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A CBD-rich hemp extract is superior to CBD alone in reducing relapse to methamphetamine-seeking in rats

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“In preclinical models, the non-intoxicating cannabis component cannabidiol (CBD) reduces relapse to methamphetamine (Meth)-seeking and Meth-induced hyperactivity in rats.

Cannabis products containing multiple cannabinoids (“full spectrum”) may offer greater therapeutic potential than single cannabinoid (“isolate”) products.

However, few studies tested this. This study examined whether a hemp extract (HE) containing multiple cannabinoids might be superior to CBD alone in reducing Meth-induced behavioural sensitisation and relapse, and whether serotonin 1 A receptors (5-HT1A) are involved.

Male Sprague-Dawley rats self-administered either Meth or sucrose via lever press, followed by extinction and reinstatement by Meth injection (1 mg/kg; i.p.) or sucrose access. Rats received vehicle, CBD isolate (80 mg/kg), HE (containing 2.5 mg/kg of CBD and other phytocannabinoids), or HE with CBD added to match the 80 mg/kg amount of the CBD isolate (CBD + HE condition). The 5-HT1A antagonist WAY-100635 was co-administered to assess receptor involvement. Separate rats were tested for conditioned place preference (CPP) to assess possible intrinsic rewarding properties of the cannabinoids. A final group was tested for Meth-induced behavioural sensitisation.

All CBD containing treatments reduced Meth-primed reinstatement, with HE and CBD + HE more effective than CBD isolate.

There was no effect of any treatment on reacquisition of sucrose seeking. WAY-100635 did not block the effects of any treatment. Neither cannabinoid treatment produced CPP. All treatments reduced the expression of Meth-induced sensitised hyperactivity with CBD + HE showing some superiority over CBD or HE alone.

This study suggests that CBD + HE may be more effective than CBD in reducing Meth relapse-like behaviour.”

https://pubmed.ncbi.nlm.nih.gov/41605363

“CBD-rich hemp extract surpasses CBD alone in reducing relapse to Meth-seeking.”

https://www.sciencedirect.com/science/article/pii/S0278584626000254?via%3Dihub

Cannabidiol Mitigates Pollution-Induced Inflammatory, Oxidative, and Barrier Damage in Ex Vivo Human Skin

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“Airborne particulate matter (PM) is a major environmental pollutant that accelerates skin aging, inflammation, and barrier impairment.

Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has shown anti-inflammatory and cytoprotective effects, yet its role in protecting full-thickness human skin from pollution-induced damage remains unclear.

In this study, human full-thickness ex vivo skin explants were topically exposed to PM (0.54 mg/cm2) and treated with CBD (6.4 mM) administered via the culture medium for 48 h. Proinflammatory mediators (interleukin-6, IL-6; matrix metalloproteinase-1, MMP-1; cyclooxygenase-2, COX-2), oxidative stress markers (reactive oxygen species, ROS; 8-hydroxy-2′-deoxyguanosine, 8-OHdG), the xenobiotic sensor aryl hydrocarbon receptor (AhR), extracellular matrix proteins (procollagen type I C-peptide, PIP; fibrillin), and the barrier protein filaggrin were quantified using ELISA and immunofluorescence.

PM exposure triggered significant inflammation, oxidative stress, AhR induction, extracellular matrix degradation, and barrier disruption. CBD selectively counteracted these effects by reducing IL-6, MMP-1, COX-2, ROS, and 8-OHdG levels, downregulating AhR expression, and restoring PIP, fibrillin, and filaggrin expression. No measurable effects were observed in unstressed control tissues.

