Tag Archives: Delta-9-Tetrahydrocannabinol

Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity.

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“To characterize the functional brain changes involved in δ-9-tetrahydrocannabinol (THC) modulation of chronic neuropathic pain.

RESULTS:

THC significantly reduced patients’ pain compared to placebo. THC-induced analgesia was correlated with a reduction in functional connectivity between the anterior cingulate cortex (ACC) and the sensorimotor cortex. Moreover, the degree of reduction was predictive of the response to THC. Graph theory analyses of local measures demonstrated reduction in network connectivity in areas involved in pain processing, and specifically in the dorsolateral prefrontal cortex (DLPFC), which were correlated with individual pain reduction.

CONCLUSION:

These results suggest that the ACC and DLPFC, 2 major cognitive-emotional modulation areas, and their connections to somatosensory areas, are functionally involved in the analgesic effect of THC in chronic pain. This effect may therefore be mediated through induction of functional disconnection between regulatory high-order affective regions and the sensorimotor cortex. Moreover, baseline functional connectivity between these brain areas may serve as a predictor for the extent of pain relief induced by THC.”

https://www.ncbi.nlm.nih.gov/pubmed/30185448

http://n.neurology.org/content/early/2018/09/05/WNL.0000000000006293

Fast extraction of cannabinoids in marijuana samples by using hard-cap espresso machines.

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Talanta

“A simple, quick and low cost procedure was developed for the extraction of Δ9-tetrahydrocannabinol, cannabidiol, and cannabinol from marijuana samples, based on the use of a hard-cap espresso extraction with 2-propanol. After extraction, cannabinoids were directly determined after appropriate dilution by gas-chromatography-mass spectrometry, reaching a limit of detection from 0.03 to 0.05 mg g-1. Extraction efficiency was evaluated by the comparison of results obtained for seized samples by the proposed method and a reference methodology based on ultrasound-assisted extraction. Moreover, ion mobility was proposed for the rapid and sensitive determination of Δ9-tetrahydrocannabinol and cannabidiol providing a quick response for the analysis of seized marijuana samples in 1 min, including extraction, dilution and determination.”

https://www.ncbi.nlm.nih.gov/pubmed/30172516

https://www.sciencedirect.com/science/article/pii/S0039914018308178?via%3Dihub

“Turns Out You Can Use Espresso Machines to Make Marijuana Extracts”  https://www.civilized.life/articles/espresso-machine-marijuana-extracts/

Should Cannabinoids Be Added to Multimodal Pain Regimens After Total Hip and Knee Arthroplasty?

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Journal of Arthroplasty Home

“This study investigated the effects of dronabinol on pain, nausea, and length of stay following total joint arthroplasty (TJA).

CONCLUSION:

These findings suggest that further investigation into the role of cannabinoid medications for non-opioid pain control in the post-arthroplasty patient may hold merit.”

https://www.ncbi.nlm.nih.gov/pubmed/30170713

“In conclusion, our study suggests that cannabinoids may have a role in post-arthroplasty pain management and may reduce patient’s need for opioid-containing pain medications. Further randomized, prospective clinical trials are warranted to shed more light onto the possible beneficial effects of cannabinoid medications in the orthopedic surgery patient population.” https://www.arthroplastyjournal.org/article/S0883-5403(18)30670-3/fulltext

Cannabis in liver disorders: a friend or a foe?

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“The recent legalization of recreational marijuana use in some parts of the world, the discovery of new indications for the clinical application of cannabis, and the acceptance of the use of cannabis in practice has been paralleled by extensive research on the active components of cannabis and the endocannabinoid system within the human body.

In this review, we evaluate the available evidence on cannabis and its constituents and the application of this evidence in clinical practice, focusing particularly on the liver and liver diseases.

Constituents of cannabis, such as cannabidiol and Δ-tetrahydrocannabinol, have shown anti-inflammatory, antioxidant, and hepatoprotective effects both in in vitro and clinical studies, and appear to have potential in the symptom management and treatment of various liver diseases that were previously considered difficult to manage conservatively.

In addition, the manipulation of the inherent endocannabinoid response system has found favor in many clinical fields and has generated considerable research and clinical interest. Moreover, evidence with regard to the adverse effects of marijuana use in liver diseases is weak, which has led to raise a question on the prior rules, with regard to a denial of liver transplantation to marijuana users.

All in all, the recent trends in research, clinical experiences, as well as the legislature, has opened up new avenues towards the widespread clinical application of cannabis and its derivatives as well as modifiers of the components of the endocannabinoid system. More research is required to fully exploit these new evidences.”

https://www.ncbi.nlm.nih.gov/pubmed/30169449

https://insights.ovid.com/crossref?an=00042737-900000000-97980

Δ9-tetrahydrocannabivarin impairs epithelial calcium transport through inhibition of TRPV5 and TRPV6.

