Self-administration of Psilocybin for the Acute Treatment of Migraine: A Case Report.

Background: Migraine is a common neurovascular disorder with a pathophysiology related to the serotonin (5-hydroxytryptamine; 5-HT) system. Pharmacologic modulation of 5-HT receptors has demonstrated efficacy in the acute treatment of migraines. Psilocybin, a classic psychedelic with 5-HT receptor activity, has demonstrated therapeutic potential in the management of neuropsychiatric conditions. To date, no reports have investigated the effect of psilocybin administered acutely during a migraine episode. Case presentation: The case of a 33-year-old male patient with a history of migraines with aura, who had acute administration of oral psilocybin (in the form of the dried fruiting body of Psilocybe cubensis mushrooms) at migraine onset is presented. Headache intensity was rated hourly using the Numerical Rating Scale (NRS) and compared to three previous migraines. Profound reductions in headache intensity and emetic episodes were reported during the migraine treated acutely with oral psilocybin administration, compared to three previous migraines. Discussion: The severe, disabling, and treatment-resistant nature of migraines warrants continued surveillance for novel pharmacologic interventions. The established congruous pathophysiology of migraine and pharmacology of psilocybin, via the 5-HT receptor system, positions psilocybin as a potential therapeutic target. Conclusion: While this report highlights the potential role of psilocybin in the acute management of migraines, it is essential to note that it should not be considered a basis for guiding clinical practice at this point. Further research is necessary to establish the safety and efficacy of psilocybin as a treatment option for migraines.

N, N-Dimethyltryptamine (DMT)-Occasioned Familiarity and the Sense of Familiarity Questionnaire (SOF-Q).

This study investigated the sense of familiarity attributed to N, N-dimethyltryptamine (DMT) experiences. 227 naturalistic inhaled-DMT experiences reporting a sense of familiarity were included. No experiences referenced a previous DMT or psychedelic experience as the source of the familiarity. A high prevalence of concomitant features discordant from ordinary consciousness were identified: features of a mystical experience (97.4%), ego-dissolution (16.3%), and a "profound experience of death" (11.0%). The Sense of Familiarity Questionnaire (SOF-Q) was developed assessing 19 features of familiarity across 5 themes: (1) Familiarity with the Feeling, Emotion, or Knowledge Gained; (2) Familiarity with the Place, Space, State, or Environment; (3) Familiarity with the Act of Going Through the Experience; (4) Familiarity with Transcendent Features; and (5) Familiarity Imparted by an Entity Encounter. Bayesian latent class modeling yielded two stable classes of participants who shared similar SOF-Q responses. Class 1 participants responded, "yes" more often for items within "Familiarity Imparted by an Entity Encounter" and "Familiarity with the Feeling, Emotion, or Knowledge Gained." Results catalogued features of the sense of familiarity imparted by DMT, which appears to be non-referential to a previous psychedelic experience. Findings provide insights into the unique and enigmatic familiarity reported during DMT experiences and offer a foundation for further exploration into this intriguing phenomenon.

Medical Care Among Individuals with a Concussion in Ontario: A Population-based Study.

BACKGROUND: Concussion affects 1.2% of the population annually; rural regions and children have higher rates of concussion. METHODS: Using administrative health care linked databases, all residents of Ontario with a physician diagnosed concussion were identified using ICD-9 code 850 or ICD-10 code S06. Cases were tracked for 2 years for concussion-related health care utilization with relevant specialist physicians (i.e., neurology, otolaryngology, physiatry, psychiatry, ophthalmology). Billing codes, specialist codes, and time from index to visit were analyzed. Factors associated with increased specialist visits were also examined. RESULTS: In total, 1,022,588 cases were identified between 2008 and 2014 with 2 years of post-concussion health care utilization available. Follow-up by physician within 3 days of injury occurred in only 14% of cases. Mean time between ED diagnosis and follow-up by a physician was 83.9 days, whereas for rural regions it was >100 days. About half of adults (51.9%) and children (50.3%) had at least 1 specialist visit following concussion. Mean time between injury and first specialist visit was 203.8 (SD 192.9) days for adults, 213.5 (SD 201.0) days for rural adults, and 276.0 (SD 202.6) days for children. There were 67,420 neurology visits, 70,404 psychiatry visits, 13,571 neurosurgery visits, 19,780 physiatry visits, 101,788 ENT visits, and 103,417 ophthalmology visits in the 2 years tracking period. Factors associated with more specialist use included age > 18 years, urban residence, and pre-injury psychiatric history. CONCLUSIONS: There are discrepancies in post-concussion health care utilization based on age group and rural/urban residence. Addressing these risk factors could improve concussion care access.

