Author Archives: David Worrell

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

A label free chemoproteomic-based platform to disclose cannabidiol molecular mechanism of action on chronic myelogenous leukemia cancer cells

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“The discovery of the interactome of cannabidiol (CBD), a non-psychoactive cannabinoid from Cannabis sativa L., has been here performed on chronic myelogenous leukemia cancer cells, using an optimized chemo-proteomic stage, which links Drug Affinity Responsive Target Stability with Limited Proteolysis Multiple Reaction Monitoring approaches. The obtained results showed the ability of CBD to target simultaneously some potential protein partners, corroborating its well-known poly-pharmacology activity. In human chronic myelogenous leukemia K562 cancer cells, the most fascinating protein partner was identified as the 116 kDa U5 small nuclear ribonucleoprotein element called EFTUD2, which fits with the spliceosome complex. The binding mode of this oncogenic protein with CBD was clarified using mass spectrometry-based and in silico analysis.”

https://pubmed.ncbi.nlm.nih.gov/38268604/

“Recent studies exposed that CBD decreases the proliferation of human chronic myelogenous leukemia K562 cancer cells by prompting apoptosis”

https://www.cell.com/heliyon/fulltext/S2405-8440(24)00227-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405844024002275%3Fshowall%3Dtrue

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

Cannabidiol and its Potential Evidence-Based Psychiatric Benefits – A Critical Review

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“The endocannabinoid system shows promise as a novel target for treating psychiatric conditions.

Cannabidiol (CBD), a naturally occurring cannabinoid, has been investigated in several psychiatric conditions, with diverse effects and an excellent safety profile compared to standard treatments. Even though the body of evidence from randomised clinical trials is growing, it remains relatively limited in most indications.

This review comprises a comprehensive literature search to identify clinical studies on the effects of CBD in psychiatric conditions. The literature search included case studies, case reports, observational studies, and RCTs published in English before July 27, 2023, excluding studies involving nabiximols or cannabis extracts containing CBD and ∆9-tetrahydrocannabinol. Completed studies were considered, and all authors independently assessed relevant publications.Of the 150 articles identified, 54 publications were included, covering the effects of CBD on healthy subjects and various psychiatric conditions, such as schizophrenia, substance use disorders (SUDs), anxiety, post-traumatic stress disorder (PTSD), and autism spectrum disorders. No clinical studies have been published for other potential indications, such as alcohol use disorder, borderline personality disorder, depression, dementia, and attention-deficit/hyperactivity disorder.

This critical review highlights that CBD can potentially ameliorate certain psychiatric conditions, including schizophrenia, SUDs, and PTSD. However, more controlled studies and clinical trials, particularly investigating the mid- to long-term use of CBD, are required to conclusively establish its efficacy and safety in treating these conditions. The complex effects of CBD on neural activity patterns, likely by impacting the endocannabinoid system, warrant further research to reveal its therapeutic potential in psychiatry.”

https://pubmed.ncbi.nlm.nih.gov/38267003/

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2228-6118

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

Research progress on the cannabinoid type-2 receptor and Parkinson’s disease

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“Parkinson’s disease (PD) is featured by movement impairments, including tremors, bradykinesia, muscle stiffness, and imbalance. PD is also associated with many non-motor symptoms, such as cognitive impairments, dementia, and mental disorders. Previous studies identify the associations between PD progression and factors such as α-synuclein aggregation, mitochondrial dysfunction, inflammation, and cell death.

The cannabinoid type-2 receptor (CB2 receptor) is a transmembrane G-protein-coupled receptor and has been extensively studied as part of the endocannabinoid system. CB2 receptor is recently emerged as a promising target for anti-inflammatory treatment for neurodegenerative diseases.

It is reported to modulate mitochondrial function, oxidative stress, iron transport, and neuroinflammation that contribute to neuronal cell death. Additionally, CB2 receptor possesses the potential to provide feedback on electrophysiological processes, offering new possibilities for PD treatment. This review summarized the mechanisms underlying PD pathogenesis. We also discussed the potential regulatory role played by CB2 receptor in PD.”

https://pubmed.ncbi.nlm.nih.gov/38264546/

“Cannabinoids, as an emerging therapeutic agent, have attracted wide attention for their great potential in the treatment of various diseases.”

https://www.frontiersin.org/articles/10.3389/fnagi.2023.1298166/full

The Effect of Nabiximols on Driving Ability in Adults with Chronic Tic Disorders: Results of a Substudy Analysis of the Double-Blind, Randomized, Placebo-Controlled CANNA-TICS Trial

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“Background: The multicenter, randomized, double-blind, parallel-group, phase IIIb CANNA-TICS (CANNAbinoids in the treatment of TICS) trial showed clear trends for improvement of tics, depression, and quality of life with nabiximols versus placebo in adult patients with Gilles de la Tourette syndrome and other chronic tic disorders. Although in general nabiximols was well tolerated, it is unclear whether treatment using this cannabis extract influences driving skills in patients with chronic tic disorders. 

