Efficacy of topical cannabinoids in the management of pain: a systematic review and meta-analysis of animal studies

2022 ◽  
pp. rapm-2021-102719
Author(s):  
Lukas D Linde ◽  
Carey M Ogryzlo ◽  
Cassandra M Choles ◽  
Brian E Cairns ◽  
John L K Kramer
Keyword(s):  
Pain Management ◽  
Side Effects ◽  
Animal Studies ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Preliminary Evidence ◽  
Human Studies ◽  
Tail Flick ◽  
Major Barrier ◽  
Pain Ratings

Background/importanceCannabinoids are emerging as an alternative pain management option, preliminarily supported by preclinical and clinical studies. Unwanted side effects from oral or inhaled cannabinoids remain, however, a major barrier to widespread use. Peripherally acting cannabinoids (eg, topically applied) may circumvent these side effects while providing localized pain management.ObjectiveOur purpose was to systematically review the literature on the effectiveness of peripherally acting cannabinoids for pain management.Evidence reviewWe searched MEDLINE, EMBASE, CENTRAL, CINAHL, and PubMed databases. Included studies examined the effect of topical/peripherally administered cannabinoids on pain ratings in humans, as well as pain-related outcomes in animals (eg, paw withdrawal). Due to a lack of trials, human studies were summarized in a narrative synthesis. Separate meta-analyses were performed for animal studies using radiant tail flick or paw withdrawal outcomes.FindingsOur search yielded 1182 studies following removal of duplicates, with 46 studies (6 human, 40 animal) included. Human studies (one randomized controlled trial and five case studies/series) reported no adverse events to topical cannabinoids and preliminary evidence of decreased pain ratings. Animal studies reporting tail flick (5) (2.81, 95% CI 1.93 to 3.69, p<0.001) and mechanical withdrawal (11) (2.74, 95% CI 1.82 to 3.67, p<0.001) reported prolonged responses (analgesia) in peripheral cannabinoid groups compared with controls.ConclusionsPreclinical animal studies provided low-quality evidence for peripherally administered cannabinoids to provide regional, antinociceptive effects. The scarcity of high-quality human studies underscores the need to translate preclinical evidence into well-controlled human trials.

scholarly journals Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kei Hayashida ◽  
Ryosuke Takegawa ◽  
Muhammad Shoaib ◽  
Tomoaki Aoki ◽  
Rishabh C. Choudhary ◽  
...  
Keyword(s):  
Systematic Review ◽  
Reperfusion Injury ◽  
Animal Studies ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Human Studies ◽  
Cochrane Library

Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.

scholarly journals Continuous Fentanyl Background Infusion Regimen Optimised by Patient-Controlled Analgesia for Acute Postoperative Pain Management: A Randomised Controlled Trial

2020 ◽  
Vol 9 (1) ◽  
pp. 211 ◽  
Author(s):  
Jihoon Hwang ◽  
Sang Kee Min ◽  
Yun Jeong Chae ◽  
Gang Mee Lim ◽  
Han Bum Joe
Keyword(s):  
Pain Management ◽  
Side Effects ◽  
Postoperative Pain ◽  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Postoperative Pain Management ◽  
Patient Controlled Analgesia ◽  
Acute Postoperative Pain ◽  
Background Infusion ◽  
Randomised Controlled

Owing to a lack of studies investigating the effect of adjustments in fentanyl background infusion (BI) with patient-controlled analgesia (PCA) on postoperative analgesia, we evaluated three BI regimens with fentanyl PCA for acute postoperative pain management. This randomised controlled trial enrolled 105 patients, who were assigned to three parallel groups: constant rate BI of 2 mL/h (CRBI group); time-scheduled decremental BI of 6, 2 and 1 mL/h (TDBI group); and BI rates optimised to the demand of PCA (POBI group). The incidence of insufficient analgesia, visual analogue scale (VAS) pain score and side effects were evaluated. The incidence of insufficient analgesia in the post-anaesthesia care unit was lower in the TDBI and POBI groups than the CRBI group. Incidence of insufficient analgesia in the ward was lower in the POBI group than the CRBI group. Postoperative VAS scores were significantly lower in the TDBI and POBI groups for up to 4 h and 24 h, respectively, compared with the CRBI group. Side effects and infused fentanyl dose were highest in the CRBI group. Adjusting BI rate based on time or patient demands could improve postoperative analgesia and reduce side effects. Compared to a constant BI rate, PCA-optimised BI achieved higher patient satisfaction.

