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

biomedicines-logo

“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

ijms-logo

“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

biomedicines-logo

“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

antibiotics-logo

“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

“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

Publication Cover

“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

Current Issue Cover Image

“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)

Go to AIDS Education and Prevention

“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

Medical Cannabis Certification Is Associated With Decreased Opiate Use in Patients With Chronic Pain: A Retrospective Cohort Study in Delaware

Cureus Competition Winners Announced - Synaptive Medical

“Opioid medications are commonly used to treat chronic pain around the world. While these medications are quite effective at reducing pain, they can create opioid dependence and lead to further drug addiction. Long-term opioid use has significantly contributed to the “opioid epidemic” that is currently ravaging the United States, leading to opioid overdoses and unintentional deaths, particularly in Delaware.

Objective To determine if medical marijuana certification helps patients in Delaware with chronic pain reduce their opiate use.

Methods In this study, we examined individuals who were provided with legal; medical cannabis certifications in the state of Delaware between June 2018 and October 2019 and were concurrently being treated with opioid medications for chronic pain at a private pain management practice. Using a posthoc analysis, we conducted a retrospective cohort study on the individuals (n = 81) to determine if there was a decrease in their opioid use following medical cannabis certification. Opioid use was measured in morphine milligram equivalent (MME) through the Delaware prescription monitoring program (PMP) database.

Results Overall, the average change in prescribed opioid use was found to be -12.3 morphine milligram equivalent (MME) units when including all individuals (p < 0.00001). Among the included individuals with baseline opioid use, medical cannabis certification was associated with a 31.3% average decrease in opioid use (n = 63). When examining subgroups based upon pain location, individuals with neck pain displayed a 41.5% average decrease in MME (n = 27), while individuals with low back pain were observed to have a 29.4% decrease in opioid use (n = 58). Similarly, individuals with knee pain (n = 14) reduced their opioid use by 32.6%.

Conclusion The results display an association between medical cannabis certification and a decrease in opiate use among the study group individuals. This study suggests that medical cannabis use may help individuals to reduce their opiate requirements along with physician intervention. More research is needed to validate these findings with appropriate controls and verification of cannabis use.”

https://pubmed.ncbi.nlm.nih.gov/35004055/

“The results of this study indicate that medical marijuana certification is associated with a decrease in prescription opiate use for chronic pain treatment and supports greater use of this adjunct treatment modality. Given the significance of opioid addiction in American society, any treatment or additional resource to reduce opioid overuse can aid in the multifactorial management of chronic pain. Although marijuana use causes a variety of side effects, the findings here suggest that the use of medical cannabis as an adjunct treatment for chronic pain may be beneficial to public health.”

https://www.cureus.com/articles/77114-medical-cannabis-certification-is-associated-with-decreased-opiate-use-in-patients-with-chronic-pain-a-retrospective-cohort-study-in-delaware

Association between county level cannabis dispensary counts and opioid related mortality rates in the United States: panel data study

The BMJ (@bmj_latest) / Twitter

“Objective: To examine county level associations between the prevalence of medical and recreational cannabis stores (referred to as dispensaries) and opioid related mortality rates.

Participants: The study used US mortality data from the Centers for Disease Control and Prevention combined with US census data and data from Weedmaps.com on storefront dispensary operations. Data were analyzed at the county level by using panel regression methods.

Main outcome measure: The main outcome measures were the log transformed, age adjusted mortality rates associated with all opioid types combined, and with subcategories of prescription opioids, heroin, and synthetic opioids other than methadone. The associations of medical dispensary and recreational dispensary counts with age adjusted mortality rates were also analyzed.

Results: County level dispensary count (natural logarithm) is negatively related to the log transformed, age adjusted mortality rate associated with all opioid types (β=-0.17, 95% confidence interval -0.23 to -0.11). According to this estimate, an increase from one to two storefront dispensaries in a county is associated with an estimated 17% reduction in all opioid related mortality rates. Dispensary count has a particularly strong negative association with deaths caused by synthetic opioids other than methadone (β=-0.21, 95% confidence interval -0.27 to -0.14), with an estimated 21% reduction in mortality rates associated with an increase from one to two dispensaries. Similar associations were found for medical versus recreational storefront dispensary counts on synthetic (non-methadone) opioid related mortality rates.

Conclusions: Higher medical and recreational storefront dispensary counts are associated with reduced opioid related death rates, particularly deaths associated with synthetic opioids such as fentanyl. While the associations documented cannot be assumed to be causal, they suggest a potential association between increased prevalence of medical and recreational cannabis dispensaries and reduced opioid related mortality rates. This study highlights the importance of considering the complex supply side of related drug markets and how this shapes opioid use and misuse.”

https://pubmed.ncbi.nlm.nih.gov/33504472/

“We studied county level associations between cannabis storefront dispensaries and opioid related mortality rates in the US between 2014 and 2018. Our study found that increased medical and recreational storefront dispensary counts are associated with reduced opioid related mortality rates during the study period. These associations appear particularly strong for deaths related to synthetic opioids such as fentanyl.”

https://www.bmj.com/content/372/bmj.m4957