Tag Archives: tetrahydrocannabinol

Potential Use of Cannabinoids for the Treatment of Pancreatic Cancer.

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“Cannabinoid extracts may have anticancer properties, which can improve cancer treatment outcomes.

The aim of this review is to determine the potentially utility of cannabinoids in the treatment of pancreatic cancer.

Results: Cannabinol receptors have been identified in pancreatic cancer with several studies showing in vitroantiproliferative and proapoptotic effects. The main active substances found in cannabis plants are cannabidiol (CBD) and tetrahydrocannabinol (THC). There effects are predominately mediated through, but not limited to cannabinoid receptor-1, cannabinoid receptor-2, and G-protein-coupled receptor 55 pathways. In vitro studies consistently demonstrated tumor growth-inhibiting effects with CBD, THC, and synthetic derivatives. Synergistic treatment effects have been shown in two studies with the combination of CBD/synthetic cannabinoid receptor ligands and chemotherapy in xenograft and genetically modified spontaneous pancreatic cancer models. There are, however, no clinical studies to date showing treatment benefits in patients with pancreatic cancer.

Conclusions: Cannabinoids may be an effective adjunct for the treatment of pancreatic cancer. Data on the anticancer effectiveness of various cannabinoid formulations, treatment dosing, precise mode of action, and clinical studies are lacking.”

 https://www.ncbi.nlm.nih.gov/pubmed/30706048
“Endogenous cannabinoids, synthetic or cannabis extracted from plants, can reduce tumor invasion and growth, induce tumor cell death, and inhibit tumor angiogenesis via cannabinoid receptor or receptor-independent pathways. Cannabinoid receptors appear to be highly expressed in pancreatic cancer compared with normal pancreatic tissue. CBD and THC appear to have antiproliferative and proapoptotic effects.”
https://www.liebertpub.com/doi/10.1089/pancan.2018.0019

Dark Classics in Chemical Neuroscience: Δ9-Tetrahydrocannabinol.

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 ACS Chemical Neuroscience

“Cannabis (Cannabis sativa) is the most widely used illicit drug in the world, with an estimated 192 million users globally.

The main psychoactive component of cannabis is (-)-trans-Δ9-tetrahydrocannabinol (Δ9-THC), a molecule with a diverse range of pharmacological actions. The unique and distinctive intoxication caused by Δ9-THC primarily reflects partial agonist action at central cannabinoid type 1 (CB1) receptors.

Δ9-THC is an approved therapeutic treatment for a range of conditions, including chronic pain, chemotherapy-induced nausea and vomiting, and is being investigated in indications such as anorexia nervosa, agitation in dementia, and Tourette’s syndrome.

It is available as a regulated pharmaceutical in products such as Marinol®, Sativex®, and Namisol®, as well as in an ever-increasing range of unregistered medicinal and recreational cannabis products.

While cannabis is an ancient medicament, contemporary use is embroiled in legal, scientific, and social controversy, much of which relates to the potential hazards and benefits of Δ9-THC itself.

Robust contemporary debate surrounds the therapeutic value of Δ9-THC in different diseases, its capacity to produce psychosis and cognitive impairment, and the addictive and “gateway” potential of the drug.

This review will provide a profile of the chemistry, pharmacology, toxicology, and recreational and therapeutic uses of Δ9-THC, as well as the historical and societal importance of this unique, distinctive, and ubiquitous psychoactive substance.”

https://www.ncbi.nlm.nih.gov/pubmed/30689342

https://pubs.acs.org/doi/10.1021/acschemneuro.8b00651

Delta-9-tetrahydrocannabinol inhibits the splenocyte proliferative response to herpes simplex virus type 2.

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“The present investigation was undertaken to determine the effect of in vivo Delta-9-tetrahydrocannabinol (Delta-9-THC) treatment on immune responsiveness to secondary exposure to herpes simplex virus type 2 (HSV2) antigens in vitro.

