“Objective: This study aims to evaluate preclinical studies on the effects and toxicity of cannabis-derived compounds against Plasmodium sp.
Methods: A literature search was conducted in Web of Science, PubMed, Scopus and LILACS databases until December 2024. Studies that assessed the activity or toxicity of cannabis against Plasmodium sp. in in vitro or in vivo studies were included. Two reviewers independently performed the study selection, data extraction and methodological assessment.
Results: Eight studies published between 2001 and 2022 were included, with the majority conducted in North America (n = 5). Most in vitro studies focused on assessing antimalarial activity through half-maximal inhibitory concentration (IC50), which ranged from 0.16 to 4.1 μg/mL, indicating mild to high activity.
For the in vivo studies, all reported positive effects, including moderate antimalarial activity and disease tolerance. The toxicity profile of these compounds has not been extensively studied, and most studies present an unknown or unclear risk of bias due to insufficient methodological information.
Conclusions: Future studies should provide more comprehensive details on study design and further validate these findings, especially concerning toxicity.”
“Introduction: Cannabis sativa L. has been used for thousands of years to treat intestinal and uterine diseases and as an anti-inflammatory, analgesic, and antiepileptic, among others. This study aimed to conduct preclinical studies based on the ethnopharmacological properties of C. sativa.
Methods: For this purpose, the police and health authorities provided the raw plant material, and a crude ethanolic extract of the aerial parts of C. sativa (APCs) was produced, which was subsequently chemically analyzed using combined chromatographic and spectrometric methods. Subsequently, APCs were administered to Swiss mice and Wistar rats for evaluation using the open field test, acetic acid-induced abdominal contraction model, hot plate test, formalin test, carrageenan-induced paw edema, Saccharomyces cerevisiae-induced fever, and primary dysmenorrhea models.
Results: Chemical analysis suggests the presence of classic cannabinoids, such as cannabidiol, tetrahydrocannabinol, and cannabigerol, as well as flavonoids and alkaloids. The doses used in the open field test were 1, 3, 10, 30, and 100 mg/kg (gavage, po), with the last two doses responsible for reducing mobility and inducing hypothermia in the animals. In subsequent pharmacological protocols, the doses used were 1, 3, and 10 mg/kg (gavage, po). In the abdominal contraction model, the number of writhing events was reduced by APCs at a dose of 10 mg/kg [median 0.5 (Q25 = 0; Q75 = 5.75, p < 0.05)]. In the hot plate test, the doses of 1, 3, and 10 mg/kg increased the latency time to 17.67 ± 1.33, 18.50 ± 1.31, and 17.33 ± 1.69 s (p < 0.05), respectively. In the formalin test, the effect was restricted to the first phase, with values of 42.33 ± 7.588, 45.50 ± 6.657, and 39.50 ± 7.869 s (p < 0.05) in paw-licking time. In paw edema, the doses of 1 and 3 mg/kg were more constant, restricting the volume to 0.168 ± 0.004 and 0.150 ± 0.004 mL (p < 0.05), respectively. In dysmenorrhea, the doses of 3 and 10 mg/kg reduced abdominal contractions [0 (Q25 = 0; Q75 = 3.0) and 1.0 (Q25 = 0; Q75 = 3.0)].
Conclusion: APCs at the tested doses did not promote an antipyretic effect. These data indicate that APCs have antinociceptive, anti-inflammatory, and anti-dysmenorrheal effects in animal models.”
“Cannabis sativa L. is a plant from the family Cannabaceae and one of the oldest to be domesticated in the world, with its use dating back to approximately 12,000 years in the Central Asian region.”
“C. sativa has a variety of indications in traditional medicine, in the most diverse forms of use (tea, smoke, vapor, etc.), and is used as a wound healing agent, analgesic, anticonvulsant, hypnotic, tranquilizer, anesthetic, anti-inflammatory, antibiotic, antiparasitic, antispasmodic, digestive, appetite stimulant, diuretic, aphrodisiac, antitussive, and expectorant.”
“Our results suggest that APCs contain classic cannabinoids, flavonoids, and alkaloids, and that classic cannabinoids, THC, and CBD are present. The administration of APCs promoted behavioral changes in the animals consistent with the pharmacological effects of these substances, such as reduced ambulation and hypothermic effect at doses of 30 and 100 mg/kg. In pharmacological studies, antinociceptive, anti-inflammatory, and anti-dysmenorrheal effects were observed in different experimental models and in the 1–10 mg/kg dose range; however, the APCs failed to show an antipyretic effect at these doses.”
“Previous studies reported that the acid congener of the cannabinoids, cannabidiolic acid, was approximately 1000 times more effective than the neutral congener, cannabidiol, in alleviating emesis.
The biological actions of cannabinoids were proposed to be mediated by the enhancement of somatodendritic 5-HT1A receptors. However, to date, the potential mechanism that may be involved in the enhancement of the 5-HT1A activity by the acid congener is still lacking. To address this gap, molecular docking and molecular dynamics simulations were performed on different pairs of neutral and acidic cannabinoids in a human 5-HT1A receptor model.
