Tag Archives: tetrahydrocannabinol

Cannabinoids Δ9-tetrahydrocannabinol and cannabidiol may be effective against methamphetamine induced mitochondrial dysfunction and inflammation by modulation of Toll-like type-4(Toll-like 4) receptors and NF-κB signaling.

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Medical Hypotheses“The neurodegeneration, neuro-inflammation and mitochondrial dysfunction which occur by methamphetamine (METH) abuse or administration are serious and motivation therapeutic approaches for inhibition of these types of neurodegeneration. As we know, METH through Toll-like receptors (TLRs), specially type 4, and NF-κB signaling pathway causes neuro-inflammation and mitochondrial dysfunction.

Neuroprotective approach for management of METH-induced neurodegeneration, inflammation and mitochondrial dysfunction, through a novel neuroprotective agent is continuously being superior to any kind of other therapeutic strategy. Therefore, the clarification, introduction and development of efficacious novel neuroprotective agent are demanded. During recent years, using new neuroprotective agent with therapeutic probability for treatment of METH-induced neuro-inflammation and mitochondrial dysfunction has been astoundingly increased.

Previous studies have stated the neuroprotective and anti-inflammatory roles of cannabinoid derivate such as cannabidiol (CBD) and delta-9-tetrahydrocannabinol (Δ9-THC) in multiple neurodegenerative events and diseases.

According to literature cannabinoid derivate, by inhibition of TLR4 and activation of NF-κB signaling pathway, exerts their anti-inflammatory and neuroprotective effects and cause mitochondrial biogenesis. Thus we hypothesized that by using cannabinoids in METH dependent subject it would provide neuroprotection against METH-induced neurodegeneration, neuro-inflammation and mitochondrial dysfunction and probably can manage sequels of METH-induced neurochemical abuses via modulation of TLR4/NF-κB signaling pathway.

In this article, we tried to discuss our hypothesis regarding the possible role of CBD and Δ9-THC, as a potent neuroprotective and anti-inflammatory agents, in inhibition or treatment of METH-induced neurodegeneration, neuro-inflammation and mitochondrial dysfunction through its effects on TLR4/NF-κB signaling pathway.”

https://www.ncbi.nlm.nih.gov/pubmed/31465975

https://www.sciencedirect.com/science/article/abs/pii/S030698771930739X?via%3Dihub

Opioid-enhancing antinociceptive effects of delta-9-tetrahydrocannabinol and amitriptyline in rhesus macaques.

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Cover image for Experimental and Clinical Psychopharmacology“Cannabinoids can enhance the antinociceptive effects of opioids in a synergistic manner, potentially reducing the analgesic dosage of opioids and improving pain therapy. This strategy has also been used as a rationale to combine certain antidepressants and opioids.

In this experiment, opioid-induced thermal antinociception was assessed in rhesus macaques using a warm-water tail-withdrawal procedure with 3 water temperatures (40, 50, and 55 °C). In general, the acute antinociceptive effects of intramuscular (i.m.) cumulative doses of heroin were studied alone or in combination with i.m. (-)-trans-delta-9-tetrahydrocannabinol (THC), cannabinol (CBN), or the tricyclic antidepressant amitriptyline.

A nonantinociceptive dose of THC (1 mg/kg) shifted the ED50 for the heroin dose-effect curve 3.6-fold leftward at 50 °C and 1.9-fold leftward at 55 °C compared with heroin alone. When the cannabinoid type-1 receptor (CB1R) antagonist, rimonabant, was administered prior to the most effective THC-heroin combination, rimonabant blocked the THC enhancement of heroin antinociception. When CBN (1-3.2 mg/kg) was administered prior to heroin, or 1 mg/kg of CBN was administered prior to a combination of 0.32 mg/kg of THC and heroin, no shifts were evident in the heroin dose-effect curves at either temperature.

