Tag Archives: tetrahydrocannabinol

KY Hemp-induced Modulation of Ovarian Cancer Cell Metastasis

Posted on by

“Our laboratory is interested in searching for a new plant-based therapeutics to treat ovarian cancer.

We are interested in studying anti-cancer effects of KY grown hemp as a potential candidate drug.

Marijuana and hemp belong to the same genus and species. However, they are different in cannabidiol (CBD) and tetrahydrocannabinol (THC) content.

Both CBD and THC are therapeutically beneficial. Hemp is harmless and non-addictive.

Major objective of this study is to investigate whether KY hemp extract can modulate the metastasis of ovarian cancer.

Based on the data here we conclude that KY hemp has significant anti-metastatic properties against ovarian cancer.”

https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.2018.32.1_supplement.667.7

Use and caregiver-reported efficacy of medical cannabis in children and adolescents in Switzerland

Posted on by

SpringerLink“Evidence on the use and efficacy of medical cannabis for children is limited. We examined clinical and epidemiological characteristics of medical cannabis treatment and caregiver-reported effects in children and adolescents in Switzerland.

We collected clinical data from children and adolescents (< 18 years) who received Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), or a combination of the two between 2008 and 2019 in Switzerland. Out of 205 contacted families, 90 agreed to participate. The median age at the first prescription was 11.5 years (interquartile range (IQR) 6-16), and 32 patients were female (36%). Fifty-one (57%) patients received CBD only and 39 (43%) THC. Patients were more likely to receive THC therapy if one of the following symptoms or signs were present: spasticity, pain, lack of weight gain, vomiting, or nausea, whereas seizures were the dominant indication for CBD therapy.

Improvements were reported in 59 (66%) study participants.

The largest treatment effects were reported for pain, spasticity, and frequency of seizures in participants treated with THC, and for those treated with pure CBD, the frequency of seizures. However, 43% of caregivers reported treatment interruptions, mainly because of lack of improvement (56%), side effects (46%), the need for a gastric tube (44%), and cost considerations (23%).

Conclusions: The effects of medical cannabis in children and adolescents with chronic conditions are unknown except for rare seizure disorders, but the caregiver-reported data analysed here may justify trials of medical cannabis with standardized concentrations of THC or CBD to assess its efficacy in the young.

What is Known: • The use of medical cannabis (THC and CBD) to treat a variety of diseases among children and adolescents is increasing. • In contrast to adults, there is no evidence to support the use of medical cannabis to treat chronic pain and spasticity in children, but substantial evidence to support the use of CBD in children with rare seizure disorders.

What is New: • This study provides important insights into prescription practices, dosages, and treatment outcomes in children and adolescents using medical cannabis data from a real-life setting.

• The effects of medical cannabis in children and adolescents with chronic conditions shown in our study support trials of medical cannabis for chronic conditions.”

https://pubmed.ncbi.nlm.nih.gov/34309706/

“For two thirds of participants treated with standardized THC or CBD preparations, the caregiver reported an improvement in their condition and well-being. Medical cannabis could be a promising and useful therapy for children and adolescents with neurological conditions.”

https://link.springer.com/article/10.1007%2Fs00431-021-04202-z

Tetrahydrocannabinol and cannabidiol as an oromucosal spray in a 1:1 ratio: a therapeutic option for patients with central post-stroke pain syndrome?

Posted on by

BMJ Journals - Northern Devon Healthcare NHS Trust“Central pain after stroke due to brainstem infarction is very rare. Treatment is difficult and specific guidelines are lacking. This is the report of a 61-year-old female patient who, after a posterolateral left medulla oblongata insult with incomplete Wallenberg syndrome, subsequently developed a burning and tingling pain in the contralateral leg and a burning and shooting pain in the ipsilateral face in trigeminal branches 1 and 2. More than 3 years of therapy with amitriptyline, gabapentin, pregabalin and various grade II and III opioids was ineffective or showed intolerable side effects. The administration of tetrahydrocannabinol and cannabidiol as an oromucosal spray in a 1:1 ratio improved the pain situation and quality of life quickly and permanently. The encouraging results in the present case may suggest that treatment with medical cannabis should be considered in similar cases when standard therapies are insufficient.”

https://pubmed.ncbi.nlm.nih.gov/34230048/

https://casereports.bmj.com/content/14/7/e243072

Effects of tetrahydrocannabinols on human oral cancer cell proliferation, apoptosis, autophagy, oxidative stress, and DNA damage

Posted on by

Archives of Oral Biology“Cannabinoids, including delta-8- and delta-9-tetrahydrocannabinol (THC) have a palliative care impact and may therefore be beneficial against cancer.

The aim of this study was to investigate the effect of Δ9-THC and Δ8-THC on oral cancer cell behaviors.

