NON-PSYCHOACTIVE CANNABIS EXTRACT PROMOTES EXTINCTION AND REDUCES REINSTATEMENT BY PRIMING DOSE IN SMOKED COCAINE-INDUCED CONDITIONED PLACE PREFERENCE

Posted on August 5, 2025 by David

“The therapeutic potential of Cannabis sativa L. and cannabidiol (CBD) for substance use disorders is being actively investigated using murine addiction models. However, the efficacy of cannabis or its constituents in attenuating dependence indicators associated with smoked cocaine consumption remains unclear.

This study employed a Conditioned Place Preference (CPP) paradigm using anhydroecgonine methyl ester and cocaine (AEME-COC) as the reinforcing agent to model smoked cocaine consumption in mice.

The model was utilized to evaluate the preclinical efficacy of a non-psychoactive cannabis extract (NPCE) and CBD on extinction parameters and reinstatement induced by stress and priming doses. Experiment 1 compared conditioning phase (Cond) and extinction times between subjects administered cocaine and those receiving AEME-COC. Experiment 2 investigated the effects of CBD and NPCE on extinction latency in AEME-COC-induced CPP. Experiment 3 examined the competitive 5-HT1A receptor antagonist WAY-100135 and CB2 receptor inverse agonist AM630 on NPCE-mediated inhibition of stress-induced and priming-induced reinstatement of AEME-COC-induced CPP.

The results showed that subjects administered cocaine exhibited greater exploration of the conditioned compartment during Cond compared to those administered AEME-COC, with the latter group displaying prolonged extinction latency (Experiment 1).

NPCE, but not CBD, significantly reduced the extinction latency of AEME-COC-induced CPP (Experiment 2). In Experiment 3, NPCE selectively inhibited priming-induced reinstatement but did not affect stress-induced reinstatement. The 5-HT1A receptor attenuated NPCE’s inhibitory effects on priming-induced reinstatement, whereas the CB2 receptor had no significant modulatory impact on this indicator.

These findings suggest that NPCE influences smoked cocaine dependence indicators primarily through serotonergic receptor modulation.”

https://pubmed.ncbi.nlm.nih.gov/40752858/

https://www.sciencedirect.com/science/article/pii/S0031938425002495?via%3Dihub

Assessing the Role of Cannabis in Managing Spasticity in Multiple Sclerosis: A Systematic Review and Meta-Analysis

Posted on August 4, 2025 by David

“Background: Multiple sclerosis (MS) is a complex, heterogeneous disease, and its management remains challenging due to varying symptoms and patient responses to treatments. While injectable therapies like glatiramer acetate and beta-interferon are common, they have limitations such as side effects and varying efficacy. Cannabis has garnered attention as a potential alternative treatment, particularly for symptoms like spasticity and pain.

Objective: This study aims to evaluate the efficacy of cannabis-based therapies for managing MS-related spasticity.

Methods: Nine clinical trials involving 2544 MS patients were included, with studies conducted between 2003 and 2021 across multiple countries. Cannabinoid therapies studied included whole-plant extracts, oils, and smoked cannabis containing delta-9-tetrahydrocannabinol and/or cannabidiol. Spasticity was assessed using standardized scales, including the Ashworth scale (AS), visual analog scale, and numeric rating scale (NRS). Effect sizes were pooled using random or fixed effects models, and heterogeneity and publication bias were evaluated using I², Tau², and funnel plots.

Results: The overall meta-analysis revealed a standardized mean difference (MD) of 39.19 (95% CI: 34.32-44.05) in spasticity scores, indicating notable improvement post-treatment. Subgroup analyses showed a MD of 20.36 (95% CI: 20.35-20.37) for AS and 1.18 (95% CI: 1.16-1.21) for NRS. However, substantial heterogeneity (I² = 100% for overall and AS analyses; 91% for NRS) and asymmetry in funnel plots suggest possible publication bias and study variability. Short-term studies demonstrated modest changes (MD = 4.53, 95% CI: -0.06 to 9.12), while long-term studies yielded larger effects (MD = 75.81, 95% CI: 66.39-85.22). Adverse events were generally mild, including dizziness and dry mouth.

