Sub-Perceptual Ibogaine, State-Dependent Memory, and Compounded Liabilities for Complex Trauma: An Accessibility-First Critical Synthesis

Abstract

Purpose

This article tests the thesis that sub-perceptual ibogaine (very low dose exposure that does not produce overt hallucinations) preserves the key precondition for state-dependent memory (a phenomenon where memories are easier to recall when your body and mind match the state you were in when you formed them) while scaling down, not eliminating, neural risks. The focus is on individuals who meet Integrative Self-Analysis (ISA) criteria for Complex Trauma (C-PTSD) as a biopsychosocial model that locates many symptoms in trauma-driven “psychogenic complexes,” which are durable patterns that bind emotion, memory, and bodily reactions.

Method

I conduct an integrative review and critical synthesis (a structured way of comparing studies and models to build a clear argument) across pharmacology, systems neuroscience, sleep physiology, and adverse psychiatric literature, and I map those findings onto ISA’s Vertical Axis Syncing / Memory Constellation framework (a process model that explains how bodily states, emotions, and memory bind together over time).

Results

Evidence shows: (1) ibogaine creates a discriminable interoceptive cue in animals, a prerequisite for state-dependent learning and recall; (2) low-dose ibogaine can still perturb sleep cycles central to emotional memory consolidation; (3) rodent work reveals increased gamma power with reduced coherence during wake, a profile that mirrors REM-like activity and implies noisier binding of perceptions; (4) polypharmacology across serotonin, dopamine, NMDA, and sigma systems remains active at low amplitude; (5) case literature documents mania, psychosis, and persistent perceptual disturbance after ibogaine; (6) controlled human evidence for benefits of “microdosing” ibogaine is minimal, and claims often rest on expectancy.

Implications

For ISA’s trauma continuum, sub-perceptual dosing can entrench Malignant Complexes (ISA’s term for deeply learned survival patterns that hijack identity) through state-locked reconsolidation, sleep-deprived suggestibility, and mis-tuned plasticity. The common label “sub-perceptual” is misleading, since many microdose participants can tell they received a drug (which breaks blinding and signals felt effects). Until prospective, harm-focused trials exist, routine use in trauma contexts is not justified.

Keywords: ibogaine; state-dependent memory (memories tied to body-mind state); C-PTSD; Integrative Self-Analysis (ISA); gamma coherence (how well brain rhythms line up); reconsolidation: Reconsolidation is the process by which a stored long-term memory is reactivated into short-term, labile form, brought under conscious, declarative control, updated in light of current affective and contextual inputs, and then written back into long-term memory as a revised trace. In simple terms, the act of recalling a declarative memory moves it from stable storage into the working system where it can be modified, after which the brain saves the altered version as the new long-term record.

Introduction

Problem and Thesis

Sub-perceptual (“microdose”) ibogaine does not eliminate the core neurological and psychological liabilities observed at higher doses. Instead, it scales them down unevenly while preserving the key precondition for state-dependent memory. In individuals consistent with ISA’s Complex Trauma profile (a model that centers trauma-driven, body-anchored learning loops), even low-amplitude perturbations of monoaminergic, glutamatergic, and sigma-mediated networks, combined with REM/NREM disruption and REM-like but incoherent gamma during wake, create a nontrivial risk of maladaptive reconsolidation, dissociation, and cognitive-map instability, with no controlled evidence of benefit beyond expectancy.

ISA’s definition of State-Dependent Memory means your brain retrieves information better when your inner state and environmental cues (Memory Constellations) matches the state you were in during learning. Reconsolidation is the “resaving” step when a memory is re-stored after you recall it, and it can pick up new features (neuroplasticity) from your current state. Gamma coherence describes how tightly different brain areas’ fast rhythms align, which supports focus and precise memory.

Why this matters in ISA terms

ISA treats many “personality disorders” and mixed symptom clusters as outputs of Psychogenic Complexes. A psychogenic complex is a durable pattern that binds feeling, body signals, and learned narrative into one driver of perception and behavior.

ISA treats many “personality disorders” and confusing mixed symptom clusters (see searchable variants below) as outputs of Psychogenic Complexes. A psychogenic complex is a durable pattern that binds feeling, body signals, and learned narrative into one driver of perception and behavior.

Confusing mixed symptom clusters

• Comorbidity / co-occurrence terms (use any): comorbidity, co-morbidity, multimorbidity, multi-morbidity, dual diagnosis, dual pathology, co-diagnosis, coexisting conditions, co-occurring disorders, concurrent disorders, overlapping disorders, overlapping phenotypes, mixed presentation, mixed clinical picture, heterotypic comorbidity, polysymptomatic presentation, polysyndromic presentation.

