Search Results (110)

Cannabis sativa contains more than 120 phytocannabinoids, with Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) being the best characterized. This review synthesizes preclinical and clinical evidence on hemp-derived extracts, cannabinoids, and active compounds. THC primarily acts as a partial agonist at cannabinoid receptor type 1 (CB1) and type 2 (CB2), producing psychoactive, appetite-stimulating, antiemetic, and analgesic effects. CBD is non-intoxicating and has a multimodal profile involving CB1 negative allosteric modulation, CB2 inverse agonism or antagonism, inhibition of anandamide inactivation, and activity at 5-HT1A receptors, transient receptor potential channels, GPR55, and peroxisome proliferator-activated receptor gamma. Preclinical models of Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, epilepsy, and pain support anti-inflammatory, antioxidant, anti-excitotoxic, and glial-modulating mechanisms, but clinical translation remains uneven. The strongest evidence supports FDA-approved cannabidiol for Lennox–Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex, and THC-based agents for refractory chemotherapy-induced nausea and vomiting and AIDS-related anorexia. Moderate-certainty evidence supports nabiximols for multiple sclerosis spasticity and small benefits in selected chronic neuropathic pain populations. Evidence remains insufficient or negative for acute pain, insomnia, most psychiatric disorders, and many promoted indications. Key risks include cannabis use disorder, cognitive and psychiatric effects, cardiovascular events, sedation, high-dose CBD hepatotoxicity, and drug interactions. Rigorous, long-term, product-standardized trials are needed. Full article

Interest is growing in the antimicrobial potential of the non-psychoactive cannabinoids, such as cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA), and their metal systems. The present study follows on from previous potentiometric and ESI-MS studies confirming the formation of stable zinc(II) species with cannabinoid acids in an alcohol–water environment under physiological conditions. The antibacterial action of the compounds was assessed against reference Gram-negative strains (Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis) and Gram-positive strains (Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis) using minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) assays. Their cytotoxicity was also evaluated in vitro using mouse fibroblasts. The tested compounds were found to demonstrate pronounced selectivity against Gram-positive bacterial strains compared to Gram-negative bacteria. The antibacterial efficacy of the free ligands was enhanced by the presence of Zn(II) in the solution: the equilibrium mixtures exhibited greater inhibitory activity against E. faecalis and S. epidermidis, with MIC and MBC values being non-cytotoxic toward L929 fibroblasts under the tested in vitro conditions. However, Gram-negative bacteria were only found to be susceptible at elevated concentrations, which also induced cytotoxic effects. Among the free ligands, CBGA exhibited slightly stronger antibacterial activity than CBDA. Full article

Cannabinoids are potential anticancer agents for the add-on treatment of malignant tumors. Here, the effects of the previously less-explored non-psychoactive phytocannabinoids cannabigerol (CBG) and cannabichromene (CBC) on survival, apoptosis, and mitochondrial function were assessed in A549 and H460 lung cancer cells. CBG and CBC triggered concentration-dependent cell death, autophagy, and mitochondrial apoptosis in both cell lines, with apoptosis indicated by Annexin V staining, activation of caspase-8, -9, and -3/7, loss of mitochondrial membrane potential, and elevated cytosolic levels of mitochondrial cytochrome c. CBG also upregulated ATF4, a stress-responsive transcription factor involved in autophagy and apoptotic signaling, and enhanced PARP cleavage. Both cannabinoids increased mitochondrial superoxide formation and reduced the mitochondrial oxygen consumption rate, with CBG additionally decreasing NDUFB8, a subunit of respiratory chain complex I. Pharmacological receptor modulation showed that CBG- and CBC-induced cell death occurred independently of CB₁, CB₂, TRPV1, TRPM8, and PPARγ, whereas CBG-mediated cell death relied on PPARα, which also contributed to its apoptotic effects. In summary, CBG and CBC induce apoptosis and cell death in A549 and H460 cells, with PPARα mediating the effects of CBG, highlighting its potential as a therapeutic target. Full article

