“Lead is a naturally occurring metal found in numerous compounds used in everyday life. Toxicity from lead is a well-known public health problem. Its effects are implicated in multiple tissues, encompassing the gastrointestinal, renal, cardiovascular, and neurological systems.
Endocannabinoid receptors are involved in each of these systems, but the effects of lead on the receptors themselves are not well elucidated. In the neurological system, lead has varying interactions with neurotransmitters and downstream regulators implicated in neuronal transmissions influenced by endocannabinoid receptor function.
Lead’s effect is likely indirect on endocannabinoid receptor function; however, its influence on neuronal function is likely inhibitory to the receptor’s functioning. Lead has also been implicated in oxidative stress states, which would influence endocannabinoid receptors’ function.
The literature clearly supports lead having a negative impact on the overall function of endocannabinoid receptors, setting the stage for pathological states related to diminished neurosynaptic function and, in embryology, altered neuronal development, especially of the neural tube.”
“Neisseria gonorrhoeae is a Gram-negative diplococcus that causes gonorrhea through sexual contact. This ancient STD remains a major public health concern due to reproductive health impacts, antimicrobial resistance (AMR), and lack of a vaccine.
Cannabis sativa contains antibacterial cannabinoids, though its role in combating antibiotic resistance is underexplored. The 2Fe-2S iron-sulfur cluster protein is a potential antibiotic target, as these clusters are vital for bacterial proteins involved in electron transport, enzyme activity, and gene regulation. Disrupting them may impair bacterial survival and function.
In this investigation, the 2Fe-2S iron sulfur cluster binding domain-containing protein (NGFG_RS03485), identified as a potential therapeutic target from the core proteome of 12 Neisseria gonorrhoeae strains, was selected for this study. Potential antimicrobial agents were explored through molecular docking studies involving 16 cannabinoid analogs-9 obtained from literature sources and 7 identified via fingerprint similarity searches.
The study revealed that four cannabinoids form favorable bonds with active regions against our targeted protein; with a high binding affinity formed from the molecular docking; 1,3-Benzenediol, 2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-, (1R-trans). Dronabinol, Cannabinolic acid A (CBNA), Cannabigerolic acid (CBGA), and Ferruginene C are derivatives identified. Drug-likeness assessments were conducted to evaluate the pharmacokinetic and toxicity properties of the cannabinoids and compared against the antibiotics.”
“Neisseria gonorrhoeae, the bacterium responsible for gonorrhoea, has developed increasing resistance to multiple antibiotics, making new treatment strategies urgently needed. This study explores the potential of cannabinoids and their derivatives as antimicrobial agents targeting N. gonorrhoeae.
Using computational methods, including molecular docking and fingerprint-based compound searches, the study identified five promising cannabinoid compounds with strong binding affinities to the 2Fe-2S iron–sulfur cluster binding domain-containing protein, a critical bacterial enzyme involved in electron transport and cellular function. These include 1,3-Benzenediol (a cannabidiol derivative), Ferruginene C, Dronabinol, Cannabinolic acid A (CBNA), and Cannabigerolic acid (CBGA). Their interactions were visualized using PyMOL and PLIP, revealing significant hydrogen bonding and hydrophobic interactions at active binding sites. Additionally, drug-likeness and pharmacokinetic assessments were performed, showing favorable absorption and low toxicity for several compounds compared to standard antibiotics.
Importantly, these cannabinoids showed potential to disrupt bacterial metabolic processes without inducing typical resistance pathways. The findings support further exploration of Phyto cannabinoids as natural alternatives for treating multidrug-resistant N. gonorrhoeae, with the 2Fe-2S cluster protein as a novel target. Further in vivo validation is recommended to confirm their therapeutic efficacy and safety.”
“The application of nanoparticles as nanomedicines, particularly for the targeted and efficacious delivery of drugs is an expanding platform in the field of cannabinoid and pharmaceutical drug delivery. By refocusing the route of drug administration beyond the oral gut pathway, this technology provides significant advancements that are especially relevant for cancer treatments.
Orally administered drugs face significant challenges as they traverse the gastrointestinal tract (GIT) and are subject to first-pass GIT metabolism. Physiological conditions encountered in the GIT such as food effects, hormones, gastric pH, emptying time, and intestinal transit time vary widely across individuals. Fluid composition and enzymatic activity in the small intestine and large bowel also influence drug dissolution and absorption. These factors in conjunction with the intestinal cohort of bacteria can metabolize drugs before absorption, contributing to poor and variable drug bioavailability, which can be exacerbated by gut dysbiosis.
