Cannabis and Cannabinoid Research最新文献

Introduction: Cannabis sativa L. is an annual herbaceous plant with a long history of multipurpose use, including food, textile, and medicinal applications. The progressive legalization in several countries has significantly increased its large-scale cultivation, consequently generating a substantial amount of biomass waste. This scenario calls for innovative and sustainable strategies to valorize Cannabis residues, aiming at promoting the circular economy and technological innovation.

Materials and methods: An integrative review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Systematic searches were performed in SCOPUS, PubMed, and SciELO, complemented by specialized platforms such as CANNUSE and CONSENSUS. Peer-reviewed empirical studies were included if they addressed the utilization, reutilization, or recycling of C. sativa by-products or residues for the development of industrial products, processes, or inputs. The analysis considered thematic and commercial domains, geographic origin, and biomass type.

Results: A total of 262 studies were included, with 144 retrieved from indexed databases and 118 from alternative methods. The most commonly explored residues were stems (48.2%), seeds (21.0%), and postextraction residuum (9.7%). The majority of applications were related to technology and innovation (37.5%) and industrial sectors (36.9%). A total of 328 technologies were identified, highlighting applications such as textile fibers, bioplastics, biofuels, functional foods, adsorbents, and natural cosmetics. Italy, China, and the United States led in scientific production. Leaves (7.0%) and roots (0.9%) were significantly underexplored despite their bioactive potential.

Discussion: The findings demonstrate a growing global interest in the valorization of C. sativa residues, with promising applications in bioeconomy, regenerative agriculture, phytoremediation, and energy transition. The integration of traditional knowledge and green technologies is a key strategy to enhance sustainability and socioterritorial inclusion. Nonetheless, regulatory gaps and a lack of robust clinical and toxicological studies limit the use of by-products in food and feed chains.

Conclusion: The residual biomass of C. sativa holds high technological, environmental, and economic value. Strategic valorization demands regulatory advancement, the development of green technologies, and the strengthening of multidisciplinary research. Industrial Cannabis emerges as a driver of ecological, social, and economic transformation toward sustainable circular production systems.

Background: Cannabis consumption among adults, including pregnant and breastfeeding women, continues to rise. However, the long-term effects of early-life exposure to cannabinoids on brain development remain unclear. Δ9-tetrahydrocannabinol (THC) is the main psychoactive cannabinoid in cannabis and is an agonist of cannabinoid type 1 receptor, a critical component of the endocannabinoid system (ECS) that functions in normal pre- and postnatal brain development. We hypothesized that perinatal exposure to THC perturbs ECS-regulated neurodevelopment and leads to lasting cognitive effects in later life.

Materials and methods: Male and female Sprague Dawley rat pups received a single intraperitoneal injection of THC (5 mg/kg) or vehicle (sesame oil) at postnatal day 3. At postnatal weeks 6-8, animals were assessed for spatial memory and anxiety-like behavior using the Barnes maze, open field, and elevated plus maze. Following behavioral testing, brains were processed using Golgi-Cox staining to examine dendritic morphology and spine density in the frontal cortex and hippocampus.

Results: THC exposure during the neonatal period induced a spatial memory deficit later in young adult female, but not male, rats. Anxiety-like behavior was not altered in either sex. THC-exposed animals of both sexes exhibited decreased spine density reductions, as well as decreases in dendritic length, branching, and complexity in cortical and hippocampal (cornu ammonis 1 [CA1], CA3, dentate gyrus) neurons.

Conclusion: These findings demonstrate that a single neonatal THC exposure induces long-lasting, sex-dependent cognitive impairment and structural alterations in cortical and hippocampal neurons in rats. Our results underscore the vulnerability of the developing brain to cannabinoid exposure.

Introduction: The prevalence of prenatal cannabis use has nearly doubled in the United States. Cannabinoid 2 receptors are predominately expressed in cells of the human immune system, and delta-9 tetrahydrocannabinol (THC), the primary active component of cannabis, has been shown to suppress immune responses. Despite these findings, there is very little evidence on the impact of cannabis use on maternal immune system. Here, we evaluate the association between urine-verified cannabis use and the levels of T helper cytokines in the maternal circulation.

