The Potential of Cannabidiol for the Treatment of Psychosis: Endocannabinoid Regulation of Serotonergic Neurotransmission via Serotonin 5-HT1A/2A Receptors

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“Cannabis, widely used for both medical and non-medical purposes, primarily contains Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD).

This review aims to clarify how the molecular and receptor-level mechanisms of CBD, compared with Δ9-THC, shape its distinct therapeutic profile and low liability for addiction, thereby informing the safer clinical application of CBD-containing interventions to schizophrenia.

CBD exerts sedative and therapeutic effects, including in treatment-resistant epilepsy, and acts in part via CB1 and CB2 receptors that also mediate Δ9-THC actions. While Δ9-THC activates these receptors as an agonist, triggering Gi-coupled signaling cascades such as MAPK pathways and suppressing presynaptic monoamine release, CBD functions as a non-competitive negative allosteric CB1 modulator and non-competitive antagonist of Δ9-THC. These distinct intracellular signaling mechanisms are considered to underlie the markedly different pharmacological profiles and abuse liabilities of Δ9-THC and CBD.

CBD also engages multiple CNS targets beyond CB1 and CB2, including GPR55, TRPV1 and ENT1, which are implicated in anticonvulsant, anti-inflammatory, analgesic and neuroprotective actions. Although GPR55 pharmacology remains controversial and Δ9-THC shows inconsistent activity at this receptor, converging evidence indicates that CBD can antagonize CB1/CB2 and modulate atypical cannabinoid-sensitive proteins. Excessive activation of certain serotonin receptors, including 5-HT1A/2A, are thought to underlie some symptoms of psychosis.

These diverse molecular actions are thought to underlie CBD’s broad therapeutic potential across seizures and other CNS disorders, providing a mechanistic rationale for exploring CBD as a treatment option for psychosis in schizophrenia and stimulant-induced psychotic states.”

https://pubmed.ncbi.nlm.nih.gov/42658346/

https://link.springer.com/article/10.1007/s11064-026-04860-1

Cannabis and Cannabinoids: The Medical Potential of Cannabidiol in Mental and Neurological Disorders

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“Background/Objectives: Mental and neurological disorders contribute substantially to the global burden of disease, affecting people of all ages and backgrounds. As their prevalence increases with age, their overall impact is expected to grow in the coming decades. Although psychological and pharmacological treatments are available, many patients fail to achieve satisfactory outcomes, underscoring the need for improved therapeutic strategies. Cannabis sativa L. has been used for medicinal purposes for centuries, and cannabidiol (CBD) has attracted increasing attention because of its broad therapeutic potential. Scientific studies indicate that CBD may be beneficial in several mental and neurological disorders. 

Methods: A comprehensive literature search was conducted to identify articles investigating the therapeutic potential of CBD and cannabis in selected disorders. 

Results: Evidence from preclinical and clinical studies, together with findings from the broader cannabis literature, indicates that CBD may offer therapeutic benefits in a range of conditions, including Alzheimer’s and Parkinson’s disease, anxiety disorders, and epilepsy. Emerging data also support its potential use as an adjunctive therapy for COVID-19. Current research has improved understanding of the neurobiological mechanisms underlying these disorders and the molecular pathways through which CBD may exert its effects. CBD has demonstrated good tolerability, with predominantly mild adverse effects and a favorable safety profile. 

Conclusions: Despite promising findings, many available studies are preclinical or involve small patient cohorts, and the mechanisms underlying the therapeutic effects of CBD remain incompletely understood. Further well-designed, randomized, controlled, multicenter trials are needed to establish the efficacy and safety of CBD and support its integration into clinical practice.”

https://pubmed.ncbi.nlm.nih.gov/42653735

“The Cannabis plant has been used for medicinal purposes for thousands of years, with therapeutic indications mentioned in the medical texts of ancient civilizations.”

“These findings support the safety and clinical applicability of CBD and further suggest its potential as a therapeutic agent.”

“CBD is a promising therapeutic candidate for several mental and neurological disorders.”,

https://www.mdpi.com/1424-8247/19/8/1238


Cannabigerol improves MK-801-induced long-term recognition memory deficit in male rats through cortical TrkB-R signaling independently of changes in BDNF.

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“Interest in the therapeutic potential of cannabigerol (CBG), a non-psychotomimetic cannabinoid derived from Cannabis sativa, has increased recently. However, preclinical studies examining its effects on cognitive impairment, a core symptom domain of schizophrenia, remain limited.

