Category Archives: Pain

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

Structure of an allosteric modulator bound to the CB1 cannabinoid receptor.

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Image result for nature chemical biology“The CB1 receptor mediates the central nervous system response to cannabinoids, and is a drug target for pain, anxiety and seizures.

CB1 also responds to allosteric modulators, which influence cannabinoid binding and efficacy.

To understand the mechanism of these compounds, we solved the crystal structure of CB1 with the negative allosteric modulator (NAM) ORG27569 and the agonist CP55940.

The structure reveals that the NAM binds to an extrahelical site within the inner leaflet of the membrane, which overlaps with a conserved site of cholesterol interaction in many G protein-coupled receptors (GPCRs).

The ternary structure with ORG27569 and CP55940 captures an intermediate state of the receptor, in which aromatic residues at the base of the agonist-binding pocket adopt an inactive conformation despite the large contraction of the orthosteric pocket.

The structure illustrates a potential strategy for drug modulation of CB1 and other class A GPCRs.”

https://www.ncbi.nlm.nih.gov/pubmed/31659318

https://www.nature.com/articles/s41589-019-0387-2

Cannabinoid receptor 2‑selective agonist JWH015 attenuates bone cancer pain through the amelioration of impaired autophagy flux induced by inflammatory mediators in the spinal cord.

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Journal Cover “Bone cancer pain (BCP) is a severe complication of advanced bone cancer.

Although cannabinoid receptor 2 (CB2) agonists may have an analgesic effect, the underlying mechanism remains unclear.

CB2 serves a protective role in various pathological states through the activation of autophagy. Therefore, the present study aimed to determine whether the analgesic effects of the selective CB2 agonist JWH015 was mediated by the activation of autophagy in BCP.

The results of the present study suggested that the impairment of autophagy flux was induced by glia‑derived inflammatory mediators in spinal neurons. Intrathecal administration of the selective CB2 agonist JWH015 ameliorated autophagy flux through the downregulation of IL‑1β and IL‑6 and attenuated BCP.”

https://www.ncbi.nlm.nih.gov/pubmed/31661120

https://www.spandidos-publications.com/10.3892/mmr.2019.10772

Utilization of medicinal cannabis for pain by individuals with spinal cord injury.

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Image result for spinal cord series and cases“A cross-sectional multi-center study using an on-line survey addressing utilization, knowledge, and perceptions of medicinal cannabis (MC) by people with spinal cord injury (SCI).

OBJECTIVE:

To characterize differences between current (CU), past (PU), and never users (NU) of MC with SCI; to determine why people with SCI use MC; to examine reports of MCs’ efficacy and tolerability by individuals with SCI.

SETTING:

Three academic medical centers in the United States.

METHODS:

Comparison of demographic and attitudinal differences between CU, PU, and NU and differences in the groups’ reports of pain, health, and quality of life (QOL). Evaluation of utilization patterns and perceived efficacy of MC among CU and PU and reports of side effects of MC versus prescription medications. Data were analyzed using either Chi Square, distribution-free exact statistics, or t-tests for continuous data.

RESULTS:

Among a nationwide sample (n = 353) of individuals with SCI, NU were less likely than CU and PU to believe that cannabis ought to be legalized and more likely to endorse risks of use. Current users and PU reported greater pain interference in daily life than did NU, but there were no between group differences in QOL or physical or emotional health. Current users and PU took MC to address pain (65.30%), spasms (63.30%), sleeplessness (32.70%), and anxiety (24.00%), and 63.30% reported it offered “great relief” from symptoms. Participants reported that MC is more effective and carries fewer side effects than prescription medications.

CONCLUSIONS:

Medicinal cannabis is an effective and well-tolerated treatment for a number of SCI-related symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/31632724

https://www.nature.com/articles/s41394-019-0208-6

Using cannabis for pain management after spinal cord injury: a qualitative study.

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Image result for spinal cord series and cases

“OBJECTIVES:

To explore why individuals with spinal cord injury (SCI) choose to use cannabis to manage their pain and their experiences in doing so.

