Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Changes in Local Community Spatial Trends of Motor Vehicle Accidents Near Cannabis Dispensaries after Recreational Cannabis Legalization

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“Introduction: In recent years, the impact of recreational cannabis legalization (RCL) on road safety and motor vehicle accidents (MVAs) has become a growing area of research, given increasing cannabis legalization and the impact of cannabis on motor control and attention. In 2023, Connecticut legalized recreational cannabis, and this study explored changes in MVAs both in a statewide analysis and in the local vicinity of recreational cannabis dispensaries. 

Materials and Methods: We conducted an ecological study to assess the impact of recreational cannabis dispensaries on MVAs in Connecticut after legalization on January 10, 2023. Using crash data from Connecticut and Maryland (as a control) for two 24-week periods before and after legalization, we performed a difference-in-differences analysis with negative binomial regression, controlling confounders. At the dispensary level, we compared MVAs within an 800-m radius 8 weeks before and after opening, employing interrupted time series analysis with negative binomial mixed-effects regression models. 

Results: In the statewide analysis comparing Connecticut with Maryland over two 24-week periods before and after RCL in Connecticut, no significant effect on MVAs was found after adjusting for autocorrelation and seasonal variations (interaction term coefficient = -0.0391, p = 0.0696). In the local analysis, examining accident rates within an 800-m radius of 13 dispensaries over 8 weeks before and after their openings, the negative binomial mixed-effects model showed no significant change (incidence rate ratio = 1.10, 95% confidence interval: 0.74-1.64, p = 0.63). 

Discussion: These findings suggest that cannabis legalization and dispensary openings did not significantly impact motor vehicle accident rates during the study period.”

https://pubmed.ncbi.nlm.nih.gov/40779507/

Hybrid Cannabis sativa L. inflorescences exert an anti-inflammatory effect through the modulation of MAPK/NF-κB/NLRP3 inflammasome and JAK1/STAT6 pathway in HaCaT cells

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“Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease accompanied by severe itching. Reducing mediators of skin inflammation and itching is crucial for the treatment of AD. Cannabis sativa L. contains many types of cannabinoids and flavonoids, which exhibit antioxidant and anti-inflammatory effects. This study aims to demonstrate the anti-inflammatory and anti-atopic dermatitis effects of hybrid C. sativa L. inflorescence extracts (HCIE) in human keratinocytes.

Methods: Cannabis sativa extracts were analyzed using UPLC. Gene expression levels in HCIE-treated HaCaT cells were measured by RT-PCR, and intracellular ROS were evaluated using DCF-DA. Protein expression levels related to MAPK, NF-κB, NLRP3 inflammasome, and JAK1/STAT6 pathways were determined by immunoblotting.

Results: The UPLC analysis revealed that a total of 8 cannabinoids were detected in HCIE. Among the cannabinoids identified in HCIE, CBDA and CBD were the most abundant, collectively accounting for approximately 28% of the total extract. The gene expression of MDC, RANTES, and TARC exhibited dose-dependent suppression in the HCIE-treated group. MAPK phosphorylation was inhibited in the HCIE-treated group. Additionally, NF-kB, p-NF-kB, NLRP3, and caspase-1 were reduced in a dose-dependent manner by HCIE. The activation of JAK1 and STAT6 was diminished in HaCaT cells treated with HCIE. Conversely, the levels of filaggrin and involucrin were significantly elevated in the HCIE-treated group compared to the control group.

Conclusion: Taken together, HCIE suppresses inflammation mediators through the regulation of the MAPK/NF-κB/NLRP3 inflammasome and JAK1/STAT6 pathways, while up-regulating skin moisturizing factors in keratinocytes. These results suggest that HCIE may be utilized in the treatment of skin inflammatory diseases, such as AD.”

https://pubmed.ncbi.nlm.nih.gov/40777996/

“HCIE exerts anti-inflammatory and anti-atopic dermatitis effects in human keratinocytes by modulating the MAPK/NF-κB/NLRP3 inflammasome, JAK1/STAT6 pathway, and skin moisturizing factors. To further elucidate the effects of HCIE on AD, additional studies using in vivo models are required. Nevertheless, considering the effects of HCIE proven in this study, HCIE is a valuable substance for improving skin inflammation, potentially serving as an effective therapeutic agent or adjuvant for AD.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1617180/full

Exploring the impact of chronic intermittent EU-GMP certified Cannabis sativa L. therapy and its relevance in a rat model of aging

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“Background: Aging is a multifaceted process marked by the progressive accumulation of cellular damage in various tissues, resulting in a decline in physiological functions. The primary aim of aging research is to identify compounds that can delay or mitigate these detrimental changes. As cannabis legalization becomes more widespread and with limited empirical studies on its effects in the aging human population, there is a pressing need for research into the impact of Cannabis and cannabinoids on healthy aging and age-related diseases.

