HoldsUp

Nolan Williams

Stanford Brain Stimulation Lab

Nolan Williams is a neuropsychiatrist and the Director of the Stanford Brain Stimulation Lab. His published research focuses on neuromodulation interventions, including transcranial magnetic stimulation, deep brain stimulation, and Stanford Neuromodulation Therapy (SAINT) for disorders such as treatment-resistant depression and obsessive-compulsive disorder. Additionally, he studies the neural correlates and therapeutic outcomes of magnesium-ibogaine treatments for post-traumatic stress disorder and traumatic brain injury.

32 claims checked on air: 2 context 3 overstated 23 supported 4 unverified

What they said on air - supported

5 citing their own research

0:06:11supportedhighOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Ibogaine interacts broadly with essentially all neurotransmitter systems.

"If you look at the pharmacology of ibogaine, it's very broad-acting, right? So it actually interacts with a with a lot of—I mean, essentially all of the neurotransmitter systems in in a unique way." (said at 0:06:11)

Pharmacological radioligand binding screens demonstrate that ibogaine exhibits broad polypharmacology, binding directly to receptors, transporters, and channels across virtually all major neurotransmitter systems. In vitro radioligand binding studies targeting over 50 receptors, ion channels, and transporters showed that ibogaine interacts at micromolar concentrations with opioid receptors (mu, delta, kappa), serotonin receptors (5-HT2, 5-HT3) and transporters, dopamine uptake sites, norepinephrine uptake sites, muscarinic acetylcholine receptors (M1, M2), and NMDA glutamate receptor channels (PMID: 7568622, PMID: 8995326).

0:09:40supportedhighOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Glial-derived neurotrophic factor (GDNF) upregulates dopamine neuron health.

"glial-derived neurotrophic factor is a neurotrophic factor that that's involved with dopamine neuron kind of health, right? And so it upregulates dopamine neuron health." (said at 0:09:40)

Glial cell line-derived neurotrophic factor (GDNF) was initially identified and characterized for its ability to promote the survival, morphological differentiation, and dopamine uptake of midbrain dopaminergic neurons. Extensive in vitro, animal, and translational studies have firmly established GDNF and its receptor signaling pathway (GFRα1/RET) as key neuroprotective and neurotrophic regulators of dopaminergic neuronal maintenance.

0:10:14supportedlowOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Administering ibogaine to rodents trained to self-administer alcohol causes them to stop self-administering alcohol.

"And if you take a mouse like that and you give them ibogaine, you can actually reverse it. They'll stop self-administering alcohol, which is cool." (said at 0:10:14)

Preclinical studies in rodents demonstrate that ibogaine administration reduces or suppresses alcohol self-administration and consumption. For example, He et al. (2005) demonstrated that ibogaine decreased ethanol intake in rats using both two-bottle choice and operant self-administration models, as well as in a relapse model. Similarly, Glick et al. (2000) showed that ibogaine reduced oral self-administration of ethanol in rats. Evidence is limited to animal (rodent) models and early preclinical research.

0:10:26supportedvery lowOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Injecting glial-derived neurotrophic factor (GDNF) directly into the ventral tegmental area of rodents causes them to stop self-administering alcohol.

"If you take a mouse and you inject glial-derived neurotrophic factor into the ventral tegmental area, which is the dopamine-producing area that's involved with more of the reward system, you can also produce the same effect. They will stop self-administering." (said at 0:10:26)

Animal research supports the claim that microinjection of glial cell line-derived neurotrophic factor (GDNF) directly into the ventral tegmental area (VTA) rapidly and selectively suppresses alcohol intake and operant self-administration in rodents. In rodent models of alcohol consumption and relapse, intra-VTA infusion of GDNF dose-dependently reduced operant self-administration of ethanol without altering sucrose intake, and blocked reacquisition after extinction. Because the evidence is derived entirely from preclinical animal models, certainty is rated very low.

0:10:47supportedvery lowOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Injecting ibogaine directly into the ventral tegmental area stops alcohol self-administration in rodents.

"Inject just ibogaine just into that area, you can recapitulate the effect, right?" (said at 0:10:47)

Preclinical animal research demonstrates that direct microinjection of ibogaine into the ventral tegmental area (VTA) significantly reduces operant ethanol self-administration in rats. This effect is anatomically site-specific (it does not occur when injected into the neighboring substantia nigra) and is mediated via the local upregulation of glial cell line-derived neurotrophic factor (GDNF). Because the evidence is derived exclusively from rodent models, the GRADE certainty is very low.

0:10:47supportedvery lowOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Direct electrical brain stimulation of the ventral tegmental area can suppress alcohol self-administration in rodent models.