Cannabinoids, including the psychoactive D9-tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD), interact with receptors within the endocannabinoid system. The major receptors within this system are CNR1 (cannabinoid receptor 1) and CNR2 (cannabinoid receptor 2), which are both seven-transmembrane G-protein-coupled receptors. In this report, we used the Catalogue of Somatic Mutations in Cancers (COSMIC) to map and analyze mutations arising in CNR1 and CNR2. The goal was to determine if any trends or signatures could be identified. We identified several mutations in both CNR1 and CNR2. In silico 3D structure of proteins reveals that these mutations cluster on the intracellular regions of CNR1 and CNR2, and certain residues may be able to destabilize the interaction with the G-alpha protein due to their close proximity. mRNA expression showed that CNR1 and CNR2 are within normal expression levels in most cancer types except kidney, where there is a tendency towards over-expression. Neither CNR1 nor CNR2 is a driver gene, and our analysis shows that mutations in cancer cells are deactivating (e.g., loss of function). Full article

Background/Objectives: Dermatomyositis is an autoimmune disease with heterogeneous symptoms and many potential drivers. Nonpsychoactive cannabinoids have shown promise in treating some subtypes of DM; however, the reasons behind this were unclear. In this project, we tested the effects of CB2R activation on PBMCs from amyopathic and classic DM patients to determine its anti-inflammatory effects on pathways biologically relevant to DM. Methods: We determined the % CB2R positivity and intracellular cytokines in PBMCs from amyopathic DM and classic DM patients. CB2R positivity was determined by analyzing patient PBMCs via flow cytometry. PBMCs were stimulated by dsRNA for RIG1, dsDNA for cGAS, LPS for TLR4, and LPS/ATP for NLRP3, with and without CB2R pretreatment, and IFNβ, IFNγ, p65 NFkB, and pSTING levels were used as markers of pathway activation. The CB2R agonist JWH133 was used to pretreat PBMCs before stimulation. Results: Amyopathic DM PBMCS were found to be 101.3% more positive for CB2R compared to classic DM PBMCS (p < 0.05). In amyopathic DM PBMCs stimulated by LPS/ATP to target the NLRP3 inflammasome, CB2R activation resulted in a significant reduction in IFNβ MFI for MoDCs (p < 0.05) and Macs (p < 0.05), with a similar trend observed in cDCs relative to classic DM PBMCS. On the other hand, no difference in IFNβ response to CB2R activation was observed across all cell types investigated between classic and amyopathic DM PBMCs stimulated with LPS only to target TLR4. Conclusions: Amyopathic DM PBMCs were significantly more positive for CB2R and had better anti-inflammatory responses to CB2R activation for many inflammatory pathways implicated in DM. Full article

Background: Cocaine use disorder (CUD) remains a major global health concern, with no FDA-approved pharmacological treatments currently available. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa L., has shown promising preclinical effects in disrupting the consolidation and retrieval of drug-associated memories, thereby attenuating relapse-like behaviors. Objectives: The present study evaluated the effects of a low-THC CBD-rich cannabis extract (NPCE) on the reinstatement and reconsolidation of cocaine-induced conditioned place preference (CPP) in male CD1 (ICR) mice, an approach not previously investigated. Methods: The extract was administered at a dose equivalent to 20 mg/kg of CBD. Treatment significantly attenuated both priming- and stress-induced reinstatement of cocaine-induced CPP. Reinstatement was triggered either by a cocaine priming injection or by acute stress exposure, whereas reconsolidation-like processes were assessed by administering the extract following memory reactivation sessions and subsequently evaluating the persistence of cocaine-associated preference over time. Results: NPCE showed a consistent result with disruption of reconsolidation-like processes of cocaine-associated memory, with effects persisting for at least two weeks. The extract alone did not induce conditioned preference or aversion. Conclusions: These findings suggest that NPCE modulates drug-associated memory processes involved in relapse-like behavior. However, the underlying mechanisms were not directly evaluated and remain to be elucidated. Further studies are warranted to include both sexes, evaluate effects across multiple behavioral paradigms, directly compare full-spectrum extracts with isolated cannabinoids, and incorporate receptor-specific approaches to clarify the mechanisms of action. Full article

