Cannabis for female orgasmic disorder/difficulty: a systematic review

Posted on by
Reply
pubmed logo

“Background: Cannabis is increasingly recommended to treat female orgasmic disorder/difficulty (FOD/difficulty), a condition that affects up to 41% of women worldwide with no conventional medications.

Aim: To systematically review the existing literature on cannabis and its impact on female orgasm function.

Methods: A systematic review based on the PRISMA model evaluated the effects of cannabis on orgasm function in females with or without FOD/difficulty. Risk of bias was assessed for randomized and nonrandomized studies. Searches were conducted in PubMed, Google Scholar, Cochrane, and Embase.

Outcomes: Primary outcomes focused on the impact of cannabis on female orgasm function.

Results: Sixteen studies met inclusion criteria: 1 randomized controlled trial and 15 observational studies, including data from 8849 females. Most were nonrandomized designs without comparator groups and high risk of bias. Most included both sexes and reported dichotomized outcomes by sex. None excluded females with self-reported orgasm difficulty; 1 controlled for its prevalence; 1 dichotomized females by the presence or absence of orgasm difficulty; and no studies used a clinical diagnosis of FOD. Nine studies investigated cannabis use prior to sexual activity. All 9 studies cited improvements in female orgasm function, including increases in frequency, ease, intensity, quality, and/or multiorgasmic capacity. However, 1 study found cases of situational anorgasmia, and 1 reported that women had more difficulty with focus, potentially leading to orgasm difficulty. Two studies assessed general cannabis use and sexual function: 1 found no association between the frequency of cannabis use and female sexual problems, while the other noted improved orgasm and reduced dysfunction with more frequent use. Five studies examined cannabis alongside other substances, before sex or not: 1 linked inhibited orgasm to combined cannabis and alcohol use, 1 to noncannabis substances, 2 found improved orgasm function with cannabis, and 1 reported improved orgasm function and cases of inability to orgasm due to a lack of focus.

Clinical implications: Cannabis appears to be a promising treatment option for FOD/difficulty.

Strengths and limitations: This review found consistent evidence that cannabis improves orgasm function in females with or without FOD/difficulty. Limitations include insufficient high-quality studies and limited reporting on cannabis dosage and timing.

Conclusion: FOD/difficulty should be recognized as a qualifying condition for medical cannabis use. Given the existing evidence supporting its potential efficacy, medical cannabis warrants consideration as a first-line treatment. More randomized controlled trials are needed to clarify optimal dosing, routes of administration, strain specificity, timing of use, and differential effects across FOD subtypes.”

https://pubmed.ncbi.nlm.nih.gov/40808870/

“Cannabis appears to be a promising treatment for FOD/difficulty, with the majority of studies reviewed reporting improvements in orgasm function and satisfaction among women who use cannabis. These benefits were observed across diverse study designs, populations, and cannabis use contexts. Given this growing body of evidence, FOD/difficulty should be considered a qualifying condition for medical cannabis, and medical cannabis should be evaluated as a potential first-line treatment. These findings suggest a strong association between cannabis use and improved orgasm function, but further RCTs are needed to establish causality and better define key parameters, such as dosage, route of administration, timing of use, strain specificity, and the differential effects on FOD subtypes.”

https://academic.oup.com/smoa/article/13/4/qfaf061/8232583?login=false

Substance Abuse and Cognitive Decline: The Critical Role of Tau Protein as a Potential Biomarker

Posted on by
Reply
pubmed logo

“Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD).

Emerging evidence suggests that similar Tau-related alterations may occur in individuals with chronic exposure to psychoactive substances. This review compiles experimental, clinical, and postmortem findings that collectively indicate a substance-specific influence on Tau dynamics.

Alcohol and opioids, for instance, promote Tau hyperphosphorylation and fragmentation through the activation of kinases such as GSK-3β and CDK5, as well as proteases like caspase-3, leading to neuroinflammation and microglial activation. Stimulants and dissociatives disrupt insulin signaling, increase oxidative stress, and impair endosomal trafficking, all of which can exacerbate Tau pathology.

