Cannabidiol Research Articles

NSW cannabis medicines advisory service retrospective enquiry analysis to inform clinical guidance resource development

AbstractBackgroundAn innovative New South Wales government funded statewide Cannabis Medicines Advisory Service (CMAS) operated between January 2018 and June 2022. The service provided comprehensive patient‐specific and evidence‐based information to support health professionals in prescribing and patient care decisions. This study aimed to describe real‐world data collected by CMAS.MethodsA sub‐set of de‐identified, patient‐specific enquiries collected between January 2021 and June 2022 (n = 123/567; 21.7%) were analyzed using R version 4.2.1. Diagnosis, indication, and comorbidities were coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology.ResultsMost patient‐specific enquiries from medical practitioners were from general practitioners (n = 103/123; 83.7%). Female (n = 53/123; 43.1%) and male (n = 59/123; 48.0%) patients were similarly represented. Sex was not specified for 8.9% (n = 11/123) of patients. The mean age of patients was 52.1 years (range <10–90). The most common three diagnoses were osteoarthritis, anxiety, and chronic pain. Indications that were most frequently reported included chronic pain, anxiety, back pain, non‐neuropathic pain, and insomnia. Comedications were most commonly non‐opioid and opioid analgesics and antidepressants. Most practitioners were considering prescribing a cannabidiol (CBD) product for their patient. Cannabinoid composition selection guidance provided by CMAS was predominantly (delta‐9‐tetrahydrocannabinol) THC:CBD ~1:1, followed by CBD‐only products. CMAS was contacted by health professionals regarding the management of potential adverse events for five patients.ConclusionThe findings of this study shed light on the information medical practitioners were seeking to inform their clinical decision‐making about medical cannabis and can inform the development of clinical guidance resources.

EFFICACY OF CANNABIDIOL (CBD) IN THE TREATMENT OF ALZHEIMER'S DISEASE: A CRITICAL REVIEW OF EVIDENCE AND CLINICAL IMPLICATIONS

Introduction: This study investigates the therapeutic potential of cannabidiol (CBD) in treating Alzheimer's disease (AD), which is characterized by progressive cognitive decline, memory impairment, and behavioral changes. As traditional treatment options are limited, the exploration of alternative therapies, including CBD, has gained prominence in recent years. Objective: The aim of this research is to evaluate the efficacy of CBD in modulating neuroinflammation and oxidative stress, as well as its potential impact on slowing the progression of Alzheimer's disease. Method: A literature review was conducted using ten articles published between 2019 and 2024. Databases such as the Virtual Health Library, LILACS Plus, and Medline were utilized, applying descriptors related to CBD and Alzheimer's disease. The articles were filtered based on specific inclusion criteria, focusing on studies published in Portuguese, Spanish, and English that are freely accessible online. Results: The reviewed literature indicates that CBD may inhibit the formation of beta-amyloid plaques, a hallmark of Alzheimer's pathology, suggesting its potential for both symptom relief and slowing disease progression. Additionally, the interaction between CBD and the endocannabinoid system (ECS) highlights its role in managing cognitive decline and memory issues associated with AD. Conclusion: While the findings are promising, there is a pressing need for more rigorous clinical studies to validate the efficacy and safety of CBD in Alzheimer's treatment. This research underscores the potential of cannabinoids as a therapeutic option in managing neurodegenerative diseases.

THE ROLE OF THE ENDOCANNABINOID SYSTEM AND CANNABIDIOL (CBD) IN THE TREATMENT OF AUTISM SPECTRUM DISORDER: EFFICACY, SAFETY, AND COMORBIDITIES

