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Motherhood and medicinal cannabis

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“Introduction: Women are emerging as a key demographic for medicinal cannabis (MC) use in countries that have implemented MC reforms. However, research on mothers’ experiences of consuming MC remains limited beyond studies on perinatal outcomes. This study explores mothers’ diverse experiences of consuming MC in New Zealand under the legal MC scheme.

Methods: Interviews with 15 mothers using MC via prescriptions, the illegal market or both in the last 12 months. Thematic analysis focused on MC use in parenting, MC conversations with children, societal stigma and risks.

Results: Mothers reported MC as an important facilitator of their ability to positively parent their children, enabling them to manage their own health needs (i.e., anxiety, endometriosis and arthritis). High costs of legal products hindered access to MC. Participants expressed unique risks that mothers face accessing the unregulated market for MC like being deemed a ‘bad mother’ and losing custody of children. Stigma was countered with narratives of empowerment through proactive MC conversations with children and agency by self-medicating with MC despite the judgement they may face for being a parent that uses cannabis.

Discussion and conclusions: Mothers felt managing their health with MC allowed them to be more present parents and better tolerate the stressors of motherhood. In-depth exploration of discussing MC with children and anticipating these conversations was a novel finding. Most mothers tried to destigmatise MC in conversations by classifying it in the same category as other medications and discussing its therapeutic benefits. Few were cautious about having these conversations too early.”

https://pubmed.ncbi.nlm.nih.gov/39967064/

“This study has provided insights into MC use among mothers, highlighting perceived therapeutic benefits for managing the unique stressors of motherhood and health and wellbeing in general. The findings illustrate the global legalisation of MC as a possible catalyst for shifting attitudes towards cannabis use in parenting, and a trend of women exercising agency in their health using complementary alternative therapies.”

https://onlinelibrary.wiley.com/doi/10.1111/dar.14027

Cannabidiol reshapes the gut microbiome to promote endurance exercise in mice

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“Cannabidiol (CBD), a nonpsychoactive compound from Cannabis, has various bioactive functions in humans and animals.

Evidence suggests that CBD promotes muscle injury recovery in athletes, but whether and how CBD improves endurance performance remains unclear.

Here we investigated the effects of CBD treatment on exercise performance in mice and assessed whether this effect involves the gut microbiome.

CBD administration significantly increased treadmill running performance in mice, accompanied by an increase in oxidative myofiber composition. CBD also increased mitochondrial biogenesis and the expression of associated genes such as PGC-1α, phosphorylated CREB and AMPK in muscle tissue. Interestingly, CBD altered the composition of the gut microbiome, and antibiotic treatment reduced the muscle endurance-enhancing effects of CBD and mitochondrial biogenesis.

We isolated Bifidobacterium animalis, a microbe increased by CBD administration, and named it KBP-1. Treatment with B. animalis KBP-1 in mice resulted in improved running performance. Whole-genome analysis revealed that B. animalis KBP-1 presented high expression of genes involved in branched-chain amino acid biosynthesis, expression of branched-chain amino acid release pumps and metabolism of lactic acid.

In summary, our study identified CBD and B. animalis KBP-1 as potential endurance exercise-promoting agents.”

https://pubmed.ncbi.nlm.nih.gov/39966566/

“In summary, we propose that both CBD and the gut bacteria B. animalis KBP-1, which is increased by CBD treatment, could be used in strategies to promote endurance exercise performance.”

https://www.nature.com/articles/s12276-025-01404-5

The role of cannabinoid-mediated signaling pathways and mechanisms in brain disorders

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“Cannabinoids play significant roles in the central nervous system (CNS), but cannabinoid-mediated physiopathological functions are not elaborated. Cannabinoid receptors (CBRs) mediate functions that include the regulation of neuroinflammation, oxidative stress, apoptosis, autophagy, and neurogenesis.

