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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

Evaluation of the antibacterial and antioxidant potential of the endophytic fungus EFY14 from Cannabis sativa L. leaves through metabolomics and molecular docking

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“Endophytic fungi are prolific sources of natural antioxidants and antibacterial agents.

This study aims to isolate and identify the endophytic fungus EFY14 from Cannabis sativa L. leaves and to evaluate the antibacterial and antioxidant activities of its culture filtrates.

Non-targeted metabolomics was employed to chemically profile the EFY14 crude extract, a potential biological targets were predicted through molecular docking and molecular dynamics simulations. EFY14 was taxonomically identified as belonging to the Chaetomium genus.

Its extract contained 20.823 ± 1.449 mg gallic acid equivalent (GAE)/L total phenolic and 0.230 ± 0.007 mg rutin equivalent (RE)/mL total flavonoids, displaying antioxidant and antibacterial activities. Metabolomic profiling identified flavonoids and phenolic compounds, including 4′,7-dihydroxy-8-methylisoflavone, scopoletin, xanthohumol, tricin, sophoraflavanone G, prenyl glucoside, melilotoside and maltol. Molecular docking indicated potential molecular targets for these metabolites.

These findings suggest that EFY14 derived endophytic fungi from C. sativa L. may represent a novel source of antioxidant and antibacterial compounds.”

https://pubmed.ncbi.nlm.nih.gov/41527465

“In this study, a strain named Chaetomium globusum EFY14 was identified from the leaves of the Cannabis genus plants. It was determined to be a new source of antioxidants and antibacterial agents. Additionally, the Cannabidiolic acid component was detected through metabolomics. The extract is rich in phenolic and flavonoid substances and has DPPH scavenging activity as well as inhibitory activity against E.coli, B.subtilis, and S.aureus. The metabolites verified through metabolomics and molecular docking provide promising candidate substances for drug development and agricultural biological control, as well as new methods for cannabinoid synthesis.”

“This research is highly relevant for professionals in the fields of pharmaceuticals, agriculture and natural products. The identification of Chaetomium globusum. EFY14 from the Cannabis genus as a source of phenolic substances, flavonoids (such as xanthohumol, tricin) and antioxidant/antibacterial metabolites provides feasible development leads for new drugs, biological pesticides and natural antioxidants. This strain offers new strains for industrial production of antioxidant and antibacterial substances.”

https://www.tandfonline.com/doi/full/10.1080/14786419.2025.2609961

Cannabinoid Signaling and Autophagy in Oral Disease: Molecular Mechanisms and Therapeutic Implications

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“Autophagy is a well-preserved biological mechanism that is essential for sustaining homeostasis by degradation and recycling damaged organelles, misfolded proteins, and other cytoplasmic detritus.

Cannabinoid signaling has emerged as a prospective regulator of diverse cellular functions, including immunological modulation, oxidative stress response, apoptosis, and autophagy. Dysregulation of autophagy contributes to pathogenesis and treatment resistance of several oral diseases, including oral squamous cell carcinoma (OSCC), periodontitis, and gingival inflammation.

This review delineates the molecular crosstalk between cannabinoid receptor type I (CB1) and type II (CB2) activation and autophagic pathways across oral tissues. Cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC), modulate key regulators like mTOR, AMPK, and Beclin-1, thereby influencing autophagic flux, inflammation, and apoptosis.

Experimental studies indicate that cannabinoids inhibit the PI3K/AKT/mTOR pathway, promote reactive oxygen species (ROS)-induced autophagy, and modulate cytokine secretion, mechanisms that underline their dual anti-inflammatory and anti-cancer capabilities. In addition, cannabinoid-induced autophagy has been shown to enhance stem cell survival and differentiation, offering promise for dental pulp regeneration. Despite these promising prospects, several challenges remain, including receptor selectivity, dose-dependent variability, limited oral bioavailability, and ongoing regulatory constraints.

A deeper understanding of the context-dependent regulation of autophagy by cannabinoid signaling could pave the way for innovative therapeutic interventions in dentistry. Tailored cannabinoid-based formulations, engineered for receptor specificity, tissue selectivity, and optimized delivery, hold significant potential to revolutionize oral healthcare by modulating autophagy-related molecular pathways involved in disease resolution and tissue regeneration.”

https://pubmed.ncbi.nlm.nih.gov/41516397

“Cannabinoids are a diverse class of bioactive lipophilic compounds derived from Cannabis sativa and other plant species, as well as synthesized endogenously and pharmacologically, and have attracted significant attention for their immunomodulatory, anti-inflammatory, antioxidant, and anticancer effects.”

