Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Risk of motor vehicle collision associated with cannabis and alcohol use among patients presenting for emergency care

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“Background: The objective of this study was to examine the relationship between cannabis and alcohol use and occurrence of motor vehicle collision (MVC) among patients in the emergency department (ED).

Methods: This was a cross-sectional study of visits to EDs in Denver, CO, Portland, OR, and Sacramento, CA by drivers who were involved in MVCs and presented with injuries (cases) and non-injured drivers (controls) who presented for medical care. We obtained blood samples and measured delta-9-THC and its metabolites. Alcohol levels were determined by breathalyzer or samples taken in the course of clinical care. Participants completed a research-assistant-administered interview consisting of questions about drug and alcohol use prior to their visit, context of use, and past-year drug and alcohol use. Multiple logistic regression was used to estimate the association between MVC and cannabis/alcohol use, adjusted for demographic characteristics. We then stratified participants based on levels of cannabis use and calculated the odds of MVC across these levels, first using self-report and then using blood levels for delta-9-THC in separate models. We conducted a case-crossover analysis, using 7-day look-back data to allow each participant to serve as their own control. Sensitivity analyses examined the influence of usual use patterns and driving in a closed (car, truck, van) versus open (motorcycle, motorbike, all-terrain vehicle) vehicle.

Results: Cannabis alone was not associated with higher odds of MVC, while acute alcohol use alone, and combined use of alcohol and cannabis were both independently associated with higher odds of MVC. Stratifying by level of self-reported or measured cannabis use, higher levels were not associated with higher odds for MVC, with or without co-use of alcohol; in fact, high self-reported acute cannabis use was associated with lower odds of MVC (odds ratio [OR] 0.18, 95% confidence interval [CI] 0.05-0.65). In the case-crossover analysis, alcohol use alone or in combination with cannabis was associated with higher odds of MVC, while cannabis use alone was again associated with decreased odds of MVC.

Conclusions: Alcohol use alone or in conjunction with cannabis was consistently associated with higer odds for MVC. However, the relationship between measured levels of cannabis and MVC was not as clear. Emphasis on actual driving behaviors and clinical signs of intoxication to determine driving under the influence has the strongest rationale.”

https://pubmed.ncbi.nlm.nih.gov/38277855/

“Decades of research have established that alcohol increases the risk for motor vehicle collision (MVC) in a dose-dependent manner.”

“Cannabis alone was not associated with higher odds of MVC,”

https://www.sciencedirect.com/science/article/abs/pii/S0001457524000046?via%3Dihub

Research progress on the cannabinoid type-2 receptor and Parkinson’s disease

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“Parkinson’s disease (PD) is featured by movement impairments, including tremors, bradykinesia, muscle stiffness, and imbalance. PD is also associated with many non-motor symptoms, such as cognitive impairments, dementia, and mental disorders. Previous studies identify the associations between PD progression and factors such as α-synuclein aggregation, mitochondrial dysfunction, inflammation, and cell death.

The cannabinoid type-2 receptor (CB2 receptor) is a transmembrane G-protein-coupled receptor and has been extensively studied as part of the endocannabinoid system. CB2 receptor is recently emerged as a promising target for anti-inflammatory treatment for neurodegenerative diseases.

It is reported to modulate mitochondrial function, oxidative stress, iron transport, and neuroinflammation that contribute to neuronal cell death. Additionally, CB2 receptor possesses the potential to provide feedback on electrophysiological processes, offering new possibilities for PD treatment. This review summarized the mechanisms underlying PD pathogenesis. We also discussed the potential regulatory role played by CB2 receptor in PD.”

https://pubmed.ncbi.nlm.nih.gov/38264546/

“Cannabinoids, as an emerging therapeutic agent, have attracted wide attention for their great potential in the treatment of various diseases.”

https://www.frontiersin.org/articles/10.3389/fnagi.2023.1298166/full

The Effect of Nabiximols on Driving Ability in Adults with Chronic Tic Disorders: Results of a Substudy Analysis of the Double-Blind, Randomized, Placebo-Controlled CANNA-TICS Trial

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“Background: The multicenter, randomized, double-blind, parallel-group, phase IIIb CANNA-TICS (CANNAbinoids in the treatment of TICS) trial showed clear trends for improvement of tics, depression, and quality of life with nabiximols versus placebo in adult patients with Gilles de la Tourette syndrome and other chronic tic disorders. Although in general nabiximols was well tolerated, it is unclear whether treatment using this cannabis extract influences driving skills in patients with chronic tic disorders. 

