Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Long-term cannabinoid therapy can ameliorate chronic sleep deprivation-induced behavioral and neuroinflammatory changes in mice

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“Endocannabinoid system is an important contributor to body’s immune responses which are significantly impaired by chronic sleep deprivation (cSD). Although cannabinoids can modulate the endocannabinoid system, most are understudied, especially regarding cSD.

To investigate the therapeutic potential of CBD, CBG, CBC and their combinations, current study analyzed cSD-induced memory impairment, depression, microglial responses, cytokine profile and therapeutic effects of cannabinoid treatments using behavioral test and ELISA. Furthermore, molecular docking of these cannabinoids was performed to deduce the binding affinity with cannabinoid receptors and possible entrouge effects.

The results showed that memory impairment and depression were more evident in cSD groups. Moreover, microglial activation and pro-inflammatory polarization was also more evident and was supported by increased pro-inflammatory cytokine concentrations in cSD groups.

These changes were significantly reversed the cannabinoid groups but the combination of CBD + CBC was more effective than other treatments in reversing these cSD-induced behavioral and neuroinflammatory changes. Whereas, the molecular docking results also corroborated with the neuroimmunological changes observed in the current study, pointing towards the possible therapeutic role.

SIGNIFICANCE STATEMENT: Chronic SD employs microglial activation/polarization, to exert behavioral impairments and neuroinflammation.

This study signifies the therapeutic potential of proper sleep and cannabinoid intake.”

https://pubmed.ncbi.nlm.nih.gov/40628367/

“This study demonstrates the therapeutic efficacy of cannabinoid treatments in ameliorating cSD-induced behavioral and neuroinflammatory alterations. Notably, a multiple-compound treatment of CBD and CBC exhibited superior effectiveness compared to single-compound treatments. These findings suggest potential avenues for developing effective interventions against cSD-induced detrimental changes.”

https://www.sciencedirect.com/science/article/abs/pii/S0304394025002022?via%3Dihub

Treatment of Migraine With Phytocannabinoids, the Involvement of Endocannabinoids in Migraine, and Potential Mechanisms of Action

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“The American Migraine Foundation estimates that over 39 million Americans and over 1 billion people worldwide suffer from some form of migraine. Treatment of migraine generally falls into two categories: treatment of attacks once they have begun, and prophylactic prevention, including lifestyle changes. The use of phytocannabinoids to reduce both the frequency and severity of migraine is widely documented in scientific, grey, and popular literature. This review provides descriptions of both preclinical and clinical studies involving the treatment of migraines with phytocannabinoids as well as the involvement of endocannabinoids and endocannabinoid-like compounds in migraine pathology, including the receptors and associated mechanisms. Currently unanswered questions and areas for further exploration are discussed.”

https://pubmed.ncbi.nlm.nih.gov/40630421/

“The clinical studies published to date strongly suggest that phytocannabinoids are useful for mitigating migraine pain and for migraine prophylaxis. Further, studies show the potential for endocannabinoid and endocannabinoid-like compounds in migraine treatment.”

https://onlinelibrary.wiley.com/doi/10.1155/prm/7181066

“Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.”

https://pubmed.ncbi.nlm.nih.gov/15159679/

Acute and chronic effects of medicinal cannabis use on anxiety and depression in a prospective cohort of patients new to cannabis

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“Introduction: Medicinal cannabis has mixed evidence for treating anxiety and depression, yet patients frequently use it as a treatment. This observational study evaluated the effects of medicinal cannabis initiation in adults with clinically significant anxiety and/or depression over a 6-month period.

Methods: Adults with clinically significant anxiety and/or depression initiating medicinal cannabis use in Maryland, USA completed ecological momentary assessment (EMA) and longitudinal follow-up evaluations. Hospital Anxiety and Depression Scale (HADS) assessments were completed at baseline and 1, 3, and 6 months after medicinal cannabis initiation. EMA measures were completed at baseline and daily for 8 weeks after cannabis initiation with measures collected before each cannabis use and at time of expected peak effect. Changes in anxiety and depression were evaluated using linear mixed effect models.