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 Pharmacological Research

“Compounds extracted from the cannabis plant, including the psychoactive Δ9-tetrahydrocannabinol (THC) and related phytocannabinoids, evoke multiple diverse biological actions as ligands of the G protein-coupled cannabinoid receptors CB1 and CB2. In addition, there is increasing evidence that phytocannabinoids also have non-CB targets, including several ion channels of the transient receptor potential superfamily.

We investigated the effects of six non-THC phytocannabinoids on the epithelial calcium channels TRPV5 and TRPV6, and found that one of them, Δ9-tetrahydrocannabivarin (THCV), exerted a strong and concentration-dependent inhibitory effect on mammalian TRPV5 and TRPV6 and on the single zebrafish orthologue drTRPV5/6. Moreover, THCV attenuated the drTRPV5/6-dependent ossification in zebrafish embryos in vivo. Oppositely, 11-hydroxy-THCV (THCV-OH), a product of THCV metabolism in mammals, stimulated drTRPV5/6-mediated Ca2+ uptake and ossification.

These results identify the epithelial calcium channels TRPV5 and TRPV6 as novel targets of phytocannabinoids, and suggest that THCV-containing products may modulate TRPV5- and TRPV6-dependent epithelial calcium transport.”

https://www.ncbi.nlm.nih.gov/pubmed/30170189

https://linkinghub.elsevier.com/retrieve/pii/S1043661818311095

The Association Between Tetrahydrocannabinol and Lower Urinary Tract Symptoms Utilizing the National Health and Nutrition Examination Survey.

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Urology Home

“To further define the relationship between tetrahydrocannabinol (THC) and lower urinary tract symptoms (LUTS), specifically how THC use associates with the frequency of LUTS in young community-dwelling men in the United States.

MATERIALS AND METHODS:

The National Health and Nutrition Examination Survey (NHANES) database was queried (2005-2008). Men ages 20-59 who completed the urinary and substance abuse questionnaires were included. The presence of LUTS was defined as having ≥2 of the following: nocturia (≥2), hesitancy, incomplete emptying, or incontinence. THC use was self-reported, and participants were considered regular smokers if they endorsed smoking at least once per month. Multivariable logistic regression was performed to analyze the relationship between THC and LUTS.

RESULTS:

Among 3,037 men who met inclusion criteria, 14.4% (n=477) of subjects reported THC use. In multivariable analyses, adjusting for clinical variables, regular THC users remained significantly less likely to report LUTS (odds ratio of 0.55; CI 95% 0.408-0.751, p<0.01) compared to non-users.

CONCLUSION:

Obesity, diabetes, and multiple co-morbidities are well-established risk factors for LUTS within the NHANES. Regular THC use, however, appears to be protective from LUTS in young community-dwelling men.”

https://www.ncbi.nlm.nih.gov/pubmed/30142408

https://www.goldjournal.net/article/S0090-4295(18)30881-1/fulltext

Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science.

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“Comprehensive literature reviews of historical perspectives and evidence supporting cannabis/cannabinoids in the treatment of pain, including migraine and headache, with associated neurobiological mechanisms of pain modulation have been well described.

Most of the existing literature reports on the cannabinoids Δ9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), or cannabis in general. There are many cannabis strains that vary widely in the composition of cannabinoids, terpenes, flavonoids, and other compounds. These components work synergistically to produce wide variations in benefits, side effects, and strain characteristics. Knowledge of the individual medicinal properties of the cannabinoids, terpenes, and flavonoids is necessary to cross-breed strains to obtain optimal standardized synergistic compositions. This will enable targeting individual symptoms and/or diseases, including migraine, headache, and pain.

OBJECTIVE:

Review the medical literature for the use of cannabis/cannabinoids in the treatment of migraine, headache, facial pain, and other chronic pain syndromes, and for supporting evidence of a potential role in combatting the opioid epidemic. Review the medical literature involving major and minor cannabinoids, primary and secondary terpenes, and flavonoids that underlie the synergistic entourage effects of cannabis. Summarize the individual medicinal benefits of these substances, including analgesic and anti-inflammatory properties.

CONCLUSION:

There is accumulating evidence for various therapeutic benefits of cannabis/cannabinoids, especially in the treatment of pain, which may also apply to the treatment of migraine and headache. There is also supporting evidence that cannabis may assist in opioid detoxification and weaning, thus making it a potential weapon in battling the opioid epidemic. Cannabis science is a rapidly evolving medical sector and industry with increasingly regulated production standards. Further research is anticipated to optimize breeding of strain-specific synergistic ratios of cannabinoids, terpenes, and other phytochemicals for predictable user effects, characteristics, and improved symptom and disease-targeted therapies.”

https://www.ncbi.nlm.nih.gov/pubmed/30152161

Variability of Multiple Sclerosis Spasticity Symptoms in Response to THC:CBD Oromucosal Spray: Tracking Cases through Clinical Scales and Video Recordings.

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“Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune demyelinating disease of the central nervous system. Patients exhibit heterogeneous patterns of disabling symptoms, including spasticity. In the majority of patients with MS spasticity, it and its associated symptoms contribute to disability, interfere with performance of everyday activities, and impair quality of life. Even under treatment with oral antispasticity drugs, about a third of patients continue to experience spasticity of moderate to severe intensity, underscoring the need for additional treatment options.