Microglia are the primary immune cells responsible for mediating neuroinflammation in the CNS. Therefore, this article primarily focuses on microglia to summarize the inflammatory pathways mediated by cannabinoids in the CNS, including nuclear factor-κB (NF-κB), NOD-like receptor protein 3 (NLRP3) inflammasome, mitogen-activated protein kinase (MAPK), protein kinase B (Akt), and cAMP-dependent protein kinase (PKA) signaling pathways. Additionally, we provide a table summarizing the role of cannabinoids in various brain diseases.

Medical use of cannabinoids has protective effects in preventing and treating brain diseases; however, excessive and repeated use can be detrimental to the CNS. We propose that cannabinoids hold significant potential for preventing and treating brain diseases, including ferroptosis, lactate metabolism, and mitophagy, providing new insights for further research on cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/39952540/

“Cannabis plants were historically used by pharmacologists as drugs to treat diseases in ancient India and China. Cannabinoids are natural compounds extracted from the cannabis plant. The most well-known component of cannabis is delta-9-tetrahydrocannabinol (delta9-THC)”

“This article reviews the role of cannabinoids in signaling pathways, including NF-κB, the NLRP3 inflammasome, MAPK, and AKT. Cannabinoids primarily combat neuroinflammation through CB2R-mediated signaling. Additionally, we discuss the effects of cannabinoids on oxidative stress, apoptosis, autophagy, and neurogenesis. Numerous studies demonstrate the neuroprotective effects of cannabinoids”

https://www.sciencedirect.com/science/article/abs/pii/S089865682500066X?via%3Dihub

Cannabidiol restores hematopoietic stem cell stemness in mouse through Atf2-Lrp6 axis after acute irradiation

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“Bone marrow serves as the residence of hematopoietic stem cells and is recognized as one of the most radiosensitive tissues. Exposure to acute radiation leads to severe damage to bone marrow hematopoiesis which can be fatal, while few clinically applicable medication or specific therapeutic targets have been discovered.

In this study, we found that the administration of cannabidiol significantly enhanced individual survival and restored the reconstitution capacity of bone marrow hematopoietic stem cells within 14 days after irradiation.

Single-cell RNA sequencing analysis demonstrated that the expression levels of genes associated with stemness along with Wnt and BMP signaling pathways were restored by the cannabidiol treatment through the upregulation of Atf2, a transcription factor possessing multifunctional properties. Atf2 upregulation induced by cannabidiol treatment potentially upregulated the expression of Lrp6 to improve the stemness of hematopoietic stem cells. Further functional experiments validated the crucial role of Atf2 in regulating multilineage differentiation potential of bone marrow hematopoietic stem and progenitor cells.

Overall, our findings provide evidence for a promising radioprotective function of cannabidiol and Atf2 as a candidate therapeutic target for acute radiation-induced hematopoietic injury, thereby paving the way for future research in the field.”

https://pubmed.ncbi.nlm.nih.gov/39949985/

“Cannabidiol (CBD) is the primary non-psychoactive chemical from Cannabis Sativa and an important component of hemp seed, a traditional Chinese medicine with a long history of application. Based on its multiple function, CBD has been investigated in fields of nervous system diseases, analgesic therapy, aging, anti-tumor therapy, and so on.2 In this study, we first assessed the potential role of CBD in preventing and treating acute irradiation-induced hematopoietic injury in bone marrow. Using single-cell RNA sequencing and functional assay, we dissected molecular alterations and potential mediator under CBD-treatment which led to the facilitated recovery of the HSC function. Collectively, this work strongly supports the therapeutic application of CBD in irradiation-induced bone marrow hematopoietic injury and highlights Atf2 as a promising therapeutic target herein.”

https://onlinelibrary.wiley.com/doi/10.1002/mco2.70092

The Presence of the Endocannabinoid System in an In Vitro Model of Gorham-Stout Disease and Its Possible Role in the Pathogenesis

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“Gorham-Stout syndrome (GSD), also known as disappearing bone disease, is an extremely rare bone disorder, characterized by a huge bone loss, which is followed by a lack of new matrix deposition and an excessive proliferation of both blood vessels and lymphatics. Unfortunately, the biological causes of GSD are still unknown. Recent studies that have tried to understand the etiopathogenesis of GSD have been principally focused on the vascular and osteoclastogenic aspects, not considering the possibility of a lack of osteoblast function. Nowadays, a diagnosis is still difficult, and is often made by exclusion of the presence of other pathologies, as well as on radiological evidence, and finally confirmed by histological examination. Treatment also remains a critical issue for clinicians today, who mostly try to control the progression of the disease.