Revisiting the ICHD-3 criteria for headache attributed to mild traumatic injury to the head: Insights from the Toronto Concussion Study Analysis of Acute Headaches Following Concussion.

BACKGROUND: There is limited prospective data on the prevalence, timing of onset, and characteristics of acute headache following concussion/mild traumatic brain injury. METHODS: Adults diagnosed with concussion (arising from injuries not related to work or motor vehicle accidents) were recruited from emergency departments and seen within one week post injury wherein they completed questionnaires assessing demographic variables, pre-injury headache history, post-injury headache history, and the Sport Concussion Assessment Tool (SCAT-3) symptom checklist, the Sleep and Concussion Questionnaire (SCQ) and mood/anxiety on the Brief Symptom Inventory (BSI). RESULTS: A total of 302 participants (59% female) were enrolled (mean age 33.6 years) and almost all (92%) endorsed post-traumatic headache (PTH) with 94% endorsing headache onset within 24 hours of injury. Headache location was not correlated with site of injury. Most participants (84%) experienced daily headache. Headache quality was pressure/squeezing in 69% and throbbing/pulsing type in 22%. Associated symptoms included: photophobia (74%), phonophobia (72%) and nausea (55%). SCAT-3 symptom scores, Brief Symptom Inventory and Sleep and Concussion Questionnaire scores were significantly higher in those endorsing acute PTH. No significant differences were found in week 1 acute PTH by sex, history of migraine, pre-injury headache frequency, anxiety, or depression, nor presence/absence of post-traumatic amnesia and self-reported loss of consciousness. CONCLUSIONS: This study highlights the very high incidence of acute PTH following concussion, the timing of onset and characteristics of acute PTH, the associated psychological and sleep disturbances and notes that the current ICHD-3 criteria for headaches attributed to mild traumatic injury to the head are reasonable, the interval between injury and headache onset should not be extended beyond seven days and could, potentially, be shorted to allow for greater diagnostic precision.

Phenomenology and content of the inhaled N, N-dimethyltryptamine (N, N-DMT) experience.

Understanding the phenomenology and content of the inhaled N, N, dimethyltryptamine (N, N-DMT) experience is critical to facilitate and support ongoing research and therapeutic models targeting mental health conditions and central nervous system pathology. A qualitative analysis was conducted of all N, N-DMT experiences posted to the r/DMT Reddit community over a 10-year period from 2009 to 2018. A total of 3778 experiences from 3305 posts were included in this study. A median dose of N, N-DMT of 40.0 mg [interquartile range (IQR), 27.5 to 50.0] and a median experience duration of 10 min (IQR, 5.0 to 15.0) were identified. The most common somatic effects were somaesthesias (n = 1415, 37.5%) and an auditory ringing (n = 583, 15.4%). Visualizations predominantly consisted of fractals, shapes, patterns (n = 1231, 32.6%) and vivid colours (n = 953, 25.2%). Entity encounters were reported in 45.5% (n = 1719) of the experiences and involved predominantly a feminine phenotype (n = 416, 24.2%); deities (n = 293, 17.0%); aliens (n = 281, 16.3%); creature-based entities (n = 158, 9.2%, including reptilian and insectoid beings); mythological beings (n = 144, 8.4%, including machine elves); and jesters (n = 112, 6.5%). Entity interactions were predominantly positive (n = 600, 34.9% of encounters) involving benevolent, comforting, protecting, or outwardly caring interactions. A companion-type, pedagogical, or guide-type interaction was identified 32.4% of encounters (n = 557). Common typology, architecture, and structural features of the "DMT world" included descriptions of alternate or higher dimensions (n = 952, 25.2%); rooms [n = 582, 15.4%, including the "waiting room" (n = 105, 2.8%)], and a tunnel (n = 390, 10.3%). Features of mystical and ego-dissolution experiences were common. Additional rewarding aspects were identified, including a sense of familiarity and the acceptance/removal of the fear of death. Challenging and difficult responses were less frequent but also documented. Statements of profundity were identified in 232 experiences (6.1%), including pronouncing the experience or an aspect of the experience as the most "beautiful" or feeling the most "beautiful" of their life (n = 47, 1.2%). This study identified common phenomenological themes and content of naturalistic inhaled N, N-DMT experiences. Major thematic domains included (1) physical and somatic experiences; (2) visualizations and imagery; (3) entity encounters including entity phenotype, descriptors, attributes, disposition, and characteristics of the interaction; (4) typology, architectural features, structural characteristics, and scenery of the "DMT world"; (5) alerations in consciousness (including mystical experiences, out-of-body experiences, and ego-dissolution); (6) emotional responses (including positive, rewarding, difficult, and challenging); and (7) statements of profundity.