Introduction: Autism Spectrum Disorder (ASD) encompasses a range of neurodevelopmental disorders characterized by persistent deficits in communication and social interaction, along with restrictive and repetitive behaviors. Conventional interventions often face limitations, prompting interest in alternative treatments, particularly those involving the endocannabinoid system (ECS) and cannabidiol (CBD). Objectives: This study aims to evaluate the role of the ECS and the efficacy of CBD as therapeutic interventions for ASD and its comorbidities. Methods: A literature review was conducted, focusing on articles published in Portuguese, Spanish, and English from 2019 to 2024. Databases such as the Virtual Health Library, LILACS Plus, and Medline were searched using descriptors: “Cannabidiol,” “Autism,” and “Endocannabinoid System”. Boolean terms “AND” and “OR” refined the results. A total of 7 articles from Medline and 3 from LILACS were initially identified. Results: The review identified 10 relevant articles that provided comprehensive insights into the effects of CBD on core ASD symptoms, including social interaction and anxiety. Most studies reported significant improvements in patients, with minimal adverse effects, emphasizing the safety of CBD compared to traditional treatments. Conclusion: The findings suggest that CBD may offer a promising alternative for treating ASD and its comorbidities, with a favorable safety profile. Continued research is essential to establish effective guidelines for clinical application.

Drug Interactions in People on Cannabidiol: Is There Cause for Concern?

Introduction: Cannabidiol (CBD) exhibits multiple therapeutic properties, but its use in advanced cancer patients raises concerns about potential drug-drug interactions (DDIs) due to polypharmacy. This study aims to look for evidence of DDIs between concomitant medications and CBD oil in a randomized placebo-controlled trial of CBD oil for symptom control (MedCan-1 parent study). Materials and Methods: Surrogate measures were used to identify possible drug interactions: (1) the maximum mL of oil self-selected by patients in CBD or placebo groups in relation to opioids, specific drug groups, or individual agents; (2) the occurrence of any new or worse adverse effect in relation to the study arm and the concomitant medication classes/medications of interest. Results: The dose of CBD self-selected by participants was not related to opioid use or medications, including benzodiazepines and antipsychotics. The likelihood of developing an adverse effect while on study or when taking specific medications was not increased by CBD. Participants on paracetamol tolerated a higher dose of CBD. Discussion: Concerns regarding the development of clinically significant drug interactions when taking CBD in the context of anti-cancer and other concomitant medications at least in the short term may be unfounded.

Exploring Cannabidiol (CBD) and Cannabigerol (CBG) Safety Profile and Skincare Potential

Cannabinoids have long been known for their bioactive properties, with their topical application as anti-inflammatory compounds being at the forefront of research for the past decade. Concurrently, the cosmetic market is a fast-growing industry in constant need of new biomolecules. In this work, we studied the safety profile for topical applications of two cannabinoids: cannabidiol (CBD) and cannabigerol (CBG) and assessed their potential as skin care ingredients. The CBG used in this work resulted from bio-fermentation, and to the best of our knowledge, there are no extensive reports on its safety and usage as a cosmetic ingredient. Our results show that CBD and CBG do not exhibit cytotoxicity, mutagenicity, or skin sensitization. Moreover, we verified an absence of primary irritability, accumulated irritability, phototoxicity and photosensitization, supporting the claims of dermatologically tested, hypoallergenic and non-irritating. While these cannabinoids did not show significant anti-aging effects by altering the extracellular matrix components (both in vitro and ex vivo), they demonstrated promise as protective agents against inflammation caused by air pollution. Specifically, they reduced the levels of pro-inflammatory cytokines, making them valuable in combating environmental skin damage. Overall, our results validate the safety of topical use of cannabinoids, while paving the way for further research in the beauty and personal care market as soothing agents.

Cannabidiol Plays a Modulatory Function on the Methamphetamine-Induced Reward Through Hippocampal D2-Like Dopamine Receptors.

Methamphetamine (METH), a stimulant that is extremely addictive, directly affects the central nervous system. METH's abuse and consumption are directly linked to mental illnesses, psychosis, and behavioral and cognitive impairments. It may disrupt the reward system and dopaminergic transmission. METH's rewarding qualities are associated with a rise in dopamine. Additionally, cannabidiol (CBD), one of the primary cannabinoid components of the cannabis plant, significantly affects dopaminergic transmission and may aid in reward- and addiction-related behaviors. To shed light on the role of the D2-like dopamine receptor (D2R) in the hippocampal dentate gyrus (DG), the present study examined the effects of CBD on the acquisition and expression of the conditioned place preference (CPP) induced by METH. The function of D2R was ascertained by delivering Sulpiride microinjections, as a D2R antagonist Sulpiride (0.25, 1, and 4μg/0.5 μL DMSO12%) into the DG. Moreover, an intracerebroventricular injection of CBD at a dose of 10μg/5 μL for CPP acquisition and 50μg/5 μL for CPP expression was given to rats. According to the current research, CBD dramatically reduced the acquisition and expression of CPP resulting from METH. However, Sulpiride suppressed the effect of CBD on METH-induced CPP acquisition and expression, with a greater impact on expression experiments. Ultimately, this study proposed that the expression experiment of METH-induced CPP appears to be heavily dependent on D2R in the DG.

