362. KETAMINE CURES PSYCHIATRIC AND NEUROLOGICAL DISEASES AND FACILITATES WITHDRAWAL FROM SSRIs AND OTHER ADDICTIVE, INEFFECTIVE PSYCH DRUGS

NEW RESOURCE: YOHO’S APOCALYPSE ALMANAC tells how to treat many diseases. It’s a little tongue-in-cheek, but it includes references and links.

A rat neuron before (top) and after (bottom) ketamine treatment. The increased number of orange nodes are restored connections in the rat’s brain.

—Ronald Duman/Yale University

Researchers from Yale and the National Institute of Mental Health (NIMH) say ketamine seems to cause a burst of new connections to form between nerve cells in parts of the brain involved in emotion and mood.

The discovery, described in Science, should speed the development of the first truly new depression drugs since the 1970s, the researchers say.

“It’s exciting,” says Ron Duman, a psychiatrist and neurobiologist at Yale University. “The hope is that this new information about ketamine is really going to provide a whole array of new targets that can be developed that ultimately provide a much better way of treating depression.”

Depression is associated with a loss of so-called synaptic connections between nerve cells, Duman says. So he and other scientists began to study mice exposed to stresses that produce symptoms a lot like those of human depression.

The stressed mice lost connections in certain parts of the brain. But a dose of ketamine was able to “rapidly increase these connections and also to rapidly reverse the deficits that are caused by stress,” Duman says.

A team at the National Institute of Mental Health also has found evidence that ketamine works by encouraging synaptic connections.

It’s possible to see the change just by studying rodent brain cells with a microscope, says Carlos Zarate from the Mood and Anxiety Disorders Program at the National Institute of Mental Health.

He says a healthy neuron looks like a tree in spring, with many branches and leaves extending toward synaptic connections with other neurons. “What happens in depression is there’s a shriveling of these branches and these leaves, and it looks like a tree in winter. And a drug like ketamine does make the tree look like one back in spring.”

And there’s also indirect evidence that ketamine is restoring synaptic connections in people, Zarate says.

His team studied 30 depressed patients who got ketamine. And they found changes in brainwave activity that indicated the drug had strengthened connections between neurons in areas of the brain involved in depression.

Yoho introduction: I met a psychiatrist who was an expert in the use of ketamine to treat psychiatric and neurological diseases. From what he said, cheap, generic ketamine could replace many profitable patent drugs and effect many cures.

The psychiatrist has a colleague who has treated five hundred patients with this drug. His medical board is hassling him, claiming without justification that its off-label use is wrong. Because of the psychiatrist’s fears that they would go after him, too, he requested anonymity. I will refer to him as James. Medical boards enforce Pharma’s monopoly.

In my past life as a cosmetic surgeon, I used ketamine in combination with dilute propofol for anesthesia several thousand times. I published a paper about it and included it here for your curiosity.

I believed I knew everything about the drug, and thought it was nearly useless. At modest doses of even 50 milligrams intravenously, I had seen depressed breathing, occasional hallucinations, and frequent blood pressure elevation. Although I had learned to cover most of this up using IV propofol, I ultimately quit using ketamine because it added nothing to my anesthesia. I dismissed its use for depression and anxiety as yet another Pharma abuse promoted by idiots.

I was wrong, and for once in my life, I listened instead of talking. James told me about his treatment successes. The psych drugs—SSRIs such as Prozac, benzodiazepines such as valium, and atypical antipsychotics work poorly compared with ketamine. Stated better—they are utter failures that have never been properly studied; see Butchered by “Healthcare.”

Special K caught on in my new friend’s practice like California wildfires on Gavin Newsom’s watch. James told me that after two years of prescribing it, he had successfully treated over 300 patients. He went from having only ineffective, addictive drugs to possessing superpowers.

Here is what he said about his protocol:

I prescribe ketamine at bedtime. I either prescribe the liquid or obtain lozenges from a compounding pharmacy, which work better. My patients hold the ketamine in their mouth as long as they can to facilitate absorption. They report a drowsy, one-drink sensation and typically sleep well.

Patients are directed to take it every four days for four doses, then every three days for four doses, then every two days, then daily. Some providers recommend more rapid introductory dosing.

I start my patients with 25 mg, but after a week on daily ketamine, the dose can be increased by 25 milligram every 1-4 weeks if necessary until we have a successful clinical response. Most respond to 50 to 100 mg doses, and the maximum dose I have prescribed is 150 mg/day. If side effects of next-day sedation or anxiety, irritability, or insomnia occur, I cut the dose in half.

Clinical improvement can be rapid for depression but happens over many months to a year or more for neurological diseases.

Most patients spontaneously quit all other psych drugs. I try to help them withdraw gradually, but many of them do it on their own without consulting me.

I heard second-hand from a reliable source about a wheelchair-bound ALS patient who recovered walking and other daily living functions within a month. He did well for a year, after which he left the area, stopped the medication, deteriorated, and disappeared.

I have treated two cases of Parkinson’s, but my results were mixed. Several colleagues have had dramatic successes, however.

Brain scans and other measures have shown neuronal improvement with treatment. THIS review of the neuroimaging literature may be the best source. There is a lot more.

Word is getting out about ketamine, but no pharma company will study it, for the drug is generic and would be unprofitable.