• Diagnostic ambiguity / “unspecified” terms: undifferentiated diagnosis, unspecified disorder, NOS (not otherwise specified), other specified, atypical presentation, variant presentation, subthreshold presentation, borderline features (descriptive, not DSM cluster), mixed features specifier, provisional diagnosis.

• Etiology uncertain / idiopathic terms: idiopathic, of unknown origin, essential (cause unknown), primary (cause unclear), cryptogenic, functional disorder, medically unexplained symptoms (MUS), psychosomatic presentation, somatoform spectrum, nonorganic etiology, diagnosis of exclusion.

• Syndrome language: syndromic diagnosis, clinical syndrome, symptom cluster, phenotype cluster, endophenotype pattern, transdiagnostic syndrome, dimensional profile, spectrum condition.

• Course/interaction descriptors: fluctuating course, episodic course, waxing-waning pattern, stress-reactive pattern, state-dependent pattern, trauma-congruent pattern, context-bound symptoms, cue-locked symptoms.

• Overlap with substance/behavioral factors: substance-associated symptoms, substance-induced features, behavioral addiction overlap, process addiction overlap, withdrawal-linked symptoms, iatrogenic effects, medication-induced features.

• Systems and networks wording (useful for ISA framing): network psychopathology, symptom network, attractor state, maladaptive attractor, prediction-error loop, memory constellation, state-trait interaction, bottom-up dysregulation, top-down control failure.

• High-level search expanders: heterogeneous symptomatology, clinical heterogeneity, diagnostic heterogeneity, pleiotropic effects, phenotypic pleomorphism, cross-cutting symptoms, transdiagnostic processes, dimensional psychopathology.

Here is the hinge from taxonomy to mechanics. If mixed presentations are best read as outputs of psychogenic complexes, the next task is to name the specific structures and rules that keep those outputs running over time.

ISA supplies that scaffold. It distinguishes when a learned survival pattern hardens into identity, how body-state and meaning fall out of alignment, and why certain cue clusters keep pulling the same reaction. It also specifies the two timing windows when memories are most editable and most vulnerable to state capture. With that frame in place, we can ask a clean question about low-dose ibogaine: does it restore alignment in everyday conditions, or does it bind updates to a rare internal state and deepen the loop?

ISA predicts that these patterns will harden into Malignant Complexes. A malignant complex is a harmful pattern (Prediction Errors) that fuses with identity and is defended as the real self.

ISA’s Vertical Axis Syncing is central. Vertical Axis Syncing means aligning bottom-up instinctual (Panksepp) and bodily states (symptoms, interoception, and drive-states) with top-down meaning so felt experience and story point the same way.

ISA’s Memory Constellation is a recurring trigger map. A memory constellation is a clustered set of cues across people, places, situations, sensations, and moods that repeatedly re-evokes the same response (Prediction Error).

State-dependent memory is a binding rule. State-dependent memory means recall works best when the internal state and external cues (Memory Constellation) at retrieval matches the state present during encoding.

Reconsolidation is a rewrite window for long-term memory predictions that impose themselves on cognitive ego awareness. Reconsolidation means a memory is resaved after recall and can absorb features of the current internal state.

ISA asks a direct question here: do low doses align the vertical axis in ordinary life or do they rewire constellations around a drug-like state?

ISA tracks binding rules that couple state, meaning, and memory. Any intervention that shifts state during encoding or reconsolidation can tilt the system toward alignment or toward repetition of a Malignant Complex's Prediction errors.

How bodily state, emotion, and memory reconnect or misalign over time, and where low-dose ibogaine effects this dynamic

After any state shift, ISA expects one of two outcomes. The system can reconnect across levels or it can misalign and deepen repetition of a Malignant Complex's Prediction Errors. Low-dose ibogaine sits inside this fork because it alters internal states while memories are plastic and can change, while disrupting reality-testing and other important and required state-dependent memories (which may be felt as negative) that created the original Malignant Complex.

Mechanisms

1. Subtle drug-state euphoria during narrative recall. Even without obvious intoxication, a small rise in energy or mood creates a distinct internal context for state-dependent memory. In ISA terms, traumatic material is retold inside a new state and the memory constellation binds that material to an ibogaine-like state rather than to ordinary waking ego cognition or the context of when the Malignant Complex was created.