Cannabidiol inhibits transient receptor potential canonical 4 and modulates excitability of pyramidal neurons in mPFC

Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has been extensively studied for its potential therapeutic effects on various central nervous system (CNS) disorders, including epilepsy, chronic pain, Parkinson’s disease, and stress-related neuropsychiatric disorders. However, the pharmacological mechanisms of CBD have not been fully elucidated due to the complexity of their targets. In this study, we reported that the transient receptor potential canonical 4 (TRPC4) channel, a calcium-permeable, non-selective cation channel, could be inhibited by CBD. TRPC4 is highly abundant in the central nervous system and plays a critical role in regulating axonal regeneration, neurotransmitter release, and neuronal network activity. Here, we used whole-cell electrophysiology and intracellular calcium measurements to identify the inhibitory effects of CBD on TRPC4, in which CBD was found to inhibit TRPC4 channel with an IC50 value of 1.52 μM TRPC4 channels function as receptor-operated channels (ROC) and could be activated by epinephrine (EP) via G proteins. We show that CBD can inhibit EP-evoked TRPC4 current in vitro and EP-evoked neuronal excitability in the medial prefrontal cortex (mPFC). These results are consistent with the action of TRPC4-specific inhibitor Pico145, suggesting that TRPC4 works as a functional ionotropic receptor of CBD. This study identified TRPC4 as a novel target for CBD in the CNS and suggested that CBD could reduce the pyramidal neuron excitability by inhibiting TRPC4-containing channels in the mPFC.

Chemical Composition of Aerosols from the E-Cigarette Vaping of Natural and Synthetic Cannabinoids.

Vaping cannabinoids in electronic (e)-cigarette devices is rapidly increasing in popularity, particularly among adolescents, although the chemistry affecting the composition of the vape aerosol is not well understood. This work investigates the formation of aerosol mass, bioactive hydroxyquinones, and harmful or potentially harmful carbonyls from the e-cigarette vaping of natural and synthetic cannabinoids e-liquids in propylene glycol and vegetable glycerin (PG/VG) solvent at a 50 mg/mL concentration in a commercial fourth-generation vaping device. The following cannabinoids were studied: cannabidiol (CBD), 8,9-dihydrocannabidiol (H2CBD), 1,2,8,9-tetrahydrocannabidiol (H4CBD), cannabigerol (CBG), and cannabidiolic acid (CBDA). Quantification of analytes was performed using liquid chromatography coupled to accurate mass spectrometry. The addition of cannabinoids significantly increased aerosol and carbonyl formation compared with the PG/VG solvent alone. All cannabinoids in the study formed hydroxyquinones during vaping (up to ∼1% mass conversion) except for CBDA, which primarily decarboxylated to CBD. Hydroxyquinone formation increased and carbonyl formation decreased, with a decreasing number of double bonds among CBD and its synthetic analogues (H2CBD and H4CBD). During the vaping process, ∼3-6% of the cannabinoid mass can be observed as carbonyls under the study conditions. Oxidation of the terpene moiety on the cannabinoids is proposed as a major contributor to carbonyl formation. CBD produced significantly higher concentrations of formaldehyde, acetaldehyde, acrolein, diacetyl, and methylglyoxal compared with the other cannabinoid samples. CBG produced significantly higher levels of acetone, methacrolein, and methylglyoxal. Conversion of CBD to tetrahydrocannabinol (THC) was not observed under the study conditions. The chemical mechanism basis for these observations is discussed. Compared with other modalities of use for CBD and other cannabinoids, vaping has the potential to adversely impact human health by producing harmful products during the heated aerosolization process.

