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.

Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders.

Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system-related receptors and other molecular targets, such as the 5-HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5-HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5-HT1A serotonergic receptor plays a key role. The aim of this review was to provide an overview of cannabinoid effects on neurological disorders, such as epilepsy, multiple sclerosis and Parkinson's diseases, and discuss their possible mechanism of action, highlighting interactions with molecular targets and the potential neuroprotective effects of phytocannabinoids. CBD has been shown to have significant therapeutic effects on epilepsy and Parkinson's disease, while nabiximols contribute to a reduction in spasticity and are a frequent option for the treatment of multiple sclerosis. Although there are multiple theories on the therapeutic potential of cannabinoids for neurological disorders, substantially greater progress in the search for strong scientific evidence of their pharmacological effectiveness is needed.

Additive anxiolytic-like effect of citicoline and ACPA in the non-acute restraint stress (NARS) and acute restraint stress (ARS) mice.

The cannabinoid system plays a key role in stress-related emotional symptoms such as anxiety. Citicoline is a supplemental substance with neuroprotective properties that alleviates anxiety-related behaviors. There is a relation between the actions of cannabinoids and cholinergic systems. So, we decided to evaluate the effects of intracerebroventricular (i.c.v.) infusion of cannabinoid CB1 receptor agents on citicoline-produced response to anxiety-like behaviors in the non-acute restraint stress (NARS) and acute restraint stress (ARS) mice. For i.c.v. microinjection of drugs, a guide cannula was inserted in the left lateral ventricle. ARS was induced by movement restraint for 4 h. Anxiety-related behaviors were assessed using an elevated plus maze (EPM). The results showed that induction of ARS for 4 h decreased the percentage of time spent in the open arms (%OAT) and the percentage of entries to the open arms (%OAE) without affecting locomotor activity, showing anxiogenic-like behaviors. i.c.v. infusion of ACPA (1 µg/mouse) induced an anxiolytic-like effect due to the enhancement of %OAT in the NARS and ARS mice. Nonetheless, i.c.v. microinjection of AM251 (1 µg/mouse) decreased %OAT in the NARS and ARS mice which suggested an anxiogenic-like response. Intraperitoneal (i.p.) administration of citicoline (80 mg/kg) induced an anxiolytic-like effect by the augmentation of %OAT in the ARS mice. Furthermore, when ACPA and citicoline were co-administrated, ACPA potentiated the anxiolytic-like effect induced by citicoline in the NARS and ARS mice. On the other hand, when AM251 and the citicoline were co-injected, AM251 reversed the anxiolytic-like response induced by the citicoline in the NARS and ARS mice. The results of this research exhibited an additive effect between citicoline and ACPA on the induction of anxiolytic-like response in the NARS and ARS mice. Our results indicated an interaction between citicoline and cannabinoid CB1 receptor drugs on the control of anxiety-like behaviors in the NARS and ARS mice.

Pharmacological management of fragile X syndrome: a systematic review and narrative summary of the current evidence.

INTRODUCTION: Fragile X syndrome (FXS) is the most common inherited cause of Intellectual Disability. There is a broad phenotype that includes deficits in cognition and behavioral changes, alongside physical characteristics. Phenotype depends upon the level of mutation in the FMR1 (fragile X messenger ribonucleoprotein 1) gene. The molecular understanding of the impact of the FMR1 gene mutation provides an opportunity to target treatment not only at symptoms but also on a molecular level. METHODS: We conducted a systematic review to provide an up-to-date narrative summary of the current evidence for pharmacological treatment in FXS. The review was restricted to randomized, blinded, placebo-controlled trials. RESULTS: The outcomes from these studies are discussed and the level of evidence assessed against validated criteria. The initial search identified 2377 articles, of which 16 were included in the final analysis. CONCLUSION: Based on this review to date there is limited data to support any specific pharmacological treatments, although the data for cannabinoids are encouraging in those with FXS and in future developments in gene therapy may provide the answer to the search for precision medicine. Treatment must be person-centered and consider the combination of medical, genetic, cognitive, and emotional challenges.

Anti-staphylococcal activity of soilless cultivated cannabis across the whole vegetation cycle under various nutritional treatments in relation to cannabinoid content.