Methods: Here we report results of the “Fitness to Drive” substudy of the CANNA-TICS trial. The key endpoint was fitness to drive as a binary criterion with a computerized assessment at baseline and after 9 weeks of stable treatment (week 13) with nabiximols or placebo. A patient was considered unfit to drive according to the German Federal Highway Research Institute guidelines. 

Results: In the substudy, a total of 64 patients (76.6% men, mean±standard deviation of age: 36.8±13.9) were recruited at two study sites. The number of patients who were fit to drive increased from 24 (55.8%) at baseline to 28 (71.8%) at week 13 among 43 patients treated with nabiximols, and decreased from 14 (66.7%) to 10 (52.6%) among 21 patients who received placebo. The risk difference (nabiximols – placebo) was 0.17 (95% confidence interval=-0.08 to 0.43) in favor of nabiximols. Specifically, only 2 of 24 (8.3%) patients in the nabiximols, but 4 of 14 (28.6%) patients in the placebo group changed for the worse from fit (at baseline) to unfit (at week 13) to drive, whereas 8 of 19 (42.1%) patients in the nabiximols, and only 2 of 7 (28.6%) patients in the placebo group improved from unfit to fit. 

Conclusion: Treatment with nabiximols does not impair skills relevant to driving in those patients with tic disorders who were fit to drive at baseline and even improved fitness to drive in a subset of patients who were unfit to drive before start of treatment.”

https://pubmed.ncbi.nlm.nih.gov/38265476/

https://www.liebertpub.com/doi/10.1089/can.2023.0114

Antiarthritic and Anti-Inflammatory Properties of Cannabis sativa Essential Oil in an Animal Model

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“Arthritis and inflammatory conditions require effective therapies, but conventional drugs have side effects. This study explored Cannabis sativa L. essential oil (CSEO) as a safer alternative.

A chemical characterization of EO conducted via GC/MS showed the presence of sesquiterpene hydrocarbons (67.63%), oxygenated sesquiterpenes (25.91%), and oxygenated monoterpenes (0.99%). The study used three established inflammation induction tests: xylene-induced ear swelling, carrageenan-induced paw inflammation, and inflammation in the paw induced by Freund’s complete adjuvant (CFA). Xylene triggered acute inflammation in the ear, while carrageenan-induced acute inflammatory responses through edema and immune-cell recruitment in the paw. CFA-induced arthritis simulated chronic inflammatory conditions.

The obtained results demonstrated that treatment with CSEO significantly reduced ear weight in the xylene-induced ear-swelling test, indicating potential inhibition of neutrophil accumulation. In the carrageenan-induced paw inflammation test, CSEO reduced paw volume, suggesting interference with edema formation and leukocyte migration. In the CFA-induced paw inflammation test, CSEO decreased contralateral paw volume, restored body weight, and reduced C-reactive protein levels.

Conclusion: this study provides compelling evidence supporting the antiarthritic and anti-inflammatory effects of CSEO. The findings indicate the therapeutic value of EO in the management of arthritis and inflammatory diseases while highlighting the need for further in-depth research to study the molecular mechanisms and validate their safety and efficacy for clinical applications. Preliminary data from this study suggests encouraging prospects for advancing the treatment and prevention of inflammation.”

https://pubmed.ncbi.nlm.nih.gov/38256854/

https://www.mdpi.com/1424-8247/17/1/20

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

Oral Cannabidiol Treatment Is Associated with an Anti-Inflammatory Gene Expression Signature in Myeloid Cells of People Living with HIV

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“Introduction: HIV-related comorbidities appear to be related to chronic inflammation, a condition characterizing people living with HIV (PLWH). Prior work indicates that cannabidiol (CBD) might reduce inflammation; however, the genetics underpinning of this effect are not well investigated. Our main objective is to detect gene expression alterations in human peripheral blood mononuclear cells (PBMCs) from PLWH after at least 1 month of CBD treatment. 

Materials and Methods: We analyzed ∼41,000 PBMCs from three PLWH at baseline and after CBD treatment (27-60 days) through single-cell RNA sequencing. 

Results: We obtained a coherent signature, characterized by an anti-inflammatory activity, of differentially expressed genes in myeloid cells. 

Conclusions: Our study shows how CBD is associated with alterations of gene expression in myeloid cells after CBD treatment.”

https://pubmed.ncbi.nlm.nih.gov/38252549/

https://www.liebertpub.com/doi/10.1089/can.2023.0139