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Cannabinoids from inflorescences fractions of Trema orientalis (L.) Blume (Cannabaceae) against human pathogenic bacteria

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“Background

Cannabinoids; tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN), might show antibacterial activity. Trema orientalis is a species in the Cannabaceae that is closely related to Cannabis through plastome phylogenetic evidence. This species is widely distributed throughout tropical Asia and is used as traditional medicine, particularly for the treatment of infectious diseases. However, no studies on the antibacterial activity of cannabinoid-containing inflorescences extracts are available. Thus, the aim of this study was to determine cannabinoid content and antibacterial activity of inflorescences fractions from T. orientalis native to Thailand.

Methods

We hypothesized that inflorescences from T. orientalis might display cannabinoids similar to Cannabis because of their close taxonomic relationship. We extracted the mature inflorescences and infructescence of T. orientalis in three disparate populations from different Thailand floristic regions. Extractions were subsequently partitioned into hydrophilic and lipophilic fractions using distilled water and chloroform. The lipophilic extracts were further fractionated by the column chromatography with gradient elution and analyzed by gas chromatography-mass spectrometry (GC-MS). Characterized cannabinoids were used in bioassays with multidrug-resistance bacteria.

Results

Lipophilic extracts and fractions of inflorescences from all Thailand floristic regions consistently displayed cannabinoids (THC, CBD and CBN) in various quantities. These extracts exhibited inhibitory activity for Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii strains with minimum inhibitory concentration values varying from 31.25 to 125 µg/mL.

Conclusion

Our study is the first to report cannabinoid detection in extracts from inflorescences of T. orientalis, a species in the Cannabaceae. These extracts and their fractions containing cannabinoids showed pronounced antibacterial activity. The use of analytic methods also demonstrated reproducible cannabinoid extraction.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126263/

“Trema orientalis is a pioneer species in the cannabis family (Cannabaceae) that is widely distributed in Thai community forests and forest edges.  T. orientalis can serve as a source of non-toxic natural lipophilic compounds that can be useful as bioactive ingredients in supplement feed development.”

https://pubmed.ncbi.nlm.nih.gov/38282858/

Risk of motor vehicle collision associated with cannabis and alcohol use among patients presenting for emergency care

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“Background: The objective of this study was to examine the relationship between cannabis and alcohol use and occurrence of motor vehicle collision (MVC) among patients in the emergency department (ED).

Methods: This was a cross-sectional study of visits to EDs in Denver, CO, Portland, OR, and Sacramento, CA by drivers who were involved in MVCs and presented with injuries (cases) and non-injured drivers (controls) who presented for medical care. We obtained blood samples and measured delta-9-THC and its metabolites. Alcohol levels were determined by breathalyzer or samples taken in the course of clinical care. Participants completed a research-assistant-administered interview consisting of questions about drug and alcohol use prior to their visit, context of use, and past-year drug and alcohol use. Multiple logistic regression was used to estimate the association between MVC and cannabis/alcohol use, adjusted for demographic characteristics. We then stratified participants based on levels of cannabis use and calculated the odds of MVC across these levels, first using self-report and then using blood levels for delta-9-THC in separate models. We conducted a case-crossover analysis, using 7-day look-back data to allow each participant to serve as their own control. Sensitivity analyses examined the influence of usual use patterns and driving in a closed (car, truck, van) versus open (motorcycle, motorbike, all-terrain vehicle) vehicle.

Results: Cannabis alone was not associated with higher odds of MVC, while acute alcohol use alone, and combined use of alcohol and cannabis were both independently associated with higher odds of MVC. Stratifying by level of self-reported or measured cannabis use, higher levels were not associated with higher odds for MVC, with or without co-use of alcohol; in fact, high self-reported acute cannabis use was associated with lower odds of MVC (odds ratio [OR] 0.18, 95% confidence interval [CI] 0.05-0.65). In the case-crossover analysis, alcohol use alone or in combination with cannabis was associated with higher odds of MVC, while cannabis use alone was again associated with decreased odds of MVC.

Conclusions: Alcohol use alone or in conjunction with cannabis was consistently associated with higer odds for MVC. However, the relationship between measured levels of cannabis and MVC was not as clear. Emphasis on actual driving behaviors and clinical signs of intoxication to determine driving under the influence has the strongest rationale.”

https://pubmed.ncbi.nlm.nih.gov/38277855/

“Decades of research have established that alcohol increases the risk for motor vehicle collision (MVC) in a dose-dependent manner.”

