Category Archives: Chronic Inflammatory and Neuropathic Pain

An evaluation of the anti-hyperalgesic effects of cannabidiolic acid-methyl ester (CBDA-ME) in a preclinical model of peripheral neuropathic pain.

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Publication cover image“Chronic neuropathic pain (NEP) is associated with growing therapeutic cannabis use. To promote quality of life without psychotropic effects, cannabinoids other than Δ9-tetrahydrocannabidiol, including cannabidiol and its precursor cannabidiolic acid (CBDA), are being evaluated. Due to its instability, CBDA has been understudied, particularly as an anti-nociceptive agent. Adding a methyl ester group (CBDA-ME) significantly enhances its stability, facilitating analyses of its analgesic effects in vivo. This study examines early treatment efficacy of CBDA-ME in a rat model of peripherally induced NEP and evaluates sex as a biological variable.

KEY RESULTS:

In males, CBDA-ME elicited a significant concentration-dependent chronic anti-hyperalgesic effect, also influencing both nociceptive and non-nociceptive mechanoreceptors, which were not observed in females at any of the concentrations tested.

CONCLUSION AND IMPLICATIONS:

Initiating treatment of a peripheral nerve injury with CBDA-ME at an early stage post-surgery provides anti-nociception in males, warranting further investigation into potential sexual dimorphisms underlying this response.”

https://www.ncbi.nlm.nih.gov/pubmed/31981216

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14997

The Role of Cannabidiol (CBD) in Chronic Pain Management: An Assessment of Current Evidence.

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 “Given the growing challenges in chronic pain management coupled with the ongoing consequences of the opioid epidemic, pain management practitioners are looking into more effective, innovative, and safer alternatives to treat pain.

Cannabis-based medicine had been described for hundreds of years but only recently have we seen the more scientific, evidence-based approach to its use, and ongoing investigations continue to explore its potential medical benefits.

While historically more attention has been paid to the psychoactive component of the cannabis plant Δ9-tetrahydrocannabinol (THC), there have been fewer scientific studies on the medical use of the cannabidiol (CBD) – a non-psychoactive component of the cannabis plant.

RECENT FINDINGS:

By examining recent literature, we investigated the use of CBD and its potential role in pain management. Since there are currently no approved pharmaceutical products that contain CBD alone for the management of pain, this review focused on nabiximols (which is a combined product of THC/CBD in a 1:1 ratio) as the only pharmaceutical product available that contains CBD and is being used for the management of pain.

It is difficult to definitely attribute the therapeutic properties to CBD alone since it is always administered with THC.

Based on the available literature, it is difficult to make a recommendation for the use of CBD in chronic pain management. It is also important to note that there are many CBD products currently available as supplements, but these products are non-pharmaceuticals and lack the appropriate clinical studies to support their efficacy claims.”

https://www.ncbi.nlm.nih.gov/pubmed/31980957 

https://link.springer.com/article/10.1007%2Fs11916-020-0835-4

β-Caryophyllene, a CB2-Receptor-Selective Phytocannabinoid, Suppresses Mechanical Allodynia in a Mouse Model of Antiretroviral-Induced Neuropathic Pain.

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molecules-logo “Neuropathic pain associated with nucleoside reverse transcriptase inhibitors (NRTIs), therapeutic agents for human immunodeficiency virus (HIV), responds poorly to available drugs.

Smoked cannabis was reported to relieve HIV-associated neuropathic pain in clinical trials. Some constituents of cannabis (Cannabis sativa) activate cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptors. However, activation of the CB1 receptor is associated with side effects such as psychosis and physical dependence.

Therefore, we investigated the effect of β-caryophyllene (BCP), a CB2-selective phytocannabinoid, in a model of NRTI-induced neuropathic pain.

BCP prevents NRTI-induced mechanical allodynia, possibly via reducing the inflammatory response, and attenuates mechanical allodynia through CB2 receptor activation. Therefore, BCP could be useful for prevention and treatment of antiretroviral-induced neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/31892132

https://www.mdpi.com/1420-3049/25/1/106

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

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

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

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

Medical Cannabis for Older Patients-Treatment Protocol and Initial Results.

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jcm-logo“Older adults may benefit from cannabis treatment for various symptoms such as chronic pain, sleep difficulties, and others, that are not adequately controlled with evidence-based therapies. However, currently, there is a dearth of evidence about the efficacy and safety of cannabis treatment for these patients.

This article aims to present a pragmatic treatment protocol for medical cannabis in older adults. We followed consecutive patients above 65 years of age prospectively who were treated with medical cannabis from April 2017 to October 2018. The outcomes included treatment adherence, global assessment of efficacy and adverse events after six months of treatment. During the study period, 184 patients began cannabis treatment, 63.6% were female, and the mean age was 81.2 ± 7.5 years (median age-82). After six months of treatment, 58.1% were still using cannabis.

Of these patients, 33.6% reported adverse events, the most common of which were dizziness (12.1%) and sleepiness and fatigue (11.2%). Of the respondents, 84.8% reported some degree of improvement in their general condition. Special caution is warranted in older adults due to polypharmacy, pharmacokinetic changes, nervous system impairment, and increased cardiovascular risk.

Medical cannabis should still be considered carefully and individually for each patient after a risk-benefit analysis and followed by frequent monitoring for efficacy and adverse events.”

https://www.ncbi.nlm.nih.gov/pubmed/31683817

https://www.mdpi.com/2077-0383/8/11/1819