scholarly journals The Impact of Consumption of Dairy Products on Phospholipid Metabolism: A Systematic Review

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1261-1261
Author(s):  
Emad Yuzbashian ◽  
Catherine B Chan
Keyword(s):  
Dairy Products ◽  
Animal Studies ◽  
Meta Analysis ◽  
Phospholipid Metabolism ◽  
Human Studies ◽  
Resistance Risk ◽  
Human Trials ◽  
Beneficial Effects ◽  
Funding Sources ◽  
The Impact

Abstract Objectives Metabolomics approach indicates that circulating phospholipid (PL) and some PL species are associated with a lower insulin resistance risk. Evidence suggests that dairy products' health beneficial effects may pertain to their regulatory influence on PL metabolism. Therefore, we aimed to systematically review the existing literature of animal and human trials to unravel the impact of dairy products on the concentration of PL and its metabolism. Methods Three online databases, including PubMed, Scopus, and Web of Science, were searched to find relevant studies published in peer-reviewed journals between January 2000 and July 2020. Included studies were interventional trials (animal and human) that investigated the effect of dairy or its subtypes on the circulating or liver content of PL and its species. The risk of bias (RoB) in trials in humans and animals was assessed using the revised Cochrane's and SYRCLE's RoB assessment, respectively. Since there was marked methodological heterogeneity, a meta-analysis did not perform. Results In this review, 2427 articles were identified and screened after removing duplicate articles. Following evaluation of the titles and abstracts and then full-text assessment, 17 studies were identified that met the inclusion criteria. Studies were classified according to their type, resulting in nine human trials and eight animal studies. For human studies, the RoB assessment indicated that more than 55% of studies had high RoB. None animal studies receive low RoB because of the lack of methodological information. Findings from human studies revealed that plasma/serum concentration of PL did not change after intervention with dairy products. PL concentration remained stable even after a high dosage of milk supplemented with dairy-derived PL; however, certain PC or LPC species were increased by interventions. These findings were also confirmed in animal studies. The interesting point in animal studies was that high fat diet-induced elevation of PL tends to be normalized after intervention with dairy products enriched with milk-PL. Furthermore, in mice, intervention with yogurt or cheese did not impact serum or liver content of PL or PC. Conclusions Dairy products can influence the blood concentration of PC and LPC species in both rodents and humans without alteration of total PL and PC. Funding Sources Alberta Diabetes Institute.

scholarly journals Vitamin C can reduce mortality in sepsis: a systematic review and meta-analysis of animal and human evidence

2020 ◽  
Author(s):  
Cong-Cong Zhao ◽  
Li-Nan Han ◽  
Gui-Jun Zhu ◽  
Zhi-Qiang Li ◽  
Zhen-Jie Hu
Keyword(s):  
Systematic Review ◽  
Mean Arterial Pressure ◽  
Vitamin C ◽  
Animal Studies ◽  
Meta Analysis ◽  
Capillary Density ◽  
Human Studies ◽  
Pooled Data ◽  
Intravenous Vitamin

Abstract Background: The effect of vitamin C on outcomes in sepsis is unclear. This systematic review and meta-analysis included animal and human studies to evaluate the value of intravenous vitamin C as a monotherapy in sepsis. Methods: We searched MEDLINE via PubMed, EMBASE, CENTRAL and CBM for animal studies, randomized controlled trials (RCTs), and quasi-RCTs dated up to August 10, 2020. The included studies compared the effect of intravenous vitamin C and control on outcomes in sepsis. No language restrictions were applied. Two authors independently assessed the eligibility and quality of the trials and extracted data. Results: A total of 7 animal studies and 5 RCTs were included. Four animal studies (n=176) and all 5 RCTs (n=472) reported mortality, the primary outcome of this meta-analysis. The mortality of the vitamin C group was lower than that of the control group (odds ratio (OR) 0.22, 95% CI 0.06 to 0.81, P = 0.02; I2 =60% in animal studies, and OR 0.48, 95% CI 0.33 to 0.71, P < 0.001; I2 =0% in human studies). The GRADE assessment showed that the outcome was downgraded from high- to moderate-quality evidence due to imprecision. With regard to the secondary outcomes, the pooled data from animal studies showed that vitamin C had a beneficial effect on mean arterial pressure (std. mean difference (SMD) 1.36, 95% CI 0.32 to 2.41, P = 0.01; I2 =78%) and capillary density (SMD 1.97, 95% CI 0.89 to 3.04, P=0.69; I2 =0%) but had no effect on the level of lactate. The pooled data from human studies showed that vitamin C was associated with a reduction in vasopressor duration (MD -18.85, 95% CI -24.61 to -11.55, P < 0.001; I2 =0%) but could not shorten the length of ICU stay or duration of mechanical ventilation. No adverse effects were reported.Conclusions: Evidence from animal and human studies suggests that intravenous vitamin C monotherapy can reduce mortality in sepsis, with a moderate quality of evidence. We also found that vitamin C had a beneficial effect on mean arterial pressure, capillary density, and reduction of vasopressor duration in sepsis.