Conclusion: Cannabis-based therapies are associated with clinically meaningful improvements in MS-related spasticity, particularly over longer durations. Despite the promising findings, high heterogeneity and suspected bias necessitate caution. Further high-quality randomized trials with standardized protocols and comprehensive safety assessments are warranted to validate efficacy and long-term outcomes.”

https://pubmed.ncbi.nlm.nih.gov/40753057/

Pilot Study of Cannabidiol for Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in Breast Cancer

Posted on August 4, 2025 by David

“Introduction: Aromatase inhibitor (AI) therapy reduces breast cancer recurrence risk. However, some patients stop treatment early because of AI-associated musculoskeletal symptoms (AIMSS). AIMSS is due in part to systemic inflammation. Cannabidiol (CBD) has anti-nociceptive and anti-inflammatory properties, making it a potential treatment option for AIMSS.

Methods: Women with stage 0-3 hormone receptor-positive breast cancer experiencing AIMSS enrolled in this phase 2 clinical trial. Patients received CBD (Epidiolex), titrated over 4 weeks to 100 mg BID, for a total of 15 weeks. Patient-reported outcomes were collected serially. The primary endpoint was the number of patients with at least a 2-point reduction in worst pain from baseline to 15 weeks. Statistical analysis was completed using paired t-tests and linear mixed models.

Results: Of 39 eligible patients, 28 completed protocol-directed study treatment. Eleven discontinued treatment due to toxicity (n = 5) or per patient preference (n = 6). Seventeen of 39 patients met the primary endpoint (43.6%, 95% CI [28%, 60%]). Worst pain improved 0.13 per week of treatment (p < 0.001) for all patients; average improvement in worst pain was 1.95 points at the end of 15 weeks. Of the 28 patients who completed the study, average reduction in worst pain was 2.36 points (95% CI [-3.22, -1.49]) between baseline and Week 15.

Conclusion: Treatment with CBD was safe, tolerable, and associated with improvement in joint pain for a subset of patients. Additional studies are needed to further understand the impact of CBD on AIMSS and which patients are most likely to benefit from CBD treatment.”

https://pubmed.ncbi.nlm.nih.gov/40751295/

“Treatment with CBD was associated with an improvement in AIMSS for a subset of patients. Use of CBD was safe and tolerable for women with hormone receptor-positive breast cancer.”

https://onlinelibrary.wiley.com/doi/10.1002/cam4.71117

Efficacy and safety of cannabidiol in a single-center pediatric drug-resistant epilepsy cohort: a retrospective study

Posted on August 4, 2025 by David

“Background: Pharmacoresistance to conventional antiseizure medications has been described in approximately 30% of the pediatric epileptic patients, making pharmacological management particularly challenging for physicians. Currently, cannabidiol (CBD) is approved as an adjunctive therapy in combination with clobazam for Dravet Syndrome (DS), Lennox-Gastaut Syndrome (LGS), and as adjunctive treatment for Tuberous Sclerosis Complex (TSC). Studies on drug-resistant epilepsy (DRE) suggested that CBD antiepileptic properties may benefit a wider range of pharmacoresistant epilepsy syndromes.

Objective: Our observational, retrospective, monocentric study aimed to evaluate the effect and safety of CBD in a real-world pediatric cohort with DRE.

Methods: We recruited 15 pediatric patients (7 females, 8 males; mean age: 12.33 ± 4.37 years) affected by pharmacoresistant epilepsy treated with CBD as adjunctive therapy. Inclusion criteria required a diagnosis of DRE, initiation of CBD treatment before 18 years of age, and at least 6 months period of follow-up after CBD initiation. Clinical, demographic, and instrumental data were retrospectively extracted from the medical records and caregivers’ reports. Based on seizure reduction, patients were stratified into “responders” (>50%), “partial responders” (30-50%), and “non-responders” (<30%) groups.

