Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Targeting Phantom Limb Pain with Cannabinoids in a Rat Model

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“Introduction: Phantom limb pain (PLP) is a debilitating neuropathic condition arising after limb loss or nerve injury, with limited effective treatments. Cannabinoids, including cannabidiol (CBD), β-caryophyllene (BCP), and Δ9-tetrahydrocannabinol (THC), possess analgesic and anti-inflammatory properties. This study evaluated their combined efficacy as preventive or delayed interventions in a rodent model of PLP.

Methods: To model PLP, a chronic constriction injury was used to mimic pre-amputation pain, followed by formalin-induced localized inflammation and complete sciatic nerve transection to simulate extremity amputation. Cannabinoid treatments (CBD/BCP/THC, CBD/BCP, or THC) or vehicle control were administered either preemptively on the day of axotomy (prevention paradigm) or after the emergence of pain behaviors (reversal paradigm). Progression of pain behaviors were assessed over a 72-day period, and modulation of spinal cytokine levels, glial reactivity, and GABAergic signaling was evaluated.

Results: Preemptive THC or CBD/BCP reduced PLP onset and severity, while the full combination was less effective. In contrast, with delayed treatment, CBD/BCP and the CBD/BCP/THC combination were most effective in mitigating PLP. Pain reduction was correlated with restoration of spinal GABAergic inhibition. All cannabinoid treatments decreased microglial and astrocyte reactivity and shifted cytokines toward an anti-inflammatory state.

Conclusion: Cannabinoid-based interventions demonstrate significant therapeutic promise for PLP, showing efficacy as both early and delayed treatments. Findings suggest that THC may exert greater therapeutic effects when administered pre-emptively, while CBD and BCP may offer greater therapeutic advantages in established pain states. These findings highlight the therapeutic potential of tailored cannabinoid interventions for neuropathic pain and underscore the importance of optimizing dosing strategies for maximal analgesic effect.”

https://pubmed.ncbi.nlm.nih.gov/42267080

“Cannabis contains a complex mixture of cannabinoids, terpenes, and flavonoids that have demonstrated therapeutic potential in a variety of pathologies and conditions. Their anti-inflammatory, analgesic, and antioxidant activities are believed to play a central role in mediating pain relief.”

“Our findings support the therapeutic potential of cannabinoid-based treatments in both preventing and reversing PLP, with efficacy varying by cannabinoid pairing and timing of treatment.

Together, these results underscore the therapeutic promise of cannabinoid-based treatments while highlighting the need to carefully consider how specific compounds and dosing strategies interact in different stages of pain.”

https://karger.com/mca/article/9/1/92/946968/Targeting-Phantom-Limb-Pain-with-Cannabinoids-in-a

Combined peripheral cannabinoid CB1 and CB2 receptor activation abolishes cystitis-induced bladder hyperalgesia

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“Cannabinoid agonists may ameliorate bladder pain associated with interstitial cystitis/bladder pain syndrome.

Visceromotor responses (VMRs) to bladder distension were recorded in urethane-anesthetised control and protamine/zymosan-treated guinea pigs. The peripherally restricted preferential CB1 receptor agonist PrNMI and the selective CB2 receptor agonist 4Q3C each reduced cystitis-induced enhancement of VMRs at high intravesical pressures.

Co-activation of CB1 and CB2 receptors abolished cystitis-induced bladder hyperalgesia.

These findings indicate that simultaneous targeting of peripheral CB1 and CB2 receptors may provide clinically meaningful benefits for the treatment of bladder pain associated with cystitis.”

https://pubmed.ncbi.nlm.nih.gov/42247877

“Combined activation of peripheral CB1 and CB2 receptors using peripherally restricted agonists effectively reverses bladder hyperalgesia in a preclinical model of IC/BPS.

These findings provide strong support for the development of peripherally acting combination therapies targeting both cannabinoid receptors as a strategy to treat bladder pain and associated symptoms in IC/BPS, while minimising central cannabinoid-related side effects.”

https://www.autonomicneuroscience.com/article/S1566-0702(26)00066-4/fulltext

The Use of Cannabis sativa L. for Pest Control: From the Ethnobotanical Knowledge to a Systematic Review of Experimental Studies

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“Background: Despite the benefits that synthetic pesticides have provided in terms of pest and disease control, they cause serious long-term consequences for both the environment and living organisms. Interest in eco-friendly products has subsequently increased in recent years. 