Based on the N-methyl-d-aspartate receptor (NMDA-R) hypofunction hypothesis of schizophrenia, MK-801, a potent NMDA-R antagonist, is widely used as a pharmacological model of schizophrenia that replicates the cognitive impairments observed in patients.

This study investigated whether repeated systemic administration of CBG (10 mg/kg/i.p.) could reverse long-term recognition memory (LTM) impairment induced by a single dose of MK-801 (0.1 mg/kg/i.p.) in male rats, using the novel object recognition paradigm. Additionally, we evaluated whether these effects were associated with changes in BDNF/TrkB receptor (TrkB-R) signaling.

ELISA and quantitative real-time PCR analyses were performed to evaluate BDNF protein levels and BDNF and TrkB-R mRNA expression in the hippocampus and medial prefrontal cortex (mPFC).

MK-801 significantly impaired LTM compared with control group, whereas co-administration of CBG prevented this deficit.

MK-801-induced memory impairment was associated with reduced hippocampal and cortical BDNF protein levels, without changes in BDNF or TrkB-R mRNA expression. CBG and MK-801 combined treatment did not restore BDNF mRNA expression and protein levels although it significantly increased TrkB-R mRNA expression in the mPFC.

These results suggest that activation of TrkB-R signaling through a BDNF-independent mechanism may contribute to the preservation of LTM by CBG.

Our results provide relevant evidence supporting the therapeutic potential of CBG for cognitive impairments associated with schizophrenia.”

https://pubmed.ncbi.nlm.nih.gov/42648374

“Results support CBG therapeutic potential for cognitive impairments in patients with schizophrenia.”

https://www.sciencedirect.com/science/article/abs/pii/S0091305726001152?via%3Dihub

Cannabis sativa-mediated biosynthesis of copper-zinc-selenium nanocomposites: phytochemical profiling, antioxidant properties, and molecular docking insights

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“Background: Nanotechnology is an emerging field widely applied across various disciplines, including medicine, to develop cost-effective and innovative therapies by delivering therapeutic compounds to targeted sites. The integration of multiple metals can yield synergistic multifunctional properties.

Aims: This study focuses on the green synthesis of copper-zinc-selenium (Cu-Zn-Se) nanocomposite, which is a straightforward and reliable method compared to chemical, physical, and mechanical techniques. Cannabis sativa, a dioecious plant from the Cannabinaceae family, has garnered significant attention due to its pharmacological properties and global cultivation.

Methods: In this research, Phytochemical analysis of extracts was carried out using Gas chromatography-mass spectrometry analysis (GC-MS). After that, a trimetallic copper-zinc-selenium (Cu-Zn-Se) nanocomposite was successfully synthesized using the floral biomass extract of Cannabis sativa and characterized by using UV-Vis spectral analysis, Scanning Electron Microscopy (SEM), and FTIR spectroscopy. Further, the potential applications of the synthesized trimetallic nanoparticles were evaluated by assessing their antioxidant activities through DPPH Free Radical Scavenging Activity, Hydrogen Peroxide Scavenging Assay, Ferric Reducing Power Assay, and Phosphomolybdate Antioxidant Activity. In addition, Molecular docking studies were used to investigate the drug target interactions for antioxidant behaviour.

Results: The UV-Vis spectrum displayed overlapping bands at 230, 290, and 327 nm, confirming the successful synthesis of the nanocomposite. FTIR analysis revealed peaks corresponding to various functional groups, notably a band at 1621.37 cm – 1 indicating C = O carbonyl stretching from amides, and a band at 1427.91 cm – 1 associated with C = C stretching (in-ring) from aromatic structures. SEM imaging showed spherical particles with an average size of 40 to 60 nm. A dose-dependent increase in antioxidant activity for the Cu-Zn-Se nanocomposite, which surpassed that of the plant extract in all assays studied and was comparable to the standard ascorbic acid. Molecular docking studies supported the experimental findings by showing that the Cu-Zn-Se nanocomposite binds stably to the antioxidant target protein, suggesting enhanced antioxidant activity.

Conclusion: This study is among the first to report the green synthesis of a Cannabis sativa-mediated Cu-Zn-Se trimetallic nanocomposite, highlighting its strong antioxidant potential and interaction pathways at the molecular level. These findings contribute novel insights into sustainable nanomaterial development and underscore the biomedical promise of phytogenic trimetallic nanocomposites as potent antioxidant agent.”

https://pubmed.ncbi.nlm.nih.gov/41131581

“The present study successfully demonstrates the synthesis, characterization, and evaluation of the antioxidant activity of the Cu-Zn-Se nanocomposite using Cannabis sativa floral biomass extract. The GC-MS analysis effectively identified the presence of key cannabinoids (THC, CBD, and CBN) and terpenes in the cannabis extract. These compounds contribute to the overall effects and therapeutic potential of the cannabis sample.”

