Lifetime Cannabis Use Is Associated with Brain Volume and Cognitive Function in Middle-Aged and Older Adults

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“Objective: Cannabis use has increased among older adults, yet the neurocognitive effects in this demographic remain unclear. Prior work has suggested cannabis may increase brain volume in areas rich in cannabinoid (CB1) receptors, though negative effects are often reported in adolescents. This study sought to clarify the relationship between cannabis use and brain health among middle-aged and older adults.

Method: Using data from the UK Biobank, which includes health information from over 500,000 adults, associations between cannabis use, regional brain volume, and cognition in participants aged 40-70 years (mean age = 54.5) were evaluated.

Results: Lifetime cannabis use was positively associated with regional brain volume in CB1-rich regions, including the caudate, putamen, hippocampus, and amygdala. Greater lifetime use was also linked to better performance in learning, processing speed, and short-term memory. Individuals reporting use limited to adolescence also showed larger regional volumes and better cognitive performance than non-users. Sex differences in cannabis effects on brain volume and cognition were also observed.

Conclusions: Results highlight that cannabis may influence brain health differently across the lifespan, potentially offering protective effects in older age while posing risks earlier in development. Protective effects may result from endocannabinoid-mediated modulation of inflammation, immune function, and neurodegeneration. Observed sex differences likely reflect variation in the endocannabinoid system and underscore the importance of considering sex as a biological variable in studies of cannabis and brain health.”

https://pubmed.ncbi.nlm.nih.gov/41379083

https://www.jsad.com/doi/10.15288/jsad.25-00346

Antioxidant and Antiproliferative Activities of Hemp Seed Proteins (Cannabis sativa L.), Protein Hydrolysate, and Its Fractions in Caco-2 and THP-1 Cells

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“This study evaluated the in vitro antioxidant and antiproliferative activity of hemp seed (Cannabis sativa L.) protein isolate, protein hydrolysate, and its fractions. The protein hydrolysate was obtained through sequential enzymatic digestion using pepsin and pancreatin, achieving a degree of hydrolysis of 48.11%. The hydrolysate was then fractionated by ultrafiltration.

Assays conducted on Caco-2 (colorectal cancer) and THP-1 (leukemia) cell lines revealed that the higher-molecular-weight fraction of (>10 kDa) exhibited the strongest, concentration-dependent antiproliferative effect, as determined by the neutral red uptake (NRU) assay for Caco-2 cells and the MTT assay for THP-1 cells. Furthermore, a significant intracellular antioxidant activity was observed, particularly in the whole hydrolysate and its low-molecular-weight fractions, as measured by the DCFH-DA assay in Caco-2 cells.

The results suggest the potential application of hemp seed protein hydrolysate and its fractions as antioxidant and chemoprotective supplements in oncologic therapies.”

https://pubmed.ncbi.nlm.nih.gov/41373886

“This study establishes that hemp seed protein hydrolysate (HSH) and its ultrafiltration fractions possess significant and dual biological activities. The principal finding is the identification of a potent, dose-dependent, and selective antiproliferative effect against colorectal adenocarcinoma (Caco-2) and monocytic leukemia (THP-1) cell lines, with the high-molecular-weight fraction (F1 > 10 kDa) demonstrating the greatest efficacy.

Collectively, these findings underscore the dual potential of hemp seed peptides as a reduction in cell viability agents and potent antioxidants, positioning them as promising candidates for development as functional food ingredients for chemoprevention and as adjuvants in oncological therapies.”

https://www.mdpi.com/1422-0067/26/23/11741

Spectroscopy-Based Evaluation of the Antioxidant Capacity of Hemp (Cannabis sativa)

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“In the present study, a comprehensive evaluation of the antioxidant properties of various parts of the hemp plant, specifically its leaves and flowers, in a new feminized variety of Cannabis sativa with an admixture of Cannabis ruderalis was investigated.

Methods such as Electron Paramagnetic Resonance (EPR) and UV-visible (UV-vis) spectroscopy were used to assess trolox equivalent antioxidant capacity (TEAC) and total polyphenol content (TPC). TEAC values of the analyzed samples ranged from 29.5 μmol TE/g DW to 150.2 μmol TE/g DW, while TPC varied between 5.4 mg GAE/g DW and 20.3 mg GAE/g DW.

The findings indicate that hemp exhibits significant antioxidant properties, especially in its leaves. This is attributed to a diverse range of antioxidants, including cannabinoids, flavonoids, and phenolic compounds, which offer notable health benefits.