“Cannabis alone was not associated with higher odds of MVC,”

https://www.sciencedirect.com/science/article/abs/pii/S0001457524000046?via%3Dihub

Development of cannabidiol derivatives as potent broad-spectrum antibacterial agents with membrane-disruptive mechanism

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“The emergence of antibiotic resistance has brought a significant burden to public health. Here, we designed and synthesized a series of cannabidiol derivatives by biomimicking the structure and function of cationic antibacterial peptides.

This is the first report on the design of cannabidiol derivatives as broad-spectrum antibacterial agents.

Through the structure-activity relationship (SAR) study, we found a lead compound 23 that killed both Gram-negative and Gram-positive bacteria via a membrane-targeting mechanism of action with low resistance frequencies. Compound 23 also exhibited very weak hemolytic activity, low toxicity toward mammalian cells, and rapid bactericidal properties.

To further validate the membrane action mechanism of compound 23, we performed transcriptomic analysis using RNA-seq, which revealed that treatment with compound 23 altered many cell wall/membrane/envelope biogenesis-related genes in Gram-positive and Gram-negative bacteria. More importantly, compound 23 showed potent in vivo antibacterial efficacy in murine corneal infection models caused by Staphylococcus aureus or Pseudomonas aeruginosa.

These findings would provide a new design idea for the discovery of novel broad-spectrum antibacterial agents to overcome the antibiotic resistance crisis.”

https://pubmed.ncbi.nlm.nih.gov/38266554/

“Natural compounds have been found as an important source of antibiotics. Cannabidiol (CBD), which is derived from the plant cannabis, has a variety of pharmacological activities, including analgesic, anti-inflammatory, anti-epileptic, anti-anxiety, anticonvulsant, anti-cancer, antipsychotic, and antibacterial activities.”

https://www.sciencedirect.com/science/article/abs/pii/S0223523424000291?via%3Dihub

An Overview of Cannabidiol as a Multifunctional Drug: Pharmacokinetics and Cellular Effects

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“Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis Sativa, has garnered increasing attention for its diverse therapeutic potential.

This comprehensive review delves into the complex pharmacokinetics of CBD, including factors such as bioavailability, distribution, safety profile, and dosage recommendations, which contribute to the compound’s pharmacological profile. CBD’s role as a pharmacological inhibitor is explored, encompassing interactions with the endocannabinoid system and ion channels.

The compound’s anti-inflammatory effects, influencing the Interferon-beta and NF-κB, position it as a versatile candidate for immune system regulation and interventions in inflammatory processes. The historical context of Cannabis Sativa’s use for recreational and medicinal purposes adds depth to the discussion, emphasizing CBD’s emergence as a pivotal phytocannabinoid.

As research continues, CBD’s integration into clinical practice holds promise for revolutionizing treatment approaches and enhancing patient outcomes. The evolution in CBD research encourages ongoing exploration, offering the prospect of unlocking new therapeutic utility.”

https://pubmed.ncbi.nlm.nih.gov/38257386/

“CBD has demonstrated a wide range of potential therapeutic effects in both preclinical and clinical studies across various neurological, psychiatric, autoimmune, and cardiovascular disorders. The pharmacological inhibitory properties of CBD, combined with its anti-inflammatory, antiapoptotic, and antioxidant characteristics, make it a versatile compound with diverse applications.”

https://www.mdpi.com/1420-3049/29/2/473

The Neurotherapeutic Arsenal in Cannabis sativa: Insights into Anti-Neuroinflammatory and Neuroprotective Activity and Potential Entourage Effects

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“Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds-cannabinoids, terpenes, and flavonoids. While major cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential.

This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis’s bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis’s sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation.

The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis’s complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects.

This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis’s full therapeutic potential within the realm of natural plant-based medicine.”

https://pubmed.ncbi.nlm.nih.gov/38257323/

https://www.mdpi.com/1420-3049/29/2/410

β-Caryophyllene Inhibits Endothelial Tube Formation by Modulating the Secretome of Hypoxic Lung Cancer Cells-Possible Role of VEGF Downregulation

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“β-Caryophyllene (BCP), a bicyclic sesquiterpene that is a component of the essential oils of various spice and food plants, has been described as a selective CB2 cannabinoid receptor agonist. In the present study, the effect of BCP on angiogenesis was investigated.