Methods: This article briefly analyzes the available ethnobotanical evidence regarding the use of Cannabis sativa as a pesticide and offers a systematic review of experimental studies. 

Results: Our findings indicate that both ethnobotanical and experimental procedures support the use of C. sativa as a pesticide, as remarkable toxicity has been observed against pest organisms. The results included in the systematic review of experimental studies (n=30) show a high degree of heterogeneity, but certain conclusions can be extracted to guide further research. For instance, promising pesticide properties were reported for most of the groups of species tested, especially Arachnida and Insecta; the efficacy of C. sativa as a pesticide can be derived from a wide variety of compounds that it contains and possible synergistic effects; it is crucial to standardize the phytochemical profile of C. sativa plants used as well as to obtain easily reproducible results; appropriate extraction methods should be explored; and upper inflorescences of the plant may be preferred for the production of the essential oil, but further studies should explore better other parts of the plant. 

Conclusion: In the coming years, as new findings are produced, the promising potential of C. sativa as a pesticide will be elucidated, and reviews such as the present one constitute useful basic tools to make these processes easier.”

https://pubmed.ncbi.nlm.nih.gov/34612729

https://journals.sagepub.com/doi/10.1089/can.2021.0095

The potential of Allium sativum and Cannabis sativa extracts for anti-tick activities against Rhipicephalus (Boophilus) microplus

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“The efficacy of Allium sativum and Cannabis sativa against Rhipicephalus microplus ticks was evaluated using the adult immersion and the larval packet test. In addition, an in silico approach was utilized by performing a docking study in order to identify the active ingredients from both plants.

Results showed a comparatively high lethal effect of A. sativum and C. sativa on egg laying (index of egg laying = 0.26 and 0.24, respectively), egg hatching (33.5 and 37.1, respectively), and total larval mortality (100%, both), at 40 mg/mL.

When applied to cattle which had been inoculated with larvae ticks, it was observed that a 45% solution of both herbal extracts significantly reduced the number of ticks by 96 h post treatment.

We analyzed in silico 27 known active molecules from both plants and identified in the PubChem database to explore the hypothesis that the effect found on ticks was based on inhibition of acetylcholinesterase (AChE).

Vitamin E and cannabidiol are the most potent AChE inhibitors with docking scores of -15.85 and -14.38, respectively.

Based on these findings, we conclude that A. sativum and C. sativa may potentially be used for the control of R. microplus, and should be further investigated as a potential supplement to or replacement of synthetic acaricides.”

https://pubmed.ncbi.nlm.nih.gov/32886258

https://link.springer.com/article/10.1007/s10493-020-00540-z

Interplay between the HPA axis and inflammation as mechanisms therapeutic targets of Cannabis sativa in depression

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“Major Depressive Disorder (MDD) is a highly prevalent and disabling psychiatric disorder, representing a major global health burden across all age groups.

Increasing evidence indicates that its pathophysiology involves a complex interplay between chronic stress, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, immune activation, and neuroinflammation. Persistent HPA axis hyperactivity, glucocorticoid resistance, and altered expression of key regulators such as FKBP51 contribute to sustained inflammatory signaling and impaired neural plasticity in brain regions involved in mood regulation. Epigenetic mechanisms, including DNA methylation and microRNA-mediated regulation, further modulate stress responsivity, inflammatory pathways, and vulnerability to major depressive disorder.

In this context, growing attention has been directed toward Cannabis sativa and its bioactive constituents as potential therapeutic agents.

Preclinical and clinical evidence suggest that cannabinoids may modulate the endocannabinoid system, attenuate HPA axis hyperactivity, reduce neuroinflammation, and influence monoaminergic and neuroplasticity-related pathways.