scholarly journals Efficacy and Safety of Proton Therapy for Medulloblastoma Patients: A Mata-Analysis

2022 ◽  
Vol 11 (2) ◽  
pp. 01-07
Author(s):  
Weiping Zhan
Keyword(s):  
Side Effects ◽  
Recurrence Rate ◽  
Proton Therapy ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Quality Criteria ◽  
Biomedical Literature ◽  
Cochrane Library ◽  
Prognostic Impact ◽  
Study Materials

Background: Currently, photon therapy is mainly used for radiotherapy, however, the long-term side effects of photon therapy are sometimes reported, especially in children, including cognitive decline, mental decline, growth retardation, endocrine dysfunction and secondary tumor.Compared with photon radiotherapy, proton therapy is a novel method of radiation therapy, which reduces acute and late radiation damage and improves patients’ quality of life. Therefore, we evaluated proton therapy on medulloblastoma patients by meta-analysis in this study. Materials and Methods: A clinical randomized controlled trial was conducted by retrieving the main databases PubMed (Medline), EMbase, Cochrane Library, Chinese Biomedical Literature Database (CBM), Chinese Zhi-wang (CNKI), Wanfang Database, and VIP Database. We analyzed the literature which matched the quality criteria for the prognostic impact of proton and photon therapy on medulloblastoma patients. Results: Ten articles were included in this study. The overall survival (OS) rate and side effects were comprehensively analyzed. The results showed that proton radiotherapy significantly reduced the side effects and recurrence rate of tumor. Conclusion: Proton therapy could significantly reduce the side effects and recurrence rate of medulloblastoma in patients.

scholarly journals Use of Intrathecal Neostigmine as an Adjunct to Other Spinal Medications in Perioperative and Peripartum Analgesia: A Meta-analysis

2005 ◽  
Vol 33 (1) ◽  
pp. 41-53 ◽  
Author(s):  
K. M. Ho ◽  
H. Ismail ◽  
K. C. Lee ◽  
R. Branch
Keyword(s):  
Side Effects ◽  
Animal Studies ◽  
Data Extraction ◽  
Meta Analysis ◽  
Detailed Data ◽  
Regional Analgesia ◽  
Rescue Analgesia ◽  
Haemodynamic Stability ◽  
Intravenous Atropine ◽  
Minor Improvement

Intrathecal neostigmine has been used as an adjunct to intrathecal local anaesthetic or opioid to prolong regional analgesia and improve haemodynamic stability, with variable results. This meta-analysis aims to evaluate the effectiveness and side-effects of intrathecal neostigmine in the perioperative and peripartum settings. The literature search was based on Cochrane Controlled Trials Register, EMBASE and MEDLINE (from 1966 to 14 November 2003) databases. Volunteer and animal studies were excluded. We identified 26 studies and 19 were considered suitable for detailed data extraction. Intrathecal neostigmine increased the incidence of nausea and vomiting (OR 5.0, 95% CI: 3.4 to 7.3; P<0.00001), bradycardia requiring intravenous atropine (OR 2.7, 95% CI: 1.4 to 5.4; P=0.005), and anxiety, agitation, or restlessness (OR 10.3, 95% CI: 3.7 to 28.9; P=0.00001). It improved the overall 24 hour VAS score (–1.4 VAS pain score, 95% CI: -1.7 to -1.2, P<0.00001), delayed the time of first request for rescue analgesia (168 min, 95% CI: 125 to 211; P<0.00001), and reduced the total number of rescue injections of nonsteroidal anti-inflammatory drug within the first 24 hours (-0.8, 95% CI: -1.1 to -0.4; P=0.00001). It did not affect the duration of motor blockade (3.5 min, 95% CI: -1.5 to 8.6; P=0.17) or the total amount of ephedrine required (-0.4 mg, 95% CI: -1.5 to 0.7; P=0.5). Adding intrathecal neostigmine to other spinal medications improves perioperative and peripartum analgesia marginally when compared with placebo. It is associated with significant side-effects and the disadvantages outweigh the minor improvement in analgesia achieved.

