Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Molecular Docking Integrated with Network Pharmacology Explores the Therapeutic Mechanism of Cannabis sativa against Type 2 Diabetes

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“The incidence of type 2 diabetes (T2D) is rising, and finding new treatments is important. C. sativa is a plant suggested as a potential treatment for T2D, but how it works needs to be clarified. This study explored the pharmacological mechanism of C. sativa in treating T2D. We identified the active compounds in C. sativa and their targets. From there, we examined the genes associated with T2D and found overlapping genes. We conducted an enrichment analysis and created a protein-protein and target-compound interactions network. We confirmed the binding activities of the hub proteins and compounds with molecular docking. We identified thirteen active compounds from C. sativa, which have 150 therapeutic targets in T2D. The enrichment analysis showed that these proteins are involved in the hormone, lipid, and stress responses. They bind transcription factors and metals and participate in the insulin, PI3K/Akt, HIF-1, and FoxO signaling pathways. We found four hub proteins (EGFR, ESR1, HSP90AA1, and SRC) that bind to the thirteen bioactive compounds. This was verified using molecular docking. Our findings suggest that C. sativa‘s antidiabetic action is carried out through the insulin signaling pathway, with the participation of HIF-1 and FoxO.”

https://pubmed.ncbi.nlm.nih.gov/37754241/

https://www.mdpi.com/1467-3045/45/9/457

Health-related quality of life in patients accessing medicinal cannabis in Australia: The QUEST initiative results of a 3-month follow-up observational study

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“Aims: Patients with chronic health conditions not responding to conventional treatment can access medicinal cannabis (MC) prescriptions from clinicians in Australia. We aimed to assess overall health-related quality of life (HRQL), pain, fatigue, sleep, anxiety, and depression in a large real-world sample of patients accessing prescribed medicinal cannabis. We hypothesized that all patient-reported outcomes (PROs) would improve from baseline to 3-months.

Methods: The QUEST Initiative is a large prospective multicenter study of patients with any chronic health condition newly prescribed medicinal cannabis between November 2020 and December 2021. Eligible patients were identified by 120 clinicians at medical centers across six Australian states. Consenting participants completed the EuroQol Group EQ-5D-5L health status questionnaire; European Organization for Research & Treatment of Cancer Quality of Life questionnaire (QLQ-C30); Patient-Reported Outcomes Measurement Information System (PROMIS) Short Forms in Fatigue and Sleep Disturbance, and the Depression Anxiety Stress Scale (DASS-21) before starting therapy, at 2-weeks titration, then monthly for 3-months.

Results: Of the 2762 consenting participants, 2327 completed baseline and at least one follow-up questionnaire. Ages ranged between 18-97 years (mean 51y; SD = 15.4), 62.8% were female. The most commonly treated conditions were chronic pain (n = 1598/2327; 68.7%), insomnia (n = 534/2327; 22.9%), generalized anxiety (n = 508/2327; 21.5%), and mixed anxiety and depression (n = 259/2327; 11%). Across the whole cohort both EQ-5D-5L utility scores and QLQ-C30 summary scores showed clinically meaningful improvement in HRQL from baseline to mean follow-up with d = 0.54 (95%CI:0.47 to 0.59) and d = 0.64 (95%CI:0.58 to 0.70) respectively; and clinically meaningful improvement in fatigue (d = 0.54; 95%CI:0.48 to 0.59). There was clinically meaningful reduction of pain for those with chronic pain (d = 0.65; 95%CI:0.57 to 0.72); significant improvements for those with moderate to extremely severe anxiety (X2 = 383; df = 4; p<0.001) and depression (X2 = 395; df = 4; p<0.001); and no changes in sleep disturbance.

Conclusions: We observed statistically significant, clinically meaningful improvements in overall HRQL and fatigue over the first 3-months in patients with chronic health conditions accessing prescribed medical cannabis. Anxiety, depression, and pain also improved over time, particularly for those with corresponding health conditions. The study continues to follow-up patients until 12-months to determine whether improvements in PROs are maintained long-term.”

https://pubmed.ncbi.nlm.nih.gov/37672515/

“Short-term findings over 3-months indicate that patients prescribed MC in practice have improved HRQL and reduced fatigue. Patients experiencing anxiety, depression, or chronic pain also improved in those outcomes over 3-months, but no changes in sleep disturbance were observed in patients with sleep disorders.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0290549

Individually tailored dosage regimen of full-spectrum Cannabis extracts for autistic core and comorbid symptoms: a real-life report of multi-symptomatic benefits

