Monthly Archives: January 2024

Acute and Extended Anxiolytic Effects of Cannabidiol in Cannabis Flower: A Quasi-Experimental ad libitum Use Study

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“Objective: Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have varying pharmacological actions with differential effects on acute and extended affective states, incuding anxiety. We aimed to study these effects on anxiety in legal market forms of cannabis. 

Method: This study makes use of a nonequivalent control group quasiexperimental design. Forty-two participants with anxiety symptions who were not using cannabis were compared to 258 participants with anxiety symptoms who used cannabis flower (∼3-4 times per week). Participants who used cannabis were randomly assigned to one of three legal market cannabis conditions; THC-dominant (24% THC, <1% CBD), THC+CBD (12% THC, 12% CBD), or CBD-dominant (<1% THC, 24% CBD). Changes in anxiety symptoms over 4-weeks were measured by the Patient Global Impression of Change (PGIC) scale and the Depression, Anxiety, and Stress Scale (DASS). Acute changes in subjective mood immediately after cannabis use were measured by the Profile of Mood States (POMS) Elation, Tension, and Paranoia subscales and the Addiction Research Center Inventory intoxication scale. 

Results: While all participants reported anxiety reductions over the 4-week study on the PGIC (F=30.65, p<0.001) and DASS anxiety measures (F=115.88, p<0.001), ad libitum CBD-dominant cannabis use was associated with lower scores on the DASS anxiety subscale compared to THC-dominant use when accounting for frequency of use (difference=-1.03, SE=0.45, p=0.02). Similarly, acute CBD-dominant cannabis use was associated with lower scores on the POMS tension and paranoia subscales (POMS tension: CBD-dominant vs. THC-dominant: difference=-0.41 SE=0.1, p<0.001; CBD-dominant vs. THC+CBD: difference=-0.28, SE=0.07, p=0.04; POMS paranoia: CBD-dominant vs. THC-dominant: difference=-0.49, SE=0.1, p<0.001; CBD-dominant vs. THC+CBD: difference=-0.33, SE=0.09, p=0.01). Participants in all cannabis conditions experienced acute changes in positive mood and subjective drug effects. 

Conclusions: This study provides novel information on the impacts of legal market cannabis with varying ratios of THC to CBD in indviduals with anxiety symptoms. Findings suggest that THC did not increase anxiety and that CBD-dominant forms of cannabis were associated with acute tension reduction that may translate to longer-term reductions in anxiety symptoms.”

https://pubmed.ncbi.nlm.nih.gov/38252547/

https://www.liebertpub.com/doi/10.1089/can.2023.0187

Cannabis Roots: Therapeutic, Biotechnological and Environmental Aspects

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“Since the legalization of recreational cannabis in Canada in 2018, the number of licenses for this crop has increased significantly, resulting in an increase in waste generated.

Nevertheless, cannabis roots were once used for their therapeutic properties, indicating that they could be valued today rather than dismissed.

This review will focus on both traditional therapeutic aspects and potential use of roots in modern medicine while detailing the main studies on active phytomolecules found in cannabis roots. The environmental impact of cannabis cultivation and current knowledge of the root-associated microbiome are also presented as well as their potential applications in biotechnology and phytoremediation. Thus, several high added-value applications of cannabis roots resulting from scientific advances in recent years can be considered to remove them from discarded residues.”

https://pubmed.ncbi.nlm.nih.gov/38252502/

https://www.liebertpub.com/doi/10.1089/can.2023.0168

Cannabidiol Combination Enhances Photodynamic Therapy Effects on MCF-7 Breast Cancer Cells

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“Cannabis sativa is a well-known plant for its psychoactive effects; however, its many derivatives, such as Cannabidiol (CBD), contain several therapeutic applications. Tetrahydrocannabinol (THC) is the main cannabis derivative responsible for psychoactive properties, while CBD is non-psychotropic. For this reason, CBD has been more exploited in the last decade.

CBD has been connected to multiple anticancer properties, and when combined with photodynamic therapy (PDT), it is possible to eradicate tumors more effectively. In this study, CBD was utilized to treat MCF-7 breast cancer cells, followed by in vitro PDT combination therapy. Conventional breast cancer treatment modalities such as chemotherapy, radiotherapy, etc. have been reported for inducing a number of undesirable side effects, recurrence of the disease, and low quality of life.

In this study, cells were exposed to varying concentrations of CBD (i.e., 1.25, 2.5, 5, 10, and 20 μg/mL) and incubated 12 and 24 h after treatment. The optimal doses were then used in combination therapy. Morphology and biochemical assays, including lactate dehydrogenase (LDH) for membrane integrity, adenosine triphosphate (ATP) for viability, and trypan blue exclusion assay for viability, were used to examine cellular responses after treatments. The optimal concentration was then utilized in Hypericin-Gold nanoparticles mediated PDT combination.

The results revealed that, in a dose-dependent manner, conventional morphological characteristics of cell death, such as vacuolization, blebbing, and floating were observed in treated cells. The biochemical responses demonstrated an increase in LDH, a decrease in ATP, and a reduction in viability. This study demonstrated that CBD induces cell death in MCF-7 breast cancer cells cultured in vitro. The immunofluorescence results of combination therapy indicated that cell death occurred via apoptosis.

In conclusion, this study proposes that the CBD and PDT combination therapy is effective in killing MCF-7 breast cancer cells in vitro by induction of apoptosis.”

https://pubmed.ncbi.nlm.nih.gov/38247877/

https://www.mdpi.com/2073-4409/13/2/187

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