Leflunomide-Associated Wound Complication After Cochlear Implantation: A Case Report.

INTRODUCTION: Cochlear implantation has become an increasingly common strategy for aural rehabilitation in patients with severe to profound hearing loss who no longer benefit from conventional amplification. In conjunction, immunosuppressive therapies (e.g. disease-modifying anti rheumatic drugs (DMARDs) have become the keystone of management in numerous autoimmune conditions. Given the increasing prevalence of both, a greater proportion of patients will undergo cochlear implantation while on immune-modulating medications. While these medications are usually well tolerated, immunosuppression may put patients a higher risk for device infections. At present, this is not extensively studied within the cochlear implant literature. METHODS: We conducted a retrospective chart review and review of the literature.Results:We present the case of an 81-year-old male who experienced wound dehiscence and infection secondary to leflunomide use for treatment of rheumatoid arthritis. Resolution of these issues was noted with a therapeutic drug holiday, and the patient has subsequently undergone re-implantation without issue.Conclusions:The case highlights a potential CI-associated wound complication in the setting of DMARD therapy. Given the increasing prevalence of both CIs and immunosuppressive therapy, future study on the potential for interaction is warranted to identify the best management strategy in the perioperative setting.

Machine Learning in Spine Oncology: A Narrative Review.

STUDY DESIGN: Narrative Review. OBJECTIVE: Machine learning (ML) is one of the latest advancements in artificial intelligence used in medicine and surgery with the potential to significantly impact the way physicians diagnose, prognose, and treat spine tumors. In the realm of spine oncology, ML is utilized to analyze and interpret medical imaging and classify tumors with incredible accuracy. The authors present a narrative review that specifically addresses the use of machine learning in spine oncology. METHODS: This study was conducted in accordance with the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) methodology. A systematic review of the literature in the PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases since inception was performed to present all clinical studies with the search terms '[[Machine Learning] OR [Artificial Intelligence]] AND [[Spine Oncology] OR [Spine Cancer]]'. Data included studies that were extracted and included algorithms, training and test size, outcomes reported. Studies were separated based on the type of tumor investigated using the machine learning algorithms into primary, metastatic, both, and intradural. A minimum of 2 independent reviewers conducted the study appraisal, data abstraction, and quality assessments of the studies. RESULTS: Forty-five studies met inclusion criteria out of 480 references screened from the initial search results. Studies were grouped by metastatic, primary, and intradural tumors. The majority of ML studies relevant to spine oncology focused on utilizing a mixture of clinical and imaging features to risk stratify mortality and frailty. Overall, these studies showed that ML is a helpful tool in tumor detection, differentiation, segmentation, predicting survival, predicting readmission rates of patients with either primary, metastatic, or intradural spine tumors. CONCLUSION: Specialized neural networks and deep learning algorithms have shown to be highly effective at predicting malignant probability and aid in diagnosis. ML algorithms can predict the risk of tumor recurrence or progression based on imaging and clinical features. Additionally, ML can optimize treatment planning, such as predicting radiotherapy dose distribution to the tumor and surrounding normal tissue or in surgical resection planning. It has the potential to significantly enhance the accuracy and efficiency of health care delivery, leading to improved patient outcomes.

Impact of obesity on adult spinal deformity (ASD) long-segment spinal fusion radiographic and clinical outcomes.

