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

Multiple classes of psychedelic compounds have shown preliminary evidence of anti-addictive effects for substances including alcohol, and more effective treatments for alcohol use disorder are needed. Ibogaine, a plant-derived dissociative psychedelic, has been reported in observational studies to interrupt addiction across several substances; 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a short-acting serotonergic tryptamine, is reported to occasion intense mystical-type experiences and has epidemiological and preclinical signals for therapeutic effects in addiction and mood disorders. Despite these lines of evidence, there were no published human neuroimaging data for either compound at the time of this report, and the mechanisms by which they might affect addiction-related brain circuits remained speculative. Barsuglia and colleagues set out to document clinical and regional cerebral blood flow changes associated with a sequential treatment protocol of ibogaine followed by vaporised 5-MeO-DMT in a single patient with alcohol use disorder. The report combines a case description, resting-state single-photon emission computed tomography (SPECT) imaging performed before and after the sequential interventions, and a theoretical rationale for why administering ibogaine and 5-MeO-DMT in sequence might produce complementary or synergistic therapeutic effects.

This paper is a single-case clinical report. The subject was a 31-year-old right-handed male US Air Force veteran with moderate alcohol use disorder and comorbid post‑traumatic stress symptoms and depressive features. Baseline clinical screening included the Beck Depression Inventory-II (BDI-II score 18) and the PTSD Checklist for DSM-5 (PCL-5 score 30); these screening measures were not repeated post-treatment in the extracted text. The patient had a history of prior psychedelic use (ayahuasca, psilocybin) and had undergone outpatient therapy without sustained benefit for alcohol use. Treatment took place in a four-day programme at a clinic in Mexico that incorporated medical screening, monitoring, psychotherapeutic preparation and post‑experience integration. Ibogaine hydrochloride (Voacanga-derived, GMP-certified) was administered on day 1 as a total dose of 1550 mg (17.9 mg/kg; patient weight 86.5 kg) delivered in an initial three-dose sequence (500, 500, 300 mg at 30 min intervals) with a fourth 250 mg dose given about 3 hours later. Clinical monitoring included telemetry ECG, vital signs and staff presence; supportive measures given included intravenous saline, magnesium sulfate and antiemetic medication. Two days later (day 3) the patient received inhaled vaporised bufotoxin from the Colorado River toad, 50 mg of bufotoxin estimated to contain 5–7 mg of 5-MeO-DMT; administration involved guided breathing, a handheld vaporiser and supervision by a physician and facilitator. Acute effects and return to baseline orientation were monitored. Resting-state SPECT imaging was performed at baseline (48 h before ibogaine) and at follow-up 5 days after ibogaine administration (110 h post-ibogaine; 73 h post-5-MeO-DMT). SPECT measured regional cerebral blood flow (rCBF) using 99mTc-HMPAO tracer and a triple-headed gamma camera. Images were reconstructed and rendered using a standardised colour (step-20) scale; visual readings were performed in three planes with semi-quantitative region-of-interest (ROI) ratings mapped to percentile bands (for example >95th percentile = 4+). The investigators report differences by subtracting post-treatment minus baseline ROI ratings. The extracted text does not clearly report some numerical ROI values within the main prose; changes are described qualitatively and summarised in a table referenced in the paper.

