Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Medical Cannabis for the Treatment of Peripheral Neuropathy due to Diabetes: A Systematic Review

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“Introduction: This systematic review evaluated randomized controlled trials (RCTs) conducted specifically in participants with diabetes and painful peripheral neuropathy to assess the effectiveness and safety of medical cannabis, isolated cannabinoids, or nationally approved cannabis-based medicines as adjuvant treatment, compared with placebo or baseline.

Materials and methods: Controlled clinical studies and RCTs in adults with diabetic peripheral neuropathy were eligible. Animal and in vitro studies were excluded. We searched PubMed, Google Scholar, Cochrane Library, and Scopus and screened 15,377 records; 35 full-text articles were assessed for eligibility, and 4 RCTs were included in the qualitative synthesis.

Results: Three of four studies reported statistically significant reductions in neuropathic pain with cannabinoid-based interventions compared with placebo, whereas one trial did not demonstrate superiority. In two trials using vaporized or sublingual Δ9-tetrahydrocannabinol (THC), doses in the range of approximately 16-18 mg were associated with clinically meaningful pain relief in participants. Adverse effects, including dizziness and cognitive symptoms, were common but generally mild-to-moderate, and discontinuations due to adverse effects varied across studies.

Discussion/conclusion: Evidence from four small, heterogeneous RCTs suggests that cannabinoid-based therapies may reduce pain in some patients with diabetic peripheral neuropathy; however, the limited number of studies, variability in formulations and comparators, and risk of bias preclude firm conclusions regarding efficacy. Observed THC doses around 16-18 mg/day delivered via vaporized or sublingual routes should be viewed as preliminary, hypothesis-generating ranges rather than definitive recommendations. Larger, contemporary RCTs with rigorous risk-of-bias control, standardized outcomes, and detailed safety reporting are needed.”

https://pubmed.ncbi.nlm.nih.gov/41714301

“three of four identified studies demonstrated statistically significant reductions in pain compared with placebo or baseline, suggesting that cannabinoid-based interventions may offer analgesic benefit for some patients with diabetic peripheral neuropathy.”

https://journals.sagepub.com/doi/10.1177/25785125261425444

The Paradoxical Effect of Cannabis Use on Cognition in Chronic Psychotic Disorders

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“Background/objectives: Cannabis use has a particularly high prevalence in individuals with psychotic disorders. Although cannabis use is generally associated with cognitive impairments in the general population, its impact on cognition in psychosis remains controversial. This study aimed to investigate the association between cannabis use and cognitive performance in a cohort of individuals affected by psychotic disorders.

Methods: A total of 105 inpatients with psychotic disorders (mean age: 40.3 years; 34 females) were recruited from the University Hospital Center “Mother Teresa” in Tirana. Data collection included socio-demographic and clinical variables. Cognitive functioning was evaluated using the Montreal Cognitive Assessment (MoCA), while psychopathology was assessed with the Brief Negative Symptom Scale (BNSS), the Calgary Depression Scale for Schizophrenia (CDSS), the Psychotic Symptom Rating Scales (PSYRATS), and the Scale for the Assessment of Thought, Language, and Communication (TLC).

Results: Cannabis users (CU) were more frequently male, younger, and exhibited an earlier onset of psychosis compared to non-users (No-CU). Importantly, CU demonstrated higher MoCA scores, with the most favorable outcomes observed among daily users.

Conclusions: Contrary to the prevailing assumption that cannabis use exacerbates cognitive decline, our findings indicate an unexpected association between cannabis use and preserved cognitive functioning in psychosis. These results underscore the need to consider dosage, frequency, and cannabinoid composition (THC/CBD ratio) when interpreting cannabis-related cognitive outcomes in psychotic disorders.”

https://pubmed.ncbi.nlm.nih.gov/41718389

“the present study highlights that, in certain cases, patients with psychosis who use cannabis may demonstrate relatively preserved or even superior cognitive performance compared with non-using patients. These results raise important clinical and research questions.”

https://www.mdpi.com/1873-149X/33/1/11

Cannabinoids and the autophagy-related signaling in brain Tumors: From mechanistic insights to therapeutic Frontiers in glioblastoma

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“Glioblastoma multiforme (GBM) is a very aggressive primary brain tumor in adults, characterized by extensive infiltration, therapeutic resistance, and a dismal prognosis, with an average life of roughly 14 months. Despite advances in oncology, therapeutic progress for GBM has been limited, prompting intensive efforts to discover novel interventions.

