[Low-dose THC in geriatric and palliative patients]

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“Background: Cannabis-containing medicines have been successfully used in our practice for more than 20 years in pain and especially in geriatric and palliative patients. While it was initially a very indication-specific use (pain, loss of appetite, etc.) and also with higher THC doses, this changed over time to low THC doses and a therapy focus on suffering-perpetuating symptoms and especially on stress (Matrix of Symptoms).

Method: As part of the legally prescribed companion survey, we evaluated our data in parallel and discussed it publicly in a series of publications. Based on these published results, the article is intended to show an overview of our experiences.

Results: Low-dose THC has a positive effect on morbidity, side effects, quality of life and mortality in geriatric and palliative patients.

Conclusion: Early therapy is particularly appropriate in geriatric and palliative patients due to the clear benefit-risk ratio of low-dose THC.”

https://pubmed.ncbi.nlm.nih.gov/36195786/

Identification of CB1 Ligands among Drugs, Phytochemicals and Natural-Like Compounds: Virtual Screening and In Vitro Verification

Go to ACS Chemical Neuroscience

“Cannabinoid receptor type 1 (CB1) is an important modulator of many key physiological functions and thus a compelling molecular target. However, safe CB1 targeting is a non-trivial task. In recent years, there has been a surge of data indicating that drugs successfully used in the clinic for years (e.g. paracetamol) show CB1 activity. Moreover, there is a lot of promise in finding CB1 ligands in plants other than Cannabis sativa. In this study, we searched for possible CB1 activity among already existing drugs, their metabolites, phytochemicals, and natural-like molecules. We conducted two iterations of virtual screening, verifying the results with in vitro binding and functional assays. The in silico procedure consisted of a wide range of structure- and ligand-based methods, including docking, molecular dynamics, and quantitative structure-activity relationship (QSAR). As a result, we identified travoprost and ginkgetin as CB1 ligands, which provides a starting point for future research on the impact of their metabolites or preparations on the endocannabinoid system. Moreover, we found five natural-like compounds with submicromolar or low micromolar affinity to CB1, including one mixed partial agonist/antagonist viable for hit-to-lead phase. Finally, the computational procedure established in this work will be of use for future screening campaigns for novel CB1 ligands.”

https://pubmed.ncbi.nlm.nih.gov/36197801/

https://pubs.acs.org/doi/10.1021/acschemneuro.2c00502

Cannabinoids in hyperhidrosis

“In our literature search for alternative treatments, we identified multiple unscientific and anecdotal sources claiming that cannabis can inhibit sweating. Our search of the medical literature revealed no evidence of a treatment attempt using cannabinoids, and thus, we initiated our study of one case with refractory generalized hyperhidrosis treated with cannabinoids from March to May 2021.

We observed a marked reduction in measured sweat and a significant improvement in the patient’s psychological well-being.

We conclude that, potentially, cannabinoids represent an effective therapeutic agent for hyperhidrosis and are worthy of further high-quality clinical investigation.”

“Hyperhidrosis can significantly curtail patient quality of life, from debilitating physical symptoms to social stigmatization and reduced life opportunities. Current treatments often prove unsatisfactory, especially in sufferers of generalized hyperhidrosis. In this open trial, we present the case of a refractory generalized hyperhidrosis treated with cannabinoids.

We found a remarkable reduction in the volume of sweat and an improvement to the patient’s quality of life using this novel low-cost and low-impact approach.”

“In summary, we report a case of precisely analyzed effects of cannabinoid therapy in generalized hyperhidrosis. We believe cannabinoids hold potential as a low side-effect and well-tolerated therapy, especially in refractory cases of hyperhidrosis. This reflects not only in the reduced perspiration, but also in the significant improvement in the participant’s quality of life.”

https://pubmed.ncbi.nlm.nih.gov/36200741/

https://www.tandfonline.com/doi/full/10.1080/09546634.2022.2127308?scroll=top&needAccess=true


Hemp microgreens as an innovative functional food: Variation in the organic acids, amino acids, polyphenols, and cannabinoids composition of six hemp cultivars

Food Research International

“Hemp (Cannabis sativa L.) is a multi-functional crop cultivated for fiber, seeds, or phytochemical extraction. Once a major industrial crop in several agro-environments, its cultivation strongly declined in developed countries since World War II. Exploiting hemp vegetative tissue as innovative food has remained largely unexplored.