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“Autism Spectrum Disorders (ASD) may significantly impact the well-being of patients and their families. The therapeutic use of cannabis for ASD has gained interest due to its promising results and low side effects, but a consensus on treatment guidelines is lacking. In this study, we conducted a retrospective analysis of 20 patients with autistic symptoms who were treated with full-spectrum cannabis extracts (FCEs) in a response-based, individually-tailored dosage regimen. The daily dosage and relative proportions of cannabidiol (CBD) and tetrahydrocannabinol (THC) were adjusted based on treatment results following periodic clinical evaluation. Most patients (80%) were treated for a minimum of 6 months. We have used a novel, detailed online patient- or caregiver-reported outcome survey that inquired about core and comorbid symptoms, and quality of life. We also reviewed patients’ clinical files, and no individual condition within the autistic spectrum was excluded. This real-life approach enabled us to gain a clearer appraisal of the ample scope of benefits that FCEs can provide for ASD patients and their families. Eighteen patients started with a CBD-rich FCE titrating protocol, and in three of them, the CBD-rich (CBD-dominant) FCE was gradually complemented with low doses of a THC-rich (THC-dominant) FCE based on observed effects. Two other patients have used throughout treatment a blend of two FCEs, one CBD-rich and the other THC-rich. The outcomes were mainly positive for most symptoms, and only one patient from each of the two above-mentioned situations displayed important side effects one who has used only CBD-rich FCE throughout the treatment, and another who has used a blend of CBD-Rich and THC-rich FCEs. Therefore, after FCE treatment, 18 out of 20 patients showed improvement in most core and comorbid symptoms of autism, and in quality of life for patients and their families. For them, side effects were mild and infrequent. Additionally, we show, for the first time, that allotriophagy (Pica) can be treated by FCEs. Other medications were reduced or completely discontinued in most cases. Based on our findings, we propose guidelines for individually tailored dosage regimens that may be adapted to locally available qualified FCEs and guide further clinical trials.”

https://pubmed.ncbi.nlm.nih.gov/37671290/

https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1210155/full

Mechanisms Involved in the Therapeutic Effect of Cannabinoid Compounds on Gliomas: A Review with Experimental Approach

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“Introduction: Brain tumors have high morbidity and mortality rates, accounting for 1.4% of all cancers. Gliomas are the most common primary brain tumors in adults. Currently, several thera-peutic approaches are used; however, they are associated with side effects that affect pa-tients’quality of life. Therefore, further studies are needed to develop novel therapeutic protocols with a more favorable side effect profile. In this context, cannabinoid compounds may serve as potential alternatives.

Objective: This study aimed to review the key enzymatic targets involved in glioma pathophysi-ology and evaluate the potential interaction of these targets with four cannabinoid derivatives through molecular docking simulations.

Methods: Molecular docking simulations were performed using four cannabinoid compounds and six molecular targets associated with glioma pathophysiology.

Results: Encouraging interactions between the selected enzymes and glioma-related targets were observed, suggesting their potential activity through these pathways. In particular, cannabigerol showed promising interactions with epidermal growth factor receptors and phosphatidylinositol 3-kinase, while Δ-9-tetrahydrocannabinol showed remarkable interactions with telomerase reverse transcriptase.

Conclusion: The evaluated compounds exhibited favorable interactions with the analyzed enzy-matic targets, thus representing potential candidates for further in vitro and in vivo studies.”

https://pubmed.ncbi.nlm.nih.gov/37649287/

https://www.eurekaselect.com/article/134162

Delta-9-tetrahydrocannabinol modulates pain sensitivity among persons receiving opioid agonist therapy for opioid use disorder: A within-subject, randomized, placebo-controlled laboratory study

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“The opioid and cannabinoid receptor systems are inextricably linked-overlapping at the anatomical, functional and behavioural levels. Preclinical studies have reported that cannabinoid and opioid agonists produce synergistic antinociceptive effects. Still, there are no experimental data on the effects of cannabinoid agonists among humans who receive opioid agonist therapies for opioid use disorder (OUD). We conducted an experimental study to investigate the acute effects of the delta-9-tetrahydrocannabinol (THC) among persons receiving methadone therapy for OUD. Using a within-subject, crossover, human laboratory design, 25 persons on methadone therapy for OUD (24% women) were randomly assigned to receive single oral doses of THC (10 or 20 mg, administered as dronabinol) or placebo, during three separate 5-h test sessions. Measures of experimental and self-reported pain sensitivity, abuse potential, cognitive performance and physiological effects were collected. Mixed-effects models examined the main effects of THC dose and interactions between THC (10 and 20 mg) and methadone doses (low-dose methadone defined as <90 mg/day; high dose defined as >90 mg/day). Results demonstrated that, for self-reported rather than experimental pain sensitivity measures, 10 mg THC provided greater relief than 20 mg THC, with no substantial evidence of abuse potential, and inconsistent dose-dependent cognitive adverse effects. There was no indication of any interaction between THC and methadone doses. Collectively, these results provide valuable insights for future studies aiming to evaluate the risk-benefit profile of cannabinoids to relieve pain among individuals receiving opioid agonist therapy for OUD, a timely endeavour amidst the opioid crisis.”

