Category Archives: THC (Delta-9-Tetrahydrocannabinol)

A Longitudinal Assessment of Endometriosis Patients Prescribed Cannabis-Based Medicinal Products: A Case Series From the UK Medical Cannabis Registry

Posted on by
pubmed logo

“Background: Although there is growing evidence supporting the use of cannabis-based medicinal products (CBMPs) for the management of chronic pain, there is a paucity of data on their effect on endometriosis-associated chronic pain.

Aims: This study aimed to perform an analysis of pain-specific and general health-related quality of life (HRQoL) outcomes for patients with endometriosis-associated chronic pain treated with CBMPs.

Materials and methods: Primary outcomes included changes in patient-reported outcome measures (PrOMs) from baseline to 1, 3, 6, 12 and 18 months. A repeated measures ANOVA was applied to assess changes in PrOMs at 1 to 18 months from baseline. Secondary outcomes included incidence and frequency of adverse events (AEs).

Results: Sixty-three patients met inclusion criteria. Initiation of CBMPs was associated with improvements in all pain-specific PrOMs from baseline to 18 months (p < 0.050). EQ-5D-5L index value showed improvements between baseline and all months (p < 0.050). Anxiety and sleep quality PrOMs showed improvements from baseline to 18 months (p < 0.050). Minimal clinically significant differences (11%-37%), moderately important improvements (5%-22%) and substantial improvements (0%-11%) were observed in the Brief Pain Inventory (BPI) and pain severity visual analogue scale. Sixty-two adverse events were reported by 16 (25.40%) participants.

Conclusions: This study observed an association between CBMP treatment and improvements in pain and HRQoL in patients with endometriosis. Causality cannot be inferred due to the nature of this observational study; however, these findings provide complementary evidence for the development of randomised controlled trials to assess the efficacy of CBMPs for endometriosis-associated chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/41305963

“Cannabis-based medicinal products (CBMPs) that contain phytocannabinoids, such as (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), have been identified with potential to manage endometriosis-related pain.”

“Overall, these results provide a signal towards improvement in short-term pain severity and interference for endometriosis patients after the initiation of CMBP treatment, although there was diversity at different pain intervals.”

https://obgyn.onlinelibrary.wiley.com/doi/10.1111/ajo.70078

Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy

Posted on by

“Tetrahydrocannabinols (THCs) antagonize the CB1 and CB2 cannabinoid receptors, whose signaling to the endocannabinoid system is essential for controlling cell survival and proliferation as well as psychoactive effects.

Most tumor cells express a much higher level of CB1 and CB2; THCs have been investigated as potential cancer therapeutic due to their cannabimimetic properties. To date, THCs have been prescribed as palliative medicine to cancer patients but not as an anticancer modality.

Growing evidence of preclinical research demonstrates that THCs reduce tumor progression by stimulating apoptosis and autophagy and inhibiting two significant hallmarks of cancer pathogenesis: metastasis and angiogenesis. However, the degree of their anticancer effects depends on the origin of the tumor site, the expression of cannabinoid receptors on tumor cells, and the dosages and types of THC.

This review summarizes the current state of knowledge on the molecular processes that THCs target for their anticancer effects. It also emphasizes the substantial knowledge gaps that should be of concern in future studies. We also discuss the therapeutic effects of THCs and the problems that will need to be addressed in the future. Clarifying unanswered queries is a prerequisite to translating the THCs into an effective anticancer regime.”

https://pubmed.ncbi.nlm.nih.gov/36696005/

https://link.springer.com/article/10.1007/s10555-023-10078-2

Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts

Posted on by

“Cannabis sativa is one of the oldest cultivated plants. Many of the medicinal properties of cannabis are known, although very few cannabis-based formulations became prescribed drugs. Previous research demonstrated that cannabis varieties are very different in their medicinal properties, likely due to the entourage effect-the synergistic or antagonistic effect of various cannabinoids and terpenes.

In this work, we analyzed 25 cannabis extracts containing high levels of delta-9-tetrahydrocannabinol (THC). We used HCC1806 squamous cell carcinoma and demonstrated various degrees of efficiency of the tested extracts, from 66% to 92% of growth inhibition of cancer cells.

Inflammation was tested by induction of inflammation with TNF-α/IFN-γ in WI38 human lung fibroblasts. The efficiency of the extracts was tested by analyzing the expression of COX2 and IL6; while some extracts aggravated inflammation by increasing the expression of COX2/IL6 by 2-fold, other extracts decreased inflammation, reducing expression of cytokines by over 5-fold.

We next analyzed the level of THC, CBD, CBG and CBN and twenty major terpenes and performed clustering and association analysis between the chemical composition of the extracts and their efficiency in inhibiting cancer growth and curbing inflammation.