The efficacy of tetrahydrocannabinol: cannabidiol (THC:CBD) oromucosal spray as add-on therapy in patients with refractory MS spasticity has been demonstrated in clinical trials and observational studies.

To gain insight into patients’ response to treatment at the individual level, in-depth changes from baseline in various clinical scales and video-assessed parameters were evaluated in patients with resistant MS spasticity before and after 1 month of treatment with THC:CBD oromucosal spray. All 6 patients showed ≥20% improvement in the spasticity Numerical Rating Scale (i.e., were initial responders to treatment), but displayed individual variability in other spasticity-related parameters.

Improved Modified Ashworth Scale scores were observed in 5 cases, with a reduction of -2/-3 points in lower limb scores for 1 patient who also showed benefit in terms of a more stable gait but modest improvement in the timed 10-meter walk test (10MWT). Improvement in the 10MWT (or 25-foot walk test) was noted in 4 of the 6 cases. THC:CBD oromucosal spray also improved upper limb function as indicated by faster 9-Hole Peg Test results.”

https://www.ncbi.nlm.nih.gov/pubmed/30140216
https://www.karger.com/Article/FullText/490376

A Brief Background on Cannabis: From Plant to Medical Indications.

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 Ingenta Connect

“Cannabis has been used as a medicinal plant for thousands of years.

As a result of centuries of breeding and selection, there are now over 700 varieties of cannabis that contain hundreds of compounds, including cannabinoids and terpenes.

Cannabinoids are fatty compounds that are the main biological active constituents of cannabis. Terpenes are volatile compounds that occur in many plants and have distinct odors.

Cannabinoids exert their effect on the body by binding to receptors, specifically cannabinoid receptors types 1 and 2. These receptors, together with endogenous cannabinoids and the systems for synthesis, transport, and degradation, are called the Endocannabinoid System.

The two most prevalent and commonly known cannabinoids in the cannabis plant are delta-9-tetrahydrocannabinol (THC) and cannabidiol.

The speed, strength, and type of effects of cannabis vary based on the route of administration. THC is rapidly distributed through the body to fatty tissues like the brain and is metabolized by the cytochrome P450 system to 11-hydroxy-THC, which is also psychoactive.

Cannabis and cannabinoids have been indicated for several medical conditions.

There is evidence of efficacy in the symptomatic treatment of nausea and vomiting, pain, insomnia, post-traumatic stress disorder, anxiety, loss of appetite, Tourette’s syndrome, and epilepsy. Cannabis has also been associated with treatment for glaucoma, Huntington’s Disease, Parkinson’s Disease, and dystonia, but there is not good evidence to support its efficacy. Side effects of cannabis include psychosis and anxiety, which can be severe.

Here, we provided a summary of the history of cannabis, its pharmacology, and its medical uses.”

https://www.ncbi.nlm.nih.gov/pubmed/30139415

http://www.ingentaconnect.com/content/aoac/jaoac/pre-prints/content-jaoac_180208;jsessionid=jbg0paav7wra.x-ic-live-03

Optimization Of A Preclinical Therapy Of Cannabinoids In Combination With Temozolomide Against Glioma.

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 Biochemical Pharmacology “Glioblastoma multiforme (GBM) is the most frequent and aggressive form of brain cancer. These features are explained at least in part by the high resistance exhibited by these tumors to current anticancer therapies. Thus, the development of novel therapeutic approaches is urgently needed to improve the survival of the patients suffering this devastating disease.

Δ9-Tetrahydrocannabinol (THC, the major active ingredient of marijuana), and other cannabinoids have been shown to exert antitumoral actions in animal models of cancer, including glioma. The mechanism of these anticancer actions relies, at least in part, on the ability of these compounds to stimulate autophagy-mediated apoptosis in tumor cells.

Previous observations from our group demonstrated that local administration of THC (or of THC + CBD at a 1:1 ratio, a mixture that resembles the composition of the cannabinoid-based medicine Sativex®) in combination with Temozolomide, the benchmark agent for the treatment of GBM, synergistically reduces the growth of glioma xenografts.

With the aim of optimizing the possible clinical utilization of cannabinoids in anti-GBM therapies, in this work we explored the anticancer efficacy of the systemic administration of cannabinoids in combination with TMZ in preclinical models of glioma.

Our results show that oral administration of THC+CBD (Sativex-like extracts) in combination with TMZ produces a strong antitumoral effect in both subcutaneous and intracranial glioma cell-derived tumor xenografts. In contrast, combined administration of Sativex-like and BCNU (another alkylating agent used for the treatment of GBM which share structural similarities with the TMZ) did not show a stronger effect than individual treatments.

Altogether, our findings support the notion that the combined administration of TMZ and oral cannabinoids could be therapeutically exploited for the management of GBM.”

https://www.ncbi.nlm.nih.gov/pubmed/30125556

https://www.sciencedirect.com/science/article/abs/pii/S0006295218303496