Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Sustained cannabis use does not predispose clinical hypertension: Findings from a national survey

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“Cannabis is among the most used recreational and medicinal drugs in the United States. The effects of chronic use on hypertension remain poorly understood.

Our study retrospectively evaluated data collected by the National Health and Nutrition Examination Survey from 2017 to 2018. Cannabis use was measured with five metrics: (1) sustained use at any point in the past, (2) sustained use within the past year, (3) frequency of use, (4) age of first cannabis use, and (5) current use. Hypertension status was determined by individuals reporting having been diagnosed in the past. Multivariable logistic regressions were performed, controlling for age, race, and gender. A total of 4565 respondents were identified, of which 867 (19.0%) reported sustained cannabis use in the past.

Participants who reported past sustained cannabis use did not have statistically different odds of having hypertension (OR: 1.12; 95% CI: .66-1.91; p = .6). Moderate (OR: 1.08; 95% CI: .36-3.25; p = .8) and highly-frequent users (OR: 1.30; 95% CI: .56-3.03; p = .4) did not have different odds of having hypertension than infrequent users. No relationship between the age of first cannabis use and hypertension was observed. The recency of sustained cannabis use was not associated with hypertension status. Current cannabis users had similar odds of hypertension as past users (OR: 1.03; 95% CI: .59-1.79; p = .9).

The findings of this study indicate that neither past nor current cannabis use is associated with clinical hypertension.”

https://pubmed.ncbi.nlm.nih.gov/36545898/

“The findings of this study indicate that neither past nor current cannabis use are associated with the likelihood of having clinical hypertension. Among cannabis users, frequency of use was not associated with hypertension. Similarly, the age of first cannabis use was not associated with hypertension status.”

https://onlinelibrary.wiley.com/doi/10.1111/jch.14623

Inhibiting Human and Leishmania Arginases Using Cannabis sativa as a Potential Therapy for Cutaneous Leishmaniasis: A Molecular Docking Study

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“Cutaneous leishmaniasis (CL), a vector-borne parasitic disease caused by the Leishmania protozoan, is a serious public health problem in Morocco. The treatment of this disease is still based on pentavalent antimonials as the primary therapy, but these have associated side effects. Thus, the development of effective, risk-free alternative therapeutics based on natural compounds against leishmaniasis is urgent. Arginase, the key enzyme in the polyamine biosynthetic pathway, plays a critical role in leishmaniasis outcome and has emerged as a potential therapeutic target.

The objective of this study was to test Cannabis sativa‘s phytochemical components (cannabinoids and terpenoids) through molecular docking against Leishmania and human arginase enzymes.

Our results showed that delta-9-tetrahydrocannabinol (THC) possessed the best binding energies of -6.02 and -6.35 kcal/mol with active sites of Leishmania and human arginases, respectively. Delta-9-THC interacted with Leishmania arginase through various amino acids including His139 and His 154 and linked to human arginase via His 126. In addition to delta-9-THC, caryophyllene oxide and cannabidiol (CBD) also showed a good inhibition of Leishmania and human arginases, respectively.

Overall, the studied components were found to inhibit both arginases active sites via hydrogen bonds and hydrophobic interactions. These components may serve as therapeutic agents or in co-administrated therapy for leishmaniasis.”

https://pubmed.ncbi.nlm.nih.gov/36548655/

“Since CL is still a public health problem in low-income and developing countries, the discovery of an efficient, less toxic, and accessible therapy is a necessity. The present in silico study was the first to investigate C. sativa’s selected constituents as selective inhibitory agents for parasitic as well as host arginases, which play an important role in this parasitic infection pathology. Interestingly, THC showed a great inhibitory potential for both species’ enzymes and will allow a better control of leishmaniasis.”

https://www.mdpi.com/2414-6366/7/12/400

The Utility of Cannabis-Based Medicine in Chronic Pain Management: A Case Report

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“Chronic pain is a common diagnosis that patients may face, resulting in increased morbidity and mortality and affecting the overall quality of life.

