Category Archives: THC (Delta-9-Tetrahydrocannabinol)

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

Ewing sarcoma-related pain: potential role of medical cannabis monotherapy in symptom management – a case report

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“Persistent, multimodal cancer pain remains a challenge, particularly in long-term survivors facing treatment-related complications. The management of high-dose opioid dependence concurrent with chronic, multi-drug resistant (MDR) periprosthetic infection presents a critical unmet need. This case reports the potential use and sustained efficacy of medical cannabis monotherapy, highlighting an unexpected temporal association with the resolution of inflammatory and infectious symptoms in a highly complex oncologic setting.

Case presentation

A 27-year-old male, a long-term survivor of high-risk Ewing Sarcoma of the proximal tibia, presented with intractable mixed pain (VAS 9–10) secondary to chronic, recurrent MDR periprosthetic osteomyelitis and multiple surgical revisions (2013–2024). Despite continuous use of high-dose opioids (up to 120 mg/day morphine equivalents), pain levels remained moderate-to-severe (VAS 6–7) and functional status was poor. The patient had previously found temporary relief with self-administered cannabis. In January 2025, after refusing limb amputation, supervised medical cannabis therapy (Bedrocan®, 22% THC, 1% CBD, 1 g/day) was initiated. Pain levels gradually stabilized at VAS 2–3, coinciding with complete opioid discontinuation within four weeks. Over nine months of follow-up, the patient maintained full autonomy and an active lifestyle. Notably, sustained cannabis monotherapy was associated with the complete closure of the chronic draining fistula and a reduction in systemic inflammatory markers (CRP from 9.6 to 2.3 mg/dL). No significant adverse effects were reported.

Conclusions

This case suggests that THC-rich medical cannabis may represent a feasible strategy for achieving opioid-free analgesia in selected patients with refractory oncologic pain. While causality cannot be established from a single observation, the correlation between cannabis initiation and the resolution of severe chronic inflammatory and infectious symptoms is intriguing and suggests a potential pleiotropic role extending beyond traditional pain management. While these findings align with emerging evidence highlighting the potent immunomodulatory and anti-inflammatory properties of cannabinoids, they contrast with some recent neutral meta-analyses in broader populations, an this would justify warrant urgent controlled investigation into the potential mechanisms of cannabinoids in complex inflammatory pain states and their role as a possible adjunct in managing long-term oncological complications.”

https://pubmed.ncbi.nlm.nih.gov/41572388

https://link.springer.com/article/10.1186/s42238-026-00388-x

The psychoactive cannabinoid THC inhibits peripheral nociceptors by targeting NaV1.7 and NaV1.8 nociceptive sodium channels

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“Δ⁹-Tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, is widely recognized for its central effects mediated by cannabinoid receptors. Here, we uncover a distinct peripheral mechanism by which THC inhibits the excitability of nociceptive neurons.

We show that THC directly targets the nociceptive voltage-gated sodium channels NaV1.7 and NaV1.8 through the conserved local anesthetic binding site. This interaction reduces sodium currents and suppresses action potential generation in peripheral sensory neurons.

Our findings demonstrate that, beyond its central psychoactivity, THC exerts direct peripheral nociceptor inhibition via modulation of NaV1.7 and NaV1.8, offering new insight into cannabinoid-based analgesia independent of cannabinoid receptor signaling.”

https://pubmed.ncbi.nlm.nih.gov/41565997

“Cannabis has been used for centuries for its analgesic properties, and its clinical relevance in pain management continues to grow.”

 “These findings reveal a previously unrecognized mechanism for THC-mediated peripheral analgesia and establish a non-canonical molecular pathway through which the psychoactive cannabinoid can inhibit nociceptor excitability and thereby pain.”

https://www.nature.com/articles/s41386-026-02355-9

Exploring the neuroprotective effects and underlying mechanisms of medical cannabinoids in ischemic stroke: a systematic meta-analysis with bibliometric mapping of cerebral ischemia research

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“Background: Ischemic stroke is an acute neurological disorder with limited treatment options. Medical cannabinoids (MCs), primary bioactive compounds extracted from cannabis plants, have shown therapeutic prospects for ischemic stroke. This study integrates bibliometrics and meta-analysis to comprehensively summarize the research landscape of MCs in cerebral ischemia and thoroughly investigate their role and potential mechanisms in ischemic stroke.

Methods: Bibliometric analysis was performed based on literature retrieved from Web of Science Core Collection (WoSCC), PubMed, and Scopus. For meta-analysis, a comprehensive search was conducted across four databases (WoSCC, PubMed, Embase, and Cochrane Library) and grey literature repositories. Studies were screened according to predefined criteria. Pooled standardized mean differences with 95% confidence interval were calculated, followed by subgroup analysis.

Results: A total of 241 publications were identified for bibliometric analysis. From 2000 to June 2025, the annual publication output on MCs in cerebral ischemia displayed a fluctuating yet overall upward trend. Keyword co-occurrence analysis revealed three major research topics: neuroprotective mechanisms of MCs, pathological models of cerebral ischemia, and bioactive components of MCs. Meta-analysis of 26 studies demonstrated that MCs provided significant neuroprotection in animal models of ischemic stroke, including cerebral infarct volume, neurological function score (NFS), cerebral blood flow (CBF), blood-brain barrier (BBB) permeability, brain water content, apoptosis (TUNEL-positive cells), oxidative stress markers, inflammation (TNF-α, IL-1β), and excitotoxicity (Glu/NAA, Lac/NAA ratio). Subgroup analysis revealed that intraperitoneal administration and a full-course of cannabidiol (CBD) treatment were associated with reduced heterogeneity and enhanced therapeutic benefit. Isoflurane was identified as a potentially suitable anesthetic.