Microencapsulation techniques for developing cannabidiol formulations: a review.

Cannabidiol (CBD), extracted from Cannabis sativa L., holds therapeutic promise without inducing psychoactive effects seen with Δ9-tetrahydrocannabinol. Its interaction with the endocannabinoid system plays a pivotal role in regulating mood, pain perception and immune function. Nevertheless, CBD encounters hurdles in clinical application due to its poor bioavailability and water solubility. To overcome these limitations, researchers are exploring microencapsulation techniques, which involve encapsulating CBD within protective matrices. This comprehensive review offers insights into various microencapsulation methods for CBD, scrutinizing their advantages, limitations and implications for formulation optimization. By elucidating the potential of microencapsulation, this review underscores its promise in refining CBD therapy and addressing challenges associated with administration.

A sleepy cannabis constituent: cannabinol and its active metabolite influence sleep architecture in rats.

Medicinal cannabis is being used worldwide and there is increasing use of novel cannabis products in the community. Cannabis contains the major cannabinoids, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), but also an array of minor cannabinoids that have undergone much less pharmacological characterization. Cannabinol (CBN) is a minor cannabinoid used in the community in "isolate' products and is claimed to have pro-sleep effects comparable to conventional sleep medications. However, no study has yet examined whether it impacts sleep architecture using objective sleep measures. The effects of CBN on sleep in rats using polysomnography were therefore examined. CBN increased total sleep time, although there was evidence of biphasic effects with initial sleep suppression before a dramatic increase in sleep. CBN increased both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The magnitude of the effect of CBN on NREM was comparable to the sleep aid zolpidem, although, unlike CBN, zolpidem did not influence REM sleep. Following CBN dosing, 11-hydroxy-CBN, a primary metabolite of CBN surprisingly attained equivalently high brain concentrations to CBN. 11-hydroxy-CBN was active at cannabinoid CB1 receptors with comparable potency and efficacy to Δ9-THC, however, CBN had much lower activity. We then discovered that the metabolite 11-hydroxy-CBN also influenced sleep architecture, albeit with some subtle differences from CBN itself. This study shows CBN affects sleep using objective sleep measures and suggests an active metabolite may contribute to its hypnotic action.

Optimization of Supercritical Extraction of Cannabidiol Using Response Surface Methodology

Hemp, also known as Cannabis sativa L., contains over 80 cannabinoids, with cannabidiol (CBD) being the primary neuroactive component. CBD possesses various pharmacological properties and is considered a non-psychoactive compound, making it a promising component for various applications, such as pharmaceuticals, cosmetics, and nutraceuticals. The aim of this study was to identify the optimal conditions for extracting CBD from hemp using supercritical fluid extraction (SFE). Response surface methodology (RSM) was employed to optimize the SFE conditions. The Box–Behnken design and the central composite design were utilized to refine the extraction parameters, including extraction time, temperature, and pressure. The statistical significance and reliability of the optimized conditions were confirmed by the significant influence of these independent variables on CBD yield. The extracted CBD was purified to a high level of purity and converted from cannabidiolic acid (CBDA) through heat treatment and then analyzed using high-performance liquid chromatography (HPLC). The following extraction conditions were considered optimal and led to a CBD yield of approximately 70.46 g/kg: pressure of 48.3 MPa, temperature of 60 °C, and extraction time of 109.2 min. Validation experiments confirmed the accuracy of the model, with experimental values closely matching the predicted values (69.93 ± 0.88 g/kg). This study demonstrates that SFE is an efficient method for obtaining high-purity CBD from hemp, highlighting its potential for industrial applications. The findings suggest that optimizing SFE conditions through RSM can significantly enhance the efficiency and yield of CBD extraction, providing a robust framework for industrial-scale production.