In addition to established multidisciplinary pain management, medical cannabis may offer an approach to improving pain outcomes and functionality. This case involves a 72-year-old female patient, with chronic neck, lower back, and diffuse arthritic pain due to comorbid osteoarthritis (OA), scleroderma, and scoliosis. Medical cannabis therapy was certified based on the goals of improving pain control and simultaneously reducing the patient’s chronic opioid medication dose.

Using potential opioid alternatives, such as medical cannabis, may prove beneficial to clinicians looking to improve pain management and reduce opioid therapy in patients.”

https://pubmed.ncbi.nlm.nih.gov/36540475/

“This case indicates that cannabinoid therapy may be useful in managing chronic pain and therein reducing its detrimental impact on patients’ overall quality of life. Potential opioid alternatives, such as medical cannabis, are becoming increasingly important in pain management to improve patients’ quality of life. Additionally, this case demonstrates that medical cannabis may prove beneficial in reducing reliance on chronic opioid therapy. Clinicians should be aware of different approaches to treatment that do not include opioids.”

https://www.cureus.com/articles/113524-the-utility-of-cannabis-based-medicine-in-chronic-pain-management-a-case-report

Clinical Outcome Data of Children Treated with Cannabis Based Medicinal Products for Treatment Resistant Epilepsy – Analysis from the UK Medical Cannabis Registry

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“Background There is a paucity of high-quality evidence of the efficacy and safety of cannabis-based medicinal products in treatment of treatment-resistant epilepsy (TRE) in children.

Methods A case series of children(<18 years old) with TRE from the UK Medical Cannabis Registry was analysed. Primary outcomes were ≥50% reduction in seizure frequency, changes in the Impact of Paediatric Epilepsy Score(IPES) and incidence of adverse events.

Results Thirty-five patients were included in the analysis. Patients were prescribed during their treatment with the following-CBD isolate oils(n=19), CBD broad-spectrum oils(n=17), and CBD/Δ9-THC combination therapy(n=17). Twenty-three(65.7%) patients achieved a ≥50% reduction in seizure frequency. 94.1%(n=16) of patients treated with CBD and Δ9-THC observed a ≥50% reduction in seizure frequency compared to 31.6%(n=6) and 17.6%(n=3) of patients treated with CBD isolates and broad-spectrum CBD products respectively(p<0.001). Twenty-six(74.3%) adverse events were reported by 16 patients(45.7%). The majority of these were mild(n=12; 34.2%) and moderate(n=10; 28.6%).

Conclusions The results of this study demonstrate a positive signal of improved seizure frequency in children treated with CBMPs for TRE. Moreover, the results suggest that CBMPs are well-tolerated in the short term. The limitations mean causation cannot be determined in this open-label, case series.”

https://pubmed.ncbi.nlm.nih.gov/36539215/

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2002-2119

Medicinal cannabis improves sleep in adults with insomnia: a randomised double-blind placebo-controlled crossover study

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“Insomnia or difficulty falling and or staying asleep is experienced by up to 30% of the general population.

This randomised crossover double-blind placebo-controlled 6-week trial aimed to assess the tolerability and effectiveness of the Entoura-10:15 medicinal cannabis oil on sleep in adults with insomnia. A total of 29 participants with self-reported clinical insomnia completed the crossover trial. Participants were randomly allocated to receive placebo or active oil containing 10 mg/ml tetrahydrocannabinol (THC) and 15 mg/ml cannabidiol (CBD) over 2-weeks titrated 0.2-1.5 ml/day, followed by a 1-week wash-out period before crossover. Tolerability was assessed by daily diary. Effectiveness was measured by saliva midnight melatonin levels, validated questionnaires, i.e., the Insomnia Severity Index, and the Fitbit activity/sleep wrist tracker.