Prediction of risk of prolonged post-concussion symptoms: Derivation and validation of the TRICORDRR (Toronto Rehabilitation Institute Concussion Outcome Determination and Rehab Recommendations) score.

BACKGROUND: Approximately 10% to 20% of people with concussion experience prolonged post-concussion symptoms (PPCS). There is limited information identifying risk factors for PPCS in adult populations. This study aimed to derive a risk score for PPCS by determining which demographic factors, premorbid health conditions, and healthcare utilization patterns are associated with need for prolonged concussion care among a large cohort of adults with concussion. METHODS AND FINDINGS: Data from a cohort study (Ontario Concussion Cohort study, 2008 to 2016; n = 1,330,336) including all adults with a concussion diagnosis by either primary care physician (ICD-9 code 850) or in emergency department (ICD-10 code S06) and 2 years of healthcare tracking postinjury (2008 to 2014, n = 587,057) were used in a retrospective analysis. Approximately 42.4% of the cohort was female, and adults between 18 and 30 years was the largest age group (31.0%). PPCS was defined as 2 or more specialist visits for concussion-related symptoms more than 6 months after injury index date. Approximately 13% (73,122) of the cohort had PPCS. Total cohort was divided into Derivation (2009 to 2013, n = 417,335) and Validation cohorts (2009 and 2014, n = 169,722) based upon injury index year. Variables selected a priori such as psychiatric disorders, migraines, sleep disorders, demographic factors, and pre-injury healthcare patterns were entered into multivariable logistic regression and CART modeling in the Derivation Cohort to calculate PPCS estimates and forward selection logistic regression model in the Validation Cohort. Variables with the highest probability of PPCS derived in the Derivation Cohort were: Age >61 years ([Formula: see text] = 0.54), bipolar disorder ([Formula: see text] = 0.52), high pre-injury primary care visits per year ([Formula: see text] = 0.46), personality disorders ([Formula: see text] = 0.45), and anxiety and depression ([Formula: see text] = 0.33). The area under the curve (AUC) was 0.79 for the derivation model, 0.79 for bootstrap internal validation of the Derivation Cohort, and 0.64 for the Validation model. A limitation of this study was ability to track healthcare usage only to healthcare providers that submit to Ontario Health Insurance Plan (OHIP); thus, some patients seeking treatment for prolonged symptoms may not be captured in this analysis. CONCLUSIONS: In this study, we observed that premorbid psychiatric conditions, pre-injury health system usage, and older age were associated with increased risk of a prolonged recovery from concussion. This risk score allows clinicians to calculate an individual's risk of requiring treatment more than 6 months post-concussion.

Trends in the Top-Cited Articles on Classic Psychedelics.

