Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Phytocannabinoids in Triple Negative Breast Cancer Treatment: Current Knowledge and Future Insights

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Anticancer Research: 43 (3)

“Triple negative breast cancer (TNBC) represents an aggressive subtype of breast cancer, which is deficient in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Thus, TNBC cells are unable to respond to the conventional hormonal therapies, making chemotherapy the only therapeutic choice. Patients with TNBC develop metastasis and recurrence over time and have reduced survival compared to patients with other subtypes of breast cancer. Therefore, there is a need for innovative therapies. Data emerged from pre-clinical studies, highlighted various antitumor activities of plant-derived Cannabis sativa and synthetic cannabinoids (CBs), including delta-9-tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD). On the contrary, some studies indicated that CBs might also promote tumor progression. At present, clinical studies on the effects of CBs from Cannabis sativa in cancer patients are few. In the present study, we reviewed known and possible interactions between cannabinoids and TNBC therapies.”

https://pubmed.ncbi.nlm.nih.gov/36854495/

“Overall, apart from the need for other studies aimed to dissect the molecular pathways underlying the antitumor CBs’ properties, phytocannabinoids should be considered as potential agents for inhibiting TNBC progression.”

https://ar.iiarjournals.org/content/43/3/993

UK medical cannabis registry: assessment of clinical outcomes in patients with headache disorders

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“Objectives: Headache disorders are a common cause of disability and reduced health-related quality of life globally. Growing evidence supports the use of cannabis-based medicinal products (CBMPs) for chronic pain; however, a paucity of research specifically focuses on CBMPs’ efficacy and safety in headache disorders. This study aims to assess changes in validated patient-reported outcome measures (PROMs) in patients with headaches prescribed CBMPs and investigate the clinical safety in this population.

Methods: A case series of the UK Medical Cannabis Registry was conducted. Primary outcomes were changes from baseline in PROMs (Headache Impact Test-6 (HIT-6), Migraine Disability Assessment (MIDAS), EQ-5D-5L, Generalized Anxiety Disorder-7 (GAD-7) questionnaire and Single-Item Sleep Quality Scale (SQS)) at 1-, 3-, and 6-months follow-up. P-values <0.050 were deemed statistically significant.

Results: Ninety-seven patients were identified for inclusion. Improvements in HIT-6, MIDAS, EQ-5D-5L and SQS were observed at 1-, 3-, and 6-months (p < 0.005) follow-up. GAD-7 improved at 1- and 3-months (p < 0.050). Seventeen (17.5%) patients experienced a total of 113 (116.5%) adverse events.

Conclusion: Improvements in headache/migraine-specific PROMs and general health-related quality of life were associated with the initiation of CBMPs in patients with headache disorders. Cautious interpretation of results is necessary, and randomized control trials are required to ascertain causality.”

https://pubmed.ncbi.nlm.nih.gov/36722292/

https://www.tandfonline.com/doi/full/10.1080/14737175.2023.2174017

Patient Reported Outcomes Using Medical Cannabis for Managing Pain in Charcot-Marie-Tooth Disease

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SAGE Journals Home

“Objective: Chronic pain is a major problem for patients with Charcot-Marie-Tooth (CMT) disease. This exploratory study examined patient reported efficacy of medical cannabis for pain management in this population. 

Methods: Participants (N = 56; 71.4% female; Age = 48.9, SD = 14.6; 48.5% CMT1) were recruited though the Hereditary Neuropathy Foundation. The online survey contained 52 multiple choice questions about demographics, medical cannabis use, symptomology, efficacy, and adverse effects. 

Results: Nearly all (90.9%) of respondents reported experiencing pain, including all (100%) females and 72.7% of males (chi-square P < .05) with 91.7% of respondents indicating cannabis provided at least 50% pain relief. The most frequent response was an 80% reduction in pain. Moreover, 80.0% of respondents reported using less opiates, 69% noted using less sleep medication, and 50.0% reported using less anxiety/antidepressant medications. Negative side effects were noted by 23.5% of respondents. However, almost all (91.7%) of that subgroup did not have plans to stop consuming cannabis. One-third (33.9%) possessed a medical cannabis certificate. Patient perceptions of their physicians’ attitudes regarding patient medical cannabis use greatly impacted whether respondents informed their providers of their usage. 