Methods: Here we report results of the “Fitness to Drive” substudy of the CANNA-TICS trial. The key endpoint was fitness to drive as a binary criterion with a computerized assessment at baseline and after 9 weeks of stable treatment (week 13) with nabiximols or placebo. A patient was considered unfit to drive according to the German Federal Highway Research Institute guidelines. 

Results: In the substudy, a total of 64 patients (76.6% men, mean±standard deviation of age: 36.8±13.9) were recruited at two study sites. The number of patients who were fit to drive increased from 24 (55.8%) at baseline to 28 (71.8%) at week 13 among 43 patients treated with nabiximols, and decreased from 14 (66.7%) to 10 (52.6%) among 21 patients who received placebo. The risk difference (nabiximols – placebo) was 0.17 (95% confidence interval=-0.08 to 0.43) in favor of nabiximols. Specifically, only 2 of 24 (8.3%) patients in the nabiximols, but 4 of 14 (28.6%) patients in the placebo group changed for the worse from fit (at baseline) to unfit (at week 13) to drive, whereas 8 of 19 (42.1%) patients in the nabiximols, and only 2 of 7 (28.6%) patients in the placebo group improved from unfit to fit. 

Conclusion: Treatment with nabiximols does not impair skills relevant to driving in those patients with tic disorders who were fit to drive at baseline and even improved fitness to drive in a subset of patients who were unfit to drive before start of treatment.”

https://pubmed.ncbi.nlm.nih.gov/38265476/

https://www.liebertpub.com/doi/10.1089/can.2023.0114

The Neurotherapeutic Arsenal in Cannabis sativa: Insights into Anti-Neuroinflammatory and Neuroprotective Activity and Potential Entourage Effects

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“Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds-cannabinoids, terpenes, and flavonoids. While major cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential.

This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis’s bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis’s sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation.

The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis’s complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects.

This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis’s full therapeutic potential within the realm of natural plant-based medicine.”

https://pubmed.ncbi.nlm.nih.gov/38257323/

https://www.mdpi.com/1420-3049/29/2/410

Role of Cannabinoids in Oral Cancer

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“Cannabinoids have incited scientific interest in different conditions, including malignancy, due to increased exposure to cannabis. Furthermore, cannabinoids are increasingly used to alleviate cancer-related symptoms. This review paper aims to clarify the recent findings on the relationship between cannabinoids and oral cancer, focusing on the molecular mechanisms that could link cannabinoids with oral cancer pathogenesis. In addition, we provide an overview of the current and future perspectives on the management of oral cancer patients using cannabinoid compounds.

Epidemiological data on cannabis use and oral cancer development are conflicting. However, in vitro studies assessing the effects of cannabinoids on oral cancer cells have unveiled promising anti-cancer features, including apoptosis and inhibition of cell proliferation. Downregulation of various signaling pathways with anti-cancer effects has been identified in experimental models of oral cancer cells exposed to cannabinoids. Furthermore, in some countries, several synthetic or phytocannabinoids have been approved as medical adjuvants for the management of cancer patients undergoing chemoradiotherapy.

Cannabinoids may improve overall well-being by relieving anxiety, depression, pain, and nausea. In conclusion, the link between cannabinoid compounds and oral cancer is complex, and further research is necessary to elucidate the potential risks or their protective impact on oral cancer.”

https://pubmed.ncbi.nlm.nih.gov/38256042/

https://www.mdpi.com/1422-0067/25/2/969

Buds and Bugs: A Fascinating Tale of Gut Microbiota and Cannabis in the Fight against Cancer

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“Emerging research has revealed a complex bidirectional interaction between the gut microbiome and cannabis. Preclinical studies have demonstrated that the gut microbiota can significantly influence the pharmacological effects of cannabinoids.