These results demonstrate that CBD protects human skin from PM-induced molecular damage and supports its potential as a functional bioactive ingredient for anti-pollution applications.”

https://pubmed.ncbi.nlm.nih.gov/41594552

“Cannabidiol (CBD), a non-psychoactive phytocannabinoid from Cannabis sativa, has shown antioxidant, anti-inflammatory, and barrier-supporting effects “

“This study provides compelling evidence that CBD protects against pollution-induced skin damage by modulating inflammatory, oxidative, and xenobiotic stress pathways. In addition to biochemical modulation, CBD restored extracellular matrix and barrier integrity, supporting its potential as a functional ingredient for promoting skin health in urban environments.”

https://www.mdpi.com/2218-273X/16/1/10

Effects of Cannabidiol on Bone Health: A Comprehensive Scoping Review

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“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.”

https://pubmed.ncbi.nlm.nih.gov/41595744

“This scoping review demonstrates that CBD exerts multifaceted and predominantly positive effects on bone biology. CBD enhances osteoblast differentiation, supports matrix formation, and suppresses osteoclast-driven resorption. These effects are mediated through a network of anti-inflammatory, antioxidant, and receptor-dependent mechanisms.”

https://www.mdpi.com/2227-9059/14/1/208


The Effect of Cannabidiol on Nociceptive Behaviour and the Endocannabinoid System in an Incisional Wound Model

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“Background/Objectives: Wound-related pain is a common, yet inadequately managed condition, and new therapeutic strategies are warranted. Limited data suggests that phytocannabinoids and cannabis may alleviate wound-related pain; however, further studies are required. This study investigated the effects of systemic administration of cannabidiol (CBD) on nociceptive behaviour following dorsum incision and on the endocannabinoid system. 

Methods: Male Sprague-Dawley rats (150-200 g on arrival, n = 9/group) underwent a 1.2 cm incision on the hairy skin of the dorsum or sham procedure. Back and hind paw mechanical withdrawal thresholds were assessed at baseline and post-surgery/sham days (PSDs) 1, 4, 7, and 8 using manual and electronic von Frey tests, respectively. On PSD 8, the effect of a single acute administration of CBD (3, 10, or 30 mg/kg, i.p.) on mechanical hypersensitivity in the dorsum and hind paws was assessed. The levels of endocannabinoids and N-acylethanolamines in the plasma and discrete brain regions following CBD administration were analysed. 

Results: Robust mechanical hypersensitivity was evident in the dorsum and hind paws following the incision. CBD (3 mg/kg) partially attenuated primary mechanical hypersensitivity in the dorsum, in a site- and dose-specific manner. CBD had no effect on secondary mechanical hypersensitivity. CBD did not alter the levels of endocannabinoids or N-acylethanolamines, but in rats that received CBD (3 mg/kg), levels of 2-AG were lower in the contralateral amygdala and levels of AEA were higher in the contralateral lumbar spinal cord, compared to the ipsilateral sides. 

Conclusions: These data provide evidence for antinociceptive effects of CBD in a model of incisional wound-related pain. Further research on CBD’s mechanism(s) of action is warranted. The potential antinociceptive effects of other phytocannabinoids in this model should also be investigated.”

https://pubmed.ncbi.nlm.nih.gov/41599645

“Cannabidiol (CBD) is a phytocannabinoid found in Cannabis sativa L.”

“These results indicate dose- and site-specific antinociceptive effects of CBD in a rat model of incisional wound-related pain, providing preclinical evidence to support the contention that CBD may have therapeutic potential for alleviating incisional wound-related pain.”

“These results also indicate that investigation of the potential antinociceptive effects of other phytocannabinoids in this model of incisional wound-related pain is warranted.”

https://www.mdpi.com/1424-8247/19/1/43


Toxicological evaluation and preliminary phytochemical characterisation of a Nigerian Cannabis sativa chemovar

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“Objectives: Different Cannabis sativa chemovars produce diverse pharmacological and behavioral effects. With the widespread use of cannabis in Nigeria, detailed toxicological effects of Nigerian chemovars are lacking. This study aimed to identify phytocannabinoids and investigate the toxic effects of an indigenous C. sativa.

Materials and methods: The plant samples were air-dried, powdered, extracted with ethanol, and characterized (phytochemical screening, Fourier Transformed Infrared Spectroscopy (FTIR), and Gas Chromatography-Mass Spectrometry (GC-MS)). Acute and subacute toxicity tests were done following Organisation for Economic Co-operation and Development (OECD) protocols.

