“Pain is one of the most pervasive health problems associated with a negative impact on thinking, mood, psychological, and social communication.
The medicinal plants and their derived compounds have recently attracted great interest as potential candidates for defeating pain because of their worldwide safety, availability, and affordability.
This review was constructed to summarize all in vitro and in vivo studies and clinical trials regarding plant-derived compounds’ analgesic and antinociceptive effects. Further, we focus on structural aspects, molecular mechanisms, and pharmacological effects. A literature survey was performed in “PubMed,” “Science Direct,” and “Google Scholar,” using the keywords “Pain, Analgesic activity, Flavonoids, Phenolics, Medicinal plants, Volatile oils, Tannins, Saponins, Alkaloids” to assess the activities of each compound.
The main natural compounds studied were flavonoids, alkaloids, phenolic acids, lignans, anthraquinones, and volatile oils. Different in vitro studies utilized nucleus pulposus cells, VK2/E6E7, End1/E6E7, and LPS-stimulated RAW264.7 cells to assess analgesic effects. The frequently defined animal models of analgesic activity included acetic acid-induced abdominal constrictions, hot-plate test, tail-flick test, formalin test, complete Freund’s adjuvant-induced pain, and hind paw incisional surgery.
For the natural compounds described, the opioids, serotonergic, and cannabinoid receptors appeared to be the most promising targets for pain management. This review suggested a wealthy resource of natural compounds as analgesic and antinociceptive candidates for pharmacists and drug researchers to launch a new drug with promising efficacy and safety.”
“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.”
“Medicinal cannabis has been the subject of extensive research, with recent studies demonstrating its potential in managing chronic pain and enhancing quality of life.
This case report examines the use of medicinal cannabis in a patient treated at the School of Dentistry of Araçatuba (FOA-UNESP). The patient, a 28-year-old female with no comorbidities, presented with chronic muscular TMD and reported poor sleep quality. Full-spectrum cannabis oil (1:1 ratio of THC to CBD), was prescribed for a period of 60 days, with a maximum dosage of 10 drops per day. Pain intensity was measured using the Visual Analog Scale (VAS), while sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Evaluations were conducted at three intervals: baseline, day 30, and day 60. To ensure patient safety, pre- and post-treatment blood tests were performed, and dosage adjustments were made every three days under the supervision of the study’s medical team.
The results revealed significant improvements in pain management, with the patient’s orofacial pain score decreasing from 7 to 3 on the NRS. Additionally, sleep quality improved, as reflected by a lower PSQI score (global sleep quality at level 6 at the end), indicating more restorative sleep. Throughout the treatment period, the patient experienced mild side effects, including drowsiness and gastrointestinal discomfort, which were effectively managed through dosage modifications.
In conclusion, full-spectrum cannabis oil shows promise as a therapeutic strategy for managing orofacial pain and improving sleep quality, providing significant relief in conditions where other interventions are ineffective or poorly tolerated. Further research is warranted to better understand the therapeutic mechanisms and potential side effects of medicinal cannabis in the management of chronic pain and related conditions.”
“In conclusion, the use of Full Spectrum Cannabis Oil in this case was associated with a clinically meaningful reduction in chronic orofacial pain and improvement in sleep quality, with no adverse effects or laboratory abnormalities observed during the treatment period. These outcomes suggest that individualized cannabinoid-based therapy may be a safe and effective approach for selected patients with temporomandibular disorders and comorbid sleep disturbances.”
“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.”
“Introduction: Endometriosis is a chronic inflammatory condition that affects around 1 in 7 women of reproductive age. Current medical treatments tend to be sub-optimal to manage the range of symptoms, with low levels of patient satisfaction. Cross-sectional and retrospective data suggests that people with endometriosis are consuming cannabis to help manage their symptoms.
Areas covered: This review discusses the evidence for consumption of medicinal cannabis to help manage endometriosis symptoms, including potential mechanisms of action from both animal models and human studies, usage in the community, the current evidence from clinical trials and observational studies, and the safety and potential drug interactions.