However, similar to THC, amitriptyline (0.32-1 mg/kg) administered prior to heroin significantly shifted the heroin dose-effect curve leftward. Heroin produced both dose- and temperature-dependent thermal antinociception in nonhuman primates and THC produced opioid-enhancing effects in a CB1R-dependent manner. These effects of THC were not shared by cannabinol, but were quantitatively similar to that of amitriptyline.”

https://www.ncbi.nlm.nih.gov/pubmed/31464475

https://psycnet.apa.org/doiLanding?doi=10.1037%2Fpha0000313

Activation of Cannabinoid Receptors Promote Periodontal Cell Adhesion and Migration.

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Journal of Clinical Periodontology banner“Medical and recreational cannabis use is increasing significantly, but its impacts on oral health remains unclear.

The aim of this study is to investigate the effects of tetrahydrocannabinol (THC), the major active component in cannabis, on periodontal fibroblast cell adhesion and migration to explore its role in periodontal regeneration and wound healing.

RESULTS:

Both CB1 and CB2 were expressed in periodontal tissues but with different expression patterns. THC promoted periodontal cell wound healing by inducing HPLF cell adhesion and migration. This was mediated by focal adhesion kinase (FAK) activation and its modulation of MAPK activities. The effect of cannabinoids on periodontal fibroblast cell adhesion and migration were mainly dependent on the CB2.

CONCLUSION:

These results suggested that cannabinoids may contribute to developing new therapeutics for periodontal regeneration and wound healing.”

https://www.ncbi.nlm.nih.gov/pubmed/31461164

https://onlinelibrary.wiley.com/doi/abs/10.1111/jcpe.13190

Clinicians’ Guide to Cannabidiol and Hemp Oils.

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Mayo Clinic“Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have become very popular over the past few years. Patients report relief for a variety of conditions, particularly pain, without the intoxicating adverse effects of medical marijuana.

In June 2018, the first CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of rare, severe epilepsy, further putting the spotlight on CBD and hemp oils.

There is a growing body of preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction.

Care must be taken when directing patients toward CBD products because there is little regulation, and studies have found inaccurate labeling of CBD and tetrahydrocannabinol quantities.

This article provides an overview of the scientific work on cannabinoids, CBD, and hemp oil and the distinction between marijuana, hemp, and the different components of CBD and hemp oil products.

We summarize the current legal status of CBD and hemp oils in the United States and provide a guide to identifying higher-quality products so that clinicians can advise their patients on the safest and most evidence-based formulations.

This review is based on a PubMed search using the terms CBD, cannabidiol, hemp oil, and medical marijuana. Articles were screened for relevance, and those with the most up-to-date information were selected for inclusion.”

https://www.ncbi.nlm.nih.gov/pubmed/31447137

https://www.mayoclinicproceedings.org/article/S0025-6196(19)30007-2/fulltext

Preclinical evidence on the anticancer properties of phytocannabinoids

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Image result for CROSBI“Phytocannabinoids are unique terpenophenolic compounds predominantly produced in the glandular trichomes of the cannabis plant (Cannabis sativa L.). The delta-9- tetrahydrocannabinol (THC) is the main active constituent responsible for the plant’s psychoactive effect and, together with the non- psychoactive cannabidiol (CBD), the most investigated naturally occurring cannabinoid.

The first report on the antitumor properties of cannabis compounds appeared more than forty years ago, but the potential of targeting the endocannabinoid system in cancer has recently attracted increasing interest. Our study aimed to review the last decade’s findings on the anticancer potential of plant- derived cannabinoids and the possible mechanisms of their activity.

A large body of in vitro data has been accumulated demonstrating that phytocannabinoids affect a wide spectrum of tumor cells, including gliomas, neuroblastomas, hepatocarcinoma as well as skin, prostate, breast, cervical, colon, pancreatic, lung and hematological cancer.

It has been found that they can stop the uncontrolled growth of cancer cells through the cell-cycle arrest, inhibition of cell proliferation and induction of autophagy and apoptosis. They can also block all the steps of tumor progression, including tumor cell migration, adhesion and invasion as well as angiogenesis. The observed effects are mainly mediated by the cannabinoid CB1 and/or CB2 receptors, although some other receptors and mechanisms unrelated to receptor stimulation may also be involved.

