“Pain is one of the most pervasive health problems associated with a negative impact on thinking, mood, psychological, and social communication.
The medicinal plants and their derived compounds have recently attracted great interest as potential candidates for defeating pain because of their worldwide safety, availability, and affordability.
This review was constructed to summarize all in vitro and in vivo studies and clinical trials regarding plant-derived compounds’ analgesic and antinociceptive effects. Further, we focus on structural aspects, molecular mechanisms, and pharmacological effects. A literature survey was performed in “PubMed,” “Science Direct,” and “Google Scholar,” using the keywords “Pain, Analgesic activity, Flavonoids, Phenolics, Medicinal plants, Volatile oils, Tannins, Saponins, Alkaloids” to assess the activities of each compound.
The main natural compounds studied were flavonoids, alkaloids, phenolic acids, lignans, anthraquinones, and volatile oils. Different in vitro studies utilized nucleus pulposus cells, VK2/E6E7, End1/E6E7, and LPS-stimulated RAW264.7 cells to assess analgesic effects. The frequently defined animal models of analgesic activity included acetic acid-induced abdominal constrictions, hot-plate test, tail-flick test, formalin test, complete Freund’s adjuvant-induced pain, and hind paw incisional surgery.
For the natural compounds described, the opioids, serotonergic, and cannabinoid receptors appeared to be the most promising targets for pain management. This review suggested a wealthy resource of natural compounds as analgesic and antinociceptive candidates for pharmacists and drug researchers to launch a new drug with promising efficacy and safety.”
“Background: Lung cancer is one of the most prevalent and lethal cancers worldwide, with limited therapeutic options in advanced stages. Cannabinoids have recently attracted attention as potential anticancer agents; however, cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, has emerged as the most promising candidate. Unlike Δ9-tetrahydrocannabinol (THC), CBD lacks psychoactive properties, is generally well tolerated, and demonstrates a favorable safety profile. Moreover, CBD influences multiple cancer-relevant pathways-including apoptosis, epithelial-to-mesenchymal transition (EMT), and immune modulation-that are particularly relevant to non-small cell lung cancer (NSCLC). These features provide a strong rationale for focusing on CBD in lung cancer therapy.
Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar, using defined keywords such as “CBD,” “lung cancer,” and “non-small cell lung cancer.” Studies from 2007 to 2025 were screened following PRISMA guidelines, and 19 studies met the inclusion criteria.
Results: Nineteen studies met the inclusion criteria, comprising 13 in vitro studies, 4 in vivo animal studies, and 2 clinical reports. Across these studies, CBD was administered at concentrations ranging from low micromolar levels (1-10 µM) in cell-based experiments to oral doses of 200-600 mg/day in human cases. Mechanistically, CBD induced apoptosis through pathways such as PPAR-γ activation, mitochondrial dysfunction, and oxidative stress. It inhibited epithelial-to-mesenchymal transition (EMT), downregulated invasive markers, and modulated the tumor microenvironment by enhancing CD8 + T cell and NK cell activity. Furthermore, CBD showed synergistic effects with conventional therapies (e.g., cisplatin, radiotherapy) by increasing drug uptake and overcoming resistance.
Conclusions: CBD holds promise as an adjunct in lung cancer therapy, addressing key cancer hallmarks such as tumor growth, metastasis, and treatment resistance. While preclinical evidence is robust, clinical trials remain limited. Future research should focus on optimizing dosing regimens, evaluating long-term safety, and validating these findings in large-scale human studies.”
“Cannabidiol (CBD) demonstrates strong preclinical activity against lung cancer, targeting multiple hallmarks of cancer including apoptosis induction, suppression of EMT and metastasis, modulation of immune responses, and sensitization to chemotherapy and radiotherapy.”
“Non-psychotropic Cannabis sativa L. chemotypes have gained increasing interest due to their diverse profiles of bioactive compounds. While cannabinoids such as cannabidiol (CBD), cannabigerol (CBG), are known for their biological effects, the role of other cannabinoids such cannabichromene (CBC) remains underexplored as for chemotype V, which lacks in cannabinoids but is characterized by other minor phytochemicals.
