Category Archives: Pain

Orally consumed cannabinoids provide long-lasting relief of allodynia in a mouse model of chronic neuropathic pain.

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Image result for neuropsychopharmacology“Chronic pain affects a significant percentage of the United States population, and available pain medications like opioids have drawbacks that make long-term use untenable.

Cannabinoids show promise in the management of pain, but long-term treatment of pain with cannabinoids has been challenging to implement in preclinical models. We developed a voluntary, gelatin oral self-administration paradigm that allowed male and female mice to consume ∆9-tetrahydrocannabinol, cannabidiol, or morphine ad libitum.

Mice stably consumed these gelatins over 3 weeks, with detectable serum levels. Using a real-time gelatin measurement system, we observed that mice consumed gelatin throughout the light and dark cycles, with animals consuming less THC-gelatin than the other gelatin groups.

Consumption of all three gelatins reduced measures of allodynia in a chronic, neuropathic sciatic nerve injury model, but tolerance to morphine developed after 1 week while THC or CBD reduced allodynia over three weeks. Hyperalgesia gradually developed after sciatic nerve injury, and by the last day of testing, THC significantly reduced hyperalgesia, with a trend effect of CBD, and no effect of morphine. Mouse vocalizations were recorded throughout the experiment, and mice showed a large increase in ultrasonic, broadband clicks after sciatic nerve injury, which was reversed by THC, CBD, and morphine.

This study demonstrates that mice voluntarily consume both cannabinoids and opioids via gelatin, and that cannabinoids provide long-term relief of chronic pain states. In addition, ultrasonic clicks may objectively represent mouse pain status and could be integrated into future pain models.”

https://www.ncbi.nlm.nih.gov/pubmed/31812152

https://www.nature.com/articles/s41386-019-0585-3

The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities.

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“Peripheral neuropathy can significantly impact the quality of life for those who are affected, as therapies from the current treatment algorithm often fail to deliver adequate symptom relief. There has, however, been an increasing body of evidence for the use of cannabinoids in the treatment of chronic, noncancer pain. The efficacy of a topically delivered cannabidiol (CBD) oil in the management of neuropathic pain was examined in this four-week, randomized and placebo-controlled trial.

RESULTS:

The study population included 62.1% males and 37.9% females with a mean age of 68 years. There was a statistically significant reduction in intense pain, sharp pain, cold and itchy sensations in the CBD group when compared to the placebo group. No adverse events were reported in this study.

CONCLUSIONS:

Our findings demonstrate that the transdermal application of CBD oil can achieve significant improvement in pain and other disturbing sensations in patients with peripheral neuropathy. The treatment product was well tolerated and may provide a more effective alternative compared to other current therapies in the treatment of peripheral neuropathy.”

https://www.ncbi.nlm.nih.gov/pubmed/31793418

http://www.eurekaselect.com/177080/article

Investigation of the Involvement of the Endocannabinoid System in TENS-induced Antinociception.

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“Transcutaneous electrical nerve stimulation (TENS) promotes antinociception by activating the descending pain modulation pathway and consequently releasing endogenous analgesic substances.

In addition, recent studies have shown that the endocannabinoid system controls pain. Thus, the present study investigated the involvement of the endocannabinoid system in TENS-induced antinociception of cancer pain using a cancer pain model induced by intraplantar (i.pl.) injections of Ehrlich tumor cells in male Swiss mice.

These results suggest that low- and high-frequency TENS is effective in controlling cancer pain, and the endocannabinoid system is involved in this effect at both the peripheral and central levels.

Perspective: TENS is a non-pharmacological strategy that may be used to control cancer pain. Identification of a new mechanism involved in its analgesic effect could lead to the development of clinical studies as well as an increase in its application, lessening the need for pharmacological treatments.”

https://www.ncbi.nlm.nih.gov/pubmed/31785404

https://www.jpain.org/article/S1526-5900(19)30868-5/fulltext

Cannabis for pain in orthopedics: a systematic review focusing on study methodology

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Image result for Can J Surg. journal“Medical cannabis use is an emerging topic of interest in orthopedics. Although there is a large amount of literature on medical cannabis use for managing various types of pain, few studies have focused on orthopedic conditions. There is little high-quality evidence in core orthopedic areas. The objective of this study was to summarize the literature on the efficacy of cannabis use for pain related to orthopedic conditions.

METHODS:

We conducted a systematic review of the literature on the use of cannabinoids for pain management in core orthopedic conditions. Two independent reviewers extracted information on reporting quality, risk of bias, drugs, population, control, duration of study, pain outcomes and the authors’ conclusions regarding efficacy for pain outcomes.

