Role of Endocannabinoid System in the Peripheral Antinociceptive Action of Aripiprazole.

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“Recently, we demonstrated that the antipsychotic dopaminergic and serotoninergic agonist aripiprazole induced peripheral antinociception. However, the mechanism underlying this effect has not been fully established.

Here, our aim was to identify possible relationships between this action of aripiprazole and the endocannabinoid system.

CONCLUSIONS:

These results provide evidence for the involvement of the endocannabinoid system in peripheral antinociception induced by aripiprazole treatment.”

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

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

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

Cannabidiol modulates serotonergic transmission and prevents allodynia and anxiety-like behavior in a model of neuropathic pain.

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“Clinical studies indicate that cannabidiol (CBD), the primary non-addictive component of cannabis that interacts with the serotonin (5-HT) 1A receptor, may possess analgesic and anxiolytic effects. However, its effects on 5-HT neuronal activity, as well as its impact in models of neuropathic pain are unknown.

Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity. Anti-allodynic effects of CBD were fully prevented by capsazepine (10 mg/kg/day, s.c., for 7 days) and partially prevented by WAY 100635 (2 mg/kg/day, s.c., for 7 days), while the anxiolytic effect was blocked only by WAY.

Overall, repeated treatment with low-dose CBD induces analgesia predominantly via TRPV1 activation, reduces anxiety via 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/30157131

https://insights.ovid.com/crossref?an=00006396-900000000-98870

“Cannabis pain relief without the ‘high’. Canadian researchers pinpoint the mechanism of cannabidiol for safe pain relief without side effects”  https://eurekalert.org/pub_releases/2018-10/muhc-cpr102418.php

“Effective dose of cannabidiol for safe pain relief without the typical ‘high'”  https://www.news-medical.net/news/20181025/Effective-dose-of-cannabidiol-for-safe-pain-relief-without-the-typical-high.aspx

Self-Reported Effectiveness and Safety of Trokie® Lozenges: A Standardized Formulation for the Buccal Delivery of Cannabis Extracts.

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“Therapeutic use of cannabinoids, the main active ingredients of Cannabissativa L., is often hindered by their limited bioavailability and undesirable psychoactivity. We conducted an observational study in December 2016 and another one in February 2018 to investigate respectively: (i) the effectiveness of Trokie® lozenges, a standardized formulation containing cannabis extracts, to deliver cannabinoids via buccal absorption and (ii) its long-term safety.

Participants were members of the Palliative Care Corporation health clinic, registered California cannabis patients, and had a diagnosis of chronic non-cancer pain. For the effectiveness study, 49 participants were asked to self-report pain perception before and after 1-12 weeks of taking Trokie® lozenges, using an 11-point pain intensity numeric rating scale (PI-NRS).

A mean reduction in PI-NRS score of 4.9 ± 2.0 points was observed. Onset of analgesia typically varied between 5 and 40 min, which seems consistent with, at least partial, buccal absorption. In the safety study, 35 participants were asked to complete a questionnaire about adverse events (AEs) associated with Trokie® lozenges. AEs were reported by 16 subjects (46%), the most common being dizziness/unsteadiness (N = 7), bad taste (N = 5), and throat irritation/dry mouth (N = 4). None of the self-reported AEs resulted in a serious medical situation and most of them had limited impact on daily functions.

Despite the AEs, 90% of participants reported being “satisfied” or “very satisfied” with the product. These observations suggest that buccal administration of standardized extracts via Trokie® lozenges may represent an efficacious and safe approach to cannabis administration.”

https://www.ncbi.nlm.nih.gov/pubmed/30154694

https://www.frontiersin.org/articles/10.3389/fnins.2018.00564/full 

Cannabis and the Health and Performance of the Elite Athlete.

 

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“Cannabis (marijuana) is undergoing extensive regulatory review in many global jurisdictions for medical and nonmedical access. Cannabis has potential impact on the health of athletes as well as on performance in both training and in competition. The aim of this general review is to identify and highlight the challenges in interpreting information with respect to elite athletic performance, and to point to important research areas that need to be addressed.

MAIN RESULTS:

Cannabis may be primarily inhaled or ingested orally for a range of medical and nonmedical reasons; evidence for efficacy is limited but promising for chronic pain management. Although evidence for serious harms from cannabis use on health of athletes is limited, one should be cognizant of the potential for abuse and mental health issues. Although the prevalence of cannabis use among elite athletes is not well-known, use is associated with certain high-risk sports. There is no evidence for cannabis use as a performance-enhancing drug.

CONCLUSIONS:

Medical and nonmedical cannabis use among athletes reflects changing societal and cultural norms and experiences. Although cannabis use is more prevalent in some athletes engaged in high-risk sports, there is no direct evidence of performance-enhancing effects in athletes. The potential beneficial effects of cannabis as part of a pain management protocol, including reducing concussion-related symptoms, deserve further attention.”

https://www.ncbi.nlm.nih.gov/pubmed/30153174

https://insights.ovid.com/crossref?an=00042752-201809000-00009

Orthopaedic surgery patients who use recreational marijuana have less pre-operative pain.

“To determine the baseline clinical characteristics of recreational marijuana users undergoing outpatient orthopaedic surgery.

We hypothesized that patients who report marijuana use would have worse pain, function, and general health status.

The results do not support our hypothesis, as marijuana use was associated with less pain and better lower extremity activity rating scale scores when compared to non-users.”

https://www.ncbi.nlm.nih.gov/pubmed/30135987

https://link.springer.com/article/10.1007%2Fs00264-018-4101-x

Patient-Reported Symptom Relief Following Medical Cannabis Consumption

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“The Releaf AppTM mobile software application (app) data was used to measure self-reported effectiveness and side effects of medical cannabis used under naturalistic conditions.

Results: Releaf AppTM responders used cannabis to treat myriad health symptoms, the most frequent relating to pain, anxiety, and depressive conditions. Significant symptom severity reductions were reported for all the symptom categories, with mean reductions between 2.8 and 4.6 points (ds ranged from 1.29–2.39, ps < 0.001). On average, higher pre-dosing symptom levels were associated with greater reported symptom relief, and users treating anxiety or depression-related symptoms reported significantly more relief (ps < 0.001) than users with pain symptoms. Of the 42 possible side effects, users were more likely to indicate and showed a stronger correlation between symptom relief and experiences of positive (94% of sessions) or a context-specific side effects (76%), whereas negative side effects (60%) were associated with lessened, yet still significant symptom relief and were more common among patients treating a depressive symptom relative to patients treating anxiety and pain-related conditions.

Conclusion: Patient-managed cannabis use is associated with clinically significant improvements in self-reported symptom relief for treating a wide range of health conditions, along with frequent positive and negative side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/30210337

https://www.frontiersin.org/articles/10.3389/fphar.2018.00916/full

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

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

 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