Results: CBD was used as an add-on therapy in 8/15 patients on-label (for DS, LGS, and TSC) and in 7/15 off-label. The maximum dose of CBD administered was 21 mg/kg/day, with an average dose of 16.5 mg/kg/day. 11/15 patients showed a reduction in seizure frequency: 7 were responders (2/7 seizure-free) and 5 were partial responders. Additionally, 11/15 patients showed improved social and environmental participation, as assessed using the Clinical Global Impression scale. Interestingly, brain magnetic resonance imaging revealed structural abnormalities in 5/15 patients, with 6/15 showing malformations of cortical development (4/6 responders, including 1 seizure-free).

Conclusion: CBD demonstrated a good safety and tolerability profile and appeared to be a promising therapeutic option for the management of DRE. It offers a valuable alternative for seizure control and has a positive impact on social interaction, with overall improvement in the quality of life for patients and their caregivers.”

https://pubmed.ncbi.nlm.nih.gov/40740850/

“In conclusion, CBD may represent a promising therapeutic option capable of enhancing the clinical management of DRE. Indeed, it offers a valuable alternative for seizure treatment and positively impacts social interaction and quality of life for the patients and their caregivers.”

https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1616480/full

Expanding the Therapeutic Profile of Topical Cannabidiol in Temporomandibular Disorders: Effects on Sleep Quality and Migraine Disability in Patients with Bruxism-Associated Muscle Pain

Posted on August 4, 2025 by David

“Background: Cannabidiol (CBD) has demonstrated potential as a therapeutic agent for muscle tension, pain, and sleep bruxism, yet its broader impact on comorbid conditions such as sleep disturbance and migraine disability remains underexplored. This study aimed to assess the effects of topical CBD on sleep quality and migraine-related disability in patients with bruxism-associated muscular pain.

Methods: In a randomized, double-blind clinical trial, 60 participants with bruxism were allocated equally into three groups: control (placebo gel), 5% CBD gel, and 10% CBD gel. Participants applied the gel intraorally to the masseter muscles nightly for 30 days. Sleep quality and migraine-related disability were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Migraine Disability Assessment Scale (MIDAS), respectively. Surface electromyography (sEMG) and the Bruxoff^® device were used for objective evaluation of muscle tension and bruxism intensity.

Results: Both CBD treatment groups demonstrated statistically significant improvements in PSQI and MIDAS scores compared to the control group (p < 0.001). No significant differences were observed between the 5% and 10% CBD groups, suggesting comparable efficacy. The sEMG findings corroborated a reduction in muscle tension. Improvements in sleep and migraine outcomes were positively correlated with reductions in muscle activity and pain.

Conclusions: Topical CBD gel significantly improved sleep quality and reduced migraine-related disability in patients with bruxism-associated muscular pain, supporting its role as a multifaceted therapeutic option in the management of TMD and related comorbidities. Further research is needed to confirm long-term benefits and determine optimal dosing strategies.”

https://pubmed.ncbi.nlm.nih.gov/40732351/

“This study demonstrates that topical application of cannabidiol (CBD) gel, at both 5% and 10% concentrations, significantly improves sleep quality and reduces migraine-related disability in patients with bruxism-associated muscular pain. These effects were observed alongside reductions in muscle tension and pain, suggesting a broader therapeutic impact of CBD beyond localized symptom relief. Notably, no substantial differences were found between the two concentrations, indicating that lower doses may achieve comparable clinical outcomes.