Methods: Our study aims to evaluate the effects of chronic, intermittent exposure, defined as 6 weeks of use of EU-GMP certified Cannabis sativa L. (Cannabixir® Medium Flos) administration, dosed at 6.25 and 25 mg/kg on neurobiological changes in naturally aged rats and its potential efficacy in mitigating age-related alterations. The impact of the Cannabixir® Medium Flos was assessed through clinical, histopathological, immunohistochemical, and behavioral evaluations.

Results: Cannabixir® Medium Flos was found to be generally safe, with no significant effects on motor performance and a neutral effect on anxiety-like behavior. Histological analysis revealed that the hippocampus of aged rats treated with this compound-an area known for its abundance of endocannabinoids and cannabinoid receptor type 1-exhibited characteristics similar to those observed in young adult rats. Additionally, the study suggests that chronic, intermittent treatment with Cannabixir® Medium Flos may modulate astrocyte function, reduce neuroinflammation, and potentially influence cell proliferation and neuronal apoptosis in a dose-dependent manner. However, these preliminary findings should be interpreted with caution, as the study’s exploratory nature.

Conclusions: These preliminary findings suggest that cannabinoid therapy targeting the endocannabinoid system may offer potential neuroprotective benefits in aging.

While the study offers valuable preclinical insights into the effects of an EU-GMP-certified cannabinoid receptor ligand in reducing age-related cognitive decline, these effects are likely mediated by a combination of mechanisms. Given the complex phytochemical composition, the observed outcomes cannot be attributed exclusively to cannabinoid receptor activation. Accordingly, these findings should be interpreted with caution, and further studies employing more targeted methodologies are needed to elucidate the underlying mechanisms.”

https://pubmed.ncbi.nlm.nih.gov/40770774/

“Targeting the ECS could be a promising strategy for developing therapies aimed at promoting healthy aging and longevity.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00313-8

Single oral administration of dronabinol increases ocular blood flow in patients with glaucoma

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“Purpose: Glaucoma is a leading cause of irreversible blindness globally, primarily driven by elevated intraocular pressure (IOP). Still, some patients progress despite significant IOP lowering, potentially due to impaired ocular blood flow. This study aimed to evaluate the effects of dronabinol, a synthetic tetrahydrocannabinol derivative, on ocular blood flow in primary open-angle glaucoma (POAG) patients.

Methods: This randomized, double-masked, placebo-controlled, cross-over study included 23 patients with treated POAG (mean age 68 ± 7 years). All participants received dronabinol (11 patients received 5 mg and 12 received 10 mg in a randomized fashion) on one study day and placebo on the other study day. The primary outcome was optic nerve head blood flow (ONHBF) measured by laser speckle flowgraphy. Mean blur rate was determined for the large vessel area (MV), the tissue area (MT) and the total ONH area (MA). Secondary outcomes included vessel densities assessed by optical coherence tomography angiography, IOP, and blood pressure.

Results: Administration of 10 mg dronabinol significantly increased ONHBF (MA: 10.8 ± 20.6%, p = 0.018, MV: 12.0 ± 24.8%, p = 0.042, and MT: 11.0 ± 22.6%, p = 0.022, each vs. placebo) up to 4 h post-administration without affecting IOP or mean arterial pressure (p > 0.548 each). Additionally, a significant increase in vessel density in the superficial vascular plexus was found after administration of 10 mg dronabinol (6.7 ± 14.7%, p = 0.040 vs. 5 mg).