The majority of available animal studies confirmed that phytocannabinoids are capable of effectively decreasing cancer growth and metastasis in vivo. THC was found to be effective against experimental glioma, liver, pancreatic, breast and lung cancer while CBD showed activity against glioma and neuroblastoma, melanoma, colon, breast, prostate and lung cancer. Further in vitro and in vivo studies also greatly support their use in combination with traditional chemotherapy or radiotherapy, which results in improved efficiency, attenuated toxicity or reduced drug resistance.

Taken together most of available preclinical results emphasize the extensive therapeutic potential of THC and CBD in various types of cancers. The potential clinical interest of cannabinoids is additionally suggested by their selectivity for tumor cells as well as their good tolerance and the absence of normal tissue toxicity, which are still the major limitations of most conventional drugs. The accumulated preclinical evidence strongly suggests the need for clinical testing of cannabinoids in cancer patients.”

 https://www.bib.irb.hr/887811

Tetrahydrocannabinol Modulates in Vitro Maturation of Oocytes and Improves the Blastocyst Rates after in Vitro Fertilization.

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Image result for Cellular Physiology & Biochemistry“Among the assisted reproductive techniques, the in vitro maturation of oocytes (IVM) is less developed than other techniques, but its implementation would entail a qualitative advance.

This technique consists in the extraction of immature oocytes from antral ovarian follicles with the patient under low hormone stimulation or without hormone to mature exogenously in culture media supplemented with different molecules to promote maturation.

In this sense, we are interested in the role that cannabinoids could have as IVM promoters because cannabinoid’s molecular pathway is similar to the one by which oocyte’s meiosis resumption is activated.

With the intention of advancing in the possible use of cannabinoids as supplements for the media for in vitro maturation of oocytes, we intend to deepen the study of the function of the phytocannabinoid Δ-9-tetrahydrocannabinol (THC) in the IVM process.

RESULTS:

This study confirms that the incubation of oocytes with THC during IVM accelerated some events of that process like the phosphorylation pattern of ERK and AKT and was able to increase the blastocyst rate in response to IVF. Moreover, it seems that both CB1 and CB2 are necessary to maintain a healthy oocyte maturation.

CONCLUSION:

Our data suggest that THC may be useful IVM supplements in clinic as is more feasible and reliable than any synthetic cannabinoid.”

https://www.ncbi.nlm.nih.gov/pubmed/31436397

https://www.cellphysiolbiochem.com/Articles/000149/

The effectiveness of self-directed medical cannabis treatment for pain

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Complementary Therapies in Medicine“The prior medical literature offers little guidance as to how pain relief and side effect manifestation may vary across commonly used and commercially available cannabis product types. We used the largest dataset in the United States of real-time responses to and side effect reporting from patient-directed cannabis consumption sessions for the treatment of pain under naturalistic conditions in order to identify how cannabis affects momentary pain intensity levels and which product characteristics are the best predictors of therapeutic pain relief.

Between 06/06/2016 and 10/24/2018, 2987 people used the ReleafApp to record 20,513 cannabis administration measuring cannabis’ effects on momentary pain intensity levels across five pain categories: musculoskeletal, gastrointestinal, nerve, headache-related, or non-specified pain. The average pain reduction was –3.10 points on a 0–10 visual analogue scale (SD = 2.16, d = 1.55, p < .001).

Whole Cannabis flower was associated with greater pain relief than were other types of products, and higher tetrahydrocannabinol (THC) levels were the strongest predictors of analgesia and side effects prevalence across the five pain categories. In contrast, cannabidiol (CBD) levels generally were not associated with pain relief except for a negative association between CBD and relief from gastrointestinal and non-specified pain.

These findings suggest benefits from patient-directed, cannabis therapy as a mid-level analgesic treatment; however, effectiveness and side effect manifestation vary with the characteristics of the product used.