2. Plasticity that favors the existing constellation. Plasticity is the brain’s capacity to change connections and it follows salience and context. In ISA terms, if a Malignant Complex still organizes meaning, plasticity strengthens the original dysphoric rule under a pleasant surface and the Malignant Complex’s Prediction Error model remains intact.

3. Sleep disruption that locks learning to the drug-like state. REM and NREM cycles support emotional memory sorting and transfer into everyday networks. In ISA terms, if sleep is altered near recall, reconsolidation binds content to the drug-like state and state-dependent memory then limits sober access.

4. Sleep disruption that reinforces the original Malignant Complex through drive states. Disturbed sleep elevates and destabilizes basic bodily urges and threat signals like hunger, fatigue, and hyperarousal. In ISA terms, amplified drive-state noise reactivates the Memory Constellation, confirms the Malignant Complex prediction, and hardens the same avoidance and control routines.

Concise risk readout

• Rebinding. Memories updated in an ibogaine-like state become harder to access when sober and easier to access when the state is mimicked (including the ritualized or therapeutic atmosphere).

• Complex reinforcement. The malignant complex strengthens as the Malignant Complex’s story, instinctual drive-state cues, and body signals fire together outside of the perceived benefits of the “low-dose” psychedelic state.

• Axis drift. Vertical Axis Syncing fails. Bottom-up signals and top-down meaning do not realign, so reported insight does not translate to ego cognition in waking ordinary life.

Low-dose ibogaine does not need visible hallucinations to bend outcomes. A small internal shift during a traumatic recall phase during the “low-dose” protocol can reunite the wrong elements and fix access to key material behind the psychedelic drug-like state. Unless alignment is restored in ordinary waking conditions, especially the conditions that made the original Malignant Complex, the constellation persists, and the complex tightens.

Field context and gaps

Under-Recognized C-PTSD

Classic psychiatry under-recognizes C-PTSD in diagnostic manuals, which encourages top-down cognitive fixes (reasoning that tries to talk symptoms away) while neglecting bottom-up state learning (instinctual and body-based cues that actually drive recall and behavior).

“Sub-Perceptual” Problem

Evidence for sub-perceptual (“microdose”) ibogaine remains thin. Human data are sparse, mostly uncontrolled, and do not show benefits beyond expectancy in a convincing way (Petranker et al., 2024; Polito et al., 2021). PMC+1 The same mechanistic liabilities seen at higher doses plausibly scale down rather than vanish, which is concerning for people with complex trauma.

What exists on “sub-perceptual” ibogaine

• Healthy-volunteer low-dose trial shows minimal effects. A single-dose, healthy-volunteer study using 20 mg ibogaine found minimal mood and cognition effects; the lone suggestive signal was weak and unreliable. It was not a randomized, adequately powered microdosing trial (Forsyth et al., 2016). OPEN Foundation

• Isolated case report in bipolar depression. One case report describes daily “microdosing” ibogaine with self-reported improvement and explicit safety cautions. A single case cannot establish efficacy or safety (Fernandes-Nascimento et al., 2022). SciELO

• Microdosing literature often breaks blind and shrinks under controls. Systematic reviews across psychedelic microdosing, largely LSD/psilocybin, document expectancy effects, frequent “breaking blind,” and outcomes that diminish under randomized, blinded designs (Polito et al., 2021; Petranker et al., 2024; Cavanna et al., 2022). Extrapolation to ibogaine is speculative without direct trials. Macquarie University+2PMC+2

• Pharmacology reviews confirm many targets, not microdose efficacy. Ibogaine’s multi-target pharmacology is reiterated in reviews, but there are no rigorous, controlled efficacy data for sub-perceptual dosing (Tewari, 2010; Sershen & Hashim, 1996). PMC+1

• Definition matters: most “microdoses” are not shown to be true microdoses. Regulators define a microdose as < 1/100th of the pharmacologically active dose and ≤ 100 µg (FDA, 2005; FDA, 2018; ICH M3(R2)). Few ibogaine reports anchor dosing to a known ED50 or meet microgram-range criteria, so many so-called “microdoses” are not demonstrably sub-perceptual to the nervous system (FDA, 2005; FDA, 2018; EMA/ICH, 2010; Roffel et al., 2024). PMC+3U.S. Food and Drug Administration+3U.S. Food and Drug Administration+3

Summary assessment

Microdosing has been widely called “sub-perceptual,” yet many participants can feel discernible drug effects, which compromises blinding and signals real internal state shifts (Polito et al., 2021; Petranker et al., 2024). Macquarie University+1 For ibogaine specifically, controlled human data are nearly absent, and known liabilities from its polypharmacology and sleep-architecture effects plausibly persist at lower amplitudes.