Analyses showed that simulated cannabinoid acids (cannabidiolic acid and tetrahydrocannabivarinic acid) and tetrahydrocannabivarin were preferentially bound at the allosteric site of 5-HT1A and were able to maintain the receptor in its active state when a full agonist, R(+)-8-OH-DPAT, was bound at the orthosteric site. Importantly, these results also suggest that the strong activity of cannabidiolic acid is not due to its strong affinity for the 5-HT1A receptor but its positive allosteric modulation of the agonist activity on 5-HT1A, presumably by blocking the exit of the orthosteric ligand, hence promoting continuous activation of the receptor. This study also demonstrates that cannabidiol and both neutral and acidic cannabigerol prefer binding at the orthosteric site and are potential partial agonists of 5-HT1A.
In conclusion, these findings propose that every cannabinoid, regardless of whether neutral or acidic, is unique on its own in terms of its binding and function.”
“Importantly, these findings indicate that every individual cannabinoids, regardless of neutral or acid congeners, is unique on its own and deserves its investigation, on its binding, function and therapeutic potential.”
“Objectives: With growing cannabis use in the US, it is crucial to understand the impact of recreational use on sinonasal diseases like chronic rhinosinusitis (CRS), allergic rhinitis (AR), and chronic rhinitis (CR).
Methods: This cross-sectional study leveraged the NIH AllOfUs database to query patient surveys assessing cannabis usage frequency (lifetime never, monthly, weekly, or daily within the past 3 months) and consumption route (smoking or non-smoking). Cannabis users were matched to never users for demographics, healthcare visit frequency, and insurance. A stringent logistic regression model calculated odds ratios (OR) of developing AR, CRS, or CR after survey completion. Cox regression hazard ratios (HR) compared consumption routes.
Results: Twenty-five thousand one hundred sixty-four cannabis users were matched with 113,418 never users. Users demonstrated significantly lower odds of AR, CRS, and CR than never users. For CRS, the ORs compared to never users are as follows: daily users 0.64 (95% CI 0.53-0.78), weekly users 0.61 (95% CI 0.48-0.77), and monthly users 0.80. For AR, the ORs were 0.64 (95% CI 0.58-0.71) for daily users, 0.62 (95% CI 0.54-0.71) for weekly users, and 0.69 (95% CI 0.58-0.80) for monthly users. For CR, the ORs were 0.61 (95% CI 0.47-0.79) for daily users, 0.64 (95% CI 0.47-0.87) for weekly users, and 0.41 (95% CI 0.26-0.65) for monthly users. There was no significant difference between smokers and non-smokers (HR 0.64, 95% CI 0.27-1.5).
Conclusion: There is an inverse, associative relationship between cannabis use and sinonasal disease. This relationship is insufficiently understood, and there remain significant concerns about the impact of cannabis use, especially smoking, on airway pathologies.”
“This is the largest study to specifically comment on the association between cannabis use and three of the most common sinonasal diseases—AR, CRS, and CR. We found lower odds of AR, CRS, and CR in patients who use cannabis compared to those who do not, which is strengthened by the size of our cohorts and by incorporating demographic and comorbidity information in our analysis. Route of consumption did not change CRS incidence. “
“Cannabigerol (CBG) is a non-psychoactive phytocannabinoid with an antioxidant and anti-inflammatory properties.
Because CBG has a promising pharmacological profile involving activation of α2adrenergic and peroxisome proliferator-activated γ (PPARγ) receptors it may have relevance in the pharmacotherapy of cardiovascular diseases.
Cannabigerol was also effective in lowering blood pressure in normotensive mice. In addition, it has been shown that cannabinoids can exhibit vasorelaxant effects in various vascular beds, and another plant cannabinoid-cannabidiol-has been shown to be effective in attenuating the development of pulmonary arterial hypertension.
In view of these reports, the aims of our study were to investigate whether CBG, exhibits a vasorelaxant effect on human pulmonary arteries (hPAs), to determine the mechanisms of CBG’s potentiating effects and to assess the influence the selected clinical factors and patients’ comorbidities on the vascular response induced by CBG.
Our study reports that CBG relaxes hPAs, and post-hoc analysis has shown that this response can be modified by hypertension and hypercholesterolaemia. We showed that the vasorelaxant effect of CBG depends on the vascular endothelium and the following mechanisms are involved: 1) cyclooxygenase-dependent pathway, 2) nitric oxide-dependent pathway, 3) voltage- and calcium-dependent K+ channels and 4) probably cannabinoid type 1 and 2, PPARγ, G-protein-coupled 55 and transient receptor potential vanilloid 1 receptors.
At all, CBG appears to be a possible vasorelaxant agent, but its therapeutic efficacy may vary based on the patient’s condition and comorbidities. CBG’s mild vasorelaxant property may provide an added benefit in addition to its anti-inflammatory and antioxidant properties in hemp preparations.”