Conclusion: The vast majority of patients with CMT reported that cannabis was effective to manage pain symptoms. These data support the need for prospective, randomized, controlled trials using standardized dosing protocols to further delineate and optimize the potential use of cannabis to treat pain related to CMT.”

https://pubmed.ncbi.nlm.nih.gov/36793224/

https://journals.sagepub.com/doi/10.1177/10499091231158388

A Retrospective Cohort Study That Examined the Impact of Cannabis Consumption on Long-Term Kidney Outcomes

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“Background: Cannabis consumption for recreational and medical use is increasing worldwide. However, the long-term effects on kidney health and disease are largely unknown. 

Materials and Methods: Post hoc analysis of cannabis use as a risk factor for kidney disease was performed using data from the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study that enrolled hospitalized adults with and without acute kidney injury from four U.S. centers during 2009-2015. Associations between self-reported cannabis consumption and the categorical and continuous outcomes were determined using multivariable Cox regression and linear mixed models, respectively. 

Results: Over a mean follow-up of 4.5±1.8 years, 94 participants without chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m2) who consumed cannabis had similar rates of annual eGFR decline versus 889 nonconsumers (mean difference=-0.02 mL/min/1.73 m2/year, p=0.9) and incident CKD (≥25% reduction in eGFR compared with the 3-month post-hospitalization measured eGFR and achieving CKD stage 3 or higher) (adjusted hazard ratio [aHR]=1.2; 95% confidence interval [CI]=0.7-2.0). Nineteen participants with CKD (eGFR <60 mL/min/1.73 m2) who consumed cannabis had more rapid eGFR decline versus 597 nonconsumers (mean difference=-1.3 mL/min/1.73 m2/year; p=0.02) that was not independently associated with an increased risk of CKD progression (≥50% reduction in eGFR compared with the 3-month post-hospitalization eGFR, reaching CKD stage 5, or receiving kidney replacement therapy) (aHR=1.6; 95% CI=0.7-3.5). Cannabis consumption was not associated with the rate of change in urine albumin to creatinine ratio (UACR) over time among those with (p=0.7) or without CKD (p=0.4). 

Conclusions: Cannabis consumption did not adversely affect the kidney function of participants without CKD but was associated with a faster annual eGFR decline among participants with CKD. Cannabis consumption was not associated with changes in UACR over time, incident CKD, or progressive CKD regardless of baseline kidney function. Additional research is needed to investigate the kidney endocannabinoid system and the impact of cannabis use on kidney disease outcomes.”

https://pubmed.ncbi.nlm.nih.gov/36791309/

https://www.liebertpub.com/doi/10.1089/can.2022.0141

Investigation of Cannabis sativa Phytochemicals as Anti-Alzheimer’s Agents: An In Silico Study

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“Cannabis sativa is a medicinal plant that has been known for years and is used as an Ayurvedic medicine. This plant has great potential in treating various types of brain diseases. Phytochemicals present in this plant act as antioxidants by maintaining synaptic plasticity and preventing neuronal loss.

Cannabidiol (CBD) and Tetrahydrocannabinol (THC) are both beneficial in treating Alzheimer’s disease by increasing the solubility of Aβ42 amyloid and Tau aggregation. Apart from these therapeutic effects, there are certain unknown functions of these phytochemicals in Alzheimer’s disease that we want to elucidate through this study.

In this research, our approach is to analyze the effect of phytochemicals in Cannabis sativa on multiple culprit enzymes in Alzheimer’s disease, such as AChE (Acetylcholinesterase), BChE (Butyrylcholinesterase), γ-secretase, and BACE-1. In this study, the compounds were selected by Lipinski’s rule, ADMET, and ProTox based on toxicity. Molecular docking between the selected compounds (THCV, Cannabinol C2, and Cannabidiorcol) and enzymes mentioned above was obtained by various software programs including AutoDock Vina 4.2, AutoDock, and iGEMDOCK.

In comparison to Donepezil (BA = -8.4 kcal/mol, Ki = 1.46 mM), Rivastigmine (BA = -7.0 kcal/mol, Ki = 0.02 mM), and Galantamine (BA = -7.1, Ki = 2.1 mM), Cannabidiorcol (BA = -9.4 kcal/mol, Ki = 4.61 mM) shows significant inhibition of AChE. On the other hand, Cannabinol C2 (BA = -9.2 kcal/mol, Ki = 4.32 mM) significantly inhibits Butyrylcholinesterase (BuChE) in comparison to Memantine (BA = -6.8 kcal/mol, Ki = 0.54 mM).