Conclusion: This pilot study demonstrates that systemic dronabinol enhances ONHBF in glaucoma patients, suggesting its potential as adjunct therapy for glaucoma by targeting vascular dysfunction. Further longitudinal studies are needed to explore its long-term impact on disease progression and visual field preservation.”

https://pubmed.ncbi.nlm.nih.gov/40772417/

“Tetrahydrocannabinol (THC) has long been considered a treatment option for glaucoma, mainly because of its IOP-lowering properties. In addition, THC may also increase ocular blood flow, at least in healthy subjects. Recent data from our laboratory confirm that even low doses of THC, which neither affect IOP nor induce systemic psychoactive side effects, can increase ocular blood flow considerably.”

“In summary, our study demonstrates that administration of 10 mg dronabinol leads to a significant increase in ocular blood flow in patients with glaucoma. The effect seems to be dose-dependent, as a single administration of 5 mg had no effect on ocular blood flow. These findings highlight the potential role of dronabinol in improving ocular perfusion in glaucoma patients but also underscore the importance of considering age and disease-related factors when assessing cannabinoid-mediated vascular effects. Further investigations with larger sample sizes, longer study durations, and multiple applications instead of single intake are warranted to evaluate the potential clinical benefits of this therapeutic approach.”

https://onlinelibrary.wiley.com/doi/10.1111/aos.17573

Neural Signatures of Cannabis Use: Reversing Cognitive Aging via Whole-Brain Functional Network Connectivity

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“Given the growing trend toward permissive societal attitudes and the legalization of cannabis, coupled with an increasing recognition of its therapeutic potential, there has been a notable rise in cannabis consumption among older adults.

Cognitive aging, one of the most prevalent concerns in this demographic, intersects with cannabis use, which shares several neural correlates. However, the precise impact of cannabis on the aging brain and cognitive function remains poorly understood.

In this study, we leveraged large-scale data from the UK Biobank, which includes over 25,000 participants, to conduct a comprehensive examination of the relationships between cannabis use, normative aging, and cognitive function. Our focus was on how these factors correlate with brain functional network connectivity (FNC), aiming to elucidate the interactive effects underlying brain neuroimaging patterns.

Our findings reveal that cannabis usage and healthy aging are associated with overlapping brain network configurations, particularly within the FNC between subcortical and sensorimotor regions, as well as between subcortical and cerebellar areas, albeit with significantly reversed effects.

Notably, cannabis users exhibited superior performance across multiple cognitive domains, and interestingly, the effects of cannabis and cognition are presented concurrently across a range of brain systems.

In conclusion, our study offers valuable insights into the potential influence of cannabis on brain aging and cognitive performance. The results suggest that cannabis users display brain network characteristics typically associated with younger brains, along with enhanced cognitive abilities, highlighting a potential modulatory role for cannabinoids and endocannabinoids in neurodegenerative processes, as explained through neural dedifferentiation and compensation theories.”

https://pubmed.ncbi.nlm.nih.gov/40766216/

https://www.researchsquare.com/article/rs-6977015/v1

Will you precrastinate? Sensitivity to potential performance costs and effort in chronic cannabis users and non-users

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“We examined whether those who chronically use cannabis (chronic users), compared to those who do not use cannabis (non-users), tend to precrastinate (start or complete a subgoal as soon as possible) and engage in reactive (vs. proactive) decision-making incurring greater potential costs in task performance and perhaps costs in cognitive and physical effort. Participants walked down a hallway and retrieved two full cups of water (one near and one far from their starting position) in the order of their choice and carried both back to their start location with the goal of not spilling. First-cup choice (near or far) and attributions of first-cup choice were recorded.

Counter to expectations, chronic users tended to choose the far cup first (i.e., avoided precrastination), the more efficient choice, and this tendency was not different from non-users. Participants’ attributions confirmed that those who chose the far cup first likely engaged in proactive decision-making while those who chose the near cup first likely engaged in reactive decision-making. Additionally, chronic users and non-users utilized proactive control in the AX-Continuous Performance Task even though chronic users had lower short-term and working memory span scores.

These results contradict research suggesting chronic users (vs. non-users) are more impulsive, lack inhibitory control, tend to invest physical effort regardless of reward, and tend not to invest cognitive effort for reward. We suggest that chronic cannabis use may not impair decision making as profoundly as previously thought if individuals are motivated by potential consequences of their decisions in tasks with low memory demand.”

https://pubmed.ncbi.nlm.nih.gov/40760056/

https://link.springer.com/article/10.1007/s00426-025-02139-8

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

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“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/