“Cannabinoid-based treatments show promise for managing oral diseases by controlling inflammation and promoting tissue regeneration through specific pathways.”

https://www.mdpi.com/1422-0067/27/1/525

Medicinal cannabis plant extract (NTI164) modifies epigenetic, ribosomal, and immune pathways in paediatric acute-onset neuropsychiatric syndrome

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“Paediatric acute-onset neuropsychiatric syndrome (PANS) is a syndrome of infection-provoked abrupt-onset obsessive-compulsive disorder (OCD) or eating restriction.

Based on the hypothesis that PANS is an epigenetic disorder of immune and brain function, a full-spectrum medicinal cannabinoid-rich low-THC cannabis (NTI164) was selected for its known epigenetic and immunomodulatory properties.

This open-label trial of 14 children with chronic-relapsing PANS (mean age 12·1 years; range 4-17; 71 % male) investigated the safety and efficacy of 20 mg/kg/day NTI164 over 12 weeks. Clinical outcomes were assessed using gold standard tools. To define the biological effects of NTI164, blood samples were collected pre- and post-treatment for bulk and single-cell transcriptomics, proteomics, phosphoproteomics, and DNA methylation.

NTI164 was well-tolerated, and 12 weeks of treatment decreased the mean Clinical Global Impression-Severity (CGI-S) score from 4·8 to 3·3 (p = 0·002). Significant improvements were observed in emotional regulation (RCADS-P, p < 0·0001), obsessive-compulsive disorder (CYBOCS-II, p = 0·0001), tics (YGTSS, p < 0·0001), attention-deficit hyperactivity disorder (Conner’s, p = 0·028), and overall quality of life (EQ-5D-Y, p = 0·011).

At baseline, the multi-omic approach revealed that leucocytes from patients with PANS had dysregulated epigenetic (chromatin structure, DNA methylation, histone modifications, transcription factors), ribosomal, mRNA processing, immune, and signalling pathways. These pathways were significantly modulated by NTI164 treatment.

NTI164 shows promise as a disease-modifying therapeutic for PANS.

Multi-omics reveal broad epigenetic and immune dysregulation in patients, which was modified by NTI164, presenting epigenetic machinery as a therapeutic target in PANS.”

https://pubmed.ncbi.nlm.nih.gov/41513541

“Cannabis sativa L. has long been used in medicine, and increasingly proposed as a treatment of psychiatric disorders and neurodevelopmental disorders (NDDs).”

https://www.neurotherapeuticsjournal.org/article/S1878-7479(25)00306-X/fulltext

Evaluation of the antimicrobial effect of cannabidiol (CBD) in a multispecies subgingival biofilm model

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“Background: This study evaluated the antimicrobial effect of cannabidiol (CBD) on a multi-species subgingival biofilm model.

Materials and methods: Biofilms were formed using 33 bacterial species on a Calgary device. Two protocols were tested: (A) biofilm in contact with CBD (125, 250 and 500 µg/mL) and chlorhexidine 0.12% (CHX) for the entire period; (B) treatments with CBD (500 and 1000 µg/mL) and CHX started on day 3, twice a day, for 1 minute. The total biofilm counts, the proportion of complexes, and the counts of each species were evaluated by DNA-DNA hybridization (Checkerboard).

Results: In Experiment A, CBD at concentrations of 250 and 500 µg/mL, as well as CHX, significantly reduced the total biofilm count. At 500 µg/mL, CBD also decreased the proportion of the red complex and reduced the counts of 10 bacterial species, whereas CHX affected 20 species. In Protocol B, both CBD at 1000 µg/mL and CHX reduced the total biofilm count and the proportion of the red complex, while increasing the proportion of the green complex. Both protocols led to a reduction in Porphyromonas gingivalis and Tannerella forsythia.

Conclusion: CBD reduced the total bacterial count and the red complex, inhibiting known periodontal pathogens. Within the limitations, the results provide exploratory evidence that CBD may reduce the total bacterial count in the proposed polymicrobial biofilm model, including the red complex bacteria, and may thus be postulated as an inhibitor of known periodontal pathogens. However, future in vivo studies with robust sample sizes and standardized CFU-based quantification are required to confirm these findings.”

https://pubmed.ncbi.nlm.nih.gov/41509036

“These exploratory observations demonstrated a notable antimicrobial activity of CBD by reducing red complex bacteria and key periodontopathogens, including Porphyromonas gingivalis and Tannerella forsythia, in a multispecies subgingival biofilm model, comparable to CHX.”

https://www.tandfonline.com/doi/full/10.1080/20002297.2025.2603706

Intravesical Cannabidiol for Inflammation and Pain in Interstitial Cystitis/Bladder Pain Syndrome via TLR4/NF-κB and TRPV1 Modulation

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“Purpose: This study explored the anti-inflammatory and analgesic mechanisms of intravesical cannabidiol (CBD) in cyclophosphamide (CYP)-induced interstitial cystitis/bladder pain syndrome (IC/BPS) rats.

