“Chronic pain lasting more than three months or persisting after normal healing is a significant global health issue. In a healthcare system, it is crucial to ensure proper chronic pain management. Traditional pharmacological and non-pharmacological pain management techniques may not fully meet the requirements of physicians regarding effectiveness and safety. Therefore, researchers are exploring natural analgesics.
Plant-based phytoconstituents show promise in relieving chronic pain associated with various diseases.
This study aims to review the latest advances in discovering natural bioactive compounds that can help alleviate chronic pain. It discusses the pathways of chronic pain and a multifactorial treatment strategy. It also organizes data on using plant- derived substances, such as cannabinoids, terpenoids, phenolics, and crude extracts. Additionally, it delves into the pharmacodynamics of cannabinoids, including their route of administration and elimination.
The review presents the results of 22 clinical trials on various cannabinoids for pain relief. It is important to note that opioids and other alkaloids from plants are not covered in this article due to their primary use in controlling acute rather than chronic pain.”
“Cannabis sativa L., a member of the Cannabaceae family, has been thoroughly investigated for its diverse therapeutic properties, primarily attributed to cannabinoids such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Secondary, metabolites like terpenes also exhibit pharmacological effects.
This study examined the genotoxicity of a whole Cannabis sativa flower extract 160.32 mg/mL using three OECD-recommended protocols: the Ames test, micronucleus test, and comet assay. Five groups of six Wistar rats were used. Three doses of the extract (500, 1000, and 2000 mg/kgbw) or negative control (placebo) were administered orally, while cyclophosphamide monohydrate (20 mg/kgbw) was used as a positive control via intraperitoneal injection. Blood was collected for the comet test, and the animals were euthanized for bone marrow collection for the micronucleus test.
The Cannabis extract did not increase the number of revertant bacterial colonies at (375, 250, 125, and 62.5 μg/plate) in TA100 or TA98, nor did it affect the number of micronucleated polychromatic erythrocytes (MNPCEs) or the ratio of polychromatic to normochromatic erythrocytes (PCEs/NCEs). It also did not alter the index or frequency of DNA damage in hematopoietic cells.
These results suggest no genotoxic effects, supporting its potential therapeutic use.”
“Cannabis sativa extract shows no significant genotoxic effects in tested models.”
“Study supports therapeutic use of whole Cannabis sativa extract.”
“Background: Cannabinoids are considered a therapeutic option to patients suffering from treatment refractory chronic pain (TRCP) insufficiently relieved by conventional analgesics or experiencing intolerable adverse events (AEs) from those. This study aimed to explore safety and effectiveness of oral cannabinoids among patients with TRCP.
Methods: A retrospective study was conducted among Danish patients with TRCP being prescribed oral cannabinoids. Data on AEs and changes in pain intensity by numeric rating scale (NRS) before and after initiation of oral cannabinoid therapy were analysed.
Results: Among 826 eligible patients ≥18 years old, 529 (64%) were included for data analysis at first follow-up (F/U1) (median 56 days from baseline) and 214 (26%) for second follow-up (F/U2) (median 126 days from F/U1). Mean age was 60 ± 15.9 years and 70% were females. AEs were in general reported mild to moderate by 42% of patients at F/U1 and 34% at F/U2. AEs were mainly related to gastrointestinal (F/U1: 17% and F/U2: 13%) and nervous system disorders (F/U1: 14% and F/U2: 11%). Reduction in NRS was significantly different at both follow-up consultations compared with baseline (<0.0001). Clinically relevant pain reduction (NRS ≥30%) was reported by 17% at F/U1 and 10% of patients at F/U2 in intention-to-treat analysis whereas the figures were 32% and 45% respectively, in per-protocol analysis.
Conclusion: Oral cannabinoid therapy seems to be safe and mildly effective in patients with TRCP. Randomized controlled trials with focus on comparable pain characteristics in diagnostical homogenous patient subgroups are needed for further improvement of evidence level for relief of chronic pain using oral cannabinoids.
Significance: The findings in this retrospective study conducted in a real-world clinical setting suggest a favourable safety profile of cannabinoids. Moreover, one-sixth (intention-to-treat) and one-third (per-protocol) of patients with chronic pain refractory to conventional analgesics, or experiencing intolerable adverse effects, benefited significantly from therapy with oral cannabinoid regimens. Combination of THC and CBD seems overall more effective than cannabinoid monotherapy. Conduction of randomized controlled trials investigating safety and efficacy of cannabinoid therapy to diagnosis specific patient subgroups with comparable clinical and pathophysiological chronic pain characteristics is warranted, hence contributing further to the process of clinical evidence clarification currently in progress.”
