Author Archives: David

Cannabis administration is associated with reduced alcohol consumption: Evidence from a novel laboratory co-administration paradigm

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“Background: Alcohol and cannabis co-use is increasingly prevalent across the U.S., concomitant with trends towards recreational cannabis legalization. While some studies have shown that cannabis co-use is associated with reductions in alcohol consumption (i.e., substitution), others have observed increases in alcohol intake (i.e., complementarity) or no change. This study aims to address this gap in the literature through investigating the effects of legal-market cannabis on alcohol consumption and craving in the laboratory.

Method: Leveraging a within-subjects design, we enrolled non-treatment seeking individuals who use both alcohol and cannabis (n = 61) to complete two laboratory sessions, wherein they were provided an alcohol priming drink alone or after self-administering cannabis. Participants were then given the opportunity to self-administer up to 4 additional drinks. We assessed differences in alcohol self-administration and craving between sessions.

Results: Cannabis self-administration was associated with a significant reduction in number of drinks self-administered. Further, exploratory analyses revealed that individuals who drank less after using cannabis (“substituters”, n = 23) experienced reductions in craving after using cannabis and alcohol compared to alcohol alone, whereas individuals who drank the same number of drinks after using cannabis show minimal differences in craving. There were no significant group differences in blood-THC concentration post-cannabis use.

Conclusion: Results indicate that for some individuals who drink heavily, cannabis may serve as a substitute for alcohol, and craving reduction is a potential mechanism through which this could occur.”

https://pubmed.ncbi.nlm.nih.gov/40915022/

“Cannabis use was associated with a reduction in alcohol intake.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871625003138?via%3Dihub

Short-term residual effects of smoked cannabis on simulated driving performance

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“Rationale: Between periods of use, chronic cannabis consumers may display residual effects on selective cognitive functions, particularly memory and attention. Whether there are comparable deficits in real-world behaviors, such as driving, has not been thoroughly examined.

Objectives: The current study explored the association between driving simulator performance, cannabis use history, and demographic factors after ≥ 48 h of abstinence. Study I examined simulator performance across a broad range of use within 191 healthy cannabis users. Study II compared performance between participants with the highest cannabis use intensity and a non-cannabis-using comparison group.

Methods: In Study I, 191 healthy cannabis users completed a 25-minute simulated drive, following ≥ 48 h of abstinence. In Study II, a pilot study comprising a subset of 18 frequent cannabis users was compared to 12 non-using controls who completed identical driving measures in a separate study. In both studies, the main outcome was the Composite Drive Score (CDS), a global measure of driving performance comprising key driving-related variables, including standard deviation of lateral position.

Results: In Study I, there was no relationship between CDS, its subtests, measures of cannabis use history, or demographic variables (all ps > 0.10). In Study II, frequent cannabis users and the non-using comparison group did not differ on CDS or performance on its subtests (all ps > 0.40).

Conclusions: The current study did not find evidence of a residual effect of cannabis on simulated driving performance during a short period of cannabis abstinence. Future studies would benefit from inclusion of larger non-cannabis-using comparison groups.”

https://pubmed.ncbi.nlm.nih.gov/40913146/

https://link.springer.com/article/10.1007/s00213-025-06880-1

UK Medical Cannabis Registry: A clinical outcomes analysis for insomnia

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“Insomnia affects approximately 10% of adults globally. Current treatments have their limitations, and there is growing evidence on the therapeutic potential of cannabis-based medicinal products for insomnia.

This study aimed to assess changes in sleep-specific and general patient-reported outcome measures (PROMs) in individuals prescribed cannabis-based medicinal products for insomnia and to assess the incidence of adverse events.

A case series was analysed with patients diagnosed with primary insomnia from the UK Medical Cannabis Registry (UKMCR). The primary outcome examined changes in the Single-Item Sleep Quality Scale (SQS), Generalised Anxiety Disorder-7 (GAD-7), and EuroQol-5 Dimension-5 Level (EQ-5D-5L). Changes in PROMs were assessed from baseline to 1-, 3-, 6-, 12- and 18-months. Adverse events were classified according to the CTCAE version 4.0. The inclusion criteria were met by 124 participants.