Cannabidiol Enhances Mitochondrial Metabolism and Antioxidant Defenses in Human Intestinal Epithelial Caco-2 Cells

Background: The reintroduction of hemp production has resulted in increased consumption of cannabidiol (CBD) products, particularly CBD oil, yet their effects on intestinal health are not fully understood. Proper mitochondrial function and antioxidant defenses are vital for maintaining the intestinal epithelial barrier. AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator (PGC)1α are key mediators of mitochondrial metabolism. Methods & Results: Using Caco-2 cells, we found that CBD oil promoted AMPK phosphorylation, upregulated differentiation markers, and enhanced PGC1α/SIRT3 mitochondrial signaling. CBD oil reduced reactive oxygen species production and increased antioxidant enzymes. Moreover, CBD oil also increased levels of citrate, malate, and succinate—key metabolites of the tricarboxylic acid cycle—alongside upregulation of pyruvate dehydrogenase and isocitrate dehydrogenase 1. Similarly, pure CBD induced metabolic and antioxidant signaling. Conclusions: CBD enhances mitochondrial metabolic activity and antioxidant defense in Caco-2 cells, making it a promising candidate for treating intestinal dysfunction.

A Review of Sturge–Weber Syndrome Brain Involvement, Cannabidiol Treatment and Molecular Pathways

Sturge–Weber syndrome (SWS) is a rare congenital neurocutaneous disorder typically caused by a somatic mosaic mutation in R183Q GNAQ. At-risk children present at birth with a capillary malformation port-wine birthmark. The primary diagnostic characteristic of the disorder includes leptomeningeal enhancement of the brain, which demonstrates abnormal blood vessels and results in impaired venous drainage and impaired local cerebral perfusion. Impaired cerebral blood flow is complicated by seizures resulting in strokes, hemiparesis and visual field deficits, hormonal deficiencies, behavioral impairments, and intellectual disability. Therefore, anti-seizure medication in combination with low-dose aspirin is a common therapeutic treatment strategy. Recently published data indicate that the underlying mutation in endothelial cells results in the hyperactivation of downstream pathways and impairment of the blood–brain barrier. Cannabidiol (CBD) has been used to treat medically refractory seizures in SWS due to its anti-seizure, anti-inflammatory, and neuroprotective properties. Pilot research suggests that CBD improves cognitive impairment, emotional regulation, and quality of life in patients with SWS. Recent preclinical studies also suggest overlapping molecular pathways in SWS and in CBD, suggesting that CBD may be uniquely effective for SWS brain involvement. This review aims to summarize early data on CBD’s efficacy for preventing and treating epilepsy and neuro-cognitive impairments in patients with SWS, likely molecular pathways impacted, and provide insights for future translational research to improve clinical treatment for patients with SWS.

Ultra-High-Performance Liquid Chromatography–Tandem Mass Spectrometry Analysis of Δ9-Tetrahydrocannabinol and Cannabidiol in Commercial Suk-Saiyasna Herbal Remedy: Applying Hansen Solubility Parameters for Sample Extraction to Ensure Regulatory Compliance

Background: Suk-Saiyasna is a traditional Thai herbal remedy that comprises 12 distinct herbs. Among these, cannabis leaves constitute 12 of the total 78 components in this formulation. This study specifically examines the portion of the cannabis plant, which accounts for approximately 15.8% of the overall herbal composition used in the entire remedy. According to the Thailand Narcotics Act of 2022, the Δ9-tetrahydrocannabinol (Δ9-THC) concentration in herbal extracts must not exceed 0.2% by weight. This study aims to quantify the levels of Δ9-THC and cannabidiol (CBD) in commercial Suk-Saiyasna products. Methodology: This research utilizes Hansen Solubility Parameters (HSPs) to identify the optimal solvent for ultrasonic extraction, thereby maximizing cannabinoid yield. An advanced method was developed employing ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS), compliant with AOAC standards to meet regulatory guidelines. The method validation emphasized specificity, linearity, sensitivity, accuracy, and precision. Results: Dichloromethane was chosen due to its favorable HSP values, enabling highly efficient extraction of Δ9-THC and CBD, achieving recovery rates of over 99.9% after the second extraction. This investigation benefits from the accuracy of the UHPLC-MS/MS technique in quantifying cannabinoids in commercial products, with Δ9-THC concentrations observed between 0.00231% and 0.14218%, and CBD concentrations ranging from 0.00002% to 0.01541%, all remaining below the legal limit. Conclusions: The variability in cannabinoid concentrations among various commercial products highlights the need for standardization in the herbal industry. This finding underscores the critical role of rigorous quality control measures in ensuring the safety and efficacy of cannabis-derived products.