“In conclusion, oral cannabinoid therapy in general appears to be safe and effective for relief of chronic pain in some patients, including a subset of patients with cancer-related pain (9%), not responding adequately to conventional treatment regimens or experiencing intolerable AEs. Moreover, beneficial effects on sleep and QoL were reported by the patients receiving oral cannabinoid therapy, although the assessment was not performed in a validated manner. Hence, our study confirms previously reported findings related to patients with chronic pain receiving oral cannabinoid therapy and in that way the study contributes further to the evidence pyramid at the level of observational studies. “
“Trichomoniasis, a globally prevalent sexually transmitted infection caused by Trichomonas vaginalis, affects approximately 278 million people each year. It presents a challenge due to resistance to the current treatment, Metronidazole (MTZ), which is also associated with side effects.
Cannabis sativa, with more than 100 phytocannabinoids and numerous studies for therapeutic applications, including parasitic infections, has undergone a significant shift in acceptance worldwide, highlighted by legalizations and substantial revenue projections.
In this context, the present study delves into the effects of cannabinoids, specifically WIN 55,212-2 (WIN), Cannabivarin (CBV) showcasing their anti-parasitic actions that influence the growth and morphology of T. vaginalis. The analysis extends to encompass the pharmacokinetic properties of these cannabinoids.
Among the analyzed cannabinoids, CBV stands out for adhering to Lipinski’s rules, indicating its potential suitability for oral drug delivery. They also demonstrated inhibitory effects on the growth of T. vaginalis trophozoites and a reduction in the parasite’s adhesion to host cells. Several morphological alterations were observed, such as membrane projections, blebbing, autophagosomes and damaged hydrogenosomes.
These results highlight the need for further research to explore the therapeutic potential of cannabinoids and understand their mechanisms of action in T. vaginalis.”
“The treatment of trichomoniasis faces significant challenges, primarily due to the limited options and drug resistance issues associated with nitroimidazole derivatives like Metronidazole. However, exploring alternative therapeutic approaches is crucial. One promising avenue is the use of C. sativa and its compounds which have demonstrated anti-parasitic properties. In conclusion, cannabinoids inhibit T. vaginalis proliferation and alter its morphology, warranting further research into their therapeutic potential and mechanisms of action. Such exploration could revolutionize the current understanding and treatment of parasitic infections, offering new hope for combating these persistent pathogens.”
“Introduction: Diabetic peripheral neuropathy (DPN) represents a prevalent neurological complication affecting millions of patients globally. This clinical investigation evaluated the therapeutic efficacy and safety profile of a novel transdermal medical cannabis formulation (THC:CBD:CBN) in treating painful DPN of the lower extremities.
Methods: This phase III, double-blind, placebo-controlled, randomized clinical trial was conducted at Don Chan Hospital, Thailand, enrolling 100 participants over a 12-week intervention period. Using a computer-generated randomization sequence, participants were allocated to receive either the standardized cannabis formulation or a matched placebo. The primary outcome measure comprised pain intensity assessment using the validated Thai version of the Neuropathic Pain Symptom Inventory (NPSI-T). Secondary outcomes encompassed treatment-emergent adverse events and dermatological manifestations. Statistical analyses were performed using SPSS Version 28.0, incorporating generalized estimating equation (GEE) modeling and Analysis of Covariance (ANCOVA). The study protocol received approval from the Institutional Review Board of Khon Kaen University and the Kalasin Provincial Public Health Office Ethics Committee, with trial registration in the Thai Clinical Trials Registry.
Results: The intervention group demonstrated statistically significant reductions in NPSI-T scores across all measured dimensions (p < 0.001). Mean total NPSI-T scores decreased markedly from 25.60 to 5.57 in the treatment cohort, contrasting with minimal reduction from 25.24 to 22.85 in the placebo group. GEE analysis revealed significant pain amelioration at weeks 4, 8, and 12 (p < 0.001). The cannabis formulation exhibited an excellent safety profile, with only 10% of participants reporting mild adverse events, comparable to placebo group outcomes.
Conclusion: This novel transdermal medical cannabis formulation (THC:CBD:CBN) demonstrated significant therapeutic efficacy in ameliorating painful DPN symptoms while maintaining a favorable safety profile. These findings provide robust clinical evidence supporting its potential as an innovative therapeutic option for managing painful DPN.”
