“Pain management costs the world billions of dollars each year, and there are limited nonopioid options to treat people suffering from chronic pain. Opioids are excellent analgesics but are liable to abuse and fatal overdoses. This Microperspective summarizes challenges and opportunities pertaining to creating nonopioid drugs that could be used to treat chronic pain, substance abuse, fatty liver, or obesity by targeting the cannabinoid receptor type 1 (CB1).”
“The endocannabinoid system (ECS) is essential for energy hemostasis, obesity, and other metabolic disorders.
Cannabidiol and polyunsaturated fatty acids (PUFAs), which are found in hemp seed oil (HSO), have been found to regulate adipose tissue through the ECS. Thus, human mesenchymal stem cells (hMSCs) were differentiated into pre-adipocytes and then treated with cannabidiol (CBD), tetrahydrocannabinol (THC), 0.05% HSO, or 0.1% HSO for 3 days (72 h).
The mixture was subsequently maintained in maintenance media for 14 days, after which the condition media (CM) was collected. In addition, THP-1 cells were used to assess the inflammatory response upon exposure to CM collected from different groups of experimental cells. Quantification for lipid accumulation (Oil red O), gene expression (RT‒qPCR), and protein levels (Western blot) were performed.
We found that HSO-treated cells matured toward brown-like adipose tissue with a spindle shape and decreased intracellular lipid accumulation. HSO treatment decreased the expression of genes associated with fat accumulation and browning (BAT), with the exception of UCP-1, which leans toward brown-like adipocytes. HSO treatment upregulated the cannabinoid receptors 2 (CB2), TRPV1, and GPCR55 mRNAs and leptin mRNA found with lower expression; no alterations were observed in cannabinoid receptors 1 (CB1), FAAH, and MGL mRNAs. In THP-1 macrophage, HSO treated CM decreased the expression of IL-6, IL-8, TNF-α, and leptin mRNAs significantly when compared to CBD and THC.
The potential of HSO in promoting brown fat characteristics through the CB2 and its effect on inflammation status offers an intriguing area for future research and therapeutic interventions.”
https://pubmed.ncbi.nlm.nih.gov/41258240
“Overall, the availability of balanced ratios of omega 3/omega 6 PUFAs and CBD in HSO favors in maintaining optimal ECS ligands in adipocytes. Our current study revealed that HSO treatment might promote the maturation of hMSC preadipocytes toward brown-like adipose tissue, which evident morphologically. ECS might mediate this effect, as HSO treatment downregulates the CB1 receptor and increases the CB2 receptor at the mRNA and protein levels. In addition, HSO treatment decreased inflammatory marker of IL-6, IL-8, TNF-α, and leptin compared to untreated cells; however, HSO treatment resulted in a minimalized the provoking of inflammatory cytokines compared with CBD and THC treatments in THP-1 cells. In conclusion, the potential of HSO in promoting the development of brown fat characteristics through the ECS and its effect on inflammation status offers an intriguing area for future research and therapeutic interventions.”
https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00343-2
(“-)-Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has been suggested to provide protective effects in neuronal systems. This work investigates its neuroprotective effect against rotenone, a mitochondrial complex I inhibitor that causes neuronal toxicity, using primary hippocampal neurons.
Rotenone treatment reduces neuronal viability with marked neurite degeneration in a concentration-dependent manner (LC50 = 189.1 nM). Administration of 2.5 µM CBD significantly increases viability to 69.9%, compared with 45.6% observed under 200 nM rotenone treatment.
Neuronal morphology is preserved under both CBD pre-treatment and co-treatment conditions, with confocal analyses further confirming the maintenance of axonal branching and overall structural integrity. Antagonist experiments reveal that TRPV1 inhibition markedly reduces the protective effect of CBD, whereas blockade of 5-HT1AR has only a minor influence.
These findings demonstrate that CBD protects primary hippocampal neurons from rotenone-induced toxicity, with TRPV1 playing a central role in the mechanism.”
https://pubmed.ncbi.nlm.nih.gov/41261085
“In summary, this study demonstrates that CBD effectively protects primary hippocampal neurons from rotenone-induced toxicity by maintaining neuronal viability and preserving neurite morphology. Both pre-treatment and co-treatment with CBD effectively attenuated rotenone-induced cell death, and morphological analyses confirmed the preservation of axonal branching and neuronal structure.