Antibiotic resistance in staphylococcal strains and its impact on public health and agriculture are global problems. The development of new anti-staphylococcal agents is an effective strategy for addressing the increasing incidence of bacterial resistance. In this study, ethanolic extracts of Cannabis sativa L. made from plant parts harvested during the whole vegetation cycle under various nutritional treatments were assessed for in vitro anti-staphylococcal effects. The results showed that all the cannabis extracts tested exhibited a certain degree of growth inhibition against bacterial strains of Staphylococcus aureus, including antibiotic-resistant and antibiotic-sensitive forms. The highest antibacterial activity of the extracts was observed from the 5th to the 13th week of plant growth across all the nutritional treatments tested, with minimum inhibitory concentrations ranging from 32 to 64 µg/mL. Using HPLC, Δ9-tetrahydrocannabinolic acid (THCA) was identified as the most abundant cannabinoid in the ethanolic extracts. A homolog of THCA, tetrahydrocannabivarinic acid (THCVA), reduced bacterial growth by 74%. These findings suggest that the cannabis extracts tested in this study can be used for the development of new anti-staphylococcal compounds with improved efficacy.

Development of an in vitro peptide-stimulated T cell assay to evaluate immune effects by cannabinoid compounds.

Previous studies demonstrated that cannabinoids exhibit immunosuppressive effects in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). To ask questions about treatment timing and investigate mechanisms for immune suppression by the plant-derived cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), an in vitro peptide stimulation of naive splenocytes (SPLC) was developed to mimic T cell activation in EAE. The peptide was derived from the myelin oligodendrocyte glycoprotein (MOG) protein, which is one component of the myelin sheath. MOG peptide is typically used with an immune adjuvant to trigger MOG-reactive T cells that attack MOG-containing tissues, causing demyelination and clinical disease in EAE. To develop the in vitro model, naïve SPLC were stimulated with MOG peptide on day 0 and restimulated on day 4. Cytokine analyses revealed that CBD and THC suppressed MOG peptide-stimulated cytokine production. Flow cytometric analysis showed that intracellular cytokines could be detected in CD4+ and CD8+ T cells. To determine if intracellular calcium was altered in the cultures, cells were stimulated for 4 days to assess the state of the cells at the time of MOG peptide restimulation. Both cannabinoid-treated cultures had a smaller population of the calcium-positive population as compared to vehicle-treated cells. These results demonstrate the establishment of an in vitro model that can be used to mimic MOG-reactive T cell stimulation in vivo.

Divergent synthesis of fractionated Cannabis sativa extract led to multiple cannabinoids C-&O-glycosides with anti-proliferative/anti-metastatic properties.

Here, we present an interesting, previously unreported method for fractionating a particular class of cannabinoids from the crude leaf extract of Cannabis sativa using HP-20 resins. In this study, we report a novel method of divergent synthesis of fractionated Cannabis sativa extract, which allows the generation of multiple cannabinoids C- and O-glycosides which react with the glycosyl donor 2,3,4,6-tetra-O-acetyl-d-mannosyl trichloroacetimidate (TAMTA) to create eight C- and O-ß-d-cannabinoids glycosides (COCG), which are separated by HPLC and whose structures are characterized by 1D, 2D NMR, and mass spectrometry. These glycosides exhibit improved anti-proliferative and anti-metastatic effects against numerous cancer cell lines in vitro and are more water-soluble and stable than their parent cannabinoids. The in vitro testing of the pure cannabinoids (1-4) and their C- & O-glycosides (1a-4a) and 1b-4b exhibited anti-proliferative and anti-metastatic activities against a panel of eight human cancer cell lines in contrast to their respective parent molecules. Different cancer cell lines' IC50 values varied significantly when their cell viability was compared. In addition to the others, compounds 2a, 3a, 4a, and 2b, 3b were highly potent, with IC50values ranging from 0.74 µM (3a) to 51.40 µM (4a).Although2a(1.42 µM) and3a(0.74 µM) exhibited lower IC50values in the MiaPaca-2 cell line than4a(2.58 µM). But, in addition to the comparable anti-clonogenic activity of4ain MiaPaca-2 and Panc-1 cells, it manifested remarkable anti-invasive activity than either 2a or 3a.In contrast to 2a, 2b, 3a, and 3b and their respective parent compounds,4ahad substantial anti-invasive/anti-metastatic capabilities and possessed anti-proliferative activity.The effects of 4a treatment on MiaPaca-2 and Panc-1 cells include a dose-dependent increase in the expression of E-cadherin and a significant decrease in the expression of Zeb-1, Vimentin, and Snail1. Our results demonstrate that divergent synthesis of fractionated Cannabis sativa extract is a feasible and efficient strategy to produce a library of novel cannabinoid glycosides with improved pharmacological properties and potential anticancer benefits.