https://pubmed.ncbi.nlm.nih.gov/37644897/

https://onlinelibrary.wiley.com/doi/10.1111/adb.13317

Therapeutic Potential of Cannabinoids in Glaucoma

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“Glaucoma is a leading cause of irreversible blindness worldwide. To date, intraocular pressure (IOP) is the only modifiable risk factor in glaucoma treatment, but even in treated patients, the disease can progress. Cannabinoids, which have been known to lower IOP since the 1970s, have been shown to have beneficial effects in glaucoma patients beyond their IOP-lowering properties. In addition to the classical cannabinoid receptors CB1 and CB2, knowledge of non-classical cannabinoid receptors and the endocannabinoid system has increased in recent years. In particular, the CB2 receptor has been shown to mediate anti-inflammatory, anti-apoptotic, and neuroprotective properties, which may represent a promising therapeutic target for neuroprotection in glaucoma patients. Due to their vasodilatory effects, cannabinoids improve blood flow to the optic nerve head, which may suggest a vasoprotective potential and counteract the altered blood flow observed in glaucoma patients. The aim of this review was to assess the available evidence on the effects and therapeutic potential of cannabinoids in glaucoma patients. The pharmacological mechanisms underlying the effects of cannabinoids on IOP, neuroprotection, and ocular hemodynamics have been discussed.”

https://pubmed.ncbi.nlm.nih.gov/37631064/

https://www.mdpi.com/1424-8247/16/8/1149

Cannabinoids and standardized cannabis extracts inhibit migration, invasion, and induce apoptosis in MCF-7 cells through FAK/MAPK/Akt/NF-κB signaling

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“Background: Breast cancer is the highest incidence of all types of cancer in women, and the cancer metastasis process accounts for a majority of cancer deaths. Two major cannabinoids, Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), from Cannabis sativa are expected to have anti-cancer activity. This study aimed to investigate the effects of THC, CBD, and standardized cannabis extracts (F1, F2, and F3) on migration, invasion, and apoptosis of human breast cancer (MCF-7) cells.

Methods: Cell viability, survival, and apoptosis were determined using the MTT, clonogenic, and nuclear staining assays, respectively, while cancer cell migration and invasion were evaluated by the wound healing, trans-well, and filopodia assays. Western blot analysis was used to find out the mechanisms of the cannabinoids against MCF-7 cells.

Results: CBD, THC, and F1 inhibited filopodia formation, migration, and invasion of MCF-7 cells through suppressing the expression of the FAK, Akt, ERK1/2, p38MAPKs, and NF-κB upstream pathways, as well as inhibiting the Rac1/Cdc42 downstream pathways. In addition, CBD significantly inhibited the mTOR pathway. Furthermore, CBD and F1 induced apoptosis in MCF-7 cells via the Bcl-2/caspase-3 pathways.

Conclusion: These results indicate that THC, CBD, and F1 have great abilities for preventing breast cancer cell metastasis in in vitro experiments.”

https://pubmed.ncbi.nlm.nih.gov/37625625/

https://www.sciencedirect.com/science/article/abs/pii/S0887233323001169?via%3Dihub

Cannabidiol and Tetrahydrocannabinol Use in Parkinson’s Disease: An Observational Pilot Study

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“Background: There is a need for more research examining the use of cannabis, tetrahydrocannabinol (THC), and cannabidiol (CBD) products in people with Parkinson’s disease (PD), especially given the recent increase in the use of these products.

Objectives: Given the recent increase in over-the-counter CBD use as well as the prescription of medical cannabis by treating physicians, the utilization method, effects on motor and non-motor symptoms, side effects, and attitude toward cannabis use were examined in a naturalistic sample of patients with PD.

Methods: A total of 15 individuals with PD, eight of whom were prescribed CBD/THC treatment and seven who were not taking any CBD/THC product, were assessed cross-sectionally. Participants completed structured neuropsychological testing, motor assessment, and questionnaires regarding mood, subjective cognition, and symptom levels. T-tests were completed for quantitative measures and descriptive data were examined and described. Due to the small sample size, Shapiro-Wilk tests for normality were utilized and Mann-Whitney U analyses were completed when appropriate.