Cannabinoids, beyond their established role as antiemetics during chemotherapy and radiotherapy, have emerged as potential cytotoxic agents against neoplastic cells.

Recent studies demonstrate that GBM harbors alterations in the endocannabinoid system, including changes in cannabinoid metabolism and receptor (CB1R, CB2R) expression. Engagement of these receptors by cannabinoids can suppress proliferation, invasion, and induce morphological changes in GBM cells, also activating intrinsic autophagy pathways.

Autophagy, a process central to cellular degradation and recycling, exerts dual roles in tumor survival and apoptosis, critically modulated by cannabinoids in glioblastoma. Preclinical work in cell lines and animal models suggests that both cannabinoids and pharmacologic modulators of autophagy reduce GBM proliferation and enhance responsiveness to chemotherapeutics. Early clinical studies indicate favorable safety profiles and potential survival benefits.

This review synthesizes the molecular mechanisms and signaling pathways underlying cannabinoid-induced autophagy and anticancer activity, and summarizes the current preclinical and clinical research on cannabinoid-based therapies for GBM.”

https://pubmed.ncbi.nlm.nih.gov/41679657

“This review demonstrates that cannabinoids, an emerging class of potential antitumor agents, promote autophagy in cancer cells and enhance the cytotoxic effects of these compounds. The study demonstrated that THC facilitates autophagy and apoptosis in diverse cancer cell types, whereas nontransformed astrocytes display resistance to cannabinoid-induced cytotoxicity. “

https://www.sciencedirect.com/science/article/abs/pii/S0006295226001127?via%3Dihub


Activation of Cannabinoid Receptor 1 Enhances Wound Healing by Promoting the Proliferative Phase

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“The mechanisms underlying wound healing mediated by cannabinoid receptor 1 (CB1)-known for its neuromodulatory functions-remain incompletely understood. Therefore, we investigated the impact of activating CB1 using specific agonists, both in vitro and in vivo, with a focus on wound healing.

In the in vitro study, fibroblasts were isolated and cultured from the dermis of human skin and treated with a CB1 agonist, 2-arachidonyl glyceryl ether (2-AGE). In the in vivo study, a mouse acute wound model was created using a skin biopsy punch and treated with the CB1 agonist arachidonoyl 2′-chloroethylamide (ACEA).

The in vitro study revealed that 2-AGE increased cell proliferation and differentiation, upregulated the expression of alpha-smooth muscle actin (α-SMA), N-cadherin, and vimentin, and enhanced cell migration as well as the synthesis of type I and III collagen and fibronectin in normal human dermal fibroblasts. The CB1 antagonist AM251 abolished 2-AGE-induced expression of α-SMA, type I collagen, and fibronectin. In vivo, ACEA treatment accelerated wound closure, increased expression of α-SMA, type I collagen, and fibronectin, and ultimately increased epidermal and dermal thickness.

Overall, these findings suggest that the activation of CB1 promotes wound healing and provides evidence for the therapeutic potential of CB1 agonists in wound treatment.”

https://pubmed.ncbi.nlm.nih.gov/41683598

“Recent research has highlighted the role of the endocannabinoid system (ECS) in skin physiology and repair.”

“Clinical evidence indicates that the topical application of Cannabis-Based Medicines (TCBMs) facilitates tissue repair and promotes complete wound closure in previously refractory wounds.”

“In conclusion, our findings support the hypothesis that CB1 receptor activation facilitates wound healing through both cellular and molecular mechanisms.”

“Thus, these findings strongly support the therapeutic potential of targeting specific agonists as a viable strategy to accelerate the proliferative or contractile phases and thereby enhance the rate of wound healing.”

https://www.mdpi.com/1422-0067/27/3/1171


Anti-inflammatory and analgesic potential of minor cannabinoids in vivo

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“The cannabis plant produces many bioactive compounds, including the major cannabinoids THC and CBD, and many lesser studied “minor” phytocannabinoids including cannabinol (CBN), cannabichromene (CBC), cannabicyclol (CBL), and cannabigerol (CBG). These compounds are touted for various ailments, including pain, inflammation, and anxiety, but experimental data on their effects are lacking, especially that of CBL, which has yet to be assessed in vivo.

