of an indication and to targeted treatment monitoring.

Cannabinoids for Cancer-related Pain Management: An Update on Therapeutic Applications and Future Perspectives.

Pain is a debilitating phenomenon that dramatically impairs the quality of life of patients. Many chronic conditions, including cancer, are associated with chronic pain. Despite pharmacological efforts that have been conducted, many patients suffering from cancer pain remain without treatment. To date, opioids are considered the preferred therapeutic choice for cancer-related pain management. Unfortunately, opioid treatment causes side effects and inefficiently relieves patients from pain, therefore alternative therapies have been considered, including Cannabis Sativa and cannabinoids. Accumulating evidence has highlighted that an increasing number of patients are choosing to use cannabis and cannabinoids for the management of their soothing and non-palliative cancer pain and other cancer-related symptoms. However, their clinical application must be supported by convincing and reproducible clinical trials. In this review, we provide an update on cannabinoid use for cancer pain management. Moreover, we tried to turn a light on the potential use of cannabis as a possible therapeutic option for cancer-related pain relief.

Integrating fecal metabolomics and intestinal microbiota to study the mechanism of cannabidiol in the treatment of idiopathic pulmonary fibrosis.

Introduction: Idiopathic pulmonary fibrosis is a chronic interstitial lung disease characterized by excessive deposition of extracellular matrix. Cannabidiol, a natural component extracted from plant cannabis, has been shown to have therapeutic effects on lung diseases, but its exact mechanism of action is unknown, hindering its therapeutic effectiveness. Methods: To establish a pulmonary fibrosis model, combined with UPLC-Q-TOF/MS metabolomics and 16S rDNA sequencing, to explore cannabidiol's mechanism in treating pulmonary fibrosis. The rats were randomly divided into the control group, pulmonary fibrosis model group, prednisone treatment group, and cannabidiol low, medium, and high dose groups. The expression levels of HYP, SOD, and MDA in lung tissue and the expression levels of TNF-α, IL-1ß, and IL-6 in serum were detected. Intestinal microbiota was detected using UPLC-QTOF/MS analysis of metabolomic properties and 16S rDNA sequencing. Results: Pathological studies and biochemical indexes showed that cannabidiol treatment could significantly alleviate IPF symptoms, significantly reduce the levels of TNF-α, IL-1ß, IL-6, MDA, and HYP, and increase the expression level of SOD (p < 0.05). CBD-H can regulate Lachnospiraceae_NK4A136_group, Pseudomonas, Clostridia_UCG-014, Collinsella, Prevotella, [Eubacterium]_coprostanoligenes_group, Fusobacterium, Ruminococcus, and Streptococcus, it can restore intestinal microbiota function and reverse fecal metabolism trend. It also plays the role of fibrosis through the metabolism of linoleic acid, glycerol, linolenic acid, and sphingolipid. Discussion: Cannabidiol reverses intestinal microbiota imbalance and attenuates pulmonary fibrosis in rats through anti-inflammatory, antioxidant, and anti-fibrotic effects. This study lays the foundation for future research on the pathological mechanisms of IPF and the development of new drug candidates.

Therapeutic Polymer-Based Cannabidiol Formulation: Tackling Neuroinflammation Associated with Ischemic Events in the Brain.

Cannabidiol (CBD) is the most relevant nonpsychostimulant phytocompound found in Cannabis sativa. CBD has been extensively studied and has been proposed as a therapeutic candidate for neuroinflammation-related conditions. However, being a highly lipophilic drug, it has several drawbacks for pharmaceutical use, including low solubility and high permeability. Synthetic polymers can be used as drug delivery systems to improve CBD's stability, half-life, and biodistribution. Here, we propose using a synthetic polymer as a nanoparticulate vehicle for CBD (NPCBD) to overcome the pharmacological drawbacks of free drugs. We tested the NPCBD-engineered system in the context of ischemic events in a relevant oxygen and glucose deprivation (OGD) model in primary cortical cells (PCC). Moreover, we have characterized the inflammatory response of relevant cell types, such as THP-1 (human monocytes), HMC3 (human microglia), and PCC, to NPCBD and observed a shift in the inflammatory state of the treated cells after the ischemic event. In addition, NPCBD exhibited a promising ability to restore mitochondrial function after OGD insult in both HMC3 and PCC cells at low doses of 1 and 0.2 µM CBD. Taken together, these results suggest the potential for preclinical use.

Anthelmintic Effect of Cannabidiol against Echinococcus granulosus sensu stricto.

