Author Archives: David Worrell

Purified cannabidiol as add-on therapy in children with treatment-resistant infantile epileptic spasms syndrome

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“Objective: The aim of this study was to assess efficacy, safety, and tolerability of highly purified cannabidiol oil (CBD) as add-on therapy for the treatment of a series of patients with infantile epileptic spasms syndrome (IESS) who were resistant to antiseizure medications and ketogenic dietary therapy.

Material and methods: We conducted a retrospective analysis of the medical records of 28 infants with treatment-resistant IESS aged 6 to 21 months who received highly purified CBD between July 2021 and June 2023. Data were collected on neurological examinations, EEG, Video-EEG and polygraphic recordings, imaging studies, laboratory testing, and seizure frequency, type, and duration, and adverse effects. As the primary outcome, a reduction of frequency of epileptic spasms (ES) was assessed. ES freedom was considered after a minimal time of 1 month without ES.

Results: Sixteen male and 12 female patients, aged 6-21 months, who received CBD for treatment-resistant IESS were included. The etiology was structural in 10, Down syndrome in seven, genetic in nine, and unknown in two. Initial CBD dose was 2 mg/kg/day, which was uptitrated to a median dose of 25 mg/kg/day (range, 2-50). Prior to CBD initiation, patients had a median of 69 ES in clusters per day (range, 41-75) and of 10 focal seizures per week (range, 7-13). After a mean and median follow-up of 15 and 12.5 months (range, 6-26 months), seven patients were ES free and 12 had a >50 % ES reduction. Five of seven patients (71 %) with Down syndrome and 3/5 (60 %) with cerebral palsy responded well. Adverse effects were mild. EEG improvements correlated with ES reductions.

Conclusion: In this study evaluating the use of CBD in children with IESS, 19/28 (67.8 %) had a more than 50 % ES reduction with good tolerability.”

https://pubmed.ncbi.nlm.nih.gov/38237316/

https://www.seizure-journal.com/article/S1059-1311(24)00018-9/fulltext

Cannabidiol effect on long-term brain alterations in septic rats: Involvement of PPARγ activation

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“Sepsis is a life-threatening condition induced by a deregulated host response to infection. Post-sepsis injury includes long-term cognitive impairment, whose neurobiological mechanisms and effective treatment remain unknown.

The present study was designed to determine the potential effects of cannabidiol (CBD) in a sepsis-associated encephalopathy (SAE) model and explore if peroxisome proliferator activated receptor gamma (PPARγ) is the putative mechanism underpinning the beneficial effects.

SAE was induced in Wistar rats by cecal ligation and puncture (CLP) or sham (control). CLP rats received vehicle, CBD (10 mg/kg), PPARγ inhibitor (GW9662 – 1 mg/kg), or GW9662 (1 mg/kg) + CBD (10 mg/kg) intraperitoneally for ten days. During this period, the survival rate was recorded, and at the end of 10 days, a memory test was performed, and the prefrontal cortex and hippocampus were removed to verify brain-derived neurotrophic factor (BDNF), cytokines (IL-1β, IL-6 and IL-10), myeloperoxidase activity, nitrite nitrate concentration, and lipid and protein carbonylation and catalase activity.

Septic rats presented cognitive decline and an increase in mortality following CLP. Only CBD alone improved the cognitive impairment, which was accompanied by restoration of BDNF, reduced neuroinflammation, and oxidative stress, mainly in the hippocampus.

This study shows that CLP induces an increase in brain damage and CBD has neuroprotective effects on memory impairment and neurotrophins, as well as against neuroinflammation and oxidative stress, and is mediated by PPARγ activation.”

https://pubmed.ncbi.nlm.nih.gov/38242525/

https://www.sciencedirect.com/science/article/abs/pii/S0006899324000258?via%3Dihub

Cannabis Use Associates With Reduced Proviral Burden and Inflammatory Cytokine in Tissues From Men With Clade C HIV-1 on Suppressive Antiretroviral Therapy

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“Background: Human immunodeficiency virus 1 (HIV-1) tissue reservoirs remain the main obstacle against an HIV cure. Limited information exists regarding cannabis’s effects on HIV-1 infections in vivo, and the impact of cannabis use on HIV-1 parenchymal tissue reservoirs is unexplored.