“This randomized controlled trial provides robust evidence supporting the therapeutic efficacy and safety profile of transdermal THC:CBD:CBN formulation in the management of painful DPN. The demonstrated significant reduction in multidimensional pain scores, combined with the pharmacokinetic advantages of transdermal delivery and favorable safety outcomes, suggests substantial clinical potential for this therapeutic approach. As the evidence base continues to expand, cannabinoid-based interventions may emerge as a valuable therapeutic option in addressing the complex challenges of neuropathic pain management.”
“Objectives To report the findings of a case-series of 10 children suffering with intractable epilepsies in the UK to determine the feasibility for using whole-plant cannabis medicines to treat seizures in children.
Setting This study was conducted retrospectively through collecting clinical data from caretakers and clinicians on study outcome variables. Participants were recruited through the MedCann Support and End our Pain charity groups which are patient representative groups that support children who are using medical cannabis to treat their epilepsies. Medicines were prescribed to patients by clinicians in both National Health Service and private medical practices. Follow-up calls were conducted throughout the period January 2021 to May 2021 to keep data recorded up to date.
Participants Ten children, 18 years old or under, with intractable epilepsies were recruited from two charities. There were no limitations on diagnosis, sex or ethnic origin.
Interventions Participants were treated with a range of whole-plant medical cannabis oils. Individual dosing regimens were determined by clinicians.
Primary outcome measure The primary outcome measure was seizure frequency.
Results Seizure frequency across all 10 participants reduced by 86% with no significant adverse events. Participants reduced use of antiepileptic drugs from an average of seven to one following treatment with medical cannabis. We also noted significant financial costs of £874 per month to obtain these medicines through private prescriptions.
Conclusions This study establishes the feasibility of whole-plant medical cannabis as an effective and well-tolerated medicine for reducing seizure frequency in children suffering with intractable epilepsies. These findings justify the potential value of further research into the reported therapeutic benefit of whole-plant medicinal cannabis products.”
“African American (AA) men experience more than twice the prostate cancer mortality as White men yet are under-represented in academic research involving prostate-specific antigen (PSA), a biomarker of prostate cancer aggressiveness.
We examined the impact of self-reported tobacco (cigarette pack-years and current tobacco use including e-cigarettes) and current regular marijuana use on serum PSA level based on clinical laboratory testing among 928 AA men interviewed 2013-2018 in Chicago. We defined outcome of elevated PSA ≥ 4.0 ng/mL for logistic regression models and continuous PSA increases for general linear models. All models were adjusted for age, sociodemographic characteristics, healthcare utilization, body mass index, and self-reported health.
Among 431 AA men age ≥ 55 years, we observed ∼ 5 times the odds of elevated PSA among those with > 1 pack-years of cigarette smoking vs. never-smokers (odds ratio [OR] = 5.09; 95% confidence interval [CI] = 1.57-16.6) and a quarter the odds of elevated PSA among current marijuana users vs. non-users (OR = 0.27; 95% CI = 0.08-0.96). PSA increased on average 1.20 ng/mL among other current tobacco users vs. non-users.
Among older AA men, cigarette smoking history and current tobacco use were positively associated with an increase in PSA levels and current marijuana use were inversely associated with PSA levels.
Future work with studies of diverse patient populations with cancer outcomes are needed to assess whether these behavioral characteristics contribute to racial/ ethnic disparities in prostate cancer outcomes.
Our study provides novel evidence regarding potential differences in PSA levels among older AA men according to behavioral characteristics.”
“Atherosclerotic disease is the leading cause of death world-wide. Our goal was to explore the effect of phytocannabinoids on the molecular mechanisms triggering the development of the atheromatous lesion.
Three cannabis sativa extracts of different chemotypes were chemically characterized by UPLC-DAD. The capacity of the extracts to prevent the oxidation of LDL, the formation of foam cells and the activation of an inflammatory response by J774 cells, were monitored by UV-Vis spectrometry, confocal-microscopy and western blot. Three varieties of cannabis sativa, with high (E1), intermediate (E2) and low (E3) THC/CBD ratios were selected.
The three cannabis extracts inhibited the oxidation of LDL by copper ions and the formation of foam cells by J774.1 cells challenged with oxLDL (ED50 5-12 μg mL-1). The effect of the cannabinoid extracts on the endocytic process was independent of the canonical cannabinoid receptors, CB1 and CB2, but related to the action of non-canonical receptors (TRPV1, TRPV4 and GPR55), involved in calcium signaling. Decreased levels of CD36 and OLR1 scavenger receptors were, at least partially, responsible for the diminished uptake of oxLDL induced by phytocannabinoids. The downregulation of CD36 and OLR1 could be explained by the observed inhibitory effect of the cannabis extracts on the activation of the NFκB pathway by oxLDL.
