Camarin Rolle

Traumatic brain injury (TBI) can result in chronic functional disability and is associated with persistent psychiatric symptoms, including posttraumatic stress disorder (PTSD), depression, and anxiety. Ibogaine, an oneirogenic alkaloid with unique pharmacological properties, has shown initial promise as a potential treatment for TBI-related sequelae. We previously observed large improvements in functional and psychiatric outcomes up to one month after a single treatment with magnesium-ibogaine in male U.S. Special Operations Veterans with a history of TBI. However, further evidence on the durability of these effects is needed. In this prospective long-term follow-up study, we evaluated the persistence of these clinical improvements over the subsequent year. Participants underwent comprehensive baseline and post-treatment assessments, with follow-up evaluations conducted at 3, 6, 9, and 12 months. Of 30 participants treated with magnesium-ibogaine, 25 completed the 12-month follow-up assessments. Outcome measures included a self-report measure of functional disability and clinician-administered assessments of psychiatric symptoms. Linear mixed-effects models demonstrated robust and sustained reductions in disability, PTSD, depression, and anxiety symptoms through 12 months post-treatment (all p < 0.001 after correction for multiple comparisons), with large effect sizes (Cohen’s d ≥ 2.18 at 12 months). In participants who achieved remission immediately post-treatment, survival analyses estimated the probability of sustained remission at 12 months as 84% for PTSD, 66% for depression, and 61% for anxiety. Notably, most participants reported using other psychedelic substances or pursuing other interventions during the follow-up period, which should be considered when interpreting long-term symptom trajectories. In this naturalistic cohort, durable, clinically meaningful symptom improvements were observed in individuals with TBI up to 12 months after ibogaine treatment. Further investigation through randomized controlled trials is warranted to validate these promising preliminary results and clarify the causal contributions of ibogaine treatment, subsequent interventions, and their combination.

Preliminary evidence suggests that the combination of magnesium and ibogaine, an atypical psychedelic, may be a promising treatment for post-traumatic stress disorder (PTSD), opioid use disorder, and traumatic brain injury (TBI). The "mystical" experience elicited by ibogaine, which is characterized by feelings of awe, selflessness, and transcendence, is correlated with improvements in PTSD symptoms. Mystical experiences with other psychedelics are associated with acute decreases in the activity and connectivity of the default mode network (DMN), which mediates self-related cognition. However, the dynamic effects of ibogaine on the DMN have not yet been studied. At baseline, immediately (3-4 days) after ibogaine, and one month after ibogaine, we acquired resting-state functional magnetic resonance imaging data in an open-label, observational trial of magnesium-ibogaine treatment for 30 U.S. veterans with TBI. Magnesium-ibogaine did not significantly alter static DMN connectivity at either the immediate-post or one-month timepoint. Since static measures cannot capture time-evolving changes in connectivity, we next used Hidden Markov Models (HMM) to measure the post-acute dynamics of DMN activity. Magnesium-ibogaine was associated with significant, sustained decreases in the switching rate (i.e., increases in the duration of) a dynamic DMN substate, which was significantly correlated with the mean score on the Revised Mystical Experience Questionnaire and clinical improvements at one month-post treatment. This DMN substate exhibited a lateral-medial spatial gradient, which was significantly associated with a gradient of externally oriented (i.e., directed to the environment) to internally oriented (i.e., self-related) perception and cognition. Taken together, our results indicate that magnesium-ibogaine alters specific dynamic substates of the DMN, which correlate with its subjective and therapeutic effects.

Post-traumatic stress disorder (PTSD) is a debilitating condition that affects millions of veterans. A recent observational study in 30 veterans showed that a single dose of the atypical psychedelic ibogaine can be highly effective at treating PTSD up to twelve months later. Although a prior study demonstrated that ibogaine transiently alters electroencephalography (EEG) power in various frequency bands, the long-term, network-level neural mechanisms targeted by ibogaine are unclear. Here, we investigated whether ibogaine-related clinical improvements are associated with the reorganization of certain brain networks. We applied a novel framework, FREQuency-resolved brain Network Estimation via Source Separation (FREQ-NESS), to identify frequency-specific brain networks in resting-state EEG data acquired at baseline, three to four days after treatment (immediate-post), and one month after ibogaine. At both the immediate-post and one month-post timepoints, high-beta (24 and 25 Hz) networks shifted away from frontal areas and towards posterior regions, an effect that was replicated in an independent EEG dataset on ibogaine treatment for opioid use disorder. This posterior shift was significantly correlated with improvements in PTSD symptoms at both timepoints. Neural field modeling demonstrated that these posterior high-beta shifts are associated with increases in corticocortical, but not corticothalamic, connectivity. Our results are consistent with prior evidence implicating aberrant frontal beta-band activity in PTSD. Overall, we demonstrate that the reconfiguration of high-beta brain networks could be a robust biomarker for ibogaine’s therapeutic effects.