This review synthesizes the current literature on the mechanistic links among the HPA axis, inflammation, and MDD, highlighting the emerging role of Cannabis sativa-derived compounds in targeting these interconnected pathways.”

https://pubmed.ncbi.nlm.nih.gov/42239513

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1801474/full

Cannabis for tic control: a systematic review and meta-analysis of its efficacy in Tourette syndrome management

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“Background: Tourette syndrome (TS) involves motor and vocal tics, often with obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). Cannabis-based medicines (CBMs) are a potential therapy due to their interaction with the endocannabinoid system, potentially reducing tics and associated symptoms. Compared to antipsychotics, CBMs may offer improved tolerability and fewer side effects. Although evidence is limited, emerging studies suggest their potential to improve quality of life in TS. This review was registered with PROSPERO (CRD420251088633).

Aim: To evaluate the effectiveness of CBMs in treating TS.

Methods: We systematically searched PubMed, Google Scholar, ScienceDirect, and the Cochrane Collaboration Database for cohort studies and randomized controlled trials (RCTs) up to July 2, 2025. Data extraction included study characteristics and efficacy outcomes measured by the Yale Global Tic Severity Scale (YGTSS) and Premonitory Urge for Tics Scale (PUTS). Meta-analysis using Review Manager 5.4 compared pre- and post-treatment scores using mean difference (MD) and 95% confidence intervals (CI).

Results: From 1,105 screened articles, eight studies met inclusion criteria for the review, and seven were included in the meta-analysis, involving 306 adult TS patients. CBMs significantly reduced YGTSS scores (MD = – 13.29, 95% CI [-21.67 to – 4.91], P = 0.002) and PUTS scores (MD = – 4.09, 95% CI [-7.24 to – 0.93], P = 0.01).

Conclusion: CBMs show promising potential in reducing tics and premonitory urges in TS. Larger, placebo-controlled trials are needed to confirm efficacy, ensure safety, and optimize dosing.”

https://pubmed.ncbi.nlm.nih.gov/42229830

“Cannabis-based medicines significantly reduced tic severity in Tourette syndrome.”

https://www.ibroneuroscience.org/article/S0306-4522(26)00367-2/abstract

Cannabinoids in Alzheimer’s disease: animal-human evidence and clinical pharmacology challenges

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“Cannabinoids have emerged as potential modulators of pathological processes in Alzheimer’s disease (AD), including neuroinflammation, synaptic dysfunction, and protein aggregation. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the main phytocannabinoids from Cannabis sativa, interact with the endocannabinoid system and may influence neuronal and glial signaling pathways relevant to AD pathology.

This mini review summarizes evidence from transgenic animal models and clinical studies evaluating CBD, THC, and their combination in AD.

Preclinical studies show that CBD and THC reduce β-amyloid accumulation, attenuate tau phosphorylation, and regulate neuroinflammatory responses, often associated with improvements in learning and memory. Cognitive outcomes appear to depend on cannabinoid composition, with CBD or THC administered individually showing more consistent effects, while combined CBD + THC effects appear dose- and ratio-dependent.

Clinical evidence in AD patients remains limited and primarily reports improvements in neuropsychiatric symptoms, such as reductions in agitation, nighttime activity, and behavioral disturbances, whereas cognitive improvements are modest. Cannabinoid-based treatments are generally well tolerated, with mild sedation, somnolence, or disorientation as the most reported adverse effects.

Overall, current data support the biological plausibility of cannabinoids as modulators of neuroinflammatory and synaptic processes in AD. However, heterogeneity in formulations, dosing, and study design limits firm conclusions. Future research should focus on dose optimization, biomarker-guided clinical trials, and long-term safety assessments to better define their therapeutic potential in AD.”

https://pubmed.ncbi.nlm.nih.gov/42211879

“The ideal treatment for AD should be able to modulate the disease through multiple mechanisms rather than targeting a single dysregulated pathway.”

 “cannabinoids should be viewed as pleiotropic modulators of AD-relevant processes rather than as agents acting through a single unified mechanism.”

“cannabinoid-derived compounds with combined receptor-mediated and intrinsic antioxidant properties may represent promising therapeutic candidates.”

https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2026.1833021/full

Antitumor Activity of Cannabinoids and Their Interaction with Chemotherapy: A Systematic Review and Meta-Analysis of Preclinical Evidence

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“Background: Cannabinoids are studied as anticancer agents, but their effects vary across tumors, compounds, and experimental settings, underscoring the need to define consistent patterns. Our objective was to map cannabinoid efficacy across cancer preclinical models and identify tumor settings with the greatest translational promise. 