Methods: To investigate whether cannabis use alters HIV-1 tissue reservoirs, we systematically collected 21 postmortem brain and peripheral tissues from 20 men with subtype C HIV-1 and with suppressed viral load enrolled in Zambia, 10 of whom tested positive for cannabis use. The tissue distribution and copies of subtype C HIV-1 LTR, gag, env DNA and RNA, and the relative mRNA levels of cytokines IL-1β, IL-6, IL-10, and TGF-β1 were quantified using PCR-based approaches. Utilizing generalized linear mixed models we compared persons with HIV-1 and suppressed viral load, with and without cannabis use.

Results: The odds of tissues harboring HIV-1 DNA and the viral DNA copies in those tissues were significantly lower in persons using cannabis. Moreover, the transcription levels of proinflammatory cytokines IL-1β and IL-6 in lymphoid tissues of persons using cannabis were also significantly lower.

Conclusions: Our findings suggested that cannabis use is associated with reduced sizes and inflammatory cytokine expression of subtype C HIV-1 reservoirs in men with suppressed viral load.”

https://pubmed.ncbi.nlm.nih.gov/38243412/

https://academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiad575/7577694?redirectedFrom=fulltext&login=false

Current cannabis use and pain management among US cancer patients

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“Background: National studies reporting the prevalence of cannabis use have focused on individuals with a history of cancer without distinction by their treatment status, which can impact symptom burden. While pain is a primary motivation to use cannabis in cancer, the magnitude of its association with cannabis use remains understudied.

Methods: We examined cannabis use and pain management among 5523 respondents of the Behavioral Risk Factor Surveillance System with a cancer history. Survey-weighted prevalence proportions of respondents’ cannabis use are reported, stratified on cancer treatment status. Regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of cancer-related pain and cannabis use.

Results: Cannabis use was slightly more prevalent in those undergoing active treatment relative to those who were not undergoing active treatment (9.3% vs. 6.2%; P=0.05). Those under active treatment were more likely to use cannabis medicinally (71.6% vs. 50.0%; P=0.03). Relative to those without cancer-related pain, persons with pain under medical control (OR 2.1, 95% CI, 1.4-3.2) or uncontrolled pain were twice as likely to use cannabis (OR 2.0, 95% CI, 1.1-3.5).

Conclusions: Use of cannabis among cancer patients may be related to their treatment and is positively associated with cancer-related pain. Future research should investigate the associations of cannabis use, symptom burden, and treatment regimens across the treatment spectrum to facilitate interventions.”

https://pubmed.ncbi.nlm.nih.gov/38236449/

https://link.springer.com/article/10.1007/s00520-024-08321-9

Recreational and Medical Cannabis Legalization and Opioid Prescriptions and Mortality

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“Importance: While some have argued that cannabis legalization has helped to reduce opioid-related morbidity and mortality in the US, evidence has been mixed. Moreover, existing studies did not account for biases that could arise when policy effects vary over time or across states or when multiple policies are assessed at the same time, as in the case of recreational and medical cannabis legalization.

Objective: To quantify changes in opioid prescriptions and opioid overdose deaths associated with recreational and medical cannabis legalization in the US.

Design, setting, and participants: This quasiexperimental, generalized difference-in-differences analysis used annual state-level data between January 2006 and December 2020 to compare states that legalized recreational or medical cannabis vs those that did not.

Intervention: Recreational and medical cannabis law implementation (proxied by recreational and medical cannabis dispensary openings) between 2006 and 2020 across US states.

Main outcomes and measures: Opioid prescription rates per 100 persons and opioid overdose deaths per 100 000 population based on data from the US Centers for Disease Control and Prevention.

Results: Between 2006 and 2020, 13 states legalized recreational cannabis and 23 states legalized medical cannabis. There was no statistically significant association of recreational or medical cannabis laws with opioid prescriptions or overall opioid overdose mortality across the 15-year study period, although the results also suggested a potential reduction in synthetic opioid deaths associated with recreational cannabis laws (4.9 fewer deaths per 100 000 population; 95% CI, -9.49 to -0.30; P = .04). Sensitivity analyses excluding state economic indicators, accounting for additional opioid laws and using alternative ways to code treatment dates yielded substantively similar results, suggesting the absence of statistically significant associations between cannabis laws and the outcomes of interest during the full study period.