RESULTS:

Eight individuals participated in this study. We interpreted six themes that captured the participants’ perspectives regarding their choice to, and perceptions of, using cannabis to manage SCI pain. Participants were motivated to use cannabis when other pain management strategies had been ineffective and were well-informed, knowledgeable cannabis consumers. Participants reported cannabis reduced their pain quickly and enabled them to engage in activities of daily living and participate in life roles without the drowsiness of traditional prescribed pain medication. Despite the positive aspects, participants were concerned about the irregularity of supply and inconsistent dosage.

CONCLUSIONS:

Findings show that cannabis is used to reduce pain after SCI and enable increased community participation. Findings suggest that future studies examining the efficacy of cannabinoids in managing pain include function and participation outcome measures rather than solely focusing on measuring pain intensity. Focusing on meaningful outcomes may contribute to a greater understanding of the experiences of people with SCI.”

https://www.ncbi.nlm.nih.gov/pubmed/31632740

https://www.nature.com/articles/s41394-019-0227-3

“Cannabis helps those with spinal cord injuries escape pain”  https://medicalxpress.com/news/2019-10-cannabis-spinal-cord-injuries-pain.html

The endocannabinoid system: Novel targets for treating cancer induced bone pain.

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Biomedicine & Pharmacotherapy“Treating Cancer-induced bone pain (CIBP) continues to be a major clinical challenge and underlying mechanisms of CIBP remain unclear.

Recently, emerging body of evidence suggested the endocannabinoid system (ECS) may play essential roles in CIBP. Here, we summarized the current understanding of the antinociceptive mechanisms of endocannabinoids in CIBP and discussed the beneficial effects of endocannabinoid for CIBP treatment.

Targeting non-selective cannabinoid 1 receptors or selective cannabinoid 2 receptors, and modulation of peripheral AEA and 2-AG, as well as the inhibition the function of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have produced analgesic effects in animal models of CIBP.

Management of ECS therefore appears to be a promising way for the treatment of CIBP in terms of efficacy and safety. Further clinical studies are encouraged to confirm the possible translation to humans of the very promising results already obtained in the preclinical studies.”

https://www.ncbi.nlm.nih.gov/pubmed/31627091

“Thus, cannabinoids may be clinically useful for treating chronic pain and CIBP.”

https://www.sciencedirect.com/science/article/pii/S075333221933731X?via%3Dihub

Cannabinoid effects on responses to quantitative sensory testing among individuals with and without clinical pain: a systematic review.

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Image result for wolters kluwer“There has been an explosion of interest in the utility of cannabinoids as potential analgesics.

This systematic review critically synthesizes the evidence for cannabinoid analgesic effects on quantitative sensory testing outcomes in both healthy adults and patients with chronic non-cancer pain (CNCP).

Our systematic review protocol is pre-registered on PROSPERO (CRD42018117367). An electronic search was made in PsycINFO, Cochrane, Google Scholar, Embase, and Pubmed of all literature published until August 2018. Of the 1,217 studies found from the search, a total 39 placebo-controlled studies that met the eligibility criteria were synthesized for the present study. Due to substantial heterogeneity of study designs, populations, cannabinoid compounds, and quantitative sensory testing outcomes, meta-analysis was not conducted.

More consistent evidence of cannabinoid analgesia was observed for inhaled cannabis than synthetic cannabinoids.

Analgesic effects were most commonly observed in tests of cold pain sensitivity, and hyperalgesic effects were most commonly observed in tests of electrical stimulation. Patterns of findings from studies with healthy subjects did not substantively differ from those with CNCP. However, these observations are qualified by the high degree of inconsistency across studies and methodological heterogeneity. We offer recommendations for future studies to improve study rigor and reproducibility.”

 https://www.ncbi.nlm.nih.gov/pubmed/31613869
https://insights.ovid.com/crossref?an=00006396-900000000-98577

Cellular Distribution of Canonical and Putative Cannabinoid Receptors in Canine Cervical Dorsal Root Ganglia.

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Image result for frontiers in veterinary science“Growing evidence indicates cannabinoid receptors as potential therapeutic targets for chronic pain.

Consequently, there is an increasing interest in developing cannabinoid receptor agonists for treating human and veterinary pain.