This study examines the effect of microfluidization on the physicochemical properties, stability, release behavior, and cytocompatibility of cannabidiol (CBD) nanoemulsions intended for topical application. CBD is a non-psychoactive cannabinoid characterized by anti-inflammatory and analgesic activity; however, its therapeutic use is limited by low solubility and poor bioavailability. To address these limitations, nanoemulsions were formulated using avocado oil and Tween 80 and optimized through a Box–Behnken experimental design evaluating microfluidization pressure (5000–20,000 PSI), CBD concentration (0–2%), and oil content (8–10%). Nanoemulsions were characterized over a 60-day period in terms of droplet size, dispersity index (D), and zeta potential. An increase in processing pressure led to a reduction in both droplet size and dispersity, with optimal conditions identified between 11,000 and 15,000 PSI. Higher oil and CBD concentrations were associated with an increase in the magnitude of the zeta potential, contributing to electrostatic stabilization of the system. Encapsulation efficiency reached approximately 81.4%. Cell viability assays in HaCaT keratinocytes indicated no significant cytotoxic effects. The optimized formulation exhibited a sigmoidal CBD release profile best described by Weibull and Gompertz models (R² ≈ 0.99), suggesting combined diffusion and interfacial mechanisms that support efficient topical delivery. Full article

The continuous emergence of New Psychoactive Substances (NPS) poses a significant challenge to public health and forensic toxicology due to their unpredictable pharmacology and rapid turnover on the illicit market. This study describes the development and validation of a high-resolution screening method for the simultaneous detection of 90 NPS in oral fluid (OF), a matrix of choice for non-invasive sampling and roadside testing. The analytical workflow utilizes a “dilute-and-shoot” approach (1:2 v/v dilution) followed by ultra-high-performance liquid chromatography coupled with a quadrupole-Orbitrap hybrid mass spectrometer (UHPLC-HRMS/MS). Chromatographic separation was achieved in 11 min using a biphenyl column and a gradient elution. The method was validated according to ANSI/ASB Standard 036 guidelines, covering 90 substances including synthetic cannabinoids (e.g., HHC, MDMB-4en-PINACA), synthetic cathinones, and high-risk synthetic opioids such as nitazenes and fentanyl analogues. Results showed high sensitivity, with limits of identification (LOI) reaching 1 ng/mL for 44.4% of the analytes and 5 ng/mL for 37.8%, while the remaining compounds showed higher LOIs ranging from 10 to 100 ng/mL. No significant matrix interference or carryover was observed. The method was successfully applied to real samples from external quality control programs and forensic cases. This robust and versatile screening tool is suitable for clinical and forensic applications, supporting the monitoring of emerging NPS trends. Full article

Reliable analytical methods are essential for the assessment, effective quality control, and guarantee of consistent and reproducible performance of chemical profiles of non-psychoactive low-THC Cannabis sativa L. samples and their products. An integrated analytical approach was applied for the first time to evaluate low-THC C. sativa products on the Serbian legal market using chemometrics combined with five complementary techniques: ultraviolet–visible spectroscopy (UV–Vis), high-performance thin-layer chromatography (HPTLC), portable Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR) and gas chromatography–mass spectrometry (GC–MS). HPTLC rapidly differentiated key cannabinoids with R_F at 0.39 and 0.61, while GC–MS enabled comprehensive identification of major cannabinoids (CBG and CBD). Spectroscopic fingerprints provided characteristic UV–Vis absorption maximum (215, 235, and 275 nm), Raman (1700, 1550, 1517, 1224, 1096 cm⁻¹) and FTIR marker bands (615, 1059, 1288, 1620, 2932 cm⁻¹), supporting robust monitoring. Principal component analysis (PCA) across all five techniques revealed two major distinct sample clusters and identified the most influential analytical signals. The combined separation, spectroscopic, and multivariate approach is proven to be effective for systematic cannabinoid content assessment, authentication, and chemical profiling within a process-oriented context, thus enabling effective quality control in the cultivation process by targeting compounds of interest. Full article