Until randomized, blinded, dose-validated trials exist, the most defensible reading is uncertain benefit with non-zero risk for state-dependent learning and downstream destabilization in trauma-exposed populations (Forsyth et al., 2016; Petranker et al., 2024).

Methods

Approach

An integrative critical synthesis was conducted, drawing on peer-reviewed animal and human studies that address: (1) drug-discrimination and state-dependent learning; (2) reconsolidation; (3) sleep architecture and emotional memory; (4) electrophysiology of gamma power and coherence; (5) polypharmacology and network stability; (6) adverse psychiatric outcomes; and (7) cerebellar toxicity signals.

Integrative critical synthesis means reading across many studies and theories, comparing them directly, and building a single, reasoned argument with clear limits.

Inclusion logic

I prioritized sources that: demonstrate internal state discrimination with ibogaine (Helsley et al., 1997), tie internal state to consolidation or reconsolidation (Osorio-Gómez et al., 2019; Sierra et al., 2013), show sleep and gamma alterations (González et al., 2018), report acute disruptions to cognitive mapping (Ivan et al., 2024), outline receptor-level actions (Bulling et al., 2012; Chen et al., 1996; Itzhak & Ali, 1998; Bowen, 2001), and document psychiatric adverse events (Marta et al., 2015; Knuijver et al., 2018, 2021; Yıldırım et al., 2024). I also note a prospective neuropsychological follow-up that emphasizes improvement signals but does not center harms (Cherian et al., 2023).

Results [8]

1) Ibogaine provides a discriminable internal cue

In rats, ibogaine functions as a discriminative stimulus (an internal signal animals can learn to recognize), with high drug-appropriate responding at standard laboratory doses (Helsley et al., 1997).

If rats can learn the “ibogaine feeling,” then the state is clear enough to tag memories.

2) Early consolidation and reconsolidation import state cues

When psychoactive agents are present during early memory consolidation, later recall improves in matching states (Osorio-Gómez et al., 2019). Reactivated memories can also absorb concurrent state features during reconsolidation (Sierra et al., 2013).

Memories “pick up” parts of whatever state you are in when you store or re-store them.

3) Sleep architecture is disrupted

Rodent studies show prolonged wakefulness and suppression of REM and NREM after ibogaine, along with altered gamma activity (González et al., 2018). Sleep loss heightens emotional reactivity and suggestibility (Goldstein & Walker, 2014; Frenda et al., 2016; Blagrove, 1996).

Disrupted sleep shakes the brain’s “night shift” that organizes feelings and memories.

4) Gamma power rises while coherence falls during wake

Ibogaine increases gamma wave power yet reduces gamma coherence and complexity in rodents, producing a disorientating REM-like signature during wake (Ivan et al., 2024).

Stronger “fast waves” do not help if they stop lining up across brain areas. Misalignment weakens focus and precise memory, thus exacerbating a Malignant Complex’s ability of creating a dissociative field.

5) Polypharmacology remains active at low amplitude

Ibogaine and noribogaine affect serotonin and dopamine transporters, and bind NMDA PCP-site and sigma receptors (Bulling et al., 2012; Chen et al., 1996; Itzhak & Ali, 1998; Bowen, 2001).

Even small doses still push many brain switches at once, which can unbalance timing and salience, thus exacerbating a Malignant Complex’s ability of creating a dissociative field.

6) Adverse psychiatric cases exist

Serious psychiatric events are documented after ibogaine, including mania, psychosis, and persistent perceptual disturbances such as HPPD-like symptoms (Marta et al., 2015; Knuijver et al., 2018, 2021; Yıldırım et al., 2024).

• Mania: Elevated mood, decreased need for sleep, grandiosity, risky behavior (Marta et al., 2015).

• Psychosis: Delusions, hallucinations, disorganized thought and behavior (Knuijver et al., 2021).

• Perceptual persistence: Visual afterimages, trails, derealization or depersonalization consistent with HPPD-like pictures (Knuijver et al., 2018; Yıldırım et al., 2024).

These events are uncommon but clinically significant. They must be part of risk planning, especially for people with unrecognized complex-trauma presentations who lack a cohesive diagnosis under current systems. Individuals with C-PTSD-type symptom constellations may be more vulnerable to destabilization, even at low doses (Yıldırım et al., 2024).