Methods

To assess in vivo activity, adult male and female C57BL/6J mice were administered each compound and tested repeatedly in the tetrad battery. The potential analgesic effects in chronic pain states were assessed using the lipopolysaccharide (LPS)-induced hindpaw inflammatory pain and chronic constriction injury (CCI) neuropathic pain paradigms. Lastly, to address common psychological comorbidities of pain, CBN, CBL, and CBG were assessed in the tail suspension and marble burying tests.

Results

Cannabinol (≥ 25 mg/kg) induced classic cannabinoid effects, including acute antinociception. These effects were differentially and partially blocked by selective antagonism of CB1, adenosine A2A, or TRPV1 receptors. CBL (≥ 50 mg/kg) induced hypothermia that was fully blocked by A2A antagonism but had no apparent CB1-mediated activity. LPS-induced edema and paw proinflammatory cytokine levels were reduced by either CBN or CBL (100 mg/kg). CCI-induced cold allodynia was attenuated by either CBN (≥ 50 mg/kg) or CBL (100 mg/kg), but only at high doses that also induce catalepsy and hypothermia. None of these minor cannabinoids displayed anxiolytic- or antidepressant-like activity without concomitant locomotor effects.

Conclusions

Together, these findings suggest that CBN produces anti-inflammatory effects via cannabinoid receptor-dependent and -independent pathways, whereas CBL acts primarily through CB receptor-independent mechanisms.”

https://pubmed.ncbi.nlm.nih.gov/41680865

https://link.springer.com/article/10.1186/s42238-025-00384-7

Health-related quality of life in patients receiving medicinal cannabis: systematic review and meta-analysis of primary research findings 2015-2025

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“Purpose: The global burden of chronic health conditions is significant. Medicinal cannabis (MC) is a legalised treatment option for patients with chronic health conditions in some countries. Health-related quality of life (HRQL) is an important patient-reported outcome across all chronic health conditions. We aimed to determine how studies of MC therapy justify, measure, and report HRQL, and assess the current evidence for HRQL following MC treatment.

Methods: Systematic review searching AMED, Medline, Web of Science, Scopus, Embase, Cinahl, and PsycINFO from Jan 2015 to Apr 2025. Studies using validated HRQL measures pre-, and post-MC treatment for any chronic health condition were included. Screening and data extraction were performed independently by two reviewers. Completeness of HRQL reporting was evaluated. Meta-analyses for short-term (2-weeks to 3-months), medium-term (> 3 to < 12-months), and long-term (≥ 12-months) HRQL outcomes were conducted, with Risk of Bias (RoB) assessed in randomised control trials (RCTs).

Results: Of 16,674 retrieved citations, 64 studies were retained for analysis:12 RCTs; 38 cohort studies; 13 case series; 1 non-randomised experimental study. Thirty-nine studies (61%) provided justification for assessing HRQL and five (8%) provided HRQL definitions. Studies used generic (n = 52, 81%) or condition-specific (n = 12, 19%) HRQL measures, with EQ-5D-5L most commonly used. Meta-analyses: RCTs showed small short-term HRQL improvements (Cohen’s d = 0.30, p = 0.03), with some concerns or low RoB. For observational studies, HRQL improved in all follow-up periods (d = 0.43 to 0.74; all p < 0.001). HRQL improvement varied between, and within, different health conditions.

Conclusion: This systematic review and meta-analyses of studies published between 2015 and 2025 found that few studies provided HRQL definitions, and a third of studies did not explain why they measured HRQL. To ensure appropriate measures are used for this important treatment outcome, future studies should define HRQL and justify the HRQL assessment in the context of research objectives.

Overall, improvements in HRQL were observed across studies of patients using MC.”

https://pubmed.ncbi.nlm.nih.gov/41621036

Plain language summary

“Medicinal cannabis (MC) is a treatment option for patients in countries where prescribing MC is legal. Health-related Quality of Life (HRQL) can mean different things to different people but remains an important treatment outcome for all patients, regardless of their specific health condition. HRQL varies depending on the context and measurement tool (questionnaire) used. We aimed to find out (1) how HRQL assessment is justified, defined and measured in MC research, and (2) if HRQL improves in patients prescribed MC. We looked at studies published over the past decade that reported HRQL in patients before and after MC treatment. Most studies (81%) used generic HRQL questionnaires (e.g., EuroQol Group: EQ-5D) and others used condition-specific questionnaires (e.g. Multiple Sclerosis Quality of Life: MSQoL-52).