“In conclusion, this study reports for the first time that CBG causes a vasorelaxant effect in hPAs. This effect is primarily mediated by vascular endothelium-dependent mechanisms. CBG-induced vasorelaxation was mediated by the 1) COX-1/COX-2-dependent pathway, 2) NO-dependent pathway, 3) voltage- and calcium-dependent K+ channels and 4) probably by the CB1, CB2, PPARγ, GPR55 and TRPV1 receptors.
This study provides evidence that CBG may be a potentially important agent with vasorelaxant effect, but its therapeutic efficacy may be modified by the patient’s condition and comorbidities. In addition to the well-documented anti-inflammatory and antioxidant properties, the mild vasorelaxant effect of CBG may be an additional advantage in the context of the use of hemp preparations.”
“Background: Impaired inhibitory control has been observed in regular cannabis users. Theories suggest that regular cannabis use is maintained by reward-driven behaviour, which may be underpinned by adaptations in neural reward and inhibitory control systems, thus increasing vulnerability to dependency.
Aims: This study investigated neural correlates of cannabis cue-specific inhibitory control in regular cannabis users and non-users using functional near-infrared spectroscopy (fNIRS).
Methods: Thirty regular cannabis users and thirty non-user controls completed two inhibitory control tasks (Go/No/Go and Stop-Signal Task), and a measure of attentional bias (Cannabis Stroop task). fNIRS recorded prefrontal and orbitofrontal haemodynamic responses (oxygenated haemoglobin and deoxygenated haemoglobin). Group comparisons and exploratory regressions examined cannabis use characteristics as predictors of behavioural and neural outcomes.
Results: No significant group differences were found in behavioural performance or haemodynamic activity across tasks. Exploratory regressions showed no significant associations between cannabis use characteristics and behavioural or neural outcomes after adjusting for covariates.
Conclusions: No evidence of impaired inhibitory control, attentional bias, or differences in prefrontal function were found in non-dependent cannabis users. Future studies should investigate whether such deficits emerge with heavier or dependent use.”
“In summary, this study found no significant differences in behavioural performance or neural activation between regular cannabis users and non-user controls during cue-specific inhibitory control tasks.”
“This review aims at highlighting the interplay between the endocannabinoids (eCBs) anandamide and 2-arachidonoylglycerol, and sphingosine-1-phosphate (S1P) signaling. The eCBs and S1P are bioactive compounds that exemplify a paradigm of crosstalk among lipid signals, with profound implications for physiological processes and disease pathogenesis.
Cross-communication between eCBs and S1P occurs through multiple mechanisms: (i) receptor heterodimerization and co-regulation, (ii) mutual metabolic modulation, and (iii) integrated regulation of downstream effectors. The latter emerged as a key mechanism underlying the bidirectional interactions between eCBs and S1P, with functional overlaps that regulate several processes including inflammation, vascular function, and neuronal activity.
In addition, cannabis-derived compounds (such as cannabidiol) can influence eCBs and S1P signaling, calling for further research into their therapeutic exploitation.
Overall, the dynamic interplay between endogenous eCBs and S1P – as well as with exogenous cannabidiol – described here offers a compelling example of the complexity of interactions among bioactive lipids. A deeper mechanistic understanding of these relationships could pave the way to novel strategies in drug design and development, emphasizing the importance of integrated approaches in the study of bioactive lipid biochemistry.”
“In conclusion, it seems apparent that eCB and S1P signaling pathways operate through interconnected networks of remarkable complexity. As yet, the biochemical crosstalk between these bioactive lipids remains incompletely understood, potentially limiting the therapeutic exploitation of these signals. Future strategies targeting the spatiotemporal dynamics of lipid transport – from intracellular trafficking to extracellular distribution – combined with selective receptor engagement, may unlock novel therapeutic opportunities that current approaches have not fully realized.”
“Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, shows promise as a therapeutic agent for conditions associated with inflammation and oxidative stress, often involving nitric oxide (NO) signaling dysregulation.
This review summarizes preclinical and clinical data on CBD’s impact on nitric oxide synthase (NOS) isoforms and NO levels in cardiovascular, neurological, metabolic, and immune systems.
Studies suggest that CBD can reduce inflammation-induced inducible NOS (iNOS) expression while maintaining or enhancing endothelial NOS (eNOS)-mediated NO production, leading to decreased oxidative stress, improved endothelial function, and reduced neuroinflammation.
The effects of CBD vary based on dose, formulation, timing, and disease state, with potential interactions with metabolites and other drugs affecting safety. Further research is needed to determine optimal dosing, formulation, pharmacokinetics, metabolite profiles, and long-term safety for specific conditions.”
“In summary, the ongoing exploration of CBD’s interaction with NOS and its broader implications for human health underscores the need for rigorous scientific inquiry. As we continue to unravel its potential, the integration of cannabinoid-based therapies into mainstream medical practice could revolutionize approaches to treating chronic diseases characterized by inflammation and oxidative stress.”
“These findings suggest that CBD may serve as a promising cannabinoid-based therapeutic agent in treating chronic diseases associated with inflammation and oxidative stress. Overall, the review underscores the need for further research to explore the clinical applications of CBD and its mechanisms in various health scenarios, paving the way for evidence-based treatments that harness the therapeutic potential of cannabinoids.”
“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.”
