Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Potential Anticancer Effect of Cannabis sativa L. Dichloromethane Extract Through Oxidative Stress-Related Pathways and the Inhibition of the Migration and Invasiveness of Human Breast Cancer Cells (MDA-MB-231 and MCF-7)

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“Breast cancer remains a leading cause of cancer-related morbidity and mortality globally, highlighting the urgent need for novel therapeutic strategies.

This study investigates the molecular mechanisms underlying the anti-proliferative potential of Cannabis sativa dichloromethane extract (C. sativa DCM) on oxidative stress, apoptosis, and invasion in human breast cancer cells.

Key biomarkers, such as antioxidant enzymes (Superoxide Dismutase (SOD) and Glutathione (GSH)), the transcription factor Nrf2, apoptotic proteins (p53, caspase-8 and 9), metalloproteinase (MMP-1 and MMP-9), and Transforming Growth Factor Beta (TGF-β) were examined. Cytotoxicity was assessed using an MTT assay in the MDA-MB-231 and MCF-7 breast cancer cell lines, with comparisons to normal skin fibroblasts (HS27). Oxidative stress biomarkers were quantified using enzymatic assays and ELISA kits, while apoptotic and anti-metastatic factors were determined by Western blotting.

Results demonstrated that C. sativa DCM extract induced significant cell death in a concentration-dependent manner, with IC50 values of 75.46 ± 0.132 μg/mL for MDA-MB-231 and 78.68 ± 0.50 μg/mL for MCF-7 cells. The extract decreased SOD and GSH levels while increasing p53 and caspase activity, confirming apoptosis activation. Additionally, C. sativa DCM inhibited migration and invasion by downregulating MMP-1, MMP-9, and TGF-β. The anti-proliferative potential of C. sativa DCM in breast cancer cells is mediated through a continuous biological pathway involving oxidative stress modulation, apoptotic signaling, and anti-invasive effects. Phytochemical analysis revealed terpenoids and steroids, including compounds like cannabidiol and tetrahydrocannabinol acid.

These findings suggest that C. sativa DCM extract holds potential as an anti-breast cancer therapeutic and warrants further preclinical and clinical investigations.”

https://pubmed.ncbi.nlm.nih.gov/41516029

“Cannabis sativa L., known in many slang languages as marijuana, bhang, ganja, for instance, is an herbaceous species originating from Central Asia and widely distributed around the world. It has been used as a source of fiber, food, oil, and for its multiple curative properties, including anti-parasitic, antipyretic, antibacterial, antitumor, vermifuge, dermatic, and pain-killing properties for centuries. Phytocannabinoids, derived from cannabis, have shown anti-cancer activity in cell lines”

“Based on these research findings, we concluded that C. sativa DCM extract possesses the potential to inhibit the proliferation of breast cancer cells (MCF-7 and MDA-MB-231), while exhibiting minimal cytotoxic effect on normal skin cells Hs27.”

“Given these conclusive findings, the presence of bioactive phytochemicals in C. sativa DCM can be considered as a potential source of anti-cancer agents.”

https://www.mdpi.com/1422-0067/27/1/152


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

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

Cross-sectional comparison of cannabis use in adults with neuropathic versus non-neuropathic pain

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“Introduction: Cannabis has been decriminalized by many states and shows promise in treating both neuropathic and non-neuropathic pain through its interaction with the endocannabinoid system and anti-inflammatory effects. This study examines differences in cannabis use for adults whose most bothersome chronic pain condition is neuropathic vs. non-neuropathic.

Materials and methods: Survey data were collected from adults receiving care at a pain clinic. Participants completed demographic questions and standardized self-report measures (PROMIS Pain Intensity/Interference and the ID-Pain tool). Participants’ most bothersome pain condition(s) were categorized as neuropathic or non-neuropathic pain based on ID-Pain scores. Linear regression models assessed differences in frequency and duration of cannabis product use between groups, adjusting for age and sex.