The current work examined the potential production of hemp microgreens. Six cultivars were assessed for yield and composition of organic acids, amino acids, polyphenols and phytocannabinoids, through IC, FLD-HPLC and UHPLC-HRMS, respectively. Bioactive composition was strongly related to the hemp variety. ‘

Silvana’ demonstrated the highest total content of amino acids and essential amino acids, high concentrations of cannflavin A and B, and moderate levels of cannabidiol and cannabigerol. ‘Finola’ distinguished by the highest concentration of cannflavins and total polyphenols, and the lowest levels of Δ9-THC. Regardless of varietal differences, hemp microgreens proved widely safe in terms of Δ9-THC content.”

https://pubmed.ncbi.nlm.nih.gov/36192985/

“Hemp microgreens are a high-quality protein source of all essential amino acids.”

https://www.sciencedirect.com/science/article/abs/pii/S0963996922009218?via%3Dihub

Cannabidiol attenuates generalized tonic-clonic and suppresses limbic seizures in the genetically epilepsy-prone rats (GEPR-3) strain

SpringerLink

“Background: Cannabidiol (CBD) has been of rapidly growing interest in the epilepsy research field due to its antiseizure properties in preclinical models and patients with pharmacoresistant epilepsy. However, little is known about CBD effects in genetic models of epilepsies. Here we assessed CBD dose-response effects in the Genetically Epilepsy Prone Rats (GEPR-3) strain, which exhibits two types of epileptic seizures, brainstem-dependent generalized tonic-clonic seizures and limbic seizures.

Results: CBD dose-dependently attenuated generalized tonic-clonic seizures in GEPR-3 s; CBD 50 and 100 mg/kg reduced brainstem-dependent seizure severity and duration. In fully kindled GEPR-3 s, CBD 10 mg/kg reduced limbic seizure severity and suppressed limbic seizure expression in 75% of animals.

Conclusions: CBD was effective against brainstem and limbic seizures in the GEPR-3 s. These results support the use of CBD treatment for epilepsies by adding new information about the pharmacological efficacy of CBD in suppressing inherited seizure susceptibility in the GEPR-3 s.”

https://pubmed.ncbi.nlm.nih.gov/36195689/

https://link.springer.com/article/10.1007/s43440-022-00416-6

The effect of medical cannabis on cognitive functions: a systematic review

Systematic Reviews logo

“Background: Cannabis-based medicines are widely used in the treatment of a number of medical conditions. Unfortunately, cognitive disturbances are often reported as adverse events, although conversely, cognitive improvements have been reported. Hence, the objective of the present study was to identify, critically appraise and synthesise research findings on the potential impact of cannabis-based medicines on cognitive functioning.

Findings: Twenty-three studies were included, comprising a total of N = 917. Eight studies used Sativex as the cannabis-based medicine two used Epidiolex, two other studies used sprays, three studies used gelatine capsules, five smoked cannabis, two other and finally one studied cannabis withdrawal. Fifteen studies reported non-significant findings; six reported cognitive impairments; one study found cognitive improvement and a single study found improvement following withdrawal. Thirteen studies had cognitive or neuropsychological functioning as the primary outcome.

Conclusions: Due to a large heterogeneity and methodological limitations across studies, it is not possible to make any definite conclusions about the impact of cannabis-based medicines on cognitive functioning. However, the majority of high-quality evidence points in the direction that the negative impact of cannabis-based medicines on cognitive functioning is minor, provided that the doses of THC are low to moderate. On the other hand, long-term use of cannabis based medicines may still adversely affect cognitive functioning. In the studies that found impaired cognitive functioning to be significant, all of the test scores were either within the normal range or below what would be characterised as a neuropsychologically cognitive impairment.”

https://pubmed.ncbi.nlm.nih.gov/36192811/

“The potential positive effect of CBMs on cognitive functioning may be due to practice effects or mediated by alleviation of other medical symptoms, such as pain, depression or sleep problems.”

https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-022-02073-5

Association of Cannabis Use During Pregnancy with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Retrospective Cohort Study

“Background and aims: Cannabis use is increasingly common among pregnant individuals and might be a risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to test whether prenatal cannabis use is associated with increased risk of SARS-CoV-2 infection during pregnancy.

Design: Retrospective cohort study.

Setting: California USA.

Participants: 58,114 pregnancies (with outcomes from 3/5/2020 to 9/30/2021) among 57,287 unique pregnant women aged 14-54 years who were screened for prenatal substance use, enrolled in Kaiser Permanente Northern California (KPNC) (a healthcare system), and had not tested positive for COVID-19 prior to pregnancy onset.

Measurements: We utilized data from the KPNC electronic health record. Cannabis use status (current, recently quit, non-user) was based on universal screenings during prenatal care (including ≥1 urine toxicology test and self-reported use on a self-administered questionnaire). SARS-CoV-2 infection (based on polymerase chain reaction (PCR) tests) was estimated in time-to-event analyses using Cox proportional hazard regression models adjusting for covariates. Secondary analyses examined differences in a) SARS-CoV-2 positivity testing rates and b) SARS-CoV-2 infection rates among those tested.