This study sheds new light and opens new avenues for elucidating the role of bioactive compounds present in Cannabis sativa in treating Alzheimer’s disease.”

https://pubmed.ncbi.nlm.nih.gov/36771595/

“In comparison to known drugs, THCV, Cannabinol C2 and Cannabidiorcol dominated cannabinoids’ inhibitory activities on AChE and BuChE. Computational approaches suggest that THCV, Cannabinol C2, and Cannabidiorcol are more appropriate for the inhibition of the enzymes AChE and BuChE, which act as the culprits of Alzheimer’s disease. Cell and animal studies are needed to improve the efficacy of these cannabinoids and to learn more about the effecting pathways.”

https://www.mdpi.com/2223-7747/12/3/510

The Cannabis Plant as a Complex System: Interrelationships between Cannabinoid Compositions, Morphological, Physiological and Phenological Traits

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“Maintaining specific and reproducible cannabinoid compositions (type and quantity) is essential for the production of cannabis-based remedies that are therapeutically effective.

The current study investigates factors that determine the plant’s cannabinoid profile and examines interrelationships between plant features (growth rate, phenology and biomass), inflorescence morphology (size, shape and distribution) and cannabinoid content. An examination of differences in cannabinoid profile within genotypes revealed that across the cultivation facility, cannabinoids’ qualitative traits (ratios between cannabinoid quantities) remain fairly stable, while quantitative traits (the absolute amount of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV) and cannabidivarin (CBDV)) can significantly vary.

The calculated broad-sense heritability values imply that cannabinoid composition will have a strong response to selection in comparison to the morphological and phenological traits of the plant and its inflorescences. Moreover, it is proposed that selection in favour of a vigorous growth rate, high-stature plants and wide inflorescences is expected to increase overall cannabinoid production. Finally, a range of physiological and phenological features was utilised for generating a successful model for the prediction of cannabinoid production.

The holistic approach presented in the current study provides a better understanding of the interaction between the key features of the cannabis plant and facilitates the production of advanced plant-based medicinal substances.”

https://pubmed.ncbi.nlm.nih.gov/36771577/

“These findings will have a significant impact on the breeding and cultivation of the chemotypically stable and reproducible cannabis genotypes that will facilitate the production of novel medicinal applications.”

https://www.mdpi.com/2223-7747/12/3/493

Cannabinoids in the Modulation of Oxidative Signaling

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“Cannabis sativa-derived compounds, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and components of the endocannabinoids system, such as N-arachidonoylethanolamide (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), are extensively studied to investigate their numerous biological effects, including powerful antioxidant effects. Indeed, a series of recent studies have indicated that many disorders are characterized by alterations in the intracellular antioxidant system, which lead to biological macromolecule damage. These pathological conditions are characterized by an unbalanced, and most often increased, reactive oxygen species (ROS) production.

For this study, it was of interest to investigate and recapitulate the antioxidant properties of these natural compounds, for the most part CBD and THC, on the production of ROS and the modulation of the intracellular redox state, with an emphasis on their use in various pathological conditions in which the reduction of ROS can be clinically useful, such as neurodegenerative disorders, inflammatory conditions, autoimmunity, and cancers. The further development of ROS-based fundamental research focused on cannabis sativa-derived compounds could be beneficial for future clinical applications.”

https://pubmed.ncbi.nlm.nih.gov/36768835/

“In conclusion, it has been reported that cannabinoids modulate oxidative stress in inflammation and autoimmunity, which makes them a potential therapeutic approach for different kinds of pathologies.”

https://www.mdpi.com/1422-0067/24/3/2513

Medical cannabis for treatment-resistant combat PTSD

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“Targeting the endocannabinoid system may have a role in the treatment of post-traumatic stress disorder (PTSD). However, few studies have examined the effectiveness of cannabis on symptoms of PTSD, and more research is needed to ascertain cannabis’ effectiveness.

In this retrospective naturalistic study, we followed 14 relatively mature (32-68 years of age), treatment-resistant, chronic combat post-traumatic patients who remained severely symptomatic despite treatment with many lines of conventional treatment prior to receiving medicinal cannabis.

