Category Archives: Chronic Pain

Cannabis Use is Associated with Lower Odds of Prescription Opioid Analgesic Use Among HIV-Infected Individuals with Chronic Pain.

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“Chronic pain is common in the United States and prescribed opioid analgesics use for noncancer pain has increased dramatically in the past two decades, possibly accounting for the current opioid addiction epidemic. Co-morbid drug use in those prescribed opioid analgesics is common, but there are few data on polysubstance use patterns.

We explored patterns of use of cigarette, alcohol, and illicit drugs in HIV-infected people with chronic pain who were prescribed opioid analgesics.

Almost half of the sample of people with HIV and chronic pain reported current prescribed opioid analgesic use (N = 372, 47.1%). Illicit drug use was common (N = 505, 63.9%), and cannabis was the most commonly used illicit substance (N = 311, 39.4%).

In multivariate analyses, only cannabis use was significantly associated with lower odds of prescribed opioid analgesic use (adjusted odds ratio = 0.57; 95% confidence interval: 0.38-0.87).

Conclusions/Importance: Our data suggest that new medical cannabis legislation might reduce the need for opioid analgesics for pain management, which could help to address adverse events associated with opioid analgesic use.”

https://www.ncbi.nlm.nih.gov/pubmed/29338578

http://www.tandfonline.com/doi/abs/10.1080/10826084.2017.1416408?journalCode=isum20

Antinociceptive effects of mixtures of mu opioid receptor agonists and cannabinoid receptor agonists in rats: impact of drug and fixed-dose ratio.

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“Pain is a significant clinical problem, and there is a need for effective pharmacotherapies with fewer adverse effects than currently available drugs (e.g., mu opioid receptor agonists).

Cannabinoid receptor agonists enhance the antinociceptive effects of mu opioid receptor agonists, but it remains unclear which drugs and in what proportion will yield the most effective and safest treatments.

The antinociceptive effects of the mu opioid receptor agonists etorphine and morphine alone and in combination with the cannabinoid receptor agonists Δ9-THC and CP55940 were studied in male Sprague-Dawley rats (n=16) using a warm water tail withdrawal procedure.

The ratio of opioid to cannabinoid (3:1, 1:1, and 1:3) varied for each mixture. Drugs administered alone or as pairwise mixtures of an opioid and a cannabinoid dose-dependently increased tail withdrawal latency. Mixtures with morphine produced supra-additive (CP55940) and additive (Δ9-THC) effects, whereas mixtures with etorphine and either cannabinoid were sub-additive. The interactions were not different among ratios for a particular mixture.

The nature of the interaction between opioids and cannabinoids with regard to antinociceptive effects varies with the particular drugs in the mixture, which can have implications for designing combination therapies for pain.”

https://www.ncbi.nlm.nih.gov/pubmed/29183835

http://www.sciencedirect.com/science/article/pii/S0014299917307719

Acetaminophen Relieves Inflammatory Pain Through CB1 Cannabinoid Receptors in the Rostral Ventromedial Medulla.

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Journal of Neuroscience

“Acetaminophen (paracetamol) is a widely used analgesic and antipyretic drug with only incompletely understood mechanisms of action.

Previous work, using models of acute nociceptive pain, indicated that analgesia by acetaminophen involves an indirect activation of CB1 receptors by the acetaminophen metabolite and endocannabinoid re-uptake inhibitor AM 404.  However, the contribution of the cannabinoid system to anti-hyperalgesia against inflammatory pain, the main indication of acetaminophen, and the precise site of the relevant CB1 receptors have remained elusive.

Here, we analyzed acetaminophen analgesia in mice of either sex with inflammatory pain and found that acetaminophen exerted a dose-dependent anti-hyperalgesic action, which was mimicked by intrathecally injected AM 404. Both compounds lost their anti-hyperalgesic activity in CB1-/- mice confirming the involvement of the cannabinoid system.

Our results indicate that the cannabinoid system contributes not only to acetaminophen analgesia against acute pain but also against inflammatory pain, and suggest that the relevant CB1 receptors reside in the RVM.

SIGNIFICANCE STATEMENT: Acetaminophen is a widely used analgesic drug with multiple but only incompletely understood mechanisms of action including a facilitation of endogenous cannabinoid signaling via one of its metabolites. Our present data indicate that enhanced cannabinoid signaling is also responsible for the analgesic effects of acetaminophen against inflammatory pain. Local injections of the acetaminophen metabolite AM 404 and of cannabinoid receptor antagonists as well as data from tissue specific CB1 receptor deficient mice suggest the rostral ventromedial medulla as an important site of the cannabinoid-mediated analgesia by acetaminophen.”

https://www.ncbi.nlm.nih.gov/pubmed/29167401

http://www.jneurosci.org/content/early/2017/11/22/JNEUROSCI.1945-17.2017

Current evidence of cannabinoid-based analgesia obtained in preclinical and human experimental settings.

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European Journal of Pain

“Cannabinoids have a long record of recreational and medical use and become increasingly approved for pain therapy. This development is based on preclinical and human experimental research summarized in this review.

