Category Archives: Pain

Endocannabinoid modulation of inflammatory hyperalgesia in the IFN-α mouse model of depression.

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Brain, Behavior, and Immunity“Depression is a well-recognised effect of long-term treatment with interferon-alpha (IFN-α), a widely used treatment for chronic viral hepatitis and malignancy. In addition to the emotional disturbances, high incidences of painful symptoms such as headache and joint pain have also been reported following IFN-α treatment.

The endocannabinoid system plays an important role in emotional and nociceptive processing, however it is unknown whether repeated IFN-α administration induces alterations in this system.

The present study investigated nociceptive responding in the IFN-α-induced mouse model of depression and associated changes in the endocannabinoid system. Furthermore, the effects of modulating peripheral endocannabinoid tone on inflammatory pain-related behaviour in the IFN-α model was examined.

In summary, increasing peripheral endocannabinoid tone attenuates inflammatory hyperalgesia induced following repeated IFN-α administration. These data provide support for the endocannabinoid system in mediating and modulating heightened pain responding associated with IFNα-induced depression.”

https://www.ncbi.nlm.nih.gov/pubmed/31505257

“Inflammatory hyperalgesia is associated with altered endocannabinoid levels. Enhancing peripheral endocannabinoid tone attenuates IFN-α related hyperalgesia.”

https://www.sciencedirect.com/science/article/pii/S0889159119306063?via%3Dihub

State marijuana laws and opioid overdose mortality.

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Image result for Injury Epidemiology “The opioid epidemic in the United States is a national public health crisis.

In recent years, marijuana legalization has been increasingly adopted by state governments as a policy intervention to control the opioid epidemic under the premise that marijuana and opioids are substitutive substances.

The purpose of this systematic review is to synthesize the empirical evidence regarding the impact of state marijuana laws on opioid overdose mortality and other opioid-related health outcomes.

RESULTS:

Of the 16 eligible studies, 4 assessed the association of state marijuana law status with opioid overdose mortality, 7 with prescription opioids dispensed, and the remaining with nonmedical use and opioid-related hospitalizations. Random effects modeling based on pooled data revealed that legalizing marijuana for medical use was associated with a statistically non-significant 8% reduction in opioid overdose mortality (95% confidence interval: - 0.21 to 0.04; p = 0.201) and a 7% reduction in prescription opioids dispensed (95% confidence interval: - 0.13 to - 0.01; p = 0.017). Legalizing marijuana for recreational use was associated with an additional 7% reduction in opioid overdose mortality in Colorado and 6% reduction in opioid prescriptions among fee-for-service Medicaid and managed care enrollees.

CONCLUSIONS:

Legalizing marijuana might contribute to a modest reduction in opioid prescriptions. Evidence about the effect of marijuana legalization on opioid overdose mortality is inconsistent and inconclusive. If any, the effectiveness of state marijuana laws in reducing opioid overdose mortality appears to be rather small and limited to states with operational marijuana dispensaries. It remains unclear whether the presumed benefit of legalizing marijuana in reducing opioid-related harms outweighs the policy’s externalities, such as its impact on mental health and traffic safety.”

https://www.ncbi.nlm.nih.gov/pubmed/31497489

“Legalizing marijuana might contribute to a modest reduction in opioid prescriptions.”

https://injepijournal.biomedcentral.com/articles/10.1186/s40621-019-0213-z

The effects of cannabis, cannabinoids, and their administration routes on pain control efficacy and safety: A systematic review and network meta-analysis.

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“To determine the effects of cannabis, cannabinoids, and their administration routes on pain and adverse euphoria events.

Randomized controlled trials investigating the effects of cannabis or cannabinoids on pain reduction.

RESULTS:

A total of 25 studies involving 2270 patients were included. We found that delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) (oromucosal route), THC (oromucosal route), and standardized dried cannabis (with THC; SCT; inhalation route) could reduce neuropathic pain score (SMD -0.41, 95% CI -0.7 to -0.1; -0.61, 95% CI -1.2 to -0.02; and -0.77, 95% CI -1.4 to -0.2; respectively). For nociceptive pain, only standardized cannabis extract (with THC; SCET) via oral route could reduce pain score (SMD -1.8, 95% C; -2.4 to -1.2). In cancer pain, THC/CBD via oromucosal route and THC via oral or oromucosal route could reduce pain score (SMD -0.7, 95% CI -1.2 to -0.2; and -2.1, 95% CI -2.8 to -1.4; respectively). No study was observed for THC/CBD via oral route or inhalation or THC via inhalation for cancer and nociceptive pain, SCET via oromucosal route or inhalation for neuropathic and cancer pain, THC via oromucosal route for nociceptive pain, and SCT via oromucosal or oral route for neuropathic, cancer, and nociceptive pain. Statistically significant increased risks of euphoria were observed in THC/CBD (oromucosal), THC (oromucosal), and SCT (inhalation).