Conclusion: MCs exert multi-target neuroprotection in ischemic stroke by improving CBF, reducing brain edema and BBB permeability, and inhibiting oxidative stress, neuroinflammation, apoptosis, and excitotoxicity. Future research should focus on high-quality clinical trials to validate these findings and translate MCs into clinical practice.”

https://pubmed.ncbi.nlm.nih.gov/41551042

“THC produces anti-inflammatory effects, reduces neuronal damage, and promotes hippocampal neurogenesis.”

“CBD acts as a negative allosteric modulator of cannabinoid receptors (CBR) and exerts brain-protective effects through multi-target regulatory properties “

 “Moreover, the results of meta-analysis consolidate preclinical evidence, demonstrating that MCs confer neuroprotection by mitigating multiple pathological processes, including cerebral tissue perfusion, BBB permeability and cerebral edema, oxidative stress, excitotoxicity, inflammatory responses, and apoptosis.”

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1731738/full

The Evidence for Medical Cannabis in Chronic Musculoskeletal Pain Management

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“Chronic musculoskeletal pain (CMP) is a pervasive condition that can impair daily functioning and quality of life. Traditional pharmaceutical therapies, including non-steroidal anti-inflammatory drugs, gabapentinoids, and opioids, often yield suboptimal results and carry notable risks, such as adverse side effects and dependence.

Increasing interest has turned toward medical cannabis, particularly combined formulations of cannabidiol (CBD) and tetrahydrocannabinol (THC), as a potential alternative or complement to current pain management strategies.

Evidence suggests that cannabinoids interact with the endocannabinoid system to modulate nociception and inflammation, offering meaningful pain relief and possibly reducing opioid requirements.

However, heterogeneity in study designs, product formulations, and regulatory frameworks presents challenges in drawing definitive conclusions. Additionally, while most adverse effects, such as fatigue, dizziness, and mild cognitive changes, are generally reported as tolerable, concerns remain about long-term safety and standardization of dosing.

Taken together, the existing literature points to a promising role for medical cannabis in CMP management, underscoring the need for further high-quality research to establish best practices, clarify patient selection, and guide clinicians in safe and effective cannabinoid therapy.”

“This scoping review highlights the potential role of medical cannabis in managing musculoskeletal pain. Evidence suggests it may reduce pain, enhance well-being, and improve quality of life, particularly as an alternative or adjunct to opioids. Adverse effects are typically mild, supporting its use as a safer long-term option. However, data on long-term efficacy, especially for CBD, remain limited.

Given the risks of opioid dependence, cannabis offers a promising therapeutic alternative.”

https://surgicoll.scholasticahq.com/article/138573-the-evidence-for-medical-cannabis-in-chronic-musculoskeletal-pain-management

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


Phytocannabinoids influence phospholipid metabolism of melanoma cells: Modulation of in vitro effects of the UVA irradiation

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“The high metastatic potential of melanoma and its poor prognosis in advanced stages motivate the search for innovative therapeutic approaches. Therefore, this study aimed to assess the effects of phytocannabinoids (cannabidiol-CBD, and cannabigerol-CBG) on the structure and function of the melanoma cell membrane, phospholipid metabolism, and the respective metabolites generated in ROS- and enzyme-dependent reactions.

Biochemical and physicochemical parameters were analyzed in melanoma cells (SK-MEL-5) cultured for 24 h with CBD (5 µM), CBG (1 µM), and their combination applied either alone or after UVA irradiation (365 nm) at a dose of 18 J/cm².

Phytocannabinoids have been shown to partially counteract changes in the levels of cell membrane components, including phospholipid polyunsaturated fatty acids (PUFAs) and sialic acid, consequently affecting surface charge density and lipid rafts, which may be a potential target for anticancer therapy. Furthermore, by changing the activity of lipolytic enzymes (PLA2/COX1/2/LOX-5), phytocannabinoids partially enhanced the UVA-induced decrease in free PUFAs. Consequently, the levels of lipid mediators, including endocannabinoids and eicosanoids, were altered.

The use of phytocannabinoids led to a significant increase in 2-AG levels, while the combined action of CBD/CBG reduced the levels of pro-inflammatory eicosanoids. UVA radiation increased the expression of G-protein-coupled receptors in melanoma cells (CB1/2/TRPV1/PPARγ), while the combined use of CBD/CBG reduced their expression.

Therefore, the results have shown that CBD and CBG modulate the metabolism of phospholipids and PUFAs by altering the functions of melanoma cell membranes, potentially offering options for the use of these phytocannabinoids in the integrative biomedicine treatment of melanoma.”

https://pubmed.ncbi.nlm.nih.gov/41529510

“Phytocannabinoids modulate endocannabinoid levels, supporting antitumor activity.”

“In summary, the results of this study indicate that phytocannabinoids (CBD and/or CBG) alter the functionality of melanoma cell membranes by modeling the structure and metabolism of phospholipids and free PUFAs, which may offer potential benefits in integrated melanoma therapy.”

https://www.sciencedirect.com/science/article/pii/S0753332226000351?via%3Dihub

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

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