Administration of 50 mg/kg or 100 mg/kg Delta-9-THC to B6C3F1 mice in concert with HSV2 infection resulted in suppression of the proliferative response to HSV2 cell-surface antigens expressed on virus-infected mouse embryo fibroblasts. Similarly, in vitro treatment of HSV2-infected cells with Delta-9-THC (10(-7) M to 10(-5) M) resulted in a dose-dependent suppression of proliferative responsiveness of splenocytes of non-drug-treated HSV2-sensitized mice.

These results suggest that Delta-9-THC inhibits immune responsiveness of B6C3F1 mice to homotypic challenge with HSV2. This inhibition may be resultant of drug action on both effector immunocytes and target HSV2 antigen-bearing cells.”

https://www.ncbi.nlm.nih.gov/pubmed/2830329

https://www.tandfonline.com/doi/abs/10.3109/08923978709035219

“Inhibition of cell-associated herpes simplex virus type 2 glycoproteins by delta 9-tetrahydrocannabinol. These results indicate that delta 9-THC inhibits the synthesis, maturation, and cellular transport of HSV2-specified glycoproteins.” https://www.ncbi.nlm.nih.gov/pubmed/3033681

A randomised controlled trial of vaporised Δ9-tetrahydrocannabinol and cannabidiol alone and in combination in frequent and infrequent cannabis users: acute intoxication effects.

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“Access to cannabis and cannabinoid products is increasing worldwide for recreational and medicinal use. Two primary compounds within cannabis plant matter, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are both psychoactive, but only THC is considered intoxicating. There is significant interest in potential therapeutic properties of these cannabinoids and of CBD in particular.

Some research has suggested that CBD may ameliorate adverse effects of THC, but this may be dose dependent as other evidence suggests possible potentiating effects of THC by low doses of CBD. We conducted a randomised placebo controlled trial to examine the acute effects of these compounds alone and in combination when administered by vaporisation to frequent and infrequent cannabis users.

Participants (n = 36; 31 male) completed 5 drug conditions spaced one week apart, with the following planned contrasts: placebo vs CBD alone (400 mg); THC alone (8 mg) vs THC combined with low (4 mg) or high (400 mg) doses of CBD. Objective (blind observer ratings) and subjective (self-rated) measures of intoxication were the primary outcomes, with additional indices of intoxication examined.

CBD showed some intoxicating properties relative to placebo.

Low doses of CBD when combined with THC enhanced, while high doses of CBD reduced the intoxicating effects of THC.

The enhancement of intoxication by low-dose CBD was particularly prominent in infrequent cannabis users and was consistent across objective and subjective measures. Most effects were significant at p < .0001.

These findings are important to consider in terms of recommended proportions of THC and CBD in cannabis plant matter whether used medicinally or recreationally and have implications for novice or less experienced cannabis users.”

https://www.ncbi.nlm.nih.gov/pubmed/30661105

https://link.springer.com/article/10.1007%2Fs00406-019-00978-2

Tetrahydrocannabinol: cannabidiol oromucosal spray for treating symptoms of multiple sclerosis spasticity: newest evidence

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“Proceedings of an Almirall-sponsored satellite symposium held at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin, Germany, 10 October 2018.” https://www.futuremedicine.com/doi/10.2217/nmt-2018-0048

“Newest evidence for tetrahydrocannabinol:cannabidiol oromucosal spray from postapproval pragmatic studies. Postapproval studies have an essential role in demonstrating that an intervention is effective and well tolerated during use in daily clinical practice. Numerous large observational and registry studies of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray have been conducted subsequent to its approval in Europe in 2011. Collectively, these studies provide valuable insight into various aspects of THC:CBD spray during real-world use in patients with multiple sclerosis spasticity, including its long-term effectiveness and tolerability. The Italian Medicines Agency’s web-based registry is the largest observational study of THC:CBD oromucosal spray conducted to date, reporting on more than 1600 patients prescribed THC:CBD spray since it was introduced in Italy in 2013, and further supporting its effectiveness and tolerability profile.” https://www.futuremedicine.com/doi/10.2217/nmt-2018-0049

