Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Long-Term Impact of Medical Marijuana Laws on the Burden of Cannabis Use Disorders in US Male and Female Adolescents and Young Adults

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“Deregulation of cannabis use has raised concerns regarding its potential effects on health, particularly in adolescents and young adults.

Here, we extracted data from the Global Burden of Disease database to estimate the long-term effect (> 5 years) of medical marijuana laws (MML) on 2019 cannabis use disorders Disability Adjusted Life Years (2019 CUD DALYs) in US male and female adolescents (15-19 years old) and young adults (20-24 years old). Socio-cultural, demographic and economic characteristics were used as baseline covariates. To improve the robustness of estimation, we took advantage of machine learning techniques.

We found no significant effect of MML on 2019 CUD DALYS in each of our four age/sex groups. Estimates from a marginal structural model taking into account age and sex strata in the same model were also non-significant.

Our findings suggest that MML may have a negligible effect (if any) on cannabis use disorders in this population group.”

https://pubmed.ncbi.nlm.nih.gov/36036345/

https://link.springer.com/article/10.1007/s10597-022-01018-5

Cannabinoid Cancer Biology and Prevention

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“Plant-based, synthetic, and endogenous cannabinoids have been shown to control a diverse array of biological processes, including regulation of cell fate across cancers. Their promise as broad-based antitumor agents in preclinical models has led to the initiation of pilot clinical trials. Session 5 of the National Cancer Institute’s Cannabis, Cannabinoids and Cancer Research Symposium provides an overview of this research topic.

Overall, the presentations highlight cannabinoid signal transduction and specific molecular mechanisms underlying cannabinoid antitumor activity. They also demonstrate the broad-based antitumor activity of the plant-based, synthetic, and endogenous cannabinoid compounds. Importantly, evidence is presented demonstrating when cannabinoids may be contraindicated as a treatment for cancer, as in the case of human papilloma virus-meditated oropharynx cancer or potentially other p38 MAPK pathway-driven cancers.

Finally, it is discussed that a key to advancing cannabinoids into the clinic is to conduct well-designed, large-scale clinical trials to determine whether cannabinoids are effective antitumor agents in cancer patients.”

https://pubmed.ncbi.nlm.nih.gov/34850900/

“These sessions present multiple lines of preclinical evidence supporting that the cannabinoids THC and CBD act as broad-based antitumor agents controlling many aspects of cancer progression, including cell proliferation, apoptosis, invasion, metastasis, and immune surveillance. “

https://academic.oup.com/jncimono/article/2021/58/99/6446216?login=false


Cannabinoids-Perspectives for Individual Treatment in Selected Patients: Analysis of the Case Series

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“Cannabinoids can be successfully used in the treatment of many symptoms and diseases; however, most often they are not the drugs of first choice. They can be added to the primary therapy, which can improve its effectiveness, or be introduced as the basic treatment when the conventional methods have failed. Small clinical trials and case reports prove the benefits of applying medicinal cannabis in various indications; however, clinical trials in larger groups of patients are scarce and often controversial. Due to limited scientific evidence, it is essential to conduct further experimental trials. Understanding the role of endocannabinoids, as well as the composition of cannabis containing both phytocannabinoids and terpenes plays an important role in their clinical use. The clinical effects of cannabinoids depend, among other things, on the activity of the endocannabinoid system, the proportion of phytocannabinoids, such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and the dosage used. The article discusses the role of phytocannabinoids and the potential of using them in different clinical cases in patients suffering from chronic pain, opioid dependence, depression and migraine, who did not respond to the conventional therapeutic methods. In each of the presented cases, the implementation of cannabinoids altered the course of the disease and resulted in symptom relief. Every decision to introduce cannabinoids to the treatment should be made individually with careful attention paid to details. Additionally, it is worth taking care of good clinical communication and education so that the implemented therapy is safe, effective and properly perceived by the patient.”