This study was designed to identify trends in the top-cited classic psychedelic publications. The top 50 publications on classic psychedelics with the greatest total of number of citations and annual citation rate were identified and pooled. Unique articles (n = 76) were dichotomized by median year of publication (2010.5); the differential distribution of study characteristics between the "Recent Cohort" (n = 38) and "Older Cohort" (n = 38) were documented. The Recent Cohort had a greater annual citation rate (median 76.0, IQR 38.5 to 101.5) compared to the Older Cohort (median10.0, IQR 5.2 to 19.3, p < .001). The Recent Cohort included a greater number of clinical studies (n = 26 [68.4%] vs. n = 9 [23.7%]) while the Older Cohort included more basic science and preclinical studies (n = 21 [55.3%] vs. n = 2 [5.3%], p < .001). Psilocybin was the predominant psychedelic studied in the Recent Cohort (n = 25 [65.8%] vs. n = 9 [23.7%]) while lysergic acid diethylamide (LSD) was predominantly studied in the Older Cohort (n = 25 [65.8%] vs. n = 18 [47.4%], p = .013). The Recent Cohort included more studies examining affective disorders (n = 15 [39.5%] vs. n = 3 [7.9%]) and substance use disorders (n = 6 [15.8%] vs. n = 0 [0.0%]), while the Older Cohort included a greater number of pharmacological outcomes (n = 29 [76.3%] vs. n = 6 [15.8%], p < .001). This study identified and documented trends in the top-cited classic psychedelic publications. The field is continuing to form a foundational understanding of the pharmacological effects of psychedelics and is now advancing with the identification of therapeutic uses within clinical populations.

Earlier time to aerobic exercise is associated with faster recovery following acute sport concussion.

OBJECTIVE: To determine whether earlier time to initiation of aerobic exercise following acute concussion is associated with time to full return to (1) sport and (2) school or work. METHODS: A retrospective stratified propensity score survival analysis of acute (≤14 days) concussion was used to determine whether time (days) to initiation of aerobic exercise post-concussion was associated with, both, time (days) to full return to (1) sport and (2) school or work. RESULTS: A total of 253 acute concussions [median (IQR) age, 17.0 (15.0-20.0) years; 148 (58.5%) males] were included in this study. Multivariate Cox regression models identified that earlier time to aerobic exercise was associated with faster return to sport and school/work adjusting for other covariates, including quintile propensity strata. For each successive day in delay to initiation of aerobic exercise, individuals had a less favourable recovery trajectory. Initiating aerobic exercise at 3 and 7 days following injury was associated with a respective 36.5% (HR, 0.63; 95% CI, 0.53-0.76) and 73.2% (HR, 0.27; 95% CI, 0.16-0.45) reduced probability of faster full return to sport compared to within 1 day; and a respective 45.9% (HR, 0.54; 95% CI, 0.44-0.66) and 83.1% (HR, 0.17; 95% CI, 0.10-0.30) reduced probability of faster full return to school/work. Additionally, concussion history, symptom severity, LOC deleteriously influenced concussion recovery. CONCLUSION: Earlier initiation of aerobic exercise was associated with faster full return to sport and school or work. This study provides greater insight into the benefits and safety of aerobic exercise within the first week of the injury.

Top-cited articles in traumatic brain injury.

A review of the top-cited articles in a scientific discipline can identify areas of research that are well established and those in need of further development, and may, as a result, inform and direct future research efforts. Our objective was to identify and characterize the top-cited articles in traumatic brain injury (TBI). We used publically available software to identify the 50 TBI articles with the most lifetime citations, and the 50 TBI articles with the highest annual citation rates. A total of 73 articles were included in this review, with 27 of the 50 papers with the highest annual citation rates common to the cohort of 50 articles with the most lifetime citations. All papers were categorized by their primary topic or focus, namely: predictor of outcome, pathology/natural history, treatment, guidelines and consensus statements, epidemiology, assessment measures, or experimental model of TBI. The mean year of publication of the articles with the most lifetime citations and highest annual citation rates was 1990 ± 14.9 years and 2003 ± 6.7 years, respectively. The 50 articles with the most lifetime citations typically studied predictors of outcome (34.0%, 17/50) and were specific to severe TBI (38.0%, 19/50). In contrast, the most common subject of papers with the highest annual citation rates was treatment of brain injury (22.0%, 11/50), and these papers most frequently investigated mild TBI (36.0%, 18/50). These findings suggest an intensified focus on mild TBI, which is perhaps a response to the dedicated attention these injuries are currently receiving in the context of sports and war, and because of their increasing incidence in developing nations. Our findings also indicate increased focus on treatment of TBI, possibly due to the limited efficacy of current interventions for brain injury. This review provides a cross-sectional summary of some of the most influential articles in TBI, and a bibliometric examination of the current status of TBI research.