New Insights in Cannabinoid Receptor Structure and Signaling.

“Cannabinoid has long been used for medicinal purposes. Cannabinoid signaling has been considered the therapeutic targets for treating pain, addiction, obesity, inflammation, and other diseases. Recent studies have suggested that in addition to CB1 and CB2, there are non-CB1 and non-CB2 cannabinoid-related orphan GPCRs including GPR18, GPR55, and GPR119. In addition, CB1 and CB2 display allosteric binding and biased signaling, revealing correlations between biased signaling and functional outcomes. Interestingly, new investigations have indicated that CB1 is functionally present within mitochondria of striated and heart muscles directly regulating intramitochondrial signaling and respiration.

CONCLUSION:

In this review, we summarize the recent progress in cannabinoid-related orphan GPCRs, CB1/CB2 structure, Gi/Gs coupling, allosteric ligands and biased signaling, and mitochondria-localized CB1, and discuss the future promise of this research.”

https://www.ncbi.nlm.nih.gov/pubmed/30767756

http://www.eurekaselect.com/170011/article

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Spontaneous, anecdotal, retrospective, open-label study on the efficacy, safety and tolerability of cannabis galenical preparation (Bedrocan).

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“Our main aim was to investigate the short-term therapeutic effects, safety/tolerability and potential side effects of the cannabis galenical preparation (Bedrocan) in patients with a range of chronic conditions unresponsive to other treatments.

METHODS:

In this retrospective, ‘compassionate use’, observational, open-label study, 20 patients (age 18-80 years) who had appealed to our ‘Second Opinion Medical Consulting Network’ (Modena, Italy), were instructed to take sublingually the galenical oil twice a day for 3 months of treatment. The usual starting dose was low (0.5 ml/day) and gradually titrated upward to the highest recommended dose (1 ml/day). Tolerability and adverse effects were assessed at baseline and monthly thereafter during the treatment period through direct contact (email or telephone) or visit if required. Patients’ quality of life was evaluated at baseline and 3 months using the medical outcome short-form health survey questionnaire (SF-36).

KEY FINDINGS:

From baseline to 6 months post-treatment, SF-36 scores showed: reductions in total pain (P < 0.03); improvements in the physical component (P < 0.02); vitality (P < 0.03); social role functioning (P < 0.02); and general health state (P < 0.02). No changes in role limitations (P = 0.02) due to emotional state (e.g. panic, depression, mood alteration) were reported. Monthly reports of psychoactive adverse effects showed significant insomnia reduction (P < 0.03) and improvement in mood (P < 0.03) and concentration (P < 0.01).

CONCLUSIONS:

These data suggest that a cannabis galenical preparation may be therapeutically effective and safe for the symptomatic treatment of some chronic diseases. Further studies on the efficacy of cannabis as well as cannabinoid system involvement in the pathophysiology are warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/30768819

https://onlinelibrary.wiley.com/doi/full/10.1111/ijpp.12514

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Combined tetrahydrocannabinol and cannabidiol to treat pain in epidermolysis bullosa: a report of three cases

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“Epidermolysis bullosa (EB) is a genetic blistering disorder characterized by intense pain related to disease pathology and care‐based interventions.

Opioid‐based therapies underpin pain care in EB; however, they are unable to provide adequate analgesia in a significant proportion of patients.

Cannabinoid‐based medicines (CBMs) have been studied increasingly for pain conditions of various aetiologies and pose as a novel dimension for pain care in EB.

We present three patients with EB who were prescribed pharmaceutical‐grade sublingually administered CBMs comprising tetrahydrocannabinol and cannabidiol.

All three patients reported improved pain scores, reduced pruritus and reduction in overall analgesic drug intake.”

https://www.ncbi.nlm.nih.gov/pubmed/30347109

https://onlinelibrary.wiley.com/doi/full/10.1111/bjd.17341

“Cannabinoids Could Help Manage EB-related Pain, Study Suggests”  https://epidermolysisbullosanews.com/2019/02/08/cannabinoids-could-help-manage-eb-related-pain-study-suggests/

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An Update of Current Cannabis-Based Pharmaceuticals in Pain Medicine.

 

“Cannabis users have long reported therapeutic properties of the plant for a variety of conditions, some of which include nausea, emesis, seizures, cancer, neurogenic diseases and pain control. Research has elucidated many cannabinoid pharmacodynamic and pharmacokinetic properties, expanding the potential use of cannabinoids as a medical therapy.

Due to the inconsistent delivery and control of the active components involved with smoking, pharmaceutical companies are investigating and prioritizing routes other than smoke inhalation for therapeutic use of cannabinoids. In this relatively new field of pharmaceutical development, ongoing drug development promises great benefit from targeted endocannabinoid receptor agonism.

Available in Canada and Europe, nabiximols, a specific extract from the Cannabis plant, has demonstrated great benefit in the treatment of pain related to spasticity in multiple sclerosis, cancer and otherwise chronic pain conditions.

The cannabidiol oral solution Epidiolex®, which is available in the USA, is indicated for management of refractory epilepsy but may offer therapeutic relief to chronic pain conditions as well.

Current investigative drugs, such as those developed by Cara Therapeutics and Zynerba Pharmaceuticals, are synthetic cannabinoids which show promise to specifically target neuropsychiatric conditions and chronic pain symptoms such as neuropathy and allodynia.

The objective of this review is to provide clinicians with an update of currently available and promising developmental cannabis pharmaceutical derivatives which may stand to greatly benefit patients with otherwise difficult-to-treat chronic conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/30721403

https://link.springer.com/article/10.1007%2Fs40122-019-0114-4

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Qualifying Conditions Of Medical Cannabis License Holders In The United States.

