Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Phytocannabinoid Compositions from Cannabis Act Synergistically with PARP1 Inhibitor against Ovarian Cancer Cells In Vitro and Affect the Wnt Signaling Pathway

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“Ovarian cancer (OC) is the single most lethal gynecologic malignancy. Cannabis sativa is used to treat various medical conditions, and is cytotoxic to a variety of cancer types. We sought to examine the effectiveness of different combinations of cannabis compounds against OC. Cytotoxic activity was determined by XTT assay on HTB75 and HTB161 cell lines. Apoptosis was determined by flow cytometry. Gene expression was determined by quantitative PCR and protein localization by confocal microscopy. The two most active fractions, F5 and F7, from a high Δ9-tetrahydrocannabinol (THC) cannabis strain extract, and their standard mix (SM), showed cytotoxic activity against OC cells and induced cell apoptosis. The most effective phytocannabinoid combination was THC+cannabichromene (CBC)+cannabigerol (CBG). These fractions acted in synergy with niraparib, a PARP inhibitor, and were ~50-fold more cytotoxic to OC cells than to normal keratinocytes. The F7 and/or niraparib treatments altered Wnt pathway-related gene expression, epithelial-mesenchymal transition (EMT) phenotype and β-catenin cellular localization. The niraparib+F7 treatment was also effective on an OC patient’s cells. Given the fact that combinations of cannabis compounds and niraparib act in synergy and alter the Wnt signaling pathway, these phytocannabinoids should be examined as effective OC treatments in further pre-clinical studies and clinical trials.”

https://pubmed.ncbi.nlm.nih.gov/36364346/

“We suggest that cannabis might be regarded as a complementary and effective anti-cancer treatment for OC. Given the favorable safety profile of phytocannabinoids, compared to standard pharmacotherapies, we propose that clinical trials with cannabis-based products are desperately needed for OC patients.”

https://www.mdpi.com/1420-3049/27/21/7523/htm

Design of a New 3D Gelatin-Alginate Scaffold Loaded with Cannabis sativa Oil

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“There is an increasing medical need for the development of new materials that could replace damaged organs, improve healing of critical wounds or provide the environment required for the formation of a new healthy tissue. The three-dimensional (3D) printing approach has emerged to overcome several of the major deficiencies of tissue engineering. The use of Cannabis sativa as a therapy for some diseases has spread throughout the world thanks to its benefits for patients. In this work, we developed a bioink made with gelatin and alginate that was able to be printed using an extrusion 3D bioprinter. The scaffolds obtained were lyophilized, characterized and the swelling was assessed. In addition, the scaffolds were loaded with Cannabis sativa oil extract. The presence of the extract provided antimicrobial and antioxidant activity to the 3D scaffolds. Altogether, our results suggest that the new biocompatible material printed with 3D technology and with the addition of Cannabis sativa oil could become an attractive alternative to common treatments of soft-tissue infections and wound repair.”

https://pubmed.ncbi.nlm.nih.gov/36365500/

“In summary, herein we show that the new biomaterial loaded with Cannabis sativa oil and printed with 3D technology could be a promising alternative to conventional treatments for wound healing.”

https://www.mdpi.com/2073-4360/14/21/4506/htm

The Characteristics of Clinical Trials on Cannabis and Cannabinoids: A Review of Trials for Therapeutic or Drug Development Purposes

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“Introduction: Patients and healthcare practitioners are increasingly interested in using cannabis and cannabinoids to address unmet clinical needs. Although we have clinical evidence on the medical use of cannabinoids, a significant portion of the data is not based on randomized clinical trials, which are considered the gold standard in clinical research. We have reviewed the registered clinical trials on cannabis and cannabinoids for therapeutic or drug development purposes to underline the past and current attempts to generate robust clinical evidence and identify existing knowledge gaps.