7) Cerebellar toxicity signals appear in preclinical work

In rodents, ibogaine produces patterned loss of Purkinje cells and implicates the olivo-cerebellar pathway, a circuit that feeds timing signals into the cerebellum (O’Hearn & Molliver, 1993; O’Hearn & Molliver, 1997).

The cerebellum supports predictive timing, error correction, sensorimotor integration, speech prosody, and parts of emotional regulation. When this system is perturbed, prediction gets noisy and feedback becomes unreliable.

Likely subclinical consequences of cerebellar toxicity are overt ataxia, clumsy or over- or undershot movements, unstable gaze, flattened or sing-song prosody, irritability, and impaired error prediction and reality-testing. The subjective outcome can be derealization or a “wobbly” sense of a orginized egoic self and world that does not settle.

ISA predicts that noisy prediction signals force the psyche to lean on a Protective Ego Construct. A Protective Ego Construct is a survival mask that keeps you looping old defenses rather than meeting real experience. Cerebellar noise can feed this mask by flooding the system with unreliable timing and salience, which the psyche then overcontrols.

Risk note. These are preclinical signals, not proof of human cerebellar injury. They are strong enough to warrant caution in populations already vulnerable to prediction-error spirals, including people with complex-trauma constellations.

8) Controlled human evidence for microdosing benefits is minimal

Claims of cognitive benefit from ibogaine microdosing lack randomized, blinded support. The only prospective human work to date is small, short, and not designed as a microdose-controlled efficacy trial (Cherian et al., 2023). In adjacent psychedelic microdosing literature, apparent gains often shrink or vanish when studies use proper blinding and expectation controls (Polito et al., 2021; Petranker et al., 2024).

The evidentiary bar for benefit is high. Current human data do not clear it.

Discussion

ISA framing shows how low-dose ibogaine can entrench Malignant Complexes

ISA asserts that Malignant Complexes are survival-built, identity-merged patterns that keep old pain running. Vertical Axis Syncing / Memory Constellation names the dynamic by which bodily state, emotion, and story “snap together” across time. Sub-perceptual ibogaine introduces three multipliers:

1. State-locked encoding. A discriminable drug state during retrieval or reconsolidation can bind that state into the memory trace (Helsley et al., 1997; Sierra et al., 2013). In ISA terms, this strengthens the Constellation around the drug-like state, not everyday life.

If the important insight happens in a drug-shaped state, your brain will look for that state again to access it.

2. Critical-period reopening without safeguards. Psychedelics can reopen windows of social reward learning via oxytocin-linked metaplasticity in nucleus accumbens (Nardou et al., 2023). In harmful contexts, this can encode bad lessons of a Malignant Complex.

The brain may become extra teachable. If the setting is messy or manipulative under the influence of a Malignant Complex, the brain can “learn the wrong thing” fast.

3. Sleep-deprived suggestibility. REM/NREM disruption plus prolonged wake increases emotional volatility and suggestibility (González et al., 2018; Goldstein & Walker, 2014; Frenda et al., 2016). In this state, Protective Ego Constructs (PECs) seek fast coherence and ego salience. They do this by binding the Malignant Complex’s prediction errors to ready-made grand narratives that feel powerful and certain.

How the loop hardens

• State shift: Sleep loss heightens reactivity and lowers critical filtering.

• Story capture: High-salience narratives offer instant meaning and group belonging.

• Memory write-in: During reconsolidation, these narratives attach to the active memory trace.

• Prediction lock: The Malignant Complex now predicts threat and purpose through the adopted story, reinforcing avoidance and control.

Common narrative magnets

• Radical politics framed as pure good versus pure evil

• Extremist or “movement” causes promising total clarity

• Radical drug-culture identities and purity hierarchies

• Charismatic gurus and cultic self-help systems

• Fanaticism around diet, biohacking, or ideology

• “Collective contagions” on social platforms that reward outrage and certainty

Net effect: Sleep-driven suggestibility lets PECs fuse dysphoric internal cues with large, identity-granting stories. The result is stronger prediction errors wearing moral armor, harder to question and easier to rehearse.

Together, these multipliers align with ISA’s warning: seemingly benign or “positive” experiences during a microdose can reinforce a Malignant Complex if the state that built the complex is not addressed directly. The person may feel better, yet the deeper pattern tightens.

Feeling relief does not prove healthy learning. The pattern might just dig in deeper.

