Category Archives: Addiction

Protective Role of CBD Against Nicotine Pouch-Induced Seizure Aggravation and Alterations in Brain Glymphatic Biomarkers

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“Introduction: Nicotine pouches are rapidly increasing in popularity, yet their long-term neurological consequences remain poorly understood. Emerging evidence suggests nicotine may influence seizure susceptibility and neuroimmune signaling, while cannabidiol (CBD) has demonstrated neuroprotective and anti-inflammatory effects. This study investigated the time-dependent impact of acute versus chronic oral nicotine exposure on seizure vulnerability, neuroinflammation, and glymphatic function, and evaluated whether inhaled CBD can reverse these pathological changes.

Methods: Mice were exposed to acute or 7-day chronic nicotine pouch prior to kainic acid-induced seizures. Seizure severity was scored using the Racine scale. Neuroinflammatory markers (IL-6, HMGB1), neuronal activation markers (BDNF, c-FOS), and AQP4 expression were quantified via flow cytometry, immunofluorescence, and Western blotting. Glymphatic function was assessed using cisterna magna injection of rhodamine dextran tracers. An ex vivo IL-6 modulation assay evaluated nicotine-induced cytokine production and CBD-mediated suppression, with or without IL-6 receptor blockade.

Results: Acute nicotine transiently reduced seizure severity, whereas chronic exposure significantly exacerbated seizures, elevated IL-6, HMGB1, BDNF, and c-FOS, and markedly downregulated AQP4. CSF tracer studies confirmed impaired glymphatic influx following chronic nicotine exposure. CBD inhalation effectively reversed seizure severity restored AQP4 expression, normalized IL-6 and HMGB1 levels, and reduced c-FOS protein expression. The IL-6R blockade assay showed that nicotine induces IL-6 production in brain-derived immune cells, while CBD suppresses this response upstream of IL-6 signaling.

Conclusions: Chronic nicotine pouch exposure promotes seizure susceptibility through converging neuroimmune and glymphatic disruptions. Inhaled CBD counteracts these effects, supporting its potential as a targeted therapeutic strategy for nicotine-associated neurological risk.”

https://pubmed.ncbi.nlm.nih.gov/41384771

https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntaf253/8377968?redirectedFrom=fulltext&login=false

Computational GWAS Meta Meta Analysis Revealing Cross Talk Between Cannabis CNR1 and DRD2 Receptors Optimizing Long-Term Outcomes for Cannabis Use Disorder (CUD) By Enhancing Dopamine Homeostasis Promoting High-Quality Cannabis Medicinals

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“This paper presents a shared perspective from scientists and clinicians seeking to harness the therapeutic potential of cannabis while addressing Cannabis Use Disorder (CUD) through reproducible scientific findings.

Rather than blocking CNR1 receptors, which may induce hypodopaminergia, we propose a pro-dopaminergic strategy using a natural nutraceutical formulation designed to enhance dopamine release and upregulate D2 receptor mRNA, thereby increasing D2 receptor density.

Given the failure of CNR1 antagonists such as Rimonabant, we argue for an opposite approach: restoring dopamine balance through CNR1 stimulation rather than inhibition.”

https://pubmed.ncbi.nlm.nih.gov/41333412

https://www.researchsquare.com/article/rs-8140327/v1


Medicinal use of non-prescribed cannabis: a cross-sectional survey on patterns of use, motives for use, and treatment access in the Netherlands

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“Background: Despite the Netherlands having one of the world’s oldest medical cannabis programs, the majority of people who use cannabis for medicinal purposes continue to rely on non-prescribed sources. This study investigates patterns of use, motives for use, perceived effectiveness, and barriers to accessing prescribed cannabis among individuals self-medicating with non-prescribed cannabis.

Methods: A cross-sectional online survey was conducted between January and April 2023, using convenience sampling primarily via social media. Participants (N = 1059) were adults (18 years or older) residing in the Netherlands who self-reported current use of non-prescribed cannabis-based products to manage physical or mental health symptoms.