Over the last two decades, clear evidence has emerged that the endocannabinoid system plays an important role in bone metabolism, leading scientists to hypothesize that it could be involved in physiological and pathological bone processes. In this work, we analyzed the presence of the ES in a primary cell line of human mesenchymal stem cells derived from a GSD patient for the first time, to understand if and how this complex network may play a role in the pathogenesis of the syndrome.

Our preliminary results demonstrated that the ES is also present in the pathological tissue. Moreover, the qRT-PCR analysis showed an altered expression of the different ES components (i.e., CNR1, CNR2, TRPV1, and GPR55). We observed an upregulation of CNR1 and TRPV1 expression, while the opposite trend was noticed for CNR2 and GPR55 expression. Thus, these results could lead us to speculate that possible deregulation of the ES may play an important role in the lack of bone regeneration in GSD patients. However, further studies will be necessary to confirm the role of the ES in the progression of GSD and understand whether the natural components of Cannabis Sativa could play a therapeutic role in the treatment of the disease.”

https://pubmed.ncbi.nlm.nih.gov/39940911/

“In conclusion, this is only a preliminary study, and further future analyses are needed to understand the role of the ES during osteogenic differentiation better and to try to comprehend what the molecular mechanisms involved in GSD pathogenesis are. In addition to this, the demonstration that the ES is present in our GSD in vitro model could pave the way to a study of the effects of the natural components of Cannabis Sativa as possible future new molecules that could be useful in the treatment of GSD and other bone diseases.”

https://www.mdpi.com/1422-0067/26/3/1143

Acute and prolonged toxicity assessment of Cannabis sativa extract in rodents and lagomorphs

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“Cannabinoids offer a novel pharmacotherapeutic approach and can complement other medications to address unmet clinical needs in numerous patients, which has led to a global increase in the use of these products.

No significant safety concerns have been identified in preclinical studies involving CBD and THC. However, the available data on the toxicity of combined CBD and THC are still inconclusive. Evaluating full-spectrum Cannabis sativa extracts is even more complex since whole extracts and isolated phytomolecules do not act in the same way.

Given the growing interest in cannabinoid-containing products for human use and the fact that most cannabis treatments utilize entire inflorescence rather than isolated compounds, the current studies aim to evaluate the preclinical safety of a full-spectrum composition (THC, CBD, minor cannabinoids, terpenes, and flavonoids) Cannabis sativa extract (CSE).

This research includes acute (single dose, with animals monitored for 14 days to assess potential effects) and long-term treatments (6 months for rodents and 9 months for rabbits) to assess safety and tolerance.

This study demonstrates that a full-spectrum Cannabis sativa extract has a favorable safety profile in both acute and prolonged toxicity studies in rodents and rabbits.

In acute toxicity tests, the extract did not show any significant behavioral or physiological changes after oral or intraperitoneal administration. Additionally, administering the extract acutely to rabbits had minimal impact on the central nervous, cardiovascular, and respiratory systems, with only a temporary reduction in motor activity at the highest dose.

Prolonged administration of 6 months in rats and 9 months in rabbits did not lead to significant changes in organ histopathology, body weight, or behavior.