Our findings show that total sleep score, subjective sleep quality, and sleep duration significantly improved (p < 0.01). Total PTSD symptom score and its subdomains (intrusiveness, avoidance, and alertness) showed improvement (p < 0.05). However, there was no improvement in the frequency of nightmares (p = 0.27). The mean follow-up time was 1.1 ± 0.8 years (range of 0.5 to 3 years).”

https://pubmed.ncbi.nlm.nih.gov/36741572/

“To the best of our knowledge, this is the first published study examining long-term cannabis efficacy in chronic combat treatment-resistant PTSD patients. The study we conducted is consistent with existing literature which indicates a decrease in PTSD symptoms under medical cannabis treatment.”

https://www.frontiersin.org/articles/10.3389/fpsyt.2022.1014630/full

Association between cannabis use and blood pressure levels according to comorbidities and socioeconomic status

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Scientific Reports

“The associations between blood pressure and cannabis use remain inconsistent. The purpose of our study was to examine gender stratified associations of cannabis use and blood pressure [systolic, diastolic blood pressure (BP), pulse pressure (PP)] levels among the general UK Biobank population based study. Among 91,161 volunteers of the UK Biobank population, cannabis use status was assessed by questionnaire and range as heavy, moderate, low and never users. Associations between cannabis use and BP were estimated using multiple gender linear regressions.

In adjusted covariates models, lifetime heavy cannabis use was associated with decrease in both SBP, DBP and PP in both genders, but with a higher effect among women (for SBP in men, b = − 1.09 (0.27), p < 0.001; in women, b = − 1.85 (0.36), p < 0.001; for DBP in men, b = − 0.50 (0.15), p < 0.001; in women, b = − 0.87 (0.17), p < 0.001; and for PP in men, b = − 0.60 (0.20), p < 0.001; in women, b = − 0.97 (0.27), p < 0.001. Among men, lower SBP and DBP levels were observed with participants without dyslipidemia and lower PP in participants with high income levels. Among women, lower SBP, DBP and PP were observed with current smokers, moderate/low alcohol levels and participants without dyslipidemia.

Current cannabis use was associated with lower SBP levels in men (b = − 0.63 (0.25), p = 0.012) and in women (b = − 1.17 (0.31), p < 0.001). Same results were observed for DBP and PP. Negative association between BP in men was found but not in women. The small association in BP differences between heavy users and never users remains too small to adopt cannabis-blood pressure public policy in clinical practice.”

https://www.nature.com/articles/s41598-022-22841-6

Do tobacco and cannabis use and co-use predict lung function: A longitudinal study

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Respiratory Medicine | Journal | ScienceDirect.com by Elsevier

“Background: Use of tobacco and cannabis is common and has been reported to predict lung function. Less is known about co-use of tobacco and cannabis and their impact on changes in lung function to early adulthood.

Research question: The study examines whether cigarette smoking or cannabis use and co-use are each associated with lung function in a population sample of young adults.

Study design and methods: Data are from a prospective cohort study of cigarette smoking, cannabis use and co-use at 21 and 30 years of age and lung function (FVC, FEV1, FEV1/FVC) measured at 30 years. Lung function results are transformed using Global Lung Function Formulae. Subjects are the children of pregnant women who were recruited into the cohort study over the period 1981-3. Respondents were administered a spirometry assessment at 21 and 30 years of age. These respondents completed a smoking and cannabis use questionnaire at 21- and 30-year follow-ups.

Results: Cigarette smoking (with or without cannabis use) is associated with reduced airflow. There is no consistent association between cannabis use and measures of lung function. The co-use of tobacco and cannabis appears to entail no additional risk to lung function beyond the risks associated with tobacco use alone.

Interpretation: Persistent cigarette smoking is associated with reduced airflow even in young adults. Cannabis use does not appear to be related to lung function even after years of use.”

https://pubmed.ncbi.nlm.nih.gov/36682602/

“•Cigarette smoking and cannabis use and co-use are risk factors for impaired lung function.

•By 30 years, those who have smoked cigarettes since adolescence already show evidence of impairment of lung function.

•By 30 years, those who used cannabis since the adolescent period do not appear to have evidence of impaired lung function.

•Co-use of tobacco and cannabis does not appear to predict lung function beyond the effects of tobacco use alone.”

https://www.resmedjournal.com/article/S0954-6111(23)00012-4/fulltext

“Smoking Cannabis Not Associated With Impaired Lung Functioning In Latest Study”

https://www.forbes.com/sites/emilyearlenbaugh/2023/02/01/smoking-cannabis-not-associated-with-impaired-lung-functioning-in-latest-study/?sh=5f2e60c6a630