The findings support the use of topical CBD as a well-tolerated, non-invasive adjunct in the multimodal management of temporomandibular disorders (TMD), especially in patients experiencing comorbid sleep and headache disturbances. Future research should explore long-term efficacy, optimal dosing, and underlying mechanisms through objective neurophysiological and sleep assessments”

https://www.mdpi.com/1424-8247/18/7/1064

The impact of cannabis use on ageing and longevity: a systematic review of research insights

Posted on July 30, 2025 by David

“With aging emerging as a global challenge linked to chronic diseases, identifying interventions that support a healthy lifespan and health span has become imperative. Cannabinoids derived from cannabis, particularly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), have gained attention for their potential to promote healthy aging through interactions with the endocannabinoid system. While CBD has often been highlighted for its benefits, emerging evidence indicates that THC, under certain conditions and doses, may also play a therapeutic role in aging. Despite this interest, significant knowledge gaps persist in understanding cannabis’s role in promoting healthy aging and longevity.Aim

We reviewed recent literature to investigate the effect of cannabinoid use, particularly CBD and THC on aging and longevity. By synthesizing findings from preclinical models, clinical studies, and real-world evidence, we aimed to elucidate the potential of cannabinoids, in fostering healthy aging, mitigate age-related decline, and promote well-being in older populations.Method

We conducted a systematic review guided by PRISMA to investigate the impact of cannabinoids on aging and longevity. Studies involving preclinical models (e.g., Caenorhabditis elegans, rodents, zebrafish, and mice) and clinical populations aged 50 years and older were included. Exclusion criteria targeted acute effects and mechanisms of action in different medical conditions. Aging was explicitly defined as biological and psychological changes associated with advancing age, and longevity was defined as the extension of lifespan and factors influencing healthy aging.Findings

Eighteen studies investigating the direct impact of cannabinoids on aging and longevity were identified in preclinical models (11) and human studies (7). Preclinical studies have shown promising results regarding the potential benefits of cannabinoids including improved lifespan, cognitive function, inflammation, memory, sleep quality, and social interaction. The effects of THC appear more complex, with potential benefits at low doses and drawbacks at higher doses, highlighting their complex role in aging. However, the limited number of human studies hinders a comprehensive understanding. Clinical studies also suggest potential therapeutic applications for cannabinoids in aging populations, although further research is needed to understand their mechanisms of action and long-term effects fully.”

Conclusion

“Cannabinoids hold promise for supporting healthy aging and enhancing the quality of life in older populations. While preliminary research suggests intriguing possibilities, more studies are needed to solidify the link between cannabis use, the ECS, and healthy aging in humans. Rigorous clinical trials are crucial to evaluate their safety and efficacy. Longitudinal studies and well-designed clinical trials are critical to understanding the safety, efficacy, and long-term effects of cannabis use in aging populations. Future research should optimize dosages, investigate mechanisms of action, and explore the influence of cannabis use initiated in aging as opposed to lifetime exposure. Clarifying these aspects is vital for informing public health strategies and developing targeted therapeutic interventions for age-related conditions.”

“These findings open exciting avenues for exploring novel therapeutic interventions for age-related cognitive decline and neurological disorders.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00267-x

https://pubmed.ncbi.nlm.nih.gov/40731362/

Clinical predictors of mortality in dual diagnosis patients receiving integrated in-patient treatment-A cohort study with 21 years follow-up

Posted on July 30, 2025 by David

“Aims: To examine mortality, and identify predictors of mortality, in a cohort of dual diagnosis (co-existing psychiatric disorder and substance use disorder) patients.

Design: Cohort study based on national register and electronic health record data.

Setting and participants: Between 2002 and 2017, 2359 dual-diagnosis patients received treatment at a specialized Danish department and were followed until death, migration or a maximum of 21 years.

Measurements: Data on diagnosis, substance use, demographics, medication use and mortality were linked to national registers. Kaplan-Meier plots illustrated mortality differences across diagnostic groups, while the Cox model identified factors associated with mortality.

Findings: In this study, 23.5% of dual diagnosis patients died within ten years of discharge and 33.7% at end of follow-up. The highest mortality risk was among those with a primary substance use disorder (SUD) and no psychiatric diagnosis, with 45.9% dying. Alcohol [adjusted hazard ratio (aHR) = 1.42; 95% confidence interval (CI) = 1.18-1.71], opioids (aHR = 1.26; 95% CI = 1.03-1.54), as well as Charlson Comorbidity Index: 1 (aHR = 1.70; 95% CI = 1.41-2.04) and 2 + (aHR = 2.56; 95% CI = 1.94-3.36), increased mortality risk.