Overall, HRQL improved in patients using MC.

However, only a few studies provided HRQL definitions, and a third of studies didn’t explain why they measured HRQL. This information is needed to ensure HRQL is measured and interpreted appropriately in future studies.”

https://link.springer.com/article/10.1007/s11136-026-04170-7

Cannabis sativa in the fight against drug-resistant bacteria and fungi

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“Drug resistance in bacteria and fungi is a global threat to public health. The purpose of this publication is to review the latest scientific achievements, mainly from 2020-2025, concerning the use of hemp compounds from Cannabis sativa in combating drug-resistant bacterial and fungal infections.

The literature review confirms that C.sativa, a plant with a documented centuries-old therapeutic history, is a rich source of cannabinoids and terpenes that combat drug-resistant bacteria: Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, and fungi: Cryptococcus neoformans, as well as species from the Candida and Aspergillus.

The potential of hemp compounds is based on their activity in interacting directly with pathogens by disrupting cell membrane integrity, eradicating biofilm, having a bactericidal effect on bacterial spores, acting synergistically, affecting host inflammatory pathways, and the human endocannabinoid system.”

https://pubmed.ncbi.nlm.nih.gov/41607163

Exploring cannabinoid modulation on autophagy mechanisms in Alzheimer’s disease: a review

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“Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of toxic protein aggregates in the brain, leading to brain cell death and cognitive impairment. Central to AD pathogenesis is the autophagy pathway, a crucial cellular self-digestion process.

Cannabinoids, the fundamental phytochemical compounds derived from the Cannabis sativa plant, have been demonstrated to exhibit neuroprotective qualities when used as a treatment at microdoses.

However, the impact of multi-cannabinoid treatments on autophagy induction and subsequent cell survival in AD in vitro models remains uncertain. This review seeks to explore the potential of a multi-cannabinoid treatment strategy in enhancing neuronal cell survival through autophagy activation within an AD in vitro model.

The proposed approach involves a combination of cannabinoids in their potential to upregulate autophagy mechanisms, potentially supporting neuronal cell resilience. By unravelling the mechanistic link between autophagy, cannabinoid treatment, and neuronal viability, this review aims to elucidate how cannabinoids influence neuronal function and survival at a cellular and molecular level. By offering insights into the exploitation of the endocannabinoid system, this review contributes to the development of novel cannabinoid-based treatment avenues for AD. This pursuit aligns with the broader objective of addressing the debilitating effects of AD on the quality of life for those affected.”

https://pubmed.ncbi.nlm.nih.gov/41601969

“Emerging evidence, including a recent case report, suggests that cannabinoid microdosing may offer a potential strategy for reducing AD-related symptoms while minimizing adverse effects.”

“Pharmacokinetic data further indicate that multi-cannabinoid formulations, particularly those combining THC and CBD, add additional minor cannabinoids, may provide enhanced therapeutic efficacy and improved safety profiles compared to monotherapy.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1748368/full


Toxicological evaluation and preliminary phytochemical characterisation of a Nigerian Cannabis sativa chemovar

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“Objectives: Different Cannabis sativa chemovars produce diverse pharmacological and behavioral effects. With the widespread use of cannabis in Nigeria, detailed toxicological effects of Nigerian chemovars are lacking. This study aimed to identify phytocannabinoids and investigate the toxic effects of an indigenous C. sativa.

Materials and methods: The plant samples were air-dried, powdered, extracted with ethanol, and characterized (phytochemical screening, Fourier Transformed Infrared Spectroscopy (FTIR), and Gas Chromatography-Mass Spectrometry (GC-MS)). Acute and subacute toxicity tests were done following Organisation for Economic Co-operation and Development (OECD) protocols.