Results: Cannabis was used to manage a wide range of conditions, most commonly chronic pain, sleep disorders, depression, and ADHD/ADD, with three out of four participants reporting use for multiple conditions. Most participants obtained cannabis from coffeeshops, although one in four also reported home cultivation as a source. Participants typically smoked cannabis with tobacco, reported (near-)daily use for therapeutic purposes, and indicated a monthly expenditure of €100. The majority was not aware of the THC and CBD content of their products. Perceived effectiveness was rated as high, and more than half of those with a history of prescription medication use reported substituting cannabis for these medications. Only a minority of participants had ever used, or were currently using, prescribed cannabis. Commonly cited barriers included perceived lower quality, higher cost, and lower ease of access compared with non-prescribed cannabis.

Conclusions: The widespread use of non-prescribed cannabis for medicinal purposes in the Netherlands reflects both unmet health needs and barriers within the regulated medical cannabis system. Risky use practices – such as smoking cannabis with tobacco and using products without knowing their cannabinoid content – raise public health concerns. The findings highlight the need for harm reduction strategies and policies that better align medical cannabis regulation with patients’ real-world behaviours and care needs.”

https://pubmed.ncbi.nlm.nih.gov/41331499

https://link.springer.com/article/10.1186/s42238-025-00355-y

Predictors of Replacing Alcohol With Cannabis Among Adult Women

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“Background: Alcohol use among women varies by age, with younger women more likely to binge drink and older women more often engaging in consistent, long-term consumption. Both groups face health risks, including chronic disease, mental health conditions, and sleep disturbance. Cannabis has been proposed as a harm reduction substitute for alcohol because of its lower risks of dependency and health harms. The aims of this study are (a) to identify differences between younger and older women regarding their choices to use cannabis products as a substitute for alcohol and (b) to explore multiple drivers (sleep, stress, health state, post-traumatic stress disorder (PTSD), depression, and severity of alcohol use) behind the choice to replace alcohol with cannabis.

Methods: A cross-sectional online survey was conducted with 413 women aged 18 years and above who reported lifetime cannabis use. Participants were stratified into younger (<56 years) and older (≥56 years) groups. Measures included sociodemographics, cannabis substitution behaviors (cannabidiol (CBD), tetrahydrocannabinol (THC), or both), self-rated health, sleep and stress difficulties, and validated scales: Alcohol Use Disorders Identification Test (AUDIT), Primary Care PTSD Screen (PC-PTSD-4), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-8 (PHQ-8). Group differences were tested using chi-square and t-tests, and logistic regression identified predictors of substitution.

Results: Younger women (mean age 44.2 years) were significantly more likely than older women (mean age 62.9 years) to substitute THC for alcohol (14.0% vs. 7.8%, p = 0.019) and reported higher rates of sleep problems (52.5% vs. 39.1%, p = 0.007) and stress-coping difficulties (37% vs. 27%, p = 0.013). They also scored higher on AUDIT, PTSD, GAD, and PHQ instruments (all p < 0.01). Older women were more likely not to substitute cannabis for alcohol (83.5% vs. 71.0%, p = 0.002). Regression analyses showed that younger women with poorer health (OR = 1.76, 95% CI: 1.04-3.00) and higher AUDIT scores (OR = 1.07, 95% CI: 1.01-1.14) were more likely to substitute both CBD and THC. Sleep problems strongly predicted THC substitution in younger women (OR = 5.82, 95% CI: 1.58-21.45). Among older women, PTSD symptoms predicted substitution of both CBD and THC (OR = 1.60, 95% CI: 1.01-2.55), and sleep problems predicted THC substitution (OR = 3.05, 95% CI: 1.00-9.32).

Conclusions: Age-related differences emerged in women’s substitution of cannabis for alcohol. Younger women more frequently substituted THC and were influenced by alcohol severity, poor health, and sleep disturbance, whereas older women substituted less often, with PTSD and sleep difficulties as key predictors. These findings underscore cannabis substitution as a nuanced harm reduction strategy that requires age-specific approaches.”

https://pubmed.ncbi.nlm.nih.gov/41328136

“This study explored cannabis substitution as a potential harm reduction strategy, and its findings may inform prevention and intervention efforts aimed at reducing alcohol-related harms and improving women’s health outcomes.”

https://www.cureus.com/articles/418147-predictors-of-replacing-alcohol-with-cannabis-among-adult-women#!