Furthermore, the method of drying hemp has been shown to influence its antioxidant properties significantly. Research indicates that freeze-dried and air-dried hemp retains higher levels of antioxidant compounds compared to other drying methods. This suggests that selecting an appropriate drying technique is essential for preserving the bioactive compounds responsible for hemp’s antioxidant activity.”

https://pubmed.ncbi.nlm.nih.gov/41373841

“Cannabis plants, in general, owe their antioxidant capabilities to compounds like polyphenols, terpenes, and cannabinoids. Among these, delta-9-tetrahydrocannabinol (THC) and the nonpsychoactive cannabidiol (CBD) are the most recognized. Both THC and CBD exhibit antioxidant activities comparable to vitamins E and C, effectively scavenging free radicals, reducing metal ions, and counteracting oxidative stress.”

“The hemp plant, C. sativa, has emerged as a promising source of natural antioxidants, with various parts of the plant exhibiting diverse levels of antioxidant activity.”

“As global interest in hemp rises, a deeper understanding of its health benefits, particularly its antioxidant properties, will be essential for fully capitalizing on this plant. Research into its bioactive compounds could pave the way for innovative natural remedies and contribute to developing new products that support well-being.”

https://www.mdpi.com/1422-0067/26/23/11696

Unraveling Cannabidiol’s Dual Modulatory Role in Schizophrenia: Network Pharmacology and In Vivo Validation of Neuroinflammatory and Behavioral Modulation

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“Schizophrenia (SCZ), a chronic psychiatric disorder, is characterized by cognitive impairment, hallucinations, and delusions, with current antipsychotic treatments offering limited efficacy and considerable side effects.

Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, has shown promise in treating neurological and psychiatric conditions, though its precise mechanisms in schizophrenia remain unclear.

Using network pharmacology, this study predicts CBD’s targets and pathways in schizophrenia, highlighting LPS-induced neuroinflammation and implicating 5-HT1AR-MAPK signaling as one potential contributor.

In vitro, CBD (10 mg/kg, i.p.) treatment significantly reduced pro-inflammatory cytokines (e.g., NO, IL-1β, IL-6, TNF-α) and modulated the 5HT1AR-MAPK pathway, including increased 5HT1AR expression and decreased MAPK/ERK1/2 phosphorylation (p < 0.05).

In vivo, CBD alleviated SCZ-like symptoms in a ketamine-induced animal model, reducing anxiety in the open field (p < 0.01) and elevated plus maze tests (p < 0.01), improving spatial memory in the Y-maze (p < 0.01) and social behavior (p < 0.0001) after 5 consecutive days of treatment. Critically, we validated CBD’s central anti-inflammatory effects by demonstrating reduced pro-inflammatory cytokine levels in both plasma and brain tissues (p < 0.05). Further correlation analysis established a direct link between brain cytokine suppression and behavioral improvements, integrating in vitro findings from BV2 microglial cells with in vivo neuroinflammatory and behavioral outcomes.

These findings suggest the potential therapeutic benefits of CBD for SCZ, though further research, particularly clinical trials, is required to validate its efficacy and establish it as a novel therapeutic strategy.”

https://pubmed.ncbi.nlm.nih.gov/41369966

“Cannabidiol (CBD), a non-intoxicating compound found in Cannabis sativa, has emerged as a promising remedy in the therapeutic landscape for a wide array of neuropsychiatric conditions.”

https://link.springer.com/article/10.1007/s12035-025-05608-8

Development and Characterization of a High-CBD Cannabis Extract Nanoemulsion for Oral Mucosal Delivery

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“The cannabidiol (CBD)-rich cannabis extract CAN296 shows anti-inflammatory and anticancer activity relevant to oral lichen planus (OLP), oral graft-versus-host disease (oGVHD), and oral squamous cell carcinoma (OSCC), but its high lipophilicity limits aqueous dispersion.

This study developed a stable Tween-based nanoemulsion optimized for oral mucosal delivery.

Ethanol-dissolved CAN296 was nanoemulsified using a 1% Tween/Span system. Physical stability was visually assessed; droplet size and morphology were examined by dynamic light scattering (DLS) and transmission electron microscopy (TEM); and wettability was measured by static contact angle (SCA). Additional evaluations included temperature stability (25 °C vs. 4 °C), in vitro release using a dialysis membrane, and scanning electron microscopy (SEM) of membrane-associated droplets.

Nanoemulsions with ≥80% Tween 80 incorporated CAN296 up to 800 µg/mL, clear at 400 µg/mL, and uniformly turbid at 800 µg/mL. DLS and TEM confirmed spherical nanoscale droplets, and SCA indicated favorable cohesion and wettability. Stability was maintained for 30 days at 4 °C. Dialysis studies demonstrated strong membrane association with limited diffusion, supported by SEM visualization of membrane-bound droplets.

