Antinociceptive effects of HUF-101, a fluorinated cannabidiol derivative.

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“Cannabidiol (CBD) is a phytocannabinoid with multiple pharmacological effects and several potential therapeutic properties. Its low oral bioavailability, however, can limit its clinical use.

Preliminary results indicate that fluorination of the CBD molecule increases its pharmacological potency. Here, we investigated whether HUF-101 (3, 10, and 30mg/kg), a fluorinated CBD analogue, would induce antinociceptive effects.

These findings show that HUF-101 produced antinociceptive effects at lower doses than CBD, indicating that the addition of fluoride improved its pharmacological profile. Furthermore, some of the antinociceptive effects of CBD and HUF-101 effects seem to involve the activation of CB1 and CB2 receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/28720466

http://www.sciencedirect.com/science/article/pii/S0278584617302233

Efficacy, tolerability, and safety of non-pharmacological therapies for chronic pain: An umbrella review on various CAM approaches.

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“Complementary and alternative medicine (CAM) therapies may be used as a non-pharmacological approach to chronic pain management. Twenty-six reviews (207 clinical trials, >12,000 participants) about 18 CAM modalities, falling under natural products, mind and body practices or other complementary health approaches were included. Inhaled cannabis, graded motor imagery, and Compound Kushen injection (a form of Chinese medicine) were found the most efficient and tolerable for chronic pain relief. When reported, adverse effects related to these CAM were minor.” https://www.ncbi.nlm.nih.gov/pubmed/28669581

Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report

“Prescription drug overdoses are the leading cause of accidental death in the United States. Alternatives to opioids for the treatment of pain are necessary to address this issue. Cannabis can be an effective treatment for pain, greatly reduces the chance of dependence, and eliminates the risk of fatal overdose compared to opioid-based medications. Medical cannabis patients report that cannabis is just as effective, if not more, than opioid-based medications for pain.

The results of this study provide implications from both a micro and macro level. First, from the macro level, there have been three previously published indicators of public health changes in states that permit medical cannabis: decreases in opioid related mortality, decreases in spending on opioids, and a decrease in traffic fatalities. While none of these studies shows a cause and effect relationship, they do suggest public health related population based changes in localities where cannabis can be accessed to treat pain. Given that the participants in this study reported a greater likelihood of using cannabis as a substitute in a less stigmatized and easily accessible environment, it makes sense why we would see these changes in locations where medical cannabis is sanctioned versus places where it is illegal.

At the micro level, there is a great deal of individual risk associated with prolonged use of opioids and perhaps even nonopioid-based pain medications. The prescribing of opioids has not been curbed in the United States, despite the growing number of fatal overdoses and reported dependence. Providing the patient with the option of cannabis as a method of pain treatment alongside the option of opioids might assist with pain relief in a safer environment with less risk. A society with less opioid dependent people will result in fewer public health harms.”

http://online.liebertpub.com/doi/10.1089/can.2017.0012

Cannabinoids could make opioids more effective, meaning pain relief with lower doses and reduced risk of dependency

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“In animal studies, four times less morphine and ten times less codeine was needed when cannabinoids were given at the same time.

The higher the dose of opioid pain relievers, the more likely it is a patient will experience side effects and complications. With the opioid epidemic becoming a pressing problem, researchers are working to find ways to provide pain relief with less risk. To understand whether therapeutic cannabinoids could be an effective strategy to reduce opioid use, researchers at the University of New South Wales and the Centre for Addiction and Mental Health analysed data from 19 pre-clinical studies and nine clinical trials.

“These studies highlight the potential beneficial effects of combining opioids and cannabinoids””

The cannabinoid system and pain.

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“Chronic pain states are highly prevalent and yet poorly controlled by currently available analgesics, representing an enormous clinical, societal, and economic burden. Existing pain medications have significant limitations and adverse effects including tolerance, dependence, gastrointestinal dysfunction, cognitive impairment, and a narrow therapeutic window, making the search for novel analgesics ever more important. In this article, we review the role of an important endogenous pain control system, the endocannabinoid (EC) system, in the sensory, emotional, and cognitive aspects of pain. Herein, we briefly cover the discovery of the EC system and its role in pain processing pathways, before concentrating on three areas of current major interest in EC pain research; 1. Pharmacological enhancement of endocannabinoid activity (via blockade of EC metabolism or allosteric modulation of CB1receptors); 2. The EC System and stress-induced modulation of pain; and 3. The EC system & medial prefrontal cortex (mPFC) dysfunction in pain states. Whilst we focus predominantly on the preclinical data, we also include extensive discussion of recent clinical failures of endocannabinoid-related therapies, the future potential of these approaches, and important directions for future research on the EC system and pain.”