SQS scores showed improvement from baseline (2.66 ± 2.41) to 1- (5.67 ± 2.65; p < 0.001), 3- (5.41 ± 2.69; p < 0.001), 6- (4.80 ± 2.89; p < 0.001), 12- (4.24 ± 3.01; p < 0.001) and 18-months (3.81 ± 2.90; p < 0.001). GAD-7 scores improved from baseline to 1-, 3-, 6-, 12- and 18-months (p < 0.050). There were also improvements in EQ-5D-5L dimensions of usual activities, pain/discomfort, anxiety/depression, and index values (p < 0.001). Eleven (8.87%) participants reported a total of 112 (90.32%) adverse events, but none were disabling or life-threatening.

The study demonstrated improvements in subjective sleep quality and other captured PROMs in insomnia patients treated with cannabis-based medicinal products. Although the treatment was generally well-tolerated, randomised controlled trials are needed to confirm the effectiveness and safety of cannabis-based medicinal products.”

https://journals.plos.org/mentalhealth/article?id=10.1371/journal.pmen.0000390

“Study finds cannabis improves sleep where other drugs fail”

https://www.sciencedaily.com/releases/2025/09/250901104658.htm

Endocannabinoid signaling in epilepsy

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“Epilepsy, characterized by recurrent abnormal neuronal discharges, can lead to severe manifestations, including prolonged seizures that may become life-threatening. Despite the availability of numerous antiseizure drugs, many patients remain refractory to existing treatments, prompting the urgent search for novel therapeutic strategies.

One pivotal factor driving epileptogenesis is the disruption of the excitatory-inhibitory balance, resulting in excessive neuronal firing and hyperexcitability. In addition, neuroinflammation not only contributes to seizure generation but also exacerbates disease progression, forming a vicious cycle of neuronal damage.

The endocannabinoid (eCB) system, including eCBs, cannabinoid receptors, as well as biosynthetic and catabolic enzymes, has emerged as a crucial regulator of brain homeostasis.

By restoring excitatory-inhibitory balance and alleviating inflammation, eCB signaling influences key processes such as synaptic transmission, neuronal plasticity, and immune responses.

This dual capacity to regulate excitability and inflammatory pathways underscores its therapeutic potential for epilepsy.

In this review, we discussed the mechanisms by which eCB signaling regulates neuronal plasticity and inflammatory responses, emphasizing the interplay between these processes in epilepsy. We also discussed preclinical findings that support the therapeutic potential of targeting the eCB system.

By integrating insights from recent studies, we aim to provide a comprehensive overview of eCB-mediated neuroprotection and highlight future directions for epilepsy research and treatment.”

https://pubmed.ncbi.nlm.nih.gov/40886859/

https://www.sciencedirect.com/science/article/pii/S0969996125002918?via%3Dihub

Assessing Inflammatory Biomarkers at the Intersection of Marijuana and PrEP Use: Preliminary findings from the NCHAT-BIO study

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“Introduction: Past research has shown that inflammation is reduced among marijuana-using HIV-negative people but not those living with HIV. We take this work a step further by assessing differences based on pre-exposure prophylaxis (PrEP) use among HIV-negative individuals.

Methods: NCHAT is a nationally-representative cohort study of 3,642 adult respondents who are married or cohabiting. Their ages range from 20 to 60 years with 45% self-identifying as non-heterosexual. Biological data (n=573; CRP, IL-6, and EBV antibody levels) were collected via finger stick dried blood spots as part of NCHAT-BIO, a sub-study. Participants self-reported demographic characteristics, PrEP use, and marijuana use. Multivariable regression analyses were used to assess the relationship between these variables and each of the measured biomarkers, adjusting for known confounders.

Results: In adjusted models, neither lifetime or current PrEP use were associated with CRP, IL-6, or EBV antibody levels. Moreover, marijuana use did not differ among those who used PrEP versus those who did not. Among PrEP users, those who reported marijuana use had lower CRP than those who did not (B=-2.31; 95% CI:-4.23, -0.40). Among non-PrEP users, no association was observed between marijuana use and CRP.

Conclusion: The current preliminary data suggest inflammation is reduced among PrEP users who also use marijuana, but the same is not true among non-PrEP users. These findings may suggest that PrEP increases inflammation which is then partially mitigated by the individual cannabinoids or cannabidiols found in marijuana, although more research is needed to confirm this hypothesis.”

https://pubmed.ncbi.nlm.nih.gov/40905335/

https://journals.lww.com/jaids/abstract/9900/assessing_inflammatory_biomarkers_at_the.709.aspx

Effect of Preoperative Cannabis Use on Postoperative Pain and Outcomes Following Cardiothoracic Surgery

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“Cannabis use has grown both recreationally and medicinally in the United States over the past decades, alongside increased legalization and social acceptance. However, there remains little research investigating the effects of preoperative cannabis use on postoperative pain in patients undergoing surgery.