In contrast, cannabinoids and psychedelics may exert protective effects by modulating kinase activity, reducing inflammation, or enhancing neuroplasticity.

Psychedelic compounds such as psilocybin and harmine have been demonstrated to decrease Tau phosphorylation and facilitate cognitive restoration in animal models. Although the molecular mechanisms differ across substances, Tau consistently emerges as a convergent target altered in substance-related cognitive disorders.

Understanding these pathways may provide not only mechanistic insights into drug-induced neurotoxicity but also identify Tau as a valuable biomarker and potential therapeutic target for the prevention or treatment of cognitive decline associated with substance use.”

https://pubmed.ncbi.nlm.nih.gov/40806766/

“Alcohol, methamphetamine, and opioids consistently elicited Tau hyperphosphorylation in cortical and subcortical regions tied to executive function, reward processing, and memory. In contrast, certain cannabinoids and psychedelics demonstrated potential neuroprotective properties, modulating Tau-related signaling in ways that reduced aberrant phosphorylation and enhanced synaptic resilience in preclinical models. “

https://www.mdpi.com/1422-0067/26/15/7638

Cannabichromene: integrative modulation of apoptosis, ferroptosis, and endocannabinoid signaling in pancreatic cancer therapy

Posted on by
Reply
pubmed logo

“Cannabichromene (CBC: C21H3O2, M.W.: 314.46 g) is a non-psychotropic phytocannabinoid derived from Cannabis sativa (hemp), and its potential therapeutic properties have attracted increasing attention. Specifically, it has demonstrated strong anti-inflammatory effects in animal models of edema through non-CB receptor mechanisms; however, further pharmacological studies based on cancer models are required.

In this study, we investigated the molecular mechanisms underlying the anti-cancer activity of CBC in human pancreatic cancer cells.

Through mRNA-seq analysis, the expression levels of many genes involved in cell death pathways were upregulated or downregulated after CBC treatment, and these included ferroptosis-related genes, such as HMOX1. We further confirmed the functional validity of apoptosis and ferroptosis induction after CBC treatment using various molecular assays. In addition, CBC preferentially increased the expression of TRPV1 and CB2.

Accordingly, the effects on cell death were reversed after treatment with TRPV1 and CB2 inhibitors, suggesting that receptor expression is necessary for the induction of apoptotic cell death. Finally, we confirmed the consistent regulation of apoptosis, ferroptosis, and endocannabinoid receptors during tumor growth inhibition after CBC treatment using in vivo xenograft models.

Therefore, we propose that CBC exhibits pharmacological activity via the integrative modulation of multiple cell death pathways, which can be exploited for pancreatic cancer therapy.”

https://pubmed.ncbi.nlm.nih.gov/40790027/

“Cannabinoids extracted from Cannabis sativa exert their effects by binding to specific receptors that play a role in tissue development and homeostasis maintenance in the human body.”

“CBC treatment induces apoptotic cell death in pancreatic cancer cells”

“Our current study demonstrates that CBC modulates multiple forms of cell death by regulating the expression of proteins involved in both apoptotic and ferroptotic pathways. Although CBC-induced apoptosis was dependent on TRPV1 and CB2 receptors, the ferroptotic pathway appeared to be independent of these receptors.

Accordingly, we propose that CBC exerts its pharmacological effects through the integrative modulation of multiple cell death pathways, which could offer therapeutic benefits for pancreatic cancer treatment.

These results enhance our understanding of how CBC induces diverse cell death mechanisms via ECS receptors, not only in pancreatic cancer but also in other cancer models.