Findings: We observed 348,810 person-months of follow-up time in our cohort with 41,064 SARS-CoV-2 PCR tests, and 6% (n=2,414) of tests being positive. At the start of follow-up, 7% of pregnant individuals had current use, 12% had recently quit, and 81% did not use cannabis. Adjusting for covariates, current use was associated with lower rates of SARS-CoV-2 infection (adjusted hazard ratio [aHR]=0.60,95% confidence interval [CI]:0.49-0.74) than non-use. Those who had recently quit did not differ from non-cannabis users in infection rates (aHR=0.96,95%CI:0.86-1.08). Sensitivity analyses among patients who received a SARS-CoV-2 test also found lower odds of infection associated with current versus no cannabis use (aOR=0.76,CI:0.61-0.93).

Conclusions: Current cannabis use appears to be associated with a reduced risk of severe acute respiratory syndrome coronavirus 2 infection among pregnant individuals.”

https://pubmed.ncbi.nlm.nih.gov/36189777/

https://onlinelibrary.wiley.com/doi/10.1111/add.16056

Lipid nano-carriers loaded with Cannabis sativa extract for epilepsy treatment – in vitro characterization and in vivo efficacy studies

Journal of Pharmaceutical Sciences

“Taking into consideration the latest reported beneficial anticolvusant effects of cannabidiol (CBD) and cannabiodiolic acid (CBDA) for clinical applications and the advantages of lipid nano-systems as carriers for targeted brain delivery, the aim of this study was set in direction of in vitro physico-chemical and biopharmaceutical characterization and in vivo evaluation of nanoliposomes and nanostructured lipid carriers loaded with Cannabis sativa extract intended for safe and efficient transport via blood-brain barrier and treatment of epilepsy. These nanoliposomes and nanostructured lipid formulations were characterized with z-average diameter <200 nm, following unimodal particle size distribution, negative values for Z-potential, high drug encapsulation efficiency and prolonged release during 24h (38.84-60.91 %). Prepared formulations showed statistically significant higher antioxidant capacity compared to the extract. The results from in vivo studies of the anticonvulsant activity demonstrated that all formulations significantly elevated the latencies for myoclonic, clonic and tonic seizures and, therefore, could be used in preventing different types of seizures. A distinction in the potential of the nano-systems was noted, which was probably anticipated by the type and the characteristics of the prepared formulations.”

https://pubmed.ncbi.nlm.nih.gov/36189477/

https://jpharmsci.org/article/S0022-3549(22)00417-8/fulltext

Will tetrahydrocannabinol be formed from cannabidiol in gastric fluid? An in vivo experiment

SpringerLink

“Cannabidiol (CBD) products have ascribed an uprising trend for their health-promoting effects worldwide. In contrast to Δ9-tetrahydrocannabinol (THC), CBD exhibits no state of euphoria. Since conversion of CBD into THC in an acidic environment has been reported, it has not been proved whether this degradation will also occur in human gastric fluid.

A total of 9 subjects ingested 400 mg CBD as a water-soluble liquid together with lecithin as an emulsifier and ethanol as a solubilizer. Blood samples were taken up to 4 h, and urine samples were submitted up to 48 h. THC, 11-hydroxy-Δ9-THC (THC-OH), 11-nor-9-carboxy-Δ9-THC (THC-COOH), CBD, 7-hydroxy cannabidiol (7-OH-CBD), and 7-carboxy cannabidiol (7-CBD-COOH) were determined in blood and THC-COOH and 7-CBD-COOH in urine by LC-MS/MS. Neither THC, THC-OH, nor THC-COOH were detectable in any serum specimen. Only two urine samples revealed THC-COOH values slightly above the threshold of 10 ng/ml, which could also be caused by trace amounts of THC being present in the CBD liquid.

It can be concluded that negative consequences for participants of a drug testing program due to a conversion of CBD into THC in human gastric fluid appear unlikely, especially considering a single intake of dosages of less than 400 mg.

Nevertheless, there is a reasonable risk for consumers of CBD products being tested positive for THC or THC metabolites. However, this is probably not caused by CBD cyclization into THC in human gastric fluid but is most likely due to THC being present as an impurity of CBD products.”

https://pubmed.ncbi.nlm.nih.gov/36190564/

https://link.springer.com/article/10.1007/s00414-022-02896-w

Cannabidiol as a personalized treatment for anxiety: clinical cases in Mexico

Drugs in Context

“Anxiety-related disorders are one of the most common mental health issues worldwide. Mexico has reported an increase in the prevalence of these ailments secondary to the confinement derived from the COVID-19 pandemic. Given the limitations of commonly used treatments for these disorders, a need arises to develop new pharmacological treatments for these patients. This paper has the primary objective of evaluating the efficacy and safety of cannabidiol isolate in drug compounding used as a personalized treatment in patients with anxiety disorders through the presentation of four clinical cases.”

https://pubmed.ncbi.nlm.nih.gov/36188636/