Results: We found a wide range of prescribed products and methods as well as variability in perceived benefits and untoward effects, even in our small sample. Individuals with PD who were taking a CBD/THC product had lower global cognition scores on the Montreal Cognitive Assessment (MoCA) but no detectable differences among more specific neuropsychological measures. They also had more non-motor symptoms of PD but no differences in motor symptom levels. Qualitatively, some participants with PD who were taking CBD/THC reported improved pain levels, sleep, and reductions in anxiety. A few negative effects were endorsed, including sleepiness, concentration difficulties, and forgetfulness.

Conclusion: CBD/THC utilization in PD is varied. In our small sample, individuals who utilized the treatment had lower MoCA scores, more non-motor symptoms, and descriptively reported improvements in sleep, anxiety, and pain, and had side effects of sleepiness and cognitive difficulty. Future studies should focus on clinical trials with standardized CBD/THC methods of use.”

https://pubmed.ncbi.nlm.nih.gov/37621812/

https://www.cureus.com/articles/169539-cannabidiol-and-tetrahydrocannabinol-use-in-parkinsons-disease-an-observational-pilot-study#!/

Oral Tetrahydrocannabinol (THC):Cannabinoid (CBD) Cannabis Extract Adjuvant for Reducing Chemotherapy-Induced Nausea and Vomiting (CINV): A Randomized, Double-Blinded, Placebo-Controlled, Crossover Trial

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“Objective: To evaluate the effects of tetrahydrocannabinol (THC):cannabinoid (CBD) (1:1) oil in reducing chemotherapy-induced nausea and vomiting (CINV) in gynecologic cancer patients who received moderate-to-high emetogenic chemotherapy.

Material and method: This was a randomized, double-blinded, crossover and placebo-controlled trial. The study was conducted at the Gynecologic Oncology Units, Bhumibol Adulyadej Hospital (BAH), Royal Thai Air Force, Bangkok, Thailand, between August and November 2022. Participants had gynecologic cancer and received moderate-to-high emetogenic chemotherapy. Subjects were randomized and divided into two groups (A and B) based on the block of four randomization method. In the first cycle, groups A and B received THC:CBD extract oil 1:1 (TCEO) and placebo before chemotherapy administration. In the second cycle, groups A and B received placebo and TCEO before chemotherapy administration. Both groups received per protocol antiemetic medication during chemotherapy. Nausea score and side effects were recorded.

Results: A total of 60 cases were recruited. After exclusion, 54 cases were included in the study. The mean age of participants was 54.4 years. The mean body mass index (BMI) was 26.5 kg/m2. Fifty-nine (21/54) percent cases were the advanced stages of cancer. The nausea score of TCEO and placebo groups were 2.11 and 2.99, respectively (P < 0.05). More than half of the participants (36/54) reported dizziness and sedation side effects. Dry mouth, confusion, anxiety, and palpitation of both groups were comparable.

Conclusion: The cannabinoid extract (THC:CBD) was an appropriate adjuvant agent to reduce CINV in patients with gynecologic cancer who received high-emetogenic chemotherapy. Dizziness and sedation were the major side effects.”

https://pubmed.ncbi.nlm.nih.gov/37608911/

https://www.dovepress.com/oral-tetrahydrocannabinol-thccannabinoid-cbd-cannabis-extract-adjuvant-peer-reviewed-fulltext-article-IJWH

A machine learning approach for understanding the metabolomics response of children with autism spectrum disorder to medical cannabis treatment

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“Autism spectrum disorder (ASD) is a neurodevelopmental condition impacting behavior, communication, social interaction and learning abilities. Medical cannabis (MC) treatment can reduce clinical symptoms in individuals with ASD. Cannabis-responsive biomarkers are metabolites found in saliva that change in response to MC treatment. Previously we showed levels of these biomarkers in children with ASD successfully treated with MC shift towards the physiological levels detected in typically developing (TD) children, and potentially can quantify the impact. Here, we tested for the first time the capabilities of machine learning techniques applied to our dynamic, high-resolution and rich feature dataset of cannabis-responsive biomarkers from a limited number of children with ASD before and after MC treatment and a TD group to identify: (1) biomarkers distinguishing ASD and TD groups; (2) non-cannabinoid plant molecules with synergistic effects; and (3) biomarkers associated with specific cannabinoids. We found: (1) lysophosphatidylethanolamine can distinguish between ASD and TD groups; (2) novel phytochemicals contribute to the therapeutic effects of MC treatment by inhibition of acetylcholinesterase; and (3) THC- and CBD-associated cannabis-responsive biomarkers are two distinct groups, while CBG is associated with some biomarkers from both groups.”

https://pubmed.ncbi.nlm.nih.gov/37608004/

https://www.nature.com/articles/s41598-023-40073-0