The present study may represent a morphological substrate to consider in order to develop therapeutic strategies against chronic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/31608295

“The anti-nociceptive potential of the endocannabinoid system has prompted the development of therapeutic cannabinoid receptors agonists or medical marjiuana to be used in pets in order to treat chronic pain.”

https://www.frontiersin.org/articles/10.3389/fvets.2019.00313/full

Cannabinoid Receptor Type 1 and Its Role as an Analgesic: An Opioid Alternative?

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 Publication Cover“Understanding how the body regulates pain is fundamental to develop rational strategies to combat the growing prevalence of chronic pain states, opioid dependency, and the increased financial burden to the medical care system.

Pain is the most prominent reason why Americans seek medical attention and extensive literature has identified the importance of the endocannabinoid pathway in controlling pain. Modulation of the endocannabinoid system offers new therapeutic opportunities for the selective control of excessive neuronal activity in several pain conditions (acute, inflammatory, chronic, and neuropathic).

Cannabinoids have a long history of medicinal use and their analgesic properties are well documented; however, there are major impediments to understanding cannabinoid pain modulation.

One major issue is the presence of psychotropic side effects associated with D9-tetrahydrocannabinol (THC) or synthetic derivatives, which puts an emphatic brake on their use. This dose-limiting effect prevents the appropriate degree of analgesia .

Animal studies have shown that the psychotropic effects are mediated via brain cannabinoid type 1 (CB1) receptors, while analgesic activity in chronic pain states may be mediated via CB1R action in the spinal cord, brainstem, peripheral sensory neurons, or immune cells.

The development of appropriate therapies is incumbent on our understanding of the role of peripheral versus central endocannabinoid-driven analgesia. Recent physiological, pharmacological, and anatomical studies provide evidence that one of the main roles of the endocannabinoid system is the regulation of gamma-aminobutyric acid (GABA) and/or glutamate release.

This article will review this evidence in the context of its implications for pain. We first provide a brief overview of CB1R’s role in the regulation of nociception, followed by a review of the evidence that the peripheral endocannabinoid system modulates nociception.

We then look in detail at regulation of central-mediated analgesia, followed up with evidence that cannabinoid mediated modulation of pain involves modulation of GABAergic and glutamatergic neurotransmission in key brain regions. Finally, we discuss cannabinoid action on non-neuronal cells in the context of inflammation and direct modulation of neurons.

This work stands to reveal long-standing controversies in the cannabinoid analgesia area that have had an impact on failed clinical trials and implementation of therapeutics targeting this system.”

https://www.ncbi.nlm.nih.gov/pubmed/31596190

https://www.tandfonline.com/doi/abs/10.1080/15504263.2019.1668100?journalCode=wjdd20

The effect of cannabis laws on opioid use.

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International Journal of Drug Policy“Many Americans rely on opioids at varying dosages to help ameliorate their suffering. However, empirical evidence is mounting that opioids are ineffective at controlling non-cancer related chronic pain, and many argue the strategies meant to relieve patient suffering are contributing to the growing opioid epidemic.

Concurrently, several states now allow the use of medical cannabis to treat a variety of medical conditions, including chronic pain. Needing more exploration is the impact of cannabis laws on general opioid reliance and whether chronic pain sufferers are opting to use cannabis medicinally instead of opioids.

METHODS:

This study investigates the effect of Medical Marijuana Laws (MML)s on opioid use and misuse controlling for a number of relevant factors using data from several years of the National Survey on Drug Use and Health and multivariate logistic regression and longitudinal analysis strategies.

RESULTS:

Results provide evidence that MMLs may be effective at reducing opioid reliance as survey respondents living in states with medical cannabis legislation are much less apt to report using opioid analgesics than people living in states without such laws, net other factors. Results further indicate that the presence of medicinal cannabis legislation appears to have no influence over opioid misuse.

CONCLUSION:

MMLs may ultimately serve to attenuate the consequences of opioid overreliance.”

https://www.ncbi.nlm.nih.gov/pubmed/31590091

https://www.sciencedirect.com/science/article/abs/pii/S0955395919302567?via%3Dihub