In contrast, cannabis use disorder (aHR = 0.77; 95% CI = 0.65-0.93) and being female (aHR = 0.83; 95% CI = 0.71-0.97) reduced it.

Psychiatric diagnoses F30-39 (aHR = 0.70; 95% CI = 0.56-0.87) and F40-49 (aHR = 0.76; 95% CI = 0.59-0.97) were associated with lower mortality risk compared with F20-29. Of 733 deaths with mortality cause data, nearly two-thirds were from natural causes, 8% from suicide and 20% from accidents or violence.

Conclusion: The observed high mortality rates among clinically confirmed dual diagnosis patients (co-existing psychiatric disorder and substance use disorder) in Denmark highlight the urgent need for comprehensive treatment for this population. The risk of death appears to be related to type of substance use, with alcohol and opioids associated with higher mortality rates than other substances.”

https://pubmed.ncbi.nlm.nih.gov/40726419/

https://onlinelibrary.wiley.com/doi/10.1111/add.70125

Evaluating the Association of Cannabis Use and Longitudinal Kidney Outcomes

Posted on July 30, 2025 by David

“Background: Cannabis is the most used federally controlled substance in the United States. Given the increasingly widespread use of cannabis, further examination of its health implications is needed. We evaluated the association of cannabis use and longitudinal kidney outcomes among a cohort of adults living in Baltimore, MD.

Methods: We used data from healthy aging in neighborhoods of diversity across the life span study. Baseline cannabis use (obtained between 2004 and 2009) was categorized as never tried, tried, never used regularly (irregular use), regular use >6 months prior (former regular use), and regular use within the past 6 months (current regular use). The primary outcome was incident chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² at follow-up (2013-2017). Risk of rapid kidney function decline (decline in eGFR of >3 mL/min per 1.73 m² per year) and incident albuminuria (albumin-to-creatinine ratio [ACR] ≥ 30 mg/g) were also assessed. Multivariable logistic regression was used to evaluate the association of cannabis use with kidney outcomes.

Results: Among 1,521 participants, the mean age was 48 years, 58% were female, and 58% were of Black race. Participants with current regular cannabis use were more likely to be younger, male, Black, and to concurrently use cigarettes, opiates, and/or cocaine.

Compared with those with no history of cannabis use, participants with current regular cannabis use were not at higher risk of incident CKD (OR: 0.79 [95% CI: 0.37-1.68]), rapid kidney function decline (OR: 0.80 [95% CI: 0.43-1.49), or incident albuminuria (OR: 0.84 [95% CI: 0.38-1.87]) after adjustment for sociodemographics, health factors, and concurrent use of cigarette, opiate, or cocaine.

Conclusion: In this Baltimore-based cohort of adults without CKD, there was no independent association between cannabis use and adverse kidney outcomes over time.”

https://pubmed.ncbi.nlm.nih.gov/40735771/

Process Development for GMP-Grade Full Extract Cannabis Oil: Towards Standardized Medicinal Use

Posted on July 30, 2025 by David

“Background/Objectives: The industrial extraction and purification processes of Cannabis sativa L. compounds are critical steps in creating formulations with reliable and reproducible therapeutic and sensorial attributes.

Methods: For this study, standardized preparations of chemotype I were chemically analyzed, and the sensory attributes were studied to characterize the extraction and purification processes, ensuring the maximum retention of cannabinoids and minimization of other secondary metabolites. The industrial process used deep-cooled ethanol for selective extraction.

Results: Taking into consideration that decarboxylation occurs in the process, the cannabinoid profile composition was preserved from the herbal substance to the herbal preparations, with wiped-film distillation under deep vacuum conditions below 0.2 mbar, as a final purification step. The profiles of the terpenes and cannabinoids in crude and purified Full-spectrum Extract Cannabis Oil (FECO) were analyzed at different stages to evaluate compositional changes that occurred throughout processing. Subjective intensity and acceptance ratings were received for taste, color, overall appearance, smell, and mouthfeel of FECO preparations.

