OPEN Foundation

B. Kelmendi

A case report SPECT study and theoretical rationale for the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder

Abstract

Ibogaine is a plant-derived alkaloid and dissociative psychedelic that demonstrates anti-addictive properties with several substances of abuse, including alcohol. 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring psychedelic known to occasion potent mystical-type experiences and also demonstrates anti-addictive properties. The potential therapeutic effects of both compounds in treating alcohol use disorder require further investigation and there are no published human neuroimaging findings of either treatment to date. We present the case of a 31-year-old male military veteran with moderate alcohol use disorder who sought treatment at an inpatient clinic in Mexico that utilized a sequential protocol with ibogaine hydrochloride (1550mg, 17.9mg/kg) on day 1, followed by vaporized 5-MeO-DMT (bufotoxin source 50mg, estimated 5-MeO-DMT content, 5-7mg) on day 3. The patient received SPECT neuroimaging that included a resting-state protocol before, and 3 days after completion of the program. During the patient’s ibogaine treatment, he experienced dream-like visions that included content pertaining to his alcohol use and resolution of past developmental traumas. He described his treatment with 5-MeO-DMT as a peak transformational and spiritual breakthrough. On post-treatment SPECT neuroimaging, increases in brain perfusion were noted in bilateral caudate nuclei, left putamen, right insula, as well as temporal, occipital, and cerebellar regions compared to the patient’s baseline scan. The patient reported improvement in mood, cessation of alcohol use, and reduced cravings at 5 days post-treatment, effects which were sustained at 1 month, with a partial return to mild alcohol use at 2 months. In this case, serial administration of ibogaine and 5-MeO-DMT resulted in increased perfusion in multiple brain regions broadly associated with alcohol use disorders and known pharmacology of both compounds, which coincided with a short-term therapeutic outcome. We present theoretical considerations regarding the potential of both psychedelic medicines in treating alcohol use disorders in the context of these isolated findings, and areas for future investigation.

Barsuglia, J. P., Polanco, M., Palmer, R., Malcolm, B. J., Kelmendi, B., & Calvey, T. (2018). A case report SPECT study and theoretical rationale for the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder. Progress in brain research242, 121-158., 10.1016/bs.pbr.2018.08.002

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Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic

Abstract

PURPOSE OF REVIEW:
Studies of the neurobiology and treatment of PTSD have highlighted many aspects of the pathophysiology of this disorder that might be relevant to treatment. The purpose of this review is to highlight the potential clinical importance of an often-neglected consequence of stress models in animals that may be relevant to PTSD: the stress-related loss of synaptic connectivity.
RECENT FINDINGS:
Here, we will briefly review evidence that PTSD might be a “synaptic disconnection syndrome” and highlight the importance of this perspective for the emerging therapeutic application of ketamine as a potential rapid-acting treatment for this disorder that may work, in part, by restoring synaptic connectivity. Synaptic disconnection may contribute to the profile of PTSD symptoms that may be targeted by novel pharmacotherapeutics.
Krystal, J. H., Abdallah, C. G., Averill, L. A., Kelmendi, B., Harpaz-Rotem, I., Sanacora, G., … & Duman, R. S. (2017). Synaptic loss and the pathophysiology of PTSD: implications for ketamine as a prototype novel therapeutic. Current Psychiatry Reports19(10), 74. 10.1007/s11920-017-0829-z
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Posttraumatic Stress Disorder: An Integrated Overview of the Neurobiological Rationale for Pharmacology

Abstract

Thirty years of research on the biology of posttraumatic stress disorder now provides a foundation for hypotheses related to the mechanisms underlying the pharmacotherapy of this disorder. Only two medications, sertraline and paroxetine, are approved by the U.S. Food and Drug Administration for the treatment of PTSD. Although these medications are somewhat effective, other treatment mechanisms must be explored to address the unmet need for effective treatment. This article provides a concise summary of advances in our understanding of the neurobiology of PTSD and novel approaches to pharmacotherapy.
Kelmendi, B., Adams, T. G., Southwick, S., Abdallah, C. G., & Krystal, J. H. (2017). Posttraumatic stress disorder: An integrated overview of the neurobiological rationale for pharmacology. Clinical Psychology: Science and Practice. 10.1111/cpsp.12202
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The role of psychedelics in palliative care reconsidered: A case for psilocybin

Kelmendi, B., Corlett, P., Ranganathan, M., D’Souza, C., & Krystal, J. H. (2016). The role of psychedelics in palliative care reconsidered: A case for psilocybin. Journal of psychopharmacology (Oxford, England), 30(12), 1212. 10.1177/0269881116675781
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