Drug delivery that bypasses the oral-GIT route and hence first-pass metabolism offers a plausible solution for enhanced safety and drug efficacy.”
“Bypassing the first-pass metabolism in the gut is a fundamental and important characteristic of nanomedicines. It is thus possible to identify nanoparticles that form clear solutions in a stable aqueous matrix. Producing relatively insoluble drug components without altering their chemical structures is an important feature of nanomedicine drug delivery platforms.
These nanomedicines provide flexibility that allows the development of nanoparticle aqueous formulations of oro-mucosal, nasal, ocular, and transdermal products without the use of alcohol for enhanced delivery which bypasses the first-pass passage and metabolism of the GIT.”
“Delta-9-Tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid and structural analog of THC, exhibits a dual pharmacological profile as a CB1 receptor agonist/antagonist and a partial CB2 agonist. This study evaluated the effects of THCV in a THC discrimination model in rats. Male Sprague-Dawley rats (n = 16, 300-340 g, PND60) were trained under a fixed ratio 20 (FR20) schedule to discriminate THC (3 mg/kg) from vehicle. Substitution tests were conducted with THC (0.325-3 mg/kg), THCV (0.75-6 mg/kg), and THC-THCV combinations. THCV produced an inverted U-shaped substitution curve, significantly differing from vehicle (p = 0.008). At 3 mg/kg, THCV partially substituted for THC (54.6% ± 17.82, p = 0.003). Response rate significantly increased during the substitution test with 3 mg/kg of THCV (p = 0.042). THCV (6 mg/kg) reversed THC (0.75 mg/kg)-induced responding (p = 0.040), with no significant change in response rate (p = 0.247). However, THCV combined with THC (1.5 mg/kg) affected response rates (p = 0.012), with 6 mg/kg significantly reducing rates vs. 3 mg/kg (p = 0.013). Blood THC and 11-OH-THC levels remained unchanged when THC was combined with THCV. The findings suggest THCV can partially mimic or block THC’s discriminative effects in a dose-dependent manner, possibly acting as a partial CB1 agonist.”
“Taken together, our findings highlight THCV’s unique pharmacological profile, characterized by partial agonism dose-dependent substitution for THC, and antagonism at higher doses. Importantly, THCV substituted for THC in a graded manner without evidence of pharmacokinetic interactions, and it also produced stimulant-like effects that distinguish it from THC. These results suggest that THCV may act as a dose-dependent modulator of cannabinoid receptor activity, capable of both mimicking and opposing THC’s discriminative stimulus effects. Such bidirectional properties are consistent with its complex receptor pharmacology and underscore the importance of dose in determining behavioral outcomes. Future studies should expand on these findings by examining sex- and strain-dependent variability, assessing the role of CB1 and CB2 receptor mechanisms using antagonist approaches, and exploring THCV’s actions across a broader range of behavioral paradigms, including those related to reward, cognition, and feeding behavior. Together, these efforts will help to clarify the pharmacology of THCV and further delineate its position within the cannabinoid spectrum.”
“We report the first isolation of a previously unknown cannabinoid, cannabizetol (CBGD, 7), from Cannabis sativa extracts, representing the third member of the rare class of methylene-bridged dimeric cannabinoids. The availability of a chemically synthesized standard was crucial for its unequivocal identification, thus confirming the natural occurrence of this new compound.
In addition to this structural discovery, we demonstrate that cannabizetol exhibits remarkable antioxidant and skin anti-inflammatory activity, significantly higher than that observed for the known dimeric cannabinoid cannabitwinol (CBDD, 6).
These results highlight cannabizetol as a promising bioactive metabolite with potential dermatological applications. To further enable its study, we developed a continuous flow approach to optimize the preparation of these dimers, achieving a substantial reduction in reaction times.”
“Several cannabinoids have demonstrated biological activities, making Cannabis sativa particularly attractive as a source of potential medicinal active principles.”
“Cannabis sativa L. is an aromatic medicinal plant with various biologically active classes of compounds such as cannabinoids, polyphenols, and terpenes.
Unlike the widely investigated inflorescence and leaf, the stembark of C. sativa has been overlooked regarding its medicinal potential. This study, therefore, was aimed at determining the chemical composition and antioxidant activity of the essential oils (EOs) obtained from the fresh and dried stembark of two C. sativa cultivars, Lifter and Cherrywine, grown in Komga, South Africa, with a view to ascertaining the more promising cultivar.