Methods: We reviewed four clinical trial registries (International Clinical Trials Registry Program [ICTRP], ClinicalTrials.gov, European Clinical Trial Registry [EUCTR], Australian New Zealand Clinical Trial Registry [ANZCTR]) to identify clinical trials on cannabinoids (phyto- or synthetic) or cannabis-based medications between January 1, 2000, and December 31, 2021. All interventional clinical trials on cannabinoids and other compounds interacting with the endocannabinoid system, regardless of the investigated medical condition, assessed health outcomes, or choice of comparator, were included, provided they had a therapeutic or drug development purpose. Data on the primary sponsor, type of sponsor, date of registration, recruitment status, number of participants, study design, the phase of the study, country, medical conditions, investigated cannabinoids, and the route of administration were extracted. The therapeutic area and class of cannabinoids were identified based on the details of each trial.

Results: We included 834 out of 2966 reviewed clinical trials. The number of registered clinical trials has constantly increased from 30 in 2013 to 103 in 2021. More than 40% of registered clinical trials in 2021 were phase II and phase III clinical trials. The mean number of trial enrollments for completed, ongoing, and terminated studies were 128, 156, and 542, respectively. Clinical research on Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and the oral routes of administration dominate the field. Approximately two-thirds of clinical trials were conducted in five therapeutic areas (i.e., ‘Chronic pain,’ ‘Mental, behavioral or neurodevelopmental disorders,’ ‘Nervous system diseases,’ ‘Endocrine, nutritional or metabolic diseases,’ and ‘Neoplasms’). Pharmaceutical companies sponsored 39% of all clinical trials. However, trial sponsorships vary noticeably in different jurisdictions, likely due to, in part, different regulatory frameworks.

Conclusion: Our review highlights the diversification of clinical trials on cannabinoid-based medications in the past 21 years. This review underlines the increased interest in conducting clinical studies on new cannabinoid administration methods such as topical applications and on the investigation of emerging phyto- and synthetic cannabinoids. Moreover, more clinical trials have been designed to explore the potential therapeutic benefits of cannabinoids in areas such as mental, behavioral, or neurodevelopmental disorders and skin diseases. There is a need for granular analyses of clinical trials on more commonly studied therapeutic areas such as chronic pain, nervous system diseases, and mental and behavioral disorders to generate more actionable information and insight for all stakeholders.”

https://pubmed.ncbi.nlm.nih.gov/36357543/

https://link.springer.com/article/10.1007/s40290-022-00447-7

Use of Medical Cannabis in Patients with Gilles de la Tourette’s Syndrome in a Real-World Setting

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“Objective: Tourette’s syndrome (TS) is a neurodevelopmental disorder characterized by vocal and motor tics and other comorbidities. Clinical recommendations for the use of medical cannabis are established, yet further guidance is needed. The aim of this study was to describe the experience of patients with TS with medical cannabis. 

Materials and Methods: TS patients were recruited from a registry of patients (“Tikun Olam” company). Questionnaires were answered before and after 6 months of treatment. Patients were divided into two groups: (A) patients who responded and (B) patients who did not respond to the follow-up questionnaire. In group A, an analysis was made to evaluate the presence and frequency of motor and vocal tics. The patients’ general mood, employment status, quality of life, and comorbidities were also included in the analysis. 

Results: Seventy patients were identified. The tetrahydrocannabinol and cannabidiol mean daily dose was 123 and 50.5 mg, respectively. In group A, a statistically significant improvement was identified in quality of life (p<0.005), employment status (p=0.027), and in the reduction of the number of medications (p<0.005). Sixty-seven percent and 89% of patients with obsessive-compulsive disorder and anxiety comorbidities, respectively, reported an improvement. No statistically significant improvement was identified in motor tics (p=0.375), vocal tics (p>0.999), tics frequency (p=0.062), or general mood (p=0.129). The most frequent adverse effects were dizziness (n=4) and increased appetite (n=3). 

