Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (NTI164) Improves Symptoms of Rett Syndrome: An Open-Label Study

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“Aim: The aim of this Phase I/II open-label study was to assess the safety and efficacy of NTI164, a novel full-spectrum medicinal cannabis plant extract 0.08% Δ-9-tetrahydrocannabinol (THC), in Rett syndrome (RTT).

Methods: Eleven female participants (5-16 years) with a pathogenic variant in the MECP2 gene were recruited to this study, receiving NTI164 twice daily for 12 weeks. The primary outcome measure was the Clinical Global Impression-Improvement (CGI-I) Scale, with secondary outcomes measured using the CGI-Severity (CGI-S), RTT Behaviour Questionnaire (RSBQ), RTT-Symptom Index Score (RTT-SIS), RTT-Domain-Specific Concerns-Visual-Analog Scale (RTT-DSC-VAS), Impact of Childhood Neurological Disability/Quality of Life (ICND+QoL), and RTT-Caregiver Burden Inventory (RTT-CBI). Paired-samples t-test was used to assess significance between baseline and Week 12.

Results: Improvements were seen in the total CGI-I score (p = 0.028), with improvements in communication skills (p = 0.003), mental alertness (p = 0.033), socialisation/eye contact (p = 0.0004), attentiveness (p = 0.001), and anxiety (p = 0.004). CGI-S also demonstrated better outcomes after NTI164 administration (p = 0.008). RSBQ showed improvements in total score (p = 0.0005), general mood (p = 0.0003), breathing problems (p = 0.041), repetitive face movements (p = 0.004), and fear/anxiety (p = 0.006). RTT-DSC-VAS showed positive developments in abilities to communicate choices (p = 0.041). ICND total score was improved (p = 0.003), as well as cognition (p = 0.027) and Quality of Life (p = 0.0002). Total score on the RTT-CBI was improved (p = 0.006).

Conclusion: NTI164 demonstrated safety and improved some clinical and functional outcomes in RTT. These improvements justify ongoing research into NTI164, which may be a potential adjunct therapy in RTT.”

https://pubmed.ncbi.nlm.nih.gov/40568811/

“This paper demonstrates efficacy of this novel medical cannabis compound in reducing complex symptoms of Rett syndrome and improving quality of life in these patients.”

https://onlinelibrary.wiley.com/doi/10.1111/jpc.70122

Cannabinol’s Modulation of Genes Involved in Oxidative Stress Response and Neuronal Plasticity: A Transcriptomic Analysis

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“Cannabis sativa is a remarkable source of bioactive compounds, with over 150 distinct phytocannabinoids identified to date. Among these, cannabinoids are gaining attention as potential therapeutic agents for neurodegenerative diseases.

Previous research showed that cannabinol (CBN), a minor cannabinoid derived from Δ9-tetrahydrocannabinol, exhibits antioxidant, anti-inflammatory, analgesic, and anti-bacterial effects.

The objective of this study was to assess the protective potential of 24 h CBN pre-treatment, applied at different concentrations (5 µM, 10 µM, 20 µM, 50 µM, and 100 µM), in differentiated neuroblastoma × spinal cord (NSC-34) cells. Transcriptomic analysis was performed using next-generation sequencing techniques.

Our results reveal that CBN had no negative impact on cell viability at the tested concentrations. Instead, it showed a significant effect on stress response and neuroplasticity-related processes. Specifically, based on the Reactome database, the biological pathways mainly perturbed by CBN pre-treatment were investigated.

This analysis highlighted a significant enrichment in the Reactome pathway’s cellular response to stress, cellular response to stimuli, and axon guidance.