This study provides a promising foundation for the development of cannabinoid-based anti-cancer drugs, offering a new strategy for targeting various types of cancer through the modulation of apoptosis and ferroptosis.”

https://www.nature.com/articles/s41420-025-02674-8

The Endocannabinoid System in PTSD: Molecular Targets for Modulating Fear and Anxiety

Posted on by
Reply
pubmed logo

“Fear and anxiety perform essential protective roles, yet when they become dysregulated, they can trap trauma survivors in persistent hypervigilance and distress. Post-traumatic stress disorder (PTSD) manifests as intrusive memories, avoidance, and heightened arousal long after the precipitating event. Although current pharmacotherapies – including selective serotonin reuptake inhibitors, adrenergic blockers, benzodiazepines, and atypical antipsychotics – provide relief for some, many patients contend with residual symptoms or intolerable adverse effects.

Recent discoveries position the endocannabinoid system as a pivotal regulator of fear acquisition, consolidation, and extinction. Clinical observations of altered anandamide levels and cannabinoid receptor CB₁ upregulation in individuals with severe PTSD underscore the therapeutic potential of restoring endocannabinoid tone.

Preclinical studies demonstrate that direct CB₁ agonists, fatty acid amide hydrolase (FAAH) inhibitors, and phytocannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD) can facilitate extinction learning and attenuate anxiety-like behaviours.

Preliminary human trials report that nabilone alleviates trauma-related nightmares and that acute cannabinoid administration modulates amygdala reactivity to a threat. Yet optimal dosing strategies, sex-specific responses, and ideal THC:CBD ratios remain to be defined. Self-medication with cannabis can offer transient relief but carries a risk of cannabis use disorder and potential worsening of PTSD symptoms. By elucidating molecular targets – including CB₁, CB₂, FAAH, and monoacylglycerol lipase – this review outlines a strategic framework for next-generation cannabinoid-based interventions.

Harnessing the endocannabinoid system promises to expand the therapeutic arsenal for PTSD, offering hope for more effective and better-tolerated treatments.”

https://pubmed.ncbi.nlm.nih.gov/40789309/

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2647-8030

α-Glucosidase Inhibitors from the Leaves of Cannabis sativa: Structure-Activity Relationship, Kinetic Investigation, and Molecular Docking

Posted on by
Reply
pubmed logo

“Cannabis sativa L. is a valuable agricultural crop, extensively utilized in various fields and comprising diverse chemical constituents. In preliminary experiments for rat intestinal α-glucosidase inhibition, the methanolic extract of Cannabis sativa demonstrated potential for inhibiting maltase and sucrase. Bioassay-guided isolation led to 30 metabolites, including five new cannabinoids (1, 2, 3, 4, 30) and four new spiroindans (5, 6, 10, 11). Their structures were elucidated using spectroscopic techniques such as NMR, and absolute configurations were determined by Mosher’s method. Cannabinoids were the main contributors to inhibitory potency (IC50: 0.09-0.8 mM), while spiroindans and simple phenolics showed lower activity (IC50: 1.0-2.2 mM). 8-Hydroxycannabinol (18) was the most potent inhibitor retarding the enzymes through a noncompetitive mechanism. Molecular dynamics simulations of compounds 15 and 18 showed that hydrogen bonding between phenolic hydroxyl groups and specific amino acid residues at the allosteric site was essential for strong α-glucosidase binding.”

https://pubmed.ncbi.nlm.nih.gov/40788893/

“Cannabis sativa L., a member of the Cannabaceae family derived from Western Asia, has been grown for centuries for food, fiber, and medicine.”

“This study reveals that the leaves of Cannabis sativa are a prolific source of α-glucosidase inhibitors with cannabinoids, particularly cannabinol derivatives exhibiting the most pronounced bioactivity.

Among 30 isolated compounds, 8-hydroxycannabinol demonstrated the strongest inhibitory effect, outperforming other cannabinoids through an uncompetitive inhibition mechanism. Structure–activity relationship analysis indicated that additional phenolic hydroxyl groups and extended aromatic rings substantially enhance inhibitory potency.

Molecular docking and molecular dynamics simulations confirmed that active cannabinol derivatives bind stably to an allosteric site on the α-glucosidase enzyme, supported by favorable binding energies and consistent hydrophobic interactions. However, the limited structural diversity of the isolated compounds restricts the full elucidation of SAR trends, underscoring the need for broader analog libraries.