Consistent with our findings, several in vivo studies have reported that cannabis-derived phytocannabinoids attenuate oxidative stress and neuronal degeneration induced by rotenone administration in animal models. These in vivo observations reinforce the neuroprotective potential of CBD and further support our in vitro findings at the cellular level.”
https://aces.onlinelibrary.wiley.com/doi/10.1002/asia.202500946
“Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest and most treatment-resistant cancers, with limited progress in improving patient survival. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has emerged as a potential anticancer agent due to its diverse molecular effects in preclinical cancer models.
This systematic review aims to evaluate the preclinical and early clinical evidence regarding CBD’s anticancer effects in PDAC, with emphasis on its molecular mechanisms, therapeutic synergies, and translational feasibility.
We systematically searched PubMed, Scopus, Web of Science, EMBASE, and Google Scholar (2006–2025) for studies examining the effects of CBD on PDAC in vitro, in vivo, and in clinical contexts. Studies were assessed for methodological quality and relevance to CBD-related antitumor activity.
Fifteen studies met the inclusion criteria, including in vitro, animal, and limited clinical investigations. CBD exhibited antitumor properties via multiple pathways, such as CerS1-mediated ER stress and apoptosis, GPR55/MAPK inhibition, immune modulation, and chemosensitization to gemcitabine. Combination therapies (CBD with cannabinoids or chemotherapeutics) enhanced therapeutic outcomes in preclinical models. However, clinical evidence remains preliminary and insufficient to establish efficacy.
CBD demonstrates promising anticancer potential in PDAC through diverse molecular mechanisms and synergistic effects with chemotherapy. Nonetheless, significant translational barriers—including formulation variability, pharmacokinetics, and a lack of clinical trials—must be addressed. Further studies are warranted to validate these findings in human settings.”
https://pubmed.ncbi.nlm.nih.gov/41257868
“This systematic review provides a comprehensive synthesis of current evidence supporting cannabidiol (CBD) as a multifactorial anticancer agent in pancreatic ductal adenocarcinoma (PDAC).”
https://cancerci.biomedcentral.com/articles/10.1186/s12935-025-04062-9
“The use of minor cannabinoids has been advanced, in part, by the idea of providing relief from pain and inflammation without the burden of unwanted psychogenic effects associated with Δ 9 THC. In this regard, investigators have focused on the effects of minor cannabinoid activation / desensitization of peripheral sensory neurons on nociceptive signaling and/or peripheral inflammation.
With a focus on peripheral nociception, four common minor cannabinoids: cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN) and cannabichromene (CBC) were studied in primary cultures of mouse Dorsal Root Ganglion (DRG) neurons.
We queried if calcium responses induced by the four cannabinoids differed in potency of activation, neuronal size preference, and dose-response relationships. Additionally, we determined the dependence of CBD and CBN on key channel-receptors that are known to mediate pain and/or antinociception.
Individually, CBD, CBG and CBC directed greater response magnitudes when compared to CBN. All four minor cannabinoids activated overlapping but distinct size populations of sensory neurons. CBD and CBG activated the widest range of DRG neuron sizes (smaller-larger) overlapping with smaller capsaicin-sensitive neurons. In contrast, CBN and CBC activated predominantly larger sensory neurons. CBD diverged from other minor cannabinoids in directing a linear dose-response profile whereas CBG and CBC directed sigmoidal dose-response profiles and CBN activated DRG neurons with an inverted U-shaped dose-response relationship. CBD-induced activation of DRG neurons was dependent on co-expression of the nociceptive channel TRPV1 plus cannabinoid receptor 1 (CB 1 R), whereas CBN-induced activation was independent of TRPV1.
Overall, we observed that minor cannabinoids CBD, CBG, CBN and CBC differed in their activation of DRG neurons and directed unique activation properties across a diverse population of sensory neurons. Such differences underly the hypothesis that a combination (entourage) of complimentary minor cannabinoids can direct synergistic antinociceptive activity.”
“Objective: Cannabis use is strongly linked with heavy drinking and worse alcohol treatment outcomes; however, it may also contribute to decreased alcohol consumption. To date, no human studies have established a causal effect of cannabis on alcohol motivation. The aim of this double-blind crossover randomized clinical trial was to examine dose-dependent acute effects of delta-9-tetrahydrocannabinol (THC) on alcohol craving and consumption.