Overall, our results suggest that CBN holds promise as an adjuvant agent for neurodegenerative diseases by modulating genes involved in neuronal cell survival and axon guidance.”

https://pubmed.ncbi.nlm.nih.gov/40563376/

“Aging and neurodegenerative diseases are characterized by a progressive decline in cellular functions, including genomic instability, epigenetic alterations, mitochondrial dysfunction, and chronic inflammation. Our study supports that CBN exerts pleiotropic effects by modulating key molecular pathways involved in oxidative stress response, DNA repair, and neuronal survival. These results suggest that CBN positively modulates the response to cellular damage, stimulating the antioxidant response through the Nrf2 pathway and reducing the sensitivity to programmed cell death, as demonstrated by the regulation of caspases and other genes related to neuronal survival. These effects indicate that CBN may be able to support neuronal health under conditions of chronic stress, a hallmark of neurodegenerative diseases. These findings pave the way for further research into CBN’s therapeutic potential, emphasizing the need for in vivo studies to validate its efficacy and safety profile in neurodegenerative disease models.”

https://www.mdpi.com/2076-3921/14/6/744

How to ESCAPE from Pain? An Observational Study on Improving Pain and Quality of Life with the Cannamedical® Hybrid Cannabis Extract

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“Introduction: Chronic pain remains a challenge, with standard therapies often providing inadequate pain relief and causing undesirable side effects. Medicinal cannabis has emerged as promising alternative. This study assessed the impact of a cannabis hybrid extract on pain intensity and quality of life in daily clinical use.

Methods: ESCAPE was an observational study and included patients aged ≥ 18 years with chronic pain in Germany. The primary objective was to evaluate the effectiveness of the Cannamedical® Hybrid Cannabis Extract THC25:CBD25 on pain during four visits (V1-V4) in clinical practice, and key secondary objectives were pain interference and quality of life. Pain intensity was measured using the Numeric Rating Scale (NRS) of the Brief Pain Inventory (BPI) questionnaire. Pain interference was evaluated with the BPI pain interference subscore, and quality of life-particularly physical and mental health-was assessed with the Short Form-12 (SF-12) questionnaire. Additionally, patient and physician satisfaction with the extract was assessed.

Results: The study included 64 patients (50% female) with chronic pain (intention-to treat population; ITT). Cannabis-naïve patients of the ITT were defined as a subgroup and analyzed separately (N = 35). Mean (± SD) NRS-assessed pain intensity decreased during the study, in both the ITT (5.46 ± 1.73 at V1 vs. 3.37 ± 2.43 at V4) and in the cannabis-naïve subgroup (5.92 ± 1.34 at V1 vs. 2.37 ± 1.69 at V4). Mean pain interference subscore decreased between V1 and V4 for the ITT (5.39 ± 1.92 vs. 3.38 ± 2.46) and the cannabis-naïve group (5.68 ± 1.46 vs. 2.54 ± 1.99). Physical and mental health improved in both groups and high satisfaction with the hybrid cannabis extract was reported by patients and physicians.

Conclusion: Treatment with the Cannamedical® Hybrid Cannabis Extract THC25:CBD25 in daily clinical practice showed positive effects on patients’ pain and quality of life.”

https://pubmed.ncbi.nlm.nih.gov/40560527/

https://link.springer.com/article/10.1007/s12325-025-03262-z

In vitro antimicrobial activity of Thai stick cannabis Hang Kra Rog Phu Phan (Cannabis sativa L.), sugar leaves extract against pathogenic bacteria

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“Objective: Cannabis sativa L. is aware of a rich source of bioactive substances with various structures that exhibit pharmacological activity in the central nervous system, cardiovascular, cerebrovascular, respiratory, reproductive, and gastrointestinal systems.

Materials and methods: In this study, cannabis sugar leaves were soaked in 99% ethanol, followed by evaporation. The antibacterial effect of the cannabis sugar leaf extract was then evaluated using the disc diffusion method. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined using broth dilution.

Results: The results of this study indicated that the cannabis sugar leaf extract inhibited Bacillus cereus, Vibrio cholerae, Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis when compared to tetracycline, but it did not inhibit Pseudomonas aeruginosa. The MIC and MBC of the cannabis sugar leaves extract against B. cereus, V. cholerae, E. coli, S. aureus, and S. epidermidis were 0.977, 1.953, 31.25, 62.5, 125, 250, 250, 500, 250, and 500 mg/ml, respectively. The bioactive compounds in cannabis sugar leaf extract were identified using high-performance liquid chromatography.