CONCLUSION:

The use of cannabis and cannabinoids via certain administration routes could reduce different types of pain. Product developers could consider our findings as part of their product design so that the effective route of cannabis and cannabinoids for pain control can be achieved.”

https://www.ncbi.nlm.nih.gov/pubmed/31495691

https://www.japha.org/article/S1544-3191(19)30353-X/fulltext

[Dronabinol in geriatric pain and palliative care patients : A retrospective evaluation of statutory-health-insurance-covered outpatient medical treatment].

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“Geriatric patients often suffer from a long history of pain and have a limited life expectancy.

Cannabinoid receptor agonists like dronabinol may be an effective, low-risk treatment option for geriatric patients with chronic pain.

OBJECTIVES:

The effectiveness and side effects of dronabinol therapy in geriatric patients are analyzed. The effects of the approval requirement are presented.

RESULTS:

By using dronabinol, 21 of the 40 geriatric patients (52.5%) achieved pain relief of more than 30%, 10% of the patients of more than 50%. On average, about four symptoms or side effects related to previous treatment were positively influenced. 26% of patients reported side effects. The rejection rates on the part of the health insurances were 38.7% (group A) and 10.3% (group B).

CONCLUSIONS:

This study is one of the few analyses of the use of Dronabinol in geriatric patients. We show that cannabis-based drugs (in this case dronabinol) are an effective, low-risk treatment option that should be considered early in therapy. Regarding the indication spectrum, further clinical studies and an approval-free test phase are necessary.”

https://www.ncbi.nlm.nih.gov/pubmed/31473816

https://link.springer.com/article/10.1007%2Fs00482-019-00408-1

Opioid-enhancing antinociceptive effects of delta-9-tetrahydrocannabinol and amitriptyline in rhesus macaques.

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Cover image for Experimental and Clinical Psychopharmacology“Cannabinoids can enhance the antinociceptive effects of opioids in a synergistic manner, potentially reducing the analgesic dosage of opioids and improving pain therapy. This strategy has also been used as a rationale to combine certain antidepressants and opioids.

In this experiment, opioid-induced thermal antinociception was assessed in rhesus macaques using a warm-water tail-withdrawal procedure with 3 water temperatures (40, 50, and 55 °C). In general, the acute antinociceptive effects of intramuscular (i.m.) cumulative doses of heroin were studied alone or in combination with i.m. (-)-trans-delta-9-tetrahydrocannabinol (THC), cannabinol (CBN), or the tricyclic antidepressant amitriptyline.

A nonantinociceptive dose of THC (1 mg/kg) shifted the ED50 for the heroin dose-effect curve 3.6-fold leftward at 50 °C and 1.9-fold leftward at 55 °C compared with heroin alone. When the cannabinoid type-1 receptor (CB1R) antagonist, rimonabant, was administered prior to the most effective THC-heroin combination, rimonabant blocked the THC enhancement of heroin antinociception. When CBN (1-3.2 mg/kg) was administered prior to heroin, or 1 mg/kg of CBN was administered prior to a combination of 0.32 mg/kg of THC and heroin, no shifts were evident in the heroin dose-effect curves at either temperature.

However, similar to THC, amitriptyline (0.32-1 mg/kg) administered prior to heroin significantly shifted the heroin dose-effect curve leftward. Heroin produced both dose- and temperature-dependent thermal antinociception in nonhuman primates and THC produced opioid-enhancing effects in a CB1R-dependent manner. These effects of THC were not shared by cannabinol, but were quantitatively similar to that of amitriptyline.”

https://www.ncbi.nlm.nih.gov/pubmed/31464475

https://psycnet.apa.org/doiLanding?doi=10.1037%2Fpha0000313

Clinicians’ Guide to Cannabidiol and Hemp Oils.

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Mayo Clinic“Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have become very popular over the past few years. Patients report relief for a variety of conditions, particularly pain, without the intoxicating adverse effects of medical marijuana.

In June 2018, the first CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of rare, severe epilepsy, further putting the spotlight on CBD and hemp oils.

There is a growing body of preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction.

Care must be taken when directing patients toward CBD products because there is little regulation, and studies have found inaccurate labeling of CBD and tetrahydrocannabinol quantities.

This article provides an overview of the scientific work on cannabinoids, CBD, and hemp oil and the distinction between marijuana, hemp, and the different components of CBD and hemp oil products.

We summarize the current legal status of CBD and hemp oils in the United States and provide a guide to identifying higher-quality products so that clinicians can advise their patients on the safest and most evidence-based formulations.

This review is based on a PubMed search using the terms CBD, cannabidiol, hemp oil, and medical marijuana. Articles were screened for relevance, and those with the most up-to-date information were selected for inclusion.”

https://www.ncbi.nlm.nih.gov/pubmed/31447137

https://www.mayoclinicproceedings.org/article/S0025-6196(19)30007-2/fulltext

Myrcene and terpene regulation of TRPV1.

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Publication Cover“Nociceptive Transient Receptor Potential channels such as TRPV1 are targets for treating pain. Both antagonism and agonism of TRP channels can promote analgesia, through inactivation and chronic desensitization.

Since plant-derived mixtures of cannabinoids and the Cannabis component myrcene have been suggested as pain therapeutics, we screened terpenes found in Cannabis for activity at TRPV1.

