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

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“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

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

“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

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“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

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“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

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“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

In silico exploration of pyrocannabinoid interactions with key protein targets

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“Cannabinoids, particularly those derived from cannabis, attract considerable attention in recent years for their therapeutic potential in treating various diseases and ailments.

In this study, we identify cannabinoid byproducts that result from the combustion of cannabidiol-henceforth referred to as pyrocannabinoids-and employ molecular docking simulations to investigate their interactions with key protein targets implicated in different physiological processes. Specifically, we focus on peroxisome proliferator-activated receptor gamma, p21-activated kinase 1, CB1, CB2, and GPR119 proteins, elucidating the binding modes and affinities of pyrocannabinoid byproducts to these receptors. This investigation is done in collaboration with Real Isolates LLC.

Our findings reveal diverse ligand-protein interactions, with some pyrocannabinoids displaying favorable binding energies and stable ligand-protein complexes. However, variations in binding affinities across different proteins underscore the complex pharmacological profiles of the pyrocannabinoids. Furthermore, the prediction of adsorption, distribution, metabolism, excretion and toxicity properties highlights both promising and concerning aspects of cannabinoid pharmacokinetics, emphasizing the need for thorough preclinical evaluation. Additionally, our investigation into potential metabolic sites using cytochrome P450 enzymes provides insights into cannabinoid metabolites.

Overall, our study contributes to the understanding of pyrocannabinoid pharmacology and informs the rational design of pyrocannabinoid-based therapeutics. Further experimental validation is warranted to translate these findings into clinically relevant applications.”

https://pubmed.ncbi.nlm.nih.gov/40718581/

https://link.springer.com/article/10.1007/s40203-025-00391-9

Cannabis-derived cellulose acetate electrospun membranes for therapeutic dressings: extraction, characterization, and prototype development

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“This work reports the development of electrospun cellulose acetate (CA) membranes derived from Cannabis sativa biomass for potential use in therapeutic dressings.

Cellulose was extracted from cannabis stalks using alkaline pulping and bleaching, followed by homogeneous acetylation to obtain CA with controlled substitution. CA solutions (13%-25%) were electrospun under varying parameters, and the 17% formulation yielded the most homogeneous, bead-free nanofibers. The resulting membranes were characterized using FTIR, XRD, Raman spectroscopy, UV-Vis spectrophotometry, and SEM. FTIR and Raman confirmed acetylation through characteristic ester and methyl group vibrations.

XRD revealed reduced crystallinity in CA compared to native cellulose. SEM analysis showed uniform fiber networks with diameters between 500 and 800 nm. A bilayer dressing prototype was fabricated by integrating the electrospun membrane with a medical-grade silicone adhesive. Adhesion performance was evaluated on synthetic skin using a FINAT-standardized 180° peel test.

The membranes demonstrated adequate mechanical cohesion and conformability, supporting their application as sustainable, plant-based biomedical patches.”

https://pubmed.ncbi.nlm.nih.gov/40698058/

“Taken together, this work presents the first full validation of cannabis-derived cellulose acetate as a processable, biocompatible, and functionally versatile material for advanced medical dressing systems.

Collectively, these findings support the use of Cannabis sativa as a viable and sustainable raw material for the development of high-performance cellulose acetate membranes. The study demonstrates not only the chemical and morphological comparability of cannabis-derived materials to commercial analogs but also their potential in next-generation biomedical and filtration technologies.”

https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2025.1624736/full

Medical Cannabis Use and Healthcare Utilization Among Patients with Chronic Pain: A Causal Inference Analysis Using TMLE

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“Introduction: Chronic pain affects approximately 20% of U.S. adults, imposing significant burdens on individuals and healthcare systems. Medical cannabis has emerged as a potential therapy, yet its impact on healthcare utilization remains unclear.

Methods: This retrospective cohort study analyzed administrative data from a telehealth platform providing medical cannabis certifications across 36 U.S. states. Patients were classified as cannabis-exposed if they had used cannabis in the past year, while unexposed patients had no prior cannabis use. Outcomes included self-reported urgent care visits, emergency department (ED) visits, hospitalizations, and quality of life (QoL), measured using the CDC’s Healthy Days measure. Targeted Maximum Likelihood Estimation with SuperLearner estimated causal effects, adjusting for numerous covariates.

Results: Medical cannabis users exhibited significantly lower healthcare utilization. Specifically, exposure was associated with a 2.0 percentage point reduction in urgent care visits (95% CI: -0.036, -0.004), a 3.2 percentage point reduction in ED visits (95% CI: -0.051, -0.012) and fewer unhealthy days per month (-3.52 days, 95% CI: -4.28, -2.76). Hospitalization rates trended lower but were not statistically significant. Covariate balance and propensity score overlap indicated well-fitting models.