Conclusions: According to sensory analysis, purified FECO was more accepted than crude FECO, which had a stronger and more polarizing taste, and received higher ratings for color and overall acceptance. In contrast, a full cannabis extract in the market resulted in lower acceptance due to taste imbalance. The purification process effectively removed non-cannabinoids, improving sensory quality while maintaining therapeutic potency. Terpene markers of the flower were remarkably preserved in SOMAÍ’s preparations’ fingerprint, highlighting a major qualitative profile reproducibility and the opportunity for their previous separation and/or controlled reintroduction. The study underscores the importance of monitoring the extraction and purification processes to optimize the cannabinoid content and sensory characteristics in cannabis preparations.”

https://pubmed.ncbi.nlm.nih.gov/40733057/

“This study highlights the effectiveness of SOMAÍ’s extraction and purification processes in optimizing the sensory and therapeutic quality of full-spectrum medicinal cannabis extracts for herbal preparations. The method employed was explicitly tailored to collect cannabinoid fractions from the natural cannabis flower oils. The resulting purified full-spectrum extract is selectively concentrated in the profiled beneficial compounds naturally found within the flower, successfully removing compounds lacking scientifically proven therapeutic value. While these unwanted compounds will have an impact on the final taste of the decarboxylated full-spectrum oil, herbal medicines created from unpurified full cannabis extract oil will, therefore, have a range of tastes, such as earthy, bitter, and grassy, all of which are strong and generally regarded as unpleasant for therapeutic adherence. The process developed herein is to obtain a standardized THC-dominant crude extract. The same process is applied to CBD-dominant crude extract. With these two extracts, the pharmaceutical company can prepare medicines with a precise and previously defined ratio between the two main bioactive components, an objective not achievable if depending exclusively on the present ratio in the herbal substance.”

https://www.mdpi.com/1999-4923/17/7/848

A Stroll Through Saffron Fields, Cannabis Leaves, and Cherry Reveals the Path to Waste-Derived Antimicrobial Bioproducts

Posted on July 30, 2025 by David

“Background: The accumulation of agri-food waste is a major environmental and economic challenge and converting these by-products into bioactive compounds fits within the circular bioeconomy. This study aimed to evaluate the antimicrobial potential of extracts derived from Cannabis sativa L. leaves (CSE), Crocus sativus tepals (CST), and Prunus avium L. cherry waste (VCE) against four key bacterial species (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa).

Methods: Minimum inhibitory concentration (MIC) assays were performed to assess antibacterial activity, while a bioinformatic pipeline was implemented to explore possible molecular targets. Full-proteome multiple sequence alignments across the bacterial strains were used to identify conserved, strain-specific proteins, and molecular docking simulations were applied to predict binding interactions between the most abundant compounds in the extracts and their targets.

Results: CSE and CST demonstrated bacteriostatic activity against S. aureus and B. subtilis (MIC = 15.6 mg/mL), while VCE showed selective activity against B. subtilis (MIC = 31.5 mg/mL). CodY was identified as a putative molecular target for CSE and CST, and ChaA for VCE. Docking results supported the possibility of spontaneous binding between abundant extract constituents and the predicted targets, with high binding affinities triggering a strong interaction network with target sensing residues.

Conclusions: This study demonstrates the antimicrobial activity of these agri-food wastes and introduces a comprehensive in vitro and in silico workflow to support the bioactivity of these agri-food wastes and repurpose them for innovative, eco-sustainable applications in the biotechnology field and beyond.”

https://pubmed.ncbi.nlm.nih.gov/40732292/

“Given the observed antimicrobial activity against foodborne and surface-associated pathogens, the findings suggest that these extracts may hold promise for use in natural food preservation or environmental hygiene applications.The approach and the evidence adopted here and provided in this study could be useful for future for more eco-friendly and cost-effective strategies to develop waste-derived bioproducts for different purposes.”

https://www.mdpi.com/1424-8247/18/7/1003