Results: Screening showed appreciable levels of alkaloids, tannins, saponins, cardiac glycosides, and phenol. FTIR analysis indicated functional groups and chemical linkages like alcohols, fatty acids, alkynes, ketones, and esters, and 11 phytocannabinoids with delta-9-tetrahydrocannabinol in abundance (35.78%) reported by GC-MS. Acute toxicity test indicated an oral lethal dose (LD50) value of ˃5000 mg/kg, a no-observed-adverse-effect-level (NOAEL) dose of ≤300 mg/kg, and a significant (P<0.05) decrease in the weight of animals in the 2000 mg/kg treatment group. The sub-acute toxicity test showed significantly (P<0.05) decreased ALP and ALT levels at 25 mg/kg body weight, and significantly lower triglyceride (P<0.01) and LDL (P<0.05) levels. Urea and some haematological parameters were significantly (P<0.05) higher in the 250 mg/kg group. Also, we observed mild to moderate necrosis in the excised pancreas and liver, and mild tubular changes in the kidney.

Conclusion: This suggests that our indigenous variety of C. sativa may be considered safe following oral consumption.”

https://pubmed.ncbi.nlm.nih.gov/41586191

Ferroptosis under fire: cannabidiol mitigates iron-dependent injury in differentiated human neuroblastoma cells following oxygen-glucose deprivation

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“Background: Perinatal hypoxia-ischemia is a major cause of long-term neurological impairments in newborns, with ferroptosis recognized as a key mechanism of injury.

Cannabidiol (CBD) is a non-psychoactive phytocannabinoid with antioxidant and neuroprotective properties.

CBD is a potential modulator of hypoxic-ischemic brain damage, however its effects on ferroptosis-related pathways remain unclear.

Purpose: In this study, we examined whether CBD can alleviate ferroptosis-associated damage in differentiated human neuroblastoma (neuron-like SH-SY5Y) cell model of hypoxic-ischemic injury.

Study design: Differentiated human neuroblastoma cells were exposed to oxygen-glucose deprivation (OGD) to simulate hypoxic-ischemic conditions.

Methods: Neuron-like SH-SY5Y cells were subjected to OGD to induce hypoxic-ischemic injury. CBD was applied to assess its neuroprotective effects. Oxidative stress markers, antioxidant enzyme activity, transcription factor activation Nrf2 (nuclear factor erythroid 2-related factor 2), iron metabolism proteins (ferroportin), hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) expression were evaluated.

Results: CBD application significantly reduced oxidative stress by improving antioxidant capacity and lowering total oxidant status. CBD also preserved the expression and enzymatic activity of glutathione peroxidase 4, a central enzyme protecting against lipid peroxidation, and enhanced the activation of Nrf2, a key regulator of antioxidant defence. Additionally, CBD prevented OGD-induced downregulation of ferroportin, potentially supporting iron efflux and reducing ferroptotic risk. HIF-1α and its downstream target VEGF were upregulated under hypoxic conditions, and CBD further enhanced VEGF expression.

Conclusion: CBD mitigates ferroptosis by modulating redox balance, antioxidant defence, and iron metabolism, supporting its potential role as a therapeutic strategy for neonatal hypoxic-ischemic brain injury.”

https://pubmed.ncbi.nlm.nih.gov/41581443

“These findings support the potential use of CBD as a therapeutic agent for hypoxia-related ferroptotic injury, such as neonatal hypoxic-ischemic encephalopathy.”

https://www.sciencedirect.com/science/article/abs/pii/S0944711326001078?via%3Dihub

In Vitro Antimicrobial Effect of Tetrahydrocannabinol on Streptococcus mutans and Its Anticariogenic Potential

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“Introduction and aims: With the increasing use of marijuana, it is vital to understand the effect of tetrahydrocannabinol (THC) on oral microbiota, especially the primary carious pathogen Streptococcus mutans.

Methods: The minimum inhibitory concentration (MIC) of THC against S mutans was determined by antimicrobial susceptibility testing. Bacterial acid production was evaluated. The effect of THC on S mutans biofilm formation and preformed biofilms was determined by crystal violet assay. The metabolic activity and viability of the biofilm were assessed using the methylthiazolyldiphenyl tetrazolium bromide assay and live/dead assay, respectively. Extracellular polysaccharide (EPS) was examined by Cascade Blue Dextran staining. S mutans membrane potential was detected by the Baclight Bacterial Membrane Potential Kit.