STUDY DESIGN: Retrospective chart review of patients receiving long-segment fusion during a five-year period. OBJECTIVE: To determine whether obese patients receive comparable benefits when receiving long-segment fusion compared to non-obese patients and to identify factors that may predict hardware failure and post-surgical complications among obese patients. METHODS: Demographic, spinopelvic radiographic, patient-reported outcome measures (PROMs), and complications data was retrospectively collected from 120 patients who underwent long-segment fusion during a five-year period at one tertiary care medical center. Radiographic measurements were pelvic incidence, pelvic tilt (PT), lumbar lordosis, L4-S1 lordosis, thoracic kyphosis, sagittal vertical axis, PI-LL mismatch, and proximal junction cobb angle at upper instrumented vertebrae + 2 (UIV+2). PROMs were Oswestry disability index, numeric rating scale (NRS) Back Pain, NRS Leg Pain, RAND SF-36 pain, and RAND SF-36 physical functioning. Included patients were adults and had at least 2-years of postoperative follow-up. Descriptive and multivariate statistical analysis was performed with α = 0.05. RESULTS: Patients with a BMI ≥ 30 (n=63) and patients with a BMI < 30 (n=57) demonstrated comparable improvements (P>0.05) for all spinopelvic radiographic measurements and PROMs. Each cohort demonstrated significant improvements from pre-assessment to post-assessment on nearly all spinopelvic radiographic measurements and PROMs (P<0.05), except PT and L4-S1 lordosis where neither group improved (p=0.95 and 0.58 for PT and P=0.23 and 0.11 for L4-S1 lordosis fornon-obese and obese cohorts respectively) and SF-36 physical functioning where the non-obese cohort not statistically improve (P=0.08). Patients with a BMI ≥ 30 demonstrated an increased incidence of cardiovascular complications (P=0.0293), acute kidney injury (P=0.0241), rod fractures (P=0.0293), and reoperations (P=0.0241) when compared to patients with a BMI < 30. CONCLUSION: This study adds to a growing body of evidence linking demographic factors with risks of hardware failure. Further, this data challenges the assumption that obese patients may not receive sufficient benefit to be long-segment surgical candidates. However, given their elevated risk for post-operative and delayed hardware complications, obese patients should be appropriately counseling before undergoing surgery.

Successful treatment of medically and surgically refractory lymphocytic hypophysitis with fractionated stereotactic radiotherapy: a single-center experience and systematic literature review.

PURPOSE: To explore the potential role of focused radiotherapy in managing the lymphocytic hypophysitis (LH) refractory to medical therapy and surgery. METHOD: A systematic literature review was conducted following PRISMA guidelines to identify the studies on radiation treatment for hypophysitis, along with the experience in our institution. RESULTS: The study included eight patients, three from our institution and five from existing literature. The age at presentation ranged from 37 to 75 years old, with a median age of 58. The presenting symptoms involved headache in seven patients and diplopia in two patients. Pre-radiation visual field defects were noticed in four patients. All patients exhibited variable degrees of hypopituitarism before radiation, with oral corticosteroids being the initial medical treatment. Immunosuppressive therapy was attempted in two patients prior to radiation. Seven patients had a history of transsphenoidal surgery with a histologically confirmed LH. Three patients underwent stereotactic radiosurgery (SRS), while the remaining received FSRT, with a mean irradiation volume of 2.2 cm3. A single-session total dose of 12 -15 Gy was administered in the SRS group. In the FSRT group, doses ranged from 24 to 30 Gy with a median dose of 25 Gy, delivered in 2 Gy fractions. Four patients achieved a resolution of visual field defects, while another two patients demonstrated improvement in their associated focal neurologic deficits. No change in pre-existing endocrine status was shown after radiation, except in one patient. Clinical response was achieved in seven patients after a single course of radiation, while one patient required the second course. Six patients remained stable on low-dose glucocorticoid during at least a 12-month follow-up period, and one discontinued it entirely without experiencing relapse. Three patients demonstrated a complete radiologic response, while the remaining showed a partial radiologic response. CONCLUSIONS: Focused radiation, including FSRT, can play a role in symptomatic relief, effective mass shrinkage, and minimizing radiation exposure to critical surrounding structures in patients with refractory LH. However, further research efforts are necessary to better clarify its effects and optimal dose planning.

Use of global sagittal flexibility to predict proximal junctional kyphosis after spinal deformity surgery.