"People have also shown that you can produce this effect by directly stimulating into those areas, right?" (said at 0:10:47)

Preclinical studies in rodent models demonstrate that direct stimulation of dopamine neurons in the ventral tegmental area (VTA) can reduce voluntary ethanol self-administration and alcohol-seeking behavior. Specifically, optogenetic stimulation mimicking tonic firing patterns in VTA dopamine neurons significantly attenuates ethanol intake and appetitive seeking in rats, whereas phasic stimulation can produce opposite effects. Because evidence is limited to animal models, GRADE certainty is very low.

0:11:18supportedlowtheir own paperOne Dose That Heals Addiction, PTSD, and Brain Injury | The

In a clinical trial published in Nature Mental Health, ibogaine administration produced a general slowing of EEG power spectra that correlated with the strength of the subjective psychedelic experience, PTSD symptom reduction, and cognitive improvement.

"The the the next piece of data that we have, we published in Nature Mental Health, I don't know, a week ago or something, which is a really interesting study where people with that in our trial that received ibogaine had had EEG, like brainwave tests, before, after, and one month after they received ibogaine. And what we saw is this kind of general slowing of all of the the kind of different power spectra of the the EEG, right? So people had a general kind of physiologic slowing of their brain after, and the slowing actually was correlated with the the strength of the trip, like the amount that they had a psychological effect... But also, interestingly, the reduction in PTSD symptoms and the improvement in cognition." (said at 0:11:18)

Evidence from an open-label study evaluating a magnesium-ibogaine protocol in 30 Special Operations Forces veterans with traumatic brain injury found that ibogaine administration was associated with post-treatment EEG slowing (including persistent reductions in peak alpha frequency) that correlated with the intensity of subjective mystical experiences and reductions in PTSD symptoms. The parent trial demonstrated marked improvements in PTSD, depression, anxiety, and functioning. However, evidence is limited by the open-label, uncontrolled study design and small sample size.

0:19:37supportedhighOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Geodon (ziprasidone) causes a significant degree of QT interval prolongation.

"Lots of drugs do that. Antipsychotics do that, right? Geodon in particular does that at a great degree." (said at 0:19:37)

Ziprasidone (Geodon) is well-established in systematic reviews, clinical trials, and real-world pharmacovigilance studies as carrying one of the highest risks of corrected QT (QTc) interval prolongation among atypical antipsychotics. Network meta-analyses and comparative cohort studies consistently rank ziprasidone near the top among second-generation antipsychotics for mean QTc prolongation and associated hazard.

0:24:53supportedmoderateOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Ibogaine was listed on the French pharmaceutical formulary from 1930 to 1966 under the brand name Lambarène as a daily microdose medication.

"The French started discovered this in the Western world in about 1900. It was on the French French formulary from 1930 to 1966. And it was actually a at lower doses called Lambarène and was a like a daily microdose essentially." (said at 0:24:53)

Historical literature on the pharmacology of ibogaine confirms that French researchers isolated the alkaloid in 1900 and that low-dose ibogaine was subsequently commercialized as a pharmaceutical product under the brand name Lambarène, alongside other retail formulations, during the 20th century.

0:25:33supportedlowOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Animal studies show that animals do not self-administer ibogaine.

"It is neither people don't self-administer it. There there's no there's no animal data to suggest that there's a self-administration." (said at 0:25:33)

Preclinical animal research demonstrates that ibogaine lacks reinforcing and rewarding properties, and animals do not self-administer it. Instead, animal models consistently show that ibogaine and related iboga alkaloids blunt or reduce the self-administration of other reinforcing substances, including opioids, cocaine, alcohol, and nicotine.

0:25:44supportedhighOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Ibogaine is classified as a Schedule I controlled substance under the United States Controlled Substances Act.

"but it was lumped in uh to the US Controlled Substance Act, Schedule I substance, which is where it's stayed uh, you know, since then and really prevented folks from using it." (said at 0:25:44)

Under federal law, ibogaine is classified as a Schedule I controlled substance under the United States Controlled Substances Act (enacted in 1970). This classification designates it as having a high potential for abuse and no accepted medical use, placing strict regulatory and legal restrictions on its possession, clinical use, and research.

0:29:10supportedmoderateOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Intravenous magnesium is recommended by American Heart Association guidelines as the treatment for torsades de pointes.

"magnesium is actually the treatment and the American Heart Association guidelines treatment for um for torsades, the fatal arrhythmia that's the result of of ibogaine." (said at 0:29:10)

Intravenous magnesium is established in clinical practice and cardiology resuscitation guidelines (such as those from the American Heart Association and American College of Cardiology) as the first-line pharmacologic therapy for torsades de pointes (TdP). In clinical studies and reviews, intravenous magnesium terminates episodes of TdP in approximately 78% of patients, though observational studies emphasize that defibrillation readiness remains necessary.