We conducted a single-center prospective study in adults undergoing cardiac surgery via sternotomy. Patients seen for preoperative consultation in clinic were asked a standardized survey about cannabis use. Clinical data was collected via chart review. Primary outcomes were morphine equivalents in the first 48 hours postoperatively and Visual Analog Scale (VAS) scores. Secondary outcomes were time to extubation, postoperative nausea/vomiting, ICU length of stay (LOS), reoperation, and in-hospital mortality. The non-cannabis user group had 50 patients, and the cannabis user group had 23 patients.

Average morphine equivalents in the first 48 hours were similar between cannabis users and non-users (60.98 vs 59.90; P = 0.93), as were VAS scores at 24 hours (5.52 vs 4.84; P = 0.414) and 48 hours (4.74 vs 3.90; P = 0.23). Average time to extubation (minutes) was nearly identical between cannabis users and non-users (718.41 vs 718.67; P = 0.99). There was also no significant difference in average LOS (days) between cannabis users and non-users (2.91 vs 3.48; P = 0.26). There were no differences in postoperative nausea/vomiting, reoperation, or in-hospital mortality.

In patients undergoing cardiac surgery via sternotomy, there was no effect of cannabis use on any outcomes, including morphine equivalents, Visual Analog Scale scores, time to extubation, ICU length of stay, postoperative nausea or vomiting, reoperation, or in-hospital mortality.”

https://pubmed.ncbi.nlm.nih.gov/40905360/

https://journals.sagepub.com/doi/10.1177/10892532251374952

Exploring therapeutic potential of Cannabis based therapy in autoimmune and rheumatic disorders

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“The medical use of cannabis is expanding across many countries, with some legalizing its use outright and others implementing medical licensure systems to approve treatment for eligible patients.

Despite this growing interest and utilization, there remains a lack of solid scientific evidence supporting its medical use, even though cannabis has been used therapeutically for thousands of years.

The goal of the following communication is to present updated data on the potential roles of cannabis-based treatments in various autoimmune and rheumatic conditions.

The information highlights that incorporating cannabis into the therapeutic armamentarium may offer benefits.

However, in many cases, despite encouraging perspectives and outcomes, the supporting evidence remains insufficient and requires further validation.

Due to social and legal barriers, the conduct of such rigorous clinical trials has been hindered, limiting the availability of high-quality evidence to guide medical practice.”

https://pubmed.ncbi.nlm.nih.gov/40907777/

https://www.sciencedirect.com/science/article/abs/pii/S1568997225001867?via%3Dihub

Cannabidiol dampens propagation of hippocampal hyperactivity and differentially modulates feedforward and feedback inhibition

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“Cannabidiol (CBD) decreases seizures in patients with severe pediatric-onset epilepsies including Dravet, Lennox-Gastaut, and Tuberous Sclerosis syndromes. However, the effects of CBD on neuronal activity and circuits remain obscure.

In the mouse hippocampus, we found that CBD causes a GPR55-independent decrease in CA1 pyramidal neuron firing frequency and a GPR55-dependent reduction in CA3 to CA1 hippocampal activity propagation. CBD-mediated decrease in high-frequency activity was mimicked by GPR55 antagonism and prevented by GPR55 deletion and blockade of GABAergic transmission. Dampening high-frequency activity was accompanied by increased recruitment of parvalbumin+ (PV)-INs and reduced recruitment of somatostatin+ (SST)-INs, leveraging the inhibitory subcircuit to limit propagation of hyperactivity. CBD-induced attenuation of high frequency spike propagation was mimicked by pharmacological enhancement and optogenetic engagement of PV-INs. Such increased on-demand recruitment of PV-INs dampened propagation of high-frequency activity to hippocampal CA1 similarly to CBD.

We predict that CBD potentially curbs propagation and perpetuation of seizure activity via these mechanisms.”

https://pubmed.ncbi.nlm.nih.gov/40909733/

https://www.biorxiv.org/content/10.1101/2025.08.26.672420v1

Dietary Cannabidiol Supplementation on Growth Performance, Behavior, Blood Profile, Metabolomic Analysis, and Fatty Acid Composition in Rabbits: A Multi-Disciplinary Approach to Improve Welfare and Productivity

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“This study evaluated the effects of dietary cannabidiol (CBD) supplementation on behavior, blood parameters, oxidative status, metabolomic profile, and the fatty acid composition of meat and liver in rabbits.