Results: A total of 113 individuals were recruited; following exclusions and missing data, 104 participants (61.5% female) were included in the final analysis. Of these, 36.5% reported neuropathic pain as their most bothersome, and 63.5% reported non-neuropathic pain. Those with neuropathic pain reported significantly more days per month of Tetrahydrocannabinol/Cannabidiol (THC/CBD) combination (b = 5.96, p = 0.02), Cannabidiol-only (CBD-only) (b = 8.82, p = 0.03), and Tetrahydrocannabinol-only (THC-only) products (b = 7.04, p = 0.02). They also used THC-only (b = 0.97, p < 0.05) and THC/CBD (b = 1.09, p < 0.01) products more frequently per day. Neuropathic pain was positively associated with pain intensity (b = 4.10, p < 0.001) and interference (b = 4.95, p < 0.001).

Discussion: Adults whose most bothersome pain condition(s) were neuropathic used cannabis, especially THC and THC/CBD combination products, more frequently than those whose most bothersome pain was non-neuropathic. Participants with neuropathic pain also reported higher levels of pain intensity and interference. Further longitudinal research is needed to confirm whether increased use of THC-rich cannabis provides symptom relief for adults with neuropathic pain.”

https://pubmed.ncbi.nlm.nih.gov/41487383

“Cannabis interacts with the endocannabinoid system, making it a potential treatment for neuropathic pain.”

“Because previous studies found THC products to be more effective in managing neuropathic pain by interacting with the endocannabinoid system, it is possible that our participants also experienced benefit; this could explain their higher use of THC containing products.

https://www.frontiersin.org/journals/pain-research/articles/10.3389/fpain.2025.1677391/full

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

Medical Cannabis Program Lowers Chronic Pain Opioid Prescriptions

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“Access to medical cannabis through a state-regulated program was associated with significantly lower rates of opioid prescriptions among adults with chronic pain, according to findings recently published in JAMA Internal Medicine.

The study included 204 adults enrolled in the New York State medical cannabis program, which provided monthly access to medical cannabis through a dispensary pharmacist, and 142 ultimately obtained the treatment. The data spanned from September 2018 through July 2023. Researchers measured prescription opioid receipt via mean daily dose in morphine milliequivalents (MME) and compared it with how many days’ worth of cannabis individuals were dispensed each month based on pharmacists’ reports.

After 18 months, the mean daily MME decreased by 22%, from 73 to 57.

The authors noted that instead of measuring medical cannabis exposure via its legalization status, they directly analyzed pharmacy dispensation amounts, a more accurate indicator of uptake. Randomized clinical trials are needed to see whether medical cannabis reduces opioid use, they added.”

https://pubmed.ncbi.nlm.nih.gov/41481315

https://jamanetwork.com/journals/jama/fullarticle/2843608

Extract engineering of Cannabis sativa yields novel antibacterial cannabinoids targeting Staphylococcus aureus and methicillin-resistant Staphylococcus aureus

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“Cannabis sativa is a phytochemically rich plant producing over 500 compounds, with cannabinoids recognized as its most bioactive constituents.

However, the natural exploration and exploitation of novel, pharmacologically active cannabinoids remain limited due to their trace abundance in the plant. To address this challenge, we employed an extract engineering strategy in which enriched fractions of major cannabinoids were chemically transformed through oxone/acetone oxidation under mild conditions.

This approach enabled the purification of seven cannabinoid analogs, including rare and previously undescribed compounds, in appreciable quantities. The structures of these analogs were elucidated using high-resolution mass spectrometry combined with comprehensive 1D and 2D NMR spectroscopy.

Antibacterial susceptibility assay revealed that out of seven compounds, Compound 1, 5, and 7 exerted significant inhibitory activity against both Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) pathogens.