This study aimed to evaluate the individual and combined contributions of cannabinoids and non-cannabinoid phenolics to the antioxidant, antimicrobial, and anti-inflammatory properties of extracts derived from four C. sativa chemotypes, including a cannabinoid-free variant as a comparison.
Ethanolic extracts were obtained from four hemp chemotypes: CBD-rich (CS1), CBG-rich (CS2), CBC-rich (CS3), and cannabinoid-free (CS4). Phytochemical profiling was conducted using UHPLC-HRMS. Antioxidant properties were assessed via DPPH, ABTS, and FRAP assays. Antimicrobial activity was tested against Gram-positive and Gram-negative bacteria through MIC, MBC, and time-kill assays. Anti-inflammatory activity was evaluated in LPS-stimulated RAW 264.7 macrophages via gene expression analysis of pro- and anti-inflammatory mediators (IL1b, IL6, Cox2, IL10, IL1Ra).
Phytochemical analysis confirmed the chemotype-specific profiles, with CS3 showing the highest levels of canniprene and the early discovered 5-methoxy-dihydrodenbinobin. Antioxidant assays revealed that cannabinoids were the main contributors to radical scavenging capacity, though CS3 exhibited additional ferric ion reducing power likely due to non-cannabinoid phenolics. Antibacterial activity was confined to Gram-positive bacteria, where CS1 showed the highest efficacy, and CS4 showed no activity, highlighting the critical role of cannabinoids. All extracts reduced LPS-induced Il1b, Il6, and Cox2 gene expression, but only cannabinoid-rich extracts upregulated the anti-inflammatory cytokines IL10 and IL1Ra, indicating a cannabinoid-dependent effect.
Both cannabinoids and non-cannabinoid phenolics contribute to the biological activity of Cannabis sativa extracts, with cannabinoids playing a central role in antimicrobial responses and stronger anti-inflammatory effect as a pure cannabinoid or as an extract. From this point of view, the cannabinoid-free chemotype V could be a valuable functional control for isolating the effects of cannabinoids, reinforcing the need for integrative analyses in evaluating the therapeutic potential of cannabis-derived formulations.”
“In this study, we provided a phytochemical characterization and biological activity of non-psychoactive Cannabis sativa L. extracts from III, IV, V and the emerging CBC chemotype. The phytochemical profile confirmed the distinct percentage of cannabinoid and non-cannabinoid composition of each chemotype, with the CS3 sample exhibiting the highest levels of canniprene and 5-methoxy-dihydrodenbinobin. Antioxidant assays demonstrated that cannabinoids significantly contribute to the radical scavenging capacity of the extracts, with an additional support from non-cannabinoid phenolics as testified by the CS4. Antimicrobial assays showed that only the cannabinoid-containing extracts exhibited potent bactericidal activity against Gram-positive pathogens, including drug-resistant MRSA, while the cannabinoid-free extract lacked such activity. Furthermore, all extracts, including the cannabinoid-free one, were able to suppress LPS-induced pro-inflammatory gene expression in macrophages. However, only the cannabinoid-rich extracts promoted the anti-inflammatory cytokines IL-10 and IL-1Ra, underscoring a cannabinoid-dependent immunomodulatory effect.
Taken together, these results highlight the importance of cannabinoid in the biological properties of Cannabis sativa with a contribution apported by non-cannabinoid phenolic compounds. Moreover, the anti-inflammatory, antimicrobial, and antioxidant effects observed with both pure cannabinoids and cannabinoid-containing extracts support their potential use in topical formulation for the treatment of chronic inflammatory skin disorders, such as atopic dermatitis and psoriasis. These conditions are often exacerbated by skin dysbiosis and colonization by Gram-positive bacteria like Staphylococcus aureus, which contribute to skin barrier dysfunction and amplify immune dysregulation (Zhang et al. 2025). Therefore, while the cannabinoid-free chemotype V serves as a valuable control for dissecting the specific contributions of individual cannabinoids within CS extracts, our findings pave the way for future investigations into the therapeutic potential of selected cannabis-derived products—particularly in the context of antimicrobial resistance and inflammatory diseases associated with dysbiosis.”