https://www.ncbi.nlm.nih.gov/pubmed/28625720

http://www.sciencedirect.com/science/article/pii/S002839081730285X

Medicinal Uses of Marijuana and Cannabinoids

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“In the past two decades, there has been increasing interest in the therapeutic potential of cannabis and single cannabinoids, mainly cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). THC and cannabis products rich in THC exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). Since 1975, 140 controlled clinical trials using different cannabinoids or whole-plant preparations for the treatment of a large number of disorders and symptoms have been conducted. Results have led to the approval of cannabis-based medicines [dronabinol, nabilone, and the cannabis extract nabiximols (Sativex®, THC:CBD = 1:1)] as well as cannabis flowers in several countries. Controlled clinical studies provide substantial evidence for the use of cannabinoid receptor agonists in cancer chemotherapy induced nausea and vomiting, appetite loss and cachexia in cancer and HIV patients, neuropathic and chronic pain, and in spasticity in multiple sclerosis. In addition, there is also some evidence suggesting a therapeutic potential of cannabis-based medicines in other indications including Tourette syndrome, spinal cord injury, Crohn’s disease, irritable bowel syndrome, and glaucoma. In several other indications, small uncontrolled and single-case studies reporting beneficial effects are available, for example in posttraumatic stress disorder, attention deficit hyperactivity disorder, and migraine. The most common side effects of THC and cannabis-based medicines rich in THC are sedation and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. In recent years there is an increasing interest in the medical use of CBD, which exerts no intoxicating side effects and is usually well-tolerated. Preliminary data suggest promising effects in the treatment of anxiety disorders, schizophrenia, dystonia, and some forms of epilepsy. This review gives an overview on clinical studies which have been published over the past 40 years.”

http://www.tandfonline.com/doi/abs/10.1080/07352689.2016.1265360?needAccess=true&journalCode=bpts20

“Review Identifies 140 Controlled Clinical Trials Related to Cannabis”  http://blog.norml.org/2017/06/04/review-identifies-140-controlled-clinical-trials-related-to-cannabis/

Problematic Use of Prescription Opioids and Medicinal Cannabis Among Patients Suffering from Chronic Pain

 

409715“To assess prevalence rates and correlates of problematic use of prescription opioids and medicinal cannabis (MC) among patients receiving treatment for chronic pain.

Problematic use of opioids is common among chronic pain patients treated with prescription opioids and is more prevalent than problematic use of cannabis among those receiving MC.”

https://academic.oup.com/painmedicine/article-abstract/18/2/294/2924709/Problematic-Use-of-Prescription-Opioids-and?redirectedFrom=fulltext

Cannabis and intractable chronic pain: an explorative retrospective analysis of Italian cohort of 614 patients.

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“Despite growing interest in the therapeutic use of cannabis to manage chronic pain, only limited data that address these issues are available. In recent years, a number of nations have introduced specific laws to allow patients to use cannabis preparations to treat a variety of medical conditions. In 2015, the Italian government authorized the use of cannabis to treat several diseases, including chronic pain generally, spasticity in multiple sclerosis, cachexia and anorexia among AIDS and cancer patients, glaucoma, Tourette syndrome, and certain types of epilepsy. We present the first snapshot of the Italian experience with cannabis use for chronic pain over the initial year of its use.

METHODS:

This is a retrospective case series analysis of all chronic pain patients treated with oral or vaporized cannabis in six hubs during the initial year following the approval of the new Italian law (December 2015 to November 2016). We evaluated routes of administration, types of cannabis products utilized, dosing, and effectiveness and safety of the treatment.

RESULTS:

As only one of the six centers has extensively used cannabinoids for intractable chronic pain (614 patients of 659), only the population from Azienda Ospedaliero Universitaria Pisana (Pisa) was considered. Cannabis tea was the primary mode of delivery, and in almost all cases, it was used in association with all the other pain treatments. Initial and follow-up cannabinoid concentrations were found to vary considerably. At initial follow-up, 76.2% of patients continued the treatment, and <15% stopped the treatment due to side effects (none of which were severe).

CONCLUSION:

We present the first analysis of Italian clinical practice of the use of cannabinoids for a large variety of chronic pain syndromes. From this initial snapshot, we determined that the treatment seems to be effective and safe, although more data and subsequent trials are needed to better investigate its ideal clinical indication.”

https://www.ncbi.nlm.nih.gov/pubmed/28579820

https://www.dovepress.com/cannabis-and-intractable-chronic-pain-an-explorative-retrospective-ana-peer-reviewed-article-JPR

The Analgesic Potential of Cannabinoids

 

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“Cannabinoids are derivatives of Cannabis sativa, the hemp plant, which evolved in the temperate regions of Central Asia. Cannabis was used as a medicine in ancient China (2700 BC) and India (1000 BC). Historically and anecdotally cannabinoids have been used as analgesic agents.

In recent years, there has been an escalating interest in developing cannabis-derived medications to treat severe pain. This review provides an overview of the history of cannabis use in medicine, cannabinoid signaling pathways, and current data from preclinical as well as clinical studies on using cannabinoids as potential analgesic agents. Clinical and experimental studies show that cannabis-derived compounds act as anti-emetic, appetite modulating and analgesic agents.

Since opioids are the only therapy for severe pain, analgesic ability of cannabinoids may provide a much-needed alternative to opioids. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis based medications deserves serious consideration to alleviate the suffering of patients due to severe pain.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728280/

[Therapeutic potential of Cannabis sativa].

SciELO - Scientific Electronic Library Online

“Cannabis sativa (marihuana) is considered an illicit drug due to its psychoactive properties. Recently, the Chilean government opened to the use cannabis in the symptomatic treatment of some patients. The biological effects of cannabis render it useful for the complementary treatment of specific clinical situations such as chronic pain. We retrieved scientific information about the analgesic properties of cannabis, using it as a safe drug. The drug may block or inhibit the transmission of nervous impulses at different levels, an effect associated with pain control. Within this context and using adequate doses, forms and administration pathways, it can be used for chronic pain management, considering its effectiveness and low cost. It could also be considered as an alternative in patients receiving prolonged analgesic therapies with multiple adverse effects.”