Baseline resting-state SPECT showed moderately decreased perfusion in the inferior orbitofrontal cortices and temporal lobes bilaterally, mild decreases in occipital lobes and medial cerebellum, and severely increased activity in the right putamen with moderate increase in the posterior cingulate. These baseline patterns were considered consistent with common SPECT abnormalities in alcohol-related brain pathology and possibly suggestive of prior brain injury. The post-treatment SPECT (110 h after ibogaine, 73 h after 5-MeO-DMT) revealed multiple changes compared with baseline. Temporal lobe hypoperfusion improved from moderate to mild. Occipital lobe and internal cerebellar perfusion also improved. Bilateral inferior orbitofrontal cortex remained moderately decreased. In an internal active view, bilateral caudate, left putamen and the right thalamo-limbic pathway showed moderate increases in perfusion, whereas the right putamen showed a decrease. The investigators report most notable ROI increases (rating change ≥1.5) in bilateral caudate, left putamen, temporal lobes (left anterior and bilateral posterior), cerebellum (medial and surface regions), occipital lobes, right insular cortex and anterior cingulate (genu). The largest decreases (rating change ≤−1.5) were noted in the right anterior temporal pole, right putamen and left insular cortex. Exact numerical ROI values from the table are not reproduced in the extracted prose. Clinically, at the time of the post-treatment SPECT (110 h post-ibogaine) the patient reported feeling physically and mentally calmer, with improved focus, clarity, mood and an absence of craving for alcohol. He described meaningful oneiric experiences during ibogaine and a profoundly spiritual, unitive mystical-type experience after 5-MeO-DMT that he judged transformational. Acute adverse effects during ibogaine included ataxia when attempting to walk, episodes of vomiting and transient panic that required staff assistance. The 5-MeO-DMT session entailed brief dry heaving followed by a 45‑minute session with full orientation restored within 60 minutes. Follow-up by phone at 1 month found the patient abstinent from alcohol with minimal cravings. At 3 months he reported resuming limited drinking (about one to two drinks per week) from a prior baseline of daily heavy drinking; he also reported enduring but attenuated improvements in mood, energy and anger regulation. The investigators note that because the follow-up imaging occurred days after both agents, noribogaine or other residual effects could plausibly have been present, and causation cannot be attributed to either compound alone.

The investigators interpret the case as showing acute clinical improvement in alcohol-related behaviour and subjective wellbeing accompanied by increased perfusion in multiple brain regions implicated in addiction. They relate the observed imaging changes to known pharmacological targets of ibogaine and 5-MeO-DMT. Specifically, they propose that increased cerebellar perfusion may be consistent with ibogaine's actions on NMDA/glutamatergic systems, dopamine transport, μ opioid and σ1 receptors, and with evidence that the cerebellum participates in reward processing, conditioned drug memories and emotional regulation. Increased perfusion in basal ganglia structures (caudate, putamen) is hypothesised to relate to dopaminergic and opioid-related effects of ibogaine, while occipital changes could reflect cholinergic/muscarinic actions relevant to cue processing. Regarding 5-MeO-DMT, the authors suggest potential contributions through prominent 5-HT receptor agonism (notably 5-HT1A and 5-HT7), σ1 activity and strong capacity to occasion mystical-type experiences that may facilitate trauma processing. They note that such acute mystical experiences have been linked to improved outcomes in studies of other serotonergic psychedelics used for addiction. The paper advances a theoretical rationale for sequencing: ibogaine's longer-acting neurochemical and oneiric effects could 'prime' neural circuits and psychological material, while a subsequent short-acting serotonergic peak from 5-MeO-DMT might occasion a rapid, intense mystical experience that consolidates psychological change. Neurobiological synergy is hypothesised via combined effects on serotonergic, glutamatergic, cholinergic and opioidergic systems, and through shared σ1 and neurotrophic mechanisms (GDNF and possible BDNF modulation) that could promote neuroplasticity. The authors explicitly acknowledge major limitations. The report is a single-case observation without controls, and sequential administration prevents attribution of effects to a single agent. Timing of the post-treatment scan (5 days post-ibogaine, 3 days post-5-MeO-DMT) means metabolites such as noribogaine may have remained and confound interpretation. Behavioural changes could partly reflect short-term abstinence, placebo effects, or non-specific programme factors; follow-up substance use was self-reported and not medically monitored. The paper therefore frames its conclusions as speculative and calls for controlled human neuroimaging studies testing each compound independently and in sequence, larger samples, in vivo measurements during the acute window, and correlation of neural changes with phenomenology and clinical outcomes. The investigators also warn of safety considerations, particularly cardiac risk with ibogaine and the potential for bufotoxin admixtures (e.g. bufotenine) when using toad-derived preparations, and recommend rigorous screening and monitoring in any future research.

Barsuglia and colleagues conclude that ibogaine and 5-MeO-DMT show initial behavioural and pharmacological signals as candidate treatments for alcohol use disorder, and that SPECT imaging in this single case demonstrated post-treatment increases in perfusion across multiple brain regions relevant to addiction. They emphasise that the patient's processing of trauma and a peak mystical-type experience coincided with a clinically meaningful period of abstinence and improved mood, but stress that larger, controlled neuroimaging studies are needed to disentangle the effects of each compound, to document in vivo dynamics during treatment, and to correlate neural changes with psychedelic phenomenology. The authors also note regulatory and practical barriers to research, as both substances are tightly scheduled in many jurisdictions, which constrains scientific investigation.