Background/objectives: Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis sativa, which has potential skeletal benefits through modulation of bone cell function and inflammatory signalling. However, evidence of its effects and mechanisms in bone health remains fragmented. This scoping review summarised the current findings on the impact of CBD on bone outcomes and its mechanisms of action. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted in October 2025 for original studies published in English, with the primary objective of examining the effects of CBD on bone health, regardless of study design. After applying inclusion and exclusion criteria, 24 primary studies were included. Data on model design, CBD formulation, treatment parameters, bone-related outcomes, and proposed mechanisms were extracted and analysed descriptively. Results: Among the studies included, eleven demonstrated beneficial effects of CBD on bone formation, mineralisation, callus quality, or strength; eleven showed mixed outcomes; and two demonstrated no apparent benefit. Previous studies have shown that CBD suppresses bone resorption by reducing osteoclast differentiation and activity while promoting osteoblast proliferation and matrix deposition. Mechanistically, CBD’s effects involve activation of cannabinoid receptor 2, modulation of the receptor activator of nuclear factor-κB ligand/osteoprotegerin pathway, and regulation of osteoblastogenic and osteoclastogenic signalling through bone morphogenetic protein, Wnt, mitogen-activated protein kinase, nuclear factor-κB, and peroxisome proliferator-activated receptor signalling. The anti-inflammatory and antioxidant actions of CBD further contribute to a favourable bone microenvironment. Conclusions: Preclinical evidence suggests that CBD has a bone-protective role through multifaceted pathways that enhance osteoblast function and suppress osteoclast activity. Nevertheless, robust human trials are necessary to confirm its efficacy, determine its optimal dosing, and clarify its long-term safety. Full article

Background: Cannabidiol (CBD) is a major non-psychoactive phytocannabinoid that exerts multiple biological effects in the body. It has been shown to exert anti-cancer effects in a variety of cancer cells, including acute lymphoblastic leukemia of pre-T cell origin (T-ALL), a highly aggressive hematological malignancy. However, the mechanisms underlying CBD’s anti-cancer effects are not fully understood. Furthermore, cancer cells abundantly express surface CD47, which is a negative regulator of phagocytosis and linked with cell survival/death. Little is known about CBD effects on the expression of CD47 in T-ALL cells. The objectives of this study were to address these issues. Methods: Studies were conducted in vitro using Jurkat cells and human peripheral blood mononuclear cells in different culture conditions, CBD concentrations, and in the presence or absence of different reagents. Results: CBD downregulates CD47 expression and induces apoptosis in Jurkat cells. Similar biological effects of CBD were also observed in primary human CD4⁺ T cells, albeit at reduced levels. The CBD’s effects on CD47 expression and apoptosis were not rescued by a cannabinoid receptor (CBR)-2 agonist, a CBR-2 antagonist, or an anion channel blocker. However, these effects on CD47 expression and apoptosis were significantly rescued by a Voltage-Dependent Anion Channel (VDAC)-1 oligomerization inhibitor. Conclusions: Overall, we conclude that CBD downregulates CD47 expression and induces apoptosis involving VDAC-1 oligomerization. Furthermore, they also suggest that CBD’s pro-apoptotic effects on primary human T cells should also be monitored if it is used as an anti-cancer adjuvant or neo-adjuvant therapeutic in cancer patients. Full article

Cannabidiol (CBD) is a non-psychoactive phyto-cannabinoid with numerous pharmacological potentials. CBD is a lipophilic drug with poor and varied bioavailability due to its low water solubility and extensive first-pass metabolism, and it is highly affected by the presence of food. A self-emulsifying drug delivery system (SEDDS) was developed to improve the aqueous solubility and oral bioavailability of CBD. The formulation strategy involved incorporating excipients that maintain drug solubility under both fasted and fed conditions, while potentially mitigating first-pass metabolism to enhance overall bioavailability and dose proportionality. Caproyl^® 90, Tween^® 20, and Transcutol^® HP were selected as the oil phase, surfactant, and cosolvent, respectively, for formulation preparation and screening. CBD SEDDS formulations containing Caproyl^® 90 ≤20% w/w and Tween^® 20 above 40% w/w yield particles below 200 nm. CBD SEDDS with Tween^® 20 65% w/w or higher showed in vitro release of more than 90%. After in vitro digestion, CTT1, CTT4, and CTT8 remained stable under gastrointestinal conditions and maintained CBD solubility of at least 50%. The most promising formulations, CTT4 and CTT8, were used for in vivo evaluations. Both formulations showed similar in vitro results; however, in vivo, CTT4 demonstrated 2.4-fold higher bioavailability than CTT8. Overall, optimizing the level of inhibitory surfactant appears to be a promising strategy for improving CBD bioavailability. Full article