The results suggest that Cannabis flower with moderate to high levels of tetrahydrocannabinol is an effective mid-level analgesic.”

https://www.ncbi.nlm.nih.gov/pubmed/31519268

https://www.sciencedirect.com/science/article/abs/pii/S0965229919308040

“UNM study confirms cannabis flower is an effective mid-level analgesic medication for pain treatment. Cannabis likely has numerous constituents that possess analgesic properties beyond THC, including terpenes and flavonoids, which likely act synergistically for people that use whole dried cannabis flower, Cannabis offers the average patient an effective alternative to using opioids for general use in the treatment of pain with very minimal negative side effects for most people.”  https://news.unm.edu/news/unm-study-confirms-cannabis-flower-is-an-effective-mid-level-analgesic-medication-for-pain-treatment

Cannabidiol and the Remainder of the Plant Extract Modulate the Effects of Δ9-Tetrahydrocannabinol on Fear Memory Reconsolidation.

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Image result for frontiers in behavioral neuroscience “Δ9-Tetrahydrocannabinol (THC, a CB1 receptor agonist) and Cannabidiol (CBD, a non-competitive antagonist of endogenous CB1 and CB2 ligands) are two primary components of Cannabis species, and may modulate fear learning in mammals.

The CB1 receptor is widely distributed throughout the cortex and some limbic regions typically associated with fear learning. Humans with posttraumatic disorder (PTSD) have widespread upregulation of CB1 receptor density and reduced availability of endogenous cannabinoid anandamide, suggesting a role for the endocannabinoid system in PTSD.

Pharmacological blockade of memory reconsolidation following recall of a conditioned response modulates the expression of learned fear and may represent a viable target for the development of new treatments for PTSD.

In this study, we focused on assessing the impact of the key compounds of the marijuana plant both singly and, more importantly, in concert on attenuation of learned fear. Specifically, we assessed the impact of THC, CBD, and/or the remaining plant materials (post-extraction; background material), on reconsolidation of learned fear.

Results: CBD alone, but not THC alone, significantly attenuated fear memory reconsolidation when administered immediately after recall. The effect persisted for at least 7 days. A combination of CBD and THC also attenuated the fear response. Plant BM also significantly attenuated reconsolidation of learned fear both on its own and in combination with THC and CBD. Finally, THC attenuated reconsolidation of learned fear only when co-administered with CBD or plant BM.

Conclusion: CBD may provide a novel treatment strategy for targeting fear-memories. Furthermore, plant BM also significantly attenuated the fear response. However, whereas THC alone had no significant effects, its effects were modulated by the addition of other compounds. Future research should investigate some of the other components present in the plant BM (such as terpenes) for their effects alone, or in combination with isolated pure cannabinoids, on fear learning.”

https://www.ncbi.nlm.nih.gov/pubmed/31417379

https://www.frontiersin.org/articles/10.3389/fnbeh.2019.00174/full

Emerging role of cannabinoids and synthetic cannabinoid receptor 1/cannabinoid receptor 2 receptor agonists in cancer treatment and chemotherapy-associated cancer management

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Journal of Cancer Research and Therapeutics“Cannabis was extensively utilized for its medicinal properties till the 19th century. A steep decline in its medicinal usage was observed later due to its emergence as an illegal recreational drug.

Advances in technology and scientific findings led to the discovery of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound of cannabis, that further led to the discovery of endogenous cannabinoids system consisting of G-protein-coupled receptors – cannabinoid receptor 1 and cannabinoid receptor 2 along with their ligands, mainly anandamide and 2-arachidonoylglycerol.  Endocannabinoid (EC) is shown to be a modulator not only for physiological functions but also for the immune system, endocrine network, and central nervous system.

Medicinal research and meta-data analysis over the last few decades have shown a significant potential for both THC and cannabidiol (CBD) to exert palliative effects. People suffering from many forms of advanced stages of cancers undergo chemotherapy-induced nausea and vomiting followed by severe and chronic neuropathic pain and weight loss.