Entoura-10:15 medicinal cannabis oil was generally well tolerated, and was effective in improving sleep, whereby 60% of participants no longer classified as clinical insomniacs at the end of the 2-week intervention period. Midnight melatonin levels significantly improved in the active group by 30% compared to a 20% decline in the placebo group (p = 0.035). Medicinal cannabis oil improved both time and quality of sleep, in particular light sleep increased by 21 min/night compared to placebo (p = 0.041). The quality of sleep improved overall by up to 80% in the active group (pPhase2 = 0.003), including higher daily functioning (p = 0.032). Observed effects were more pronounced in Phase 2 due to the period effect and loss of blinding.

Entoura-10:15 medicinal cannabis oil was well tolerated and effective in improving sleep in adults with insomnia.”

https://pubmed.ncbi.nlm.nih.gov/36539991/

“In summary, our short-term trial suggests Entoura 10:15 medicinal cannabis oil, containing THC:CBD 10:15 and lesser amounts of other CBs and naturally occurring terpenes, to be well tolerated and effective in significantly improving sleep quality and duration, midnight melatonin levels, quality of life, and mood within 2-weeks in adults with insomnia.”

https://onlinelibrary.wiley.com/doi/10.1111/jsr.13793

Cannabis sativa L. alleviates loperamide-induced constipation by modulating the composition of gut microbiota in mice

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Frontiers - Crunchbase Company Profile & Funding

“MaZiRenWan (MZRW) is the most frequently used Traditional Chinese Medicine formula to treat chronic constipation, Cannabis sativa L. is regarded as a monarch drug in MZRW. However, the targets of Cannabis sativa L. that enhance colonic motility and improve constipation symptoms remain unknown.

This study was designed to investigate the laxative effect and underlying mechanism of the water extract of Cannabis sativa L. (WECSL) using a loperamide-induced constipation mouse model.

We found that WECSL treatment significantly improved intestinal motility and water-electrolyte metabolism, decreased inflammatory responses, prevented gut barrier damage, and relieved anxiety and depression in constipated mice. WECSL also structurally remodeled the composition of the gut microbiota and altered the abundance of bacteria related to inflammation, specifically Butyricicoccus and Parasutterella. Moreover, WECSL failed to relieve constipation symptoms following intestinal flora depletion, indicating that WECSL alleviates constipation symptoms depending on the gut microbiota.

Our research provides a basis for WECSL to be further investigated in the treatment of constipation from the perspective of modern medicine.”

https://pubmed.ncbi.nlm.nih.gov/36532754/

“In conclusion, this study demonstrated that WECSL can improve constipation symptoms, reduce anxiety and depression behaviors, and inhibit intestinal inflammation. WECSL also structurally remodeled the composition of the gut microbiota, altering the abundance of bacteria related to inflammation.

Our research provides a basis for WECSL to be further investigated in the treatment of constipation from the perspective of modern medicine. Constipation may be prevented and improved by targeting these possible gut bacteria.”

https://www.frontiersin.org/articles/10.3389/fphar.2022.1033069/full


The use of medical cannabis concomitantly with immune checkpoint inhibitors in non-small cell lung cancer: A sigh of relief?

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European Journal of Cancer

“Background: The use of medical cannabis has rapidly increased among cancer patients worldwide. Cannabis is often administered concomitantly with cancer medications, including immune checkpoint inhibitors (ICIs). As the cannabinoid receptors are abundantly expressed and modulate immune cells, it has been hypothesised that cannabis may attenuate the activity of ICIs. We aimed to assess the effect of cannabis on ICIs’ efficiency in patients having non-small cell lung cancer (NSCLC).

Method: The murine model of CT26 tumour-bearing mice treated with an anti-PD-1 antibody and Δ9-tetrahydrocannabinol (THC) was used to evaluate the interaction between THC and ICIs in vivo. Correlation between use of medical cannabis and clinical outcome was evaluated in a cohort of 201 consecutive metastatic NSCLC patients treated with monotherapy pembrolizumab as a first-line treatment.