These findings not only highlight the therapeutic potential of C. sativa leaf cannabinoids as natural antidiabetic agents but also lay a foundation for future research. In particular, the semisynthesis of novel cannabinol derivatives via rational modifications such as halogenation or esterification represents a promising strategy to enhance α-glucosidase inhibitory activity and to systematically probe the structure–activity relationship of this pharmacophore class.”

https://pubs.acs.org/doi/10.1021/acs.jafc.5c08443

“Alpha-glucosidase inhibitors are a class of medications used to treat type 2 diabetes by slowing down the digestion and absorption of carbohydrates from the small intestine.”

Lifetime Cannabis Use and Incident Hypertension: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Posted on by
Reply
pubmed logo

“Background: Observational evidence investigating associations between cannabis use and hypertension is inconsistent.

Methods: The association between cumulative lifetime cannabis use (cannabis-years) and incident hypertension was examined over 35 years in a sample of CARDIA study (Coronary Artery Risk Development in Young Adults) participants free of hypertension at baseline. Marginal structural models with inverse probability weighting were used to adjust for potential time-dependent confounding and censoring. Hazard ratios and 95% CIs were estimated using Cox proportional hazards regression. Sensitivity analyses included modeling cannabis-years using restricted cubic splines, stratifying the primary analyses by sex, race, alcohol and cigarette smoking, and evaluating an additional exposure measure (days of use in the past month).

Results: The analytic sample consisted of 4328 participants at baseline and 64.9% (n=2810) at year 35. Median cannabis-years increased minimally and remained low across visits: 0.0 (Q1-Q3, 0.0-0.3) at baseline and 0.2 (Q1-Q3, 0.0-0.7) by year 35. There were 2478 cases of incident hypertension over 88 292 person-years (28.1 cases per 1000 person-years). Cannabis-years were not significantly associated with incident hypertension (adjusted hazard ratio, 0.99 [95% CI, 0.97-1.00]; P=0.18). The association remained unchanged in sensitivity analyses.

Conclusions: In a cohort of Black and White young adults with 35 years of follow-up, no association was found between cumulative lifetime use of cannabis and risk of incident hypertension. This finding was robust to restricted cubic spline analyses, analyses stratified by sex, race, alcohol use and tobacco cigarette smoking, and an additional measure of exposure (days of use in the past month).”

https://pubmed.ncbi.nlm.nih.gov/40785536/

“No association was found between cumulative lifetime use of cannabis, measured as cannabis-years, and incident hypertension over 35 years of follow-up in a cohort of relatively young Black and White adults free of hypertension at baseline. This finding was consistent across sensitivity analyses, including post hoc RCS analyses, analyses stratified by sex, race, alcohol use, and tobacco cigarette smoking, and an alternative measure of cannabis exposure (days of use in the past month).”

“Our findings suggest that cannabis use, even when accumulated over decades, may not independently elevate hypertension risk.”

https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.125.25005

Opioid reduction in patients with chronic non-cancer pain undergoing treatment with medicinal cannabis

Posted on by
Reply
pubmed logo

“Introduction: Opioid sparing by co-prescription of cannabinoids may enable patients to reduce their opioid consumption prescribed for chronic benign pain.

Methods: One cohort attending a small private pain clinic (N = 102), already taking opioids, was co-prescribed cannabinoids and another cohort (N = 53) attending a separate pain clinic nearby received only opioids. The two groups were studied prospectively for a year before their drug consumption was assessed.

Results: At baseline, median opioid consumption was 40 mg/day in both cohorts. Medicinal cannabis was administered daily in an oil formulation usually starting at 2.5 mg/day and was titrated to maximize benefits. At 12 months, the median dose contained 15 mg delta-9-tetrahydrocannabinol and 15 mg cannabidiol. At one-year follow-up, 46 of 102 cases had dropped out compared with only one of 53 controls. Opioid consumption had decreased significantly at one-year follow-up, the final median dose being lower in cases (2.7 mg/day) than controls (42.3 mg/day) (p < 0.05 in an intention-to-treat analysis). Disability and insomnia had also decreased in cases.