A positive correlation was found between the presence of terpinene (pval = 0.002) and anti-cancer property; eucalyptol came second, with pval of 0.094. p-cymene and β-myrcene positively correlated with the inhibition of IL6 expression, while camphor correlated negatively. No significant correlation was found for COX2. We then performed a correlation analysis between cannabinoids and terpenes and found a positive correlation for the following pairs: α-pinene vs. CBD, p-cymene vs. CBGA, terpenolene vs. CBGA and isopulegol vs. CBGA.

Our work, thus, showed that most of high-THC extracts demonstrate anti-cancer activity, while only certain selected extracts showed anti-inflammatory activity. Presence of certain terpenes, such as terpinene, eucalyptol, cymene, myrcene and camphor, appear to have modulating effects on the activity of cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/36144796

“Cannabis sativa is a plant with a long history of consumption as food and medicine. Delta-9-tetrahydrocannabinol (THC) is one of the main cannabinoids in cannabis; it has many properties, including anti-cancer, anti-inflammatory, analgetic and others.”

https://www.mdpi.com/1420-3049/27/18/6057/htm

Administration of Δ9-Tetrahydrocannabinol Following Controlled Cortical Impact Restores Hippocampal-Dependent Working Memory and Locomotor Function

Posted on by

“Hypothesis: Administration of the phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) will enhance brain repair and improve short-term spatial working memory in mice following controlled cortical impact (CCI) by upregulating granulocyte colony-stimulating factor (G-CSF) and other neurotrophic factors (brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF]) in hippocampus (HP), cerebral cortex, and striatum. 

Materials and Methods: C57BL/6J mice underwent CCI and were treated for 3 days with Δ9-THC 3 mg/kg intraperitoneally (i.p.). Short-term working memory was determined using the spontaneous alternations test during exploratory behavior in a Y-maze. Locomotor function was measured as latency to fall from a rotating drum (rotometry). These behaviors were recorded at baseline and 3, 7, and 14 days after CCI. Groups of mice were euthanized at 7 and 14 days. Extent of microgliosis, astrocytosis, and G-CSF, BDNF, and GDNF expression were measured at 7 and 14 days in cerebral cortex, striatum, and HP on the side of the trauma. Levels of the most abundant endocannabinoid (2-arachidonoyl-glycerol [2-AG]) was also measured at these times. 

Results: Δ9-THC-treated mice exhibited marked improvement in performance on the Y-maze indicating that treatment with the phytocannabinoid could reverse the deficit in working memory caused by the CCI. Δ9-THC-treated mice ran on the rotarod longer than vehicle-treated mice and recovered to normal rotarod performance levels at 2 weeks. Δ9-THC-treated mice, compared with vehicle-treated animals, exhibited significant upregulation of G-CSF as well as BDNF and GDNF in the cerebral cortex, striatum, and HP. Levels of 2-AG were also increased in the Δ9-THC-treated mice. 

Conclusion: Administration of the phytocannabinoid Δ9-THC promotes significant functional recovery from traumatic brain injury (TBI) in the realms of working memory and locomotor function. This beneficial effect is associated with upregulation of brain 2-AG, G-CSF, BDNF, and GDNF. The latter three neurotrophic factors have been previously shown to mediate brain self-repair following TBI and stroke.”

https://pubmed.ncbi.nlm.nih.gov/34747647

https://www.liebertpub.com/doi/10.1089/can.2021.0053

The association between marijuana use and oral cancer risk: a systematic review and meta-analysis of case-control studies

Posted on by

“The relationship between marijuana use and oral cancer risk remains controversial, with conflicting evidence from epidemiological studies. This systematic review and meta-analysis aimed to synthesize available evidence on the association between marijuana consumption and oral cancer incidence.

Following PRISMA guidelines, we conducted comprehensive searches across Scopus, PubMed, Web of Science, and Embase databases up to August 2025. We included only case-control studies reporting quantitative risk estimates for marijuana use and histologically confirmed oral cancer (ICD-10 codes C00-C06). Data extraction followed standardized protocols, and study quality was assessed using the Joanna Briggs Institute checklist. Statistical analyses were performed using Comprehensive Meta-Analysis software with random-effects models. Heterogeneity was evaluated using I2 statistics, and publication bias was assessed through funnel plots and Egger’s regression test. Six case-control studies involving 4,686 cases and 10,370 controls were included.

The pooled odds ratio demonstrated a statistically significant inverse association between marijuana use and oral cancer risk (OR = 0.659, 95% CI: 0.500-0.869, p = 0.003, I2 = 47.35).