Results: Significant decreases from baseline in anxiety and depression were observed, with mean scores dropping below clinically significant levels within three months of initiation. EMA data indicated that most participants selected THC-dominant cannabis and acute reductions in anxiety, depression, and perceived driving ability along with increased ratings of feeling “high”. Acute effects were dose-dependent: 10-15 mg of oral THC and at least 3 puffs of vaporized cannabis yielded the most robust reductions in anxiety and depression.

Conclusions: Initiation of THC-dominant medicinal cannabis was associated with acute reductions in anxiety and depression, and sustained reductions in overall symptom severity over a 6-month period. Controlled clinical trials are needed to further investigate the efficacy and safety of medicinal cannabis for acute anxiety and depression symptom management.”

https://pubmed.ncbi.nlm.nih.gov/40623642/

“In this prospective, observational study, medicinal cannabis use was associated with significant decreases in self-reported anxiety and depression compared with pre-cannabis use initiation baseline assessments among individuals with clinically significant anxiety and/or depression. Reductions in anxiety and depression were observed acutely following individual episodes of cannabis use and overall symptom reductions were sustained over the six-month period of observation.”

https://www.sciencedirect.com/science/article/abs/pii/S0165032725012716?via%3Dihub

Evaluating the impact of cannabis oil for autistic children with and without concomitant medications: Insights from an open-label study

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“Background: Although only two drugs are FDA approved for autism spectrum disorder (ASD), clinical practice treatment includes off-label use of medications to address the troubling symptoms of ASD. Several trials showed the beneficial effects of medical cannabis for alleviating symptoms of ASD. However, data are lacking regarding its safety and effectiveness as a single agent compared to add-on therapy.

Aims: To compare the safety and effectiveness of medical cannabis as a monotherapy and add-on therapy in autistic children.

Methods: An open-label trial recruiting autistic children was performed and treated with medical cannabis oil with a THC:CBD ratio of 1:20, respectively. Tests were conducted at baseline and after 6 months of therapy. A secondary analysis was done to compare physical and behavior parameters, using tests such as Autism Diagnostic Observation Schedule and Wechsler tests in the two groups.

Results: Out of 109 participants, 81 completed the treatment. Thirty received cannabis as add-on therapy to a pre-existing treatment, whereas 51 received cannabis as monotherapy, with no observed differences in baseline characteristics between the groups. The mean maximal CBD dose was 3.1 mg/kg/day in the monotherapy group, compared to 2.8 mg/kg/day in the add-on group (p = 0.40). In patients treated with drugs for psychosis, the mean maximal dose was 2.48 mg/kg/day (p = 0.12). No differences were observed in most physical and behavioral parameters. In addition, no differences in CBD blood levels were observed.

Conclusions: Add-on cannabis therapy is as safe as monotherapy treatment, without significant differences in efficacy.”

https://pubmed.ncbi.nlm.nih.gov/40613426/

https://journals.sagepub.com/doi/10.1177/02698811251332841

Oral Cannabis for Taxane-Induced Neuropathy: A Pilot Randomized Placebo-Controlled Study

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“Introduction: Taxane-induced peripheral neuropathy (TIPN) is experienced by most patients with breast cancer, and there is no efficacious treatment. In pre-clinical studies, co-administration of two constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), synergistically reduces TIPN. 

Materials and Methods: The goal of this 8-week, double-blind, randomized pilot study, conducted from 2019 to 2021, was to test the feasibility and tolerability of oral cannabis (100 mg CBD: 5 mg THC, TID) relative to placebo on pain resulting from TIPN. Participants with painful TIPN completed daily questionnaires online about their pain, sleep, and medication use, and weekly questionnaires on neuropathy. 