Conclusion: Subjective reports from TS patients suggest that medical cannabis may improve their quality of life and comorbidities. More studies are needed to evaluate the efficacy and safety of medical cannabis.”

https://pubmed.ncbi.nlm.nih.gov/36342913/

https://www.liebertpub.com/doi/10.1089/can.2022.0112

Medical Cannabis Use and Inflammatory Cytokines and Chemokines Among Adult Chronic Pain Patients

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“Background: Utilizing cannabis as a therapeutic option for chronic pain (CP) has increased significantly. However, data regarding the potential immunomodulatory effects of cannabis in CP patients remain scarce. We aimed at exploring the relationship between cannabis use and inflammatory cytokines and chemokines among a cohort of CP patients. 

Methods: Adult patients with a CP diagnosis and medical authorization of cannabis were enrolled. Patients completed validated clinical questionnaires and self-reported the effectiveness of cannabis for symptom management. Patients’ blood and cannabis samples were analyzed for the presence of four major cannabinoids, two major cannabinoid metabolites, 29 different cytokines/chemokines, and cortisol. The multivariable linear regression model was used to identify cannabis and patient factors associated with immune markers. 

Results: Fifty-six patients (48±15 years; 64% females) were included, with dried cannabis (53%) being the most common type of cannabis consumed. Seventy percent of products were considered delta-9-tetrahydrocannabinol (Δ9-THC)-dominant. The majority of patients (96%) self-reported effective pain management, and 76% reported a significant decrease in analgesic medication usage (p≤0.001). Compared with males, female patients had higher plasma levels of cannabidiol (CBD), cannabidiolic acid, Δ9-THC, and 11-hydroxy-Δ9-tetrahydrocannabinol but lower concentrations of delta-9-tetrahydrocannabinolic acid and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH). Females had significantly lower eotaxin levels (p=0.04) in comparison to male patients. The regression analysis indicated that high cannabis doses were related to increased levels of interleukin (IL)-12p40 (p=0.02) and IL-6 (p=0.01), whereas female sex was associated with decreased eotaxin (p≤0.01) concentrations. Blood CBD levels were associated with lower vascular endothelial growth factor (p=0.04) concentrations, and THC-COOH was a factor related to decreased tumor necrosis factor alpha (p=0.02) and IL-12p70 (p=0.03). 

Conclusion: This study provides further support for the patient-perceived effectiveness of cannabis in managing CP symptoms and reducing analgesic medication consumption. The results suggest a potential sex difference in metabolizing cannabinoids, and the varying immune marker concentrations may support a possible immunomodulatory effect associated with patient sex and cannabis product type. These preliminary findings provide grounds for further validation using larger, well-designed studies with longer follow-up periods.”

https://pubmed.ncbi.nlm.nih.gov/36342776/

https://www.liebertpub.com/doi/10.1089/can.2022.0143

Endocannabinoids and related compounds as modulators of angiogenesis: Concepts and clinical significance

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“Vasculogenesis (the process of differentiation of angioblasts toward endothelial cells and de novo formation of crude vascular networks) and angiogenesis (the process of harmonized sprouting and dispersal of new capillaries from previously existing ones) are two fundamentally complementary processes, obligatory for maintaining physiological functioning of vascular system. In clinical practice, however, the later one is of more importance as it guarantees correct embryonic nourishment, accelerates wound healing processes, prevents uncontrolled cell growth and tumorigenesis, contributes in supplying nutritional demand following occlusion of coronary vessels and is in direct relation with development of diabetic retinopathy. Hence, discovery of novel molecules capable of modulating angiogenic events are of great clinical importance. Recent studies have demonstrated multiple angio-regulatory activities for endocannabinoid system modulators and endocannabinoid-like molecules, as well as their metabolizing enzymes. Hence, in present article, we reviewed the regulatory roles of these molecules on angiogenesis and described molecular mechanisms underlying them.”

https://pubmed.ncbi.nlm.nih.gov/36317321/

https://onlinelibrary.wiley.com/doi/10.1002/cbf.3754

“Inhibition of tumor angiogenesis by cannabinoids”

https://pubmed.ncbi.nlm.nih.gov/12514108/

The role of Cannabis in treatment-resistant Fibromyalgia women

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“Background: Fibromyalgia is a complex pain-focused syndrome. Previous studies showed that Cannabis is efficacious in promoting sleep, deepening and lengthening the sleep cycle, and good pain relief (compared to SSRIs and SNRIs).