Subgroup analyses were performed based on the duration of use, gender, and age at initiation of marijuana use; however, no clear dose-response relationship was observed. Sensitivity analyses confirmed robustness of findings, with ORs ranging from 0.599 to 0.708 across iterations. No significant publication bias was detected (Egger’s test p = 0.532). Three individual studies showed statistically significant protective effects, while three others were non-significant.

This meta-analysis suggests marijuana use is associated with reduced oral cancer risk.

However, given methodological limitations, heterogeneity in exposure assessment, and conflicting recent evidence, these findings require cautious interpretation. Future large-scale prospective cohort studies with standardized exposure measurements are essential for definitive conclusions.”


https://pubmed.ncbi.nlm.nih.gov/41236922/

https://www.tandfonline.com/doi/full/10.1080/15332640.2025.2581692

Cannabinoids shift the basal ganglia microRNA m6A methylation profile towards an anti-inflammatory phenotype in SIV-infected rhesus macaques

Posted on by
pubmed logo

“Epitranscriptomic modifications [N6-methyladenosine (m6A)] regulate various diseases, including cancer and inflammation. Despite their functional relevance in neural development and differentiation, the role of m6A modifications in HIV neuropathogenesis is unknown. Using anti-N6-methyladenosine (m6A) antibody-immunoprecipitation and microarray profiling, we identified m6A modifications in miRNAs in basal ganglia (BG) of uninfected (VEH) and SIV-infected Rhesus macaques (RMs) on combination anti-retroviral therapy (ART) and either VEH-treated (VEH/SIV/ART) or THC:CBD-treated (THC:CBD/SIV/ART).

HIV/SIV infection promoted an overall hypomethylated miRNA m6A profile. While THC:CBD did not significantly impact the overall hypomethylated m6A profile, specific miRNAs predicted to target proinflammatory genes showed marked m6A hypomethylation compared to VEH-treated RMs. Additionally, specific BG m6A-modified miRNAs were detected in BG-derived extracellular vesicles. Mechanistically, the DRACH motif in the miR-194-5p seed region was significantly m6A hypomethylated in THC:CBD/SIV/ART RMs. Unlike wild-type, in-vitro transfected m6A-modified miR-194-5p mimics failed to downregulate STAT1 protein expression. Further, compared to VEH/SIV/ART RMs, THC:CBD significantly reduced m6A methylation of 44 miRNAs directly involved in regulating CNS network genes.

Our findings indicate that m6A epi-transcriptomic marks in the seed nucleotides can impair miRNA function and that cannabinoids may preserve it by reducing m6A methylation levels, thus providing a mechanistic explanation underlying their anti-neuroinflammatory effects in HIV/SIV infection.”

https://pubmed.ncbi.nlm.nih.gov/41286161

https://www.nature.com/articles/s42003-025-09049-w

Advances in the Quest for Safe and Effective Drugs That Target the Cannabinoid Receptor Type 1 (CB1)

Posted on by
pubmed logo

“Pain management costs the world billions of dollars each year, and there are limited nonopioid options to treat people suffering from chronic pain. Opioids are excellent analgesics but are liable to abuse and fatal overdoses. This Microperspective summarizes challenges and opportunities pertaining to creating nonopioid drugs that could be used to treat chronic pain, substance abuse, fatty liver, or obesity by targeting the cannabinoid receptor type 1 (CB1).”

https://pubmed.ncbi.nlm.nih.gov/41257001

https://pubs.acs.org/doi/10.1021/acsmedchemlett.5c00402

Acute Effects of Cannabis on Alcohol Craving and Consumption: A Randomized Controlled Crossover Trial

Posted on by
pubmed logo

“Objective: Cannabis use is strongly linked with heavy drinking and worse alcohol treatment outcomes; however, it may also contribute to decreased alcohol consumption. To date, no human studies have established a causal effect of cannabis on alcohol motivation. The aim of this double-blind crossover randomized clinical trial was to examine dose-dependent acute effects of delta-9-tetrahydrocannabinol (THC) on alcohol craving and consumption.

Methods: Across three experimental days, 157 participants reporting heavy alcohol use and cannabis use two or more times weekly were randomized to smoke cannabis cigarettes containing 7.2% THC, 3.1% THC, or 0.03% THC (placebo), followed by exposures to neutral and personalized alcohol cues and an alcohol choice task for alcohol self-administration. A total of 138 participants completed two or more experimental sessions (mean age, 25.6 years [SD=5.1]; 35% women; 45% racial/ethnic minorities). Primary outcomes included craving, Alcohol Craving Questionnaire-Short Form, Revised (ACQ-SF-R), and an alcohol urge question; the secondary outcome was percent of total available milliliters of alcohol consumed.