Results: All participants (12 women; 51 ± 6 years) randomized to placebo (n = 6) or active (n = 6) cannabis capsules completed the trial. Participants in both medication groups requested dose reductions (mean ± SEM capsules/day: placebo: 2.4 ± 0.4; active: 2.0 ± 0.4). In a preliminary evaluation of efficacy, measures of pain, pain interference, sleep, and functional well-being significantly improved over time (p < 0.03), but participants receiving cannabis had significantly higher ratings of neuropathy at each week (p < 0.035) and lower ratings of functional well-being in the last 3 weeks of treatment compared with participants receiving placebo (p < 0.02). Similarly, cannabis significantly worsened ratings of sleep and pain interference relative to placebo (p < 0.05). 

Discussion: This study demonstrates that: (1) double-blind, placebo-controlled testing of cannabis capsules in this dose range is feasible and well tolerated in women with TIPN and (2) ratings of pain, neuropathy, and well-being significantly improved over 8 weeks, but cannabis significantly worsened several endpoints relative to placebo. These findings highlight the necessity of placebo control when assessing the therapeutic utility of cannabis. Although there was no signal of efficacy herein, a fully powered study testing a range of cannabis doses for TIPN is warranted, given its impact on most patients with breast cancer, promising pre-clinical data, and the widespread use of cannabis among patients with cancer.”

https://pubmed.ncbi.nlm.nih.gov/40611810/

https://www.liebertpub.com/doi/10.1089/can.2025.0028

Cannabidiol interactions with Δ-9-tetrahydrocannabinol on antinociception after carrageenan-induced inflammatory pain in male and female rats

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“Cannabis products used for pain typically contain Δ-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) in varied amounts, but data on the effects of specific cannabinoid formulations on different pain types are lacking.

This study used the carrageenan-induced inflammatory pain model to test oral Δ9-THC, CBD, or their combination on acute edema and pain hypersensitivity.

Male and female Sprague-Dawley rats (n = 10-14 per sex/group) were pretreated (1 hour) with vehicle (sesame oil), Δ9-THC (1, 3, and 10 mg/kg, p.o.), CBD (10, 30, 100 mg/kg, p.o.), or select doses of Δ9-THC + CBD combinations prior to an intraplantar λ-carrageenan injection into the hind paw.

The nonsteroidal anti-inflammatory drug ketoprofen (10 and 20 mg/kg i.p.) or its vehicle (1:1:18 ethanol:Cremophor EL:saline [Millipor Sigma]) was administered to a separate group as a positive control. Measurements were conducted at baseline and 1, 3, and 5 hours after carrageenan injection. Carrageenan produced edema and hypersensitivity to radiant heat (hyperalgesia) and mechanical pressure (allodynia).

Δ9-THC alone sex- and dose-dependently decreased hyperalgesia and allodynia but not inflammation, with effects of Δ9-THC being greater in females than males, and the lowest Δ9-THC dose was proinflammatory in males. CBD alone did not affect pain sensitivity but had modest anti-inflammatory effects in males. Isobolographic and dose addition analyses indicated Δ9-THC + CBD was subadditive relative to Δ9-THC alone.

These data demonstrate that prophylactic oral Δ9-THC alleviates acute inflammatory pain with sex-dependent effects, and CBD diminishes Δ9-THC antinociception when combined.

The findings suggest oral Δ9-THC is superior to CBD or combined Δ9-THC + CBD for acute inflammatory pain.

SIGNIFICANCE STATEMENT: Despite the popularity of cannabis for pain management, empirical data on how specific cannabinoid formulations affect acute inflammatory pain are limited. This study in rats found that pure Δ-9-tetrahydrocannabinol (Δ9-THC) formulations were most effective at improving inflammatory pain compared to pure cannabidiol or Δ9-THC + cannabidiol combinations, and females were more sensitive than males to the antinociceptive effects of Δ9-THC.”

https://pubmed.ncbi.nlm.nih.gov/40609153/

https://jpet.aspetjournals.org/retrieve/pii/S0022356525398381

Neutrophil extracellular traps and cannabinoids: potential in cancer metastasis

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“Cancer is the second leading cause of global mortality after cardiovascular diseases, with breast, lung, colon, and prostate cancers being the most common. WHO projects around 30 million new cancer cases worldwide by 2045, with breast cancer being the most common in women and lung cancer in men.