Methods: Across three experimental days, 157 participants reporting heavy alcohol use and cannabis use two or more times weekly were randomized to smoke cannabis cigarettes containing 7.2% THC, 3.1% THC, or 0.03% THC (placebo), followed by exposures to neutral and personalized alcohol cues and an alcohol choice task for alcohol self-administration. A total of 138 participants completed two or more experimental sessions (mean age, 25.6 years [SD=5.1]; 35% women; 45% racial/ethnic minorities). Primary outcomes included craving, Alcohol Craving Questionnaire-Short Form, Revised (ACQ-SF-R), and an alcohol urge question; the secondary outcome was percent of total available milliliters of alcohol consumed.
Results: There were no significant effects of cannabis on ACQ-SF-R ratings after smoking and during alcohol cue exposure, but 7.2% THC reduced alcohol urge immediately after smoking. Participants consumed significantly less alcohol after smoking cannabis with 3.1% THC and 7.2% THC, reducing consumption by 19% and 27%, respectively.
Conclusions: Following overnight cannabis abstinence, smoking cannabis acutely decreased alcohol consumption compared to placebo. Further controlled research on a variety of cannabinoids is needed to inform clinical alcohol treatment guidelines.”
https://pubmed.ncbi.nlm.nih.gov/41254853
“These data provide preliminary evidence that cannabis may reduce alcohol consumption under some conditions”
“Cannabis sativa L. (Cannabaceae) has long been valued in traditional medicine, including Ayurveda, for managing disorders such as diabetes, cancer, and kidney diseases.
Although the plant itself is known to influence glucose metabolism, the therapeutic potential of its associated endophytic fungi remains underexplored. In this study, 56 fungal isolates were obtained from different tissues of C. sativa and evaluated for antidiabetic activity.
Two isolates, identified by ITS1/4 rDNA sequencing as Aspergillus micronesiensis and Nodulisporium verrucosum, exhibited strong inhibitory effects on α-amylase, α-glucosidase, DPP-IV, and lipase (IC₅₀ < 100 µg/mL). Their ethyl acetate extracts demonstrated low cytotoxicity, enhanced cell viability, and significantly promoted insulin secretion in MIN6 pancreatic β-cells. GC-MS analysis revealed bioactive metabolites, including 1-butyl-4-tert-butylbenzene, 7,9-di-tert-butyl-1-oxaspiro (4,5) deca-6,9-diene-2,8-dione, 2-methylcinnamic acid, and tetraneurin-A, which are reported to possess antidiabetic potential. FTIR further confirmed the presence of functional groups corresponding to these compounds.
Together, these findings highlight C. sativa-derived endophytic fungi as promising sources of novel antidiabetic agents, bridging traditional knowledge with modern drug discovery.”
https://pubmed.ncbi.nlm.nih.gov/41249583
https://link.springer.com/article/10.1007/s00203-025-04539-1
“The term “endophytic fungi” refers to fungi that live in plant tissues throughout the entire or partial life cycle by establishing a mutually beneficial symbiotic relationship with its host plant without causing any adverse effect or disease.” https://pmc.ncbi.nlm.nih.gov/articles/PMC8877053/
“Endometriosis is a chronic, inflammatory, and multifactorial disease characterized by the presence of endometrial tissue outside the uterine cavity, often associated with debilitating symptoms. It affects approximately 10% of women of reproductive age and is also related to infertility. Endometriosis can be classified as peritoneal, ovarian, or deep endometriosis, with primary symptoms including chronic pelvic pain, dysmenorrhea, and dyspareunia. Diagnosis and treatment are challenging, with laparoscopy and biopsy of ectopic tissue being the gold standard.
Cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC) are two major cannabinoids found in the Cannabis sativa plant, widely known for their medicinal properties.
An experimental study conducted in rats demonstrated the anti-inflammatory, antioxidant, and antiangiogenic effects of intraperitoneal CBD use in the treatment of endometriosis. The objective of the present study was to conduct a literature review on the therapeutic potential of Cannabidiol (CBD) and ∆9-Tetrahydrocannabinol (THC) in the signs and symptoms of endometriosis. Research on PubMed, Embase, and Scopus platforms was conducted to determine the reproducibility and safety of treatment in humans, including dosage and administration route, as the current use is off-label.”