“These results signify the immense bioactive potential of the green synthesized Cu-Zn-Se nanocomposite using Cannabis sativa extract, which can find applications in the pharmaceutical and industrial fields.”

https://link.springer.com/article/10.1186/s42238-025-00320-9

Mechanical, Electrical, and Thermal Performance of Hemp Fiber-Reinforced Elium Biocomposites Modified with Activated Carbon Nanoparticles: Experiment and Simulation

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“This research examines the influence of various concentrations (0%, 1%, 1.4% and 1.8% by weight) of activated carbon nanoparticles (AC NPs) on the performance of Elium biocomposites reinforced with hemp fibers.

Unidirectional [0°/0°] laminates with 20% fiber volume fraction were fabricated via hand layup using two layers of 150 GSM hemp fabric and compression molded to achieve 0.9 mm cured thickness.

Quasi-static tensile testing (ASTM D3039, 2 mm/min, 100 mm gauge length) revealed a pronounced non-monotonic relationship between AC NPs loading and mechanical properties, with optimal performance at 1.0 wt.% fillers and catastrophic degradation at 1.8 wt.%. AC NPs filled composites, which were then characterized by their electrical and thermal behavior.

Electrically, it also achieved minimum resistivity (1.62 Ω·m) and maximum conductivity (0.62 S·m-1), in contrast to the elevated resistance (42.5 kΩ) found in samples with a higher filler content.

Thermal analysis showed a slight effect on the degradation of the onset temperature (300 °C) and a higher charring after addition of AC NP. Finite element analysis (FEA) provided a corroboration for these experimental findings, with simulations verification.

Microscopy revealed cohesive fractures in the 1.0 wt.% composite whereas voids and brittle failure were evident in samples with higher loading. Hence, the concentration of 1.0 wt.% AC NP offers the best trade off of mechanical, electrical, and thermal properties.”

https://pubmed.ncbi.nlm.nih.gov/41516850

https://www.mdpi.com/2073-4360/18/1/66


In Situ Synthesis of ZnO Nanoparticles Using Soy Protein Isolate for Sustainable and Multifunctional Finishing of Hemp Fabrics

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“This study presents an environmentally sustainable finishing approach for hemp fabrics by combining soy protein isolate (SPI) pretreatment with an in situ infrared (IR)-assisted synthesis of zinc oxide nanoparticles (ZnO NPs).

IR heating was employed to reduce energy consumption while promoting efficient nanoparticle formation compared to conventional thermal processing, while SPI acted as a bio-based stabilizer to enable uniform ZnO NP distribution on the fabric surface. Transmission electron microscopy revealed predominantly spherical to polyhedral ZnO NPs with minimal agglomeration, and X-ray diffraction confirmed their characteristic wurtzite crystalline structure. Scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy mapping further verified the homogeneous deposition of ZnO NPs on hemp fibers.

The treated fabrics exhibited multifunctional performance, showing significantly enhanced ultraviolet (UV) protection with a UV protection factor (UPF) of 50+ compared with untreated hemp.

Antibacterial activity against Staphylococcus aureus and Escherichia coli was confirmed by the AATCC TM147 test, while a quantitative AATCC TM100 assessment demonstrated an excellent antibacterial efficiency of 99.99% bacterial reduction against S. aureus. Additionally, the incorporation of 2 wt% SPI significantly improved fabric hydrophilicity and wettability.

Overall, this work demonstrates a green and effective strategy for producing antibacterial and UV-protective hemp textiles.”

https://pubmed.ncbi.nlm.nih.gov/41516899

“This study successfully developed a novel antibacterial finishing process for hemp fabrics by combining SPI pretreatment with an IR-assisted in situ synthesis of ZnO NPs.”

“Consequently, this work provides a generalized and scalable framework for the development of eco-friendly antibacterial and UV-protective textile finishes.”

https://www.mdpi.com/2073-4360/18/1/116


Cannabidiol-Loaded Mucoadhesive PLGA Nanosphere-Chitosan Hydrogel Patch for Oral Therapeutic Applications

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“Cannabidiol (CBD), the primary bioactive element of cannabis, has shown promise in alleviating pain and inflammation, although mechanisms in periodontal inflammation are not fully understood.

