Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Cannabidiol/tetrahydrocannabinol-enrich extract decreases neuroinfalmmation and improves locomotor outcome following spinal cord injury

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“Neuroinflammation is one of the main players in lesion expansion and locomotor deficits after spinal cord injury (SCI), thus treatments to control the inflammatory process emerge as novel therapeutic strategies. In this context, the anti-inflammatory effects of tetrahydrocannabinol (THC) and cannabidiol (CBD), the main phytocannabinoids of Cannabis sativa, are increasingly recognized.

The aim of this work was to investigate the effects of a standardized Cannabis sativa extract (CSE), which is mainly composed by THC/CBD in equimolar concentration, on neuroinflammation, secondary damage and locomotor outcome after SCI in rats.

After acute SCI, CSE therapy increased the number of non-inflammatory (arginase-1 positive) microglial cells in the epicenter of the lesion and decreased the number of pro-inflammatory ones (arginase-1 negative) in the epicenter and in the rostral and caudal regions of the lesion. CSE also reduced the number of reactive astrocytes in the grey matter of the rostral and caudal regions.

These results are consistent with the downregulation of mRNAs of inflammatory mediators (IL-1β, TNFα, IL-6, C3) and the upregulation of anti-inflammatory markers (ARG-1, MRC). In the chronic phase, CSE treatment prevented cyst expansion and also increased the volume of spared grey and white matter. Regarding locomotor outcome, CSE-treated rats showed better locomotor scores (open field test), higher latency to fall (Rotarod test) and lower number of hindlimb foot misplacements (horizontal ladder walking test) than untreated injured rats.

These results suggest that this standardized CSE offers a promising perspective for reducing acute neuroinflammation and promoting functional recovery after SCI.”

https://pubmed.ncbi.nlm.nih.gov/40157632/

https://www.ibroneuroscience.org/article/S0306-4522(25)00258-1/abstract

Evaluating Vaporized Cannabinoid Therapy in Multiple Sclerosis: Findings from a Prospective Single-Center Clinical Study

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“Introduction: Multiple Sclerosis (MS) is associated with a wide range of debilitating symptoms, and conventional therapies often fail to adequately address the disease’s multifaceted challenges. Cannabidiol (CBD) 13.0% + Delta9-tetrahydrocannabinol (THC) 9.0% (CBD13/THC9), a vaporized cannabis-based medicinal product, presents a novel therapeutic option for managing MS symptoms. 

Methods: This single-center longitudinal study followed 69 MS patients over a six-month period. Participants were assessed at treatment initiation and at three- and six-month intervals. Key measures included muscle spasticity, urine bladder dysfunction, and the evaluation of disability progression rate. The evaluation included the Modified Ashworth Scale (MAS), the Post Void Residual (PVR) volume, and the Expanded Disability Status Scale (EDSS). 

Results: Significant improvement was observed across all outcome assessments. The EDSS score was decreased over time (p = 0.009), indicating a slight reduction in disability progression rate, while MAS scores showed substantial improvement in muscle spasticity (p < 0.001). Urine bladder function improved significantly, with PVR volume showing notable improvement between baseline and the six-month assessment (p < 0.001). Correlation analyses revealed that a gradual increase in vaporized CBD13/THC9 dose was correlated with slightly lower EDSS scores, while the adverse effects were negatively associated with the frequency of cannabinoid use. Finally, patients who were smokers used CBD13/THC9 more frequently. 

Conclusions: The vaporized CBD13/THC9 formulation demonstrated notable efficacy in slightly improving disability progression rate via reduction in muscle spasticity and urine bladder dysfunction in MS patients. This highlights its addon therapeutic value during rehabilitation in MS patients with debilitating disability symptoms.”

https://pubmed.ncbi.nlm.nih.gov/40142928/

https://www.mdpi.com/2077-0383/14/6/2121

Transcriptomic Alterations Induced by Tetrahydrocannabinol in SIV/HIV Infection: A Systematic Review

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“Given the high prevalence of cannabis use among people with HIV (PWH) and its potential to modulate immune responses and reduce inflammation, this systematic review examines preclinical evidence on how tetrahydrocannabinol (THC), a key compound in cannabis, affects gene and micro-RNA expression in simian immunodeficiency virus (SIV)-infected macaques and HIV-infected human cells.