The cannabinoid receptor type 2 (CB₂) is increasingly recognized as a crucial regulator of neuroimmune balance in the brain. In addition to its well-established role in immunity, the CB₂ receptor has been identified in specific populations of neurons and glial cells throughout various brain regions, and its expression is dynamically increased during inflammatory and neuropathological conditions, positioning it as a potential non-psychoactive target for modifying neurological diseases. The expression of the CB₂ gene (CNR2) is finely tuned by epigenetic processes, including promoter CpG methylation, histone modifications, and non-coding RNAs, which regulate receptor availability and signaling preferences in response to stress, inflammation, and environmental factors. CB₂ signaling interacts with TRP channels (such as TRPV1), nuclear receptors (PPARγ), and orphan G Protein-Coupled Receptors (GPCRs, including GPR55 and GPR18) within the endocannabinoidome (eCBome), influencing microglial characteristics, cytokine production, and synaptic activity. We review how these interconnected mechanisms affect neurodegenerative and neuropsychiatric disorders, underscore the species- and cell-type-specificities that pose challenges for translation, and explore emerging strategies, including selective agonists, positive allosteric modulators, and biased ligands, that leverage the signaling adaptability of the CB₂ receptor while reducing central effects mediated by the CB₁ receptor. This focus on the neuro-centric perspective repositions the CB₂ receptor as an epigenetically informed, context-dependent hub within the eCBome, making it a promising candidate for precision therapies in conditions featuring neuroinflammation. Full article

Cannabidiol (CBD) is a chemical produced by the cannabis plant that acts as an allosteric modulator of cannabinoid receptors resulting in non-competitive receptor antagonism in the central nervous system. This mechanism of action leads to anti-convulsant, anti-anxiety, and analgesic properties with minimal psycho-activity, which has led to significant interest in the use of CBD as a medication. Legislation around cannabis has changed in recent years, with many states permitting the use of CBD-based products as “medication” without approval from the Federal Drug Administration. This has led to a proliferation of products with associated marketing claims that are often unsubstantiated. This review summarizes the evidence for cannabidiol as a medical treatment, focusing on epilepsy, mental health, behavioral and substance use disorders occurring in pediatric and adolescent populations for which information is available. CBD preparations have been approved by the FDA to treat epilepsy in childhood; no other indications currently exist, and the literature remains inconclusive. Few adverse effects related to CBD use have been reported. However, endogenous cannabinoids play an important role in guiding brain development, and the long-term impact of modulating the endocannabinoid system during periods of brain growth during childhood and adolescence is unknown. While there is excitement about the potential for the development of CBD medications, currently, there is very limited information about the long-term safety of CBD, especially in children and adolescents, and caution is recommended regarding the use of unregulated, unapproved CBD preparations that are currently available over the counter. Full article

The incorporation of Cannabis sativa L. seeds into barley wort was investigated to enhance the functional profile of beer. Hemp seeds (cv. Henola) were malted via controlled steeping, germination, and kilning, then added to barley malt at 10% and 30% (w/w) in both malted and unmalted forms. Standard congress mashing produced worts whose physicochemical parameters (pH, extract, colour, turbidity, filtration and saccharification times) were assessed, alongside profiles of fermentable sugars, polyphenols, B-group vitamins, and cannabinoids. Addition of hemp seeds reduced extract yield without impairing saccharification or filtration and slightly elevated mash pH and turbidity. Maltose and glucose levels declined significantly at higher hemp dosages, whereas sucrose remained stable. Wort enriched with 30% unmalted seeds exhibited the highest levels of trans-ferulic (20.61 µg/g), gallic (5.66 µg/g), trans-p-coumaric (3.68 µg/g), quercetin (6.07 µg/g), and trans-cinnamic (4.07 µg/g) acids. Malted hemp addition enhanced thiamine (up to 0.302 mg/mL) and riboflavin (up to 178.8 µg/mL) concentrations. Cannabinoids (THCA-A, THCV, CBDV, CBG, CBN) were successfully extracted at µg/mL levels, with the total cannabinoid content peaking at 14.59 µg/mL in the 30% malted treatment. These findings demonstrate that hemp seeds, particularly in malted form, can enrich barley wort with bioactive polyphenols, vitamins, and non-psychoactive cannabinoids under standard mashing conditions, without compromising key brewing performance metrics. Further work on fermentation, sensory evaluation, stability, and bioavailability is warranted to realise hemp-enriched functional beers. Full article