THC and CBD exhibit effective analgesic, anxiolytic, and appetite-stimulating effect on patients suffering from cancer. Drugs currently available in the market to treat such chemotherapy-induced cancer-related ailments are Sativex (GW Pharmaceutical), Dronabinol (Unimed Pharmaceuticals), and Nabilone (Valeant Pharmaceuticals).

Apart from exerting palliative effects, THC also shows promising role in the treatment of cancer growth, neurodegenerative diseases (multiple sclerosis and Alzheimer’s disease), and alcohol addiction and hence should be exploited for potential benefits.

The current review discusses the nature and role of CB receptors, specific applications of cannabinoids, and major studies that have assessed the role of cannabinoids in cancer management.

Specific targeting of cannabinoid receptors can be used to manage severe side effects during chemotherapy, palliative care, and overall cancer management. Furthermore, research evidences on cannabinoids have suggested tumor inhibiting and suppressing properties which warrant reconsidering legality of the substance.

Studies on CB1 and CB2 receptors, in case of cancers, have demonstrated the psychoactive constituents of cannabinoids to be potent against tumor growth.

Interestingly, studies have also shown that activation of CB1 and CB2 cannabinoid receptors by their respective synthetic agonists tends to limit human cancer cell growth, suggesting the role of the endocannabinoid system as a novel target for treatment of cancers.

Further explorations are required to exploit cannabinoids for an effective cancer management.”

http://www.cancerjournal.net/preprintarticle.asp?id=263538

“Could Cannabis Kill Cancer Cells? A New Study Looks Promising”  https://www.portlandmercury.com/blogtown/2019/08/15/26977361/could-cannabis-kill-cancer-cells-a-new-study-looks-promising

“Study Reviews How Marijuana Compounds Inhibit Tumor Growth And Kill Cancer Cells” https://www.marijuanamoment.net/study-reviews-how-marijuana-compounds-inhibit-tumor-growth-and-kill-cancer-cells/

Cannabinoids and inflammation: Implications for People Living with HIV.

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Image result for wolters kluwer “Thanks to the success of modern antiretroviral therapy (ART), people living with HIV (PLWH) have life expectancies which approach that of persons in the general population. However, despite the ability of ART to suppress viral replication, PLWH have high levels of chronic systemic inflammation which drives the development of comorbidities such as cardiovascular disease, diabetes and non-AIDS associated malignancies.

Historically, cannabis has played an important role in alleviating many symptoms experienced by persons with advanced HIV infection in the pre-ART era and continues to be used by many PLWH in the ART era, though for different reasons.

Δ-tetrahydrocannabinol (Δ-THC) and cannabidiol (CBD) are the phytocannabinoids which have received most attention for their medicinal properties. Due to their ability to suppress lymphocyte proliferation and inflammatory cytokine production, there is interest in examining their therapeutic potential as immunomodulators.

CB2 receptor activation has been shown in vitro to reduce CD4 T-cell infection by CXCR4-tropic HIV and to reduce HIV replication.

Studies involving SIV-infected macaques have shown that Δ-THC can reduce morbidity and mortality and has favourable effects on the gut mucosal immunity. Furthermore, ΔTHC administration was associated with reduced lymph node fibrosis and diminished levels of SIV proviral DNA in spleens of rhesus macaques compared with placebo-treated macaques.

In humans, cannabis use does not induce a reduction in peripheral CD4 T-cell count or loss of HIV virological control in cross-sectional studies. Rather, cannabis use in ART-treated PLWH was associated with decreased levels of T-cell activation, inflammatory monocytes and pro-inflammatory cytokines secretion, all of which are related to HIV disease progression and co-morbidities.

Randomized clinical trials should provide further insights into the ability of cannabis and cannabinoid-based medicines to attenuate HIV-associated inflammation. In turn, these findings may provide a novel means to reduce morbidity and mortality in PLWH as adjunctive agents to ART.”

https://www.ncbi.nlm.nih.gov/pubmed/31408029

https://insights.ovid.com/crossref?an=00002030-900000000-96855