Through a comprehensive search, 19 studies were identified, primarily involving SIV-infected macaques, with a pooled sample size of 176, though methodological quality varied across the studies. Pathway analysis of differentially expressed genes (DEGs) and miRNAs associated with THC revealed enrichment in pathways related to inflammation, epithelial cell proliferation, and adhesion. Notably, some DEGs were targets of the differentially expressed miRNAs, suggesting that epigenetic regulation may contribute to THC’s effects on gene function.

These findings indicate that THC may help mitigate chronic immune activation in HIV infection by altering gene and miRNA expression, suggesting its potential immunomodulatory role. However, the evidence is constrained by small sample sizes and inconsistencies across studies. Further research employing advanced methodologies and larger cohorts is essential to confirm THC’s potential as a complementary therapy for PWH and fully elucidate the underlying mechanisms, which could inform targeted interventions to harness its immunomodulatory effects.”

https://pubmed.ncbi.nlm.nih.gov/40141240/

https://www.mdpi.com/1422-0067/26/6/2598

The use of cannabinoid therapy in treatment-refractory isolated REM sleep behavior disorder: a case report

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“Current treatments for rapid eye movement (REM) sleep behavior disorder (RBD) are not always effective and can lead to dose-limited adverse events, and new treatments are needed for this condition.

We present a case of a patient with treatment-refractory isolated RBD who had a dramatic and sustained improvement in dream enactment behaviors using oral tinctures containing cannabidiol and tetrahydrocannabinol without adverse events over 5 years of follow-up.”

https://pubmed.ncbi.nlm.nih.gov/40130438/

https://jcsm.aasm.org/doi/10.5664/jcsm.11704

UK Medical Cannabis Registry: An Analysis of Outcomes of Medical Cannabis Therapy for Hypermobility-Associated Chronic Pain

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“Objective: The study aims to evaluate the clinical outcomes in patients with hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) with chronic pain following treatment with cannabis-based medicinal products (CBMPs).

Methods: This was a case series conducted with the UK Medical Cannabis Registry. The primary outcomes were changes in the following validated patient-reported outcome measures at 1, 3, 6, 12, and 18 months compared with baseline: Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2), pain visual analog scale score (Pain-VAS), Brief Pain Inventory (BPI), five-level EQ-5D (EQ-5D-5L), Single-Item Sleep Quality Scale (SQS), General Anxiety Disorder Seven-Item Scale (GAD-7), and Patient Global Impression of Change. The incidence of adverse events was analyzed as secondary outcomes. Statistical significance was defined as P <0.050.

Results: A total of 161 patients met inclusion criteria. Improvements were observed in BPI severity and interference subscales, SF-MPQ-2, and Pain-VAS (P < 0.001). Changes were also seen in the EQ-5D-5L index value, SQS, and GAD-7 (P < 0.001). A total of 50 patients (31.06%) reported one or more adverse event with a total incidence of 601 (373.29%). The most frequent rating for adverse events was moderate (n = 258; 160.25%), with headache being the most common (n = 44; 27.33%).

Conclusion: An association was identified between patients with HSD/hEDS with chronic pain and improvements in pain-specific and general health-related quality of life following the commencement of CBMPs. CBMPs were also well tolerated at 18 months. These findings must be interpreted within the context of the limitations of study design but add further weight to calls for randomized controlled trials.”

https://pubmed.ncbi.nlm.nih.gov/40079426/

“Cannabis-based medicinal products (CBMPs) have emerged as a potential alternative for chronic pain management, acting on the endocannabinoid system (ECS), which plays a pivotal role in pain regulation.”

“This study reports an association between CBMP treatment and reported improvements in pain and HRQoL among patients with HSD/hEDS.”

https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr2.70024

A Pilot Randomized Placebo-Controlled Crossover Trial of Medicinal Cannabis in Adolescents with Tourette Syndrome

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“Introduction: Medicinal cannabis (MC) has potential therapeutic effects in Tourette Syndrome (TS), however there has been limited research in adolescent patients. This pilot study aimed to investigate the feasibility of conducting a randomized placebo-controlled crossover trial of MC in adolescents with TS. 

Method: This was a phase I/II double-blind, cross-over pilot study comparing MC with matched placebo in adolescents aged 12-18 years with TS. The active medication was Δ9-tetrahydrocannabinol (THC) 10 mg/mL and CBD 15 mg/mL in peppermint-flavored medium-chain triglyceride oil. The dose titration schedule was stratified into two participant weight bands: below 50 kg (max THC 10 mg/day) or ≥50 kg (max THC 20 mg/day). Each treatment phase lasted 10 weeks, with a 4-week washout period. 