Conclusion: The introduction of cannabinoids can produce useful reductions in opioid consumption in real-world settings, with additional benefits for disability and insomnia. However, this treatment is tolerated by only a subgroup of patients.”

https://pubmed.ncbi.nlm.nih.gov/40788193/

“Plain language summary

Morphine-like drugs (opioids) decrease pain but can cause severe breathing problems and death if these drugs are consumed in excessive amounts. Stopping these drugs suddenly (going “cold turkey”) can cause severe adverse effects and, as time goes on, increasing amounts may be required to reduce pain. It might be possible to reduce opioid consumption by also taking medicinal cannabis; otherwise, reduction can be difficult to achieve. Cannabis treatment is safe when the hallucinatory component of cannabis is kept to low levels, causing minimal euphoric effects (a “stoned” sensation).In this study, two groups of patients with chronic pain were studied. Both were taking opioid drugs, but one group also took medicinal cannabis. About half of the medicinal cannabis group were not able to keep taking it due to unpleasant side effects. In the remainder, opioid consumption decreased significantly after both 6 and 12 months. Physical activity and sleep also improved. These findings indicate that medicinal cannabis can help patients to reduce their opioid consumption and improve their physical activity and sleep.”

“These findings indicate that medicinal cannabis can help patients to reduce their opioid consumption and improve their physical activity and sleep.”

https://www.tandfonline.com/doi/full/10.1080/17581869.2025.2544511

Local release of fibroblast growth factor 21 and cannabidiol promoting spinal cord nerve injury repair through activation of cannabinoid receptor 2

Posted on by
Reply
pubmed logo

“Spinal cord injury (SCI) is a debilitating condition that leads to severe motor and sensory dysfunction, largely due to inflammation, neuronal damage, and disrupted neural circuits.

In this study, we developed an injectable hydrogel (C/F/Gel) co-loaded with fibroblast growth factor 21 (FGF21) and cannabidiol micelles (CBDm) to enhance SCI repair. The hydrogel, composed of PF127 and α-cyclodextrin (α-CD), provides sustained drug release and improves drug stability at the injury site.

Our findings demonstrate that C/F/Gel effectively modulates the inflammatory microenvironment by promoting microglial polarization toward the anti-inflammatory M2 phenotype via cannabinoid receptor 2 (CB2R) activation.

Additionally, it regulates the balance between excitatory and inhibitory neurons, and significantly improves motor function in SCI mice. Behavioral assessments, histological analysis, and molecular studies confirmed the superior therapeutic efficacy of C/F/Gel compared to single-agent treatments.

These results highlight C/F/Gel as a promising biomaterial-based strategy for SCI repair, offering a synergistic approach that integrates inflammation modulation, neuroprotection, and functional recovery.”

https://pubmed.ncbi.nlm.nih.gov/40782447/

“Our study shows that the developed C/F/Gel is a promising therapeutic strategy for SCI repair, offering a multi-faceted approach through controlled drug release, inflammation modulation, neural regeneration, and motor function recovery. The synergy between FGF21 and CBDm, particularly via CB2R activation, highlights a novel mechanistic pathway for SCI treatment.”

https://www.sciencedirect.com/science/article/abs/pii/S0142961225005289?via%3Dihub

Medical cannabis for the management of pain in chronic pancreatitis with recurrent exacerbations: a case report

Posted on by
Reply
pubmed logo

“Introduction: Control of pain in patients affected by chronic pancreatitis with recurrent exacerbations is a challenging condition, with conventional therapies often providing limited relief. This case report describes the use of medical cannabis as a novel approach in a patient with refractory chronic pancreatitis, contributing to the growing interest in alternative treatments for pain and inflammation in similar complex cases.