Methods: This was an ancillary study of a prospective cohort of pregnant women who participated in the Michigan Archive for Research on Child Health study. Pregnant women (age ≥18 years) were recruited from 22 prenatal clinics in Michigan and matched on age, race, and tobacco smoking (n = 144). The urinary metabolite of delta-9 THC, 11-nor-9-carboxy-delta-9-THC (THC-COOH), was used to define cannabis use status. A bead-based assay was used for the simultaneous detection of maternal cytokines associated with cannabis use and pregnancy outcomes in previous studies.

Results: Repeated-measures linear mixed models indicated that urine-verified cannabis use was associated with the suppression of maternal pro-inflammatory cytokines including interferon gamma (β = -0.5; 95% confidence interval [CI] = -0.8, -0.1) and interleukin (IL)-12 (β = -0.3; 95% CI = -0.6, -0.05), as well as the anti-inflammatory IL-4 (β = -0.7; 95% CI = -1.3, -0.2) and IL-10 (β = -0.4; 95% CI = -0.7, -0.03). Similar results were observed when heavy cannabis use was defined using the top tertile of urinary THC-COOH at each trimester.

Conclusions: Urine-verified cannabis use was associated with the suppression of pro- and anti-inflammatory T helper cytokines in a cohort of pregnant women, suggesting that cannabis use can lead to modest dysregulation of the maternal immune system. Additional studies are needed to investigate the role of maternal immune responses in explaining birth outcomes linked to cannabis use.

Introduction: Aromatase inhibitors (AIs) are commonly used for postmenopausal women with hormone receptor-positive breast cancer. Nearly two-thirds of women on AIs have arthralgias, joint stiffness, and/or bone pains referred to as aromatase inhibitor-induced musculoskeletal syndrome (AIMSS), leading to poor adherence. Preclinical and clinical data suggest topical cannabinoids can reduce inflammation in arthritis.

Materials and methods: We conducted a randomized trial assessing feasibility, tolerability, and preliminary efficacy of topical cannabis for women with stage 1-3 breast cancer experiencing AIMSS. Women were randomized 1:1 to cannabidiol (CBD) vs. delta-9-tetrahydrocannabinol (THC) balms. The balm was applied three times daily to hands for 2 weeks, followed by a 2-week extension with the balm of their choice. Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affectations of the Hands (M-SACRAH), brief pain inventory, and skin toxicity measures were captured weekly.

Results: A total of 21 women completed the study over 14 months. The mean age was 54, 86% White, 43% received adjuvant chemotherapy, and 48% reported no lifetime cannabis use. Compliance was high, with 71% continuing an additional 2 weeks and 86% of weekly surveys completed. We found 86% of participants reported improvement in M-SACRAH from baseline to week 2 with a higher percentage of the THC balm group reporting a >50% improvement (50% vs. 18%). Minor skin irritation was reported by 24%, and one patient discontinued balm due to "greasy" texture.

Conclusions: Conducting a randomized trial of topical cannabis using state-approved dispensaries is feasible. Both THC and CBD balms are well tolerated. Placebo-controlled trials are needed to determine if balms can reduce AIMSS severity in breast cancer survivors.

Neurological disorders such as epilepsy, Alzheimer's disease, Parkinson's disease, and multiple sclerosis present significant global health care challenges, with complex pathophysiology and limited therapeutic options that often carry substantial side effects. Hemp-derived compounds, particularly from Cannabis sativa seeds, leaves, and flowers, have gained attention for their potential neuroprotective properties. This review aims to synthesize the current evidence surrounding the therapeutic benefits of hemp-derived compounds, focusing on their bioactive phytochemical profiles, mechanisms of action, and therapeutic efficacy in treating neurological disorders. A comprehensive review of pre-clinical and clinical studies was conducted, analyzing the phytochemical composition of hemp extracts, including cannabinoids (such as cannabidiol, CBD), terpenes, flavonoids, and polyunsaturated fatty acids. We explored their mechanisms of action through interactions with the endocannabinoid system, neurotransmitter receptors, inflammatory pathways, and oxidative stress mechanisms. The review highlights the therapeutic potential of hemp-derived extracts in mitigating various neurological conditions. Pre-clinical and clinical studies have demonstrated their efficacy in reducing seizure frequency in epilepsy, protecting dopaminergic neurons in Parkinson's disease, alleviating neuroinflammation and oxidative stress in Alzheimer's disease, and promoting remyelination in multiple sclerosis. The entourage effect, where cannabinoids, terpenes, and flavonoids work synergistically, enhances these therapeutic effects. Innovations in extraction technologies have optimized yield and preserved bioactivity, further enhancing clinical relevance. Hemp-derived compounds exhibit significant neuroprotective and therapeutic potential for managing neurological disorders. However, challenges such as product standardization, safety profiles, and regulatory frameworks must be addressed for clinical translation. Further research is essential to optimize dosing, establish safety parameters, and develop standardized formulations, which will be crucial for fully harnessing the therapeutic potential of hemp-derived products in treating neurological conditions.