To improve its limited solubility and mucosal permeability, the developed chitosan-based mucoadhesive hydrogel incorporating CBD-loaded PLGA nanospheres (CPN hydrogel) was characterized by FT-IR, SEM, particle size, rheological, swelling, and diffusion analyses, followed by biological evaluations, including wound-healing and RT-qPCR-based anti-inflammatory assays.

The improved CPN hydrogel had a homogeneous shape, better viscoelastic behavior, and sustained drug release. Over 90% of CBD was released within 96 h, and Franz cell experiments showed improved permeability (124.1 μg/cm2 after 72 h). The gellan gum-based mucosal substrate significantly increased adhesion (1137.33 ± 142.25 s) compared to the control groups.

Antioxidant studies indicated 73.65% DPPH radical scavenging, whereas antibacterial tests showed more than 99% suppression of Staphylococcus aureus. Furthermore, in vitro studies validated its wound healing and the downregulation of the inflammatory cytokines IL-6 and TNF-α.

The results indicate that the CPN-loaded chitosan hydrogel has extended mucosal retention, strong antibacterial activity, and steady release of CBD. This underscores its significant potential as a targeted treatment for inflammatory oral diseases such as gingivitis and periodontitis.”

https://pubmed.ncbi.nlm.nih.gov/41596768

“Cannabidiol (CBD), a non-psychoactive phytocannabinoid from Cannabis sativa with anti-inflammatory, immunomodulatory, and antimicrobial properties, is a promising bioactive compound for oral health applications [9,10,11]. In addition, CBD not only reduces inflammation, but also fights P. gingivalis very well.”

https://www.mdpi.com/1422-0067/27/2/1127


Development of smart/active chitosan/Kapppa-carrageenan films incorporating Aronia anthocyanin and ginger essential oil Pickering emulsion stabilized by hempseed protein nanoparticles

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“The present study aimed to develop a multipurpose edible film with active (antioxidant/antimicrobial) and intelligent (food freshness monitoring) capabilities.

A Pickering nanoemulsion containing ginger essential oil (PNGEO) was prepared using hempseed protein as a stabilizer.

The effect of incorporating varying concentrations of PNGEO (0%, 5%, 10%w/v) and Aronia anthocyanin extract (AE) (0%, 4%, 8%w/v) on the physicochemical properties of films were evaluated using RSM and CCD, then optimal samples were identified using the utility function method, and their properties were examined.

The results demonstrated that the PNGEO formed a stable O/W emulsion with a Z-potential of -18.3 mV, a particle size of 108 nm, and PDI of 0.44. The encapsulation efficiencies were 91.72% for PNGEO. The AE exhibited pH-responsive color changes, transitioning from red to green across a pH range of 2-13. Increasing the AE and PNGEO enhanced the films’ water vapor barrier, antioxidant and antimicrobial properties. Elongation at break and tensile strength increased from 19.21% to 45.89% and from 6.25 to 15.97 MPa, respectively.

The pH color changes and sensitivity to ammonia gas confirmed the smart functionality of films. SEM and FTIR revealed minor changes in the chemical structure and strong molecular interactions between the biopolymer matrix and the incorporated components. XRD and DSC analyses indicated an increase in crystallinity index and a slight reduction in thermal stability. Release kinetics studies showed that higher temperatures and GEO content can increase the release rate and D values.

In conclusion, the film containing 8% AE and 10% PNGEO showed the best performance by simultaneously providing improvements in antioxidant/antimicrobial properties and sensitive color response to volatile spoilage compounds, and is introduced as a bio-based system with dual capabilities for maintaining quality and monitoring food freshness.”

https://pubmed.ncbi.nlm.nih.gov/41904862

“A novel active/smart edible film based on chitosan/kappa-carrageenan was developed using a Pickering nanoemulsion containing ginger essential oil and stabilized with hempseed protein and aronia anthocyanin extract to enhance the biopolymer’s properties.”

https://www.sciencedirect.com/science/article/abs/pii/S0308814626009222?via%3Dihub


Green Synthesis and Characterization of Nanographene-MnO Composite Nanoparticles for CO2 Capture: Adsorption Performance, Isotherm Analysis, and Reusability

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“In this study, hybrid composite nanoparticles (MnO-NG/green) containing nanographene (NG) and manganese oxide (MnO) were produced by using an environmentally friendly synthesis approach, and their CO2 adsorption performance was investigated in detail.

The conventional method was used to synthesize MnO-NG composites, which were then compared with MnO-NG/green composites prepared via green synthesis using bioextract from the hemp plant.

