Search Results (413)

Background/Objective: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting adverse effect of various chemotherapeutic agents. Previous work demonstrated that cannabis alleviates symptoms of oxaliplatin-induced CIPN. To evaluate the effects of cannabis components, cannabidiol (CBD) and tetrahydrocannabinol (THC), on CIPN-related symptoms. Methods: We reviewed a patient-reported outcomes dataset from “Tikun Olam,” a major medical cannabis provider. Of 1493 patients, 802 reported at least one CIPN symptom at baseline, including a burning sensation, cold sensation, paresthesia (prickling) and numbness, and 751 of them met the study inclusion criteria. Patients were categorized into THC-high/CBD-low and CBD-high/THC-low groups. Symptom changes after six months of cannabis use were analyzed using K-means clustering and logistic regression, incorporating interactions between baseline symptoms and THC and CBD doses. Linear regression assessed changes in activities of daily living (ADL) and quality of life (QOL). Results: Both groups reported symptom improvement. The THC-high group showed significantly greater improvement in burning sensation and cold sensation (p = 0.024 and p = 0.008). Improvements in ADL and QOL were also significantly higher in the THC group (p = 0.029 and p = 0.006). A significant interaction between THC and CBD was observed for symptom improvement (p < 0.0001). Conclusions: Cannabis effectively reduces CIPN symptoms and improves QOL and ADL. Higher THC doses were more effective than lower doses, with combined CBD and THC doses yielding greater symptom relief. Full article

Background/Objectives: Cannabinoid use is rising among patients undergoing spinal fusion, yet its influence on bone healing is poorly defined. The endocannabinoid system (ECS)—through cannabinoid receptors 1 (CB1) and 2 (CB2)—modulates skeletal metabolism. We reviewed preclinical, mechanistic and clinical evidence to clarify how individual cannabinoids affect fracture repair and spinal arthrodesis. Methods: PubMed, Web of Science and Scopus were searched from inception to 31 May 2025 with the terms “cannabinoid”, “CB1”, “CB2”, “spinal fusion”, “fracture”, “osteoblast” and “osteoclast”. Animal studies, in vitro experiments and clinical reports that reported bone outcomes were eligible. Results: CB2 signaling was uniformly osteogenic. CB2-knockout mice developed high-turnover osteoporosis, whereas CB2 agonists (HU-308, JWH-133, HU-433, JWH-015) restored trabecular volume, enhanced osteoblast activity and strengthened fracture callus. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with CB2 bias, accelerated early posterolateral fusion in rats and reduced the RANKL/OPG ratio without compromising final union. In contrast, sustained or high-dose Δ⁹-tetrahydrocannabinol (THC) activation of CB1 slowed chondrocyte hypertrophy, decreased mesenchymal-stromal-cell mineralization and correlated clinically with 6–10% lower bone-mineral density and a 1.8–3.6-fold higher pseudarthrosis or revision risk. Short-course or low-dose THC appeared skeletal neutral. Responses varied with sex, age and genetic background; no prospective trials defined safe perioperative dosing thresholds. Conclusions: CB2 activation and CBD consistently favor bone repair, whereas chronic high-THC exposure poses a modifiable risk for nonunion in spine surgery. Prospective, receptor-specific trials stratified by THC/CBD ratio, patient sex and ECS genotype are needed to establish evidence-based cannabinoid use in spinal fusion. Full article

Background/Objectives: Cannabidiol (CBD) is a non-intoxicating cannabinoid touted for a variety of medical benefits, including alleviation of anxiety. While legalization of hemp-derived products in the United States (containing ≤0.3% delta-9-tetrahydrocannabinol [d9-THC] by weight) has led to a rapid increase in the commercialization of hemp-derived CBD products, most therapeutic claims have not been substantiated using clinical trials. This trial aimed to assess the impact of 6 weeks of treatment with a proprietary hemp-derived, full-spectrum, high-CBD sublingual solution similar to those available in the marketplace in patients with anxiety. Methods: An open-label pilot clinical trial (NCT04286594) was conducted in 12 patients with at least moderate levels of anxiety. Patients self-administered a hemp-derived, high-CBD sublingual solution twice daily during the 6-week trial (target daily dose: 30 mg/day CBD). Clinical change over time relative to baseline was assessed for anxiety, mood, sleep, and quality of life, as well as changes in cognitive performance on measures of executive function and memory. Safety and tolerability of the study product were also evaluated. Results: Patients reported significant reductions in anxiety symptoms over time. Concurrent improvements in mood, sleep, and relevant quality of life domains were also observed, along with stable or improved performance on all neurocognitive measures. Few side effects were reported, and no serious adverse events occurred. Conclusions: These pilot findings provide initial support for the efficacy and tolerability of the hemp-derived, high-CBD product in patients with moderate-to-severe levels of anxiety. Double-blind, placebo-controlled studies are indicated to obtain robust data regarding efficacy and tolerability of these types of products for anxiety. Full article