OBJECTIVE: Sagittal alignment is an important predictor of functional outcomes after surgery for adult spinal deformity (ASD). A rigid spinal column may create a large lever arm that may impact the rate of proximal junctional kyphosis (PJK) after ASD surgery. In this study, the authors sought to determine whether relatively low preoperative global spinal flexibility (i.e., rigid spine) predicts increased incidence of PJK at 1 year after ASD surgery. METHODS: The authors retrospectively reviewed long-segment thoracolumbar fusions with pelvic fixation performed at a single tertiary care center between October 2015 and September 2020 in patients with a minimum of 1-year radiographic and clinical follow-up. Two cohorts were established on the basis of the optimal value for spinal flexibility, as defined by the absolute difference between the preoperative standing and supine C7 sagittal vertical axes, which the authors termed global sagittal flexibility (GSF). Demographic information, radiographs, various associated complications, and patient-reported outcome measures (PROMs) were analyzed. RESULTS: Eighty-five patients met the inclusion criteria. Receiver operating characteristic (ROC) analysis using GSF to predict an increase in the proximal junctional sagittal Cobb angle (PJCA) greater than or equal to 10° at 1-year follow-up provided an area under the curve of 0.64 and identified an optimal GSF threshold value of 3.7 cm. Patients with GSF > 3.7 cm were considered globally flexible (48 patients), and those with GSF ≤ 3.7 cm were classified as rigid (37 patients). Rigid patients were noted to have a significantly higher risk of ΔPJCA ≥ 10° at 1-year follow-up (51.4% vs 29.3%, p = 0.049). No changes in the reoperation rates or PROMs based on GSF were observed in the 1- or 2-year postoperative window. CONCLUSIONS: Based on these retrospective data, preoperative global spinal rigidity portends an independently elevated risk for the development of PJK after ASD surgery. No differences in other complication rates or PROMs data were observed between groups. Data collection was limited to a 2-year postoperative window; therefore, longer follow-up is required to further elucidate the relationship between rigidity and reoperation rates. Based on these retrospective data, flexibility may influence the outcomes of patients with ASD.

Investigating Deferral Rates in Cochlear Implantation: How Often Do Candidates Defer and Why?

OBJECTIVE: Evaluate the rate at which cochlear implant (CI) candidates decline surgery and identify associated factors. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Four hundred ninety-three CI candidates from July 1989 to December 2020 with complete demographic and socioeconomic data. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: Age, sex, race, marital and employment status, median household income percentile, distance-to-CI-center, and residence in a medically underserved county. RESULTS: Of the 493 CI candidates included, 80 patients (16.2%) declined surgery. Based on chart checking, the most common reason patients did not receive the implant was due to loss of follow-up (38%). African American patients were 73% less likely to undergo implantation compared with White patients (odds ratio [OR], 0.27 [0.11-0.68]; p = 0.005). Asian patients were 95% less likely to undergo implantation (OR, 0.05 [0.009-0.25]; p = 0.0003) compared with White patients. For every 1-year age increase, patients were 4% less likely to undergo implantation (OR, 0.96 [0.94-0.98]; p < 0.0001) and for every 10-year age increase, the patients were 33% less likely. Compared with their single counterparts, married patients were more likely to undergo implantation (OR, 1.87 [1.12-3.15]; p = 0.02). No differences were observed when comparing implanted and nonimplanted CI candidates in sex, employment status, distance-to-CI-center, or median family income percentile. A χ2 test of independence showed no association between receiving CIs and living in medically underserved counties ( χ2 = 2; N = 493; 0.3891; p = 0.53). CONCLUSIONS: Not infrequently, CI candidates decline surgery. Although demographic factors (race, age, and marital status) were associated with the cochlear implantation decision, socioeconomic factors (median family income and residence in a medically underserved community) were not. Perhaps cultural components of a patient's race have a larger impact on whether or not the patients get implanted.

Noise-induced hearing loss in the contralateral ear during otologic and neurotologic surgeries.

OBJECTIVE: Noise-induced hearing loss in the non-surgical ear during otologic/neurotologic surgery has not been well studied. The purpose of this study was to evaluate changes in hearing that may occur in the contralateral (i.e., non-surgical) ear after various otologic/neurotologic surgeries due to noise generated by drills. We hypothesized that otologic/neurotologic surgeries, longer in duration, would suggest longer drilling times and result in decreased hearing in the contralateral ear as evidenced by a change post-operative pure tone air conduction thresholds when compared to pre-operative thresholds. METHODS: A retrospective chart review at a tertiary referral center. Adult patients (18-75 years old) who underwent otologic/neurotologic surgeries from May 1, 2016 through May 1, 2021 were considered for inclusion. Surgeries included vestibular schwannoma resection (translabyrinthine, middle cranial fossa, or retrosigmoid approaches), endolymphatic sac/shunt and labyrinthectomy for Meniere's disease, and tympanomastoid surgery for middle ear pathology (e.g., cholesteatoma). Patient characteristics obtained through record review included age, sex, surgical procedure, pre-operative and post-operative audiometric thresholds and word recognition scores (WRS) for the contralateral ear, and duration of surgery. RESULTS: No significant differences were observed for change in audiometric thresholds in the contralateral ear for any surgery when considering individual frequencies. Additionally, no significant change in WRS was observed for any surgical approach. CONCLUSIONS: The risk of hearing loss in the non-surgical ear during various otologic/neurotologic surgeries appears to be minimal when measured via routine clinical tests.