Gamma and cognitive maps: why “power without coherence” matters

REM-like gamma during wake suggests diffuse, unstable top-down control (the brain’s steering system that selects and suppresses information) with poor binding of features. That profile compromises cognitive maps in hippocampo-cortical networks (Ivan et al., 2024).

If fast brain rhythms are strong but out of sync, the “inner GPS” gets fuzzy.

Cerebellar Signals: Predictive timing and derealization risk

Preclinical cerebellar toxicity raises concern about precision-weighting of sensory and interoceptive signals. Even subclinical drift can magnify derealization and somatic misreadings in trauma-loaded systems (O’Hearn & Molliver, 1993, 1997).

If the timing center goes off, your world can feel less real and your body signals harder to trust.

“Sub-perceptual” is a moving target

Historically, microdosing was called sub-perceptual (too small to feel). Yet many microdose participants can tell they received a drug, which breaks blinding. The field is shifting toward a definition of “sub-hallucinogenic” or “low-dose without loss of function.”

“Not tripping” does not equal “not feeling” anything. If you can experience a difference, your brain can tag memories with that state.

Diagnostic politics: DSM-5-TR, ICD-11, and the top-down bias

Western nosology underplays C-PTSD, which funnels care toward top-down cognitive strategies and away from bottom-up state learning. ISA treats C-PTSD as a continuum of drive-state and complex dynamics. In this lens, microdosing without state-aware safeguards risks tightening loops rather than freeing them.

If the current psychological and educational systems in the West ignore instinctual and body-based learning, the traditional frameworks will miss how symptoms are actually maintained.

Conclusion

Sub-perceptual ibogaine preserves the key mechanism that worries trauma clinicians: state-dependent tagging of highly salient material, now paired with REM/NREM disruption, REM-like but incoherent gamma during wake, broad polypharmacology, and documented psychiatric adverse events.

Within ISA’s framework, these ingredients can reinforce Malignant Complexes through mis-tuned reconsolidation and context-bound insight. Claims of safe benefit at low dose lack controlled, blinded evidence. For trauma populations, the rational stance is restraint: do not assume “small” equals “safe,” and do not call it “sub-perceptual” when participants can feel it.

Practical implications and testable predictions

1. State-locked access. Trauma memories reactivated during low-dose ibogaine will show poorer sober recall unless drug-like interoceptive cues are reinstated (Helsley et al., 1997; Sierra et al., 2013).

2. Context drives learning. Adverse, dissociative, confused, or coercive post-session contexts will increase symptoms at one to three months, consistent with maladaptive reconsolidation (Nardou et al., 2023).

3. Sleep as a moderator. Degree of REM/NREM suppression in the first seventy-two hours will predict worse regulation and weaker neutral-state recall (González et al., 2018; Goldstein & Walker, 2014).

4. Cognitive-map fragility. Ibogaine-day electrophysiology that shows high gamma power with low coherence will track navigation or planning errors on sensitive tasks (Ivan et al., 2024).

5. Cerebellar precision. Subtle timing deficits will correlate with dissociation and interoceptive prediction errors (O’Hearn & Molliver, 1993, 1997).

Limitations

This synthesis relies on cross-species inference and a small human evidence base for low-dose ibogaine. Adverse events are primarily case-based. Nonetheless, the convergence of mechanisms across independent domains justifies caution.

References

Baumann, M. H., Rothman, R. B., Pablo, J., & Mash, D. C. (2001). In vivo neurobiological effects of ibogaine and its O-desmethyl metabolite, 12-hydroxyibogamine (noribogaine), in rats. The Journal of Pharmacology and Experimental Therapeutics, 297(2), 531–539.

Blagrove, M. (1996). Effects of length of sleep deprivation on interrogative suggestibility. Journal of Experimental Psychology: Applied, 2(1), 48–59. https://doi.org/10.1037/1076-898X.2.1.48

Bowen, W. D. (2001). Sigma receptors and iboga alkaloids. The Alkaloids: Chemistry and Biology, 56, 173–191. https://doi.org/10.1016/S0099-9598(01)56013-7

Bulling, S., Schicker, K., Zhang, Y.-W., Steinkellner, T., Stockner, T., Gruber, C. W., … Sitte, H. H. (2012). The mechanistic basis for noncompetitive ibogaine inhibition of serotonin transporter. Proceedings of the National Academy of Sciences, 109(44), 17179–17184. https://doi.org/10.1073/pnas.1203886109