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

Cannabis vaping, particularly involving cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), rapidly delivers highly concentrated cannabinoids to the brain, potentially affecting the hippocampus. This study examined differential expression of long noncoding RNAs (lncRNAs) and mRNAs in the hippocampus after acute exposure to vaporized CBD or THC. Male ICR mice were exposed to vaporized CBD or THC (50 mg, n = 5/group), and hippocampal tissues were collected at 1, 3, and 14 days post-exposure. Total RNA sequencing was conducted on day 1 samples, and selected transcripts were validated using qRT-PCR across multiple time points. CBD led to significant up- or downregulation of L3mbtl1, Wnt7a, and Camk2b at day 1. However, Wnt7a showed gradual recovery at days 3 and 14. In the THC group, Grin2a, Gria3, and Golga2 were significantly upregulated, while Drd1, Drd2, Gnal, and Adcy5 were significantly downregulated at day 1. Time-course analysis showed that Drd2 expression returned to baseline by day 14, whereas Adcy5 remained persistently downregulated through days 3 and 14. In the CBD group, NONMMUT069014.2 was upregulated, while NONMMUT033147.2 and NONMMUT072606.2 were downregulated at day 1; notably, NONMMUT072606.2 showed a transient increase at day 3 before returning to baseline. In the THC group, NONMMUT085523.1 and NONMMUT123548.1 were upregulated, whereas NONMMUT019734.2, NONMMUT057101.2, and NONMMUT004928.2 were downregulated, with most showing gradual recovery by day 14. Correlation analysis revealed that THC-responsive lncRNAs—including NONMMUT004928.2, NONMMUT057101.2, and NONMMUT019734.2—were strongly associated with downregulated mRNAs such as Drd2 and Adcy5. These findings highlight cannabinoid-specific hippocampal transcriptomic responses and suggest potential regulatory roles for lncRNA–mRNA interactions in cannabinoid-induced neural changes. Full article

Mental health disorders, particularly depression and anxiety, have become increasingly prevalent among elite athletes, exacerbated by factors such as competitive pressure and the Coronavirus Disease 19 (COVID-19) pandemic. This study analyzes trends in the use of antidepressants, anxiolytics, and cannabinoids (delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD)) among Italian athletes from 2011 to the first half of 2023 (FH2023), referring to anti-doping reports published by the Italian Ministry of Health. Data from 13,079 athletes were examined, with a focus on non-prohibited medications, banned substances, and regulatory impacts, including threshold adjustments for THC since 2013 and the legalization of CBD. The results show fluctuating use of antidepressants/anxiolytics, with peaks in 2021 and the FH2023, coinciding with post-pandemic awareness. Positive THC cases rose following regulatory changes, reflecting socio-cultural trends. Gender disparities emerged, with THC use predominantly among males (e.g., nine males vs. one female in 2013), though female athletes were underrepresented in testing. This study highlights the need for personalized, evidence-based strategies that balance therapeutic efficacy and anti-doping compliance. Clinicians should carefully consider prescribing selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines to address depression and anxiety and should monitor the risks of CBD contamination. Future research should adopt longitudinal, gender-sensitive approaches to refining guidelines and combating stigma in professional sports. Full article