The chemical profiles of the hydro-distilled EOs were analyzed by gas chromatography-mass spectrometry (GC-MS), while an in vitro antioxidant activity assessment of the EOs was performed using DPPH and H2O2 spectrophotometric methods. The identified constituents from the EOs were molecularly docked against NOX2, a protein implicated in oxidative stress. The afforded EOs were colorless with a mild skunk-like odor. A total of thirty-two constituents were identified in both fresh and dry oils from the Lifter cultivar while the Cherrywine cultivar contained a total of forty-two constituents.
The EOs of both cultivars contained twenty compounds, notably Cannabidiol (0.25-85.03%), Caryophyllene oxide (1.27-19.58%), Caryophyllene (0.64-16.61%), Humulene (0.37-8.15%), Octacosane (3.37-6.55%), Humulene-1,2-epoxide (0.45-5.78%), Nerolidol (0.32-4.99%), Palmitic acid (1.45-4.45%), Tetracosane (1.75-2.91%), Dronabinol (0.86-2.86%), Cannabinol (0.54-1.64%), 7-epi-γ-eudesmol (0.53-1.00%), Guaiol (0.37-0.66%), Linoleic acid (0.22-0.60%), γ-Selinene (0.15-0.48%), β-Eudesmol (0.34-0.50%), and Linalool (0.24-0.30%).
The dried Lifter stembark oil (DLSO) gave the best antioxidant activity among the four investigated cannabis oils, exhibiting the lowest IC50 values of 21.68 ± 1.71 and 26.20 ± 1.34 µg/mL against DPPH and H2O2 radicals, respectively. The notable antioxidant activity of the DLSO may be attributed to the higher number (30) of constituents compared to the fresh Lifter stembark oil (LSO) with 11 constituents. Additionally, the DLSO showed a unique chemical profile comprising monoterpenes, oxygenated and hydrocarbon sesquiterpenes. Further in silico studies on the putative constituents in the Lifter cultivar revealed Cannabinol, Cannabidiol, and Linalool as the promising constituents based on their higher binding energy scores of -9.7, -8.5, and -6.5 kcal/mol, respectively, compared to L-Ascorbic acid (-5.7 kcal/mol).
It can be inferred from this study that the EOs from the stembark of C. sativa contain promising compounds, such as Cannabinol, Cannabidiol, and Linalool, which might be responsible for the displayed antioxidant activity of the oils. Thus, the study findings underscore the biological importance of C. sativa stembark in the management of oxidative stress-related conditions.”
“Cannabis compounds are well-known for their therapeutic applications in the treatment of various health issues.
These substances, mainly cannabinoids, are known for their antimicrobial properties and ability to interact with various cells through endocannabinoid receptors. However, the limitations of cannabis extract, particularly its viscosity, stickiness, and low bioavailability when applied topically, limit its use in dermatology.
To enhance topical applications for treating bacterial infections and dermatophytosis, cannabis extracts were encapsulated in chitosan nanoparticles, an easily accessible and cost-effective. Cannabis extracts were prepared from three cannabis strains differing in content of major cannabinoids, namely Chocolope (THCA-A), Jonas 1 (CBDA), and Hemp G (CBGA), and subsequently were encapsulated in chitosan nanoparticles. The resulting particles were characterized, and antimicrobial and cytotoxic activity was evaluated. The mean size of particles ranged from 89.1 ± 24.8 nm for empty nanoparticles to 355.6 ± 101.6 nm for particles containing Hemp G extract. Considering the extract:chitosan ratio (1:10 w/w, 1:20 w/w respectively) and the encapsulation efficiency (EE) range from 44.65 ± 4.39% to 94.44 ± 0.93%, total amount of extracts encapsulated in chitosan nanoparticles ranged from 2.96 ± 0.05 to 5.61 ± 0.19% in 1 g of chitosan nanopowder.
Most significant antimicrobial effect was observed against the fungi Nannizzia fulva CCF 6025, where the MIC80 of the pure extract from Jonas 1 variety was 256 μg/mL while the encapsulated extract in chitosan nanoparticles (1:10 w/w extract:chitosan ratio) inhibited growth at a concentration of 256 μg/mL of nanoparticles (corresponding to 13.05 ± 0.13 μg/mL of extract).
Overall, encapsulation reduced the amount of extract required to inhibit the growth of pathogenic microorganisms by up to several times, notably in case of dermatophytes, compared to non-encapsulated extracts. Encapsulation also reduced the cytotoxic effects of the extracts on human keratinocytes. Furthermore, pure high-THCA-A extract and encapsulated extract in chitosan nanoparticles slightly increased cell viability after 72 h exposure in low concentrations compared to control.