Results: The MIC of THC against S mutans was 2 µg/mL (P < .0001). A total of ≥2 µg/mL THC reduced bacterial acidogenicity and inhibited over 90% of biofilm formation (P < .0001). Additionally, ≥1 µg/mL THC reduced biofilm viability and EPS production (P < .0001), as assessed by fluorescence measurements and microscopy. While 1 to 64 µg/mL THC did not degrade preformed biofilm, metabolic activity was reduced by 16 to 64 µg/mL THC (P < .01), and 8 to 32 µg/mL THC reduced biofilm viability in a time- and dose-dependent manner (P < .001). Moreover, 2 to 8 µg/mL THC promoted membrane hyperpolarization after a 5-minute treatment (P < .01).

Conclusion: THC inhibits S mutans growth and biofilm formation while also reducing bacterial viability, EPS production, and acid production. Although it does not degrade preformed biofilm biomass, THC diminishes its metabolic activity and viability. These effects may be linked to THC-induced membrane hyperpolarization. This in vitro study suggests that THC may reduce the cariogenic capacity of S mutans.

Clinical relevance: This study shows that THC inhibits S mutans growth, biofilm formation, properties of preformed biofilms, and acid production. It provides preliminary scientific evidence on the impact of THC on oral health, specifically cannabinoid consumption on cariogenesis, and a potential new avenue for developing a new anticariogenic agent.”

https://pubmed.ncbi.nlm.nih.gov/41576726

“Among the cannabinoids, THC is the most abundant and exhibits a range of therapeutic effects, including analgesic, antiemetic, anti-inflammatory, anticancer, and antiseizure properties, as well as offering neuroprotective benefits in cases of neurodegeneration.”

Taken together, we herein provide evidence of the efficacy of THC in antibacterial and antibiofilm activity against S mutans by reducing planktonic growth of S mutans, inhibiting biofilm formation, and interfering with preexisting biofilm activity and function.

In addition, it may be a potential new avenue for developing new anticariogenic agents by suppressing the growth of S mutans and decelerating the acidification process that leads to enamel demineralization.”

https://www.sciencedirect.com/science/article/pii/S0020653925086678?via%3Dihub

“Anticariogenic (meaning “anti-cavity”) describes substances or practices that prevent or arrest the development of dental caries (tooth decay).”

Plant Growth-Promoting Rhizobacteria Colonize Δ9-Tetrahydrocannabinolic Acid Drug-Type Cannabis sativa L. Roots and Modulate Cannabinoid Metabolism

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“Plant growth-promoting rhizobacteria (PGPR) establish beneficial associations with plants, enhancing nutrient uptake, growth, and stress tolerance.

Cannabis sativa L., a medicinal plant producing over 300 specialized metabolites with relevant medicinal properties, remains underexplored for PGPR influence on its metabolism. This study assessed the ability of four PGPR taxa: Bacillus, Pseudomonas, Flavobacterium, and Burkholderia to colonize roots and modulate cannabinoid metabolism.

Two Δ9-tetrahydrocannabinolic acid (THCA) drug-type C. sativa cultivars, Amnesia Haze and Gorilla Glue, were tested. Plants grown hydroponically were inoculated under controlled conditions. Root colonization was confirmed via endophyte-specific assays.

Phenotypic analyses revealed no effects on plant phenotype, while chemical analyses revealed a response shared across taxa and cultivars. Bacterial inoculation increased the precursor cannabinoid Cannabigerolic acid (CBGA) concentration significantly by +27.37% while reducing Δ9-tetrahydrocannabinol (Δ9-THC) by -15.76%. The CBGA/THCA and THCA/CBDA ratios shifted significantly, indicating a favored CBGA accumulation and CBDA production, respectively.