Results: Screening showed appreciable levels of alkaloids, tannins, saponins, cardiac glycosides, and phenol. FTIR analysis indicated functional groups and chemical linkages like alcohols, fatty acids, alkynes, ketones, and esters, and 11 phytocannabinoids with delta-9-tetrahydrocannabinol in abundance (35.78%) reported by GC-MS. Acute toxicity test indicated an oral lethal dose (LD50) value of ˃5000 mg/kg, a no-observed-adverse-effect-level (NOAEL) dose of ≤300 mg/kg, and a significant (P<0.05) decrease in the weight of animals in the 2000 mg/kg treatment group. The sub-acute toxicity test showed significantly (P<0.05) decreased ALP and ALT levels at 25 mg/kg body weight, and significantly lower triglyceride (P<0.01) and LDL (P<0.05) levels. Urea and some haematological parameters were significantly (P<0.05) higher in the 250 mg/kg group. Also, we observed mild to moderate necrosis in the excised pancreas and liver, and mild tubular changes in the kidney.

Conclusion: This suggests that our indigenous variety of C. sativa may be considered safe following oral consumption.”

https://pubmed.ncbi.nlm.nih.gov/41586191

In Vitro Antimicrobial Effect of Tetrahydrocannabinol on Streptococcus mutans and Its Anticariogenic Potential

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“Introduction and aims: With the increasing use of marijuana, it is vital to understand the effect of tetrahydrocannabinol (THC) on oral microbiota, especially the primary carious pathogen Streptococcus mutans.

Methods: The minimum inhibitory concentration (MIC) of THC against S mutans was determined by antimicrobial susceptibility testing. Bacterial acid production was evaluated. The effect of THC on S mutans biofilm formation and preformed biofilms was determined by crystal violet assay. The metabolic activity and viability of the biofilm were assessed using the methylthiazolyldiphenyl tetrazolium bromide assay and live/dead assay, respectively. Extracellular polysaccharide (EPS) was examined by Cascade Blue Dextran staining. S mutans membrane potential was detected by the Baclight Bacterial Membrane Potential Kit.

Results: The MIC of THC against S mutans was 2 µg/mL (P < .0001). A total of ≥2 µg/mL THC reduced bacterial acidogenicity and inhibited over 90% of biofilm formation (P < .0001). Additionally, ≥1 µg/mL THC reduced biofilm viability and EPS production (P < .0001), as assessed by fluorescence measurements and microscopy. While 1 to 64 µg/mL THC did not degrade preformed biofilm, metabolic activity was reduced by 16 to 64 µg/mL THC (P < .01), and 8 to 32 µg/mL THC reduced biofilm viability in a time- and dose-dependent manner (P < .001). Moreover, 2 to 8 µg/mL THC promoted membrane hyperpolarization after a 5-minute treatment (P < .01).

Conclusion: THC inhibits S mutans growth and biofilm formation while also reducing bacterial viability, EPS production, and acid production. Although it does not degrade preformed biofilm biomass, THC diminishes its metabolic activity and viability. These effects may be linked to THC-induced membrane hyperpolarization. This in vitro study suggests that THC may reduce the cariogenic capacity of S mutans.

Clinical relevance: This study shows that THC inhibits S mutans growth, biofilm formation, properties of preformed biofilms, and acid production. It provides preliminary scientific evidence on the impact of THC on oral health, specifically cannabinoid consumption on cariogenesis, and a potential new avenue for developing a new anticariogenic agent.”

https://pubmed.ncbi.nlm.nih.gov/41576726

“Among the cannabinoids, THC is the most abundant and exhibits a range of therapeutic effects, including analgesic, antiemetic, anti-inflammatory, anticancer, and antiseizure properties, as well as offering neuroprotective benefits in cases of neurodegeneration.”

Taken together, we herein provide evidence of the efficacy of THC in antibacterial and antibiofilm activity against S mutans by reducing planktonic growth of S mutans, inhibiting biofilm formation, and interfering with preexisting biofilm activity and function.

In addition, it may be a potential new avenue for developing new anticariogenic agents by suppressing the growth of S mutans and decelerating the acidification process that leads to enamel demineralization.”

https://www.sciencedirect.com/science/article/pii/S0020653925086678?via%3Dihub

“Anticariogenic (meaning “anti-cavity”) describes substances or practices that prevent or arrest the development of dental caries (tooth decay).”