Results: Ten adolescents were randomized (mean age 14.8 years, 50% male) and seven completed the full study protocol. Two adolescents discontinued due to adverse events (one on MC, one placebo) and one was lost to follow-up. The most common adverse event was dizziness (67%). There were no serious adverse events. Among actively enrolled participants, protocol adherence was excellent: study visits 100%, blood test completions 100%, and online questionnaire completion 97.6%. Medication adherence was acceptable in 63.6%. Parents reported a high degree of study design acceptability. On the Clinical Global Impression-Improvement scale, three participants were rated as much improved on MC compared with one on placebo at 10 weeks. 

Discussion: The findings suggest that the study protocol is feasible and acceptable to patients with TS and their families. A fully powered study is needed to evaluate the efficacy of MC in adolescent TS.”

https://pubmed.ncbi.nlm.nih.gov/40082070/

https://www.liebertpub.com/doi/10.1089/can.2024.0188

Low doses of cannabis extract ameliorate non-motor symptoms of Parkinson’s disease patients: a case series

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“Introduction: Parkinson’s disease (PD) is mainly characterized by motor symptoms including muscle rigidity, resting tremor and bradykinesia. However, the management of the non-motor symptoms represent a relevant clinical challenger in PD. These non-motor symptoms include cognitive and sleep disturbance and there is evidence that cannabinoids may represent alternative and effective treatments for non-motor symptoms of PD.

Methods: Therefore, this study addressed the effects of oral treatment with cannabis extract on cognition, insomnia, and daytime sleepiness in six patients with moderate PD. The patients were randomized to receive two different doses of a cannabis extract: THC:CBD 250:28 μg/day (n = 3) or 1000:112 μg/day (n = 3). The assessment of cannabis administration related to the cognitive field was measured by the Montreal Cognitive Assessment test (MoCA test), the insomnia was assessed by the Insomnia Severity Index (ISI), and daytime sleepiness was assessed using the Epworth sleepiness scale (ESS). All clinical evaluations were performed before treatment and at 15, 30, 60, and 90 days of treatment.

Results: The statistical analysis indicated a significant benefit of the cannabis extract treatment, at dose of 1000:112 μg/day after 60 days of treatment, on insomnia assessed by ISI. Moreover, the statistical analysis of data from ISI and MoCA tests showed a trend toward improvement over time, while no significant effect was observed in the ESS. There were no reports of significant adverse effects during the cannabis extract treatment.

Discussion: These results demonstrate benefits of short-time treatment (60 days) with low doses of cannabis extract on insomnia in PD patients. This study provide novel findings of the potential of combining CBD and THC as safe and effective treatments for non-motor symptoms of PD.”

https://pubmed.ncbi.nlm.nih.gov/40066073/

“In conclusion, these results demonstrate a possible benefit of short-time treatment (3 months) with low doses of cannabis extract on cognition and insomnia in PD patients. This study provide novel findings of the potential of combining CBD and THC as safe and effective treatments for non-motor symptoms of PD.”

https://www.frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2024.1466438/full

Improvement in the Cognitive Function in Chronic Pain: Therapeutic Potential of the Endocannabinoid System

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“Chronic pain presents as a complex condition encompassing sensory (Zhang Z et al. Cell Rep 12;752-759, 2015) and emotional components, often accompanied by anxiety, depression, insomnia, and cognitive impairment. These factors significantly hinder daily activities and rehabilitation efforts.

The widespread prevalence of chronic pain imposes substantial clinical, societal, and economic burdens. While current analgesics have limitations and associated side effects such as tolerance, dependency, cognitive deficits, and a narrow therapeutic window, the search for new analgesic options remains imperative.

The endocannabinoid system (ECS), a key modulator in pain processing pathways, plays a crucial role in executive functions. This review specifically focuses on the cognitive impairments associated with chronic pain and highlights the pivotal role of the ECS in the cognitive aspects of pain. Additionally, the effectiveness of cannabinoid-based medications in improving executive functions in patients with chronic pain is evaluated.”

https://pubmed.ncbi.nlm.nih.gov/40059255/

https://link.springer.com/article/10.1007/s12035-025-04814-8

Spinal dorsal horn neurons involved in the alleviating effects of cannabinoid receptor agonists on neuropathic allodynia-like behaviors in rats

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“Mechanical allodynia, the pain caused by innocuous tactile stimuli, is a hallmark symptom of neuropathic pain that is often resistant to currently available treatments.