PGPR treatments reduced in vivo and post-harvest decarboxylation of THCA into Δ9-THC, preserving the acidic cannabinoid profile. Under a standardized, soilless hydroponic regimen with a single shared reservoir and identical fertigation across groups, PGPR colonization was associated with shifts in cannabinoid metabolism and reduced decarboxylation.

This study demonstrates that PGPR can influence the specialized metabolism of high-THCA C. sativa, offering insights into sustainable cultivation and pharmaceutical exploitation of this relevant medicinal plant species.”

https://pubmed.ncbi.nlm.nih.gov/41578722

“Plants and bacteria share a long history that spans over a 100 million years. Since then, they have co-evolved to form complex relationships that facilitate the survival of both.”

“PGPRs can promote growth in several ways.”

“The findings and methodology of this research lay the groundwork for further evaluating and exploiting the potential beneficial relationship between PGPRs and C. sativa and implementing their sustainable applications in the agricultural, biotechnological, and pharmaceutical sectors.”

https://onlinelibrary.wiley.com/doi/10.1111/ppl.70756

Therapeutic potential of acidic cannabinoids: an update

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“Cannabis sativa yields a wide range of bioactive compounds, including terpenes, flavonoids, and cannabinoids.

Tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and cannabichromenic acid (CBCA) are the acidic biosynthetic precursors of the neutral cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which have been the subject of much research.

This review examines the biosynthesis, decarboxylation, molecular pharmacology, and therapeutic significance of acidic cannabinoids, intending to address a significant knowledge gap. Peer-reviewed literature from major scientific databases was used in a systematic narrative review with an emphasis on investigations of acidic cannabinoid chemistry, pharmacology, pharmacokinetics, and disease-specific applications.

According to the reviewed data, acidic cannabinoids exhibit unique biological activities that distinguish them from their neutral counterparts. These include neuroprotective, anti-inflammatory, anticonvulsant, and anti-proliferative actions, which are mediated by molecular targets such as serotonin 5-HT1A receptors, cyclooxygenase-2 (COX-2), transient receptor potential (TRP) channels, and peroxisome proliferator-activated receptor-γ (PPARγ).

Acidic cannabinoids are more appealing for therapeutic usage in children and the elderly, considering that they are not intoxicating like THC; however, this distinction applies primarily to non‑heated consumption. Chemical instability, low bioavailability, and a dearth of controlled human trials impede clinical translation despite their potential.

According to the findings, acidic cannabinoids are an underutilized yet potentially valuable class of precision medicines.

In this study, we outline existing understanding on acidic cannabinoids, discuss their production and transformation, and identify research needs that could influence cannabis science research.”

https://pubmed.ncbi.nlm.nih.gov/41545891

https://link.springer.com/article/10.1186/s42238-026-00387-y

“Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis”

https://pmc.ncbi.nlm.nih.gov/articles/PMC7409346


The Exploration of Cannabis Beverage Substitution for Alcohol: A Novel Harm Reduction Strategy

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“Alcohol consumption is associated with nearly 200 health conditions. As cannabis-infused beverages emerge in the legal market, their potential as a substitute for alcohol is of growing interest.

This study investigates whether cannabis beverages may reduce alcohol use.

A total of 438 anonymous adults who used cannabis in the past year completed a survey including cannabis use and alcohol consumption items from the Behavioral Risk Factor Surveillance System (BRFSS). Chi-square and t-tests compared alcohol use between cannabis beverage users and non-users, and before vs. after cannabis beverage initiation.About one-third (33.6%) of respondents used cannabis beverages, typically consuming one per session.

Users were more likely to report substituting cannabis for alcohol (58.6%) than non-users (47.2%). They also reported fewer weekly alcoholic drinks after starting cannabis beverages (M = 3.35) compared to before (M = 7.02), and binge drank less frequently (80.7% reported less than monthly or never, vs. 47.2% before). Those who cited reducing other substance use were more likely to use cannabis beverages (45.8%).

Findings suggest cannabis beverages may support alcohol substitution and reduce alcohol-related harms, offering a promising alternative for individuals seeking to lower alcohol intake.”

https://pubmed.ncbi.nlm.nih.gov/41533430

https://www.tandfonline.com/doi/full/10.1080/02791072.2026.2614506