These results may suggest the chitosan nanoparticles-encapsulated formulations as a suitable topical delivery form of cannabis extracts, offering a possible adjunctive treatment of dermatophytosis and wound healing.”
“Background: Alcohol and cannabis co-use is increasingly prevalent across the U.S., concomitant with trends towards recreational cannabis legalization. While some studies have shown that cannabis co-use is associated with reductions in alcohol consumption (i.e., substitution), others have observed increases in alcohol intake (i.e., complementarity) or no change. This study aims to address this gap in the literature through investigating the effects of legal-market cannabis on alcohol consumption and craving in the laboratory.
Method: Leveraging a within-subjects design, we enrolled non-treatment seeking individuals who use both alcohol and cannabis (n = 61) to complete two laboratory sessions, wherein they were provided an alcohol priming drink alone or after self-administering cannabis. Participants were then given the opportunity to self-administer up to 4 additional drinks. We assessed differences in alcohol self-administration and craving between sessions.
Results: Cannabis self-administration was associated with a significant reduction in number of drinks self-administered. Further, exploratory analyses revealed that individuals who drank less after using cannabis (“substituters”, n = 23) experienced reductions in craving after using cannabis and alcohol compared to alcohol alone, whereas individuals who drank the same number of drinks after using cannabis show minimal differences in craving. There were no significant group differences in blood-THC concentration post-cannabis use.
Conclusion: Results indicate that for some individuals who drink heavily, cannabis may serve as a substitute for alcohol, and craving reduction is a potential mechanism through which this could occur.”
“Rationale: Between periods of use, chronic cannabis consumers may display residual effects on selective cognitive functions, particularly memory and attention. Whether there are comparable deficits in real-world behaviors, such as driving, has not been thoroughly examined.
Objectives: The current study explored the association between driving simulator performance, cannabis use history, and demographic factors after ≥ 48 h of abstinence. Study I examined simulator performance across a broad range of use within 191 healthy cannabis users. Study II compared performance between participants with the highest cannabis use intensity and a non-cannabis-using comparison group.
Methods: In Study I, 191 healthy cannabis users completed a 25-minute simulated drive, following ≥ 48 h of abstinence. In Study II, a pilot study comprising a subset of 18 frequent cannabis users was compared to 12 non-using controls who completed identical driving measures in a separate study. In both studies, the main outcome was the Composite Drive Score (CDS), a global measure of driving performance comprising key driving-related variables, including standard deviation of lateral position.
Results: In Study I, there was no relationship between CDS, its subtests, measures of cannabis use history, or demographic variables (all ps > 0.10). In Study II, frequent cannabis users and the non-using comparison group did not differ on CDS or performance on its subtests (all ps > 0.40).
Conclusions: The current study did not find evidence of a residual effect of cannabis on simulated driving performance during a short period of cannabis abstinence. Future studies would benefit from inclusion of larger non-cannabis-using comparison groups.”
“Cannabis use has grown both recreationally and medicinally in the United States over the past decades, alongside increased legalization and social acceptance. However, there remains little research investigating the effects of preoperative cannabis use on postoperative pain in patients undergoing surgery.
We conducted a single-center prospective study in adults undergoing cardiac surgery via sternotomy. Patients seen for preoperative consultation in clinic were asked a standardized survey about cannabis use. Clinical data was collected via chart review. Primary outcomes were morphine equivalents in the first 48 hours postoperatively and Visual Analog Scale (VAS) scores. Secondary outcomes were time to extubation, postoperative nausea/vomiting, ICU length of stay (LOS), reoperation, and in-hospital mortality. The non-cannabis user group had 50 patients, and the cannabis user group had 23 patients.
Average morphine equivalents in the first 48 hours were similar between cannabis users and non-users (60.98 vs 59.90; P = 0.93), as were VAS scores at 24 hours (5.52 vs 4.84; P = 0.414) and 48 hours (4.74 vs 3.90; P = 0.23). Average time to extubation (minutes) was nearly identical between cannabis users and non-users (718.41 vs 718.67; P = 0.99). There was also no significant difference in average LOS (days) between cannabis users and non-users (2.91 vs 3.48; P = 0.26). There were no differences in postoperative nausea/vomiting, reoperation, or in-hospital mortality.
In patients undergoing cardiac surgery via sternotomy, there was no effect of cannabis use on any outcomes, including morphine equivalents, Visual Analog Scale scores, time to extubation, ICU length of stay, postoperative nausea or vomiting, reoperation, or in-hospital mortality.”