Cameron, L. P., Tombari, R. J., Lu, J., Pell, A. J., Hurley, Z. Q., Ehinger, Y., … Olson, D. E. (2021). A non-hallucinogenic psychedelic analogue with therapeutic potential. ACS Pharmacology & Translational Science, 4(3), 1009–1023. https://doi.org/10.1021/acsptsci.1c00014

Cavanna, F., McLoughlin, S., & Harmer, C. J. (2022). Investigating and mitigating bias in psychedelic microdosing randomised controlled trials. Journal of Psychopharmacology, 36(12), 1381–1396. https://doi.org/10.1177/02698811221138461 search.lib.uts.edu.au

Chen, K., Rover, S., & Schwarcz, R. (1996). Ibogaine block of the NMDA receptor: In vitro and in vivo studies. European Journal of Pharmacology, 309(2), 135–140. https://doi.org/10.1016/0014-2999(96)00437-2

Cherian, K. N., Scheiermann, A., Neylan, A. J., et al. (2023). The effect of ibogaine on cognitive functioning. Journal of the International Neuropsychological Society, 29(S1), 22. https://doi.org/10.1017/S1355617723011049

Fernandes-Nascimento, J., Velásquez-Rodríguez, C. M., Assis, M. A., Gastaud, M. B., Sbicigo, J. B., & Wang, Y.-P. (2022). Case report: Daily microdoses of ibogaine for the treatment of bipolar depression. Revista Brasileira de Psiquiatria, 44(4), 462–463. https://doi.org/10.1590/1516-4446-2021-0047 SciELO

Food and Drug Administration. (2005). Exploratory IND studies: Guidance for industry. https://www.fda.gov/media/72325/download U.S. Food and Drug Administration

Food and Drug Administration. (2018). Exploratory IND studies (webpage, updated). https://www.fda.gov/regulatory-information/search-fda-guidance-documents/exploratory-ind-studies U.S. Food and Drug Administration

Forsyth, B., Machado, L., Jowett, T., Jakobi, H., Garbe, K., Winter, H., & Glue, P. (2016). Effects of low dose ibogaine on subjective mood state and psychological performance. Journal of Ethnopharmacology, 189, 10–18. https://doi.org/10.1016/j.jep.2016.05.022 OPEN Foundation

Frenda, S. J., Berkowitz, S. R., Loftus, E. F., & Fenn, K. M. (2016). Sleep deprivation and false confessions. Proceedings of the National Academy of Sciences, 113(8), 2047–2050. https://doi.org/10.1073/pnas.1521518113

Goldstein, A. N., & Walker, M. P. (2014). The role of sleep in emotional brain function. Annual Review of Clinical Psychology, 10, 679–708. https://doi.org/10.1146/annurev-clinpsy-032813-153716

González, J., Pirez, N., Tang, Q., Di Paolo, T., & Urbano, F. J. (2018). Ibogaine acute administration in rats promotes wakefulness and suppresses REM sleep. Frontiers in Pharmacology, 9, 374. https://doi.org/10.3389/fphar.2018.00374

Helsley, S., Rabin, R. A., & Winter, J. C. (1997). The effects of noribogaine and harmaline in rats trained with ibogaine as a discriminative stimulus. Life Sciences, 60(9), PL147–PL153. https://doi.org/10.1016/S0024-3205(96)00703-5

International Council for Harmonisation. (2010). ICH guideline M3(R2): Non-clinical safety studies for the conduct of human clinical trials and marketing authorisation (Step 5). European Medicines Agency. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-m3r2-non-clinical-safety-studies-conduct-human-clinical-trials-and-marketing-authorisation-pharmaceuticals-step-5_en.pdf European Medicines Agency (EMA)

Itzhak, Y., & Ali, S. F. (1998). Effect of ibogaine on the various sites of the NMDA receptor complex and sigma binding sites. Annals of the New York Academy of Sciences, 844(1), 245–249. https://doi.org/10.1111/j.1749-6632.1998.tb08240.x

Ivan, V. E., Kim, M., Bradley, E. C., Sweeney, P. J., Guerra, A., & Beggs, J. M. (2024). The nonclassic psychedelic ibogaine disrupts cognitive maps. Biological Psychiatry: Global Open Science, 4(1), 46–58. https://doi.org/10.1016/j.bpsgos.2023.11.006

