Magnesium-ibogaine therapy in veterans with traumatic brain injuries.

"Competing interests N.R.W. and I.H.K. are inventors on a patent application (no. 18/467,324) related to the safety of MISTIC administration as described in the paper. J.P.C. and N.R.W. are inventors on a patent application (no. 18/467,343) related to the use of ibogaine to treat disorders associated with brain aging. J.D., J.I. and T.M. are shareholders in Ambio Life Sciences, which offers ibogaine treatments. J.D, J.I. and T.M. are inventors in a related provisional patent application no. 63/523,774. The application is related to adjunct treatment with various compounds during ibogaine therapy to improve safety. J.D. is founder of Terragnosis, Inc., a company dedicated to the sourcing and semisynthetic conversion of ibogaine precursors to ibogaine. The other authors declare no competing interests."

"We thank all the veterans who participated in the present study. We thank the entire Brain Stimulation Lab past and present for their support of this project, particularly I. D. Bandeira, J. Bishop, D. Buchanan, A. Chaiken, P. Crittenden, F. Espil, M. Feyder, G. Lin, T. J. Ford, R. Malenka, R. Rapier, S. Sami, D. Spiegel and C. Veerapal. We thank VETS, Inc. for facilitating recruitment of participants. Stanford received no funding from VETS, Inc. or Ambio. We thank S. Jurvetson and G. Jurvetson and the Sergey Brin Family Foundation for their independent support of the Stanford component of the study. The funders played no role in study design, execution, data analysis or manuscript preparation, review or approval. Author contributions: K.N.C. performed screening, psychological and cognitive assessments and supervised related scoring and data entry, led study execution at Stanford for all participants, provided guidance and feedback on statistical analyses and participated in the writing and subsequent revision of the paper. J.N.K. designed, performed and interpreted the statistical analyses and participated in the writing and subsequent revision of the paper. L.A. supported study execution at Stanford, psychological and cognitive assessments, scoring of assessments and data entry and reviewed and critiqued the paper. A.F. performed cognitive testing scoring, data entry and statistical analysis, contributed to the interpretation of cognitive testing and reviewed and critiqued the paper. R.E.B. performed cognitive assessments, scoring of assessments and data entry and reviewed and critiqued the paper. A.S., J.P.C. and G.L.S. assisted with study design, supported study execution at Stanford and reviewed and critiqued the paper. O.K. performed cognitive assessments, scoring of assessments and data entry. J.-M.B., A.P. and N.J.B. supported study execution at Stanford. J.I., T.M. and J.D. coordinated logistics at Ambio, supervised ibogaine treatment and monitoring and reviewed and critiqued the paper. C.E.R. performed a literature review and contributed to the critique and revision of the paper. J.K. contributed to the design of the standardized assessments and reviewed and critiqued the paper. M.A. contributed to study design, provided guidance and feedback on statistical analyses and reviewed and critiqued the paper. I.H.K. assisted with study design, supported study execution at Stanford, supervised all data analysis, assumed the role of protocol director while N.R.W. was on leave and led the writing and subsequent revision of the paper. N.R.W. conceived the study; supervised study design, budgeting and execution at Stanford; was protocol director of the study until his leave; and reviewed and critiqued the paper and its revision. All authors approved the final manuscript. K.N.C. and J.N.K were co-first authors; L.A. and A.F. were co-second authors; I.H.K. and N.R.W were co-senior authors."

"Traumatic brain injury (TBI) is a leading cause of disability. Sequelae can include functional impairments and psychiatric syndromes such as post-traumatic stress disorder (PTSD), depression and anxiety. Special Operations Forces (SOF) veterans (SOVs) may be at an elevated risk for these complications, leading some to seek underexplored treatment alternatives such as the oneirogen ibogaine, a plant-derived compound known to interact with multiple neurotransmitter systems that has been studied primarily as a treatment for substance use disorders. Ibogaine has been associated with instances of fatal cardiac arrhythmia, but coadministration of magnesium may mitigate this concern. In the present study, we report a prospective observational study of the Magnesium–Ibogaine: the Stanford Traumatic Injury to the CNS protocol (MISTIC), provided together with complementary treatment modalities, in 30 male SOVs with predominantly mild TBI. We assessed changes in the World Health Organization Disability Assessment Schedule from baseline to immediately (primary outcome) and 1 month (secondary outcome) after treatment. Additional secondary outcomes included changes in PTSD (Clinician-Administered PTSD Scale for DSM-5), depression (Montgomery–Åsberg Depression Rating Scale) and anxiety (Hamilton Anxiety Rating Scale). MISTIC resulted in significant improvements in functioning both immediately (Pcorrected < 0.001, Cohen’s d = 0.74) and 1 month (Pcorrected < 0.001, d = 2.20) after treatment and in PTSD (Pcorrected < 0.001, d = 2.54), depression (Pcorrected < 0.001, d = 2.80) and anxiety (Pcorrected < 0.001, d = 2.13) at 1 month after treatment. There were no unexpected or serious adverse events. Controlled clinical trials to assess safety and efficacy are needed to validate these initial open-label findings. ClinicalTrials.gov registration: NCT04313712."