Case presentation: A 54-year-old woman with a 24-year history of chronic pancreatitis caused by recurrent acute pancreatitis presented with persistent, severe abdominal pain and recurrent exacerbations despite undergoing numerous conventional interventions, including cholecystectomy, enzyme supplementation, repeated endoscopic retrograde cholangiopancreatographies (ERCPs), and stent placements. Imaging and laboratory findings confirmed chronic pancreatitis, with evidence of Oddi sphincter stenosis and microlithiasis. The patient was initially managed with standard pain relief therapy, digestive enzymes, and endoscopic interventions, all of which failed to provide lasting relief. In February 2024, she began treatment with a medical cannabis formulation rich in Cannabidiol, under the supervision of her healthcare provider. This intervention led to substantial pain reduction, cessation of acute episodes, improved appetite, and enhanced quality of life.

Conclusion: This case illustrates that medical cannabis may offer a promising alternative for managing chronic pancreatitis, especially when conventional treatments prove ineffective. This outcome underscores the need for further research on cannabinoids as a therapeutic option in chronic pain and inflammation management for pancreatitis and other challenging conditions.”

https://pubmed.ncbi.nlm.nih.gov/40781340/

“This case illustrates the potential of medical cannabis as an effective treatment option for chronic, treatment-resistant pancreatitis, a condition notoriously difficult to manage with conventional therapies. The patient’s experience demonstrates how cannabinoids can provide substantial pain relief, reduce inflammation, and improve quality of life, even when standard interventions fail to yield lasting benefits. Her case underscores the importance of exploring alternative therapies for complex, chronic conditions like pancreatitis, suggesting that medical cannabis may offer a transformative option for patients with few viable treatment paths.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00303-w

Recent Advances in the Therapeutic Potential of Cannabinoids Against Gliomas: A Systematic Review (2022-2025)

Posted on by
Reply
pubmed logo

“Glioma is the most common and lethal primary brain tumor in adults, with glioblastoma (GBM) representing the most aggressive subtype, characterized by diffuse infiltration, resistance to therapy, and a poor prognosis. Despite standard treatments, survival remains only approximately 14 months.

Cannabinoids have been increasingly investigated for their therapeutic potential in gliomas, particularly GBM. Although multiple reviews on this field of research have been published, most are current only up to 2022. This systematic review aims to provide an updated summary of studies published between 2022 and 2025, capturing recent developments in anti-glioma mechanisms, combinational strategies, immune modulation, and novel therapeutic platforms.

Following PRISMA guidelines, PubMed, Scopus, ScienceDirect, and SpringerLink were searched for original English-language journal articles published between January 2022 and February 2025, using search terms related to cannabinoids and brain cancer. From 1031 records, 45 original research articles were included after removing duplicates, non-primary studies, and irrelevant topics. The studies were categorized into seven thematic domains based on content.

Recent studies have elaborated on the anti-cancer mechanisms of cannabinoids beyond endocannabinoid signaling via the CB1/CB2 receptor, including ferroptosis induction, mitochondrial dysfunction, integrated stress response activation, and epigenetic modulation. Synthetic cannabinoids and their analogs demonstrated enhanced blood-brain barrier penetration and cytotoxicity in glioma models.

Cannabinoids have been shown to modulate immune responses in glioma, influencing T cell infiltration, myeloid suppressor cell recruitment, and tumor-associated macrophage function. Novel formulation and delivery strategies have improved cannabinoid solubility, stability, and tumor targeting. Combination therapies, particularly cannabidiol with temozolomide or radiotherapy, exhibited additive or synergistic anti-tumor effects, although variability between glioma subtypes suggests the need for personalized approaches.

Although cannabinoid-based glioma research has expanded our understanding of the mechanisms, discrepancies between preclinical findings and clinical data highlight the need for rigorous clinical trials and mechanistic research before cannabinoid-based treatments can be reliably integrated into standard glioma care.”

https://pubmed.ncbi.nlm.nih.gov/40781861/

https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.70160