Expert opinion: While there is a lack of high-quality clinical trial evidence, significant self-reported evidence from cross-sectional surveys and retrospective observational data suggests that those consuming medicinal cannabis report reductions in endometriosis symptoms such as pelvic pain, dysmenorrhea and gastrointestinal symptoms, and improve mental health and sleep. Given the low levels of satisfaction with current treatment options, consideration should be given to trialing medicinal cannabis as part of the interdisciplinary management of endometriosis in those who express interest and who do not demonstrate any significant contraindications.”
“Less than 25% of women with endometriosis report satisfaction with current conventional treatments with high discontinuation rates due to ineffectiveness and side effects.
Dysregulation of the endocannabinoid system in endometriosis, including reduced CB₁ receptors and elevated endocannabinoid levels, provides biological plausibility for therapeutic intervention through TRPV1 modulation and PPARγ activation.
Cannabis consumption is associated with self-reported reductions in pain, gastrointestinal symptoms and nausea, and improvements in sleep quality and mental health.
Cannabis consumption is associated with reductions in potentially addictive medications such as opioids and benzodiazepines; however these reductions should be done under the guidance of a physician.
Despite promising preclinical data and substantial observational evidence, robust randomized controlled trial data in humans remains lacking, preventing recommendation of more widespread adoption as a treatment.”
“The favorable lipid profile of hemp seed could be a potential source of unsaponifiable matter rich in fat-soluble phytochemicals such as phytosterols, vitamin E, and cannabidiol (CBD). Despite its nutritional value, studies investigating the functional properties of hemp seed, particularly its anti-obesity potential, remain limited.
The aim of this study was to obtain unsaponifiable matter from hemp seed (HUSM), analyze its fat-soluble phytochemicals and evaluate its anti-obesity activity using both in vitro and in vivo experimental models.
The results showed that HUSM contained abundant carotenoids, vitamin E, phytosterols, policosanols, and CBD, with trace amounts of THC (0.06%), Furthermore, HUSM inhibited adipocyte differentiation and lipid accumulation in a dose-dependent manner, significantly reducing lipid accumulation by up to 79% without cytotoxicity in 3T3-L1 adipocytes.
HUSM treatment led to reduced abdominal size and body weight gain, decreased adipose tissue and liver size, and lower plasma triglycerides, total cholesterol, and LDL cholesterol levels. These effects were mediated through the AMPK signalling pathway, which plays a pivotal role in regulating adipogenesis and lipogenesis. Additionally, HUSM improved adipokine balance, reducing leptin and increasing adiponectin levels, indicating recovery of dysfunctional adipose tissues.
These findings highlight the potential of HUSM as a natural anti-obesity therapeutic, offering new avenues for the treatment and prevention of obesity and related metabolic disorders through the AMPK signalling pathway.”
“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.”
“Background: Behavioral and psychological symptoms of dementia (BPSD) affect patients’ and caregivers’ well-being. Cannabinoids may offer a promising therapeutic option for managing BPSD.
Aims: This systematic review aims to explore the strengths of using this class of substances in the context of dementia care.
Methods: We conducted a comprehensive search across Embase Ovid, PubMed, Cochrane Library, APA PsycInfo, and Web of Science, identifying 1839 studies, with 14 selected for full review. Quality was assessed using the Newcastle-Ottawa and the modified Jadad Scales.
Results/outcomes: Ten studies (278 participants) were finally included. They showed cannabinoids helped reduce agitation and nocturnal disturbances.
Conclusions/interpretation: In conclusion, cannabinoids show promise in managing BPSD in dementia, with good tolerability and safety. Further studies could solidify these findings.”
“Introduction: Chronic low back pain (CLBP) affects over half a billion people worldwide. Current pharmacologic treatments, comprising mainly non-steroidal anti-inflammatory drugs and opioids, offer limited efficacy and pose significant risks, warranting the development of tolerable, safe and effective alternatives.