Evaluating cannabis substitution for alcohol within the context of a canadian managed alcohol program

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“Introduction: Managed Alcohol Programs (MAPs) provide beverage alcohol alongside housing and social supports to mitigate alcohol-related harms among individuals experiencing severe alcohol use disorder (AUD) and unstable housing. MAPs have been shown to stabilize alcohol use, reduce alcohol-related harms, improve quality of life, and decrease emergency service utilization. However, concerns about the long-term health risks associated with high levels of alcohol use have driven interest in cannabis substitution as an additional harm reduction strategy. Given the lower harm profile of cannabis, its integration into MAPs offers a promising avenue for further reducing alcohol-related harms. This study evaluates a novel cannabis substitution program within a Canadian MAP, leveraging the unique context of cannabis legalization and harm reduction programming.

Methods: Beginning in January 2023, participants (N = 35) were offered the choice of a pre-rolled cannabis joint or their prescribed alcohol dose multiple times per day. Data were drawn from five waves of quantitative surveys (January 2023 to February 2024; n = 20), two years of program records (January 2022 to February 2024; N = 35), and qualitative interviews (n = 14). Hierarchical mixed-effects models were used to predict alcohol use by cannabis use and time. Qualitative data were analyzed using interpretive description methodology.

Results: The final model found evidence of a substitution effect: participants who used more cannabis on average also consumed less alcohol overall. Specifically, each additional 0.4-gram joint consumed (approximately 15.2 standard THC units or 76 mg THC) was associated with an estimated 2.43 fewer mean daily standard drinks. Within-person cannabis use was not a significant predictor, indicating that short-term fluctuations in cannabis use were not associated with concurrent changes in alcohol consumption. Alcohol use also declined over time. Qualitative findings provide insights into the dynamic factors shaping drinking and cannabis use patterns.

Conclusion: This study highlights the potential for cannabis substitution to meaningfully reduce alcohol-related harms. Implications for program development and future research evaluating changes in health, wellbeing, and harm outcomes are discussed.”

https://pubmed.ncbi.nlm.nih.gov/41313909

“Emerging evidence suggests that cannabis substitution for alcohol may offer a promising approach to mitigating alcohol-related harms. Cannabis is associated with lower toxicity, fewer long-term health risks, and a lower likelihood of overdose compared to alcohol.”

https://www.sciencedirect.com/science/article/pii/S0955395925003792?via%3Dihub

Cannabidiol alleviates methamphetamine-induced autophagy and oxidative stress by suppressing sigma 1 receptor expression

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“Methamphetamine (METH) is currently considered one of the most notorious drugs globally. Chronic long-term METH abuse results in severe neurotoxicity, wherein oxidative stress and autophagy are key pathological phenomena and toxic phenotypes. However, the molecular mechanism by which METH induces oxidative stress and autophagy remains elusive.

In this study, METH-induced autophagy and oxidative stress were replicated in both HT22 cells and C57BL/6 J mice. Notably, METH up-regulated the expression of chaperon protein sigma 1 receptor (S1R). However, METH-induced autophagy and oxidative stress were alleviated after targeted intervention with S1R using the chemical inhibitor, gene knockdown, or knockout techniques.

More importantly, cannabidiol (CBD), a non-psychoactive natural cannabinoid derived from cannabis, exhibited therapeutic efficacy by down-regulating the high expression of S1R, autophagy, and oxidative stress following METH exposure both in vivo and in vitro.

Overall, these results suggest that METH mediates autophagy and oxidative stress by up-regulating S1R expression, whereas CBD alleviates METH-induced autophagy and oxidative stress by suppressing S1R expression.

This study expands our understanding of METH-induced neurotoxicity, identifying S1R as a potential therapeutic target against aberrant autophagy and oxidative stress, and further validates the medical value of CBD for the treatment of METH use disorder.”

https://pubmed.ncbi.nlm.nih.gov/41314517

“Cannabidiol (CBD), a non-psychoactive natural cannabinoid derived from cannabis, exerts distinct pharmacological effects, such as antioxidant, anti-inflammatory, and neuroprotective effects, demonstrating therapeutic potential in several neurological diseases.”

“CBD alleviated METH-induced autophagy and oxidative stress by suppressing S1R expression.”

https://www.sciencedirect.com/science/article/abs/pii/S0898656825006953?via%3Dihub

Cannabis Laws and Opioid Use Among Commercially Insured Patients With Cancer Diagnoses

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“Importance: Pain is a prevalent cancer-related symptom, but limited research investigates whether cannabis is an effective analgesic for cancer pain.