Treatment of heroin dependence with ibogaine

2016 ◽  
Vol 33 (S1) ◽  
pp. S10-S11
Author(s):  
A. Schellekens ◽  
T. Oosteren ◽  
T. Knuijver ◽  
R.J. verkes ◽  
M. Belgers
Keyword(s):  
Systematic Review ◽  
Substance Use ◽  
Animal Studies ◽  
Meta Analysis ◽  
Human Studies ◽  
Opiate Withdrawal ◽  
Close Monitoring ◽  
Qtc Prolongation ◽  
Self Administration ◽  
Number Of Patients

BackgroundThe use of the hallucinogen ibogaine as an anti-addiction agent has been described in several case reports, dating back to the eighties. The anti-addiction properties of ibogaine have been confirmed in a large body of animal work. Ibogaine has been shown to be effective in reducing withdrawal severity and substance use for a variety of substances, including cocaine and opiates. Animal studies also show some potentially dangerous adverse reactions, including cerebellar toxicity and potential cardiac effects. While pharmacological treatment options for opiate and cocaine dependence are still limited, ibogaine assisted treatment might be a promising new option. Therefore more systematic studies on its toxicity and efficacy are warranted. In our studies we address these two research questions: is ibogaine treatment for opiate dependence safe and effective for treating opiate withdrawal and relapse prevention? A secondary objective is to explore the pharmacokinetic properties of ibogaine.MethodsAnimal work: first we performed a systematic review and meta-analysis of animal studies on ibogaine. Thirty studies were included in the systematic review, of which 27 could be analyzed in meta-analysis. Human studies: fifteen opiate dependent patients will be treated with ibogaine (10 mg/kg), on top of treatment as usual. Ibogaine toxicity will be assessed through close monitoring with electrocardiography, with QTc prolongation as main outcome measure, repeated assessments of ataxia using the (SARA) and observation of psychotic symptoms by using the Delirium Observations Scale (DOS). Ibogaine efficacy will be measured, using repeated evaluations of opiate withdrawal severity (Subjective Opiate Withdrawal Scale: SOWS; Objective Opiate Withdrawal Scale: OOWS), craving intensity (using a Visual Analogue Scale) and substance use, with a six-month follow-up. Clinical observations in ibogaine treated individuals will be compared with a cohort of opiate dependent patients treated with a rapid detoxification procedure. Both acute and long-term effects will be linked with serum ibogaine and noribogaine levels.ResultsAnimal work: overall, ibogaine reduced drug self-administration, particularly during the first 24 hours after administration. Ibogaine had no effect on drug-induced conditioned place preference. Ibogaine administration resulted in motor impairment in the first 24 hours after supplementation, and cerebral cell loss even weeks after administration. Data on ibogaines effect on cardiac rhythm as well as on its neuropharmacological working mechanisms are limited. Human studies: human data are still being collected. Treatment of the first patients confirmed strong effects of ibogaine on heart rhythm (QTc prolongation) and ataxia, while the opiate withdrawal symptoms were relatively mild. The first observations on the clinical effect of ibogaine on craving and substance use will also be shared.ConclusionsBased on our meta-analysis of animal data, there is strong evidence that ibogaine is effective in reducing drug self-administration in animals. This warrants further studies into the clinical efficacy of ibogaine in substance dependent patients in reducing craving and substance use. Our first clinical experiences in a limited number of patients confirm that ibogaine treatment may be effective in reducing opiate withdrawal, but can potentially have transient cardiac and cerebellar toxicity.Disclosure of interestThe authors have not supplied his declaration of competing interest.

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