Introduction: Tolerance and dependence are known to occur with prolonged cannabis use. Few animal experiments on spontaneous withdrawal from delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, have been conducted. The experiments that have been conducted use extremely high doses and report relatively mild symptoms. The objective of the present experiment was to determine the magnitude and duration of spontaneous THC withdrawal in male and female rats using voluntary home cage wheel running as a sensitive, objective, and continuous measure of withdrawal.

Materials and methods: Male and female Sprague-Dawley rats were injected with THC (3 mg/kg, s.c.) or vehicle twice daily for 7 days to induce tolerance and dependence. Spontaneous withdrawal was assessed for 5 days beginning 24 h after the day 8 tolerance test in which all rats received a THC injection.

Results: On day 1, THC profoundly decreased wheel running in male and female rats compared to vehicle-treated rats. On day 8, THC given to vehicle-treated rats produced a significantly greater decrease in running than in rats previously treated with THC, indicating tolerance development. There was no sex difference in the magnitude of the decrease in wheel running caused by THC injections or in the development of tolerance. There were no significant changes in wheel running associated with spontaneous THC withdrawal.

Discussion: These data suggest that spontaneous THC withdrawal in male and female rats is mild at best despite profound locomotor suppression and tolerance to repeated injections. The lack of spontaneous THC withdrawal contrasts sharply with the pronounced changes in wheel running produced by opioid withdrawal.

Background: Human studies indicate a relationship between delta-9-tetrahydrocannabinol (THC) and alcohol use, yet research on their codependency remains limited. Rodent models have shown that cannabinoids can enhance the incentive salience and hedonic value of sucrose and alcohol. However, results seem to vary by the functions of THC dose and route of administration.

Materials and methods: The present study addresses these discrepancies by using a translational model of THC consumption, using lower oral doses of synthetic THC (Dronabinol). Male Long-Evans (n = 24) rats consumed a vehicle or THC-containing cookie (0.05 mg/kg or 0.5 mg/kg) before testing the palatability of rewarding and aversive substances in the taste reactivity paradigm.

Results: Separate, linear, mixed-effect models revealed that THC dose-dependently increased hedonic reactions to both sucrose (0.1 M and 0.5 M) and alcohol (10% and 40% ETOH) compared with control. Comparatively, THC reduced aversion to alcohol (10% and 40%) and quinine compared with vehicle. Western blot data analyzed via one-way Analysis of Variance (ANOVA) followed by Tukey's post hoc analysis revealed that repeated oral THC consumption dose-dependently downregulated cannabinoid receptor 1 receptor expression in the dorsal hippocampus, while no significant changes were observed in the nucleus accumbens or amygdala. Conclusions:These findings suggest that oral THC enhances the hedonic value of rewarding and aversive substances and provide insights into the neurobiological mechanisms that may contribute to the bidirectional use of cannabis and alcohol.

There is a large and growing population of individuals aged over 65 in the United States, many of whom drive automobiles. Elements of aging may adversely impact driving ability; in some individuals, mild cognitive impairment and early dementia are responsible for further deterioration. Older drivers have more crashes per mile driven and are more likely to be injured or die in crashes of similar magnitude. At the same time, an increasing number of older people are using cannabis for medical and recreational purposes. Cannabis (mostly due to its delta-9 tetrahydrocannabinol [THC] content) compromises sensory and neurocognitive abilities necessary for safe driving, and acute use is associated with an increased rate of motor vehicle crashes, including fatal ones. Evidence suggests that older individuals are more likely to be impaired by cannabis, possibly reflecting altered THC metabolism (due to changes in bodily composition and pharmacokinetics), as well as age-related changes in neurocognitive function and in the brain's endocannabinoid system. Consequently, older drivers who use cannabis may be at substantially increased risk of involvement in motor vehicle crashes. Despite this confluence of age-related factors, the amount of research on cannabis' effects on the driving ability of older adults is negligible, and public health messaging related to this situation is lacking. We suggest that more attention be paid to this topic.