Arthroscopic Assisted, Lateral Ligament Reconstruction with Suture Tape Augmentation and Knotless All Suture Anchors: A Technique Guide.

More than 30,000 ankle sprains occur each day in the United States, and the majority of ankle sprains involve the anterior talofibular ligament. Up to 30% of patients develop functional ankle instability and chronic pain after a severe ankle sprain. When nonoperative measures are unsuccessful, operative reconstruction of the lateral ankle ligaments is recommended. To further strengthen the repair, accelerate rehabilitation, and allow for a quicker return to sport, augmentation with suture tape has recently become an alternative among surgeons in the reconstruction of the lateral ankle ligaments. Moreover, the advent of knotless all-suture anchors decreases the number of knots required in the procedure and, in theory, reduces lateral soft tissue irritation and accentuates recovery after surgery. Here we present our technique for arthroscopic assisted, lateral ligament reconstruction with suture tape augmentation and knotless all suture anchors.

Demineralized Bone Matrix and Fibers in Spinal Fusion.

Formation of bony fusion after arthrodesis depends on osteoinduction, osteoconduction, and osteogenesis. Traditionally, the patient's own bone, or autograft, has been used to provide biological material necessary for these steps. However, the amount of autograft obtainable is often inadequate. Modern spine surgery has adopted the use of many autograft extenders or replacements, such as demineralized bone matrix or fibers. The present article covers the history of bone grafting, the production and technical details of demineralized bone matrix, and the evidence supporting its use in spine fusions.

Unlocking the Healing Potential: Cannabinoids in Spine Surgery for Pain Relief and Recovery.

¼ Cannabinoids, such as D9-tetrahydrocannabinol and cannabidiol, interact with endocannabinoid receptors in the central nervous system and immune system, potentially offering pain relief. The entourage effect, resulting from the interaction of multiple cannabis components, may enhance therapeutic impact and efficacy, making them promising candidates for exploring pain relief in spine operations, known to be among the most painful operative procedures.¼ The use of cannabinoids in pain management requires careful consideration of safety, including their cognitive and psychomotor effects, potential cardiovascular risks, risk of dependence, mental health implications, and drug interactions.¼ Few studies have analyzed cannabinoid use in relation to spine surgery, with variable results reported, indicating possible effects on reoperation rates, mortality, complications, postoperative opioid use, and length of hospital stay.¼ Current knowledge gaps exist in the understanding of cannabinoid effects on spine surgery, including the exploration of different administration routes, timing, dosage, and specific outcomes. In addition, mechanistic explanations for the observed results are lacking.¼ Ethical considerations related to informed consent, medical expertise, societal impact, and legal compliance must also be thoroughly addressed when considering the utilization of cannabinoids in spinal pathologies and back pain treatment.

Resection of intradural intramedullary subependymoma of the cervicothoracic spine: 2-dimensional operative video.

This video presents the case of a 44-year-old male with a 2-year history of pain in the left upper extremity that had worsened over the course of the last 6 months with associated weakened grip strength and had extended into his right arm. T2-weighted sagittal and axial MRI demonstrated an expansive nonenhancing solid intramedullary lesion extending from C5 to T1. The patient underwent a C5-T1 laminectomy and laminoplasty with near-complete resection of the intradural intramedullary subependymoma. At 3 months' follow-up, he reported doing well and had experienced significant improvement in motor strength with ongoing therapies.

Real-time ultrasound guidance in the endoscopic endonasal resection of a retro-odontoid pannus: Technical note and case illustration.