New psychoactive substances (NPSs) are emerging narcotics or psychotropics that pose a public health risk. The most commonly reported NPSs are synthetic cannabinoids and synthetic cathinones. Synthetic cannabinoids mimic the effects of Δ9-tetrahydrocannabinol (Δ9-THC), often with greater potency, while synthetic cathinones act as stimulants, frequently serving as cheaper alternatives to amphetamines, 3,4-methylenedioxymethamphetamine (MDMA) and cocaine. While some synthetic cannabinoids exhibit chirality depending on their synthesis precursors, synthetic cathinones are intrinsically chiral. Biotargets can recognize and differentiate between enantiomers, leading to distinct biological responses (enantioselectivity). Understanding these differences is crucial; therefore, the development of enantioresolution methods to assess the biological and toxicological effects of enantiomer is necessary. This work systematically compiles enantioselectivity studies and enantioresolution methods of synthetic cannabinoids and synthetic cathinones, following PRISMA guidelines. The main aim of this review is to explore the impact of chirality on these NPSs, improving our understanding of their toxicological behavior and evaluating advances in analytical techniques for their enantioseparation. Key examples from both groups are presented. This review highlights the importance of continuing research in this field, as demonstrated by the differing properties of synthetic cannabinoid and synthetic cathinone enantiomers, which are closely linked to variations in biological and toxicological outcomes. Full article

5F-ADB, MDMB-4en-PINACA and ADB-4en-PINACA are three potent indazole-carboxamide synthetic cannabinoids (SCs) that have been widely abused in recent years. However, the pharmacological research on these compounds remains limited, especially in vivo research data. The purpose of the present study was to investigate the pharmacological effects of 5F-ADB, MDMB-4en-PINACA and ADB-4en-PINACA in mice, comparing their in vivo effects with those caused by Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the main psychoactive substance in cannabis. We evaluated the cannabinoid-specific pharmacological effects of 5F-ADB, MDMB-4en-PINACA and ADB-4en-PINACA using the tetrad assay (locomotion inhibition, hypothermia, analgesia and catalepsy). Then we conducted conditioned place preference (CPP) and precipitated withdrawal assay to assess the rewarding effect and physical dependence, with Δ⁹-THC as a positive control. The results showed that all of the three SCs exhibited potential tetrad effects in a dose-dependent manner, with median effective dose (ED₅₀) values ranging from 0.03 to 0.77 mg/kg. In the CPP tests, they all exhibited a significant biphasic effect of conditioned place preference (CPP) and conditioned place aversion (CPA). A significant increase in paw tremors and head twitches was observed in the rimonabant-precipitated withdrawal assay, indicating that the repeated administration of these SCs can lead to potential physical dependence. All effective doses were lower than Δ⁹-THC. These findings strongly suggested that the three SCs exhibited similar but stronger cannabinoid-specific tetrad effects, rewarding effect and physical dependence compared with Δ⁹-THC, indicating their high abuse potential and possible threats to human health. The rank order of abuse potential for these drugs was 5F-ADB > MDMB-4en-PINACA > ADB-4en-PINACA > Δ⁹-THC. Full article

Background/Objectives: The industrial extraction and purification processes of Cannabis sativa L. compounds are critical steps in creating formulations with reliable and reproducible therapeutic and sensorial attributes. Methods: For this study, standardized preparations of chemotype I were chemically analyzed, and the sensory attributes were studied to characterize the extraction and purification processes, ensuring the maximum retention of cannabinoids and minimization of other secondary metabolites. The industrial process used deep-cooled ethanol for selective extraction. Results: Taking into consideration that decarboxylation occurs in the process, the cannabinoid profile composition was preserved from the herbal substance to the herbal preparations, with wiped-film distillation under deep vacuum conditions below 0.2 mbar, as a final purification step. The profiles of the terpenes and cannabinoids in crude and purified Full-spectrum Extract Cannabis Oil (FECO) were analyzed at different stages to evaluate compositional changes that occurred throughout processing. Subjective intensity and acceptance ratings were received for taste, color, overall appearance, smell, and mouthfeel of FECO preparations. Conclusions: According to sensory analysis, purified FECO was more accepted than crude FECO, which had a stronger and more polarizing taste, and received higher ratings for color and overall acceptance. In contrast, a full cannabis extract in the market resulted in lower acceptance due to taste imbalance. The purification process effectively removed non-cannabinoids, improving sensory quality while maintaining therapeutic potency. Terpene markers of the flower were remarkably preserved in SOMAÍ’s preparations’ fingerprint, highlighting a major qualitative profile reproducibility and the opportunity for their previous separation and/or controlled reintroduction. The study underscores the importance of monitoring the extraction and purification processes to optimize the cannabinoid content and sensory characteristics in cannabis preparations. Full article