“While chronic pain is challenging to manage, it always co-exists with depression. Currently, chronic pain and depression are usually treated separately with distinct approaches, yet effectiveness remains elusive. Consequently, the development of integrated therapeutic strategies for pain while addressing depression is a high public health priority and unmet need that affects millions of people.
This study aims to determine if the combination of the two phytocannabinoids Beta-Caryophyllene (BCP) and cannabidiol (CBD) is effective for chronic pain while simultaneously showing antidepressant effects.
We used a chronic inflammatory pain model (Complete Freund’s Adjuvant, CFA) and a battery of pain and depression-like behavior tests in mice. Proteomics and immunohistochemistry (IHC) were used to explore the potential mechanisms of the effect of the combination on pain and depression.
We found that mice treated with the CBD and BPC combination produced a synergistic pain-relieving effect in the chronic inflammatory pain model and exhibited antidepressant properties.
Our IHC data also show that the CBD and BCP combination significantly reduced the neuroinflammation produced by CFA, and the proteomics showed downregulation of selected proteins involved in inflammation by the combination, compared to the individual effects of CBD and BCP.
In conclusion, our current findings show that, in the CFA pain model, the combination of CBD and BCP produces a synergistic pain-relief effect while also having antidepressant properties. Additionally, our data show that the anti-inflammatory action of this combination may explain its beneficial effects on pain and depression. Therefore, our data suggest this combination as a potentially effective treatment for chronic pain and related depression.”
“In conclusion, our current findings show that, in the CFA pain model, the combination of CBD and BCP produces a synergistic analgesic effect while also having antidepressant properties. Additionally, our data show that the anti-inflammatory action of this combination may explain its beneficial effects on pain and depression. Therefore, our data suggest this combination as a potentially effective treatment for the co-occurrence of chronic pain and depression.”
“Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder that typically emerges in late adolescence or early adulthood. In rats, administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM) on gestational day (GD) 17 induces several features resembling those observed in SCZ patients.
Preclinical and clinical studies suggest that cannabidiol (CBD) has antipsychotic-like effects.
Here, we evaluated whether acute CBD treatment attenuates behavioral deficits and the enhanced dopamine (DA) system activity in the ventral tegmental area (VTA) of adult male and female MAM rats.
Pregnant rats received saline or MAM (20 mg/kg) on GD17. In adulthood, offspring were tested in the elevated plus-maze (EPM), novel object recognition (NOR) test, and locomotor responses to the NMDA receptor antagonist MK-801. The in vivo electrophysiological activity of VTA DA neurons was also recorded. CBD (60 mg/kg) was administered 1 h before each behavioral test and electrophysiological recording.
Male and female MAM rats exhibited anxiety-like behavior in the EPM, which was not reversed by CBD. In the NOR test, CBD reversed memory impairment in male MAM rats, whereas female MAM rats showed no deficits. Neither male nor female MAM rats exhibited increased locomotor responses to MK-801, and CBD did not affect this behavior. Both male and female MAM rats showed increased VTA DA neuron population activity, which was reversed by CBD in both sexes.
Our findings indicate that CBD attenuates cognitive deficits and enhanced DA system activity in the MAM model, supporting the hypothesis that CBD produces antipsychotic-like effects.”
“Cannabidiol (CBD) is a non-psychotomimetic compound of the Cannabis sativa plant and has demonstrated antipsychotic-like properties in clinical (Leweke et al., 2012, Leweke et al., 2021; McGuire et al., 2018; Zuardi et al., 2006) and preclinical studies employing different animal models of SCZ (Gomes et al., 2015a, Gomes et al., 2015b; Long et al., 2012; Osborne et al., 2019; Osborne et al., 2017b; Rodrigues da Silva et al., 2020), including the MAM model (Stark et al., 2019, Stark et al., 2020; Thériault et al., 2021).”