Methods: The protocol was registered on PROSPERO (CRD42025543744); PubMed, Embase, and CENTRAL were searched on 4 April 2024 for in vitro and in vivo studies assessing cannabinoid antitumor effects alone or with chemotherapy versus vehicle or chemotherapy only. Random-effects models yielded pooled mean differences (MD) with 95% confidence intervals (CI). MDs of viable cells were calculated for in vitro assays and tumor volume (mm3) for in vivo studies. Reports of various compounds, cannabidiol (CBD), tetrahydrocannabinol (THC) or synthetic cannabinoids, were pooled. 

Results: We included 189 studies in the final analysis. In vitro, cannabinoids reduced cell viability modestly overall, with significant effects in glioblastoma (MD -18.77 [CI: -27.15; -10.39]) and a nonsignificant trend in breast cancer (MD -6.75 [CI: -13.90; 0.40]). For in vivo, monotherapy showed the most consistent efficacy in glioblastoma, significantly reducing tumor volume by MD -980.58 mm3; [CI: -1270.2; -690.88]. Addition to temozolomide produced a favorable but nonsignificant decrease of MD -220.65 mm3; [CI: -579.34; 138.03, vs. temozolomide]. In breast cancer, cannabinoids achieved smaller yet significant tumor reductions (MD -402.64 mm3); [CI: -671.84; -133.45]. Synthetic agents had the largest effect (MD -1295.19 mm3); [CI: -1664.33; -928.05] -CBD plus doxorubicin vs. doxorubicin). Lung cancer (MD -562.17 mm3); [CI: -693.99; -430.35] and prostate cancer (MD -1136.59 mm3); [95% CI: -1320.97; -952.21] also had a significant response, whereas colon, pancreatic, and hepatocellular carcinoma models showed inconsistent or null responses. 

Conclusions: Cannabinoids show promise as adjuncts in oncotherapy, particularly in glioblastoma and breast cancer, to enhance chemotherapy efficacy. These findings should be interpreted with caution given the high inter-study heterogeneity typical of preclinical research and should be considered hypothesis-generating, warranting further validation in standardized and clinically relevant models.”

https://pubmed.ncbi.nlm.nih.gov/42198443

“Cannabinoids have attracted growing attention in oncology as both supportive agents and potential direct antitumor therapies.”

“Beyond symptom management, preclinical studies over the past two decades have demonstrated that exogenous cannabinoids can influence key hallmarks of cancer, including proliferation, apoptosis, angiogenesis, and metastasis.”

“Notably, multiple studies indicate that cannabinoids can act synergistically with chemotherapy or radiotherapy, amplifying antitumor effects while potentially attenuating treatment-related toxicity. These interactions are clinically appealing, as they suggest a capacity to sensitize tumor cells to conventional agents and possibly enable dose reductions that limit systemic adverse effects.”

“Cannabinoids show emerging potential as adjuncts in oncological treatment, with relatively consistent signals observed particularly in glioblastoma and breast cancer models.”

https://www.mdpi.com/1424-8247/19/5/768

Computational Characterization of Nabilone-Induced Disruption of the CB2-HER2 Receptor Complex in HER2+ Breast Cancer

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“Human epidermal growth factor receptor 2-positive (HER2+) breast cancer, accounting for 15% to 20% of cases, is often resistant to treatment.

Delta-9-tetrahydrocannabinol (THC) disrupts HER2-cannabinoid receptor (2CB2) receptor complexes and inhibits HER2 activation.

This study evaluates whether Nabilone, a synthetic cannabinoid, can similarly disrupt HER2-CB2 interactions.

A CB2-HER2 complex model was generated via protein-protein docking. Three 1-µs molecular dynamics simulations (CB2-HER2, CB2-HER2-THC, CB2-HER2-Nabilone) were performed using the Schrodinger Desmond with membrane embedding and solvent. Structural stability (root mean square deviation [RMSD] and root mean square fluctuation [RMSF]), binding free energy (molecular mechanics/generalized born surface area [MM/GBSA]), and intracellular/extracellular distances between receptors were analyzed. Intermolecular interactions were assessed using the MAPIYA server.