Results: Both cannabinoids were found to decrease cell viability/proliferation by blocking the cell cycle progression from the S to the G2/M phase and enhancing their apoptosis and autophagy. Δ9-THC and Δ8-THC also suppressed the migration/invasion by inhibiting epithelial-mesenchymal transition markers, such as E-cadherin, in addition to decreasing reactive oxygen species (ROS) production and increasing glutathione (GSH) and the expression of mtMP. Δ9-THC and Δ8-THC also downregulated cyclin D1, p53, NOXA, PUMAα, and DRAM expressions but increased p21 and H2AX expression.

Conclusion: We demonstrated that cannabinoids (Δ9-THC and Δ8-THC) were able to decrease oral cancer cell growth through various mechanisms, including apoptosis, autophagy, and oxidative stress. These results suggest a potential use of these molecules as a therapy against oral cancer.”

https://pubmed.ncbi.nlm.nih.gov/34146926/

“Cannabinoids (Δ9-THC and Δ8-THC) decrease oral cancer cell viability/ proliferation.”

https://www.sciencedirect.com/science/article/abs/pii/S0003996921001631?via%3Dihub

A Phase 2 Randomised Clinical Trial Assessing the Tolerability of Two Different Ratios of Medicinal Cannabis in Patients With High Grade Gliomas

Posted on by

Frontiers in Oncology (@FrontOncology) | Twitter“Background: Cannabis for cancer is very topical and, given the use of illicit cannabis preparations used in this vulnerable population, research investigating standardised, quality-assured medicinal cannabis is critical to inform clinicians and assist patient safety.

Methods: A randomized trial involving adult patients diagnosed with a high-grade glioma, no history of substance abuse, liver or kidney damage or myocardial infarction were eligible for inclusion in a tolerability study on two different ratios of medicinal cannabis. Baseline screening of brain morphology, blood pathology, functional status, and cognition was conducted. A retrospective control group was used for comparison for secondary outcomes.

Results: Participants (n=88) were on average 53.3 years old. A paired t-test assessed the Functional Assessment of Cancer Therapy for Brain Cancer (FACT-Br) between groups from baseline to week 12 found that the 1:1 ratio favoured both physical (p=0.025) and functional (p=0.014) capacity and improved sleep (p=0.009). Analysis of changes from baseline to week 12 also found 11% of 61 participants had a reduction in disease, 34% were stable, 16% had slight enhancement, and 10% had progressive disease. No serious adverse events occurred. Side effects included dry mouth, tiredness at night, dizziness, drowsiness.

Conclusion: This study demonstrated that a single nightly dose of THC-containing medicinal cannabis was safe, had no serious adverse effects and was well tolerated in patients. Medicinal cannabis significantly improved sleep, functional wellbeing, and quality of life.”

https://pubmed.ncbi.nlm.nih.gov/34094937/

“From this study we have shown that a single nightly dose of THC-containing cannabis was well tolerated in patients in both groups with high-grade gliomas and significantly improved sleep, functional wellbeing and contentment with QoL in a sample of patients compared to baseline. From this trial, the 1:1 ratio has been identified as the preferred combination the moving forward to further trials. This study significantly informs MC product choice for ongoing studies into cannabis being a potential adjunct treatment option for this patient population.”

https://www.frontiersin.org/articles/10.3389/fonc.2021.649555/full

Prolonged Medical Cannabis Treatment is Associated With Quality of Life Improvement and Reduction of Analgesic Medication Consumption in Chronic Pain Patients

Posted on by

Frontiers in Pharmacology (@FrontPharmacol) | Twitter“Introduction: Chronic non-cancer pain (CNCP) is one of the most prevalent indications for medical cannabis (MC) treatment globally. In this study, we investigated CNCP parameters in patients during prolonged MC treatment, and assessed the interrelation between CNCP parameters and the chemical composition of MC chemovar used. 

Methods: A cross-sectional questionnaire-based study was performed in one-month intervals for the duration of six months. Subjects were adult patients licensed for MC treatment who also reported a diagnosis of CNCP by a physician. Data included self-reported questionnaires. MC treatment features included administration route, cultivator, cultivar name and monthly dose. Comparison statistics were used to evaluate differences between the abovementioned parameters and the monthly MC chemovar doses at each time point. 

Results: 429, 150, 98, 71, 77 and 82 patients reported fully on their MC treatment regimens at six one-month intervals, respectively. Although pain intensities did not change during the study period, analgesic medication consumption rates decreased from 46 to 28% (p < 0.005) and good Quality of Life (QoL) rates increased from 49 to 62% (p < 0.05). These changes overlapped with increase in rates of (-)-Δ9–trans-tetrahydrocannabinol (THC) and α-pinene high dose consumption. 

