Cannabis and Anxiety: A Critical Review.

Introduction: Cannabis has been reported to have both anxiogenic and anxiolytic effects. Habitual cannabis use has been associated with anxiety disorders (AD). The causal pathways and mechanisms underlying the association between cannabis use (CU)/cannabis use disorder (CUD) and anxiety remain unclear. We examined the literature via a systematic review to investigate the link between cannabis and anxiety. The hypotheses studied include causality, the common factor theory, and the self-medication hypothesis. Methods: Critical systematic review of published literature examining the relationship of CU/CUD to AD or state-anxiety, including case reports, literature reviews, observational studies, and preclinical and clinical studies. A systematic MEDline search was conducted of terms including: [anxiety], [anxiogenic], [anxiolytic], [PTSD], [OCD], [GAD], [cannabis], [marijuana], [tetrahydrocannabinol], [THC]. Results: While several case-control and cohort studies have reported no correlation between CU/CUD and AD or state anxiety (N = 5), other cross-sectional, and longitudinal studies report significant relationships (N = 20). Meta-analysis supports anxiety correlating with CU (N = 15 studies, OR = 1.24, 95% CI: 1.06-1.45, p = 0.006) or CUD (N = 13 studies, OR = 1.68, 95% CI: 1.23-2.31, p = 0.001). PATH analysis identifies the self-medication hypothesis (N = 8) as the model that best explains the association between CU/CUD and AD or state-anxiety. Despite the support of multiple large cohort studies, causal interpretations (N = 17) are less plausible, while the common factor theory (N = 5), stress-misattribution hypothesis, and reciprocal feedback theory lack substantial evidential support. Conclusion: The association between cannabis and anxiety is best explained by anxiety predisposing individuals toward CU as a method of self-medication. A causal relationship in which CU causes AD incidence is less likely despite multiple longitudinal studies suggesting so.

Smoking As a Risk Factor for Postcraniotomy 30-Day Mortality.

BACKGROUND: There is limited information on the impact of smoking on postcraniotomy mortality. In this study we used the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) to examine this issue. METHODS: We identified 16,280 postcraniotomy patients in the ACS-NSQIP database. Indications for surgery were categorized by vascular, trauma, epilepsy, malignant tumor, and benign tumor. Univariate and multivariable logistic regression analyses were used to identify risk factors associated with mortality. RESULTS: In the ACS-NSQIP dataset, postcraniotomy mortality within 30 days of surgery was 5.03%. An area under the curve analysis indicated 30 pack-years as the optimal discriminating threshold for risk stratification in terms of 30-day postcraniotomy mortality. Using this threshold, multivariate analyses revealed 3 variables that were closely associated with 30-day post-craniotomy mortality: male gender (P = 0.002), indication for operation (P < 0.001), and a smoking history of ≥30 pack-years (P < 0.001). In subsequent stratified analyses, smoking-associated mortality risk was observed only in males (odds ratio of 2.33 comparing males with ≥30 and <30 pack-years of smoking history; 97.5% confidence interval 1.36-4.03). When the analysis was further stratified by surgical indications, the mortality association with smoking was found only in male patients who underwent craniotomy as treatment for neurovascular diseases (odds ratio 3.88, 97.5% confidence interval 1.39-11.65). Such an association was not seen in patients who underwent craniotomy for traumatic brain injury, malignant tumors, benign tumors, or epilepsy. CONCLUSIONS: This study identified ≥30 pack-years as a risk factor for male patients undergoing craniotomy as treatment for neurovascular diseases.

An fMRI investigation of the neural correlates underlying the autonomous sensory meridian response (ASMR).

Introduction : The "autonomous sensory meridian response" (ASMR) is a neologism used to describe an internal sensation of deep relaxation and pleasant head tingling which is often stimulated by gentle sounds, light touch, and personal attention. Methods : An fMRI-based methodology was employed to examine the brain activation of subjects prescreened for ASMR-receptivity (n=10) as they watched ASMR videos and identified specific moments of relaxation and tingling. Results : Subjects who experienced ASMR showed significant activation in regions associated with both reward (NAcc) and emotional arousal (dACC and Insula/IFG). Brain activation during ASMR showed similarities to patterns previously observed in musical frisson as well as affiliative behaviors. Conclusion : This is the first study to measure the activation of various brain regions during ASMR and these results may help to reveal the mechanistic underpinnings of this sensation.

Intraoperative Magnetic Resonance Imaging-Guided Biopsy in the Diagnosis of Suprasellar Langerhans Cell Histiocytosis.