Results: There were no significant effects of cannabis on ACQ-SF-R ratings after smoking and during alcohol cue exposure, but 7.2% THC reduced alcohol urge immediately after smoking. Participants consumed significantly less alcohol after smoking cannabis with 3.1% THC and 7.2% THC, reducing consumption by 19% and 27%, respectively.

Conclusions: Following overnight cannabis abstinence, smoking cannabis acutely decreased alcohol consumption compared to placebo. Further controlled research on a variety of cannabinoids is needed to inform clinical alcohol treatment guidelines.”

https://pubmed.ncbi.nlm.nih.gov/41254853

“These data provide preliminary evidence that cannabis may reduce alcohol consumption under some conditions”

https://psychiatryonline.org/doi/10.1176/appi.ajp.20250115

Cannabidiol and ∆9-Tetrahydrocannabinol in Endometriosis: A Literature Review on Therapeutic Applications and Mechanisms

Posted on by
pubmed logo

“Endometriosis is a chronic, inflammatory, and multifactorial disease characterized by the presence of endometrial tissue outside the uterine cavity, often associated with debilitating symptoms. It affects approximately 10% of women of reproductive age and is also related to infertility. Endometriosis can be classified as peritoneal, ovarian, or deep endometriosis, with primary symptoms including chronic pelvic pain, dysmenorrhea, and dyspareunia. Diagnosis and treatment are challenging, with laparoscopy and biopsy of ectopic tissue being the gold standard.

Cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC) are two major cannabinoids found in the Cannabis sativa plant, widely known for their medicinal properties.

An experimental study conducted in rats demonstrated the anti-inflammatory, antioxidant, and antiangiogenic effects of intraperitoneal CBD use in the treatment of endometriosis. The objective of the present study was to conduct a literature review on the therapeutic potential of Cannabidiol (CBD) and ∆9-Tetrahydrocannabinol (THC) in the signs and symptoms of endometriosis. Research on PubMed, Embase, and Scopus platforms was conducted to determine the reproducibility and safety of treatment in humans, including dosage and administration route, as the current use is off-label.”

https://pubmed.ncbi.nlm.nih.gov/41248202


A Balanced Cannabinoids Mixture Protects Neural Stem/progenitor Cells from CoCl2 Induced Injury by Regulating Autophagy and Inflammation: An in Vitro Study

Posted on by
pubmed logo

“Although tetrahydrocannabinol (THC) and cannabidiol (CBD) have been individually studied for their neuroprotective roles, few studies have addressed the effects of their balanced 1:1 formulation Satinex (STX) under pathologic conditions like hypoxia. Moreover, the effect of STX on embryonic neural stem/progenitor cells (ENS/PCs) derived from the rat embryonic brain, which are highly vulnerable during early development, remains unexplored.

Considering the pivotal role of hypoxia in numerous neuropathological situations, this study examined the impact of STX on rat ENS/PCs exposed to chemically induced hypoxia.

ENS/PCs were isolated from rat embryos and subjected to hypoxia using 100 µM cobalt (II) chloride hexahydrate (CoCl₂0.6 H₂O) for 48 h. Cytotoxic activity of STX andCoCl2was assessed using the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2 H-tetrazolium (MTT) assay, while stem cell identity was confirmed via flow cytometry (Nestin, SOX2). STX (0.1 and 0.5 µM) was applied under both normoxic and hypoxic conditions. Expression levels of hypoxia-inducible factor 1-alpha (Hif1α) mRNA, autophagy markers (Beclin-1, microtubule-associated protein 1 light chain 3-II [LC3-II]), and pro-inflammatory proteins nuclear factor kappa B [NF-κB], Toll-like receptor 2 [TLR2], Toll-like receptor 4 [TLR4]) were assessed using reverse transcription polymerase chain reaction (RT-PCR) and western blot techniques following STX treatment.

Based on flow cytometric assays, over 70% of cultivated cells were positive for Nestin and SOX2. Hypoxia significantly reduced cell viability and proliferation, accompanied by increased Hif1α mRNA expression. Treatment with STX (0.1 µM and 0.5 µM) significantly reversed these changes, restoring cell viability and proliferation while reducing Hif1α levels. Hypoxia also elevated autophagy markers (Beclin-1, LC3-II) and pro-inflammatory proteins (NF-κB, TLR2, TLR4), which STX suppressed in a dose-dependent manner.

This study provides novel evidence that STX mitigates hypoxia-induced neural damage by downregulating Hif1α and its downstream inflammatory and autophagic signaling pathways. The use of a clinically relevant cannabinoids mixture and a developmentally sensitive cell model underline the translational potential of balanced THC/CBD formulations in the treatment of hypoxia-related neurodegenerative and neurodevelopmental conditions.”

https://pubmed.ncbi.nlm.nih.gov/41240218

https://link.springer.com/article/10.1007/s12640-025-00770-2