One notable finding is the ability of the gut microbiota to metabolise cannabinoids, including Δ9-tetrahydrocannabinol (THC). This metabolic transformation can alter the potency and duration of cannabinoid effects, potentially impacting their efficacy in cancer treatment. Additionally, the capacity of gut microbiota to activate cannabinoid receptors through the production of secondary bile acids underscores its role in directly influencing the pharmacological activity of cannabinoids.

While the literature reveals promising avenues for leveraging the gut microbiome-cannabis axis in cancer therapy, several critical considerations must be accounted for. Firstly, the variability in gut microbiota composition among individuals presents a challenge in developing universal treatment strategies. The diversity in gut microbiota may lead to variations in cannabinoid metabolism and treatment responses, emphasising the need for personalised medicine approaches.

The growing interest in understanding how the gut microbiome and cannabis may impact cancer has created a demand for up-to-date, comprehensive reviews to inform researchers and healthcare practitioners. This review provides a timely and invaluable resource by synthesizing the most recent research findings and spotlighting emerging trends. A thorough examination of the literature on the interplay between the gut microbiome and cannabis, specifically focusing on their potential implications for cancer, is presented in this review to devise innovative and effective therapeutic strategies for managing cancer.”

https://pubmed.ncbi.nlm.nih.gov/38255944/

https://www.mdpi.com/1422-0067/25/2/872

The Effect of Oil-Based Cannabis Extracts on Metabolic Parameters and Microbiota Composition of Mice Fed a Standard and a High-Fat Diet

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“The prevalence of obesity and obesity-related pathologies is lower in frequent cannabis users compared to non-users. It is well established that the endocannabinoid system has an important role in the development of obesity.

We recently demonstrated that prolonged oral consumption of purified Δ-9 Tetrahydrocannabinol (THC), but not of cannabidiol (CBD), ameliorates diet-induced obesity and improves obesity-related metabolic complications in a high-fat diet mouse model. However, the effect of commercially available medical cannabis oils that contain numerous additional active molecules has not been examined.

We tested herein the effects of THC- and CBD-enriched medical cannabis oils on obesity parameters and the gut microbiota composition of C57BL/6 male mice fed with either a high-fat or standard diet. We also assessed the levels of prominent endocannabinoids and endocannabinoid-like lipid mediators in the liver.

THC-enriched extract prevented weight gain by a high-fat diet and attenuated diet-induced liver steatosis concomitantly with reduced levels of the lipid mediators palmitoyl ethanolamide (PEA) and docosahexaenoyl ethanolamide (DHEA) in the liver. In contrast, CBD-enriched extract had no effect on weight gain, but, on the contrary, it even exacerbated liver steatosis. An analysis of the gut microbiota revealed that mainly time but not treatment exerted a strong effect on gut microbiota alterations.

From our data, we conclude that THC-enriched cannabis oil where THC is the main constituent exerts the optimal anti-obesity effects.”

https://pubmed.ncbi.nlm.nih.gov/38256146/

https://www.mdpi.com/1422-0067/25/2/1073

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

A randomised phase II trial of temozolomide with or without cannabinoids in patients with recurrent glioblastoma (ARISTOCRAT): protocol for a multi-centre, double-blind, placebo-controlled trial

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“Background: Glioblastoma (GBM) is the most common adult malignant brain tumour, with an incidence of 5 per 100,000 per year in England. Patients with tumours showing O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation represent around 40% of newly diagnosed GBM. Relapse/tumour recurrence is inevitable. There is no agreed standard treatment for patients with GBM, therefore, it is aimed at delaying further tumour progression and maintaining health-related quality of life (HRQoL). Limited clinical trial data exist using cannabinoids in combination with temozolomide (TMZ) in this setting, but early phase data demonstrate prolonged overall survival compared to TMZ alone, with few additional side effects.