https://pubmed.ncbi.nlm.nih.gov/36009411/

“Evidence derived from observational studies suggest that using cannabis may help to reduce symptoms, alleviate the course of many diseases, as well as withdrawal symptoms in substance abuse disorder, such as opioid abuse and dependence. The endocannabinoid system undoubtedly plays a vital role in the modulation of functioning of many systems, but further observations and clinical trials are necessary to assess both efficacy and dosage of cannabinoids in certain disorders. Unfortunately, so far there is still not enough clinical data, which would enable us to draw credible conclusions and establish standardized doses in the selected disorders. Every patient should be approached individually with careful assessment of their condition and treated according to the “start low, go slow” principle in order to determine the lowest effective dose. In the series of presented cases cannabinoids were not used as a first-line therapy, but proved their efficacy as a complementary or alternative approach when other available treatment methods did not deliver expected and satisfactory results. Prospective approach to using cannabis in everyday clinical practice, devoid of bias and apprehension on the physicians’ part, aims to study the research and other countries’ experience, where both plant form and pure extract already have medical usage. Although today it may seem unlikely, in the near future cannabis may become widely accessible and remarkably beneficial for our patients.”

https://www.mdpi.com/2227-9059/10/8/1862/htm

Cannabinoids and Chronic Liver Diseases

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“Nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and viral hepatitis are the main causes of morbidity and mortality related to chronic liver diseases (CLDs) worldwide. New therapeutic approaches to prevent or reverse these liver disorders are thus emerging.

Although their etiologies differ, these CLDs all have in common a significant dysregulation of liver metabolism that is closely linked to the perturbation of the hepatic endocannabinoid system (eCBS) and inflammatory pathways. Therefore, targeting the hepatic eCBS might have promising therapeutic potential to overcome CLDs.

Experimental models of CLDs and observational studies in humans suggest that cannabis and its derivatives may exert hepatoprotective effects against CLDs through diverse pathways. However, these promising therapeutic benefits are not yet fully validated, as the few completed clinical trials on phytocannabinoids, which are thought to hold the most promising therapeutic potential (cannabidiol or tetrahydrocannabivarin), remained inconclusive. Therefore, expanding research on less studied phytocannabinoids and their derivatives, with a focus on their mode of action on liver metabolism, might provide promising advances in the development of new and original therapeutics for the management of CLDs, such as NAFLD, ALD, or even hepatitis C-induced liver disorders.”

https://pubmed.ncbi.nlm.nih.gov/36012687/

“Given the significant contribution of the hepatic eCBS and its downstream pathways in the regulation of liver metabolism and the setting of liver abnormalities, pharmacologically targeting peripheral CBRs may have promising potential therapeutic benefits for the treatment of CLDs. Besides this, the use of cannabis by people at risk of developing chronic liver disorders has also suggested hepatoprotective effects by reducing the frequency of NAFLD, ALD, or HCV-induced liver disorders, which would suggest that cannabinoid-based medicine may be effective in treating CLDs.”

https://www.mdpi.com/1422-0067/23/16/9423/htm

The Antimicrobial Properties of Cannabis and Cannabis-Derived Compounds and Relevance to CB2-Targeted Neurodegenerative Therapeutics

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“Cannabinoid receptor 2 (CB2) is of interest as a much-needed target for the treatment or prevention of several neurogenerative diseases. However, CB2 agonists, particularly phytocannabinoids, have been ascribed antimicrobial properties and are associated with the induction of microbiome compositional fluxes. When developing novel CB2 therapeutics, CB2 engagement and antimicrobial functions should both be considered. This review summarizes those cannabinoids and cannabis-informed molecules and preparations (CIMPs) that show promise as microbicidal agents, with a particular focus on the most recent developments. CIMP-microbe interactions and anti-microbial mechanisms are discussed, while the major knowledge gaps and barriers to translation are presented. Further research into CIMPs may proffer novel direct or adjunctive strategies to augment the currently available antimicrobial armory. The clinical promise of CIMPs as antimicrobials, however, remains unrealized. Nevertheless, the microbicidal effects ascribed to several CB2 receptor-agonists should be considered when designing therapeutic approaches for neurocognitive and other disorders, particularly in cases where such regimens are to be long-term. To this end, the potential development of CB2 agonists lacking antimicrobial properties is also discussed.”

https://pubmed.ncbi.nlm.nih.gov/36009504/

https://www.mdpi.com/2227-9059/10/8/1959/htm

Antibacterial, Antibiofilm, and Antioxidant Activity of 15 Different Plant-Based Natural Compounds in Comparison with Ciprofloxacin and Gentamicin