Phytocannabinoids interfere with the main events leading to the development of the atheromatous plaque, opening new venues on atherosclerosis therapy.”
“Our results highlight the capacity of phytocannabinoids to ameliorate the processes leading to the development and progression of atherosclerotic lesions through inhibiting LDL oxidation, decreasing the formation of foam cells after oxLDL challenge and reducing scavenger receptor synthesis by interfering with NFκB activation, supporting the therapeutic potential of medicinal cannabis in atherosclerosis and the need to unravel the molecular mechanisms of phytocannabinoids on the cardiovascular system.”
“Cannabis sativa L. contains numerous compounds with antioxidant and anti-inflammatory properties, including the flavonoids and the cannabinoids, particularly Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).
Cannabinoids have an effect on the endocannabinoid system (ECS), a cellular communication network, and are, hence, widely studied for medical applications.
Epidiolex®, a 99% pure oral CBD extract, has been approved by the FDA for the treatment of epilepsy. Nabiximols (Sativex) is an oromucosal spray containing equal volume of THC and CBD, and it is commonly used as an add-on treatment for unresponsive spasticity in multiple sclerosis (MS) patients.
Several in vitro and in vivo studies have also shown that cannabinoids can be used to treat various types of cancer, such as melanoma and brain glioblastoma; the first positive clinical trials on the anticancer effect of a THC:CBD blend with temozolomide (TMZ) in the treatment of highly invasive brain cancer are very promising.
The cannabinoids exert their anticancer properties in in vitro investigations by the induction of cell death, mainly by apoptosis and cytotoxic autophagy, and the inhibition of cell proliferation. In several studies, cannabinoids have been found to induce tumor regression and inhibit angiogenic mechanisms in vitro and in vivo, as well as in two low-numbered epidemiological studies.
They also exhibit antiviral effects by inhibiting ACE2 transcription, blocking viral replication and fusion, and acting as anti-inflammatory agents; indeed, prior CBD consumption (a study of 93,565 persons in Chicago) has also been associated with a much lower incidence of SARS-CoV-2 infections.
It is postulated that cannabis extracts can be used in the treatment of many other diseases such as systemic lupus erythematosus, type 1 diabetes, or various types of neurological disorders, e.g., Alzheimer’s disease.
The aim of this review is to outline the current state of knowledge regarding currently used medicinal preparations derived from C. sativa L. in the treatment of selected cancer and viral diseases, and to present the latest research on the potential applications of its secondary metabolites.”
“C. sativa L. is an extraordinary plant that provides a valuable raw material for medical applications. Its secondary metabolites, cannabinoids, have attracted growing interest in the fight against illness, mainly due to their effect on CB1 and CB2 cannabinoid receptors.”
“Antibiotic resistance in staphylococcal strains and its impact on public health and agriculture are global problems. The development of new anti-staphylococcal agents is an effective strategy for addressing the increasing incidence of bacterial resistance.
In this study, ethanolic extracts of Cannabis sativa L. made from plant parts harvested during the whole vegetation cycle under various nutritional treatments were assessed for in vitro anti-staphylococcal effects.
The results showed that all the cannabis extracts tested exhibited a certain degree of growth inhibition against bacterial strains of Staphylococcus aureus, including antibiotic-resistant and antibiotic-sensitive forms. The highest antibacterial activity of the extracts was observed from the 5th to the 13th week of plant growth across all the nutritional treatments tested, with minimum inhibitory concentrations ranging from 32 to 64 µg/mL. Using HPLC, Δ9-tetrahydrocannabinolic acid (THCA) was identified as the most abundant cannabinoid in the ethanolic extracts. A homolog of THCA, tetrahydrocannabivarinic acid (THCVA), reduced bacterial growth by 74%.
These findings suggest that the cannabis extracts tested in this study can be used for the development of new anti-staphylococcal compounds with improved efficacy.”
“In summary, the present study demonstrated the antistaphylococcal activity of ethanolic extracts of C. sativa L. against both of the bacterial strains tested, MSSA and MRSA, across all the vegetation stages, especially from the 5th to the 13th week. The various nutritional treatments had no impact on the resulting antibacterial effect.”
