cannabidiol + THC (CogniCann)

Cyto-genotoxic potential and in silico analysis of emerging contaminants of the Ganges River water.

Akhtar Shirin S, Malik Abdul A

The Ganges River, vital for drinking water, agriculture, fisheries, and socio-religious practices, is increasingly threatened by contaminants, compromising its ecological and biological integrity. Present study was undertaken to identify contaminants in the river water using chemical profiling integrated with bacterial and plant bioassays, complemented by in silico analysis. GC-MS analysis of hexane and chloroform extracts revealed the presence of pharmaceuticals, phenolic substances, siloxanes, hormone-disrupting agents, and antibiotics, including spironolactone, nalmefene, desmethylverapamil, bisphenol B, aminopterin, and minocycline. Solvent extracts of the Ganges water demonstrated concentration-dependent mutagenicity in Ames Salmonella reversion assay, exceeding more than two-fold spontaneous reversion frequency. Chloroform extracts exhibited significant mutagenic potential with strain TA98 compared to TA100, suggesting prevalence of frameshift mutagens in the test samples. DNA repair-defective Escherichia coli K-12 mutants revealed decline in survival after 6 h of exposure; recA and lexA mutants displayed higher sensitivity compared to wild-type counterparts, confirming DNA-damaging potential of the samples. Allium cepa assay demonstrated suppression of mitotic index from 51.63% to 20.62%, along with increased chromosomal abnormalities from 2.33% to 26.17%. In Vigna radiata seeds, germination and seedling growth were reduced, followed by root tip damage and reduced root cell viability as detected by confocal microscopy. Computational docking analysis and 100-ns molecular dynamics simulations revealed stable binding of selected contaminants to molecular targets involved in nucleotide biosynthesis, DNA replication, topological regulation, and cell division. These findings suggested that the bioactive compounds may induce genetic and cellular damage, contributing to the biological effects associated with contaminant mixtures in river water.

Mechanisms by which cannabidiol promotes peripheral nerve regeneration.

Li Juncheng J, Xin Yishan Y, You Wenkang W, Zhou Jingwei J et al.

Cannabidiol, a cannabis-derived non-psychoactive compound, possesses neuroprotective potential; however, the specific mechanisms by which it promotes peripheral nerve repair remain unclear. This study aimed to elucidate the mechanisms underlying the neurorepair effects of cannabidiol, focusing on the regulation of nerve injury and repair through the "gut-nerve axis." We used a sciatic nerve crush model, combined with multi-omics analyses and molecular validation, to investigate and verify the mechanisms underlying cannabidiol mediated peripheral nerve injury repair both in vivo and in vitro. Following peripheral nerve injury, the abundance of the probiotic Akkermansia muciniphila was significantly reduced. cannabidiol treatment restored Akkermansia muciniphila abundance and was accompanied by increased levels of 3-hydroxyphenylacetic acid in both the serum and injured sciatic nerve. Oral administration of cannabidiol promoted PNI repair by improving the morphology of the injured nerve, increasing the static sciatic index in mice, and alleviating gastrocnemius muscle atrophy. Importantly, antibiotic-induced dysbiosis significantly attenuated the therapeutic efficacy of cannabidiol, whereas Akkermansia muciniphila supplementation restored these neuroregenerative effects. Mechanistically, transcriptomic sequencing indicated that 3-hydroxyphenylacetic acid effectively inhibited MAPK signaling activation in Schwann cells, thereby reducing the secretion of inflammatory factors and alleviating inflammation to create a favorable microenvironment for repair of peripheral nerve injury. Exogenous 3-hydroxyphenylacetic acid supplementation similarly promoted recovery of peripheral nerve injury. This study reveals, for the first time, a novel "cannabidiol-Akkermansia muciniphila-3-hydroxyphenylacetic acid-mitogen-activated protein kinase axis" that plays a pivotal role in peripheral nerve repair. These findings deepen our understanding of the neuroprotective mechanisms of cannabidiol and provide an important theoretical foundation for developing novel therapeutic strategies targeting the gut microbiome to promote repair of peripheral nerve injury.

Multi-target molecular mechanisms underlying the protective effects of cannabidiol against methamphetamine-induced neurotoxicity.

Zhao Wei W, Shan Di D, Liu Ming M, Wang Yifan Y

Methamphetamine is a widely abused psychostimulant and its neurotoxic effects involve multiple pathological processes, including oxidative stress, neuroinflammation, mitochondrial dysfunction, autophagy-apoptosis imbalance, and neurotransmitter dysregulation, posing a serious threat to the nervous system of individuals who abuse it. Currently, treatment options for methamphetamine-induced neural injury are limited, indicating the urgent need to develop safe and effective pharmacological interventions. Cannabidiol, a non-psychoactive component of Cannabis sativa, has emerged as a research hotspot because of its neuroprotective effects mediated through multiple targets and pathways. This review systematically summarizes the latest evidence on the protective effects of cannabidiol against methamphetamine-induced neurotoxicity, focusing on its regulation of oxidative stress, inhibition of neuroinflammation, stabilization of mitochondrial function, modulation of autophagy and apoptosis pathways, and effects on neurotransmitter systems. The aim of this paper is to clarify the multitarget mechanisms underlying cannabidiol-mediated neuroprotection and provide a theoretical basis for its potential use as an adjunctive therapy for methamphetamine abuse and associated neural injury.

Nanodispersible cannabidiol (150 mg/mL) for generalized anxiety disorder: Comparative emerging clinical evidence with first-line anxiolytics and mechanistic insights from network pharmacology and pharmacogenomics.

Gundugurti Prasad Rao PR, Komaravalli Prasanna Latha PL, Chatterjee Amrita A, Byregowda Bharath Harohalli BH et al.