Medical cannabis for chronic pain: can it make a difference in pain management?

 “Globally, chronic pain is a major therapeutic challenge and affects more than 15% of the population. As patients with painful terminal diseases may face unbearable pain, there is a need for more potent analgesics.

Although opioid-based therapeutic agents received attention to manage severe pain, their adverse drug effects and mortality rate associated with opioids overdose are the major concerns.

Evidences from clinical trials showed therapeutic benefits of cannabis, especially delta-9-tetrahydrocannabinol and cannabinoids reduced neuropathic pain intensity in various conditions. Also, there are reports on using combination cannabinoid therapies for chronic pain management.

The association of cannabis dependence and addiction has been discussed much and the reports mentioned that it can be comparatively lower than other substances such as nicotine and alcohol.

More countries have decided to legalise the medicinal use of cannabis and marijuana.

Healthcare professionals should keep themselves updated with the changing state of medical cannabis and its applications.”

https://www.ncbi.nlm.nih.gov/pubmed/31535218

https://link.springer.com/article/10.1007%2Fs00540-019-02680-y

The Impact of Cannabinoid Receptor 2 Deficiency on Neutrophil Recruitment and Inflammation.

View details for DNA and Cell Biology cover image“Neutrophil trafficking into damaged or infected tissues is essential for the initiation of inflammation, clearance of pathogens and damaged cells, and ultimately tissue repair. Neutrophil recruitment is highly dependent on the stepwise induction of adhesion molecules and promigratory chemokines and cytokines.

A number of studies in animal models have shown the efficacy of cannabinoid receptor 2 (CB2) agonists in limiting inflammation in a range of preclinical models of inflammation, including colitis, atherosclerosis, multiple sclerosis, and ischemia-reperfusion injury.

Recent work in preclinical models of inflammation raises two questions: by what mechanisms do CB2 agonists provide anti-inflammatory effects during acute inflammation and what challenges exist in the translation of CB2 modulating therapeutics into the clinic.”

Modulation of the endocannabinoid system: vulnerability factor and new treatment target for stimulant addiction

Image result for frontiers in psychiatry“Interestingly, increasing recent evidence points toward the involvement of the endocannabinoid system (ECBS) in the neurobiological processes related to stimulant addiction.

This article presents an up-to-date review with deep insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. This article aims to: (1) review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and (2) evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction.

A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoids in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants.

Interestingly, emerging human data supports a role for ECBS modulation in vulnerability to psychostimulant addiction, and more significantly in addictive behaviors among dependent individuals. Accumulating evidence thus points to the ECBS as a critical target for the development of pharmacotherapies for the treatment of addiction to psychostimulants.

Given the various neuropharmacological actions of exogenous cannabinoids, and their ability to modulate the acute reinforcing effects of drugs, data on Δ9-THC and CBD is particularly promising as to the potential use of cannabinoids in relapse prevention strategies for psychostimulant-dependent individuals.”

https://www.frontiersin.org/articles/10.3389/fpsyt.2013.00109/full

Reduced urinary opioid levels from pain management patients associated with marijuana use

Future Medicine Logo“Aim: Marijuana use has been postulated to modulate opioid use, dependence and withdrawal. Broad target drug testing results provide a unique perspective to identify any potential interaction between marijuana use and opioid use.

Materials & methods: Using a dataset of approximately 800,000 urine drug test results collected from pain management patients of a time from of multiple years, creatinine corrected opioid levels were evaluated to determine if the presence of the primary marijuana marker 11-nor-carboxy-tetrahydrocannabinol (THC-COOH) was associated with statistical differences in excreted opioid concentrations.

Results & conclusion: For each of the opioids investigated (codeine, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone, fentanyl and buprenorphine), marijuana use was associated with statistically significant lower urinary opiate levels than in samples without indicators of marijuana use.”

https://www.futuremedicine.com/doi/10.2217/pmt-2019-0017

Medical Cannabis in Treatment of Resistant Familial Mediterranean Fever.

 Logo“Colchicine-resistant familial Mediterranean fever can be treated by anti-IL-1 biologic therapy; however, such treatment needs approval by the health insurance company, and many patients are denied such treatment or do not respond to it.

CASE REPORT Two familial Mediterranean fever (FMF) patients, both homozygous for M694V mutation and resistant to colchicine treatment, were treated with medical cannabis. Prior to that, 1 patient was denied biologic treatment and the other had no significant response to anakinra.