Cannabis Science and Therapeutics: An Overview for Clinicians.

Cannabis-based therapeutics have garnered increasing attention in recent years as patients seek alternative treatments for various medical conditions. This narrative review provides a comprehensive overview of the science behind the medical use of cannabis, focusing on the medical evidence for commonly treated conditions. In addition, the review addresses the practical considerations of using cannabis as a therapeutic agent, offering insights into dosing strategies, variations in cannabinoid formulation, and individual patient responses. Precautions, adverse consequences, and drug interactions are also discussed, with a focus on patient safety and the potential risks associated with cannabis use.

In Vitro Evidence of Selective Pro-Apoptotic Action of the Pure Cannabidiol and Cannabidiol-Rich Extract.

Plant cannabinoids, secondary metabolites of species belonging to the Cannabis genus, can mimic the endocannabinoids' action and exert biological effects. Considering the contribution of the endocannabinoid system in cell cycle and apoptotic regulation, there is an interest in exploring the potential anti-cancer activities of natural and synthetic cannabinoids. Cannabidiol (CBD), an abundant plant cannabinoid, reveals a low affinity to cannabinoid receptors and, contrary to various cannabinoids, lacks psychoactive action. Here, we present the in vitro assessment of the pro-apoptototic potential of CBD-rich extracts of Cannabis sativa L. (eCBD) compared to purified CBD (pCBD). As demonstrated, both eCBD and pCBD decreased the viability of breast cancer cell line MDA-MB-231 and human prostate cancer cell line PC-3 in a concentration-dependent fashion. Endoplasmic reticulum stress-related apoptosis and morphological changes were induced only in low-serum conditions. Moreover, the effects of eCDB and pCDB were also assessed in non-malignant cell lines (MCF-10A and PNT2) with no alterations of viability noted, ultimately suggesting a selective action of CBD in tumor cells. The results suggest the possible involvement of reactive oxygen species in the response mechanism to eCBD and pCBD, but no clear pattern was observed. We also demonstrated significant changes in gene expression involved in apoptosis and cell cycle control upon extract treatment. Altogether, our study shows the potential of eCBD and pCBD as novel pro-apoptototic agents that can be considered promising in future preclinical and clinical testing.

Hemp-Derived CBD Used in Food and Food Supplements.

Cannabis sativa L., a plant historically utilized for textile fibers, oil, and animal feed, is progressively being recognized as a potential food source. This review elucidates the nutritional and functional attributes of hemp and cannabidiol (CBD) within the context of food science. Hemp is characterized by the presence of approximately 545 secondary metabolites, among which around 144 are bioactive cannabinoids of primary importance. The study looks in detail at the nutritional components of cannabis and the potential health benefits of CBD, encompassing anti-inflammatory, anxiolytic, and antipsychotic effects. The review deals with the legislation and potential applications of hemp in the food industry and with the future directions of cannabis applications as well. The paper emphasizes the need for more scientific investigation to validate the safety and efficacy of hemp components in food products, as current research suggests that CBD may have great benefits for a wide range of consumers.

Pharmacohistory of Cannabis Use-A New Possibility in Future Drug Development for Gastrointestinal Diseases.

Humans have employed cannabis for multiple uses including medicine, recreation, food, and fibre. The various components such as roots, flowers, seeds, and leaves have been utilized to alleviate pain, inflammation, anxiety, and gastrointestinal disorders like nausea, vomiting, diarrhoea, and inflammatory bowel diseases (IBDs). It has occupied a significant space in ethnomedicines across cultures and religions. Despite multi-dimensional uses, the global prohibition of cannabis by the USA through the introduction of the Marijuana Tax Act in 1937 led to prejudice about the perceived risks of cannabis, overshadowing its medicinal potential. Nevertheless, the discovery of tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, and the endocannabinoid system renewed scientific interest in understanding the role of cannabis in modulating different conditions, including gastrointestinal disorders. Preparations combining cannabidiol and THC have shown promise in mitigating gut symptoms through anti-inflammatory and motility-enhancing effects. This review revisits the ethnomedicinal use of cannabis in gastrointestinal diseases and emphasizes the need for further research to determine optimal dosages, formulations, and safety profiles of cannabis-based medicines. It also underscores the future potential of cannabinoid-based therapies by leveraging the role of the expanded endocannabinoid system, an endocannabinoidome, in the modulation of gastrointestinal ailments.

Encapsulation of Hemp (Cannabis sativa L.) Essential Oils into Nanoemulsions for Potential Therapeutic Applications: Assessment of Cytotoxicological Profiles.