Metastasis is responsible for nearly 90% of cancer-related deaths. Breast and lung cancers tend to metastasize to the bones, lymph nodes, lungs, liver, and brain. Lungs remains one of the most common organs to which various forms of cancer metastasize.

An important factor in metastasis is NETosis – it can initially help to eliminate cancer cells, but it can also promote metastasis. Phytocannabinoids, compounds derived from Cannabis sativa, and the endocannabinoid system (ECS) offer promising therapeutic potential to inhibit NETosis and consequently cancer development and metastasis.

Although the precise effects of phytocannabinoids on neutrophil functions and NETosis are not fully understood and require further research in the context of cancer, preliminary studies suggest their potential to inhibit NET release in various disease models.

This review consolidates current knowledge and provides new insights into how phytocannabinoids and the ECS may serve as effective therapeutic tools to limit cancer metastasis.”

https://pubmed.ncbi.nlm.nih.gov/40599866/

“Research indicates that metastatic progression is responsible for most deaths caused by breast cancer, with metastatic processes accounting for nearly 90% of cancer-related mortality.”

“Phytocannabinoids, together with the endocannabinoid system (ECS), represent a highly promising therapeutic avenue for attenuating neutrophil effector functions, particularly the process of NETosis.

We believe that these compounds have significant potential as agents capable of effectively inhibiting metastatic progression.

Phytocannabinoids, derived primarily from the Cannabis sativa plant, are a group of organic compounds that interact with the endocannabinoid system (ECS) in the human body.”

“Both phytocannabinoids and the endocannabinoid system (ECS) show significant therapeutic potential in cancer treatment. Research indicates that these agents affect the proliferation, apoptosis, migration, and invasiveness of cancer cells. In addition, they modulate the tumor microenvironment, particularly the cells of the immune system.”

https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1595913/full

Differential metabolic pathways underlie THC- and CBD-mediated inhibition of B-cell activation in both young and aged mice

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“Objective: B lymphocytes play a crucial role in immunity but also contribute to the pathogenesis of various diseases. Cannabis plants produce numerous biologically active compounds, including cannabinoids. The two most studied phytocannabinoids are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). These cannabinoids exert diverse and potent biological effects primarily through the endocannabinoid system (ECS), which also plays a key role in mature B-cell function. Both the immune system and the ECS undergo age-related changes that lead to a clinically significant decline in function.

Methods: This study compares the effects of THC and CBD on B-cell activity in young and aged mice. Murine B lymphocytes were activated using lipopolysaccharide (LPS) and interleukin-4 (IL-4), and the impact of cannabinoid treatments was assessed in terms of cell phenotype, proliferation, antibody secretion, tumor necrosis factor-alpha (TNFα) secretion, extracellular signal-regulated kinase (ERK) phosphorylation, and the cellular metabolome.

Results: Both THC and CBD exhibited dose-dependent inhibitory effects on B-cell activation in young and aged mice. However, we show here, for the first time, that the treatments induce distinct metabolic profiles. Although some metabolites, such as glucose-6-phosphate, pentose phosphate pathway (PPP) and nucleotide metabolites, were reduced by both cannabinoids, THC selectively reduced the levels of a distinct set of amino acids, while only CBD increased the levels of Citrulline and Allantoin. Additionally, the effects of THC and CBD differed between young and aged B cells, suggesting that age-related changes in the ECS may influence cannabinoid sensitivity.