Cystic echinococcosis is a global parasitic zoonosis caused by infection with the larval stage of Echinococcus granulosus sensu lato. Cystic echinococcosis affects more than 1 million people worldwide, causing important economic costs in terms of management and livestock associated losses. Albendazole is the main drug used in treating human cystic echinococcosis. In spite of this, its low aqueous solubility, poor absorption, and consequently erratic bioavailability are the cause of its chemotherapeutic failures. Based on the described problem, new treatment alternatives urgently need to be developed. The aim of the present research was to study the in vitro and in vivo efficacy of cannabidiol (CBD), the second most abundant component of the Cannabis sativa plant, was demonstrated against E. granulosus sensu stricto. CBD (50 µg/mL) caused a decrease in protoscoleces viability of 80 % after 24 h of treatment which was consistent with the observed tegumental alterations. Detachment of the germinal layer was observed in 50 ± 10% of cysts treated with 50 µg/mL of CBD during 24 h. In the clinical efficacy study, all treatments reduced the weight of cysts recovered from mice compared with the control group. However, this reduction was only significant with ABZ suspension and the CBD + ABZ combination. As we could observe by the SEM study, the co-administration of CBD with ABZ suspension caused greater ultrastructural alteration of the germinal layer in comparison with that provoked with the monotherapy. Further in vivo research will be conducted by changing the dose and frequency of CBD and CBD + ABZ treatments and new available CBD delivery systems will also be assayed to improve bioavailability in vivo.

Repeated cannabidiol treatment affects neuroplasticity and endocannabinoid signaling in the prefrontal cortex of the Flinders Sensitive Line (FSL) rat model of depression.

Delayed therapeutic responses and limited efficacy are the main challenges of existing antidepressant drugs, thereby incentivizing the search for new potential treatments. Cannabidiol (CBD), non-psychotomimetic component of cannabis, has shown promising antidepressant effects in different rodent models, but its mechanism of action remains unclear. Herein, we investigated the antidepressant-like effects of repeated CBD treatment on behavior, neuroplasticity markers and lipidomic profile in the prefrontal cortex (PFC) of Flinders Sensitive Line (FSL), a genetic animal model of depression, and their control counterparts Flinders Resistant Line (FRL) rats. Male FSL animals were treated with CBD (10 mg/kg; i.p.) or vehicle (7 days) followed by Open Field Test (OFT) and the Forced Swimming Test (FST). The PFC was analyzed by a) western blotting to assess markers of synaptic plasticity and cannabinoid signaling in synaptosome and cytosolic fractions; b) mass spectrometry-based lipidomics to investigate endocannabinoid levels (eCB). CBD attenuated the increased immobility observed in FSL, compared to FRL in FST, without changing the locomotor behavior in the OFT. In synaptosomes, CBD increased ERK1, mGluR5, and Synaptophysin, but failed to reverse the reduced CB1 and CB2 levels in FSL rats. In the cytosolic fraction, CBD increased ERK2 and decreased mGluR5 expression in FSL rats. Surprisingly, there were no significant changes in eCB levels in response to CBD treatment. These findings suggest that CBD effects in FSL animals are associated with changes in synaptic plasticity markers involving mGluR5, ERK1, ERK2, and synaptophysin signaling in the PFC, without increasing the levels of endocannabinoids in this brain region.

Investigation of neuroprotective and therapeutic effects of cannabidiol in an acute coronary syndrome model.

PURPOSE: The ischemia-reperfusion (I/R) injury seen in the heart can cause severe damage to essential organs such as the brain. Cannabidiol (CBD) obtained from Cannabis sativa is used today to treat various diseases. This study aimed to demonstrate CBD's neuroprotective and therapeutic properties in rats with brain damage caused by I/R in the heart. MATERIALS: Rats were divided into four groups; sham, I/R, I/R + Prophylactic CBD, and I/R + Therapeutic CBD. End of the experiment, brain tissues were collected for biochemical, histopathological, and genetic examinations. RESULTS: I/R damage increased the number of degenerative neurons, caspase-3 and TNF-α immunoexpression, total oxidant status levels, and oxidative stress index. Both prophylactic and therapeutic CBD administration reduced these increased values. In addition, the relative fold changes of AMPK, PGC-1α, SIRT1, and Bcl 2 decreased in the I/R group, and the relative fold change of Bax increased, which are indicators of ER stress and apoptosis. Both administrations of CBD reversed these genes' relative fold changes. CONCLUSION: CBD can be protective against brain injury caused by cardiac I/R damage through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.

Alzheimer's disease, aging, and cannabidiol treatment: a promising path to promote brain health and delay aging.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive memory loss, neurodegeneration, and cognitive decline. Aging is one of the risk factors for AD. Although the mechanisms underlying aging and the incidence rate of AD are unclear, aging and AD share some hallmarks, such as oxidative stress and chronic inflammation. Cannabidiol (CBD), the major non-psychoactive phytocannabinoid extracted from Cannabis sativa, has recently emerged as a potential candidate for delaying aging and a valuable therapeutic tool for the treatment of aging-related neurodegenerative diseases due to its antioxidant and anti-inflammation properties. This article reviews the relevant literature on AD, CBD treatment for AD, cellular senescence, aging, and CBD treatment for aging in recent years. By analyzing these published data, we attempt to explore the complex correlation between cellular senescence, aging, and Alzheimer's disease, clarify the positive feedback effect between the senescence of neurocytes and Alzheimer's disease, and summarize the role and possible molecular mechanisms of CBD in preventing aging and treating AD. These data may provide new ideas on how to effectively prevent and delay aging, and develop effective treatment strategies for age-related diseases such as Alzheimer's disease.