Results: Median overall survival (OS) of the mice receiving a control vehicle, THC, anti-PD-1 antibody or their combination was 21, 24, 31 and 54 days, respectively (p < 0.05 for the combination treatment compared to a control vehicle), indicating that THC did not reduce the efficacy of anti-PD-1 therapy. Of 201 NSCLC patients treated with first-line monotherapy pembrolizumab for metastatic disease, 102 (50.7%) patients received licence for cannabis within the first month of treatment. Cannabis-treated patients were younger compared to the cannabis naïve patients (median age 68 versus 74, p = 0.003), with female predominance (62, 60.8% versus 34, 34.3%, p = 0.002) and with more prevailing brain metastasis (15.7% versus 5%, p = 0.013). Similar distribution of histology, smoking status, ECOG (Eastern Cooperative Oncology Group) and programmed death-ligand 1 expression was noted between the groups. Liver metastases were marginally significant (19.6% versus 10.1%, p = 0.058). The most common indication for cannabis was pain (71%) followed by loss of appetite (34.3%). Time to tumour progression was similar for cannabis-naive and cannabis-treated patients (6.1 versus 5.6 months, respectively, 95% confidence interval, 0.82 to 1.38, p = 0.386), while OS was numerically higher in the cannabis-naive group (54.9 versus 23.6 months) but did not reach statistical significance (95% confidence interval 0.99 to 2.51, p = 0.08). In multivariate analyses, we did not identify cannabis use as an independent predictor factor for mortality.

Conclusions: Preclinical and clinical data suggest no deleterious effect of cannabis on the activity of pembrolizumab as first-line monotherapy for advanced NSCLC. The differences in OS can most likely be attributed to higher disease burden and more symptomatic disease in the cannabis-treated group. These data provide reassurance regarding the absence of a deleterious effect of cannabis in this clinical setting.”

https://pubmed.ncbi.nlm.nih.gov/36535195/

https://www.ejcancer.com/article/S0959-8049(22)01767-1/fulltext


Selective Cytotoxicity of Medical Cannabis ( Cannabis sativa L.) Extracts Across the Whole Vegetation Cycle Under Various Hydroponic and Nutritional Treatments

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“Introduction: The use of Cannabis sativa L. in health care requires stringent care for the optimal production of the bioactive compounds. However, plant phenotypes and the content of secondary metabolites, such as phytocannabinoids, are strongly influenced by external factors, such as nutrient availability. It has been shown that phytocannabinoids can exhibit selective cytotoxicity against various cancer cell lines while protecting healthy tissue from apoptosis. 

Research Aim: This study aimed to clarify the cytotoxic effect of cannabis extracts on colorectal cell lines by identifying the main active compounds and determining their abundance and activity across all developmental stages of medical cannabis plants cultivated under hydroponic conditions. 

Materials and Methods: Dimethyl sulfoxide extracts of medical cannabis plants bearing the genotype classified as chemotype I were analyzed by high-performance liquid chromatography, and their cytotoxic activity was determined by measuring cell viability by methylthiazolyldiphenyl-tetrazolium bromide assay on the human colon cancer cell lines, Caco-2 and HT-29, and the normal human epithelial cell line, CCD 841 CoN. 

Results: The most abundant phytocannabinoid in cannabis extracts was tetrahydrocannabinolic acid (THCA). Its maximum concentrations were reached from the 7th to the 13th plant vegetation week, depending on the nutritional cycle and treatment. Almost all extracts were cytotoxic to the human colorectal cancer (CRC) cell line HT-29 at lower concentrations than the other cell lines. The phytocannabinoids that most affected the cytotoxicity of individual extracts on HT-29 were cannabigerol, Δ9-tetrahydrocannabinol, cannabidiol, cannabigerolic acid, and THCA. The tested model showed almost 70% influence of these cannabinoids. However, THCA alone influenced the cytotoxicity of individual extracts by nearly 65%. 