“Newest evidence for tetrahydrocannabinol:cannabidiol oromucosal spray from randomized clinical trials. Subsequent to EMA approval of tetrahydrocannabinol (THC): cannabidiol (CBD) oromucosal spray based on results of various studies, including an enriched-design clinical trial, two newer postapproval randomized trials have confirmed its efficacy and safety for treating resistant multiple sclerosis spasticity, while simultaneously addressing specific authorities’ concerns. A double-blind, placebo-controlled, Phase IV trial, conducted as part of the EMA’s risk management plan, found no effect of THC:CBD spray on cognition and mood after 50 weeks of treatment. In the Sativex® as add-on therapy versus further optimized first-line ANTispastics (SAVANT)  study, add-on THC:CBD spray was significantly more effective than readjusting standard antispasticity therapy and provided new evidence of efficacy as requested by German authorities. SAVANT results support practical recommendations for treating resistant multiple sclerosis spasticity in daily practice.”  https://www.futuremedicine.com/doi/10.2217/nmt-2018-0050

Cannabis and Mood Disorders.

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 “The present review will provide an overview of the neurobiology, epidemiology, clinical impact, and treatment of cannabis use disorder (CUD) in mood disorders.

Patients with mood disorders including major depressive disorder (MDD) and bipolar disorder (BD) have higher rates of cannabis use, and CUD compared to the general population. Reasons for this association are not clear, nor are the putative therapeutic effects of cannabis use, or its components delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in these illnesses.

Cannabis use may be associated mood disorders, but more research is needed to increase our understanding of the mechanisms for this association, and to develop more effective treatments for this comorbidity.”

https://www.ncbi.nlm.nih.gov/pubmed/30643708

https://link.springer.com/article/10.1007%2Fs40429-018-0214-y

“Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Results of this study show that Delta(9)-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis.”   https://www.ncbi.nlm.nih.gov/pubmed/20332000

∆9-Tetrahydrocannabinol, a major marijuana component, enhances the anesthetic effect of pentobarbital through the CB1 receptor.

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 “∆9 –Tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), major psychoactive constituents of marijuana, induce potentiation of pentobarbital-induced sleep in mice.

We have elucidated the mechanism of enhancement of the anesthetic effect of pentobarbital by cannabinoids.

These results suggest that binding of ∆9-THC to the CB1 receptor is involved in the synergism with pentobarbital, and that potentiating effect of CBD with pentobarbital may differ from that of ∆9-THC. We successfully demonstrated that ∆9-THC enhanced the anesthetic effect of pentobarbital through the CB1 receptor.”

https://www.ncbi.nlm.nih.gov/pubmed/30636988

“The pharmacological results indicate the effect of ∆9-THC co-administered with pentobarbital was a synergistic, but not additive, action in mice. Further evidence suggests the CB1 receptor plays an important role as a trigger in potentiating pentobarbital-induced sleep by ∆9-THC.”

https://link.springer.com/article/10.1007%2Fs11419-018-0457-2

Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer.

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 Related image“In the last decades, a lot of attention has been paid to the compounds present in medicinal Cannabis sativa L., such as Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and their effects on inflammation and cancer-related pain.

The National Cancer Institute (NCI) currently recognizes medicinal C. sativa as an effective treatment for providing relief in a number of symptoms associated with cancer, including pain, loss of appetite, nausea and vomiting, and anxiety.

Several studies have described CBD as a multitarget molecule, acting as an adaptogen, and as a modulator, in different ways, depending on the type and location of disequilibrium both in the brain and in the body, mainly interacting with specific receptor proteins CB1 and CB2.