The Tween-dominant (≥80%) nanoemulsion stably incorporated CAN296 up to 800 µg/mL, demonstrated nanoscale uniformity, improved 4 °C stability, and strong membrane retention under static conditions, suggesting potential for localized oral delivery.”

https://pubmed.ncbi.nlm.nih.gov/41373676

“Cannabis-derived extracts rich in cannabidiol (CBD) have significant therapeutic potential in immune-mediated and oncologic oral diseases due to their anti-inflammatory, immunomodulatory, and pro-apoptotic effects.”

“This research established a Tween-dominant nanoemulsion capable of stabilizing a robust concentration of CBD-rich cannabis extract. This optimized system remains stable under refrigeration, exhibits favorable wettability and membrane retention, and provides a physically stable, ethanol-compatible platform for oral mucosal delivery of cannabis extract.”

https://www.mdpi.com/1422-0067/26/23/11525

Molecular Modeling and Analysis of Cannabinoid and Cannabinoid-like Molecules Combining K-Means Clustering with Pearson Correlation and PCA

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“More recently, cannabinoid molecules have been widely studied for their potential to treat various diseases.

We used a multidisciplinary approach, combining molecular docking and machine learning tools, to identify cannabinoid-based molecules as potential acetylcholinesterase inhibitors.

We brought together molecules from the classes of cannabinoids, stilbenoids, isoflavones, and other natural products, along with their electronic structure and absorption, distribution, metabolism, excretion and tolerable toxicity (ADMET) data. A novel machine learning framework (MolSimEx, Molecular Similarity Explorer) combining K-means clustering,

Pearson correlation, and principal component analysis was developed to address the similarities of these groups. From the dataset, 30 molecules were selected based on docking scores below -11 kcal/mol. The K-means clustering yielded high classification accuracy on the dataset, correctly grouping the cannabinoid analogues. Additionally, these analogues clustered with classical acetylcholinesterase inhibitors such as huprine-X, huprine-W, and donepezil when considering ADMET and electronic descriptor data.

Radulanin J showed the highest correlation (0.41) with donepezil’s profile, suggesting the potential of cannabinoid-derived compounds as acetylcholinesterase inhibitors.”

https://pubmed.ncbi.nlm.nih.gov/41373674

“We have identified a set of 30 molecules, out of 253 derived from phytocannabinoids, flavonoids, and terpenoids, as potential new inhibitors against the hAChE (6O4W) enzyme.”

https://www.mdpi.com/1422-0067/26/23/11520

“Acetylcholinesterase inhibitors (AChEIs) are drugs that block the enzyme acetylcholinesterase, preventing the breakdown of the neurotransmitter acetylcholine, thus increasing its levels in the brain to improve nerve cell communication. They are used primarily to treat symptoms of Alzheimer’s disease”

“Provides a blueprint for developing new treatments for Alzheimer’s by targeting AChE, a key enzyme in neurotransmission.”

The Endocannabinoid System: Scientific Insight and Biblical Reflection

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“The endocannabinoid system (ECS) is typically associated with using cannabis or cannabinoids. However, the ECS is a complex regulatory network within the human body that plays a vital role in maintaining physiological homeostasis. The ECS can become dysregulated through various mechanisms.

This article describes the physiology of the ECS using a biblical worldview. Nurses who understand the causes of ECS dysfunction can help lead patients toward lifestyle habits that reflect God’s design for balance, resilience, and wholeness.”

https://pubmed.ncbi.nlm.nih.gov/41359460

“The endocannabinoid system (ECS) is a crucial regulatory network in the human body, often linked to cannabis use but primarily responsible for maintaining physiological balance. This article explores the ECS from a biblical perspective, emphasizing its role in health and homeostasis.

Dysregulation of the ECS can occur through various mechanisms, and nurses who grasp these causes can guide patients towards lifestyle choices that align with a holistic approach to health, reflecting a divine design for balance and resilience.

Understanding the ECS can empower healthcare professionals to support patients in achieving overall well-being.”

https://journals.lww.com/journalofchristiannursing/abstract/2026/01000/the_endocannabinoid_system__scientific_insight_and.11.aspx

“Natural and synthetic cannabinoids finely regulate the endogenous cannabinoid system.”

https://www.sciencedirect.com/science/article/pii/S1043661825004475

The History and Use of Medical Cannabis

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“Archaeological and historical evidence indicate that cannabis has been used for medicinal purposes for almost 5,000 years. Although cannabis once was valued for its therapeutic properties, shifting social norms and political influences led to its criminalization and widespread stigma. This article explores the historical trajectory of medical cannabis from early therapeutic uses to integration into Western medicine, subsequent prohibition, and cautious resurgence. Implications for Christian healthcare providers are discussed. Key historical milestones are noted along with a comprehensive view of cannabis’ evolving role in health and healing across cultures and centuries.”