Although liver enzymes were elevated at the highest doses, other biochemical and hematological parameters remained unchanged. CSE was well-tolerated, as no serious adverse effects were observed; however, a reduction in motor activity was noted in the highest dose group, highlighting the need for further investigation, which is proposed for future studies.”

https://pubmed.ncbi.nlm.nih.gov/39917037/

https://www.sciencedirect.com/science/article/pii/S2214750025000368?via%3Dihub

Cannabidiol protects lung against inflammation and apoptosis in a rat model of blunt chest trauma via Bax/Bcl-2/Cas-9 signaling pathway

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“Purpose: This study aimed to investigate the hypothesis that cannabidiol (CBD), with known anti-inflammatory and anti-apoptotic effects, would reduce the severity of acute lung injury in pulmonary contusion following blunt chest trauma.

Methods: Forty male Wistar Albino rats were randomly divided into four groups, each consisting of 10 rats: Sham, Trauma, Trauma + CBD, and CBD. The rats were treated with a single dose of 5 mg/kg CBD intraperitoneally 30 min before trauma. Then, the trauma were exposed to a weight of 200 g and a height of 1 m. After sacrifice, the lung tissues were removed for histopathological, immunohistochemical, biochemical, and genetic analyses.

Results: Pulmonary injury of trauma group led to increases in tumor necrosis factor α, caspase-3, caspase-9, Bcl-2-associated X protein expressions, total oxidant status, oxidative stress index levels, and decreases in B-cell lymphoma expression and total antioxidant levels. Additionally, inflammatory cell infiltration, damage-related emphysema, pronounced hyperemia, and increased septal tissue thickness were observed histopathologically. CBD treatment ameliorated all these findings.

Conclusion: CBD reduces lung damage in lung contusions caused by blunt chest trauma through its anti-inflammatory and antiapoptotic effects. More detailed studies investigating other important intracellular pathways are needed.”

https://pubmed.ncbi.nlm.nih.gov/39918746/

“In conclusion, it has been observed that CBD reduces lung damage in lung contusions caused by blunt chest trauma through its anti-inflammatory and antiapoptotic effects. In addition, the effects of a single dose of CBD were examined in this study, and more detailed molecular studies are needed in which longer-term use or higher doses are preferred, in addition to this study, which highlights the acute effects of CBD. The ability to perform analyses at the gene level at the protein level via the western blot method will increase the effectiveness of the study.”

https://link.springer.com/article/10.1007/s00068-025-02767-0

Advances in cannabinoid receptors pharmacology: from receptor structural insights to ligand discovery

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“The medicinal and recreational uses of Cannabis sativa have been recognized for thousands of years.

Today, cannabis-derived medicines are used to treat a variety of conditions, including chronic pain, epilepsy, multiple sclerosis, and chemotherapy-induced nausea. However, cannabis use disorder (CUD) has become the third most prevalent substance use disorder globally.

Cannabinoid receptors are the primary targets that mediate the effects of cannabis and its analogs. Despite their importance, the mechanisms of modulation and the full therapeutic potential of cannabinoid receptors remain unclear, hindering the development of the next generation of cannabinoid-based drugs.

This review summarizes the discovery and medicinal potential of phytocannabinoids and explores the distribution, signaling pathways, and functional roles of cannabinoid receptors. It also discusses classical cannabinoid drugs, as well as agonists, antagonists, and inverse agonists, which serve as key therapeutic agents.

Recent advancements in the development of allosteric drugs are highlighted, with a focus on positive and negative allosteric modulators (PAMs and NAMs) that target CB1 and CB2 receptors. The identification of multiple allosteric sites on the CB1 receptor and the structural basis for allosteric modulation are emphasized, along with the structure-based discovery of ago-BAMs for CB1.

This review concludes by examining the future potential of allosteric modulators in cannabinoid drug development, noting that ongoing progress in cannabinoid-derived drugs continues to open new avenues for therapeutic use and paves the way for future research into their full medicinal potential.”

https://pubmed.ncbi.nlm.nih.gov/39910211/

https://www.nature.com/articles/s41401-024-01472-9

The effects of recreational cannabis laws on alcohol and tobacco use among US adults, 2012 to 2022

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“Introduction: Many states have legalized cannabis for medicinal and recreational purposes in the past decade. However, it is unclear how recreational cannabis laws (RCLs) may affect alcohol and tobacco use among adults.