Conclusions: Phytocannabinoid extracts from plants of the THCA-dominant chemotype interacted synergistically and showed selective cytotoxicity against the CRC cell line, HT-29. This positive extract response indicates possible therapeutic value.”

https://pubmed.ncbi.nlm.nih.gov/36459627/

https://www.liebertpub.com/doi/10.1089/can.2022.0243


Receptor-mediated effects of Δ9 -THC & CBD on the inflammatory response of alveolar macrophages

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“Δ9 -tetrahydrocannabinol (Δ9 -THC) and cannabidiol (CBD) are cannabinoids found in Cannabis sativa. While research supports cannabinoids reduce inflammation, the consensus surrounding receptor(s) mediated effects has yet to be established.

Here, we investigated the receptor-mediated properties of Δ9 -THC and CBD on alveolar macrophages, an important pulmonary immune cell in direct contact with cannabinoids inhaled by cannabis smokers.

MH-S cells, a mouse alveolar macrophage cell line, were exposed to Δ9 -THC and CBD, with and without lipopolysaccharide (LPS). Outcomes included RNA-sequencing and cytokine analysis. Δ9 -THC and CBD alone did not affect the basal transcriptional response of MH-S cells.

In response to LPS, Δ9 -THC and CBD significantly reduced the expression of numerous pro-inflammatory cytokines including TNF-α, IL-1β and IL-6, an effect that was dependent on CB2 . The anti-inflammatory effects of CBD- but not Δ9 -THC- were mediated through a reduction in signaling through NF-κB and ERK1/2.

These results suggest that CBD and Δ9 -THC have potent immunomodulatory properties in alveolar macrophages, a cell type important in immune homeostasis in the lungs. Further investigation into the effects of cannabinoids on lung immune cells could lead to the identification of therapies that may ameliorate conditions characterized by inflammation.”

https://pubmed.ncbi.nlm.nih.gov/36510483/

https://onlinelibrary.wiley.com/doi/10.1111/imcb.12614


Cannabis sativa Cannabinoids as Functional Ingredients in Snack Foods-Historical and Developmental Aspects

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“The published health benefits of Cannabis sativa has caught the attention of health-conscious consumers and the food industry. Historically, seeds have long been utilized as a food source and currently there is an increasing number of edibles on the market that contain cannabis. Cannabinoids include the psychoactive constituent, delta-9-tetrahydrocannabinol (THC), and the non-psychoactive cannabidiol (CBD) that are both compounds of interest in Cannabis sativa.

This paper looks at the distribution of nutrients and phytocannabinoids in low-THC Cannabis sativa, the historical uses of hemp, cannabis edibles, and the possible side-effects and concerns related to cannabis edibles. Several authors have pointed out that even though the use of cannabis edibles is considered safe, it is important to mention their possible side-effects and any concerns related to its consumption that negatively influence consumer acceptance of cannabis edibles. Such risks include unintentional overdose by adults and accidental ingestion by children and adolescents resulting in serious adverse effects. Therefore, cannabis edibles should be specifically packaged and labelled to differentiate them from known similar non-cannabis edibles so that, together with tamperproof packaging, these measures reduce the appeal of these products to children.”

https://pubmed.ncbi.nlm.nih.gov/36501366/

“Cannabis sativa possesses many health-promoting qualities and so it has played an effective role as a traditional medicine to treat a variety of ailments from pain, anxiety and weight gain through to conditions such as cardiovascular disease and diabetes, as well as infectious diseases such as malaria, and cancer.

Opinion regarding cannabis edibles is changing amongst consumers and most countries around the world are shifting towards the legalization of the recreational and medicinal use of cannabis leading to a rapid increase in the global acceptance and availability of cannabis edibles. “

https://www.mdpi.com/2223-7747/11/23/3330