Traumatic brain injury (TBI) can result in chronic functional disability and is associated with persistent psychiatric symptoms, including posttraumatic stress disorder (PTSD), depression, and anxiety. Ibogaine, an oneirogenic alkaloid with unique pharmacological properties, has shown initial promise as a potential treatment for TBI-related sequelae. We previously observed large improvements in functional and psychiatric outcomes up to one month after a single treatment with magnesium-ibogaine in male U.S. Special Operations Veterans with a history of TBI. However, further evidence on the durability of these effects is needed. In this prospective long-term follow-up study, we evaluated the persistence of these clinical improvements over the subsequent year. Participants underwent comprehensive baseline and post-treatment assessments, with follow-up evaluations conducted at 3, 6, 9, and 12 months. Of 30 participants treated with magnesium-ibogaine, 25 completed the 12-month follow-up assessments. Outcome measures included a self-report measure of functional disability and clinician-administered assessments of psychiatric symptoms. Results demonstrated robust and sustained reductions in disability, PTSD, depression, and anxiety symptoms through 12 months post-treatment, with large effect sizes (Cohen’s d ≥ 2.18 at 12 months). Survival analyses estimated the probability of sustained remission at 12 months as 84% for PTSD, 66% for depression, and 61% for anxiety. These findings suggest that ibogaine treatment may lead to durable, clinically meaningful improvements in TBI-related symptoms. Further investigation through randomized controlled trials is warranted to validate these promising preliminary results.

Due to the rapidly improving capability of large language models such as Generative Pre-trained Transformer models (GPT), artificial intelligence (AI) based tools have entered use in education at scale. However, empirical data are largely lacking on the effects of AI tools on learning. Here, we determine the impact of four GPT-based tools on college-aged participants’ comprehension of standardized American College Test (ACT)-derived passages and associated tests using a randomized cross-over online study (n=195). The four tools studied were AI-generated summaries, AI-generated outlines, a question-and-answer tutor chatbot, and a Socratic discussion chatbot. Consistent with our pre-registered hypotheses, we found a differential effect of AI tools based on baseline reading comprehension ability. AI tools significantly improved comprehension in lower performing participants and significantly worsened comprehension in higher performing participants. With respect to specific tools, low performers were most benefited by the Socratic chatbot while high performers were worsened most by the summary tool. These findings suggest that while AI tools have massive potential to enhance learning, blanket implementation may cause unintended harm to higher-performing students, calling for caution and further empirical study from developers and educators.

BACKGROUND Mental health conditions, including depression and anxiety disorders, are significant global concerns. Many people with these conditions don't get the help they need because of the high costs of medical treatment and the stigma attached to seeking help. Digital technologies represent a viable solution to these challenges. However, these technologies are often characterized by relatively low adherence and their effectiveness largely remains empirical unverified. While digital technologies may represent a viable solution for this persisting problem, they often lack empirical support for their effectiveness and are characterized by relatively low adherence. Conversational agents using artificial intelligence capabilities have the potential to offer a cost-effective, low-stigma and engaging way of getting mental health care. OBJECTIVE The objective of this study was to evaluate the feasibility, acceptability, and effectiveness of Youper, a mobile application that utilizes a conversational interface and artificial intelligence capabilities to deliver cognitive behavioral therapy-based interventions to reduce symptoms of depression and anxiety in adults. METHODS 1,012 adults with symptoms of depression and anxiety participated in a real-world setting study, entirely remotely, unguided and with no financial incentives, over an 8-week period. Participants completed digital versions of the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder scale (GAD-7) at baseline, 2, 4, and 8 weeks. RESULTS After the eight-week study period, depression (PHQ-9) scores of participants decreased by 48% while anxiety (GAD-7) scores decreased by 43%. The RCI was outside 2 standard deviations for 93.0% of the individuals in the PHQ-9 assessment and 90.7% in the GAD-7 assessment. Participants were on average 24.79 years old (SD 7.61) and 77% female. On average, participants interacted with Youper 0.9 (SD 1.56) times per week. CONCLUSIONS Results suggest that Youper is a feasible, acceptable, and effective intervention for adults with depression and anxiety. CLINICALTRIAL Since this study involved a nonclinical population, it wasn't registered in a public trials registry.