Urinalysis and perceived effects following 2-week use of a commercial broad-spectrum cannabidiol product.

A growing number of hemp-derived cannabidiol (CBD) products are available with negligible amounts (< 100 ppm) of delta-9-tetrahydrocannabinol (THC) due in part to consumer concerns regarding the risk of positive drug screens. There are, however, no published studies that report whether repeated use of these products may lead to positive urine drug tests for THC. There is also scant research on the effects of these products on physical and mental well-being. Twenty healthy adults consumed a hemp-derived broad-spectrum CBD product every day for 2 weeks. Participants attended study visits at the beginning and end of the 2-week period. At each visit, participants underwent urinalysis testing for CBD, THC, and metabolites (analyzed via liquid chromatography with tandem mass spectrometry) and completed a validated assessment of physical and mental well-being. Participants reported using an average of 1.09 ± 0.51 ml (34.20 ± 16.00 mg CBD) of study product per day. Neither tetrahydrocannabinol nor its metabolites were detectable in urine following the 2-week period of use. Ingestion of the broad-spectrum product was associated with a significant reduction in sleep disturbance and pain intensity symptoms (p < .05), which remained significant after correcting for possible confounds (i.e., age, sex, dosage). No adverse events were reported. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Chemical analysis and concentrations of cannabidiol substances used for refractory epilepsy in Chilean patients. An underestimated worldwide risk.

The purpose of this study is to analyze composition of HMS (homemade CBD), NLS (non-licensed commercial products), and bioequivalent CBD (BES) collected from Chilean patients that voluntary accepted to analyze the "CBD-substance." Samples were collected through an open invitation for different patients to anonymously and free of charge participate in the analysis of CBD oil. The analysis of the active principle was performed using High-Resolution Liquid Chromatography (HPLC). A total of 35 samples were collected between March 2020 and September 2021, including two BES, six NLS, and 27 HMS products. The BES had an average CBD concentration of 89.15 mg/mL and an average THC concentration of 0.015 mg/mL, which complied with the maximum THC levels required by regulatory authorities (<0.2% THC.). The NLS (six samples) exhibited significant variability in CBD concentrations, ranging from a maximum of 78.5 mg/mL to a minimum of 0.1 mg/mL, with an average of 25.41 mg/mL. The THC concentrations ranged from 0 mg/mL to 2.43 mg/mL with an average of 0.62 mg/mL. The HMS products exhibited even higher variations of CBD concentrations, ranging from 0 to a maximum of 6.6 mg/mL. THC concentrations were even more variable, ranging from 0 mg/mL to 388 mg/mL. The medical community and patients involved should be aware that Hemp products are not pure and/or innocuous. HMS are likely to have high levels of THC and very low CBD, far away from therapeutic doses of CBD. CBD used in epilepsy should be restricted to licensed products, especially in children where THC toxicity is much more harmful. The study analyzed three types of CBD (cannabidiol) oils: homemade, non-licensed, and bioequivalent. Homemade and non-licensed products showed nonacceptable variance of CBD and THC concentration (tetrahydrocannabinol), in some cases with 0 mgs of CBD and many beyond THC maximum accepted. The THC is another component found in cannabis and is responsible for the neurotoxic effects. Only bioequivalent products showed concentrations of CBD and THC acceptable for epilepsy treatment, therefore are the only products recommended for such purpose.

Structure–Tissue Exposure/Selectivity Relationship (STR) on Carbamates of Cannabidiol

The structure–tissue exposure/selectivity relationship (STR) aids in lead optimization to improve drug candidate selection and balance clinical dose, efficacy, and toxicity. In this work, butyrocholinesterase (BuChE)-targeted cannabidiol (CBD) carbamates were used to study the STR in correlation with observed efficacy/toxicity. CBD carbamates with similar structures and same molecular target showed similar/different pharmacokinetics. L2 and L4 had almost same plasma exposure, which was not correlated with their exposure in the brain, while tissue exposure/selectivity was correlated with efficacy/safety. Structural modifications of CBD carbamates not only changed drug plasma exposure, but also altered drug tissue exposure/selectivity. The secondary amine of carbamate can be metabolized into CBD, while the tertiary amine is more stable. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters can be used to predict STR. Therefore, STR can alter drug tissue exposure/selectivity in normal tissues, impacting efficacy/toxicity. The drug optimization process should balance the structure–activity relationship (SAR) and STR of drug candidates for improving clinical trials.