Health Affairs

“The evidence for cannabis‘s treatment efficacy across different conditions varies widely, and comprehensive data on the conditions for which people use cannabis are lacking. We analyzed state registry data to provide nationwide estimates characterizing the qualifying conditions for which patients are licensed to use cannabis medically. We also compared the prevalence of medical cannabis qualifying conditions to recent evidence from the National Academies of Sciences, Engineering, and Medicine report on cannabis‘s efficacy in treating each condition. Twenty states and the District of Columbia had available registry data on patient numbers, and fifteen states had data on patient-reported qualifying conditions. Chronic pain is currently and historically the most common qualifying condition reported by medical cannabis patients (64.9 percent in 2016). Of all patient-reported qualifying conditions, 85.5 percent had either substantial or conclusive evidence of therapeutic efficacy. As medical cannabis use continues to increase, creating a nationwide patient registry would facilitate better understanding of trends in use and of its potential effectiveness.”

https://www.ncbi.nlm.nih.gov/pubmed/30715980

https://www.healthaffairs.org/doi/10.1377/hlthaff.2018.05266

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Ketamine induces central antinociception mediated by endogenous cannabinoids and activation of CB1 receptors.

Neuroscience Letters

“The participation of endocannabinoids in central and peripheral antinociception induced by several compounds has been shown by our group.

In this study, we investigated the effect of endocannabinoids on the central antinociception induced by ketamine.

It was concluded that central antinociception induced by ketamine involves the activation of CB1 cannabinoidreceptors.

Mobilization of cannabinoids might be required for the activation of those receptors, since inhibitors of the endogenous cannabinoids potentiate the effect of Ketamine.”

https://www.ncbi.nlm.nih.gov/pubmed/30716423

https://www.sciencedirect.com/science/article/abs/pii/S0304394019300771?via%3Dihub

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Novel Approaches for Treating Pain in Children.

Logo SpringerLink“Good pain management in children, especially those at end of life, is a crucial component of palliative medicine. The current review assesses some of the new and/or innovative ways to manage pain in children. The article focuses on some recent medications/pharmaceutical options such as cannabinoids and also innovative ways to administer medication to children, such as intranasal and inhalation.

RECENT FINDINGS:

Current approaches to pain management now include (1) new uses of old drugs such as ketamine and lidocaine, (2) use of new drugs/medications such as cannabinoids, and (3) creative use of old technology such as atomizers, intranasal drops, and inhalation. Typically, novel approaches to care rarely start in pediatrics or palliative care. The current review has presented some new and old drugs being utilized in new and old ways.”

https://www.ncbi.nlm.nih.gov/pubmed/30714078

https://link.springer.com/article/10.1007%2Fs11912-019-0766-6

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Recreational marijuana legalization and prescription opioids received by Medicaid enrollees.

Drug and Alcohol Dependence

“Medical marijuana use may substitute prescription opioid use, whereas nonmedical marijuana use may be a risk factor of prescription opioid misuse. This study examined the associations between recreational marijuana legalization and prescription opioids received by Medicaid enrollees. In models comparing eight states and DC, legalization was not associated with Schedule II opioid outcomes; having recreational marijuana legalization effective in 2015 was associated with reductions in number of prescriptions, total doses, and spending of Schedule III opioids by 32%, and 31%, respectively. In models comparing eight states and DC to six states with medical marijuana legalization, recreational marijuana legalization was not associated with any opioid outcome. No evidence suggested that recreational marijuana legalization increased prescription opioids received by Medicaid enrollees. There was some evidence in some states for reduced Schedule III opioids following the legalization.” https://www.ncbi.nlm.nih.gov/pubmed/30390550

https://www.sciencedirect.com/science/article/pii/S0376871618307567?via%3Dihub

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Impact of Medical Marijuana Legalization on Opioid Use, Chronic Opioid Use, and High-risk Opioid Use.

“Medical marijuana legalization was found to be associated with a lower odds of any opioid use. In states where marijuana is available through medical channels, a modestly lower rate of opioid and high-risk opioid prescribing was observed. Policy makers could consider medical marijuana legalization as a tool that may modestly reduce chronic and high-risk opioid use.” https://www.ncbi.nlm.nih.gov/pubmed/30684198

https://link.springer.com/article/10.1007%2Fs11606-018-4782-2

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A Cost-Effectiveness Model for Adjunctive Smoked Cannabis in the Treatment of Chronic Neuropathic Pain

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“A recent meta-analysis affirmed the benefit of medicinal cannabis for chronic neuropathic pain, a disabling and difficult-to-treat condition. As medicinal cannabis use is becoming increasingly prevalent among Americans, an exploration of its economic feasibility is warranted. We present this cost-effectiveness analysis of adjunctive cannabis pharmacotherapy for chronic peripheral neuropathy.

A growing body of scientific literature demonstrates reproducible efficacy of cannabis in the treatment of several medical conditions, including chronic neuropathic pain. Clinical trials of oral, smoked, and vaporized cannabis and cannabinoids have all demonstrated analgesic benefit of medicinal cannabis in the treatment of this costly and disabling condition. A recent meta-analysis of individual patient data from five randomized controlled trials of inhaled cannabis demonstrated pain relief comparable to gabapentin. Treatment guidelines for neuropathic pain recommend consideration of cannabinoids as third-line agents.

As recently proposed willingness-to-pay thresholds for the United States health marketplace range from $110,000 to $300,000 per QALY, cannabis appears cost-effective when augmenting second-line treatment for painful neuropathy. Further research is warranted to explore the long-term benefit of smoked cannabis and standardization of its dosing for chronic neuropathic pain.”

https://www.liebertpub.com/doi/10.1089/can.2018.0027

“New study analyzes cost effectiveness of smoked cannabis to treat chronic neuropathic pain” https://www.eurekalert.org/pub_releases/2019-01/mali-nsa012919.php

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