Methods: This is a cross-sectional study of 4.8 million adults from the 2012-2022 Behavioral Risk Factor Surveillance System. A difference-in-differences approach was used to examine the impact of RCLs on the use of alcohol and tobacco, adjusting for individual-level characteristics and time-varying state-level factors. The analyses were performed in 2024.

Results: Three alcohol use outcomes (current drinking, binge drinking, and heavy drinking) and two tobacco use outcomes (current tobacco use and smokeless tobacco use) were examined. Considering passage of cannabis laws as RCL implementation,

RCLs were not associated with any alcohol or tobacco use outcomes in the fully adjusted model. However, considering operational dispensary as RCL implementation, RCLs were associated with a decrease of 0.95 percentage point (95% CI, 1.80 to 0.09) in current drinking and a decrease of 0.48 percentage point (95% CI, 0.85 to 0.10) in current cigarette use.

Subgroup analysis showed that RCLs were associated with reductions in current drinking, binge drinking, and current cigarette use in multiple groups. However, RCLs were associated with increases in current smokeless tobacco use for some groups.

Conclusions: The findings suggest that while the overall effects of RCLs on the use of alcohol and tobacco may be limited, there are heterogeneous associations of RCLs with drinking and smoking by age, sex, race and ethnicity, education, and income.”

https://pubmed.ncbi.nlm.nih.gov/39909135/

https://www.ajpmonline.org/article/S0749-3797(25)00038-8/abstract

Cannabidiol-Induced Autophagy Ameliorates Tau Protein Clearance

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“Tau is a neuronal protein that confers stability to microtubules; however, its hyperphosphorylation and accumulation can lead to an impairment of protein degradation pathways, such as autophagy. Autophagy is a lysosomal catabolic process responsible for degrading cytosolic components, being essential for cellular homeostasis and survival.

In this context, autophagy modulation has been postulated as a possible therapeutic target for the treatment of neurodegenerative diseases.

Studies point to the modulatory and neuroprotective role of the cannabinoid system in neurodegenerative models and here it was investigated the effects of cannabidiol (CBD) on autophagy in a human neuroblastoma strain (SH-SY5Y) that overexpresses the EGFP-Tau WT (Wild Type) protein in an inducible Tet-On system way.

The results demonstrated that CBD (100 nM and 10 µM) decreased the expression of AT8 and total tau proteins, activating autophagy, evidenced by increased expression of light chain 3-II (LC3-II) protein and formation of autophagosomes.

Furthermore, the cannabinoid compounds CBD, ACEA (CB1 agonist) and GW-405,833 (CB2 agonist) decreased the fluorescence intensity of EGFP-Tau WT; and when chloroquine, an autophagic blocker, was used, there was a reversal in the fluorescence intensity of EGFP-Tau WT with CBD (1 and 10 µM) and GW-405,833 (2 µM), demonstrating the possible participation of autophagy in these groups.

Thus, it was possible to conclude that CBD induced autophagy in EGFP-Tau WT cells which increased tau degradation, showing its possible neuroprotective role. Hence, this study may contribute to a better understanding of how cannabinoids can modulate autophagy and present a potential therapeutic target in a neurodegeneration model.”

https://pubmed.ncbi.nlm.nih.gov/39900844/

“CBD induces autophagy promoting tau clearance in an in vitro model of tauopathy. Moreover, CBD, ACEA and GW-405,833 decreased tau expression, which was reversed by chloroquine indicating that autophagy participates in tau clearance.

Our results support the relevance of cannabinoid compounds in the autophagic process involved in the degradation of accumulated tau, which has been associated with several neuropathies. Therefore, autophagy is a potential therapeutic target of cannabinoids in neurodegenerative diseases.”

https://link.springer.com/article/10.1007/s12640-025-00729-3