https://pubmed.ncbi.nlm.nih.gov/41359459

“Cannabis has been used medicinally for nearly 5,000 years, but its acceptance has fluctuated due to changing social norms and political pressures. Initially valued for its therapeutic benefits, cannabis faced criminalization and stigma, impacting its use in Western medicine. This article traces the history of medical cannabis, highlighting key milestones from its early use to its prohibition and recent cautious re-emergence. It also examines the implications for Christian healthcare providers, offering a broad perspective on cannabis’ role in health and healing across different cultures and eras.”

https://journals.lww.com/journalofchristiannursing/abstract/2026/01000/the_history_and_use_of_medical_cannabis.10.aspx

Bioreactor-Based Suspension Cultures of Cannabis sativa for Enhanced Production of Anti-Inflammatory Cannabinoid Derivatives

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“Cannabis sativa synthesizes diverse cannabinoids with significant pharmacological value, but existing suspension cultures show low metabolite yields and limited scalability.

This study establishes bioreactor-based cell suspension system to enhance cannabinoid biosynthesis in C. sativa. Petiole explants cultured on MS medium with 4 mg/L BAP and 0.01 mg/L NAA produced 95.83 ± 0.74% friable callus. Suspension cultures accumulated 352.29 ± 3.90 g/L fresh biomass in 28 days, showing 22.4-fold increase upon scale-up in stirred-tank bioreactor.

Methanolic extracts (60 °C) showed strong anti-inflammatory activity, reducing TNF-α and IL-6 by 88.40 ± 0.87 and 92.03 ± 1.55% at 30 μg mL-1 without cytotoxicity. Metabolomic profiling identified putative cannabinoid derivatives, with THCA-C1 (0.05%) exhibiting highest binding affinity (-8.4 kcal/mol) to inflammatory targets based on docking and dynamics analyses.

Overall, these results provide the first evidence for scalable cannabinoid biosynthesis in bioreactor-grown C. sativa cell suspensions, underscoring their potential for sustainable production of anti-inflammatory therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/41359809

https://pubs.acs.org/doi/10.1021/acs.jafc.5c10683


Medical Cannabis and Opioid Receipt Among Adults With Chronic Pain

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“Importance: Medical cannabis is increasingly considered a substitute for prescription opioid medications for chronic pain, driven by the urgent need for opioid alternatives to combat the ongoing epidemic.

Objective: To determine the association between participation in the New York State (NYS) medical cannabis program and prescription opioid receipt among adults with chronic pain.

Design, setting, and participants: This cohort study used data from the NYS Prescription Monitoring Program (PMP) from September 2018 through July 2023. Adults prescribed opioids for chronic pain who were newly certified for medical cannabis use in NYS were recruited from a large academic medical center and nearby medical cannabis dispensaries in the Bronx, New York. Monthly dispensation of medical cannabis to study participants was monitored for 18 months. Data analyses were performed from February 3, 2025, to July 15, 2025.

Exposure: Portion of days covered each month by pharmacist report of dispensed medical cannabis.

Main outcomes and measures: Prescription opioid receipt, defined as NYS PMP-reported prescription monthly opioid dispensation (mean daily dose in morphine milliequivalents [MME]), was assessed with marginal structural models adjusted for time-invariant and time-varying confounders, including self-reported unregulated cannabis use. Nonprescribed opioid use was also assessed during the study period.

Results: Among 204 participants, the mean (SD) age at baseline was 56.8 (12.8) years, and 113 (55.4%) were female. At baseline, participants’ mean (SD) pain severity score was 6.6 (1.8) out of 10, and mean (SD) pain interference score was 6.8 (1.9) out of 10. Baseline mean (SD) daily MME was 73.3 (133.0). During the 18-month follow-up period, participants’ mean (SD) daily MME decreased to 57.4 (127.8). This reduction in mean daily MME was associated with the monthly portion of days covered with medical cannabis; compared with no medical cannabis dispensed, participants dispensed a 30-day supply of medical cannabis were exposed to 3.53 fewer MME per day (β = -3.53; 95% CI, -6.68 to -0.04; P = .03).

Conclusions and relevance: In this cohort study, participation in NYS’s medical cannabis program was associated with reduced prescription opioid receipt during 18 months of prospective follow-up, accounting for unregulated cannabis use.”

https://pubmed.ncbi.nlm.nih.gov/41359313

“These findings suggest that participation in a pharmacist-directed medical cannabis program may help reduce prescription opioid receipt among adults with chronic pain.”

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2842414