Improved Therapeutic Efficacy of Doxorubicin Chemotherapy With Cannabidiol in 4T1 Mice Breast Cancer Model.

High dose chemotherapy is one of the therapeutic strategies for breast cancer and doxorubicin (DOX) as a chemotherapy agent is widely used. DOX indication is limited due to its dose-depended cardiotoxicity. Recently, cannabidiol (CBD) shows antitumoral and cardioprotective effects, so we hypothesized that CBD administration with high-dose DOX chemotherapy can improve anticancer activity and reduce cardiotoxic side effects. Mice breast cancer model established by injecting 4T1 cell lines. One group was not injected by 4T1 cells as a not cancerous group and received normal saline (NS, 0.1 mL). In cancerous groups, first group was considered as cancerous control and received NS (0.1 mL); the second group received CBD (5 mg/kg, IP) on Days 1,7, and 14; in the third group DOX (5 mg/kg, IV) as CBD schedule was administrated; the fourth group treated with CBD 1 day before DOX injection as pretreatment, and the last group was treated with CBD and DOX at same time with previous doses and schedules. On Day 21, all mice were sacrificed, heart and lungs tissues were obtained and histological sections were isolated. SOD2, iNOS, MMP2, MMP9 were evaluated through western blot and TUNEL test preformed for breast tumor. Tumor size and weight significantly decreased in DOX, pretreatment CBD + DOX and CBD + DOX groups. Administration of CBD with DOX could not prevent weight loss. TUNEL test demonstrated the highest tumor cell apoptosis in pretreatment CBD + DOX and CBD + DOX. In lungs belonged to CBD + DOX, there was not any sign of metastasis. Cardiac histopathological examination of pretreatment CBD + DOX and CBD + DOX did not show any sign of congestion or inflammation. In CBD + DOX SOD2 increased, also iNOS, MMP2, and MMP9 decreased compared to DOX. This study demonstrated that simultaneous administration of CBD and DOX can increase antitumoral effect and reduce DOX cardiotoxicity. Nevertheless, CBD can induce cardiotoxicity as administrated alone.

Quantitative summary on the human pharmacokinetic properties of cannabidiol to accelerate scientific clinical application of cannabis.

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

Boosting Acetylcholine Signaling by Cannabidiol in a Murine Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a challenging medical issue that requires efficacious treatment options to improve long-term quality of life. Cannabidiol (CBD) is a cannabis-derived phytocannabinoid with potential health benefits, including reports from our laboratory and others showing a therapeutic role in the pre-clinical treatment of AD; however, the mechanisms whereby CBD affects AD progression remain undefined. Innate lymphoid cells (ILCs) are recently discovered immune cells that initiate and orchestrate inflammatory responses. ILC2, a sub-class of ILCs, is proposed to have a role in cognitive function via unknown mechanisms. In this present study, we explored whether CBD ameliorates AD symptoms via the enhancement of acetylcholine (ACh), a cholinergic neurotransmitter involved in cognition that may regulate ILC2. 5xFAD mice were chronically treated by inhalation of a formulation of broad-spectrum CBD for seven months. ACh production, ILC2s profile, brain histopathology, and long-term behavior were assessed. Together, our studies showed that long-term inhalation of CBD improved cognitive function and reduced senile plaques in a murine AD model, effects that were associated with enhanced ACh production and altered ILC2s distribution within the CNS. These findings indicate that inhaled CBD could offer a cost-effective, non-invasive, and effective treatment for managing AD. The beneficial effects of CBD inhalation may be linked to increased ACh production and an altered distribution of ILC2s, highlighting the need for further research in this area.