Industrial hemp (Cannabis sativa L.), due to its bioactive compounds (terpenes and cannabinoids), has gained increasing interest in different fields, including for medical purposes. The evaluation of the safety profile of hemp essential oil (EO) and its encapsulated form (nanoemulsion, NE) is a relevant aspect for potential therapeutic applications. This study aimed to evaluate the toxicological effect of hemp EOs and NEs from cultivars Carmagnola CS and Uso 31 on three cell lines selected as models for topical and inhalant administration, by evaluating the cytotoxicity and the cytokine expression profiles. Results show that EOs and their NEs have comparable cytotoxicity, if considering the quantity of EO present in the NE. Moreover, cells treated with EOs and NEs showed, in most of the cases, lower levels of proinflammatory cytokines compared to Etoposide used as a positive control, and the basal level of inflammatory cytokines was not altered, suggesting a safety profile of hemp EOs and their NEs to support their use for medical applications.

Comparing dehulled hemp meal and canola meal as a protein supplement for lactating dairy cows.

Effects of replacing canola meal with dehulled hemp meal in the diet of lactating dairy cows on the dry matter intake (DMI), milk production, milk fatty acid profile, blood metabolites, total-tract nutrient digestibility, and transfer of cannabinoids were determined in 12 lactating, nonpregnant Holstein cows. These cows were used in a 3 × 3 Latin square design with three 3-wk experimental periods consisting of 2 wk of adaptation and 1 wk of sampling. Cows received basal partial mixed rations supplemented with either 15% dry matter (DM) canola meal (CM15), 15% DM dehulled hemp meal (HM15), or 7.5% DM dehulled hemp meal and 7.5% DM canola meal (CM7.5HM7.5). Diets were formulated to be isoenergetic and isonitrogenous, but the HM15 and CM7.5HM7.5 diets contained, on average 1.2 percentage units more crude protein (CP) that the CM15 diet. The CP of the dehulled hemp meal contained less soluble protein than that of canola meal. Hence, the intake of soluble protein did not differ among diets. Canola meal contained less crude fat than hemp seed meal (3.46% vs. 8.25% DM). The lipid fraction of canola meal fat contained more oleic acid (C18:1 cis-9; 47.3 vs. 14.9 g/100 g of fatty acids, FA) and vaccenic acid (18:1 cis-11; 13.7 vs. 1.2 g/100 g of FA) and less linoleic acid (C18:2n-6; 21.9 vs. 55.7 g/100 g of FA) and α linolenic acid (C18:3n-3; 3.2 vs. 8.9 g/100 g of FA) than the lipid fraction of hemp seed meal. The hemp seed meal contained 4.9 µg/g cannabidiol, 5.1 µg/g cannabidiolic acid, and 0.1 µg/g tertahydroxycannabinolic acid A. Treatments did not differ in DMI, yields of milk, milk protein and milk fat, total-tract neutral detergent fiber digestibility, and blood plasma concentrations of ß-hydroxybutyrate and nonesterified FA. Apparent total-tract DM digestibility was lowest in the HM15 treatment, whereas the CP digestibility and the concentrations of urea in blood, urine, and milk were lowest in the CM15 treatment. Cannabinoids were not detected in urine, milk, and blood plasma. Replacing canola meal with hemp seed meal increased milk fat contents of polyunsaturated fatty acids (PUFA), which were 3.42, 3.90, and 4.25 g/100 g of FA for the CM15, CM7.5HM7.5, and HM15 treatments, respectively. Especially, the milk fat contents of 18:2n-6 (1.99 vs. 1.56 g/100 g FA) and 18:3n-3 (0.31 vs. 0.43 g/100 g FA) were increased by hemp meal feeding. Especially, the milk fat contents of 18:2n-6 (1.99 vs. 1.56 g/100 g FA) and 18:3n-3 (0.31 vs. 0.43 g/100 g FA) were increased by hemp meal feeding. Our data show that hemp seed meal is a suitable and safe replacement for canola meal as a feed for lactating dairy cows and that this replacement increases CP digestibility and urea in urine, milk, and blood plasma, as well the PUFA content of milk fat.

Cannabinoid mechanisms contribute to the therapeutic efficacy of the kratom alkaloid mitragynine against neuropathic, but not inflammatory pain.

