Category Archives: Spinal Cord Injury

Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury

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SpringerLink

“Cannabidiol (CBD), a non-psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury.

Rats were distributed into five experimental groups. Animals were submitted to laminectomy in vertebral segment T10 followed or not by application of liquid nitrogen for 5 s into the spinal cord at the same level to cause cryoinjury. The animals received injections of vehicle or CBD (20 mg/kg) immediately before, 3 h after and daily for 6 days after surgery. The Basso, Beattie, and Bresnahan motor evaluation test was used to assess motor function post-lesion one day before surgery and on the first, third, and seventh postoperative days. The extent of injury was evaluated by hematoxylin-eosin histology and FosB expression.

Cryogenic lesion of the spinal cord resulted in a significant motor deficit. Cannabidiol-treated rats exhibited a higher Basso, Beattie, and Bresnahan locomotor score at the end of the first week after spinal cord injury: lesion + vehicle, day 1: zero, day 7: four, and lesion + Cannabidiol 20 mg/kg, day 1: zero, day 7: seven. Moreover, at this moment there was a significant reduction in the extent of tissue injury and FosB expression in the ventral horn of the spinal cord.

The present study confirmed that application of liquid nitrogen to the spinal cord induces reproducible and quantifiable spinal cord injury associated with locomotor function impairments.

Cannabidiol improved locomotor functional recovery and reduced injury extent, suggesting that it could be useful in the treatment of spinal cord lesions.”

https://pubmed.ncbi.nlm.nih.gov/21915768/

https://link.springer.com/article/10.1007/s12640-011-9273-8

The Impact of Isolated Baseline Cannabis Use on Outcomes Following Thoracolumbar Spinal Fusion: A Propensity Score-Matched Analysis

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“Background: There is limited literature evaluating the impact of isolated cannabis use on outcomes for patients following spinal surgery. This study sought to compare 90-day complication, 90-day readmission, as well as 2-year revision rates between baseline cannabis users and non-users following thoracolumbar spinal fusion (TLF) for adult spinal deformity (ASD).

Results: 704 patients were identified (n=352 each), with comparable age, sex, race, primary insurance, Charlson/Deyo scores, surgical approach, and levels fused between cohorts (all, p>0.05). Cannabis users (versus non-users) incurred lower 90-day overall and medical complication rates (2.4% vs. 4.8%, p=0.013; 2.0% vs. 4.1%, p=0.018). Cohorts had otherwise comparable complication, revision, and readmission rates (p>0.05). Baseline cannabis use was associated with a lower risk of 90-day medical complications (OR=0.47, p=0.005). Isolated baseline cannabis use was not associated with 90-day surgical complications and readmissions, or two-year revisions.

Conclusion: Isolated baseline cannabis use, in the absence of any other diagnosed substance abuse disorders, was not associated with increased odds of 90-day surgical complications or readmissions or two-year revisions, though its use was associated with reduced odds of 90-day medical complications when compared to non-users undergoing TLF for ASD. Further investigations are warranted to identify the physiologic mechanisms underlying these findings. Level of Evidence: III.”

https://pubmed.ncbi.nlm.nih.gov/35821925/

“Compared to patients with ASD who underwent TLF without baseline cannabis use, patients with isolated baseline cannabis use were found to have no increase in odds of incurring 90-day surgical complications or readmissions or revisions two years postoperatively, though reduced odds of experiencing 90-day medical complications were observed.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210439/

Promoting Oligodendrocyte Differentiation from Human Induced Pluripotent Stem Cells by Activating Endocannabinoid Signaling for Treating Spinal Cord Injury

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“Transplantation of oligodendrocyte progenitor cell (OPC) at the injury site is being developed as a potential therapeutic strategy for promoting remyelination and locomotor function recovery after spinal cord injury (SCI). To this end, the development of expandable and functional human OPCs is crucial for testing their efficacy in SCI.