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“Plant-based natural compounds (PBCs) are comparatively explored in this study to identify the most effective and safe antibacterial agent/s against six World Health Organization concern pathogens. Based on a contained systematic review, 11 of the most potent PBCs as antibacterial agents are included in this study. The antibacterial and antibiofilm efficacy of the included PBCs are compared with each other as well as common antibiotics (ciprofloxacin and gentamicin). The whole plants of two different strains of Cannabis sativa are extracted to compare the results with sourced ultrapure components. Out of 15 PBCs, tetrahydrocannabinol, cannabidiol, cinnamaldehyde, and carvacrol show promising antibacterial and antibiofilm efficacy. The most common antibacterial mechanisms are explored, and all of our selected PBCs utilize the same pathway for their antibacterial effects. They mostly target the bacterial cell membrane in the initial step rather than the other mechanisms. Reactive oxygen species production and targeting [Fe-S] centres in the respiratory enzymes are not found to be significant, which could be part of the explanation as to why they are not toxic to eukaryotic cells. Toxicity and antioxidant tests show that they are not only nontoxic but also have antioxidant properties in Caenorhabditis elegans as an animal model.”

https://pubmed.ncbi.nlm.nih.gov/36009966/

“Some of the PBCs tested, including THC, CBD, cinnamaldehyde, and carvacrol, showed quite promising antibacterial and antibiofilm potency in comparison with common antibiotics (ciprofloxacin and gentamicin). They are not only non-toxic but also have antioxidant properties as well.”

https://www.mdpi.com/2079-6382/11/8/1099/htm

Cannabinoids Lead to Significant Improvement in Gastroparesis—Related Abdominal Pain

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“Neuropathy plays a large role in the pathogenesis of gastroparesis. Neuropathic pain in gastroparesis is an often difficult—to—treat symptom of the disease, despite 80—90% of patients with gastroparesis reporting abdominal pain as a symptom. Treatment for gastroparesis—related pain is especially limited. Neuromodulators are used for this purpose despite a lack of evidence supporting their effectiveness.

Cannabinoids, primarily delta—9—tetrahydrocannabinol (THC) and cannabidiol (CBD), are increasingly utilized for medicinal purposes. In New York medical marijuana is approved for the treatment of neuropathy with severe pain. Similarly, Dronabinol (a synthetic THC analogue) has been used for nausea vomiting and anorexia for years.

We showed that cannabinoids are effective in the treatment of gastroparesis—related abdominal pain.”

“Conclusion: Our study shows that cannabinoids may play an important role in the management of gastroparesis—related abdominal pain. There are currently no treatments shown to be effective for gastroparetic pain in clinical trials, and cannabinoids may serve a niche for this under—treated symptom.”

https://journals.lww.com/ajg/fulltext/2018/10001/cannabinoids_lead_to_significant_improvement_in.1204.aspx

Gastroparesis with Cannabis Use: A Retrospective Study from the Nationwide Inpatient Sample

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“Background: With increasing utilization of cannabis in the United States (US), clinicians may encounter more cases of Gastroparesis (GP) in coming years.

Objective: The primary outcome was inpatient mortality for GP with cannabis use. Secondary outcomes included system-based complications and the burden of the disease on the US healthcare system.

Methods: From the Nationwide Inpatient Sample (NIS), we identified adult hospitalizations with a primary discharge diagnosis of GP for 2016 and 2017. Individuals ≤18 years of age were excluded. The study population was subdivided based on a secondary diagnosis of cannabis use. The outcomes included biodemographic characteristics, mortality, complications, and burden of disease on the US healthcare system.

Results: For 2016 and 2017, we identified 99,695 hospitalizations with GP. Of these hospitalizations, 8,870 had a secondary diagnosis of cannabis use while 90,825 served as controls. The prevalence of GP with cannabis use was 8.9%. For GP with cannabis use, the patients were younger (38.5 vs 48.1 years, p < 0.001) with a Black predominance (Table 1) and lower proportion of females (52.3 vs 68.3%, p < 0.001) compared to the non-cannabis use cohort. Additionally, the cannabis use cohort had higher percentage of patients with co-morbidities like hypertension, diabetes mellitus and a history of smoking. The inpatient mortality for GP with cannabis use was noted to be 0.27%. Furthermore, we noted shorter mean length of stay (LOS) (3.4 vs 4.4 days, aMD: -0.7, 95%CI: -0.9 – [-0.5], p < 0.001), lower mean total hospital charge (THC) ($30,400 vs $38,100, aMD: -5100, 95%CI: -6900 – [-3200], p < 0.001), and lower rates of sepsis (0.11 vs 0.60%, aOR: 0.22, 95% CI: 0.05-0.91, p = 0.036) for GP hospitalizations with cannabis use compared to the non-cannabis use cohort.