Conclusion: Even though we observed that pain intensities did not improve during the study, QoL did improve and the rate of analgesic medication consumption decreased alongside with increasing rates of high dose THC and α-pinene consumption. Understanding MC treatment composition may shed light on its long-term effects.”

https://pubmed.ncbi.nlm.nih.gov/34093173/

“In this study, although pain intensities did not change under long-term MC treatment, analgesic medication consumption rates decreased and ‘better’ QoL rates increased. These changes coincided with the increased rates of patients’ consumption of high dose THC and α pinene. These results may shed light on the long-term beneficial effects of MC on CNCP.”

https://www.frontiersin.org/articles/10.3389/fphar.2021.613805/full

Therapeutic Prospects of Cannabinoids in the Immunomodulation of Prevalent Autoimmune Diseases

Posted on by

View details for Cannabis and Cannabinoid Research cover image“Cannabinoids such as ▵-9-THC and CBD can downregulate the immune response by modulating the endocannabinoid system. This modulation is relevant for the treatment of prevalent autoimmune diseases (ADs), such as multiple sclerosis (MS), systemic lupus erythematosus (SLE), diabetes mellitus type 1 (DMT1), and rheumatoid arthritis (RA). These conditions require new therapeutic options with fewer side effects for the control of the autoimmune response. Objective: to conduct a literature review of preclinical scientific evidence that supports further clinical investigations for the use of cannabinoids (natural or synthetic) as potential immunomodulators of the immune response in ADs. 

Methodology: A systematic search was carried out in different databases using different MeSH terms, such as Cannabis sativa L., cannabinoids, immunomodulation, and ADs. Initially, 677 journal articles were found. After filtering by publication date (from 2000 to 2020 for SLE, DMT1, and RA; and 2010 to 2020 for MS) and removing the duplicate items, 200 articles were selected and analyzed by title and summary associated with the use of cannabinoids as immunomodulatory treatment for those diseases. 

Results: Evidence of the immunomodulatory effect of cannabinoids in the diseases previously mentioned, but SLE that did not meet the search criteria, was summarized from 24 journal articles. CBD was found to be one of the main modulators of the immune response. This molecule decreased the number of Th1 and Th17 proinflammatory cells and the production of the proinflammatory cytokines, interleukin (IL)-1, IL-12, IL-17, interferon (IFN)-γ, and tumor necrosis factor alpha, in mouse models of MS and DMT1. Additionally, new synthetic cannabinoid-like molecules, with agonist or antagonist activity on CB1, CB2, TRPV1, PPAR-α, and PPAR-γ receptors, have shown anti-inflammatory properties in MS, DMT1, and RA. 

Conclusion: Data from experimental animal models of AD showed that natural and synthetic cannabinoids downregulate inflammatory responses mediated by immune cells responsible for AD chronicity and progression. Although synthetic cannabinoid-like molecules were evaluated in just two clinical trials, they corroborated the potential use of cannabinoids to treat some ADs. Notwithstanding, new cannabinoid-based approaches are required to provide alternative treatments to patients affected by the large group of ADs.”

https://pubmed.ncbi.nlm.nih.gov/34030476/

https://www.liebertpub.com/doi/10.1089/can.2020.0183

Recovery from Traumatic Brain Injury Following Treatment with Δ9-Tetrahydrocannabinol Is Associated with Increased Expression of Granulocyte-Colony Stimulating Factor and Other Neurotrophic Factors

Posted on by

Δ9-THC promoted recovery after traumatic brain injury in mice. Animals treated with THC for three days after a controlled cortical impact performed better on motor testing and returned to normal motor performance within two weeks.

The recovery was accompanied by increased expression of G-CSF, BDNF, and GDNF in brain regions including the cortex, striatum, and hippocampus. These neurotrophic factors are involved in neuronal survival, brain repair, and recovery after injury.

The findings suggest that THC may support recovery after traumatic brain injury by increasing the brain’s own repair-related signaling. In this study, the effect went beyond symptom relief and was associated with biological changes tied to neuroprotection and regeneration.

“Introduction: The hematopoietic cytokine granulocyte-colony stimulating factor (G-CSF) is well known to stimulate proliferation of blood stem/progenitor cells of the leukocyte lineage, but is also recognized as a neurotrophic factor involved in brain self-repair processes. G-CSF administration has been shown to promote recovery from experimental models of traumatic brain injury (TBI) and to modulate components of the endocannabinoid system (eCS). Conversely, Δ9-tetrahydrocannabinol (Δ9THC) treatment of normal mice has been shown to increase blood levels of G-CSF in the periphery. 

Hypothesis: Administration of the phytocannabinoid Δ9THC will enhance brain repair following controlled cortical impact (CCI) by upregulating G-CSF and other neurotrophic factors (brain-derived neurotrophic factor [BDNF] and glial-derived neurotrophic factor [GDNF]) in brain regions. 