Nabilone induced comparable structural instability to THC, with increased RMSD and RMSF. The MM/GBSA analysis showed Nabilone increased the binding free energy between CB2 and HER2, indicating stronger disruption. Intracellular and extracellular distances between CB2 and HER2 increased, especially intracellularly, with Nabilone. Intermolecular interaction analysis revealed that Nabilone decreased the number of contacts, particularly hydrophobic interactions, between CB2 and HER2.

Our in silico model predicts that Nabilone may disrupt the HER2-CB2 complex, suggesting a hypothesis that it could serve as a potential therapeutic agent. These computational findings warrant urgent experimental validation.”

https://pubmed.ncbi.nlm.nih.gov/42164472

“Cannabinoids have produced antitumor responses in preclinical models of cancer, including HER2+ BC, via binding and activating cannabinoid receptors, CB1 and CB2, both G-protein coupled receptors (GPCRs).”

“Nabilone, a synthetic analog of THC, was Food and Drug Administration (FDA)-approved in 1985 as a relief treatment for chemotherapy-related side effects, such as vomiting and nausea.”

“Our results indicate that Nabilone effectively disrupts the oncogenic CB2-HER2 complex, weakening the heterodimer interface through a mechanism of structural instability similar to THC but with superior binding affinity to CB2. While these findings rely on in silico predictions, limited by simulation timescales and simplified membrane models, they highlight a distinct opportunity for repurposing Nabilone from symptom management to active cancer therapy. We conclude that these data provide a robust theoretical framework that justifies urgent experimental validation in living systems to confirm the therapeutic potential of disrupting CB2-HER2 signaling.”

https://journals.sagepub.com/doi/10.1177/11779322261449332

The association between prenatal exposure to cannabis with and without tobacco and early cognitive and language development in a sample of polysubstance-exposed children

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“Background: Prenatal cannabis exposure may have adverse effects on development which could be amplified by co-exposure with tobacco.

Objective: This study examined whether prenatal cannabis exposure was associated with disrupted language or cognitive development, and whether co-exposure to tobacco was associated with worse outcomes than to cannabis alone.

Methods: In this historical cohort study, we compared children from the Danish Family Outpatient Clinics who had prenatal exposure to cannabis (n = 106), tobacco (n = 138), cannabis and tobacco (n = 112), or no exposure to either drug (control group, n = 454) on the Bayley-III Language and Cognitive scales at 1-58 months of age (99.7% at ≤36 months). Roughly half were tested at multiple ages, yielding 1362 language assessments (49.2% tested ≥ twice) and 1549 cognitive assessments (53.6% tested ≥ twice). Most children had additional prenatal exposure to other drugs (49.8%), including the control group (63.9%). Scores were investigated in linear mixed models with factors Exposure Group, Age, and Exposure Group ∗ Age, and covariates alcohol exposure, other drug exposure, maternal medical diagnoses, and maternal education.

Results: Children with prenatal cannabis exposure scored significantly higher on the Language scale compared with controls (3.26 points; 95% CI = 0.26-6.26). There was a positive association between Language scores and age at assessment for children with cannabis and tobacco exposure (0.31 points/month; 95% CI = 0.11-0.51) but not the other groups. There were no significant effects of Exposure Group or Exposure Group × Age for the Bayley-III Cognitive scale.

Conclusion: Prenatal exposure to cannabis, alone or with tobacco, was not associated with disrupted cognitive or language development during the first three years of life in this sample of high-risk children.”

https://pubmed.ncbi.nlm.nih.gov/41990599

“Cannabis exposure was not associated with impaired cognitive or language development.”

“Using a sample of children with prenatal drug and alcohol exposure from the Danish FOCs, this study found that children with prenatal exposure to cannabis had higher scores on the Bayley-III Language scale compared with control children, and children with prenatal exposure to cannabis and tobacco had a greater increase in Bayley-III Language scores with age compared with all other groups. There were no differences on the Bayley-III Cognitive scale between children with prenatal exposure to cannabis, tobacco, both, or neither.

These results suggest that prenatal exposure to cannabis, alone or in combination with tobacco, is not associated with disrupted cognitive or language development during the first three years of life among polysubstance-exposed children. This could help to reduce the stigma experienced by women who use cannabis during pregnancy and potentially lower the barrier for seeking help in this group.”

https://www.sciencedirect.com/science/article/pii/S0378378226000745?via%3Dihub