These data establish TRPV1 as a target of Myrcene and suggest the therapeutic potential of analgesic formulations containing Myrcene.”

https://www.ncbi.nlm.nih.gov/pubmed/31446830

https://www.tandfonline.com/doi/full/10.1080/19336950.2019.1654347

The effectiveness of self-directed medical cannabis treatment for pain

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Complementary Therapies in Medicine“The prior medical literature offers little guidance as to how pain relief and side effect manifestation may vary across commonly used and commercially available cannabis product types. We used the largest dataset in the United States of real-time responses to and side effect reporting from patient-directed cannabis consumption sessions for the treatment of pain under naturalistic conditions in order to identify how cannabis affects momentary pain intensity levels and which product characteristics are the best predictors of therapeutic pain relief.

Between 06/06/2016 and 10/24/2018, 2987 people used the ReleafApp to record 20,513 cannabis administration measuring cannabis’ effects on momentary pain intensity levels across five pain categories: musculoskeletal, gastrointestinal, nerve, headache-related, or non-specified pain. The average pain reduction was –3.10 points on a 0–10 visual analogue scale (SD = 2.16, d = 1.55, p < .001).

Whole Cannabis flower was associated with greater pain relief than were other types of products, and higher tetrahydrocannabinol (THC) levels were the strongest predictors of analgesia and side effects prevalence across the five pain categories. In contrast, cannabidiol (CBD) levels generally were not associated with pain relief except for a negative association between CBD and relief from gastrointestinal and non-specified pain.

These findings suggest benefits from patient-directed, cannabis therapy as a mid-level analgesic treatment; however, effectiveness and side effect manifestation vary with the characteristics of the product used.

The results suggest that Cannabis flower with moderate to high levels of tetrahydrocannabinol is an effective mid-level analgesic.”

https://www.ncbi.nlm.nih.gov/pubmed/31519268

https://www.sciencedirect.com/science/article/abs/pii/S0965229919308040

“UNM study confirms cannabis flower is an effective mid-level analgesic medication for pain treatment. Cannabis likely has numerous constituents that possess analgesic properties beyond THC, including terpenes and flavonoids, which likely act synergistically for people that use whole dried cannabis flower, Cannabis offers the average patient an effective alternative to using opioids for general use in the treatment of pain with very minimal negative side effects for most people.”  https://news.unm.edu/news/unm-study-confirms-cannabis-flower-is-an-effective-mid-level-analgesic-medication-for-pain-treatment

THE EFFECTS OF MEDICAL MARIJUANA DISPENSARIES ON ADVERSE OPIOID OUTCOMES

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 Publication cover image“As more states enact laws liberalizing marijuana use and the U.S. opioid epidemic surges to unprecedented levels, understanding the relationship between marijuana and opioids is growing increasingly important.

Using a unique self‐constructed marijuana dispensary dataset, I estimate the impact of increased marijuana access on opioid‐related harms.

I exploit within‐ and across‐state variation in dispensary openings and find county‐level prescription opioid‐related fatalities decline by 11% following the opening a dispensary.

The estimated dispensary effects are qualitatively similar for opioid‐related admissions to treatment facilities. These results are strongest for males and suggest a substitutability between marijuana and opioids.”

https://onlinelibrary.wiley.com/doi/full/10.1111/ecin.12825

“I find that core-based statistical areas (CBSAs) with dispensary openings experience a 20 percentage point relative decrease in painkiller treatment admissions over the first two years of dispensary operations.”

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3012381

“Access to medical marijuana reduces opioid prescriptions”  https://www.health.harvard.edu/blog/access-to-medical-marijuana-reduces-opioid-prescriptions-2018050914509

THE EFFECTS OF RECREATIONAL MARIJUANA LEGALIZATION AND DISPENSING ON OPIOID MORTALITY

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Publication cover image“This study documents how the changing legal status of marijuana has impacted mortality in the United States over the past two decades.

We use a difference‐in‐difference approach to estimate the effect of medical marijuana laws (MML) and recreational marijuana laws (RML) on fatalities from opioid overdoses, and we find that marijuana access induces sharp reductions in opioid mortality rates.

Our research corroborates prior findings on MMLs and offers the first causal estimates of RML impacts on opioid mortality to date, the latter of which is particularly important given that RMLs are far more expansive in scope and reach than MMLs.

In our preferred econometric specification, we estimate that RMLs reduce annual opioid mortality in the range of 20%–35%, with particularly pronounced effects for synthetic opioids. In further analysis, we demonstrate how RML impacts vary among demographic groups, shedding light on the distributional consequences of these laws.

Our findings are especially important and timely given the scale of the opioid crisis in the United States and simultaneously evolving attitudes and regulations on marijuana use.”

https://onlinelibrary.wiley.com/doi/full/10.1111/ecin.12819

“Marijuana legalization reduces opioid deaths. A new Economic Inquiry study finds that marijuana access leads to reductions in opioid-related deaths.” https://medicalxpress.com/news/2019-08-marijuana-legalization-opioid-deaths.html