BACKGROUND: Magnetic resonance imaging (MRI)-guided biopsy is an emerging diagnostic technique that holds great promise for otherwise difficult to access neuroanatomy. CASE DESCRIPTION: Here we describe MRI-guided biopsy of a suprasellar lesion located posterior and superior to the pituitary stalk. The approach was implemented successfully in a 38-year-old woman who had developed progressive visual deterioration. CONCLUSION: Intraoperative MRI revealed the need for trajectory adjustment due to an unintended, minor deviation in the burr hole entry point, demonstrating the benefit of an MRI-guided approach. Langerhans cell histiocytosis was diagnosed after biopsy, and the lesion regressed after cladribine treatment. Technical nuances of the case are reviewed in the context of the available literature.

The Use of Cannabis for Headache Disorders.

Headache disorders are common, debilitating, and, in many cases, inadequately managed by existing treatments. Although clinical trials of cannabis for neuropathic pain have shown promising results, there has been limited research on its use, specifically for headache disorders. This review considers historical prescription practices, summarizes the existing reports on the use of cannabis for headache, and examines the preclinical literature exploring the role of exogenous and endogenous cannabinoids to alter headache pathophysiology. Currently, there is not enough evidence from well-designed clinical trials to support the use of cannabis for headache, but there are sufficient anecdotal and preliminary results, as well as plausible neurobiological mechanisms, to warrant properly designed clinical trials. Such trials are needed to determine short- and long-term efficacy for specific headache types, compatibility with existing treatments, optimal administration practices, as well as potential risks.

Management and Survival Patterns of Patients with Gliomatosis Cerebri: A SEER-Based Analysis.

OBJECTIVE: We used the SEER (Surveillance Epidemiology and End Results) database (1999-2010) to analyze the clinical practice patterns and overall survival in patients with gliomatosis cerebri (GC), or glioma involving 3 or more lobes of the cerebrum. METHODS: We identified 111 patients (age ≥18 years) with clinically or microscopically diagnosed GC in the SEER database. Analyses were performed to determine clinical practice patterns for these patients and whether these practices were associated with survival. RESULTS: Fifty-eight percent of the 111 patients with GC received microscopic confirmation of their diagnosis. Of the remaining patients, 40% were diagnosed via imaging or laboratory tests, and 2% had unknown methods of diagnosis. Seven percent of patients who did not have microscopic confirmation of their diagnosis received radiation therapy. Radiation therapy and surgery were not associated with survival. The only variable significantly associated with overall survival was age at diagnosis. Patients aged 18-50 years showed improved survival relative to patients aged >50 years (median survival, 11 and 6 months, respectively; P = 0.03). For patients aged >50 years, improved overall survival was observed in the post-temozolomide era (2005-2010) relative to those treated in the pre-temozolomide era (1999-2004) (median survival, 9 and 4 months, respectively; P = 0.005). CONCLUSIONS: In the SEER database, ∼40% of the patients with glioma with imaging findings of GC do not receive microscopic confirmation of their diagnosis. We propose that tissue confirmation is warranted in patients with GC, because genomic analysis of these specimens may provide insights that will contribute to meaningful therapeutic intervention.

Mouse Model for Protein Tyrosine Phosphatase D (PTPRD) Associations with Restless Leg Syndrome or Willis-Ekbom Disease and Addiction: Reduced Expression Alters Locomotion, Sleep Behaviors and Cocaine-Conditioned Place Preference.

The receptor type protein tyrosine phosphatase D (PTPRD) gene encodes a cell adhesion molecule likely to influence development and connections of addiction-, locomotion- and sleep-related brain circuits in which it is expressed. The PTPRD gene harbors genome-wide association signals in studies of restless leg syndrome (Willis-Ekbom disease [WED]/restless leg syndrome [RLS]; p < 10-8) and addiction-related phenotypes (clusters of nearby single nucleotide polymorphisms [SNPs] with 10-2 > p > 10-8 associations in several reports). We now report work that seeks (a) association between PTPRD genotypes and expression of its mRNA in postmortem human brains and (b) RLS-related, addiction-related and comparison behavioral phenotypes in hetero- and homozygous PTPRD knockout mice. We identify associations between PTPRD SNPs and levels of PTPRD mRNA in human brain samples that support validity of mouse models with altered PTPRD expression. Knockouts display less behaviorally defined sleep at the end of their active periods. Heterozygotes move more despite motor weakness/impersistence. Heterozygotes display shifted dose-response relationships for cocaine reward. They display greater preference for places paired with 5 mg/kg cocaine and less preference for places paired with 10 or 20 mg/kg. The combined data provide support for roles for common, level-of-expression PTPRD variation in locomotor, sleep and drug reward phenotypes relevant to RLS and addiction. Taken together, mouse and human results identify PTPRD as a novel therapeutic target for RLS and addiction phenotypes.