Under medical cannabis treatment, both patients had remarkable improvement in the severity of the attacks and also a decrease in the frequency of the attacks, from once every 2 weeks to 1 attack every month in 1 patient; this patient had also a remarkable reduction in the C-reactive protein level during the attacks.

CONCLUSIONS Cannabis is a therapeutic option for treating the most complex patients with FMF.”

https://www.ncbi.nlm.nih.gov/pubmed/31501406

https://www.amjcaserep.com/abstract/index/idArt/917180

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

“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

Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways.

 Image result for frontiers in immunology“Multiple sclerosis (MS) is a chronic and disabling disorder of the central nervous system (CNS) characterized by neuroinflammation leading to demyelination.

Recently a combination of Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) extracted from Cannabis has been approved in many parts of the world to treat MS-related spasticity. THC+CBD combination was also shown to suppresses neuroinflammation, although the mechanisms remain to be further elucidated.

In the current study, we demonstrate that THC+CBD combination therapy (10 mg/kg each) but not THC or CBD alone, attenuates murine experimental autoimmune encephalomyelitis (EAE) by reducing neuroinflammation and suppression of Th17 and Th1 cells.

Collectively, this study suggests that combination of THC+CBD suppresses neuroinflammation and attenuates clinical EAE development and that this effect is associated with changes in miRNA profile in brain-infiltrating cells.”

https://www.ncbi.nlm.nih.gov/pubmed/31497013

“Combination of THC+CBD has been used to treat human MS. This treatment is known to decrease not only muscle spasticity but also suppress neuroinflammation.”

https://www.frontiersin.org/articles/10.3389/fimmu.2019.01921/full

Real world experience of patients with amyotrophic lateral sclerosis (ALS) in the treatment of spasticity using tetrahydrocannabinol:cannabidiol (THC:CBD).

Image result for bmc neurology“Treatment of spasticity poses a major challenge in amyotrophic lateral sclerosis (ALS) patient management.

Delta-9-tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (THC:CBD), approved for the treatment of spasticity in multiple sclerosis, serves as a complementary off-label treatment option in ALS-related spasticity.

The mean dose THC:CBD were 5.5 daily actuations (range < 1 to 20). Three subgroups of patients were identified: 1) high-dose daily use (≥ 7 daily actuations, 34%, n = 11), 2) low-dose daily use (< 7 daily actuations, 50%, n = 16), 3) infrequent use (< 1 daily actuation, 16%, n = 5). Overall NPS was + 4.9 (values above 0 express a positive recommendation to fellow patients). Remarkably, patients with moderate to severe spasticity (NRS ≥ 4) reported a high recommendation rate (NPS: + 29) in contrast to patients with mild spasticity (NRS < 4; NPS: - 44). For the three main domains of TSQM-9 high mean satisfaction levels were found (maximum value 100): effectiveness 70.5 (±22.3), convenience 76.6 (±23.3) and global satisfaction 75.0 (±24.7).

CONCLUSION:

THC:CBD is used in a wide dose range suggesting that the drug was applied on the basis of individual patients’ needs and preferences. Contributing to this notion, moderate to severe spasticity was associated with an elevated number of daily THC:CBD actuations and stronger recommendation rate (NPS) as compared to patients with mild spasticity. Overall, treatment satisfaction (TSQM-9) was high. The results suggest that THC:CBD may serve as a valuable addition in the spectrum of symptomatic therapy in ALS. However, prospective studies and head-to-head comparisons to other spasticity medications are of interest to further explore the effectiveness of THC:CBD in the management of spasticity, and other ALS-related symptoms.”

“Overall, patients reported outcomes as assessed by TSQM-9 revealed a high treatment satisfaction with THC:CBD. The results of our study suggest that THC:CBD may serve as an important addition to the spectrum of treatment options of spasticity in ALS.”

The Effectiveness of Cannabinoids in the Treatment of Posttraumatic Stress Disorder (PTSD): A Systematic Review.

Publication CoverPosttraumatic stress disorder (PTSD) is a potentially debilitating mental health problem.

There has been a recent surge of interest regarding the use of cannabinoids in the treatment of PTSD.

We therefore sought to systematically review and assess the quality of the clinical evidence of the effectiveness of cannabinoids for the treatment of PTSD.

We found that cannabinoids may decrease PTSD symptomology, in particular sleep disturbances and nightmares.

Evidence that cannabinoids may help reduce global PTSD symptoms, sleep disturbances, and nightmares indicates that future well-controlled, randomized, double-blind clinical trials are highly warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/31479625

https://www.tandfonline.com/doi/full/10.1080/15504263.2019.1652380