0:29:35supportedmoderateOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Ibogaine interacts with hERG potassium channels to produce cardiac arrhythmias.

"when the ibogaine interacts with the um with the potassium um channels that are involved in the hERG potassium channels are involved in this arrhythmia, that they won't throw the heart into the rhythm." (said at 0:29:35)

Electrophysiological studies in cell models and clinical toxicology literature demonstrate that ibogaine and its primary active metabolite, noribogaine, directly bind to and inhibit human ether-à-go-go-related gene (hERG) potassium channels. Because hERG channels conduct the rapid delayed rectifier potassium current (IKr) essential for cardiac repolarization, their blockade delays repolarization, prolongs the QT interval, and can trigger potentially fatal cardiac arrhythmias such as torsades de pointes.

0:35:45supportedvery lowtheir own paperOne Dose That Heals Addiction, PTSD, and Brain Injury | The

An analysis using an AI-based MRI brain age pipeline showed that patients treated with ibogaine had brains that appeared an average of 1.5 years younger at one month post-treatment.

"And what this what this is showing is um, as a group average, people have about a year and a half younger-looking brain at one month." (said at 0:35:45)

A prospective observational study evaluated structural MRI changes in Special Operations Forces veterans with blast-induced traumatic brain injury undergoing a magnesium-ibogaine protocol. Using T1-weighted MRI scans to estimate predicted brain age, researchers found a statistically significant reduction in predicted brain age of 1.3 years at 1-month post-treatment compared to baseline (n = 22). While this matches the speaker's statement of "about a year and a half younger-looking brain," the evidence comes from a small, open-label, uncontrolled cohort study.

0:37:57supportedmoderateOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Noribogaine exhibits a cardiac risk profile similar to ibogaine, and ibogaine is metabolized into noribogaine via the CYP2D6 enzyme over roughly 8 to 12 hours.

"So, the noribogaine does have a similar cardiac profile. Ibogaine is metabolized into noribogaine through 2D6. And so you see people with getting ibogaine and they they metabolize um to noribogaine uh in in roughly 12 hour, 8 to 12 hours or something like that." (said at 0:37:57)

Published pharmacological and clinical pharmacokinetic evidence supports the speaker's assertions. Ibogaine is primarily metabolized via O-demethylation to its active metabolite noribogaine by the hepatic cytochrome P450 enzyme CYP2D6. Pharmacokinetic studies in humans demonstrate that ibogaine has an elimination half-life of roughly 8 to 12 hours (reported as ~10.2 hours in extensive/intermediate metabolizers, though highly variable based on CYP2D6 phenotype). Furthermore, toxicological reviews and cardiac studies indicate that noribogaine possesses a cardiotoxicity profile similar to ibogaine, both mediating hERG potassium channel blockade and carrying risks of QT interval prolongation.

0:38:34supportedlowtheir own paperOne Dose That Heals Addiction, PTSD, and Brain Injury | The

In EEG research on ibogaine, the magnitude of the subjective psychological experience correlated with the degree of PTSD symptom improvement.

"What we found with the EEG stuff that I published a week ago is the degree of that subjective effect is correlated with the degree of the of the PTSD improvement." (said at 0:38:34)

A published open-label study evaluating magnesium-ibogaine therapy in 30 male veterans with traumatic brain injury examined subjective experience using the Mystical Experiences Questionnaire (MEQ30), electroencephalography (EEG) measures, and PTSD symptom severity. The study found that greater intensity of the subjective mystical experience during ibogaine treatment significantly correlated with larger reductions in PTSD symptom severity both immediately (p < 0.001) and one month post-treatment (p = 0.007), as well as with persistent reductions in EEG peak alpha frequency.

0:45:20supportedhighOne Dose That Heals Addiction, PTSD, and Brain Injury | The

In pivotal clinical trials for oral antidepressants such as Prozac, the difference between active drug and placebo was only 2 to 3 points on a 60-point scale, matching the inter-rater reliability margin of error.

"I mean, if you look at oral antidepressant differences between active and placebo for some of the pivotal trials that led to approval for something like Prozac, you're you're talking about a two-to-three-point difference on a 60-point scale, and the inter-rater reliability um on that scale is two points." (said at 0:45:20)

Comprehensive analyses of clinical trial datasets submitted to the US FDA for antidepressant licensing (including fluoxetine/Prozac) confirm that the mean overall difference between active drug and placebo on the Hamilton Rating Scale for Depression (HAM-D) is modest, typically ranging between 1.75 and 2.5 points. For instance, an individual participant data analysis of 232 randomized placebo-controlled trials submitted to the FDA between 1979 and 2016 found an overall random-effects mean difference of 1.75 points (95% CI: 1.63 to 1.86) favoring antidepressants.