Cannabinoids are widely used for pain management; however, their therapeutic mechanisms for neuropathic mechanical allodynia remain unclear.

Using transgenic rats that enable to optogenetically stimulate touch-sensing Aβ fibers in the skin, we found that the intrathecal administration of the synthetic cannabinoid, WIN 55,212-2, alleviated the Aβ fiber-derived neuropathic allodynia. Furthermore, we injected adeno-associated virus vectors incorporating the rat cannabinoid receptor 1 (CB1 receptor) (encoded by Cnr1) promoter and tdTomato or short hairpin RNA targeting the CB1 receptor into the spinal dorsal horn (SDH) and demonstrated that the conditional knockdown of CB1 receptors in Cnr1+ SDH neurons attenuates the anti-allodynic effects of intrathecally administered WIN 55,212-2. Electrophysiological analysis revealed that Cnr1+ SDH neurons received excitatory synaptic inputs from the primary afferent Aβ fibers.

Collectively, our results suggest that the CB1 receptors in Cnr1+ SDH neurons are molecular and cellular targets of intrathecal WIN 55,212-2 to alleviate neuropathic allodynia.”

https://pubmed.ncbi.nlm.nih.gov/40058945/

https://linkinghub.elsevier.com/retrieve/pii/S1347861325000180

“WIN 55,212-2 is a chemical described as an aminoalkylindole derivative, which produces effects similar to those of cannabinoids such as tetrahydrocannabinol (THC) “

A Green Microwave-Assisted Extraction of Cannabis sativa L. Extract and Its Cytotoxic Activity Against Cancer Cells

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“Objectives: This study aimed to explore the use of D-limonene and some vegetable oils with different amounts of saturated and unsaturated fatty acids as alternative green solvents for microwave-assisted extraction (MAE) of cannabis (Cannabis sativa L.). A standardized cannabis extract was selected to evaluate its potential as a chemopreventive agent.

Materials and methods: Alternative green solvents, powder-to-solvent ratios, and irradiation cycles were determined to optimize the MAE conditions. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to assess the cytotoxic effects against human breast cancer (MCF-7), liver cancer (HepG2), and mammary epithelium (hTert-HME1) cell lines.

Results: The extracts obtained from D-limonene and palm oil contained the highest concentrations of cannabidiol (CBD) and D-tetrahydrocannabinol (THC). A standardized D-limonene extract of cannabis (DEC) containing 0.03% w/w CBD and 1.37% w/w THC was selected for the evaluation of cytotoxic activity compared with CBD and THC. The results revealed that CBD and THC exhibited significant cytotoxic effects (p<0.05) against MCF-7 and HepG2, with the 50% inhibitory concentration (IC50) values of 18.5 and 12.37 μg/mL for CBD and 24.21 and 4.30 μg/mL for THC, respectively, whereas DEC exhibited moderate cytotoxicity against MCF-7 (IC50 of 488.85 μg/mL). However, CBD and THC exhibited significant cytotoxicity (p<0.05) against hTert-HME1 (IC50 values of 35.61 and 25.63 μg/mL, respectively), whereas DEC exhibited low cytotoxicity against hTert-HME1 (IC50 of 1.537.03 μg/mL).

Conclusion: DECs containing appropriate levels of THC and CBD have the potential to be candidates for cancer treatment. However, further investigations are required to improve the efficacy and safety profiles.”

https://pubmed.ncbi.nlm.nih.gov/40052396/

“The present study identified D-limonene and palm oil as promising alternative green solvents for extracting cannabinoids from cannabis inflorescences under MAE optimal conditions. The MAE method offers several advantages, including reduced time and energy consumption. In this study, DEC exhibited moderate cytotoxicity against MCF-7 cells with higher selectivity than CBD and THC. Therefore, DEC containing an appropriate amount of THC and CBD may exhibit a more satisfying anticancer effect and be a promising candidate for cancer treatment. However, additional research is required to understand the mechanisms of anticancer activity and to investigate additional efficacy and safety profiles.”

https://www.turkjps.org/articles/a-green-microwave-assisted-extraction-of-c-lessemgreatersativalessemgreater-l-extract-and-its-cytotoxic-activity-against-cancer-cells/doi/tjps.galenos.2025.33490