Conclusion: The results indicated that the major bioactive compounds were Δ-9- tetrahydrocannabinol (THC) and cannabidiol (CBD). While minor bioactive compounds included gallic acid and tannic acid. These results support the benefits of cannabis sugar leaf extract, which has been used for its pharmacological properties and may be useful as an alternative antimicrobial agent in medicine.”

https://pubmed.ncbi.nlm.nih.gov/40568500/

https://www.ejmanager.com/mnstemps/39/39-1729498509.pdf?t=1750936743

The endocannabinoidomes: Pharmacological redundancy and promiscuity, and multi-kingdom variety of sources and molecular targets

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“The endocannabinoid system (eCB) is a complex signaling network discovered in mammals during the 1980s-1990s.

It conventionally revolves around two arachidonic acid-derived mediators, N-arachidonoyl-ethanolamine (anandamide) and 2-arachidonoyl-glycerol; their main receptors, the cannabinoid receptors of type 1 (CB1) and type 2 (CB2), and the transient receptor potential vanilloid-1 channels; and the enzymes responsible for their biosynthesis and degradation. However, drawing on these discoveries, numerous eCB-like signaling lipids beyond the classical eCBs, have been unveiled, together with their receptors and metabolic enzymes, thus forming a more complex signaling network known as the endocannabinoidome (eCBome).

This review explores the physiology, pharmacological complexity, and molecular targets of the mammalian eCBome, highlighting its versatility and redundancy in the context of global health. Emerging mediators, metabolic pathways and mechanisms, receptors, and their implications in human physiology and pathology are described, particularly concerning metabolic disorders, pain, inflammation, neurodegenerative diseases, and cancer.

The importance of other “eCBomes” in nonmammalian forms of life that constitute the external and internal environments of mammals is also discussed for the first time in this context. The overarching objective of this article is to gain insights into the potential of eCBome-based therapeutic strategies aimed at enhancing both human and environmental well-being.

SIGNIFICANCE STATEMENT: Lipid-based signaling molecules are ubiquitous in nature, yet their study remains challenging due to intricate regulatory mechanisms. Among lipid signaling pathways, the endocannabinoid (eCB) system and its extended version, the endocannabinoidome (eCBome), are particularly remarkable. Comprising hundreds of mediators, and dozens of receptors and metabolic enzymes, the eCBome regulates critical physiological processes not only in mammals but also across diverse organisms, including plants, fungi, and bacteria. This article examines the evolutionary and functional diversity of eCBomes and highlights their untapped potential as multikingdom therapeutic targets to address pressing challenges in global health.”

https://pubmed.ncbi.nlm.nih.gov/40554266/

https://pharmrev.aspetjournals.org/article/S0031-6997(25)07478-2/abstract

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Δ9-Tetrahydrocannabinol and cannabidiol selectively suppress toll-like receptor (TLR) 7- and TLR8-mediated interleukin-1β production by human CD16+ monocytes by inhibiting its post-translational maturation

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“Monocytes are innate immune cells that release inflammatory factors upon detection of infectious and injurious stimuli. CD16+ monocytes, a subset of the total monocyte population, are associated with acute and chronic inflammation in human immunodeficiency virus-associated neurocognitive disorder and rheumatoid arthritis. Given the role monocytes play in regulating the host immune response, this investigation explored the effects of cannabinoids on the monocyte secretome for potential therapeutic applications.

Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are major cannabis-derived compounds established to have immune-modulating properties. Despite a rise in medical cannabis use, the specific mechanism by which THC and CBD modulate the inflammatory response, including by human monocytes remains poorly understood.

We hypothesized that THC and CBD suppress toll-like receptor (TLR) 7- or TLR8-induced inflammatory profiles by CD16+ and CD16– monocytes, specifically interleukin (IL) 1β maturation. Cannabinoid receptor 2 selective agonist, JWH-015, was used to deduce whether cannabinoid receptor 2 signaling alone can mimic immune-modulating properties of THC. Primary human CD16+ and CD16– monocytes were pretreated with THC, CBD, or JWH-015 and then activated through TLR7 or TLR8. Activated monocytes mainly produced IL-1β, tumor necrosis factor-⍺, and IL-6.