Objective: To examine the association of medical and recreational cannabis dispensary availability on prescription opioid dispensing among commercially insured patients with cancer.

Design, setting, and participants: This cross-sectional study used synthetic control to investigate the association of cannabis dispensary openings with pain medication dispensing among patients with cancer. Data were extracted from Optum’s deidentified Clinformatics Data Mart database from January 1, 2007, to December 31, 2020. The study population included patients aged 18 to 64 years with a cancer diagnosis and at least 6 months of continuous enrollment. Associations were estimated by age, race and ethnicity, and sex. Data were analyzed between December 2024 and February 2025.

Exposures: Exposures included indicators for whether a medical or recreational cannabis dispensary was open in each state-quarter.

Main outcomes and measures: The outcome measures for opioids prescriptions were (1) the rate of patients with a prescription per 10 000 patients, (2) the quarterly mean days’ supply per prescription, and (3) the quarterly mean number of prescriptions per patient.

Results: The study included a mean (SD) of 3.05 (0.86) million patients annually across the US (mean [SD] age, 43.7 [9.6] years; mean [SD] 59.0% [0.32%] female). Medical cannabis dispensary openings were associated with significant reductions in all opioid outcomes. The rate of patients with cancer with opioid prescriptions changed by -41.07 per 10 000 (95% CI, -54.78 to -27.36 per 10 000; P < .001), the quarterly mean days’ supply by -2.54 days (95% CI, -3.16 to -1.92 days; P < .001), and the mean number of prescriptions per patient by -0.099 (95% CI, -0.121 to -0.077; P < .001). Recreational dispensary openings were also associated with reductions in opioid outcomes, though estimated treatment effects were smaller. The rate of prescriptions changed by -20.63 per 10 000 (95% CI, -35.35 to -5.91 per 10 000; P = .049), the mean daily supply by -1.09 days supplied per prescription (95% CI, -1.72 to -0.46 days; P = .04), and the mean number of prescriptions per patient by -0.097 (95% CI, -0.134 to -0.060; P = .01).

Conclusions and relevance: This study’s findings indicate cannabis may be a substitute for opioids in the management of cancer-related pain. However, further research directly observing cannabis use is needed to evaluate the efficacy of cannabis as a treatment for cancer-related pain.”

https://pubmed.ncbi.nlm.nih.gov/41105418

“Results of this study suggest that cannabis may serve as a substitute for opioids in managing cancer-related pain, underscoring the potential of cannabis policies to impact opioid use.”

https://jamanetwork.com/journals/jama-health-forum/fullarticle/2840030

A Preliminary Investigation of Brain Cannabinoid Receptor Type 1 (CB1R) Availability in Men with Opioid Use Disorder

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“The endocannabinoid (eCB) system has been proposed as a potential target for developing new medications for opioid use disorder (OUD). However, the status of the eCB system, specifically brain cannabinoid receptor type 1 (CB1R) in OUD, is unknown.

In this study, CB1R availability was measured in males with OUD on stable opioid agonist treatment (OAT) (n = 10) versus healthy controls (HC) (n = 18), using High-Resolution Research Tomography (HRRT) and the CB1R-specific radiotracer, [ 11 C]OMAR. The average volume of distribution ( V T ) across 13 regions was compared between the OUD and HC groups. Average V T was 15% lower in OUD vs. HC subjects (p = 0.04). Lower V T in OUD compared to HC was also observed in several corticolimbic areas.

Within OUD no effects on CB1R availability were observed for treatment medication (methadone vs. buprenorphine), current stress levels, or antidepressant medication. No associations between the average V T and duration of OAT treatment or time since the last illicit opioid use were observed.

This preliminary study suggests lower CB1R availability in men with OUD. Larger studies are necessary to replicate these findings. Future research should also draw from a more heterogeneous population, particularly by incorporating females, to better assess the potential confounding and moderating clinical factors. If confirmed, the observed alterations in CB1R availability in OUD may provide a rationale for targeting the eCB system in the treatment of OUD.”

https://pubmed.ncbi.nlm.nih.gov/41282260

https://www.researchsquare.com/article/rs-7715611/v1

Cannabidiol modulates brain molecular alterations, gut microbiota dysbiosis and alcohol self-administration in a mouse model of fetal alcohol spectrum disorder

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“Fetal Alcohol Spectrum Disorder (FASD) is a range of neurodevelopmental abnormalities caused by Perinatal Alcohol Exposure (PAE), leading to profound behavioral and molecular disturbances in the offspring. Unraveling the central and peripheral mechanisms involved, including the microbiota-gut-brain axis, is crucial to improving our understanding of the disease and developing new treatment strategies from a sex perspective.