A Checkerboard study revealed the synergistic interaction between active hits and Rifampin in both S. aureus and MRSA. The biofilm-based assay demonstrated the antibiofilm potential of the identified hits. The mechanistic exploration elucidated the cell membrane-based targeting of the potent hits, validated through scanning electron microscopy. Moreover, the Propidium iodide assay performed using flow cytometry and fluorescence microscopy revealed the membrane disruption effect of the identified hits. In addition, the ATP quantification study demonstrated a major decline in ATP levels along with an augmentation in ROS production in the MRSA pathogen.

Thus, this work establishes extract engineering as a powerful strategy to unlock rare cannabinoid scaffolds and highlights their potential as leads for combating multidrug-resistant Staphylococcus infections.”

https://pubmed.ncbi.nlm.nih.gov/41478197


“Cannabis sativa has diverse phytochemical composition and therapeutic potential.”

“In summary, comprehensive antistaphylococcal evaluation of the cannabinoid-based molecules demonstrated strong antibacterial activity against both S. aureus and MRSA pathogens, along with synergistic interaction when combined with standard drugs. Notably, the potent molecules expressed low propensity for the development of resistance in the MRSA strain. Moreover, the antibiofilm action of the potent hits highlighted their curative role…”

https://www.sciencedirect.com/science/article/abs/pii/S0045206825013288?via%3Dihub

Vaporized cannabis versus placebo for acute migraine: A randomized, double-blind, placebo-controlled crossover trial

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“Objective: To assess the efficacy of cannabis for the treatment of acute migraine.

Background: Preclinical and retrospective studies suggest cannabinoids may be effective in migraine treatment. However, there have been no randomized clinical trials examining the efficacy of cannabinoids for acute migraine.

Methods: In this randomized, double-blind, placebo-controlled, crossover trial, adults with migraine treated up to four separate migraine attacks, one each with vaporized (1) 6% Δ9-tetrahydrocannabinol (THC) (THC-dominant), (2) 11% cannabidiol (CBD) (CBD-dominant), (3) 6% THC + 11% CBD, and (4) placebo cannabis flower in a randomized order. Washout period between treated migraine attacks was ≥1 week. The primary endpoint was pain relief, and secondary endpoints were pain freedom and most bothersome symptom freedom, all assessed at 2-h post-vaporization.

Results: Ninety-two participants were enrolled and randomized, and 247 migraine attacks were treated. THC + CBD was superior to placebo at achieving pain relief (67.2% vs. 46.6%, odds ratio [95% confidence interval] 2.85 [1.22, 6.65], p = 0.016), pain freedom (34.5% vs. 15.5%, 3.30 [1.24, 8.80], p = 0.017), and most bothersome symptom freedom (60.3% vs. 34.5%, 3.32 [1.45, 7.64], p = 0.005) at 2 h, as well as sustained pain freedom at 24 h and sustained most bothersome symptom freedom at 24 and 48 h. THC-dominant was superior to placebo for pain relief (68.9% vs. 46.6%, 3.14 [1.35, 7.30], p = 0.008) but not pain freedom or most bothersome symptom freedom at 2 h. CBD-dominant was not superior to placebo for pain relief, pain freedom, or most bothersome symptom freedom at 2 h. There were no serious adverse events.

Conclusion: Acute migraine treatment with 6% THC + 11% CBD was superior to placebo at 2-h post-treatment with sustained benefits at 24 and 48 h.”

https://pubmed.ncbi.nlm.nih.gov/41469488

“Many people with migraine self-treat with cannabinoids or are interested in using cannabinoids to treat migraine. In this double-blind study, people with migraine treated up to 4 migraine attacks, 1 attack was treated with each of 3 vaporized cannabis flower treatments (THC 6%, CBD 11%, and THC 6% + CBD 11%) or placebo cannabis flower without THC or CBD, within the first 4 h of migraine attack onset. Four puffs of cannabis flower containing THC 6% + CBD 11% was superior to placebo at treating migraine attacks, though the study did not examine the long-term effects of frequent use.”

https://headachejournal.onlinelibrary.wiley.com/doi/10.1111/head.70025