Conclusion: Inpatient mortality for GP hospitalizations with cannabis use was 0.27%. Additionally, these patients had shorter LOS, lower THC, and lower sepsis rates.”

https://pubmed.ncbi.nlm.nih.gov/34096455/

https://www.tandfonline.com/doi/abs/10.1080/00325481.2021.1940219?journalCode=ipgm20

Trends and Socioeconomic Health Outcomes of Cannabis Use Among Patients With Gastroparesis: A United States Nationwide Inpatient Sample Analysis

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“Background: Although cannabis may worsen nausea and vomiting for patients with gastroparesis, it may also be an effective treatment for gastroparesis-related abdominal pain. Given conflicting data and a lack of current epidemiological evidence, we aimed to investigate the association of cannabis use on relevant clinical outcomes among hospitalized patients with gastroparesis.

Materials and methods: Patients with a diagnosis of gastroparesis were reviewed from the National Inpatient Sample (NIS) database between 2008 and 2014. Gastroparesis was identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes with patients classified based on a diagnosis of cannabis use disorder. Demographics, comorbidities, socioeconomic status, and outcomes were compared between cohorts using χ2 and analysis of variance. Logistic regression was then performed and annual trends also evaluated.

Results: A total of 1,473,363 patients with gastroparesis were analyzed [n=33,085 (2.25%) of patients with concomitant cannabis use disorder]. Patients with gastroparesis and cannabis use disorder were more likely to be younger and male gender compared with nonusers (36.7±18.8 vs. 51.9±16.8; P<0.001 and 52.9% vs. 33.5%; P<0.001, respectively). Race/ethnicity was different between groups (P<0.001). Cannabis users had a lower median household income and were more likely to have Medicaid payor status (all P<0.001). Controlling for confounders, length of stay, and mortality were significantly decreased for patients with gastroparesis and cannabis use (all P<0.001).

Conclusion: While patients with gastroparesis and cannabis use disorder were younger, with a lower socioeconomic status, and disproportionately affected by psychiatric diagnoses, these patients had better hospitalization outcomes, including decreased length of stay and improved in-hospital mortality.”

https://pubmed.ncbi.nlm.nih.gov/33780213/

https://journals.lww.com/jcge/Abstract/2022/04000/Trends_and_Socioeconomic_Health_Outcomes_of.7.aspx

“Cannabis Use Disorder in Patients With Gastroparesis Associated With Better Hospitalization Outcomes”

https://www.gastroenterologyadvisor.com/stomach-disorders/cannabis-use-disorder-in-patients-with-gastroparesis-associated-with-better-hospitalization-outcomes/

Cannabis Use as a Protective Factor Against Overweight in HIV-Hepatitis C Virus Co-Infected People (ANRS CO13 HEPAVIH Cohort)

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“Overweight is increasingly prevalent in people living with HIV (PLWH), and is a high risk factor for metabolic disorders in this population. PLWH co-infected with hepatitis C virus (HCV) have a higher risk of metabolic disorders than their mono-infected counterparts.

The putative relationship between cannabis use and body weight found in the general population has never been documented in HIV-HCV co-infected people. We tested whether cannabis use is associated with body mass index (BMI), overweight, and underweight in HCV co-infected PLWH (N = 992). Mixed-effects linear and logistic regression models were used to study the association between cannabis use and the three outcomes over time.

After multivariable adjustment, cannabis use was inversely associated with BMI. Cannabis use was associated with a lower and higher risk of overweight and underweight, respectively. Cannabis use should be assessed and taken into account in the clinical management of the HIV-HCV co-infected population.”

https://pubmed.ncbi.nlm.nih.gov/35994579/

https://guilfordjournals.com/doi/10.1521/aeap.2022.34.4.272