Magnesium–ibogaine therapy in veterans with traumatic brain injuries

Summary & key facts

In a prospective, open-label study of 30 male Special Operations veterans with mostly mild traumatic brain injury, a treatment protocol combining magnesium and oral ibogaine (MISTIC), given with other supportive care, was associated with large, statistically significant improvements in functioning and in clinician-rated PTSD, depression and anxiety scores immediately after treatment and at 1 month. For example, the average disability score (WHODAS) fell from 30.2 at baseline to 19.9 immediately after treatment and to 5.1 at 1 month. No unexpected or serious treatment-emergent adverse events were reported in this group. The authors note that controlled clinical trials are needed to test safet

Key facts:

• Study type: prospective, observational, open-label study of 30 male Special Operations veterans with predominantly mild traumatic brain injury (30 completed baseline and 1-month clinical measures).
• Dose: participants received mean oral ibogaine of 12.1 ± 1.2 mg per kg of body weight as part of the MISTIC protocol.
• Primary outcome (functioning): WHODAS-2.0 total score decreased from 30.2 ± 14.7 at baseline to 19.9 ± 16.3 immediately after treatment (Pcorrected < 0.001; Cohen’s d = 0.74), and to 5.1 ± 8.1 at 1 month (Pcorrected < 0.001; d = 2.20).
• PTSD, depression and anxiety: clinician-rated scores improved with large effect sizes at 1 month — CAPS-5 for PTSD (Pcorrected < 0.001; d = 2.54), MADRS for depression (Pcorrected < 0.001; d = 2.80) and HAM-A for anxiety (Pcorrected < 0.001
• Safety: the study reported no unexpected or serious treatment-emergent adverse events and no clinically meaningful bradycardia, tachycardia or Q–T interval events in these participants.
• Sample characteristics: mean age was 44.9 ± 7.5 years; 23 of 30 met criteria for PTSD; 15 met criteria for major depressive disorder; 14 met criteria for an anxiety disorder (some participants had more than one diagnosis).
• Context and limits: ibogaine is a Schedule I substance with prior reports of cardiac risk (Q–T prolongation) in other settings; the study used coadministration of magnesium because prior work suggests magnesium can reduce Q–T prolongation.
• Registration: the study is registered on ClinicalTrials.gov under identifier NCT04313712.

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Anxiety Depression (economics) Economics Hamilton Anxiety Rating Scale Internal medicine Macroeconomics Medicine Psychiatry Psychology Traumatic brain injury