The 2018 Farm Bill legalized hemp-derived cannabidiol (CBD) products containing less than 0.3% tetrahydrocannabinol (THC) in the United States. This legislative shift catalyzed both public and scientific interest in CBD’s potential health benefits. However, the rapid expansion of the CBD market has considerably outpaced rigorous scientific research, leaving many health claims largely unsubstantiated. While preclinical studies suggest that CBD may exert antitumorigenic effects in colorectal cancer (CRC) by modulating cell proliferation, apoptosis, and inflammation, clinical evidence supporting these effects remains limited. This review critically examines the current evidence on the role of CBD in colorectal tumorigenesis, with particular attention to its molecular mechanisms and interactions with the serotonergic system—a signaling pathway implicated in the development of CRC and possessing potential dual anti- and pro-tumorigenic properties. By influencing the serotonergic system, CBD may confer both protective and potentially deleterious effects during CRC development. This review underscores the need for further research to elucidate the complex mechanisms of CBD in colorectal tumorigenesis and to evaluate its therapeutic potential in clinical settings. Understanding these interactions could pave the way for novel prevention and treatment strategies, optimizing the anticancer efficacy of CBD while mitigating unintended risks. Full article

Delta-9-tetrahydrocannabinol (THC) is a psychoactive element of Cannabis sativa and affects the human cannabinoid system through its receptors, CB1R and CB2R. CB1R was found in several brain areas, including the hippocampal formation (HF), and it is responsible for most THC side effects. We investigated THC’s effects in the HF of female Wistar rats to assess changes in its neurotransmission. Female Wister rats (n = 20) were gonadectomized under anesthesia at 8 weeks old. Afterwards, they received estradiol benzoate (EB) and/or THC. Immunohistochemistry was performed to assess the expression of the cholinergic receptor alpha 7 subunit (CHRNA7), the vesicular acetylcholine transporter (VAChT), the vesicular glutamate transporter (VGLUT), the gamma-aminobutyric acid type A receptor (GABRA), the CB1 receptor, and estradiol receptor alpha (EBα). In the HF, the expression of CHRNA7 was increased by EB and by THC in the Oil groups but decreased by THC in the EB groups. The same is true for VGLUT expression in the DG and hilum and for GABRA expression in the hilum. The expression of VAChT and CB1 is reduced by EB, while the concomitant administration of THC increases it. GAD expression is reduced by EB administration in CA1, CA3, and DG. Our results may help with decision-making regarding the prescription of low doses of THC as a therapeutical approach. Full article

Cannabinoid receptor 1 (CB₁) signalling is critical for weight gain and for milk intake in newborn pups. This is important as in humans, low birth weight increases the risk for attention-deficit hyperactivity disorder (ADHD). Moreover, some children with ADHD also have Tourette syndrome (TS). However, it remains unclear if insufficient CB₁ receptor signalling may promote ADHD/TS-like behaviours. Here, ADHD/TS-like behaviours were studied from postnatal to adulthood by exposing postnatal wild-type CB₁ and Cannabinoid receptor 2 (CB₂) knockout mouse pups to SR141716A (rimonabant), a CB₁ receptor antagonist/inverse agonist. Postnatal disruption of the cannabinoid system by SR141716A induced vocal-like tics and learning deficits in male mice, accompanied by excessive vocalisation, hyperactivity, motor-like tics and/or high-risk behaviour in adults. In CB₁ knockouts, rearing and risky behaviours increased in females. In CB₂ knockouts, vocal-like tics did not develop, and males were hyperactive with learning deficits. Importantly, females were hyperactive but showed no vocal-like tics. The appearance of vocal-like tics depends on disrupted CB₁ receptor signalling and on functional CB₂ receptors after birth. Inhibition of CB₁ receptor signalling together with CB₂ receptor stimulation underlie ADHD/TS-like behaviours in males. This study suggests that the ADHD/TS phenotype may be a single clinical entity resulting from incorrect cannabinoid signalling after birth. Full article