“Background: Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality, yet effective therapeutic options remain limited. Preclinical data suggest that modulation of the hepatic endocannabinoid system, particularly via cannabidiol (CBD), may reduce alcohol-induced liver injury. Due to CBD’s limited clinical use, we sought to evaluate the association between cannabis use and ALD risk among patients with alcohol use disorder (AUD).
Methods: Using the TriNetX US Collaborative Network, we identified adult patients with AUD between 2010 and 2022. Three cohorts were constructed: cannabis use disorder (CUD), cannabis users without cannabis abuse or dependence (CU) and non-cannabis users (non-CU). Outcomes included ALD, hepatic decompensation and composite all-cause mortality over 3 years. Incidence and hazard ratios were calculated using Kaplan-Meier analysis and Cox regression.
Results: After matching, 33 114 patients were included in each of the CUD and non-CU groups. Compared to non-CU, CUD was associated with a lower risk of ALD (HR 0.60, 95% CI 0.53-0.67; p < 0.001), hepatic decompensation (HR 0.83, 95% CI 0.73-0.95; p =0.005) and all-cause mortality (HR 0.86, 95% CI 0.80-0.94; p < 0.001) among individuals with AUD. Although CU was associated with lower risks of ALD, its risks of hepatic decompensation and all-cause mortality were similar to those of the non-CU cohort with AUD.
Conclusion: In this propensity-matched cohort study of patients with AUD, cannabis use was associated with a reduced risk of ALD, with the greatest risk reduction seen in patients with CUD compared to CU and non-CU. Our findings suggest that modulation of cannabinoid receptors may offer a new target for the development of pharmacological therapies for ALD.”
“Intestinal fibrosis is a common and serious complication of inflammatory bowel diseases, often leading to strictures that require endoscopic or surgical intervention.
Despite advances in anti-inflammatory therapies, effective antifibrotic treatments is currently not available. Therefore, new treatment methods for intestinal fibrosis are sought with the endocannabinoid system (ECS) as a potential therapeutic target.
Cannabinoid receptors 1 and 2 (CB1/2) are classic receptors of the ES involved in the modulation of intestinal inflammation and permeability of the mucosal barrier. Experimental evidence from liver and lung models suggests that CB1 receptor activation promotes fibrosis through enhancement of the TGF-β/Smad pathway, interaction with the renin-angiotensin system, and upregulation of profibrotic markers, such as collagen and α-SMA.
In contrast, CB2 receptor signaling appears to exert protective effects by limiting inflammation, fibroblast activation, and extracellular matrix deposition. Recent findings also suggest cross-talk between cannabinoid signaling and platelet-derived growth factor pathways, which are key drivers of myofibroblast proliferation and fibrogenesis. Although these mechanisms are well-established in hepatic, pulmonary and skin fibrosis, data from small and large intestine is scarce. However, direct evidence in intestinal fibrosis is scarce, representing a major knowledge gap.
Elucidating ECS mechanisms in the alimentary tract could enable targeted antifibrotic strategies, complement current therapies, and reduce progression to fibrostenotic disease.”
“The ECS is widespread in the human body, which proves its many functions in the body. Due to its presence in the digestive system and immune cells, it can influence the modulation of inflammation and the process of fibrosis in IBD. Numerous studies, both in animal models, cell cultures and in human tissue, show that the activation or inhibition of individual elements of the ECS can affect the process of intestinal fibrosis. Hence, the ECS may be a potential target aiming at the fibrosis reduction.”
“Background: Cholangiocarcinoma (CCA) incidence in Northeastern Thailand is very high and a major cause of mortality. CCA patients typically have a poor prognosis and short-term survival rate due to late-stage diagnosis. Thailand is the first Southeast Asian country to approve medicinal cannabis treatment, especially for palliative care with advanced cancer patients.
