Category Archives: Uncategorized

Nanotechnology for the Efficacious Delivery of Medicinal Cannabis and Pharmaceutical Medicines

Posted on by
Reply
pubmed logo

“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.”

https://pubmed.ncbi.nlm.nih.gov/41011252/

“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.”

https://www.mdpi.com/1424-8247/18/9/1385

Tetrahydrocannabivarin (THCV) Dose Dependently Blocks or Substitutes for Tetrahydrocannabinol (THC) in a Drug Discrimination Task in Rats

Posted on by
Reply
pubmed logo

“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.”

https://pubmed.ncbi.nlm.nih.gov/41008636/

“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.”

https://www.mdpi.com/2218-273X/15/9/1329

Cannabizetol, a Novel Cannabinoid: Chemical Synthesis, Anti-inflammatory Activity and Extraction from Cannabis sativa L

Posted on by
Reply
pubmed logo

“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.”

https://pubmed.ncbi.nlm.nih.gov/40994228/

“Several cannabinoids have demonstrated biological activities, making Cannabis sativa particularly attractive as a source of potential medicinal active principles.”

https://pubs.acs.org/doi/10.1021/acs.jnatprod.5c00826

Chemical Composition and Antioxidant Activity of the Stembark Essential Oils of Two Cannabis sativa L. Cultivars from Komga, South Africa

Posted on by
Reply
pubmed logo

“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.”

https://pubmed.ncbi.nlm.nih.gov/40943472/

https://www.mdpi.com/1422-0067/26/17/8552

Chitosan nanoparticles-encapsulated cannabis extracts and their antimicrobial potential against skin pathogens

Posted on by
Reply
pubmed logo

“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.”

https://pubmed.ncbi.nlm.nih.gov/40917837/

https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1644502/full

Cannabis administration is associated with reduced alcohol consumption: Evidence from a novel laboratory co-administration paradigm

Posted on by
Reply
pubmed logo

“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.”

https://pubmed.ncbi.nlm.nih.gov/40915022/

“Cannabis use was associated with a reduction in alcohol intake.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871625003138?via%3Dihub

Short-term residual effects of smoked cannabis on simulated driving performance

Posted on by
Reply
pubmed logo

“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.”

https://pubmed.ncbi.nlm.nih.gov/40913146/

https://link.springer.com/article/10.1007/s00213-025-06880-1

Effect of Preoperative Cannabis Use on Postoperative Pain and Outcomes Following Cardiothoracic Surgery

Posted on by
Reply
pubmed logo

“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.”

https://pubmed.ncbi.nlm.nih.gov/40905360/

https://journals.sagepub.com/doi/10.1177/10892532251374952

Dietary Cannabidiol Supplementation on Growth Performance, Behavior, Blood Profile, Metabolomic Analysis, and Fatty Acid Composition in Rabbits: A Multi-Disciplinary Approach to Improve Welfare and Productivity

Posted on by
Reply
pubmed logo

“This study evaluated the effects of dietary cannabidiol (CBD) supplementation on behavior, blood parameters, oxidative status, metabolomic profile, and the fatty acid composition of meat and liver in rabbits.

A total of 42 New Zealand White × California rabbits (60 days old; 1:1 sex ratio; average weight 1621.3 ± 46.2 g) were randomly assigned to two groups (a control group, CTRL, and a CBD group, n = 21 each). Both groups received the same commercial diet, with the CBD group additionally supplemented with 0.1 mL of cannabis extract in coconut oil, corresponding to 10 mg CBD/animal/day. At 92 days of age, rabbits were slaughtered, and samples were collected for analyses.

Results showed that CBD supplementation significantly improved body weight gain, reduced plasma triglyceride levels, and enhanced oxidative status.

Behavioral observations indicated increased motor and grooming activities in CBD-supplemented animals, suggesting enhanced psychological well-being. The fatty acid profile of meat and liver was not significantly altered by CBD supplementation.

Overall, dietary CBD demonstrated the potential to positively influence physiological and behavioral responses, representing a promising strategy to enhance animal welfare and productivity in rabbit farming. Although no adverse effects on lipid profiles were observed, further studies are warranted to explore CBD’s role in lipid metabolism and cholesterol regulation.”

https://pubmed.ncbi.nlm.nih.gov/40905739/

“Animal health and welfare are essential for ethical farming and high-quality food production. This study evaluated the effects of dietary cannabidiol (CBD) supplementation on behavior, some blood parameters, and fatty acid composition in meat and liver of rabbits. CBD is gaining attention for its pharmacological properties and its role in the endocannabinoid system. The results suggest that CBD supplementation can influence behavioral and physiological responses in rabbits, offering potential benefits for both animal welfare and meat quality.”

https://www.mdpi.com/2306-7381/12/8/759

[Low Abuse Potential of Plant-Derived Highly Purified Cannabidiol: A Narrative Review]

Posted on by
Reply
pubmed logo

“Cannabidiol (CBD) is an abundant phytocannabinoid extracted from Cannabis sativa L., along with delta-9-tetrahydrocannabinol.

Plant-derived, highly purified CBD oral solution (100 mg/mL) is approved as Epidiolex® in the United States and as Epidyolex® in Europe for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex with country-specific labels.

CBD appears to reduce the neuronal hyperexcitability through a multimodal mechanism of action, although the precise mechanism remains unknown. Notably, unlike delta-9-tetrahydrocannabinol, CBD has low affinity for the euphoria-inducing cannabinoid receptor type 1 therefore lacks euphoric effects.

Preclinical and clinical studies have demonstrated a low abuse and dependence potential, as well as an absence of withdrawal syndrome of CBD.

Despite the lack of abuse potential for CBD, there are concerns related to cannabis and consequently cannabis-derived pharmaceutical products in Japan. Plant-derived, highly purified CBD is currently under investigation for the treatment of drug-resistant seizures in Japanese patients with early-onset epilepsies (jRCT2031220041).

This narrative review aims to update healthcare professionals in Japan with results from preclinical and clinical studies evaluating the abuse and dependence potentials of CBD.”

https://pubmed.ncbi.nlm.nih.gov/40887246/

https://www.jstage.jst.go.jp/article/yakushi/145/9/145_25-00086/_article/-char/ja/