The composite nanoparticles were structurally characterized using various analytical methods, including FTIR, XRD, SEM, TEM, EDX, and BET analyses. The surface morphology of the composites obtained through green synthesis demonstrated a more homogeneous and regular distribution of MnO nanoparticles on the NG surface.

BET analysis revealed that the specific surface area of the MnO-NG/green composites was 629 m2/g, with a mean pore diameter of 4.65 nm. CO2 adsorption tests were conducted at 273 and 298 K under 1 bar, and it was determined that the MnO-NG/green composites achieved 5.81 and 4.94 mmol/g CO2 uptake capacities, respectively.

These values were significantly higher than those of NG (2.59-2.07 mmol/g) and conventional MnO-NG (4.43-3.74 mmol/g) composites. Analysis of the adsorption isotherm models indicated that the experimental data were better fitted by the Langmuir model. The calculated isosteric heat of adsorption (Q st, 19.4-24.5 kJ/mol) suggests that the adsorption of CO2 by MnO-NG/green composites predominantly occurs via physisorption. The MnO-NG/green composites demonstrated high structural stability and thermal resistance in five-cycle reusability tests, showing a reuse efficiency of 97%.

This study clearly demonstrates that the production of MnO-NG/green composite nanoparticles via a green synthesis offers a promising approach.”

https://pubmed.ncbi.nlm.nih.gov/42110753

“This study provides a strong demonstration of the successful production of nanographene-manganese oxide (NG-MnO) composite nanoparticles via an environmentally friendly green synthesis method and of the use of this structure as a high-performance adsorbent for CO2 capture applications. Superior properties were exhibited by MnO-NG/green composites produced using bioextracts from the hemp plant”

“In conclusion, the achievement of sustainable material production through a green synthesis approach with low environmental impact is not the study’s only accomplishment. The development of a high-performance, reusable, and environmentally friendly adsorbent that can contribute to the reduction of CO2 emissions is another. The resulting MnO-NG/green nanocomposites could be used in many different ways, from in the lab to in industry, which makes them a good choice for next-generation adsorbents in carbon capture technologies.”

https://pubs.acs.org/acsodf/article/11/17/25730/5145806/Green-Synthesis-and-Characterization-of


Plant-derived neuroprotective compounds and nanoformulations targeting Parkinson’s disease: a semi-systematic review of mechanisms and therapeutic potential

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“Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by aggregates of α-synuclein and the degeneration of dopaminergic neurons in the substantia nigra. Current pharmaceutical therapies mainly alleviate symptoms without halting disease progression.

Evidence suggests that traditional plant-based interventions may serve as supplementary therapies by targeting oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis.

This review explores the neuroprotective properties of ten medicinal plants commonly used in traditional medicine: Bacopa monnieri, Curcuma longa, Mimosa pudica, Zingiber officinale, Ocimum sanctum, Emblica officinalis, Camellia sinensis, Cannabis sativa, Panax ginseng, and Withania somnifera. A systematic and comprehensive search of PubMed, Scopus, and Web of Science identified relevant in vitro, in vivo, and clinical studies.

This study highlights the mechanisms by which plant-derived chemicals influence cellular pathways associated with PD, emphasising their therapeutic potential despite limited clinical validation.

Studies have shown that bioactive compounds such as curcumin, bacoside, Epigallocatechin-3-gallate (EGCG), cannabidiol, ginsenosides, and withanolides exhibit antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective effects in PD models.

Nanotechnology offers promising strategy to enhance the efficacy of herbal compounds, addressing challenges of poor solubility, rapid metabolism, low bioavailability, and restricted blood-brain barrier penetration. Nano-delivery systems including liposomes, polymeric nanoparticles, nanoemulsions, and metal nanoparticles can improve stability, brain targeting, controlled release, and cellular uptake of these bioactives, thereby enhancing therapeutic efficiency while reducing systemic toxicity.

Green-synthesized plant-based nanoparticles further provide synergistic neuroprotective benefits, positioning phyto-nanomedicine as a multi-target approach for PD therapy. However, extensive clinical studies are required to confirm safety and effectiveness.”

https://pubmed.ncbi.nlm.nih.gov/42154395

“Current pharmaceutical therapies mainly alleviate symptoms without halting disease progression.”

“Evidence suggests that traditional plant-based interventions may serve as supplementary therapies by targeting oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis.”

“Studies have shown that bioactive compounds such as curcumin, bacoside, Epigallocatechin-3-gallate (EGCG), cannabidiol, ginsenosides, and withanolides exhibit antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective effects in PD models.”

https://link.springer.com/article/10.1007/s11011-026-01868-y