It was found that conditioned media (CM) from BCP-treated hypoxic A549 lung cancer cells exhibited a concentration-dependent inhibitory effect on human umbilical vein endothelial cell (HUVEC) tube formation induced by CM from vehicle-treated hypoxic A549 cells. There was an associated concentration-dependent decrease in the proangiogenic factor vascular endothelial growth factor (VEGF) in the CM, with both BCP inhibitory effects (tube formation, VEGF secretion) being CB2 receptor-dependent. A reduction of the transcription factor hypoxia-inducible factor 1α (HIF-1α) was furthermore detected.

The antiangiogenic and VEGF-lowering properties of BCP were confirmed when CM from another lung cancer cell line, H358, were tested. When directly exposed to HUVECs, BCP showed no significant effect on tube formation, but at 10 µM, impaired VEGF receptor 2 (VEGFR2) phosphorylation triggered by recombinant VEGF in a CB2 receptor-independent manner. In summary, BCP has a dual antiangiogenic effect on HUVECs, manifested in the inhibition of tube formation through modulation of the tumor cell secretome and additionally in the inhibition of VEGF-induced VEGFR2 activation. Because the CB2 agonist has no psychoactive properties, BCP should continue to be evaluated preclinically for further antitumor effects.”

https://pubmed.ncbi.nlm.nih.gov/38255884/

https://www.mdpi.com/1422-0067/25/2/810

“Beta-caryophyllene is a dietary cannabinoid.” https://www.ncbi.nlm.nih.gov/pubmed/18574142

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934


Cannabinerol (CBNR) Influences Synaptic Genes Associated with Cytoskeleton and Ion Channels in NSC-34 Cell Line: A Transcriptomic Study

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“Cannabinoids are receiving great attention as a novel approach in the treatment of cognitive and motor disabilities, which characterize neurological disorders. To date, over 100 phytocannabinoids have been extracted from Cannabis sativa, and some of them have shown neuroprotective properties and the capacity to influence synaptic transmission.

In this study, we investigated the effects of a less-known phytocannabinoid, cannabinerol (CBNR), on neuronal physiology.

Using the NSC-34 motor-neuron-like cell line and next-generation sequencing analysis, we discovered that CBNR influences synaptic genes associated with synapse organization and specialization, including genes related to the cytoskeleton and ion channels. Specifically, the calcium, sodium, and potassium channel subunits (Cacna1b, Cacna1c, Cacnb1, Grin1, Scn8a, Kcnc1, Kcnj9) were upregulated, along with genes related to NMDAR (Agap3, Syngap1) and calcium (Cabp1, Camkv) signaling. Moreover, cytoskeletal and cytoskeleton-associated genes (Actn2, Ina, Trio, Marcks, Bsn, Rtn4, Dgkz, Htt) were also regulated by CBNR.

These findings highlight the important role played by CBNR in the regulation of synaptogenesis and synaptic transmission, suggesting the need for further studies to evaluate the neuroprotective role of CBNR in the treatment of synaptic dysfunctions that characterize motor disabilities in many neurological disorders.”

https://pubmed.ncbi.nlm.nih.gov/38255294/

https://www.mdpi.com/2227-9059/12/1/189

Antimicrobial Effect of Cannabidiol on Intracellular Mycobacterium tuberculosis

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“Introduction: Mycobacterium tuberculosis, the etiologic agent of tuberculosis (TB), has killed nearly one billion people during the last two centuries. Nowadays, TB remains a major global health problem ranked among the top 10 causes of death worldwide. One of the main challenges in developing new strategies to fight TB is focused on reducing the duration and complexity of drug regimens. Cannabidiol (CBD) is the main nonpsychoactive ingredient extracted from the Cannabis sativa L. plant, which has been shown to be biologically active against bacteria. The purpose of this work was to investigate the antimicrobial effect of CBD on M. tuberculosis intracellular infection. 

