The oneirogen ibogaine reduced the long-term effects of brain injury
U.S. and Canadian researchers reported success in a phase I clinical trial of a combination of ibogaine and magnesium for the long-term effects of traumatic brain injury in Special Forces veterans. The treatment was well tolerated and produced a pronounced effect. A report of the work is published in Nature Medicine.
Craniocerebral injury is a common injury in combat veterans (typical mechanism is shock wave exposure). Its long-term consequences may include neurologic and psychiatric disorders, including post-traumatic stress disorder (PTSD), major depressive and anxiety disorders, and suicidal tendencies. The effectiveness of available treatments for them is inadequate, especially in the ex-military population.
The psychoactive indole alkaloid ibogaine is extracted from the roots of the African tropical iboga shrub (Tabernanthe iboga). It and its major metabolite noribogaine have weak to moderate affinity for receptors for numerous neurotransmitters, including glutamate NMDA, opioid κ and μ, nicotinic acetylcholine, σ-1 and σ-2, and serotonin and dopamine transporters. In addition, ibogaine enhances transcription of some neurotrophic factors and increases the complexity of dendritic branching in vitro. When administered in therapeutic doses, it induces a dream-like state of consciousness that, under suitable conditions, promotes prolonged self-reflection and introspection. Because of its diverse effects, ibogaine can be classified as an atypical psychedelic, an atypical dissociative and an oneirogen. It is of some interest as a potential treatment for substance use disorder, but such studies are limited by its ability to prolong the QT interval, which can lead to fatal ventricular arrhythmias.
Stanford Medical School researchers, led by Nolan Williams, set out to find out the therapeutic potential of ibogaine to help with the effects of brain injury. They invited 30 U.S. Special Forces veterans (all male) with disabilities due to this condition to participate in a Phase I clinical trial of MISTIC. They all underwent a preliminary interview via video link with a neuropsychologist, after which they were given a full medical evaluation, including lab tests, EKGs and brain MRIs. They were then sent to the clinic of the Canadian company Ambio Life Sciences in Mexico (ibogaine experiments are prohibited in the U.S.), where, after further evaluation and detailed instruction, they received an average of 12.1 ± 1.2 milligrams of synthetic ibogaine per kilogram of body weight orally. They were administered magnesium preparations to prevent cardiac complications. During the substance, they followed the recommendations received and did not receive additional psychotherapy (only assistants were with them to provide immediate needs and monitor physiologic parameters).
The primary endpoint was the change in the level of disability according to the World Health Organization WHODAS-2.0 scheme compared to baseline. The dynamics of PTSD on the CAPS-5 scale, depression on the MADRS scale, and anxiety on the HAM-A scale were also assessed. All measurements were performed immediately after the ibogaine session and one month later. Statistical processing of the data was performed using linear mixed-effects models.
It was found that the total WHODAS-2.0 score on average significantly decreased from 30.2 ± 14.7 (moderate disability) to 19.9 ± 16.3 (borderline disability; adjusted p < 0.001; d = 0.74) immediately after the session and 5.1 ± 8.1 (no disability; adjusted p < 0.001; d = 2.20) one month later. Improvement was observed in all six domains of the schema, strongest in the cognitive domain. There was also significant improvement on the CAPS-5 (adjusted p < 0.001; d = 2.54); MADRS (adjusted p < 0.001; d = 2.80); and HAM-A (adjusted p < 0.001; d = 2.13) one month after the session, with an average percent symptom reduction, response rate, and remission rate exceeding 80 percent. Suicidal tendencies decreased from 47 percent at baseline to 0 and 1 percent immediately after the session and one month later, respectively.
No serious side effects, including cardiac and hemodynamic effects, were reported. All participants experienced mild transient cerebellar symptoms, such as ataxia and intensional tremor, which resolved completely within 24 hours. During ibogaine, participants were treated for headache (40 percent), nausea (10 percent), anxiety (7 percent) and insomnia (3 percent).
The results of the pilot open-label trials were deemed successful. The efficacy and safety of such therapy needs to be confirmed and refined in randomized controlled trials, the authors of the paper conclude.