We show that THC and CBD, but not JWH-015, exert anti-inflammatory effects on primary human monocyte apoptosis-associated speck-like protein-incorporating inflammasome formation and subsequent caspase-1 activity, contributing to suppressed IL-1β production. In addition, mRNA expression of IL1B, CASP1, NLRP3, and PYCARD were unaffected by THC. Minimal THC effects were observed on TLR8-mediated AIM2 mRNA expression.

Collectively, results from these studies suggest THC and CBD may be useful in mitigating IL-1β-mediated acute or chronic inflammation.

SIGNIFICANCE STATEMENT: This current investigation aimed to understand the role of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in mediating virally activated CD16+ monocyte inflammatory cytokine production. Further, the results indicated that THC and CBD selectively suppress monocyte interleukin 1β production, though THC is more efficacious, through its maturation, as evidenced by suppressed caspase-1 activity and apoptosis-associated speck-like protein-incorporating inflammasome formation.

This work provides evidence to support that THC, and to an extent CBD, exert anti-inflammatory effects that could be useful in mitigating monocyte interleukin 1β-mediated chronic inflammation.”

https://pubmed.ncbi.nlm.nih.gov/40553974/

https://jpet.aspetjournals.org/article/S0022-3565(25)39828-9/abstract

Effectiveness of Full Spectrum Cannabis Extracts in the Treatment of Chronic Pain: An Open Label Study

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“The aim of this work was to assess the effectiveness of full-spectrum cannabis (THC and CBD) extracts as adjuvants in the treatment of chronic pain. This is a prospective, open label, longitudinal study.

Major cannabinoids were analyzed in herbal preparations using high performance liquid chromatography (HPLC). Subjects were included when chronic pain diagnosis criteria was met according to physicians’ diagnosis. A patient stratification protocol was developed using a visual analogue scale to measure pain, a numerical scale for life quality parameters and a self-administered health survey. Eighty-eight patients aged between 35 and 88 years were included.

A significant decrease in both pain and other life quality parameters was observed between time zero and subsequent time intervals, excepting the “appetite” variable.

Overall, 51 individuals reported a decrease in pain, 38 a decrease in anxiety and 48 in insomnia, with “decrease” defined as symptom reduction of 50% or more between the first and last consultation. In addition, 23 subjects reduced or discontinued other analgesics and/or anti-inflammatory drugs during the trial. Adverse effects were mild and reversible.

These results are consistent with previous studies, supporting effectiveness and safety of cannabis extracts as adjuvants in the treatment of chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/40526158/

https://www.tandfonline.com/doi/full/10.1080/15360288.2025.2517778

Exploring Cannabis sativa L for Anti-Alzheimer Potential: An Extensive Computational Study including Molecular Docking, Molecular Dynamics, and ADMET Assessments

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“Introduction: Cholinesterase enzymes play a pivotal role in hydrolyzing acetylcholine, a neurotransmitter crucial for memory and cognition, into its components, acetic acid, and choline. A primary approach in addressing Alzheimer’s disease symptoms is by inhibiting the action of these enzymes.

Methods: With this context, our study embarked on a mission to pinpoint potential Cholinesterase (ChE) inhibitors using a comprehensive computational methodology. A total of 49 phytoconstituents derived from Cannabis sativa L underwent in silico screening via molecular docking, pharmacokinetic and pharmacotoxicological analysis, to evaluate their ability to inhibit cholinesterase enzymes. Out of these, two specific compounds, namely tetrahydrocannabivarin and Δ-9- tetrahydrocannabinol, belonging to cannabinoids, stood out as prospective therapeutic agents against Alzheimer’s due to their potential as cholinesterase inhibitors. These candidates showcased commendable binding affinities with the cholinesterase enzymes, highlighting their interaction with essential enzymatic residues.

Results: They were predicted to exhibit greater binding affinities than Rivastigmine and Galantamine. Their ADMET assessments further classified them as viable oral pharmaceutical drugs. They are not expected to induce any mutagenic or hepatotoxic effects and cannot produce skin sensitization. In addition, these phytoconstituents are predicted to be BBB permeable and can reach the central nervous system (CNS) and exert their therapeutic effects. To delve deeper, we explored molecular dynamics (MD) simulations to examine the stability of the complex formed between the best candidate (Δ-9-tetrahydrocannabinol) and the target proteins under simulated biological conditions. The MD study affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes.