“Although obesogenic high-fat/high-sugar diets impair memory function in humans and rodents, the underlying mechanisms remain elusive. Given that the brain endocannabinoid system and type-1 cannabinoid receptors (CB1Rs) control memory processes and are overactive under obesogenic conditions, we studied whether the effects of obesogenic diet consumption on memory function are dependent on this system.
Using an object recognition memory (ORM) task in male mice, we showed that CB1R activity is required for obesogenic-diet-induced impairment of long-term memory performance. This impairment was prevented by post-training systemic blockade of CB1R, which also normalized training-induced hippocampal cellular and synaptic overactivation.
Consistently, the obesogenic diet potentiated the increase in hippocampal endocannabinoid levels and enhanced CB1R expression induced by ORM, and genetic CB1R deletion from hippocampal glutamatergic neurons abolished diet-induced memory deficits. Strikingly, the obesogenic diet enhanced the hippocampal mechanistic target of rapamycin (mTOR) pathway in a CB1R-dependent manner, and pharmacological mTOR inhibition after training rescued diet-induced ORM consolidation deficits.
Together, these results establish how an obesogenic environment can lead to hippocampal overactivation of the endocannabinoid system and the mTOR pathway to eventually impair memory consolidation. Thus, these results shed light on the mechanisms of diet-induced cognitive alterations and may pave the way for novel therapeutic strategies.”
https://pubmed.ncbi.nlm.nih.gov/41237773
“Foodomics Reveals Anti-Obesity Properties of Cannabinoids from Hemp Oil”
https://pubmed.ncbi.nlm.nih.gov/36382382
“Anti-obesity effect of unsaponifiable matter from hemp seed in 3T3-L1 adipocytes and high-fat diet-induced obese mice”
https://pubmed.ncbi.nlm.nih.gov/41047880
“Anti-Obesity diet drug from cannabis works!“
“Although tetrahydrocannabinol (THC) and cannabidiol (CBD) have been individually studied for their neuroprotective roles, few studies have addressed the effects of their balanced 1:1 formulation Satinex (STX) under pathologic conditions like hypoxia. Moreover, the effect of STX on embryonic neural stem/progenitor cells (ENS/PCs) derived from the rat embryonic brain, which are highly vulnerable during early development, remains unexplored.
Considering the pivotal role of hypoxia in numerous neuropathological situations, this study examined the impact of STX on rat ENS/PCs exposed to chemically induced hypoxia.
ENS/PCs were isolated from rat embryos and subjected to hypoxia using 100 µM cobalt (II) chloride hexahydrate (CoCl₂0.6 H₂O) for 48 h. Cytotoxic activity of STX andCoCl2was assessed using the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2 H-tetrazolium (MTT) assay, while stem cell identity was confirmed via flow cytometry (Nestin, SOX2). STX (0.1 and 0.5 µM) was applied under both normoxic and hypoxic conditions. Expression levels of hypoxia-inducible factor 1-alpha (Hif1α) mRNA, autophagy markers (Beclin-1, microtubule-associated protein 1 light chain 3-II [LC3-II]), and pro-inflammatory proteins nuclear factor kappa B [NF-κB], Toll-like receptor 2 [TLR2], Toll-like receptor 4 [TLR4]) were assessed using reverse transcription polymerase chain reaction (RT-PCR) and western blot techniques following STX treatment.
Based on flow cytometric assays, over 70% of cultivated cells were positive for Nestin and SOX2. Hypoxia significantly reduced cell viability and proliferation, accompanied by increased Hif1α mRNA expression. Treatment with STX (0.1 µM and 0.5 µM) significantly reversed these changes, restoring cell viability and proliferation while reducing Hif1α levels. Hypoxia also elevated autophagy markers (Beclin-1, LC3-II) and pro-inflammatory proteins (NF-κB, TLR2, TLR4), which STX suppressed in a dose-dependent manner.
This study provides novel evidence that STX mitigates hypoxia-induced neural damage by downregulating Hif1α and its downstream inflammatory and autophagic signaling pathways. The use of a clinically relevant cannabinoids mixture and a developmentally sensitive cell model underline the translational potential of balanced THC/CBD formulations in the treatment of hypoxia-related neurodegenerative and neurodevelopmental conditions.”
https://pubmed.ncbi.nlm.nih.gov/41240218
https://link.springer.com/article/10.1007/s12640-025-00770-2