0:47:21supportedlowtheir own paperOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Ibogaine treatment has produced 20- to 30-point improvements on the 60-point Montgomery-Åsberg Depression Rating Scale (MADRS).

"Yeah. I mean, we're seeing, you know, in some cases a 20- or 30-point change on a 60-point scale, where that scale as a generality people don't really score above mid-30s on on the on the Montgomery-Åsberg Depression Rating Scale." (said at 0:47:21)

A prospective open-label observational study of magnesium-ibogaine therapy in 30 Special Operations Forces veterans with mild traumatic brain injuries evaluated depressive symptoms using the Montgomery-Åsberg Depression Rating Scale (MADRS). The study reported large and statistically significant improvements in depression at one month post-treatment (Cohen's d = 2.80), with individual and mean reductions in MADRS scores aligning with the 20- to 30-point drop described. Because the published evidence comes from an uncontrolled, open-label trial, certainty is graded as low, and randomized controlled trials are required to confirm efficacy.

0:48:25supportedhighOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Cannabidiol (CBD) has received regulatory approval for the treatment of pediatric epilepsy syndromes, specifically Lennox-Gastaut syndrome and Dravet syndrome.

"GW Pharmaceuticals was as it relates to cannabinoids, you know, and so there's an approval, I don't know if it's like a full approval or an orphan approval, but there's an approval for um CBD, cannabidiol, for uh pediatric epilepsy syndromes. So, Lennox-Gastaut and Dravet syndrome, right?" (said at 0:48:25)

Cannabidiol (CBD oral solution, formulated as Epidiolex by GW Pharmaceuticals) received regulatory approval from the U.S. Food and Drug Administration (FDA) in 2018 and the European Medicines Agency (EMA) in 2019 for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in pediatric patients, supported by phase 3 randomized, double-blind, placebo-controlled clinical trials.

0:56:58supportedlowtheir own paperOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Veterans treated with ibogaine exhibited a statistically significant improvement in measures of cognition, specifically in frontal executive control.

"So, what we observed in the veterans was that they had an improvement in cog-- statistically significant improvement in some aspects of cognition, particularly around frontal control." (said at 0:56:58)

Published observational studies investigating ibogaine (including the Stanford MISTIC protocol of magnesium-ibogaine and clinic programs in Special Operations Forces veterans with traumatic brain injuries) reported statistically significant improvements in functional disability, psychiatric symptoms, and cognitive measures from baseline to follow-up. However, the available evidence is from open-label, uncontrolled observational cohorts and retrospective surveys, warranting cautious interpretation until validated in randomized, placebo-controlled trials.

1:07:45supportedmoderateOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Clinical OCD data shows that large therapeutic effects can be achieved by isolating and modifying a single brain circuit.

"It looks like from our OCD data, that you can get big effects from just isolating one brain circuit and modifying it." (said at 1:07:45)

Clinical data from targeted neuromodulation in treatment-resistant obsessive-compulsive disorder (OCD)—including deep brain stimulation (DBS) and circuit-guided transcranial magnetic stimulation targeting specific cortico-striato-thalamo-cortical pathways—demonstrate large therapeutic effects. Meta-analyses of DBS trials targeting defined nodes and white matter tracts (such as the anterior limb of the internal capsule and inferior thalamic peduncle) demonstrate substantial symptom reductions on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), with response rates around 60% and significant differentiation in clinical efficacy based on specific anatomical circuit targeting.

1:11:01supportedmoderateOne Dose That Heals Addiction, PTSD, and Brain Injury | The

Johns Hopkins psilocybin trials demonstrated personality changes that persisted out to one year.

"the Hopkins group demonstrated this profound personality change that um they observed out to a year, I think, uh early on with their trials with psilocybin." (said at 1:11:01)

Early psilocybin trials conducted at Johns Hopkins University evaluated personality changes across the five-factor model and demonstrated significant increases in the personality trait of Openness following high-dose psilocybin sessions. In participants who had a 'complete' mystical experience during their session, these increases in Openness persisted and remained significantly elevated above baseline at more than one year follow-up.

1:13:06supportedmoderateOne Dose That Heals Addiction, PTSD, and Brain Injury | The

According to the World Health Organization, 1 in 2 people will receive a DSM psychiatric diagnosis or dementia diagnosis at some point in their lifetime.

"there was a WHO statistic that really struck me, which is one out of two people will have a DSM diagnosis at some point in their lifetime. Purely psychiatric or dementia. One out of two." (said at 1:13:06)

A 2023 cross-national analysis of the World Health Organization (WHO) World Mental Health surveys across 29 countries (n = 156,331) published in The Lancet Psychiatry estimated that approximately 50% (1 in 2) of individuals will develop at least one DSM mental disorder by age 75. The lifetime morbid risk was estimated at 46.4% for males and 53.1% for females across 13 common DSM-IV disorders.

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