Jazz Pharmaceuticals (previously GW Pharma Ltd.) have developed nabiximols (trade name Sativex®), an oromucosal spray containing a blend of cannabis plant extracts, that we aim to assess for preliminary efficacy in patients with recurrent GBM.

Methods: ARISTOCRAT is a phase II, multi-centre, double-blind, placebo-controlled, randomised trial to assess cannabinoids in patients with recurrent MGMT methylated GBM who are suitable for treatment with TMZ. Patients who have relapsed ≥ 3 months after completion of initial first-line treatment will be randomised 2:1 to receive either nabiximols or placebo in combination with TMZ. The primary outcome is overall survival time defined as the time in whole days from the date of randomisation to the date of death from any cause. Secondary outcomes include overall survival at 12 months, progression-free survival time, HRQoL (using patient reported outcomes from QLQ-C30, QLQ-BN20 and EQ-5D-5L questionnaires), and adverse events.

Discussion: Patients with recurrent MGMT promoter methylated GBM represent a relatively good prognosis sub-group of patients with GBM. However, their median survival remains poor and, therefore, more effective treatments are needed. The phase II design of this trial was chosen, rather than phase III, due to the lack of data currently available on cannabinoid efficacy in this setting. A randomised, double-blind, placebo-controlled trial will ensure an unbiased robust evaluation of the treatment and will allow potential expansion of recruitment into a phase III trial should the emerging phase II results warrant this development.”

https://pubmed.ncbi.nlm.nih.gov/38225549/

“Phytocannabinoids occur naturally in cannabis plants and have been used medicinally for centuries for a variety of purposes . Δ9-tetrahydrocannabinol (THC) is the major psychoactive constituent in cannabis, and cannabidiol (CBD) the major non-psychoactive constituent.

In vivo studies have found that the administration of CBD and THC reduced tumour growth in animal models of glioma.

Jazz Pharmaceuticals (previously GW Pharma Ltd.) have developed nabiximols (trade name Sativex®), an oromucosal spray of a complex botanical mixture containing THC and CBD as the principal cannabinoids, with additional cannabinoid constituents and non-cannabinoid components.”

https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11792-4

“Sativex is a standardized medication containing 2.5 mg/actuation CBD and 2.7 mg/ actuation THC.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836266/

Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19-A Scoping Review

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“Coronavirus disease-19 (COVID-19) is a highly contagious illness caused by the SARS-CoV-2 virus.

The clinical presentation of COVID-19 is variable, often including symptoms such as fever, cough, headache, fatigue, and an altered sense of smell and taste. Recently, post-acute “long” COVID-19 has emerged as a concern, with symptoms persisting beyond the acute infection. Vaccinations remain one of the most effective preventative methods against severe COVID-19 outcomes and the development of long-term COVID-19. However, individuals with underlying health conditions may not mount an adequate protective response to COVID-19 vaccines, increasing the likelihood of severe symptoms, hospitalization, and the development of long-term COVID-19 in high-risk populations.

This review explores the potential therapeutic role of cannabinoids in limiting the susceptibility and severity of infection, both pre- and post-SARS-CoV-19 infection.

Early in the SARS-CoV-19 infection, cannabinoids have been shown to prevent viral entry, mitigate oxidative stress, and alleviate the associated cytokine storm.

Post-SARS-CoV-2 infection, cannabinoids have shown promise in treating symptoms associated with post-acute long COVID-19, including depression, anxiety, post-traumatic stress injury, insomnia, pain, and decreased appetite.

While current research primarily focuses on potential treatments for the acute phase of COVID-19, there is a gap in research addressing therapeutics for the early and post-infectious phases. This review highlights the potential for future research to bridge this gap by investigating cannabinoids and the endocannabinoid system as a potential treatment strategy for both early and post-SARS-CoV-19 infection.”

https://pubmed.ncbi.nlm.nih.gov/38202234/

https://www.mdpi.com/2077-0383/13/1/227