In this study, we investigated the impact of PAE on emotional behavior, brain biomarkers, and gut microbiota composition and diversity in a preclinical C57BL/6 J mouse model, as well as the extent of their vulnerability to alcohol consumption. Furthermore, we have also explored the potential modulatory effects of cannabidiol (CBD) administered chronically (30 mg/kg/day, i.p.) from weaning on PAE-induced sex-dependent emotional and brain molecular impairments, gut microbiota dysbiosis, and increased alcohol reinforcing and motivational actions.

FASD model mice showed increased anxiety- and depressive-like behavior accompanied by sex-dependent changes in synaptic density, dopamine D2/D3 receptors availability, cannabinoid receptors 1 and 2 (Cnr1/Cnr2), tyrosine hydroxylase (Th), and serotonin transporter (Slc6a4) gene expression, and gut microbiota dysbiosis.

Interestingly, CBD sex-dependently improved and/or normalized PAE-induced behavioral and molecular disturbances. In addition, females but not males exposed to the animal model of FASD showed a higher motivation to drink alcohol, which CBD abolished.

Our findings provide new insights into the brain and gut microbiota sex-dependent mechanisms involved in FASD pathophysiology and further highlight the therapeutic potential of CBD to improve the management of FASD-induced emotional disturbances and alcohol addiction from a sex-oriented approach.”

https://pubmed.ncbi.nlm.nih.gov/41273930

“FASD model mice displayed emotional disturbances (anxiety- and depressive-like behaviors), which CBD alleviated.”

“Together, our findings reveal that PAE profoundly alters gut microbiota and that CBD can modulate this dysbiosis, promoting beneficial taxa and modifying community structure in a sex-dependent manner.

CBD administration also mitigated anxiety- and depression-like behaviors and modulated gene expression of endocannabinoid and monoaminergic markers.

This study opens the door to the development of personalized interventions aimed at restoring the microbiota and modulating the gut-brain axis to mitigate the cognitive and behavioral deficits characteristic of this disorder.”

https://www.sciencedirect.com/science/article/pii/S0753332225009850?via%3Dihub

Acute Effects of Cannabis on Alcohol Craving and Consumption: A Randomized Controlled Crossover Trial

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“Objective: Cannabis use is strongly linked with heavy drinking and worse alcohol treatment outcomes; however, it may also contribute to decreased alcohol consumption. To date, no human studies have established a causal effect of cannabis on alcohol motivation. The aim of this double-blind crossover randomized clinical trial was to examine dose-dependent acute effects of delta-9-tetrahydrocannabinol (THC) on alcohol craving and consumption.

Methods: Across three experimental days, 157 participants reporting heavy alcohol use and cannabis use two or more times weekly were randomized to smoke cannabis cigarettes containing 7.2% THC, 3.1% THC, or 0.03% THC (placebo), followed by exposures to neutral and personalized alcohol cues and an alcohol choice task for alcohol self-administration. A total of 138 participants completed two or more experimental sessions (mean age, 25.6 years [SD=5.1]; 35% women; 45% racial/ethnic minorities). Primary outcomes included craving, Alcohol Craving Questionnaire-Short Form, Revised (ACQ-SF-R), and an alcohol urge question; the secondary outcome was percent of total available milliliters of alcohol consumed.

Results: There were no significant effects of cannabis on ACQ-SF-R ratings after smoking and during alcohol cue exposure, but 7.2% THC reduced alcohol urge immediately after smoking. Participants consumed significantly less alcohol after smoking cannabis with 3.1% THC and 7.2% THC, reducing consumption by 19% and 27%, respectively.

Conclusions: Following overnight cannabis abstinence, smoking cannabis acutely decreased alcohol consumption compared to placebo. Further controlled research on a variety of cannabinoids is needed to inform clinical alcohol treatment guidelines.”

https://pubmed.ncbi.nlm.nih.gov/41254853

“These data provide preliminary evidence that cannabis may reduce alcohol consumption under some conditions”

https://psychiatryonline.org/doi/10.1176/appi.ajp.20250115