Cannabidiol Combination Enhances Photodynamic Therapy Effects on MCF-7 Breast Cancer Cells.

Cannabis sativa is a well-known plant for its psychoactive effects; however, its many derivatives, such as Cannabidiol (CBD), contain several therapeutic applications. Tetrahydrocannabinol (THC) is the main cannabis derivative responsible for psychoactive properties, while CBD is non-psychotropic. For this reason, CBD has been more exploited in the last decade. CBD has been connected to multiple anticancer properties, and when combined with photodynamic therapy (PDT), it is possible to eradicate tumors more effectively. In this study, CBD was utilized to treat MCF-7 breast cancer cells, followed by in vitro PDT combination therapy. Conventional breast cancer treatment modalities such as chemotherapy, radiotherapy, etc. have been reported for inducing a number of undesirable side effects, recurrence of the disease, and low quality of life. In this study, cells were exposed to varying concentrations of CBD (i.e., 1.25, 2.5, 5, 10, and 20 µg/mL) and incubated 12 and 24 h after treatment. The optimal doses were then used in combination therapy. Morphology and biochemical assays, including lactate dehydrogenase (LDH) for membrane integrity, adenosine triphosphate (ATP) for viability, and trypan blue exclusion assay for viability, were used to examine cellular responses after treatments. The optimal concentration was then utilized in Hypericin-Gold nanoparticles mediated PDT combination. The results revealed that, in a dose-dependent manner, conventional morphological characteristics of cell death, such as vacuolization, blebbing, and floating were observed in treated cells. The biochemical responses demonstrated an increase in LDH, a decrease in ATP, and a reduction in viability. This study demonstrated that CBD induces cell death in MCF-7 breast cancer cells cultured in vitro. The immunofluorescence results of combination therapy indicated that cell death occurred via apoptosis. In conclusion, this study proposes that the CBD and PDT combination therapy is effective in killing MCF-7 breast cancer cells in vitro by induction of apoptosis.

Pharmacovigilance of unlicensed cannabidiol in European countries.

Cannabidiol (CBD) is a multitarget agent possessing anti-inflammatory and antioxidant properties. Unlicensed CBD gained public favor for the care of general health and well-being as well as to get comfort from inflammatory complaints, pain, anxiety, mood, and sleep disorders. Safety profile of unlicensed CBD has been not sufficiently described. For this reason, suspected adverse reactions (SARs) to CBD unlicensed products were analyzed. Serious SARs to unlicensed CBD products in EudraVigilance, a system purchased by the European Medicines Agency, were analyzed for age, sex of the patient, adverse reactions, indication for use, and concomitant drugs. Serious SARs were 18.9% of all adverse events to unlicensed CBD; they were more frequent in men and adult people and, to a less extent, in children (3-11 years). About sex, in EudraVigilance serious Individual Cases Safety Reports of SARs to CBD in men are in the largest number (58.8%) with respect to women. Unlicensed CBD was used in the 38.8% of cases for treatment of epilepsy; more frequent adverse effects were: mental disorders, hepatic disorders, and aggravation of pre-existing epilepsy. Drugs or substances more frequently associated with SARs were the antiepileptics clobazam and valproic acid, followed by cannabis. Results suggest that precautions and appropriate surveillance of adverse effects should be taken when unlicensed CBD is used.

Phytocannabinoids for the Treatment of Neuropathic Pain: A Scoping Review of Randomised Controlled Trials Published Between 2012 and 2023.

PURPOSE OF REVIEW: Neuropathic pain (NP) remains a challenge to treat, with 50% of patients experiencing limited efficacy from current treatments. Medicinal cannabis, which contains tetrahydrocannabinol (THC), cannabidiol (CBD) and other minor cannabinoids, is garnering attention as an alternative treatment for NP. This paper reviews the clinical evidence for phytocannabinoid treatment of NP. RECENT FINDINGS: Seventeen randomised controlled trials (RCT) were identified for inclusion in this review. Of these, ten studies using phytocannabinoid preparations containing THC alone had the most evidence for pain relief. Four studies investigating THC/CBD combinations showed some reductions in pain scores, although not all findings were statistically significant, whereas studies investigating CBD (two studies) or cannabidivarin (one study) showed no analgesic effect over placebo. However, CBD studies were of small sample size when compared to other studies in the review and short duration. Results for treatment of diabetic peripheral neuropathy patients with THC showed better improvements over those for NP induced by chemotherapy and multiple sclerosis, with these trials using vaporised whole plant cannabis. This formulation may have trace amounts of other minor cannabinoids, compared with synthetic cannabinoids such as dronabinol or nabilone that were investigated in other studies. This review provides an overview of RCTs that have investigated phytocannabinoid use for the treatment of NP. There appears to be evidence to necessitate further high quality RCTs into novel formulations of phytocannabinoids for the treatment of NP.