Ivan, V. E., Tomàs-Cuesta, D. P., Esteves, I. M., Curic, D., Mohajerani, M., McNaughton, B. L., Davidsen, J., & Gruber, A. J. (2024). The nonclassic psychedelic ibogaine disrupts cognitive maps. Biological Psychiatry: Global Open Science, 4(1), 275–283. https://doi.org/10.1016/j.bpsgos.2023.07.008

Knuijver, T., Lieverse, R., & Klein, H. C. (2018). Hallucinogen persisting perception disorder after ibogaine. Journal of Clinical Psychopharmacology, 38(4), 401–403. https://doi.org/10.1097/JCP.0000000000000902

Knuijver, T., Lieverse, R., & Klein, H. C. (2021). Safety of ibogaine administration in detoxification of opioid-dependent individuals. Journal of Clinical Psychopharmacology, 41(4), 428–436. https://doi.org/10.1097/JCP.0000000000001411

Marta, C. J., Ryan, W., Kopelowicz, A., & Koek, R. J. (2015). Mania following use of ibogaine: A case series. The American Journal on Addictions, 24(3), 203–205. https://doi.org/10.1111/ajad.12209

Nardou, R., Sawyer, E., Song, Y. J., Wilkinson, M., Padovan-Hernandez, Y., de Deus, J. L., Wright, N., Lama, C., Faltin, S., Goff, L. A., Stein-O’Brien, G. L., & Dölen, G. (2023). Psychedelics reopen the social reward learning critical period. Nature, 618, 790–798. https://doi.org/10.1038/s41586-023-06204-3

Osorio-Gómez, D., Saldivar-Mares, K. S., Perera-López, A., McGaugh, J. L., & Bermúdez-Rattoni, F. (2019). Early memory consolidation window enables drug induced state-dependent memory. Neuropharmacology, 146, 84–94. https://doi.org/10.1016/j.neuropharm.2018.11.033

O’Hearn, E., & Molliver, M. E. (1993). Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Neuroscience, 55(2), 303–310. https://doi.org/10.1016/0306-4522(93)90500-F

O’Hearn, E., & Molliver, M. E. (1997). The olivocerebellar projection mediates ibogaine-induced degeneration of Purkinje cells: A model of indirect, trans-synaptic excitotoxicity. The Journal of Neuroscience, 17(22), 8828–8841. https://doi.org/10.1523/JNEUROSCI.17-22-08828.1997

Petranker, R., Puil, L., Garcia-Romeu, A., Gorman, I., Perkins, D., Reiff, C., & Gravitz, M. A. (2024). A critique of the current state of microdosing research. Frontiers in Psychiatry, 15, 1325842. https://doi.org/10.3389/fpsyt.2024.1325842 PMC

Polito, V., Stevenson, R. J., Gratton, C., & Razi, A. (2021). A systematic study of microdosing psychedelics. Human Psychopharmacology: Clinical and Experimental, 36(6), e2803. https://doi.org/10.1002/hup.2803 Macquarie University

Roffel, A. F., et al. (2024). The application of Phase 0 and microtracer approaches in drug development. Frontiers in Pharmacology, 15, 1369079. https://doi.org/10.3389/fphar.2024.1369079 Frontiers

Sershen, H., & Hashim, A. (1996). Ibogaine: Neurochemical and pharmacological overview. In New Research Directions in Drug Abuse (NIDA Research Monograph 164), 24–38. (Sigma and NMDA site interactions discussed). PubMed

Sierra, R. O., Cassini, L. F., Santana, F., Crestani, A. P., Duran, J. M., Haubrich, J., de Oliveira Alvares, L., & Quillfeldt, J. A. (2013). Reconsolidation may incorporate state-dependency into previously consolidated memories. Learning & Memory, 20(7), 379–387. https://doi.org/10.1101/lm.030023.112

Tewari, T., et al. (2010). Microdosing: Concept, application and relevance. Indian Journal of Pharmacology, 42(3), 153–159. https://doi.org/10.4103/0253-7613.66832

van der Helm, E., Yao, J., Dutt, S., Rao, V., Saletin, J. M., & Walker, M. P. (2011). REM sleep de-potentiates amygdala activity to previous emotional experiences. Current Biology, 21(23), 2029–2032. https://doi.org/10.1016/j.cub.2011.10.052

Yıldırım, B., Şahin, S. S., Gee, A., Jauhar, S., Rucker, J., Salgado-Pineda, P., Pomarol-Clotet, E., & McKenna, P. (2024). Adverse psychiatric effects of psychedelic drugs: A systematic review of case reports. Psychological Medicine, 54(15), 4035–4047. https://doi.org/10.1017/S0033291724002496