AIMS: Mitragynine (MG) is an alkaloid found in Mitragyna speciosa (kratom), a plant used to self-treat symptoms of opioid withdrawal and pain. Kratom products are commonly used in combination with cannabis, with the self-treatment of pain being a primary motivator of use. Both cannabinoids and kratom alkaloids have been characterized to alleviate symptoms in preclinical models of neuropathic pain such as chemotherapy-induced peripheral neuropathy (CIPN). However, the potential involvement of cannabinoid mechanisms in MG's efficacy in a rodent model of CIPN have yet to be explored. MAIN METHODS: Prevention of oxaliplatin-induced mechanical hypersensitivity and formalin-induced nociception were assessed following intraperitoneal administration of MG and CB1, CB2, or TRPV1 antagonists in wildtype and cannabinoid receptor knockout mice. The effects of oxaliplatin and MG exposure on the spinal cord endocannabinoid lipidome was assessed by HPLC-MS/MS. KEY FINDINGS: The efficacy of MG on oxaliplatin-induced mechanical hypersensitivity was partially attenuated upon genetic deletion of cannabinoid receptors, and completely blocked upon pharmacological inhibition of CB1, CB2, and TRPV1 channels. This cannabinoid involvement was found to be selective to a model of neuropathic pain, with minimal effects on MG-induced antinociception in a model of formalin-induced pain. Oxaliplatin was found to selectively disrupt the endocannabinoid lipidome in the spinal cord, which was prevented by repeated MG exposure. SIGNIFICANCE: Our findings suggest that cannabinoid mechanisms contribute to the therapeutic efficacy of the kratom alkaloid MG in a model of CIPN, which may result in increased therapeutic efficacy when co-administered with cannabinoids.

Monoacylglycerol Lipase Protects the Presynaptic Cannabinoid 1 Receptor from Desensitization by Endocannabinoids after Persistent Inflammation.

Cannabinoid-targeted pain therapies are increasing with the expansion of cannabis legalization, however, their efficacy may be limited by pain-induced adaptations in the cannabinoid system. Cannabinoid receptor subtype 1 (CB1R) inhibition of spontaneous, GABAergic miniature IPSCs (mIPSCs) and evoked IPSCs (eIPSCs) in the ventrolateral periaqueductal gray (vlPAG) were compared in slices from naive and inflamed male and female Sprague Dawley rats. Complete Freund's Adjuvant (CFA) injections into the hindpaw induced persistent inflammation. In naive rats, exogenous cannabinoid agonists robustly reduce both eIPSCs and mIPSCs. After 5-7 d of inflammation, the effects of exogenous cannabinoids are significantly reduced because of CB1R desensitization via GRK2/3, as function is recovered in the presence of the GRK2/3 inhibitor, Compound 101 (Cmp101). Inhibition of GABA release by presynaptic µ-opioid receptors in the vlPAG does not desensitize with persistent inflammation. Unexpectedly, while CB1R desensitization significantly reduces the inhibition produced by exogenous agonists, depolarization-induced suppression of inhibition protocols that promote 2-arachidonoylglycerol (2-AG) synthesis exhibit prolonged CB1R activation after inflammation. 2-AG tone is detected in slices from CFA-treated rats when GRK2/3 is blocked, suggesting an increase in 2-AG synthesis after persistent inflammation. Inhibiting 2-AG degradation with the monoacylglycerol lipase (MAGL) inhibitor JZL184 during inflammation results in the desensitization of CB1Rs by endocannabinoids that is reversed with Cmp101. Collectively, these data indicate that persistent inflammation primes CB1Rs for desensitization, and MAGL degradation of 2-AG protects CB1Rs from desensitization in inflamed rats. These adaptations with inflammation have important implications for the development of cannabinoid-based pain therapeutics targeting MAGL and CB1Rs.SIGNIFICANCE STATEMENT Presynaptic G-protein-coupled receptors are resistant to desensitization. Here we find that persistent inflammation increases endocannabinoid levels, priming presynaptic cannabinoid 1 receptors for desensitization on subsequent addition of exogenous agonists. Despite the reduced efficacy of exogenous agonists, endocannabinoids have prolonged efficacy after persistent inflammation. Endocannabinoids readily induce cannabinoid 1 receptor desensitization if their degradation is blocked, indicating that endocannabinoid concentrations are maintained at subdesensitizing levels and that degradation is critical for maintaining endocannabinoid regulation of presynaptic GABA release in the ventrolateral periaqueductal gray during inflammatory states. These adaptations with inflammation have important implications for the development of cannabinoid-based pain therapies.

The Anti-Inflammatory Effects of Cannabis sativa Extracts on LPS-Induced Cytokines Release in Human Macrophages.