Conclusions: Medical cannabis use was associated with reduced healthcare utilization and improved self-reported QoL among chronic pain patients.”

https://pubmed.ncbi.nlm.nih.gov/40700267/

“The findings of this study suggest, in line with existing research, that medical cannabis is likely an effective treatment option for patients with chronic pain. Moreover, we found that, in addition to an increase in QoL, medical cannabis exposure is associated with lower risk of urgent care and ED visits, when comparing patients who used medical cannabis for at least one year to cannabis-naïve patients. This underscores the potential for not only QoL gains associated with medical cannabis use, but also positive downstream effects on the healthcare system resulting from treatment.”

https://www.mdpi.com/2226-4787/13/4/96

Inflammatory bowel disease patients believe cannabis and cannabidiol oil relieve symptoms

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“Background: Patients with Inflammatory bowel disease (IBD) often seek alternative therapies for symptom management. This study investigates the perceptions, consumption patterns, and reported outcomes of cannabis and cannabidiol (CBD) oil use among IBD patients and controls.

Methods: A 37-question survey was administered to 139 participants (IBD patients, n = 93; control/non-IBD participants, n = 33) to assess usage frequency and beliefs regarding cannabis and CBD oil as treatment for IBD. The survey also evaluated the impact of these substances on IBD symptoms, quality of life, and opioid use.

Results: Cannabis consumption was higher in IBD patients (57, 53.8%) than controls (15, 45.5%) with both groups strongly supporting medical cannabis use (IBD; 92, 86.8% vs. controls; 29, 84.9%). Most IBD patients believed cannabis (67, 63.2%), CBD oil (60, 56.6%), corticosteroids (77, 73.3%), and biologics/immunosuppressants (85, 81.0%) had a somewhat-extremely beneficial effect in relieving IBD symptoms. Over 50% of IBD cannabis users reported relief from abdominal pain, other pain, stress, anxiety, depression, and nausea/vomiting, with Crohn’s disease patients experiencing significantly more relief than ulcerative colitis patients for certain symptoms (p < 0.05). Notably, 19.4% of IBD patients reported decreased opioid use, and 14.5% reported induced remission with cannabis or CBD oil.

Conclusions: Consumption of cannabis and CBD oil was perceived as beneficial for relieving IBD, with many reporting significant symptom relief from using these substances. The strong support of cannabis and CBD oil as medical treatments and therapeutic effects highlights the potential for cannabis and CBD oil as treatments in IBD.”

https://pubmed.ncbi.nlm.nih.gov/40687272/

“Recent preclinical studies have suggested that cannabinoids, including CBD and THC, may reduce gastrointestinal inflammation and modulate intestinal motility. The presence of cannabinoid receptors in the gut, along with the anti-inflammatory effects of some cannabinoids, has led researchers to explore the potential for therapeutic applications of cannabis in the treatment of IBD.”

“Animal studies of the chemistry and physiology of cannabinoids have shown potential anti-inflammatory, antidiarrheal, and nociceptive-limiting effects, paralleling the growing interest in cannabis as a treatment option for IBD.

Human studies have also indicated that there may be a benefit in controlling IBD symptoms and improving quality of life. Additionally, anecdotal reports and observational studies have highlighted potential benefits in reducing disease activity and managing symptoms like abdominal pain, cramping, joint pain, and diarrhea.”

https://www.academia.edu/2994-435X/2/2/10.20935/AcadMed7773

The effects of nabiximols (Sativex®) on spasticity and non-motor symptoms in chronic spinal cord injury (SCI): a longitudinal prospective study

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“Objectives: This study aimed to evaluate the effects of Nabiximols (Sativex®) on spasticity in chronic spinal cord injury (SCI) individuals refractory to conventional therapy. Secondary objectives included assessing its impact on functional independence, neuropathic pain, sleep quality, and depression.

Setting: Institute Guttmann, a neurorehabilitation hospital in Badalona, Catalonia (Spain).

Methods: Adult participants ( >18 years) with chronic SCI ( >6 months) and moderate to severe spasticity refractory to conventional treatments were recruited. All participants underwent baseline assessments and were followed up at one and two months after initiating treatment with nabiximols oromucosal spray, with individualised dose adjustments on a weekly basis. Assessed variables included spasticity, functional independence, neuropathic pain, sleep quality, depression, quality of life, and Patient Global Impression of Improvement (PGI-I).

Results: Statistically significant improvements in spasticity were observed after one month (VAS decrease of 30%, p < 0.001; MAS decrease of 60%, p = 0.001) and two months (VAS decrease of 30%, p < 0.001; MAS decrease of 52%, p = 0.011) of treatment. A positive PGI-I was reported in 67% of participants. However, no significant changes were noted in spasms frequency, functional independence, neuropathic pain, or sleep quality. No significant differences in spasticity change or non-motor symptoms were found between participants with complete and incomplete SCI.

Conclusions: Nabiximols may effectively reduce spasticity in individuals with SCI resistant to conventional therapies. Given the significant impact of spasticity associated with SCI, it could be considered a viable add-on therapy for this population.”

https://pubmed.ncbi.nlm.nih.gov/40675989/

https://www.nature.com/articles/s41394-025-00712-2