Purpose: This study aimed to use the World Health Organization Quality of Life Bref questionnaire (WhoQoL-bref) to characterize the impact of Cannabis Treatment initiation on the quality of life in women suffering from treatment-resistant fibromyalgia.

Methods: a prospective cohort study involving 30 women aged 18-70 years old diagnosed with fibromyalgia, exhausted pharmacological fibromyalgia treatment, and started Cannabis treatment. Pregnant women were excluded. WhoQoL-bref was filled before Cannabis treatment initiation and one month following treatment.

Results: Women’s average age was 46 years(±5), with a poor general quality of life (1.47±0.63), poor general health (1.47±0.78), pain and discomfort, and dependence on medication (3.77±1.3 and 3.07±1.74 respectively) prior to Cannabis intervention. Cannabis treatment for 30 days showed a marked improvement in general quality of life (1.97 scores, p < 0.01), general health (1.83, p<0.01), physical health ( 1.5, p<0.01), and psychological domain (1.3, p<0.01). Financial resources and home environment were not influenced by cannabis treatment (p=0.07, p=0.31, respectively).

Conclusion: Results suggest a potentially significant role of Cannabis in treatment-resistant Fibromyalgia women. Early Cannabis treatment may result in a beneficial short-term effect on the quality of life through its influence on pain, sleep, physical and psychological domains. Further studies are still indicated to understand this potential and its long-term beneficial impact.”

https://pubmed.ncbi.nlm.nih.gov/36333278/

https://onlinelibrary.wiley.com/doi/10.1111/papr.13179

A 1:1 ratio of cannabidiol: tetrahydrocannabinol attenuates methamphetamine conditioned place preference in mice: A prospective study of antidopaminergic mechanism

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Brain Research Bulletin

“A 1:1 ratio of cannabidiol to tetrahydrocannabinol (CT) was suggested to be safer for therapeutic purposes in many illnesses. However, CT effects on methamphetamine (METH) conditioned place preference (CPP) remained largely unexplored. This study aimed to examine the effects of CT on METH CPP mice evaluated by animal behaviors accompanied by local field potential (LFP) signals analysis. Male ICR mice were implanted with the LFP electrode in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Animals were next subjected to induce METH CPP by peritoneal injection with 1mg/kg METH and 0.9% NaCl on an alternate day for ten sessions and confined to the corresponding compartment for 30min meanwhile control mice were given normal saline all day for both compartments. On testing day, either 10mg/kg CT or 20mg/kg bupropion (BP), a dopamine reuptake inhibitor, and VTA GABAergic suppressor were orally administered before CPP testing. The results exposed that CPP scores elevation was observed in the METH+vehicle and METH+BP mice, but this was reversed by CT treatment. Although both METH+vehicle and METH+BP enhanced the VTA delta power, NAc gamma I power, NAc delta-gamma coupling, and VTA-NAc gamma I coherence, changes in opposite trends of all mentioned parameters were seen by CT application. These improvements were postulated to involve the antidopaminergic effects of CT via modulations of neural signaling in the VTA and NAc. Altogether, the evidence-based study may suggest the using CT in alternative drugs for METH-seeking and craving therapy.”

https://pubmed.ncbi.nlm.nih.gov/36336144/

“From the encouraging results, the CT would be developed and deployed as a novel drug for the treatment of METH dependence.”

https://www.sciencedirect.com/science/article/pii/S0361923022003112?via%3Dihub

Ghana’s preparedness to exploit the medicinal value of industrial hemp

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“Background: Interest in industrial hemp is increasing steadily, as can be seen by the growing number of countries that have either decriminalized industrial hemp or are contemplating its decriminalization. In line with this trend, Ghana recently decriminalized the cultivation of industrial hemp (the cannabis variety with low Δ9-tetrahydrocannabinol (THC) and high cannabidiol (CBD) content), resulting in the need for research into its benefits to Ghanaians. This article examines cannabis (including industrial hemp) production, facilities for industrial hemp exploitation, and the potential benefits of industrial hemp in Ghana.