Background and Objectives: Odontoidectomy is a surgical procedure indicated in the setting of various pathologies, with the main goal of decompressing the ventral brain stem and spinal cord as a result of irreducible compression at the craniovertebral junction. The endoscopic endonasal approach has been increasingly used as an alternative to the transoral approach as it provides a straightforward, panoramic, and direct approach to the odontoid process. In addition, intraoperative ultrasound (US) guidance is a technique that can optimize safety and surgical outcomes in this context. It is used as an adjunct to neuronavigation and provides intraoperative confirmation of decompression of craniovertebral junction structures in real time. The authors aim to present the use and safe application of real-time intraoperative US guidance during endonasal endoscopic resection of a retro-odontoid pannus. Methods: A retrospective chart review of a single case was performed and presented herein as a case report and narrated operative video. Results: A minimally invasive US transducer was used intraoperatively to guide the resection of a retro-odontoid pannus and confirm spinal cord decompression in real time. Postoperative examination of the patient revealed immediate neurological improvement. Conclusions: Intraoperative ultrasonography is a well described and useful modality in neurosurgery. However, the use of intraoperative US guidance during endonasal endoscopic approaches to the craniovertebral junction has not been previously described. As demonstrated in this technical note, the authors show that this imaging modality can be added to the ever-evolving armamentarium of neurosurgeons to safely guide the decompression of neural structures within the craniocervical junction with good surgical outcomes.

Long-term safety of MRI-guided administration of AAV2-GDNF and gadoteridol in the putamen of individuals with Parkinson's disease.

Direct putaminal infusion of adeno-associated virus vector (serotype 2) (AAV2) containing the human glial cell line-derived neurotrophic factor (GDNF) transgene was studied in a phase I clinical trial of participants with advanced Parkinson's disease (PD). Convection-enhanced delivery of AAV2-GDNF with a surrogate imaging tracer (gadoteridol) was used to track infusate distribution during real-time intraoperative magnetic resonance imaging (iMRI). Pre-, intra-, and serial postoperative (up to 5 years after infusion) MRI were analyzed in 13 participants with PD treated with bilateral putaminal co-infusions (52 infusions in total) of AAV2-GDNF and gadoteridol (infusion volume, 450 mL per putamen). Real-time iMRI confirmed infusion cannula placement, anatomic quantification of volumetric perfusion within the putamen, and direct visualization of off-target leakage or cannula reflux (which permitted corresponding infusion rate/cannula adjustments). Serial post-treatment MRI assessment (n = 13) demonstrated no evidence of cerebral parenchyma toxicity in the corresponding regions of AAV2-GDNF and gadoteridol co-infusion or surrounding regions over long-term follow-up. Direct confirmation of key intraoperative safety and efficacy parameters underscores the safety and tissue targeting value of real-time imaging with co-infused gadoteridol and putative therapeutic agents (i.e., AAV2-GDNF). This delivery-imaging platform enhances safety, permits delivery personalization, improves therapeutic distribution, and facilitates assessment of efficacy and dosing effect.

Use of a novel ball-joint guide array for magnetic resonance imaging-guided cannula placement and convective delivery: technical note.

OBJECTIVE: The objective of this study was to assess the feasibility, accuracy, effectiveness, and safety of an MRI-compatible frameless stereotactic ball-joint guide array (BJGA) as a platform for cannula placement and convection-enhanced delivery (CED). METHODS: The authors analyzed the clinical and imaging data from consecutive patients with aromatic l-amino acid decarboxylase (AADC) deficiency who underwent infusion of adeno-associated virus (AAV) containing the AADC gene (AAV2-AADC). RESULTS: Eleven patients (7 females, 4 males) underwent bilateral MRI-guided BJGA cannula placement and CED of AAV2-AADC (22 brainstem infusions). The mean age at infusion was 10.5 ± 5.2 years (range 4-19 years). MRI allowed for accurate real-time planning, confirmed precise cannula placement after single-pass placement, and permitted on-the-fly adjustment. Overall, the mean bilateral depth to the target was 137.0 ± 5.2 mm (range 124.0-145.5 mm). The mean bilateral depth error was 0.9 ± 0.7 mm (range 0-2.2 mm), and the bilateral radial error was 0.9 ± 0.6 mm (range 0.1-2.3 mm). The bilateral absolute tip error was 1.4 ± 0.8 mm (range 0.4-3.0 mm). Target depth and absolute tip error were not correlated (Pearson product-moment correlation coefficient, r = 0.01). CONCLUSIONS: Use of the BJGA is feasible, accurate, effective, and safe for cannula placement, infusion MRI monitoring, and cannula adjustment during CED. The low-profile universal applicability of the BJGA streamlines and facilitates MRI-guided CED.

Effects of exogenous ghrelin administration and ghrelin receptor blockade, in combination with alcohol, on peripheral inflammatory markers in heavy-drinking individuals: Results from two human laboratory studies.