Materials and Methods: C57BL/6J mice underwent CCI and were treated for 3 days with THC 3 mg/kg intraperitoneally. Motor function on a rotarod was recorded at baseline and 3, 7, and 14 days after CCI. Groups of mice were euthanized at 7 and 14 days. G-CSF, BDNF, and GDNF expression were measured at 7 and 14 days in cerebral cortex, striatum, and hippocampus on the side of the trauma. 

Results: Δ9THC-treated mice ran on the rotarod longer than vehicle-treated mice and recovered to normal rotarod performance levels at 2 weeks. These mice, compared to vehicle-treated animals, exhibited significant upregulation of G-CSF as well as BDNF and GDNF in cerebral cortex, striatum, and hippocampus. Conclusion: Administration of the phytocannabinoid Δ9THC promotes significant recovery from TBI and is associated with upregulation of brain G-CSF, BDNF, and GDNF, neurotrophic factors previously shown to mediate brain self-repair following TBI and stroke.”

https://pubmed.ncbi.nlm.nih.gov/33998887/

https://journals.sagepub.com/doi/10.1089/can.2020.0119

Need this THC study explained? thcXplained.com

THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner

Posted on by

cancers-logo

“Glioblastoma (GBM) is the most frequent malignant tumor of the central nervous system in humans with a median survival time of less than 15 months.

∆9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best-characterized components of Cannabis sativa plants with modulating effects on cannabinoid receptors 1 and 2 (CB1 and CB2) and on orphan receptors such as GPR18 or GPR55. Previous studies have demonstrated anti-tumorigenic effects of THC and CBD in several tumor entities including GBM, mostly mediated via CB1 or CB2.

In this study, we investigated the non-CB1/CB2 effects of THC on the cell cycle of GBM cells isolated from human tumor samples.

Cell cycle entry was measured after 24 h upon exposure by immunocytochemical analysis of Ki67 as proliferation marker. The Ki67-reducing effect of THC was abolished in the presence of CBD, whereas CBD alone did not cause any changes. To identify the responsible receptor for THC effects, we first characterized the cells regarding their expression of different cannabinoid receptors: CB1, CB2, GPR18, and GPR55. Secondly, the receptors were pharmacologically blocked by application of their selective antagonists AM281, AM630, O-1918, and CID16020046 (CID), respectively. All examined cells expressed the receptors, but only in presence of the GPR55 antagonist CID was the THC effect diminished. Stimulation with the GPR55 agonist lysophosphatidylinositol (LPI) revealed similar effects as obtained for THC. The LPI effects were also inhibited by CBD and CID, confirming a participation of GPR55 and suggesting its involvement in modifying the cell cycle of patient-derived GBM cells.”

https://pubmed.ncbi.nlm.nih.gov/33802282/

“Glioblastoma (GBM) is the most frequent primary brain tumor entity with poor prognosis and resistance to current standard therapies. Cannabinoids, such as tetrahydrocannabinol (THC) and cannabidiol (CBD) are discussed as promising compounds for individualized treatment, as they exert anti-tumor effects by binding to cannabinoid-specific receptors. However, their pharmacology is highly diverse and complex. The present study was designed to verify (1) whether cannabinoids show even any effect in GBM cells derived from primary human tumor samples and (2) to identify the receptor responsible for those effects. Our findings revealed that THC reduces the number of Ki67 immunoreactive nuclei, a cell cycle marker through the orphan cannabinoid receptor GPR55. The data suggest a therapeutic potential of cannabinoids in those GBM with functional and responsive GPR55.”

https://www.mdpi.com/2072-6694/13/5/1064

A phase 1b randomised, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma

Posted on by

British Journal of Cancer“Preclinical data suggest some cannabinoids may exert antitumour effects against glioblastoma (GBM). Safety and preliminary efficacy of nabiximols oromucosal cannabinoid spray plus dose-intense temozolomide (DIT) was evaluated in patients with first recurrence of GBM.

Results: The most common treatment-emergent adverse events (TEAEs; both parts) were vomiting, dizziness, fatigue, nausea and headache. Most patients experienced TEAEs that were grade 2 or 3 (CTCAE). In Part 2, 33% of both nabiximols- and placebo-treated patients were progression-free at 6 months. Survival at 1 year was 83% for nabiximols- and 44% for placebo-treated patients (p = 0.042), although two patients died within the first 40 days of enrolment in the placebo arm. There were no apparent effects of nabiximols on TMZ PK.

Conclusions: With personalised dosing, nabiximols had acceptable safety and tolerability with no drug-drug interaction identified. The observed survival differences support further exploration in an adequately powered randomised controlled trial.”

https://pubmed.ncbi.nlm.nih.gov/33623076/

https://www.nature.com/articles/s41416-021-01259-3