A total of 42 New Zealand White × California rabbits (60 days old; 1:1 sex ratio; average weight 1621.3 ± 46.2 g) were randomly assigned to two groups (a control group, CTRL, and a CBD group, n = 21 each). Both groups received the same commercial diet, with the CBD group additionally supplemented with 0.1 mL of cannabis extract in coconut oil, corresponding to 10 mg CBD/animal/day. At 92 days of age, rabbits were slaughtered, and samples were collected for analyses.

Results showed that CBD supplementation significantly improved body weight gain, reduced plasma triglyceride levels, and enhanced oxidative status.

Behavioral observations indicated increased motor and grooming activities in CBD-supplemented animals, suggesting enhanced psychological well-being. The fatty acid profile of meat and liver was not significantly altered by CBD supplementation.

Overall, dietary CBD demonstrated the potential to positively influence physiological and behavioral responses, representing a promising strategy to enhance animal welfare and productivity in rabbit farming. Although no adverse effects on lipid profiles were observed, further studies are warranted to explore CBD’s role in lipid metabolism and cholesterol regulation.”

https://pubmed.ncbi.nlm.nih.gov/40905739/

“Animal health and welfare are essential for ethical farming and high-quality food production. This study evaluated the effects of dietary cannabidiol (CBD) supplementation on behavior, some blood parameters, and fatty acid composition in meat and liver of rabbits. CBD is gaining attention for its pharmacological properties and its role in the endocannabinoid system. The results suggest that CBD supplementation can influence behavioral and physiological responses in rabbits, offering potential benefits for both animal welfare and meat quality.”

https://www.mdpi.com/2306-7381/12/8/759

Synergistic Anticancer Effects of Fibroblast Growth Factor Receptor Inhibitor and Cannabidiol in Colorectal Cancer

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“Background/objectives: Colorectal cancer (CRC) remains a significant global health concern, with limited treatment options for metastatic stage 4 CRC. Fibroblast Growth Factor Receptor (FGFR) is a promising therapeutic target in CRC, while cannabidiol (CBD) has shown potential for inducing cell death and overcoming drug resistance. This study evaluates the efficacy of FGFR inhibitors and explores the synergistic effects of combining FGFR inhibitors with CBD in inducing apoptosis in CRC cells.

Methods: Cannabidiol and FGFR inhibitors were applied, and protein expression was analyzed via Western blot. Cell viability was assessed using the WST-1 assay, while apoptosis was measured through flow cytometry using Annexin V-FITC/PI staining. CHOP-specific siRNA transfection was performed to study gene silencing effects, followed by RNA sequencing for differential expression and pathway analysis. Statistical significance was determined using ANOVA and t-tests, with p < 0.05.

Results: FGFR expression patterns were confirmed in various cancer cell lines, with NCI-H716 showing high FGFR2 expression. Treatment with CBD (4 µM) and AZD4547 (10 nM) resulted in significant cell death, especially when used in combination, indicating the effectiveness of this combined therapy. Increased apoptosis in NCI-H716 cells was confirmed with the combined treatment. RNA sequencing and heatmap analysis suggested that ER stress might be related to the observed synergistic effect. The role of ER stress in the combination-induced apoptosis of NCI-H716 cells was further validated.

Conclusions: The combination of FGFR inhibitors and cannabidiol exhibited a synergistic effect in inducing cell death in colorectal cancer cells, likely through the ER stress pathway. This study supports the potential of combined FGFR inhibitor and CBD therapy as a promising strategy for enhancing anticancer effects in CRC.”

https://pubmed.ncbi.nlm.nih.gov/40871637/

“In conclusion, the data from this preclinical study indicate that the combination of cannabidiol (CBD) and FGFR inhibitors such as AZD4547 represents a potential therapeutic approach for metastatic colorectal cancer (CRC). This synergistic effect could help address resistance mechanisms that currently limit the efficacy of anticancer drugs. Our findings also suggest that ER stress-mediated apoptosis may be an important mechanism underlying this synergy. While these results are encouraging, further validation in appropriate preclinical animal models and, ultimately, clinical studies will be essential to confirm efficacy, assess safety, and determine the translational applicability of this combination strategy.”

https://www.mdpi.com/2072-6643/17/16/2609