Jasmonates have emerged as a prominent elicitor for enhancing trichome development and cannabinoid production in Cannabis sativa L. (cannabis). These glandular trichomes synthesize and store important cannabinoids, including tetrahydrocannabinol (THC) and cannabidiol (CBD), which determine the yield, potency, and quality of cannabis flowers. Methyl jasmonate (MeJA) acts through the COI1–JAZ–MYC signaling pathway to upregulate genes associated with trichome initiation and cannabinoid precursor formation. Evidence suggests that moderate MeJA concentrations (typically 50–100 µM) can effectively boost trichome density, elevate hexanoyl-CoA availability, and modestly enhance key biosynthetic enzyme activities, ultimately increasing THC and CBD content. However, higher methyl jasmonate doses can amplify these benefits, yet pose a risk of excessive vegetative stunting, highlighting the crucial trade-off between enhancing cannabinoid potency and maintaining overall biomass yield. Interaction with hormones like gibberellins, salicylic acid, and ethylene further shapes the plant’s stress responses and secondary metabolism. Application in controlled environments, such as greenhouses or vertical farms, shows promise for enhancing resin production while minimizing biomass loss. In outdoor conditions, the application may offer additional defense benefits against pests and pathogens. These responses can vary depending on the cultivar, underscoring the importance of cultivar-specific optimization. As demand for high-cannabinoid cannabis products continues to grow and agrochemical options remain limited, leveraging MeJA treatments offers a practical, non-genetically modified approach to optimize yield, quality, and resilience in cannabis cultivation. Full article

The increasing environmental and health concerns associated with synthetic pesticides underscore the need for sustainable alternatives in pest management. This study investigates the chemotactic responses of five nematode species—Heterorhabditis bacteriophora, Steinernema carpocapsae, Steinernema feltiae, Phasmarhabditis papillosa, and Oscheius myriophilus—to three major cannabinoids from Cannabis sativa: Δ⁹-tetrahydrocannabinol (THC), cannabigerol (CBG), and cannabidiol (CBD). Using a standardized chemotaxis assay, we quantified infective juvenile movement and calculated Chemotaxis Index (CI) values across varying cannabinoid concentrations. Our results revealed strong species-specific and dose-dependent responses. THC and CBG elicited significant attractant effects in P. papillosa, S. feltiae, and H. bacteriophora, with CI values ≥ 0.2, indicating their potential as behavioral modulators. In contrast, CBD had weaker or repellent effects, particularly at higher concentrations. O. myriophilus exhibited no consistent response, underscoring species-specific variation in chemosensory sensitivity. These findings demonstrate the potential utility of cannabinoids, especially THC and CBG, as biocompatible cues to enhance the efficacy of nematode-based biological control agents in integrated pest management (IPM). Further field-based studies are recommended to validate these results under realistic agricultural conditions. Full article

Cannabis remains the most widely used illicit drug worldwide, identifying it is a routine procedure in forensic toxicology. Due to its widespread use, there is a need for analytical methods that can detect it in biological samples. Hair is of particular interest in forensic toxicology as it is the only biological sample that enables retrospective analysis of consumption. In addition, collecting hair is non-invasive, and the specimens can be stored at room temperature. However, the sample preparation process for hair is tedious and multi-step. To address this issue, this study introduces a novel approach to preparing hair samples for analysis, based on air-assisted liquid–liquid microextraction (AALLME). This technique is a modification of dispersive liquid–liquid microextraction (DLLME), which eliminates the need for dispersants and chlorinated organic solvents as extractants. Both techniques offer sustainable alternatives to conventional liquid–liquid extraction (LLE) and solid-phase extraction (SPE), making them of interest in forensic toxicology. This study is the first to report the application of AALLME to the hair matrix. A mixture of cyclohexane and ethyl acetate (9:1) was used as the extractant solvent. Gas chromatography–mass spectrometry (GC–MS) was then used to determine and quantify THC. The method was validated according to FDA guidelines and demonstrated good linearity within the 0.01–4 ng/mg range. The limits of detection (LOD) and quantification (LOQ) were 0.008 and 0.01 ng/mg, respectively. Finally, the applicability of the method was evaluated by analyzing hair samples received by the Forensic Toxicology Service. Full article