In mice and rats, the endocannabinoid signaling system is crucial for the survival, differentiation, and maturation of OPCs. Similar studies in humans are lacking currently. Endocannabinoids and exogenous cannabinoids exert their effects mainly via cannabinoid receptors (CB1R and CB2R). We demonstrated that these receptors were differentially expressed in iPSC-derived human NSCs and OPCs, and they could be activated by WIN55212-2 (WIN), a potent CB1R/CB2R agonist to upregulate the endocannabinoid signaling during glial induction.

WIN primed NSCs generated more OLIG2 + glial progenitors and migratory PDGFRα + OPC in a CB1/CB2 dependent manner compared to unprimed NSCs. Furthermore, WIN-induced OPCs (WIN-OPCs) robustly differentiated into functional oligodendrocytes and myelinate in vitro and in vivo in a mouse spinal cord injury model. RNA-Seq revealed that WIN upregulated the biological process of positive regulation of oligodendrocyte differentiation. Mechanistically, WIN could act as a partial smoothed (SMO) inhibitor or activate CB1/CB2 to form heteromeric complexes with SMO leading to the inhibition of GLI1 in the Sonic hedgehog pathway.

The partial and temporal inhibition of GLI1 during glial induction is shown to promote OPCs that differentiate faster than control’s. Thus, CB1R/CB2R activation results in more efficient generation of OPCs that can mature and efficiently myelinate.”

https://pubmed.ncbi.nlm.nih.gov/35725998/

https://link.springer.com/article/10.1007/s12015-022-10405-0


Will Cannabigerol Trigger Neuroregeneration after a Spinal Cord Injury? An In Vitro Answer from NSC-34 Scratch-Injured Cells Transcriptome

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“Spinal cord injury affects the lives of millions of people around the world, often causing disability and, in unfortunate circumstances, death. Rehabilitation can partly improve outcomes and only a small percentage of patients, typically the least injured, can hope to return to normal living conditions. Cannabis sativa is gaining more and more interest in recent years, even though its beneficial properties have been known for thousands of years. Cannabigerol (CBG), extracted from C. sativa, is defined as the “mother of all cannabinoids” and its properties range from anti-inflammatory to antioxidant and neuroprotection. Using NSC-34 cells to model spinal cord injury in vitro, our work evaluated the properties of CBG treatments in motor neuron regeneration. While pre-treatment can modulate oxidative stress and increase antioxidant enzyme genes, such as Tnx1, decreasing Nos1 post-treatment seems to induce regeneration genes by triggering different pathways, such as Gap43 via p53 acetylation by Ep300 and Ddit3 and Xbp1 via Bdnf signaling, along with cytoskeletal remodeling signaling genes Nrp1 and Map1b. Our results indicate CBG as a phytocompound worth further investigation in the field of neuronal regeneration.”

https://pubmed.ncbi.nlm.nih.gov/35215230/

Analyzing the Impact of Cannabinoids on the Treatment of Spinal Disorders

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“Purpose of review: Cannabis is among the most used illicit substances globally, with medical applications, increased legalization, and shifting social attitudes leading to increased use in recent years. Cannabinoids are a group of psychoactive substances found within the cannabis plant, with the most common being Δ9-tetrahydrocannabinol and cannabidiol. Due to the high prevalence of use, it is increasingly important to evaluate the effects of cannabis and cannabinoids on spine patients, in both operative and nonoperative settings.

Recent findings: Cannabis and cannabinoids may be effective in treating patients with chronic conditions such as back pain and spinal cord injuries. Longitudinal effects and implications on surgical outcomes and complications are poorly understood. High-quality, outcomes-focused research can inform approaches for clinicians to approach cannabis and cannabinoid use. Studies to elucidate the standardization of cannabis regimens can help develop guidelines for potential therapeutic applications. Cannabis and cannabinoids may be useful alternatives or additions for many spine patients, but future research is needed for recommendations to be determined. Our manuscript reviews the available literature regarding cannabis use and various spinal conditions, organizing our findings into the following narrative themes: (1) the management of chronic lower back pain, (2) perioperative outcomes, (3) cannabis use in general orthopaedic procedures, and (4) spinal cord injuries.”

https://pubmed.ncbi.nlm.nih.gov/35132567/

Systematic review of the impact of cannabinoids on neurobehavioral outcomes in preclinical models of traumatic and nontraumatic spinal cord injury

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Spinal Cord“Objectives: To evaluate the impact of cannabinoids on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic spinal cord injury (SCI), with the aim of determining suitability for clinical trials involving SCI patients.