Cannabinoid CB1 receptors are widely expressed throughout the nociceptive system. Their activation by endogenous or exogenous cannabinoids modulates the release of neurotransmitters. This is reflected in antinociceptive effects of cannabinoids in preclinical models of inflammatory, cancer and neuropathic pain, and by nociceptive hypersensitivity of cannabinoid receptor-deficient mice.

Cannabis-based medications available for humans mainly comprise Δ9 -tetrahydrocannabinol (THC), cannabidiol (CBD) and nabilone.

During the last 10 years, six controlled studies assessing analgesic effects of cannabinoid-based drugs in human experimental settings were reported. An effect on nociceptive processing could be translated to the human setting in functional magnetic resonance imaging studies that pointed at a reduced connectivity within the pain matrix of the brain. However, cannabinoid-based drugs heterogeneously influenced the perception of experimentally induced pain including a reduction in only the affective but not the sensory perception of pain, only moderate analgesic effects, or occasional hyperalgesic effects. This extends to the clinical setting.

While controlled studies showed a lack of robust analgesic effects, cannabis was nearly always associated with analgesia in open-label or retrospective reports, possibly indicating an effect on well-being or mood, rather than on sensory pain. Thus, while preclinical evidence supports cannabinoid-based analgesics, human evidence presently provides only reluctant support for a broad clinical use of cannabinoid-based medications in pain therapy.

SIGNIFICANCE:

Cannabinoids consistently produced antinociceptive effects in preclinical models, whereas they heterogeneously influenced the perception of experimentally induced pain in humans and did not provide robust clinical analgesia, which jeopardizes the translation of preclinical research on cannabinoid-mediated antinociception into the human setting.”

https://www.ncbi.nlm.nih.gov/pubmed/29160600

http://onlinelibrary.wiley.com/doi/10.1002/ejp.1148/abstract?systemMessage=Wiley+Online+Library+usage+report+download+page+will+be+unavailable+on+Friday+24th+November+2017+at+21%3A00+EST+%2F+02.00+GMT+%2F+10%3A00+SGT+%28Saturday+25th+Nov+for+SGT+

Modulating the endocannabinoid pathway as treatment for peripheral neuropathic pain: a selected review of preclinical studies.

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“Chemotherapy-induced neuropathic pain is a distressing and commonly occurring side effect of many commonly used chemotherapeutic agents, which in some cases may prevent cancer patients from being able to complete their treatment.

Cannabinoid based therapies have the potential to manage or even prevent pain associated with this syndrome.

Pre-clinical animal studies that investigate the modulation of the endocannabinoid system (endogenous cannabinoid pathway) are being conducted to better understand the mechanisms behind this phenomenon.

Five recent pre-clinical studies identified from Medline published between 2013 and 2016 were selected for review. All studies evaluated the effect of small-molecule agonists or antagonists on components of the endocannabinoid system in rats or mice, using cisplatin or paclitax-el-induced allodynia as a model of chemotherapy-induced neuropathic pain. Activation of the cannabinoid receptor-2 (CB-2) receptor by AM1710 blocked paclitaxel-induced mechanical and cold allodynia in one study.

Four studies investigating the activation of both cannabinoid receptor-1 (CB-1) and CB-2 receptors by dual-agonists (WIN55,21 and CP55,940), or by the introduction of inhibitors of endocannabinoid metabolisers (URB597, URB937, JZL184, and SA-57) showed reduction of chemotherapy-induced al-lodynia. In addition, their results suggest that anti-allodynic effects may also be mediated by additional receptors, including TRPV1 and 5-hydroxytryptamine (5-HT1A).

Pre-clinical studies demon-strate that the activation of endocannabinoid CB-1 or CB-2 receptors produces physiological effects in animal models, namely the reduction of chemotherapy-induced allodynia. These studies also provide in-sight into the biological mechanism behind the therapeutic utility of cannabis compounds in managing chemotherapy-induced neuropathic pain, and provide a basis for the conduct of future clinical studies in patients of this population.”

https://www.ncbi.nlm.nih.gov/pubmed/29156899
http://apm.amegroups.com/article/view/16320

Associations between medical cannabis and prescription opioid use in chronic pain patients: A preliminary cohort study.

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“Current levels and dangers of opioid use in the U.S. warrant the investigation of harm-reducing treatment alternatives.

PURPOSE:

A preliminary, historical, cohort study was used to examine the association between enrollment in the New Mexico Medical Cannabis Program (MCP) and opioid prescription use.

RESULTS:

By the end of the 21 month observation period, MCP enrollment was associated with 17.27 higher age- and gender-adjusted odds of ceasing opioid prescriptions (CI 1.89 to 157.36, p = 0.012), 5.12 higher odds of reducing daily prescription opioid dosages (CI 1.56 to 16.88, p = 0.007), and a 47 percentage point reduction in daily opioid dosages relative to a mean change of positive 10.4 percentage points in the comparison group (CI -90.68 to -3.59, p = 0.034). The monthly trend in opioid prescriptions over time was negative among MCP patients (-0.64mg IV morphine, CI -1.10 to -0.18, p = 0.008), but not statistically different from zero in the comparison group (0.18mg IV morphine, CI -0.02 to 0.39, p = 0.081). Survey responses indicated improvements in pain reduction, quality of life, social life, activity levels, and concentration, and few side effects from using cannabis one year after enrollment in the MCP (ps<0.001).