RESULTS:

We identified 33 orthopedic studies, including 21 primary studies and 12 reviews. Study quality was generally low to moderate. Six of the included studies had a control group and 15 were noncontrolled studies. Methodologies, drugs and protocols of administration varied greatly across studies. Study conclusions were generally positive in noncontrolled studies and mixed in controlled studies. Studies using higher doses tended to conclude that cannabis use was effective, but the potential for harmful effects may also be increased with higher doses.

CONCLUSION:

Variability in the methodologies used in cannabis research makes it challenging to draw conclusions about dosing, routes and frequency of administration. Most of the existing evidence suggests that medical cannabis use is effective, but this efficacy has been demonstrated only when either there is no comparator or cannabis is compared with placebo. Studies using an active comparator have not demonstrated efficacy. Future research should focus on improving study reporting and methodologic quality so that protocols that optimize pain control while minimizing harmful effects can be determined.”

https://www.ncbi.nlm.nih.gov/pubmed/31782292

Does Integrative Medicine Reduce Prescribed Opioid Use for Chronic Pain? A Systematic Literature Review.

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Image result for pain medicine journal“Chronic pain (CP) is a major public health problem. Many patients with CP are increasingly prescribed opioids, which has led to an opioid crisis.

Integrative medicine (IM), which combines pharmacological and complementary and alternative medicine (CAM), has been proposed as an opioid alternative for CP treatment.

The majority of the studies showed that opioid use was reduced significantly after using IM. Cannabinoids were among the most commonly investigated approaches in reducing opioid use, followed by multidisciplinary approaches, cognitive-behavioral therapy, and acupuncture. The majority of the studies had limitations related to sample size, duration, and study design.

CONCLUSIONS:

There is a small but defined body of literature demonstrating positive preliminary evidence that the IM approach including CAM therapies can help in reducing opioid use. As the opioid crisis continues to grow, it is vital that clinicians and patients be adequately informed regarding the evidence and opportunities for IM/CAM therapies for CP.”

https://www.ncbi.nlm.nih.gov/pubmed/31755962

https://academic.oup.com/painmedicine/advance-article-abstract/doi/10.1093/pm/pnz291/5637803?redirectedFrom=fulltext

Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis.

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Image result for plos medicine“Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management.

We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain.

The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34-0.74, p < 0.001).

 

We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/31743343

“In conclusion, we found evidence to suggest that frequent use of cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain in Vancouver. The findings of this study have implications for healthcare and harm reduction service providers. In chronic pain patients with complex socio-structural and substance use backgrounds, cannabis may be used as a means of treating health problems or reducing substance-related harm. In the context of the current opioid crisis and the recent rollout of a national regulatory framework for cannabis use in Canada, frequent use of cannabis among PWUD with pain may play an important role in preventing or substituting frequent illicit opioid use.”

https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002967

Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study.

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Publication Cover “Chronic pain is highly prevalent in most of the industrialized nations around the world. Despite the documented adverse effects, opioids are widely used for pain management. Cannabinoids, and specifically Cannabidiol, is proposed as an opioid alternative, having comparable efficacy with better safety profile.

Objectives: We aim to investigate the impact of full hemp extract cannabidiol (CBD) on opioid use and quality of life indicators among chronic pain patients.

Results: Over half of chronic pain patients (53%) reduced or eliminated their opioids within 8 weeks after adding CBD-rich hemp extract to their regimens. Almost all CBD users (94%) reported quality of life improvements. The results indicated a significant relationship between CBD and PSQI (p = 0.003), and PEG (p = 0.006). There was a trend toward improvement but no significant relationship between CBD use and PHQ and PDI.

Conclusion: CBD could significantly reduce opioid use and improve chronic pain and sleep quality among patients who are currently using opioids for pain management.

Key Message: This is a prospective, single-arm cohort study for the potential role of cannabinoids as an alternative for opioids. The results indicate that using the CBD-rich extract enabled our patients to reduce or eliminate opioids with significant improvement in their quality of life indices.”

https://www.ncbi.nlm.nih.gov/pubmed/31711352

“Cannabis, the plant source of cannabinoids (CB), have been used for millennia for different purposes such as pain control and stress relief. Recent evidence highlights cannabinoids’ efficacy and safety for pain control. Besides its potential direct effects on pain, cannabinoids are suggested to have a role in reducing opioid intake. This study concludes that using CBD for chronic pain in patients using opioids has a significant effect on reducing opioid intake, reducing pain and improving quality of life (QoL). Over half of the participants who added CBD hemp extract reduced or eliminated opioids over the course of 8 weeks, and almost all CBD users reported improvements in QoL.”

https://www.tandfonline.com/doi/full/10.1080/00325481.2019.1685298

Myorelaxant Effect of Transdermal Cannabidiol Application in Patients with TMD: A Randomized, Double-Blind Trial.