Main body: Indigenous cannabis strains in Ghana have high THC to CBD ratios suggesting the need for the government to purchase foreign hemp seeds, considering that the alternative will require significant research into decreasing the THC to CBD ratio of indigenous cannabis strains. Furthermore, there are several facilities within the country that could be leveraged for the production of medicinal hemp-based drugs, as well as the existence of a number of possible regulatory bodies in the country, suggesting the need for less capital. Research has also shown the potential for treatment of some medical conditions prevalent among Ghanaians using medicinal hemp-based products. These reasons suggest that the most feasible option may be for the government to invest in medicinal hemp.

Conclusion: Considering the challenges associated with the development of other hemp-based products, the availability of resources in the country for exploitation of medicinal hemp, and the potential benefits of hemp-based drugs to Ghanaians, investing in medicinal hemp may be the best option for the government of Ghana.”

https://pubmed.ncbi.nlm.nih.gov/36329502/

“Considering the challenges associated with the development of other hemp-based products, the availability of resources in the country for exploitation of medicinal hemp, and the potential benefits of hemp-based drugs to Ghanaians, investing in medicinal hemp may be the best option for the government of Ghana.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-022-00167-4

” Flower Power”: Controlled Inhalation of THC-Predominant Cannabis Flos Improves Health-Related Quality of Life and Symptoms of Chronic Pain and Anxiety in Eligible UK Patients

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“In November 2018, the UK’s Home Office established a legal route for eligible patients to be prescribed cannabis-based products for medicinal use in humans (CBPMs) as unlicensed medicines. These include liquid cannabis extracts for oral administration (“oils”) and dried flowers for inhalation (“flos”). Smoking of CBPMs is expressly prohibited. To date, THC-predominant cannabis flowers remain the most prescribed CBPMs in project Twenty21 (T21), the first multi-center, prospective, observational UK cannabis patient registry. This observational, prospective data review analyzes patient-reported outcome measures (PROMS) collected by T21 associated with the inhalation of KHIRON 20/1, the most prescribed CBPM in the project. PROMS collected at baseline and at subsequent 3-month follow-up included health-related quality of life (HRQoL), general mood, and sleep. Condition-specific measures of illness severity were performed with the Brief Pain Inventory Short Form (BPI-SF) and the Generalized Anxiety Disorder 7-Item Scale (GAD-7). Participants (N = 344) were mostly males (77.6%, average age = 38.3) diagnosed mainly with chronic pain (50.9%) and anxiety-related disorders (25.3%). Inhalation of KHIRON 20/1 was associated with a marked increase in self-reported HRQoL, general mood, and sleep (N = 344; p < 0.001). Condition-specific assessments showed significant improvements in pain severity (T = 6.67; p < 0.001) and interference (T = 7.19; p < 0.001) in patients using KHIRON 20/1 for chronic pain (N = 174). Similar results were found for patients diagnosed with anxiety-related disorders (N = 107; T = 12.9; p < 0.001). Our results indicate that controlled inhalation of pharmaceutical grade, THC-predominant cannabis flos is associated with a significant improvement in patient-reported pain scores, mood, anxiety, sleep disturbances and overall HRQoL in a treatment-resistant clinical population.”

https://pubmed.ncbi.nlm.nih.gov/36289837/

“Our results indicate that controlled inhalation of pharmaceutical grade, THC-predominant cannabis flos was associated with a robust improvement in patient-reported pain scores, general mood, anxiety, sleep, and overall HRQoL in a treatment-resistant clinical population.”

https://www.mdpi.com/2227-9059/10/10/2576/htm