Results: The search returned 8714 studies, 19 of which met our inclusion criteria. Sample sizes ranged from 23 to 390 animals. WIN 55,212-2 (n = 6) and AM 630 (n = 8) were the most used cannabinoid receptor agonist and antagonist respectively. Acute SCI models included traumatic injury (n = 16), ischaemia/reperfusion injury (n = 2), spinal cord cryoinjury (n = 1) and spinal cord ischaemia (n = 1). Assessment tools used assessed locomotor function, pain and anxiety. Cannabinoid receptor agonists resulted in statistically significant improvement in locomotor function in 9 out of 10 studies and pain outcomes in 6 out of 6 studies.

Conclusion: Modulation of the endo-cannabinoid system has demonstrated significant improvement in both pain and locomotor function in pre-clinical SCI models; however, the risk of bias is unclear in all studies. These results may help to contextualise future translational clinical trials investigating whether cannabinoids can improve pain and locomotor function in SCI patients.”

https://pubmed.ncbi.nlm.nih.gov/34392312/

“The results of these studies demonstrate that modulation of the endo-cannabinoid system has significant benefit for both pain and locomotor function across a range of pre-clinical models of acute spinal cord injury.”

https://www.nature.com/articles/s41393-021-00680-y

The Therapeutic Potential and Usage Patterns of Cannabinoids in People with Spinal Cord.

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“People with spinal cord injuries (SCI) commonly experience pain and spasticity, but limitations of current treatments have generated interest in cannabis as a possible therapy.

We conducted this systematic review to: 1) examine usage patterns and reasons for cannabinoid use, and 2) determine the treatment efficacy and safety of cannabinoid use, in people with SCI.

Though 26 studies addressed cannabinoid usage, only 8 investigated its therapeutic potential on outcomes such as pain and spasticity.

The most common usage method was smoking. Relief of pain, spasticity and pleasure were the most common reasons for use. Statistically significant reduction of pain and spasticity was observed with cannabinoid use in 80% and 90% of experimental studies, respectively.

 

CONCLUSIONS:

Current evidence suggests cannabinoids may reduce pain and spasticity in people with SCI, but its effect magnitude and clinical significance is unclear. Existing information is lacking on optimal dosage, method of use, composition and concentration of compounds. Longterm, double-blind, RCTs, assessing a wider range of outcomes should be conducted to further understanding of the effects of cannabinoid use in people with SCI.”

https://www.ncbi.nlm.nih.gov/pubmed/32310048

http://www.eurekaselect.com/181078/article

“Cannabis cures the spine” https://www.jtcvs.org/article/S0022-5223(18)32080-4/fulltext

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 and its Modulation by Cannabidiol (CBD).

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Image result for Altern Ther Health Med. “The endocannabinoid system (ECS) is an extensive endogenous signaling system with multiple elements, the number of which may be increasing as scientists continue to elucidate its role in human health and disease. The ECS is seemingly ubiquitous in animal species and is modulated by diet, sleep, exercise, stress, and a multitude of other factors, including exposure to phytocannabinoids, like Cannabidiol (CBD). Modulating the activity of this system may offer tremendous therapeutic promise for a diverse scope of diseases, ranging from mental health disorders, neurological and movement disorders, pain, autoimmune disease, spinal cord injury, cancer, cardiometabolic disease, stroke, TBI, osteoporosis, and others.”

https://www.ncbi.nlm.nih.gov/pubmed/31202198