Materials and methods: Female Sprague-Dawley rats were divided into four groups of control, IC/BPS, IC/BPS+10 mg/kg CBD, and IC/BPS+100 mg/kg CBD (n=5/group). IC/BPS was induced by CYP injections, followed by intravesical CBD administration. Pain sensitivity and bladder function were assessed via Von Frey tests and cystometrograms. Histological, Western blot, and immunofluorescence analyses were performed on bladder tissues. SV-HUC1 cells were analyzed using western blot and scratch assays.

Results: CBD improved bladder function, reducing instability, prolonging intercontractile intervals, and enhancing detrusor contraction pressure. The CBD 100 mg/kg group showed greater pain relief in Von Frey tests compared with other groups. Histology revealed reduced inflammation, mast cell infiltration, and fibrosis in bladder tissues. CBD decreased TNF-α, COX2, IL-6, and TRPV1 levels and inhibited the TLR4/MyD88/pNF-κB pathway. In SV-HUC1 cells, CBD suppressed epithelial injury and downregulated TRPV1, TLR4, MyD88, p-NF-κB, and Bax/Bcl-xL, demonstrating anti-inflammatory and anti-apoptotic effects.

Conclusions: Intravesical CBD alleviates inflammation by inhibiting the TLR4/MyD88/pNF-κB pathway, reduces neuropathic pain via TRPV1 channels, and improves cell apoptosis and migration in CYP-induced IC/BPS model animals.”

https://pubmed.ncbi.nlm.nih.gov/41508393

“Cannabidiol (CBD) is a non-psychoactive cannabinoid with a variety of biological activities and a wide range of benefits such as antioxidant, anti-inflammatory, and immunomodulatory effects. Research has demonstrated the therapeutic significance of CBD in neurological disorders, cardiomyopathy, diabetes, and other diseases.”

“In the present study, we investigated the potential therapeutic effects of CBD in IC/BPS. We conducted intravesical instillation of CBD in a rat model of IC/BPS and evaluated the effects on inflammation and bladder function and pain. We further analyzed its mechanism of action. Our study provides evidence of the potential effectiveness of CBD in the treatment of IC/BPS.”

https://wjmh.org/DOIx.php?id=10.5534/wjmh.250152

Ultrasound-Assisted Green Extraction of Antioxidant and Antimicrobial Resins from Cannabis sativa for Potential Pharmaceutical Applications

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“Objective: To develop a green and efficient ultrasound-assisted extraction (UAE) process to obtain bioactive resins from Cannabis sativa with potential pharmaceutical applications, optimizing extraction parameters to maximize antioxidant capacity and total polyphenol content.

Significance: UAE using ethanol under mild temperature and time conditions as a green technique was applied to reduce solvent consumption, energy demand, and extraction time while preserving thermolabile bioactive compounds. Optimizing UAE enables the recovery of cannabinoid- and terpene-rich extracts that may serve as natural active pharmaceutical ingredients or functional excipients for drug development. This study integrate a Doehlert-based optimization of UAE with a functional evaluation of antioxidant efficiency and antimicrobial activity, providing a comprehensive framework for the development of cannabis-derived pharmaceutical ingredients.

Methods: A Doehlert experimental design combined with response surface methodology was employed to optimize temperature and extraction time. The optimized extract was characterized for its phytochemical composition. Antimicrobial activity was evaluated against Gram-positive and Gram-negative bacterial strains to assess potential therapeutic relevance.

Results: Under optimal conditions (54.5 °C, 28 min 25 s), the extract showed a total phenolic content of approximately 0.11 mg gallic acid/mg resin and an IC50 value of about 0.24 mg resin/mL extract, indicating enhanced antioxidant performance compared to non-optimized conditions. Also, showed selective bactericidal activity against Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis ATCC 12228, while Gram-negative strains remained resistant.

Conclusions: UAE extraction efficiently recovered antioxidant and selectively antimicrobial compounds from Cannabis sativa resins under mild, eco-friendly conditions, supporting their potential use as bioactive ingredients in pharmaceuticals.”

https://pubmed.ncbi.nlm.nih.gov/41489477

https://www.tandfonline.com/doi/full/10.1080/03639045.2025.2612300