Conclusion: Our research outcomes provide valuable insights, offering a clear direction for the pharmaceutical sector in the pursuit of effective anti-Alzheimer treatments.”

https://pubmed.ncbi.nlm.nih.gov/40525419/

https://www.eurekaselect.com/article/142967

Single cell multiomic analysis of the impact of Delta-9-tetrahydrocannabinol on HIV infected CD4 T cells

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“Cannabis use is prevalent among individuals living with HIV in the United States, but the impact of cannabis exposure on the reservoir of latently infected cells that persists during antiretroviral therapy (ART) remains unclear. To address this gap, we analyzed the effect of Δ-9-tetrahydrocannabinol (THC) on primary CD4 T cells that were latently infected with HIV.

We found that THC had no detectable effect on baseline or latency reversing agent (LRA) stimulated HIV expression, or on expression of an activation marker (CD38). However, using an integrated multiomic single-cell analysis of genome-wide chromatin accessibility and gene expression, we observed altered expression of several hundred genes in HIV infected CD4 T cells after THC exposure, including transcriptional downregulation of genes involved in protein translation and antiviral pathways, indicating that THC suppresses innate immune activation in infected cells. Additionally, chromatin accessibility analysis demonstrated upregulated chromatin binding activity for the transcriptional regulator CTCF, and reduced activity for members of the ETS transcription factor family in infected cells after THC exposure.

These findings provide insights into the mechanisms by which cannabis use could influence the persistence of HIV within cellular reservoirs and the molecular phenotype of latently infected cells. Further elucidation of the underlying mechanisms involved in THC-mediated changes to HIV infected cells, will lead to an improved understanding of the impact of cannabis use on the HIV reservoir.

Importance: Cannabis use is common among individuals living with HIV, but the long-term effects of cannabis use on the HIV reservoir are not yet studied completely. We employed advanced single-cell technologies to reveal how cannabis components, specifically THC, influence HIV-infected immune cells and their pattern of gene expression. We found that, while THC doesn’t reactivate virus in latently infected cells, it alters the molecular characteristics of these infected immune cells. These findings are important because they underscore how cannabis could regulate persistent infection in people living with HIV. Understanding these cellular changes in response to THC could be helpful for successful treatment for people living with HIV.”

https://pubmed.ncbi.nlm.nih.gov/40502036/

https://www.biorxiv.org/content/10.1101/2025.06.02.657468v1

“Yes, there is growing evidence that cannabis could play a role in regulating persistent HIV infection. Studies suggest that cannabinoids, particularly THC, can alter the molecular characteristics of HIV-infected immune cells without reactivating the virus. These changes might be beneficial in reducing inflammation and improving treatment outcomes for people living with HIV.”

Activation of CB1R alleviates autism spectrum disorder-like behavior and synaptic impairments

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“We previously found that enhancing the levels of 2-arachidonoylglycerol (2-AG) and anandamide (AEA) could improve autism spectrum disorder (ASD) symptoms. This study investigated the effect of cannabinoid type 1 receptor (CB1R) in ASD with pharmacological, genetic and brain-targeted intervention and the underlying mechanisms.

Results showed that blocking CB1R counteracted the beneficial effects of boosting 2-AG or AEA on ASD-like behaviors in valproic acid (VPA)-exposed mice. Besides, CB1R knockout mice exhibited ASD-like behaviors and synaptic deficits.

In CB1R-specific brain-targeted regulation, activating CB1R ameliorated synaptic dysfunction, including neuronal complexity, spine density, dendritic integrity, synaptic protein expression, and neuronal damage. Moreover, activating CB1R enhanced the expression and current density of Kir4.1, indicating that CB1R may influence synaptic activity by modulating Kir4.1.

Collectively, our findings indicated a critical role for CB1R in the improvement of ASD-like behavior and synaptic dysfunction, which may offer promising avenues for developing effective treatments for ASD.”

https://pubmed.ncbi.nlm.nih.gov/40484367/

“Brain-specific activation of CB1R improves synaptic impairments in ASD model mice.”

https://www.sciencedirect.com/science/article/abs/pii/S0024320525004321?via%3Dihub