Conclusions: These findings provide insights into the distinct mechanisms by which THC and CBD regulate immune activation and may open the door for investigating the mechanisms behind cannabinoids effects on the immune system. They also highlight the need for further research into phytocannabinoid-based therapies, particularly in age-specific contexts. Given the immunoregulatory properties of cannabinoids, especially CBD, tailored therapeutic strategies may enhance their clinical applications.”

https://pubmed.ncbi.nlm.nih.gov/40599768/

“These findings emphasize the need for further investigation into phytocannabinoid-based therapies, particularly for age-specific applications. Given the immunoregulatory properties of cannabinoids, especially CBD, tailored therapeutic strategies may be developed to optimize their clinical use.”

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1605474/full

Revisiting the Gateway Drug Hypothesis for Cannabis: A Secondary Analysis of a Nationwide Survey Among Community Users in Japan

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“Aim: Cannabis has historically been used for medicinal and industrial purposes, but is strictly regulated worldwide due to the psychoactive effects of THC. In Japan, cannabis is frequently labeled a “gateway drug,” yet strong causal evidence for progression to other substances is limited. This study investigates whether cannabis acts as a gateway drug among Japanese users.

Methods: An anonymous online survey was conducted in January 2021 with 3900 individuals reporting lifetime cannabis use in Japan. Participants were recruited via social media. The survey gathered data on demographics, cannabis and other substance use history, order of substance initiation, psychiatric background, and criminal records. A Sankey diagram visualized substance use progression, and odds ratios were calculated to assess the likelihood of using other substances following cannabis use.

Results: Of all respondents, 81.5% were male, with the largest age group being 20-24. Tobacco and alcohol were the most common initial substances, while cannabis was typically the third. Odds for subsequent use of alcohol, tobacco, methamphetamine, and other illicit drugs after cannabis use were 1.25, 0.77, 0.08, and 0.78, respectively, suggesting low probabilities of progression. Nearly half of those who reported cannabis as their third drug did not use other substances afterward.

Conclusion: Cannabis use in Japan typically follows alcohol and tobacco, and rarely leads to further drug use. These findings challenge the gateway hypothesis in the Japanese context. Shared vulnerabilities and strict drug policies may shape these patterns. Further research is warranted to explore the impact of legal changes on drug use behavior.”

https://pubmed.ncbi.nlm.nih.gov/40590180/

Cannabis Use and Outcomes in Patients with Chronic Pancreatitis: A National Inpatient Sample Analysis

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“Background and aims: Cannabis is a commonly used recreational and medicinal substance and has been shown to have anti-inflammatory and analgesic effects. Previous studies have shown that cannabis may reduce disease severity of pancreatitis. We aim to use nationally available data to further investigate the impact of cannabis on outcomes among patients with chronic pancreatitis (CP).

Methods: Nationwide Inpatient Sample (NIS) 2016-2020 was used to identify patients with CP. Patients were stratified based on the presence of cannabis use. Data was collected regarding patient demographics, comorbidities, and Charlson Comorbidity Index (CCI). The outcomes assessed were sepsis, acute kidney injury (AKI), deep vein thrombosis (DVT), pulmonary embolism (PE), intensive care unit (ICU) admission, acute pancreatitis (AP), pancreatic cancer, total charges, and length of stay. The relationships were analyzed using multivariate logistic regression.

Results: Out of 907,790 hospitalized patients in this study; 52,360 (5.8%) were cannabis users. After adjusting for confounding factors, cannabis use was associated with decreased odds of mortality (aOR=0.47, p<0.001), DVT (aOR=0.71, p<0.001), PE (aOR=0.622, p=0.002), ICU admission (aOR=0.705, p<0.001), pancreatic cancer (aOR=0.730, p=0.021). There was no difference in odds of AKI, sepsis or AP between the two groups.

Conclusions: Our study found that cannabis use is associated with reduced disease severity and better outcomes among patients hospitalized with CP. Further studies are needed to confirm our findings and explore the role of cannabinoids in pancreatitis.”

https://pubmed.ncbi.nlm.nih.gov/40580529/

https://jgld.ro/jgld/index.php/jgld/article/view/6066