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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

Pharmacological, Molecular Mechanisms, and Therapeutic Potential of β-Caryophyllene and β-Caryophyllene-Rich Plants in Liver Diseases

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“β-caryophyllene, a bicyclic sesquiterpene widely abundant in various plant essential oils, has garnered growing attention for its potential biological effects and therapeutic benefits in liver diseases. This review systematically evaluates preclinical evidence on the pharmacological properties of BCP with emphasis on its hepatoprotective effects primarily through its anti-inflammatory, antioxidant, antifibrotic, and immunomodulatory actions.

BCP is classified as a dietary cannabinoid due to its ability to activate cannabinoid type 2 receptors in the endocannabinoid system and thereby influence key cellular signaling pathways involved in lipid metabolism and tissue remodeling. Emerging studies also highlight BCP interaction with PPAR nuclear receptor and AMPK signaling, further corroborating its role in regulating lipid homeostasis.

In the present review, we compile, summarize, and critically analyze findings from in vitro and in vivo studies on nonalcoholic fatty liver disease, recently termed as metabolic dysfunction-associated fatty liver disease (MAFLD), alcoholic liver disease, and liver fibrosis, highlighting the pharmacological and molecular mechanisms underlying therapeutic effects. These studies consistently demonstrate a reduction in hepatic steatosis, collagen deposition, and hepatocellular markers reflecting a broad spectrum of hepatoprotective effects.

Taken together, the pharmacological properties and mechanistic insights place BCP as a promising natural compound with nutraceutical, phytopharmaceutical, or dietary supplement applications for liver diseases. Despite the robust preclinical evidence, clinical validation remains scarce. Therefore, regulatory toxicology and efficacy studies are needed to establish the therapeutic potential of BCP in liver diseases and its integration as a nutraceutical or phytopharmaceutical in the clinical usage.”

https://pubmed.ncbi.nlm.nih.gov/41489519

“BCP is one of the important constituents in Cannabis with an abundance of 35%. In addition to its presence in Cannabis, BCP is largely present in numerous edible plants.”

“In conclusion, BCP represents a promising therapeutic avenue for managing liver diseases due to its ability to modulate multiple interrelated molecular and cellular pathways.”

“With continued research, BCP has the potential to evolve from a natural product with hepatoprotective properties to an effective adjunct or alternative in liver disease therapy, offering new hope for patients and advancing the field of liver health management.”

https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202502436R


Effect of patient marijuana use on perioperative opioid requirements

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“The effect of chronic marijuana use on patients is unknown, including in the surgical setting. Marijuana produces many effects on the body, which should be considered when providing medical care.

Chronic marijuana use may affect surgical opioid requirements. To explore this possibility, an observational study was completed by conducting a retrospective chart review of patients who underwent surgery with general anesthesia.

Patients were identified in the electronic medical record via self-reporting as marijuana users (users) or nonmarijuana users (nonusers). Users and nonusers were case-matched based on age, gender, weight, and procedure. After case matching, 570 patients’ charts were analyzed, and intraoperative opioid, intraoperative propofol, and post-anesthesia care unit opioid requirements were compared.

Marijuana users required less intraoperative opioids (mean [standard deviation (SD)] 27.2 [20.5] morphine milligram equivalents [MMEs]) compared to those who were marijuana nonusers (31.3 [22.1] MME).

These results show a statistically significant difference in the intraoperative opioid requirement between case-matched users and nonusers (p = 0.02), with p = 0.013 after statistical adjustment for racial differences between the marijuana user and nonuser cohorts. Users and nonusers required similar amounts of intraoperative propofol (242.2 [220.2] and 257.8 [250.9], respectively) and post-operative opioids (7.3 [6.0] and 8.0 [9.0], respectively). The differences in intraoperative propofol and post-operative opioid requirements were not different statistically with p-values of 0.43 and 0.31, respectively.

Based on this study population, marijuana users required less intraoperative opioids when compared to case-matched marijuana nonusers, with no difference in intraoperative propofol or post-operative opioid requirements.

Perspective: Typical preoperative screening includes queries about patient substance use including marijuana, but details such as frequency and length of use are infrequently asked. The addition of these details to the assessment may provide improved understanding of a patient’s surgical opioid requirements.”

https://pubmed.ncbi.nlm.nih.gov/41123263

https://wmpllc.org/ojs/index.php/jom/article/view/3918

Medical Cannabis and Opioid Receipt Among Adults With Chronic Pain

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“Question  Is participation in the New York State (NYS) medical cannabis program associated with reduced prescription opioid receipt among adults with chronic pain?

Findings  In this cohort study of 204 adults with chronic pain, participation in the NYS medical cannabis program, defined as monthly dispensation of medical cannabis reported by the dispensary pharmacist, was associated with significantly reduced prescription opioid receipt.

Meaning  These findings suggest that participation in a pharmacist-directed medical cannabis program may help reduce prescription opioid receipt among adults with chronic pain.

Abstract

Importance  Medical cannabis is increasingly considered a substitute for prescription opioid medications for chronic pain, driven by the urgent need for opioid alternatives to combat the ongoing epidemic.

Objective  To determine the association between participation in the New York State (NYS) medical cannabis program and prescription opioid receipt among adults with chronic pain.

Design, Setting, and Participants  This cohort study used data from the NYS Prescription Monitoring Program (PMP) from September 2018 through July 2023. Adults prescribed opioids for chronic pain who were newly certified for medical cannabis use in NYS were recruited from a large academic medical center and nearby medical cannabis dispensaries in the Bronx, New York. Monthly dispensation of medical cannabis to study participants was monitored for 18 months. Data analyses were performed from February 3, 2025, to July 15, 2025.

Exposure  Portion of days covered each month by pharmacist report of dispensed medical cannabis.

Main Outcomes and Measures  Prescription opioid receipt, defined as NYS PMP-reported prescription monthly opioid dispensation (mean daily dose in morphine milliequivalents [MME]), was assessed with marginal structural models adjusted for time-invariant and time-varying confounders, including self-reported unregulated cannabis use. Nonprescribed opioid use was also assessed during the study period.

Results  Among 204 participants, the mean (SD) age at baseline was 56.8 (12.8) years, and 113 (55.4%) were female. At baseline, participants’ mean (SD) pain severity score was 6.6 (1.8) out of 10, and mean (SD) pain interference score was 6.8 (1.9) out of 10. Baseline mean (SD) daily MME was 73.3 (133.0). During the 18-month follow-up period, participants’ mean (SD) daily MME decreased to 57.4 (127.8). This reduction in mean daily MME was associated with the monthly portion of days covered with medical cannabis; compared with no medical cannabis dispensed, participants dispensed a 30-day supply of medical cannabis were exposed to 3.53 fewer MME per day (β = −3.53; 95% CI, −6.68 to −0.04; P = .03).

Conclusions and Relevance  In this cohort study, participation in NYS’s medical cannabis program was associated with reduced prescription opioid receipt during 18 months of prospective follow-up, accounting for unregulated cannabis use.”

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2842414