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jcm-logo “The healing properties of cannabidiol (CBD) have been known for centuries.

In this study, we aimed to evaluate the efficiency of the myorelaxant effect of CBD after the transdermal application in patients with myofascial pain.

Results: in Group1, the sEMG masseter activity significantly decreased (11% in the right and 12.6% in the left masseter muscles). In Group2, the sEMG masseter activity was recorded as 0.23% in the right and 3.3% in the left masseter muscles. Pain intensity in VAS scale was significantly decreased in Group1: 70.2% compared to Group2: 9.81% reduction. Patients were asked to apply formulation twice a day for a period of 14 days.

Conclusion: The application of CBD formulation over masseter muscle reduced the activity of masseter muscles and improved the condition of masticatory muscles in patients with myofascial pain.”

https://www.ncbi.nlm.nih.gov/pubmed/31698733

https://www.mdpi.com/2077-0383/8/11/1886

Perceived Efficacy of Medical Cannabis in the Treatment of Co-Occurring Health-Related Quality of Life Symptoms.

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 Publication Cover“For persons living with chronic conditions, health-related quality of life (HRQoL) symptoms, such as pain, anxiety, depression, and insomnia, often interact and mutually reinforce one another.

There is evidence that medical cannabis (MC) may be efficacious in ameliorating such symptoms and improving HRQoL.

As many of these HRQoL symptoms may mutually reinforce one another, we conducted an exploratory study to investigate how MC users perceive the efficacy of MC in addressing co-occurring HRQoL symptoms. We conducted a cross-sectional online survey of persons with a state medical marijuana card in Illinois (N = 367) recruited from licensed MC dispensaries across the state. We conducted tests of ANOVA to measure how perceived MC efficacy for each HRQoL symptom varied by total number of treated symptoms reported by participants.

Pain was the most frequently reported HRQoL treated by MC, followed by anxiety, insomnia, and depression. A large majority of our sample (75%) reported treating two or more HRQoL symptoms. In general, perceived efficacy of MC in relieving each HRQoL symptom category increased with the number of co-occurring symptoms also treated with MC. Perceived efficacy of MC in relieving pain, anxiety, and depression varied significantly by number of total symptoms experienced.

This exploratory study contributes to our understanding of how persons living with chronic conditions perceive the efficacy of MC in treating co-occurring HRQoL symptoms. Our results suggest that co-occurring pain, anxiety, and depression may be particularly amenable to treatment with MC.”

https://www.ncbi.nlm.nih.gov/pubmed/31693457

https://www.tandfonline.com/doi/abs/10.1080/08964289.2019.1683712?journalCode=vbmd20

Considering abuse liability and neurocognitive effects of cannabis and cannabis-derived products when assessing analgesic efficacy: a comprehensive review of randomized-controlled studies.

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Publication Cover “Pain is the most frequent indication for which medical cannabis treatment is sought.

Objectives: The clinical potential of cannabis and cannabis-derived products (CDPs) relies on their efficacy to treat an indication and potential adverse effects that impact outcomes, including abuse liability and neurocognitive effects. To ascertain the extent to which these effects impact therapeutic utility, studies investigating cannabis and CDPs for pain were reviewed for analgesic efficacy and assessments of abuse liability and neurocognitive effects.

Methods: A comprehensive review of placebo-controlled studies investigating cannabis and CDP analgesia was performed. Methods and findings related to adverse effects, abuse liability, and neurocognitive effects were extracted.

Results: Thirty-eight studies were reviewed; 29 assessed cannabis and CDPs for chronic pain, 1 for acute pain, and 8 used experimental pain tests. Most studies ascertained adverse effects through self-report (N = 27). Fewer studies specifically probed abuse liability (N = 7) and cognitive and psychomotor effects (N = 12).

Many studies related to chronic and experimental pain (N = 18 and N = 5, respectively) found cannabis and CDPs to reduce pain. Overall, adverse effects were mild to moderate, and dose-related. Studies investigating the impact of cannabis and CDPs on abuse liability and neurocognitive endpoints were mostly limited to inhaled administration and confirmed dose-related effects.

Conclusion: Few studies investigating cannabis and CDP analgesia assess abuse liability and cognitive endpoints, adverse effects that impact the long-term clinical utility of these drugs. Future studies should include these measures to optimize research and clinical care related to cannabis-based therapeutics.”

https://www.ncbi.nlm.nih.gov/pubmed/31687845

https://www.tandfonline.com/doi/abs/10.1080/00952990.2019.1669628?journalCode=iada20