Methods: This randomized controlled trial on adults with CLBP was designed to confirm the superior efficacy and gastrointestinal tolerability of VER-01, a novel, standardized full-spectrum extract from Cannabis sativa DKJ127 L., over opioids. Subjects were randomized (1:1) to receive VER-01 or a range of commercially available opioids. After a 3-week titration, subjects underwent 24 weeks of treatment, followed by 2 weeks of wash-out. The primary endpoint was the relative risk of constipation occurrence after 27 weeks treatment. Secondary endpoints included changes in pain and sleep scores, determined using an 11-point numeric rating scale (NRS), with key secondary endpoints defined for week 27.
Results: A total of 384 individuals were randomized to receive VER-01 (n = 192) or opioids (n = 192). Subjects receiving VER-01 were fourfold less likely to develop constipation than those receiving opioids (relative risk [RR] VER-01/opioids 0.25; 95% confidence interval [CI] 0.09-0.69; p = 0.007) and threefold less likely to use laxatives (RR 0.34; 95% CI 0.18-0.65; p < 0.001). Longitudinal analysis revealed that VER-01 was superior to opioids in terms of pain reduction over 6 months of treatment, although differences in secondary endpoints limited to week 27 alone were not significant. Throughout the 6 months of treatment, mean pain reduction was 2.50 NRS points with VER-01 versus 2.16 with opioids (mean difference [MD] 0.34; 95% CI 0.00-0.67; p = 0.048), and sleep improved by 2.52 points with VER-01 versus 2.07 with opioids (MD 0.45; 95% CI 0.11-0.79; p = 0.009). These benefits were particularly pronounced in participants with severe pain, with greater pain reduction (MD 0.58; 95% CI 0.01-1.15) and sleep improvement (MD 0.66, 95% CI 0.05-1.27) compared to opioids.
Conclusions: VER-01 demonstrated superiority over opioids in treating CLBP, both in terms of efficacy and gastrointestinal tolerability.”
“In summary, this study provides robust evidence that VER-01 offers better tolerability, as well as superior pain relief and sleep quality compared to opioids in patients with CLBP. These findings highlight its potential as a promising new pharmacological option within a multimodal treatment approach that could fundamentally shift the paradigm in the treatment of chronic pain.”
“Chronic low back pain (CLBP) affects over half a billion people worldwide. Current pharmacologic treatments offer limited efficacy and carry substantial risks, warranting the development of safe and effective alternatives.
This multicenter, randomized, placebo-controlled phase 3 trial evaluated the efficacy and safety of VER-01 in CLBP. It enrolled 820 adults with CLBP (VER-01, n = 394; placebo, n = 426) and included a double-blind 12-week treatment phase (phase A), a 6-month open-label extension (phase B), followed by either a 6-month continuation (phase C) or randomized withdrawal (phase D). The primary endpoint of phase A was a change in mean numeric rating scale (NRS) pain intensity, with a change in total neuropathic pain symptom inventory (NPSI) score as a key secondary endpoint in participants with a neuropathic pain component (PainDETECT > 18). The primary endpoint for phase D was time to treatment failure.
The study met its primary endpoint in phase A, with a mean pain reduction of -1.9 NRS points in the VER-01 group (mean difference (MD) versus placebo = -0.6, 95% confidence interval (CI) = -0.9 to -0.3; P < 0.001). Pain further decreased to -2.9 NRS points in phase B, with effects sustained through phase C.
The study also met its key secondary endpoint of phase A, with a mean NPSI decrease of -14.4 (standard error, 3.3) points from baseline in the VER-01 arm (MD versus placebo = -7.3, 95% CI = -13.2 to -1.3; P = 0.017). Although phase D did not meet its primary endpoint (hazard ratio = 0.75, 95% CI = 0.44-1.27; P = 0.288), pain increased significantly more with placebo upon withdrawal (MD = 0.5, 95% CI = 0.0-1.0; P = 0.034). In phase A, the incidence of adverse events-mostly mild to moderate and transient-was higher with VER-01 than with placebo (83.3% versus 67.3%; P < 0.001). VER-01 was well-tolerated, with no signs of dependence or withdrawal.
VER-01 shows potential as a new, safe and effective treatment for CLBP.”