Investigation of alternative two-phase solvent systems for purification of natural products by centrifugal partition chromatography.

INTRODUCTION: Centrifugal partition chromatography (CPC) is a liquid-liquid chromatography characterised by its solvent flexibility. The compounds undergoing separation are subjected to a continuous partition process between two immiscible phases in a column space free of solid support. In the context of green chemistry, it is important to substitute halogenated and petroleum-based solvents commonly used in purification processes. OBJECTIVES: The main goal of the current study was to replace classical solvents used in CPC (e.g., hexane and methanol) by green and renewable alternatives. METHODS: Solvents were first selected based on literature. Their commercial availability, price, recyclability, toxicity and ability to form two phases were particularly sought after. KEY FINDINGS: The new two-phase solvent systems were evaluated for the purification of two compounds of interest: piperine and cannabidiol. Using these alternative two-phase solvent systems allows us to isolate natural products with a high purity level (> 95%). CONCLUSION: Substituting petroleum-based solvents with bio-sourced, renewable alternatives reduces the environmental impact of CPC. Herein, new biphasic solvent systems were built using hexamethyldisiloxane, ethyl isobutyrate and 2-methyl tetrahydrofuran in combination with ethanol and water. Furthermore, this research provides a scientific basis for developing new and sustainable solvent systems in CPC.

Tolerability of long-term cannabidiol supplementation to healthy adult dogs.

BACKGROUND: Cannabidiol (CBD) has therapeutic potential in companion animals. Shorter-term studies have determined that CBD is well tolerated in dogs with mild adverse effects and an increase in alkaline phosphatase (ALP) activity. There is need to assess CBD's long-term tolerability. HYPOTHESIS: Determine the long-term tolerability of CBD administered PO to healthy dogs for 36 weeks at dosages of 5 and 10 mg/kg body weight (BW)/day. Our hypothesis was that CBD would be well tolerated by dogs. METHODS: Eighteen healthy adult beagle dogs were randomly assigned to 3 groups of 6 each that received 0, 5, or 10 mg/kg BW/day CBD PO. Dogs were adapted to their housing for 3 weeks and received treatment for 36 weeks once daily with food. Adverse events (AEs) were recorded daily. Blood biochemistry profiles were monitored every 4 weeks. Data were analyzed as repeated measures over time using a mixed model, with significance at α = 0.05. RESULTS: The 0 and 5 mg/kg treatment groups had similar fecal scores, and the 10 mg/kg treatment group had higher frequency of soft feces. No other significant AEs were noted. An increase (P < .0001) in ALP activity occurred in groups that received CBD. Remaining blood variables were within reference range. CONCLUSIONS AND CLINICAL IMPORTANCE: Chronic administration of CBD in healthy dogs at 5 mg/kg was better tolerated than 10 mg/kg, and both dosages caused an increase in ALP activity. Although our data does not indicate hepatic damage, it is recommended to monitor liver function in dogs receiving CBD chronically.

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.

A Descriptive Review of Cannabis sativa Patents for Cancer Treatment.

BACKGROUND: Cannabis use for tumor treatment has been explored in several areas, and its potential for tumor remission is currently being studied after the discovery of the endogenous cannabinoid. OBJECTIVE: The study aimed to conduct a critical patent review to identify and explore the latest advances and therapeutic strategies using Cannabis to treat cancer. METHODS: The research was carried out in the free and online database Espacenet, using the descriptors "cancer" and "Cannabis or cannabidiol" in the title or abstract. A total of 95 patents were identified for preliminary evaluation in the database. Six duplicate patents were excluded, 12 referring to traditional Chinese medicine and 36 with a title in disagreement with the scope of this review. In addition the final selection involved 21 patents that were in line with the objective of the study. RESULTS: As observed in the reading of patents, the interest of pharmaceutical industries and researchers and the development of new products to fight cancer have increased in recent years. The main cannabinoids present in the patents are tetrahydrocannabinol, cannabidiol, and hemp. Moreover, the patents were classified and the main applicant countries were the United States followed by Japan, with a higher filing rate in 2019 and, mainly by the industry. CONCLUSION: In conclusion we can say that, the importance of parliamentary approval in the cultivation and investments that, in addition to bringing innovation to the industrial sector, enriches research in the area, contributing to the creation of new medicines.