Inflammation is the response of the innate immune system to any type of injury. Although acute inflammation is critical for survival, dysregulation of the innate immune response leads to chronic inflammation. Many synthetic anti-inflammatory drugs have side effects, and thus, natural anti-inflammatory compounds are still needed. Cannabis sativa L. may provide a good source of anti-inflammatory molecules. Here, we tested the anti-inflammatory properties of cannabis extracts and pure cannabinoids in lipopolysaccharide (LPS)-induced inflammation in human THP-1 macrophages. We found that pre-treatment with cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC), or extracts containing high levels of CBD or THC reduced the level of induction of various cytokines. The CBD was more efficient than THC, and the extracts were more efficient than pure cannabinoids. Finally, IL-6, IL-10, and MCP-1 cytokines were most sensitive to pre-treatments with CBD and THC, while IL-1ß, IL-8, and TNF-α were less responsive. Thus, our work demonstrates the potential of the use of cannabinoids or/and cannabis extracts for the reduction of inflammation and establishes IL-6 and MCP-1 as the sensitive markers for the analysis of the effect of cannabinoids on inflammation in macrophages.

Cannabis: Drug of Abuse and Therapeutic Agent, Two Sides of the Same Coin.

The consumption of Cannabis sativa plant, known as marijuana in the Western world, for different purposes (therapeutic, intoxicating, and spiritual) due to its psychoactive effects, can be traced back to ancient times. Cannabis is the most used illicit drug worldwide; however, its legal status is changing rapidly. Cannabis regulation will allow a better understanding of its effects as a misused drug, including new challenges, such as the availability of highly potent Cannabis extracts. Furthermore, scientific research is making significant efforts to take advantage of the potential therapeutic uses of Cannabis active compounds. The science of Cannabis derivatives started with the identification of the phytocannabinoids Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), allowing the formal study of the complex set of effects triggered by Cannabis consumption and the deciphering of its pharmacology. Δ9-THC is recognized as the compound responsible for the psychoactive and intoxicating effects of Cannabis. Its study led to the discovery of the endocannabinoid system, a neuromodulatory system widespread in the human body. CBD does not induce intoxication and for that reason, it is the focus of the search for cannabinoid potential clinical applications. This review examines the current state of knowledge about contrasting perspectives on the effects of Cannabis, Δ9-THC, and CBD: their abuse liability and potential therapeutic use; two sides of the same coin.

Cannabidiol for Oral Health: A New Promising Therapeutical Tool in Dentistry.

The medical use of cannabis has a very long history. Although many substances called cannabinoids are present in cannabis, Δ9tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD) and cannabinol (CBN) are the three main cannabinoids that are most present and described. CBD itself is not responsible for the psychotropic effects of cannabis, since it does not produce the typical behavioral effects associated with the consumption of this drug. CBD has recently gained growing attention in modern society and seems to be increasingly explored in dentistry. Several subjective findings suggest some therapeutic effects of CBD that are strongly supported by research evidence. However, there is a plethora of data regarding CBD's mechanism of action and therapeutic potential, which are in many cases contradictory. We will first provide an overview of the scientific evidence on the molecular mechanism of CBD's action. Furthermore, we will map the recent developments regarding the possible oral benefits of CBD. In summary, we will highlight CBD's promising biological features for its application in dentistry, despite exiting patents that suggest the current compositions for oral care as the main interest of the industry.

The current role of cannabis and cannabinoids in health: A comprehensive review of their therapeutic potential.

There has been an increased interest of the scientific community in cannabis and its constituents for therapeutic purposes. Although it is believed that cannabinoids can be effective for a few different conditions and syndromes, there are little objective data that clearly support the use of cannabis, cannabis extracts or even cannabidiol (CBD) oil. This review aims to explore the therapeutic potential of phytocannabinoids and synthetic cannabinoids for the treatment of several diseases. A broad search covering the past five years, was performed in PubMed and ClinicalTrial.gov databases, to identify papers focusing on the use of medical phytocannabinoids in terms of tolerability, efficacy and safety. Accordingly, there are preclinical data supporting the use of phytocannabinoids and synthetic cannabinoids for the management of neurological pathologies, acute and chronical pain, cancer, psychiatric disorders and chemotherapy-induced emetic symptoms. However, regarding the clinical trials, most of the collected data do not fully support the use of cannabinoids in the treatment of such conditions. Consequently, more studies are still needed to clarify ascertain if the use of these compounds is useful in the management of different pathologies.