Methods: A retrospective cohort study compared survival among 491 newly diagnosed advanced CCA patients between September 2019 and June 2021. Of these, 404 received standard palliative pain management (ST), and 87 received medicinal cannabis treatment (CT). Patients were enrolled from four tertiary hospitals and two secondary hospitals in five provinces of Northeast Thailand. Cumulative survival was calculated by the Kaplan-Meier method, and independent prognostic factors were analyzed using Cox regression.
Results: For ST patients, follow-up time was 790 person-months, with a mortality rate of 48.35/100 person-months. For CT patients, follow-up time was 476 person-months, with a mortality rate of 10.9/100 person-months. The median survival time after registration at a palliative clinic was 0.83 months (95% CI: 0.71-0.95) for ST and 5.66 months (95% CI: 1.94-9.38) for CT. Multivariate analysis showed CT was significantly associated with prolonged survival (HRadj = 0.28; 95% CI: 0.20-0.37; p < 0.001).
Conclusions: The medical cannabis increased overall survival rates among CCA patients. In this retrospective cohort, Medicinal cannabis treatment was associated with more prolonged survival among advanced CCA patients in Northeastern Thailand. While this association remained significant after multivariable adjustment, unmeasured or residual confounding factors may have influenced the observed outcomes. Although the association remained significant after adjustment, unmeasured or residual confounders may have influenced outcomes. Further prospective studies are warranted to confirm these findings and explore potential mechanisms.”
“Introduction: Cannabis-based medicine (CBM) is recommended for the treatment of tics in otherwise treatment-resistant adult patients with Tourette syndrome (TS). However, evidence in children with TS is very limited. Long-term effects of CBM in this population are unknown.
Case presentations: We present two cases of long-term follow-up over six and five years, respectively, in male adolescents with TS who were administered CBM starting at the age of eight and 12 years, respectively. In one patient CBM treatment was initiated with pure tetrahydrocannabinol (THC) and was later changed to current treatment with an oral THC-dominant cannabis extract (THC:cannabidiol (CBD)=25:<0.5) with a daily dose of 0.5-0.6 mL (corresponding to 12.5-15 mg THC/day). The other patient was from the beginning up to now medicated by his parents, who are physicians, with vaporized THC-dominant (24%) medicinal cannabis flowers with a dose of 0.2 g between once to thrice per day (corresponding to 48-144 mg THC/day). While in one patient, there was a moderate dose increase over the years, in the other patient dosages were adjusted individually depending on tic severity. In both patients, CBM treatment resulted in continued benefit with significant improvement of tics and psychiatric comorbidities without severe adverse effects. Academic performance of both adolescents was excellent. Neurocognitive assessments demonstrated average results in the domain of working memory and average to above average results in the domain of processing speed.
Conclusions: We present two cases of minors with TS who started CBM treatment at the age of eight and 12 years, respectively, and continued treatment for five to six years resulting in clinically relevant symptom improvement without any severe adverse effects or negative impact on cognitive and academic performance.”
“In summary, we present two cases of minors with TS who started CBM treatment before puberty at the age of eight and 12 years, respectively, and continued treatment for five to six years resulting in sustained clinically relevant symptom improvement without severe adverse effects or negative impact on cognitive and academic performance. Although generalizability from our case reports of two single patients is limited, we suggest to take treatment with THC-containing drugs into consideration in severely affected and otherwise treatment refractory children and adolescents before thinking of surgical treatment using deep brain stimulation.”
“This study reviews the anti-inflammatory potential of cannabidiol (CBD) in the management of type 1 diabetes (T1D).
A comprehensive search was conducted across PubMed, Scopus, and ScienceDirect databases using the terms “type 1 diabetes”, “cannabidiol”, “anti-inflammatory effect”, and “CBD”. Articles published between 2005 and 2025 were screened, and studies involving animal models that examined CBD as a therapeutic intervention for T1D and reported on its anti-inflammatory effects were included. Of the 62 retrieved articles, only 6 met the predefined inclusion criteria.
Although limited in number, the available studies show promising outcomes. CBD demonstrates potential as an adjuvant therapy for T1D due to its immunomodulatory and anti-inflammatory actions. Nonetheless, further research is required to establish safe and effective clinical application protocols.”