The ghrelin system has been garnering interest for its role in different neuropsychiatric disorders, including alcohol use disorder (AUD). Accordingly, targeting the ghrelin system is under investigation as a potential novel therapeutic approach. While alcohol provokes the immune system and inflammatory responses, ghrelin has potent immunomodulatory and anti-inflammatory properties. The present study aimed to shed light on the "crosstalk" between ghrelin and inflammation by examining the effects of exogenous ghrelin administration and ghrelin receptor blockade on peripheral inflammatory markers in the context of two human laboratory studies with alcohol administration. Non-treatment-seeking, heavy-drinking individuals with alcohol dependence, the majority of whom were African American males, were enrolled. In the first randomized, crossover, double-blind, placebo-controlled human laboratory study, participants underwent two experimental paradigms - an intravenous alcohol self-administration (IV-ASA) and an intravenous alcohol clamp (IV-AC) - each consisting of two counterbalanced sessions (ghrelin, placebo). A loading dose of intravenous ghrelin (3 mcg/kg) or placebo, followed by a continuous ghrelin (16.9 ng/kg/min) or placebo infusion was administered. In the second dose-escalating, single-blind, placebo-controlled human laboratory phase 1b study, participants were dosed with an oral ghrelin receptor blocker (PF-5190457) and underwent an oral alcohol challenge. Repeated blood samples were collected, and plasma concentrations of the following inflammatory markers were measured: C-reactive protein (CRP), interleukin (IL)-6, IL-10, IL-18, and tumor necrosis factor alpha (TNF-α). During the IV-ASA experiment, significant drug × time interaction effects were observed for IL-6 (F3,36 = 3.345, p = 0.030) and IL-10 (F3,53.2 = 4.638, p = 0.006), indicating that ghrelin, compared to placebo, significantly reduced blood concentrations of the proinflammatory cytokine IL-6, while increasing blood concentrations of the anti-inflammatory cytokine IL-10. No significant drug × time interaction effects were observed during the IV-AC experiment, possibly because of its much shorter duration and/or smaller sample. Treatment with PF-5190457, compared to placebo, had no significant effect on the inflammatory markers investigated. In conclusion, a supraphysiologic pharmacological challenge with exogenous ghrelin in heavy-drinking individuals produced anti-inflammatory effects in the context of intravenous alcohol administration. On the contrary, ghrelin receptor blockade did not lead to any change in the inflammatory markers included in this study. Mechanistic studies are required to better understand the interaction between ghrelin, alcohol, and inflammatory processes.

Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: a randomized, double-blind, placebo-controlled, human laboratory study.

As perspectives on cannabis continue to shift, understanding the physiological and behavioral effects of cannabis use is of paramount importance. Previous data suggest that cannabis use influences food intake, appetite, and metabolism, yet human research in this regard remains scant. The present study investigated the effects of cannabis administration, via different routes, on peripheral concentrations of appetitive and metabolic hormones in a sample of cannabis users. This was a randomized, crossover, double-blind, placebo-controlled study. Twenty participants underwent four experimental sessions during which oral cannabis, smoked cannabis, vaporized cannabis, or placebo was administered. Active compounds contained 6.9 ± 0.95% (~50.6 mg) ∆9-tetrahydrocannabinol (THC). Repeated blood samples were obtained, and the following endocrine markers were measured: total ghrelin, acyl-ghrelin, leptin, glucagon-like peptide-1 (GLP-1), and insulin. Results showed a significant drug main effect (p = 0.001), as well as a significant drug × time-point interaction effect (p = 0.01) on insulin. The spike in blood insulin concentrations observed under the placebo condition (probably due to the intake of brownie) was blunted by cannabis administration. A significant drug main effect (p = 0.001), as well as a trend-level drug × time-point interaction effect (p = 0.08) was also detected for GLP-1, suggesting that GLP-1 concentrations were lower under cannabis, compared to the placebo condition. Finally, a significant drug main effect (p = 0.01) was found for total ghrelin, suggesting that total ghrelin concentrations during the oral cannabis session were higher than the smoked and vaporized cannabis sessions. In conclusion, cannabis administration in this study modulated blood concentrations of some appetitive and metabolic hormones, chiefly insulin, in cannabis users. Understanding the mechanisms underpinning these effects may provide additional information on the cross-talk between cannabinoids and physiological pathways related to appetite and metabolism.