CBD is present in both medicinal and fibre-type C. sativa plants, but, unlike Δ9-THC, it is completely nonpsychoactive. Fibre-type C. sativa (hemp) differs from medicinal C. sativa, since it contains only few levels of Δ9-THC and high levels of CBD and related nonpsychoactive compounds.

In recent years, a number of preclinical researches have been focused on the role of CBD as an anticancer molecule, suggesting CBD (and CBD-like molecules present in the hemp extract) as a possible candidate for future clinical trials.

CBD has been found to possess antioxidant activity in many studies, thus suggesting a possible role in the prevention of both neurodegenerative and cardiovascular diseases. In animal models, CBD has been shown to inhibit the progression of several cancer types. Moreover, it has been found that coadministration of CBD and Δ9-THC, followed by radiation therapy, causes an increase of autophagy and apoptosis in cancer cells. In addition, CBD is able to inhibit cell proliferation and to increase apoptosis in different types of cancer models.

These activities seem to involve also alternative pathways, such as the interactions with TRPV and GRP55 receptor complexes. Moreover, the finding that the acidic precursor of CBD (cannabidiolic acid, CBDA) is able to inhibit the migration of breast cancer cells and to downregulate the proto-oncogene c-fos and the cyclooxygenase-2 (COX-2) highlights the possibility that CBDA might act on a common pathway of inflammation and cancer mechanisms, which might be responsible for its anticancer activity.

In the light of all these findings, in this review we explore the effects and the molecular mechanisms of CBD on inflammation and cancer processes, highlighting also the role of minor cannabinoids and noncannabinoids constituents of Δ9-THC deprived hemp.”

https://www.ncbi.nlm.nih.gov/pubmed/30627539

https://www.hindawi.com/journals/bmri/2018/1691428/

Special Considerations and Assessment in Patients with Multiple Sclerosis.

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Physical Medicine and Rehabilitation Clinics of North America

“Multiple sclerosis is a progressive autoimmune neurologic disorder that may affect any region of the central nervous system. Spasticity in patients with multiple sclerosis can be debilitating and detrimental to the function and quality of life of patients. Treatment options include oral medications, chemodenervation, physical therapy, and modalities.

Cannabinoids in the form of a delta-9-tetrahydrocannabinol/cannabidiol oro-mucosal spray has been shown to be effective in addressing spasticity in multiple sclerosis.

Successful treatment of spasticity will be integrated, multimodal, and individualized.”

https://www.ncbi.nlm.nih.gov/pubmed/30626509

https://www.sciencedirect.com/science/article/pii/S1047965118307617?via%3Dihub

The effects of cannabinoids on the endocrine system.

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“Cannabinoids are the derivatives of the cannabis plant, the most potent bioactive component of which is tetrahydrocannabinol (THC). The most commonly used drugs containing cannabinoids are marijuana, hashish, and hashish oil.

These compounds exert their effects via interaction with the cannabinoid receptors CB1 and CB2. Type 1 receptors (CB1) are localised mostly in the central nervous system and in the adipose tissue and many visceral organs, including most endocrine organs. Type 2 cannabinoid receptors (CB2) are positioned in the peripheral nervous system (peripheral nerve endings) and on the surface of the immune system cells.

Recently, more and more attention has been paid to the role that endogenous ligands play for these receptors, as well as to the role of the receptors themselves. So far, endogenous cannabinoids have been confirmed to participate in the regulation of food intake and energy homeostasis of the body, and have a significant impact on the endocrine system, including the activity of the pituitary gland, adrenal cortex, thyroid gland, pancreas, and gonads.

Interrelations between the endocannabinoid system and the activity of the endocrine system may be a therapeutic target for a number of drugs that have been proved effective in the treatment of infertility, obesity, diabetes, and even prevention of diseases associated with the cardiovascular system.”

 https://www.ncbi.nlm.nih.gov/pubmed/30618031
https://journals.viamedica.pl/endokrynologia_polska/article/view/58487