Conclusions and relevance: The results of this study suggest that, after accounting for biases due to possible heterogeneous effects and simultaneous assessment of recreational and medical cannabis legalization, the implementation of recreational or medical cannabis laws was not associated with opioid prescriptions or opioid mortality, with the exception of a possible reduction in synthetic opioid deaths associated with recreational cannabis law implementation.”

https://pubmed.ncbi.nlm.nih.gov/38241056/

https://jamanetwork.com/journals/jama-health-forum/fullarticle/2813866

Hemp Seed Cake Flour as a Source of Proteins, Minerals and Polyphenols and Its Impact on the Nutritional, Sensorial and Technological Quality of Bread

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“Hemp (Cannabis sativa L.) seeds contain a high concentration of proteins and biologically active compounds. The protein content is even higher in case of lipid part removal in oil production. The remaining part is considered a leftover, usually being used in animal feed. The aim of this study was to investigate the physicochemical composition of hemp seed cake flour, its nutritional quality and its impact on bread quality parameters. The properties of hemp seed cake flour were assessed in terms of protein quality, mineral composition, polyphenols and antioxidant activity.

Hemp seed cake proved to be an important source of high-quality protein (31.62% d.m.) with the presence of eight essential amino acids.

The biologically active potential of hemp seed cake has been demonstrated by the high content of polyphenols, especially those from the Cannabisin group. Hemp seed cake flour was incorporated in wheat flour at levels from 5 to 40% (w/w) to investigate its influence on bread quality parameters.

The addition of hemp seed cake flour increased the total phenol content of bread, thus greatly enhancing the antioxidant activity. The protein content of bread was found to be enhanced from 11.11% d.m (control sample) to 18.18% d.m (for sample with 40% hemp seed cake flour). On the other hand, the addition of hemp seed cake flour led to decreased bread porosity, increased hardness and decreased resilience in the seed cake. Although, all bread samples recorded sensorial attributes ranging between “slightly like” and “like it very much”.”

https://pubmed.ncbi.nlm.nih.gov/38231840/

“Hemp (Cannabis sativa L.) is a low-cost, unconventional feed resource with a unique phytochemical composition and various uses (pharmaceutical industry, food industry, etc)”

https://www.mdpi.com/2304-8158/12/23/4327

Alzheimer’s disease, aging, and cannabidiol treatment: a promising path to promote brain health and delay aging

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“Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by progressive memory loss, neurodegeneration, and cognitive decline. Aging is one of the risk factors for AD. Although the mechanisms underlying aging and the incidence rate of AD are unclear, aging and AD share some hallmarks, such as oxidative stress and chronic inflammation.

Cannabidiol (CBD), the major non-psychoactive phytocannabinoid extracted from Cannabis sativa, has recently emerged as a potential candidate for delaying aging and a valuable therapeutic tool for the treatment of aging-related neurodegenerative diseases due to its antioxidant and anti-inflammation properties.

This article reviews the relevant literature on AD, CBD treatment for AD, cellular senescence, aging, and CBD treatment for aging in recent years. By analyzing these published data, we attempt to explore the complex correlation between cellular senescence, aging, and Alzheimer’s disease, clarify the positive feedback effect between the senescence of neurocytes and Alzheimer’s disease, and summarize the role and possible molecular mechanisms of CBD in preventing aging and treating AD.

These data may provide new ideas on how to effectively prevent and delay aging, and develop effective treatment strategies for age-related diseases such as Alzheimer’s disease.”

https://pubmed.ncbi.nlm.nih.gov/38227160/

https://link.springer.com/article/10.1007/s11033-023-09162-1

The Therapeutic Potential of Cannabidiol in Revolutionising Opioid Use Disorder Management

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“Opioid use disorder (OUD) is a significant cause of morbidity and mortality worldwide and is linked to a complex interplay of biopsychosocial factors as well as the increasing overprescription and availability of opioid medications. Current OUD management relies on the controlled provision of opioid medications, such as methadone or buprenorphine, known as opioid replacement therapy. There is variable evidence regarding the long-term efficacy of these medications in improving the management of OUD, thereby necessitating an exploration into innovative approaches to complement, or even take the place of, existing treatment paradigms.

Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has garnered attention for its diverse pharmacological properties, including anti-inflammatory, analgesic, and anxiolytic effects. Preliminary studies suggest that CBD may target opioid withdrawal pathways that make CBD a potential therapeutic option for OUD.

This narrative review synthesises current literature surrounding OUD and offers a nuanced review of the current and future role of CBD in managing this condition. In doing so, we highlight the potential avenues to explore with respect to CBD research for the guidance and development of further research opportunities, framework and policy development, and clinical considerations before medicinal CBD can be integrated into evidence-based clinical guidelines.”

https://pubmed.ncbi.nlm.nih.gov/38226097/

https://www.cureus.com/articles/214898-the-therapeutic-potential-of-cannabidiol-in-revolutionising-opioid-use-disorder-management#!/

The impact of cannabis on non-medical opioid use among individuals receiving pharmacotherapies for opioid use disorder: a systematic review and meta-analysis of longitudinal studies

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“Background: The relationship between cannabis use and the risk of returning to using opioids non-medically during treatment for opioid use disorder (OUD) remains unclear.

Objective: We sought to quantify the impact of cannabis use on the risk of non-medical opioid use among people receiving pharmacotherapies for OUD.

Methods: A comprehensive search was performed using multiple databases from March 1 to April 5 of 2023. Eligible studies longitudinally assessed the association between cannabis use and non-medical opioid use among people with OUD receiving treatment with buprenorphine, methadone, or naltrexone. We utilized a random-effects model employing the restricted maximum likelihood method. A sensitivity analysis was conducted to understand potential differences between each OUD treatment modality.

Results: A total of 10 studies were included in the final meta-analysis. There were 8,367 participants (38% female). The average follow-up time across these studies was 9.7 months (SD = 3.77), ranging from 4 to 15 months. The pharmacotherapies involved were methadone (76.3%) buprenorphine (21.3%), and naltrexone (2.4%). The pooled odds ratio did not indicate that cannabis use significantly influenced non-medical opioid use (OR: 1.00, 95% CI: 0.97-1.04, p = .98). There is evidence of moderate heterogeneity and publication bias.

Conclusion: There was no significant association between cannabis use and non-medical opioid use among patients receiving pharmacotherapies for OUD. These findings neither confirm concerns about cannabis increasing non-medical opioid use during MOUD, nor do they endorse its efficacy in decreasing non-medical opioid use with MOUD.

This indicates a need for individualized approaches for cannabis use and challenges the requirement of cannabis abstinence to maintain OUD pharmacotherapies.”

https://pubmed.ncbi.nlm.nih.gov/38225727/

https://www.tandfonline.com/doi/full/10.1080/00952990.2023.2287406

The impact of cannabidiol placebo on responses to an acute stressor: A replication and proof of concept study

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“Background: Our group has previously reported that cannabidiol (CBD) expectancy alone blunts markers of stress, particularly during anticipation, but it is not clear the extent to which such findings were specific to the methods utilized.

Aims: To examine CBD-related placebo effects on stress reactivity and anticipation and to validate a protocol to be used in a neuroimaging study.

Methods: Forty-eight healthy adults (24 female) were randomly assigned to be informed that they ingested a CBD-containing oil or a CBD-free oil despite receiving the same oil (CBD-free). Following oil administration, participants engaged in a laboratory stressor and were then incorrectly informed that they would engage in a second more difficult task following a waiting period. Subjective state (sedation, energy, stress, anxiety) and heart rate were assessed at baseline, post-oil administration, immediately following the first stressor, and while anticipating the second stressor.

Results: Subjective stress and anxiety were significantly elevated immediately following the stressor (p-values < 0.001). CBD expectancy was associated with increased subjective sedation (p < 0.01) and tended to be associated with blunted subjective stress (p = 0.053). Post hoc within-condition pairwise compassions suggested a return to pre-stressor levels during the anticipation period in the CBD condition for subjective stress and anxiety (p = 0.784, 0.845), but not the CBD-free condition (p = 0.025, 0.045).

Conclusion: Results replicate and extend previous findings that CBD expectancy alone can impact stress- and anxiety-relevant responses in the laboratory context.”

https://pubmed.ncbi.nlm.nih.gov/38214314/

https://journals.sagepub.com/doi/10.1177/02698811231219060