CONCLUSIONS:

The clinically and statistically significant evidence of an association between MCP enrollment and opioid prescription cessation and reductions and improved quality of life warrants further investigations on cannabis as a potential alternative to prescription opioids for treating chronic pain.” https://www.ncbi.nlm.nih.gov/pubmed/29145417

“In summary, if cannabis can serve as an alternative to prescription opioids for at least some patients, legislators and the medical community may want to consider medical cannabis programs as a potential tool for combating the current opioid epidemic.”   http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187795

“Study finds medical cannabis is effective at reducing opioid addiction”  http://news.unm.edu/news/study-finds-medical-cannabis-is-effective-at-reducing-opioid-addiction

Availability and approval of cannabis-based medicines for chronic pain management and palliative/supportive care in Europe: A survey of the status in the chapters of the European Pain Federation.

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European Journal of Pain

“There is considerable public and political interest in the use of cannabis products for medical purposes.

METHODS:

The task force of the European Pain Federation (EFIC) conducted a survey with its national chapters representatives on the status of approval of all types of cannabis-based medicines, the covering of costs and the availability of a position paper of a national medical association on the use of medical cannabis for chronic pain and for symptom control in palliative/supportive care.

RESULTS:

Thirty-one out of 37 contacted councillors responded. Plant-derived tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray is approved for spasticity in multiple sclerosis refractory to conventional treatment in 21 EFIC chapters. Plant-derived THC (dronabinol) is approved for some palliative care conditions in four EFIC chapters. Synthetic THC analogue (nabilone) is approved for chemotherapy-associated nausea and vomiting refractory to conventional treatment in four EFIC chapters’. Eight EFIC chapters’ countries have an exceptional and six chapters an expanded access programme for medical cannabis. German and Israeli pain societies recommend the use of cannabis-based medicines as third-line drug therapies for chronic pain within a multicomponent approach. Conversely, the German medical association and a team of finish experts and officials do not recommend the prescription of medical cannabis due to the lack of high-quality evidence of efficacy and the potential harms.

CONCLUSIONS:

There are marked differences between the countries represented in EFIC in the approval and availability of cannabis-based products for medical use. EFIC countries are encouraged to collaborate with the European Medicines Agency to publish a common document on cannabis-based medicines.

SIGNIFICANCE:

There are striking differences between European countries in the availability of plant-derived and synthetic cannabinoids and of medical cannabis for pain management and for symptom control in palliative care and in the covering of costs by health insurance companies or state social security systems.”

https://www.ncbi.nlm.nih.gov/pubmed/29134767

http://onlinelibrary.wiley.com/doi/10.1002/ejp.1147/abstract

Cannabinoids offer alternatives to opioids for pain relief, experts say.

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“Alternatives to opioids can be used alone or in combination with opioids for pain relief, to help prevent medical exposure to narcotics being an entry point to misuse, said experts at a medical education forum in Washington, DC on 3 November.

Endocannabinoid compounds found in marijuana can greatly enhance the potency of opioids in relieving pain.

The synergy from using these drugs together can result in more effective pain relief from lower doses of opioids,”

https://www.ncbi.nlm.nih.gov/pubmed/29113969

http://www.bmj.com/content/359/bmj.j5140.full

Medical cannabis for the treatment of chronic pain and other disorders: misconceptions and facts.

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“Recently, many countries have enacted new cannabis policies, including decriminalization of cannabis possession, medical cannabis legalization, and legalization of recreational cannabis.  In this context, patients and their physicians have had an increasing number of conversations about the risks and benefits of cannabis.  While cannabis and cannabinoids continue to be evaluated as pharmacotherapy for medical conditions, currently, the best evidence exists for the following medical conditions: chronic pain, neuropathic pain, and spasticity resulting from multiple sclerosis.  We also reviewed the current state of evidence for cannabis and cannabinoids for a number of other medical conditions while addressing the potential acute and chronic effects of cannabis use, which are issues that physicians must consider before making an official recommendation on the use of medical cannabis to a patient.  As patient requests for medical cannabis increase, physicians must become knowledgeable on the science of medical cannabis and open to a discussion about why the patient feels that medical cannabis may be helpful to them.”

https://www.ncbi.nlm.nih.gov/pubmed/29067992

http://pamw.pl/en/issue/article/29067992

Efficacy, tolerability and safety of cannabis-based medicines for chronic pain management – An overview of systematic reviews.

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European Journal of Pain

“Medicinal cannabis has already entered mainstream medicine in some countries.

Cannabis-based medicines undoubtedly enrich the possibilities of drug treatment of chronic pain conditions.

It remains the responsibility of the health care community to continue to pursue rigorous study of cannabis-based medicines to provide evidence that meets the standard of 21st century clinical care.”

https://www.ncbi.nlm.nih.gov/pubmed/29034533

http://onlinelibrary.wiley.com/doi/10.1002/ejp.1118/abstract