Materials and Methods: To assess the minimum inhibitory concentration (MIC) of CBD on mycobacterial strains, the MTT assay was performed on Mycobacterium smegmatis, and the Colony-Forming Unit (CFU) assay was conducted on MtbH37Rv. Additionally, the cytotoxic effect of CBD on THP-1 cells was assessed by MTT assay. Moreover, macrophages derived from the THP-1 cell were infected with MtbH37Rv (multiplicity of infection 1:10) to evaluate the intracellular activity of CBD by determining the CFU/mL. 

Results: Antimicrobial activity against M. smegmatis (MIC=100 μM) and MtbH37Rv (MIC=25 μM) cultures was exhibited by CBD. Furthermore, the effect of CBD was also evaluated on MtbH37Rv infected macrophage cells. Interestingly, a reduction in viable intracellular MtbH37Rv bacteria was observed after 24 h of treatment. Moreover, CBD exhibited a safe profile toward human THP-1 cells, since it showed no toxicity (CC50=1075 μM) at a concentration of antibacterial effect (selectivity index 43). 

Conclusion: These results extend the knowledge regarding the antimicrobial activity of CBD and demonstrate its ability to kill the human intracellular pathogen M. tuberculosis.”

https://pubmed.ncbi.nlm.nih.gov/38252548/

https://www.liebertpub.com/doi/10.1089/can.2023.0124

Cannabis Roots: Therapeutic, Biotechnological and Environmental Aspects

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“Since the legalization of recreational cannabis in Canada in 2018, the number of licenses for this crop has increased significantly, resulting in an increase in waste generated.

Nevertheless, cannabis roots were once used for their therapeutic properties, indicating that they could be valued today rather than dismissed.

This review will focus on both traditional therapeutic aspects and potential use of roots in modern medicine while detailing the main studies on active phytomolecules found in cannabis roots. The environmental impact of cannabis cultivation and current knowledge of the root-associated microbiome are also presented as well as their potential applications in biotechnology and phytoremediation. Thus, several high added-value applications of cannabis roots resulting from scientific advances in recent years can be considered to remove them from discarded residues.”

https://pubmed.ncbi.nlm.nih.gov/38252502/

https://www.liebertpub.com/doi/10.1089/can.2023.0168

Recreational and Medical Cannabis Legalization and Opioid Prescriptions and Mortality

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“Importance: While some have argued that cannabis legalization has helped to reduce opioid-related morbidity and mortality in the US, evidence has been mixed. Moreover, existing studies did not account for biases that could arise when policy effects vary over time or across states or when multiple policies are assessed at the same time, as in the case of recreational and medical cannabis legalization.

Objective: To quantify changes in opioid prescriptions and opioid overdose deaths associated with recreational and medical cannabis legalization in the US.

Design, setting, and participants: This quasiexperimental, generalized difference-in-differences analysis used annual state-level data between January 2006 and December 2020 to compare states that legalized recreational or medical cannabis vs those that did not.

Intervention: Recreational and medical cannabis law implementation (proxied by recreational and medical cannabis dispensary openings) between 2006 and 2020 across US states.

Main outcomes and measures: Opioid prescription rates per 100 persons and opioid overdose deaths per 100 000 population based on data from the US Centers for Disease Control and Prevention.

Results: Between 2006 and 2020, 13 states legalized recreational cannabis and 23 states legalized medical cannabis. There was no statistically significant association of recreational or medical cannabis laws with opioid prescriptions or overall opioid overdose mortality across the 15-year study period, although the results also suggested a potential reduction in synthetic opioid deaths associated with recreational cannabis laws (4.9 fewer deaths per 100 000 population; 95% CI, -9.49 to -0.30; P = .04). Sensitivity analyses excluding state economic indicators, accounting for additional opioid laws and using alternative ways to code treatment dates yielded substantively similar results, suggesting the absence of statistically significant associations between cannabis laws and the outcomes of interest during the full study period.

Conclusions and relevance: The results of this study suggest that, after accounting for biases due to possible heterogeneous effects and simultaneous assessment of recreational and medical cannabis legalization, the implementation of recreational or medical cannabis laws was not associated with opioid prescriptions or opioid mortality, with the exception of a possible reduction in synthetic opioid deaths associated with recreational cannabis law implementation.”

https://pubmed.ncbi.nlm.nih.gov/38241056/

https://jamanetwork.com/journals/jama-health-forum/fullarticle/2813866