We have many encouraging case reports:

1. Improvement in ulnar nerve damage

2. Improvement for complex regional pain syndromes

3. ADHD and OCD have been successfully treated at the University of Colorado.

4. MRIs show growth of brain tissue.

I believe from what I have read and seen that patients may be able to quit ketamine and consider themselves cured at about three years.

James kindly sent me journal articles about all this, and I amalgamated their information and summarized them for you in the following essay:

How Ketamine and Psychedelics Are Revolutionizing Mental Health Treatment

Depression and other mental health disorders treatment is moving beyond traditional chemical imbalance theories toward physical restoration of damaged brain connections. This revolutionary approach centers on compounds that promote neural plasticity—the brain’s ability to form new connections and reshape existing circuits. Ketamine, originally developed as an anesthetic, demonstrated rapid antidepressant effects within hours rather than the weeks required by conventional medications. Following this breakthrough, scientists identified that psychedelic compounds including LSD, DMT, and psilocin (psilocybin) operate through similar mechanisms, creating an entirely new therapeutic category called “psychoplastogens.” These discoveries are the most significant advance in psychiatry in five decades. They offer hope for patients who have not responded to conventional treatments.

The Discovery and Mechanism of Ketamine’s Antidepressant Properties

Calvin Stevens, an organic chemistry professor at Wayne State, was the first to synthesize ketamine. In 1963, scientists at Parke-Davis developed it as a safer alternative to PCP (phencyclidine) for short-acting anesthesia without PCP’s severe side effects. The FDA approved the anesthetic in 1970, and the World Health Organization has listed it as an “Essential Medicine” since 1985. Although it is now made in labs, ketamine is a natural medicine and not a synthetic drug; in 2020, researchers found that a fungus called Pochonia chlamydosporia produces the same substance.

Unlike traditional antidepressants that require weeks to demonstrate benefits, ketamine provides relief almost instantly in some cases. Ron Duman, a psychiatrist and neurobiologist at Yale, describes this breakthrough as “maybe one of the biggest findings in the field over the last 50 years.” The hope surrounding ketamine stems from new understanding of its mechanisms, potentially providing numerous new targets for developing better depression treatments.

Yoho note: this was a paraphrase from one of the articles. What it means is that Pharma’s interest is in developing slightly changed compounds they can patent and charge a fortune for.

Rapid Structural Brain Changes

Research teams at Yale and the National Institute of Mental Health determined that ketamine’s effectiveness lies not in its effects on neurotransmitters like serotonin,* but in its ability to cause rapid structural changes in brain cells. These changes occur within hours and last for days or weeks, explaining why a single treatment can provide sustained relief from depression symptoms. The compound works even in treatment-resistant populations, offering hope to patients who have exhausted other options.

*Yoho note: The serotonin theory of depression is nonsense, but it still used in ads and found in literature like this. From Butchered by “Healthcare:”

The Selective Serotonin Re-uptake Inhibitor (SSRI) name was pseudoscience dreamed up in the marketing department of SmithKline Beecham. The “chemical imbalance in the brain” idea was the brainstorm of a sales copywriter in the 1950s. Knowledge of serotonin and other neurotransmitters was even more sketchy when Prozac was invented than it is now. Today, this seductive but mythical gibberish embarrasses researchers.

Clinical studies reveal ketamine’s effectiveness for different forms of depression. Controlled trials demonstrate response rates of 55-80% in subjects with major depression, with effects lasting 7-10 days from a single dose. The drug shows promise for bipolar depression, which is challenging to treat. The consistency of these results across multiple studies solidifies ketamine’s position as a legitimate therapeutic breakthrough.

Depression involves the loss of connections between nerve cells, particularly in brain regions that control emotion and mood. Scientists studying mice exposed to stress—which produces symptoms resembling human depression—found that stressed animals lost connections in specific brain areas. However, a dose of ketamine rapidly increased these connections and reversed the deficits caused by stress. This discovery provided the first clear mechanism for understanding how ketamine achieves its rapid antidepressant effects.

The Tree Metaphor and Neural Restoration

Carlos Zarate from the Mood and Anxiety Disorders Program at NIMH explains that brain changes are visible when studying rodent brain cells under a microscope. A healthy neuron resembles a tree in spring, with many branches and leaves extending toward connections with other neurons. In depression, these branches and leaves shrivel, making the neuron look like a bare winter tree. Ketamine makes the tree look like spring again, restoring the full, healthy appearance of neural connections.

Evidence from human studies supports the animal research findings. Zarate’s team studied 30 depressed patients who received ketamine and found changes in brainwave activity indicating that the drug had strengthened connections between neurons in brain areas involved in depression. These measurable changes in brain function correspond with the rapid improvement in mood and other depression symptoms that patients experience.

Neural Plasticity and the Birth of Psychoplastogens

The success of ketamine prompted researchers to investigate whether other compounds might work through similar mechanisms. This search led to the discovery that classical psychedelic compounds—including LSD, DMT, psilocin, and MDMA—promote structural and functional neural plasticity comparable to or even greater than ketamine. These findings emerged from comprehensive studies testing psychedelics from different chemical families.

Research using cultured cortical neurons demonstrated that psychedelics increase dendritic arbor complexity, meaning they cause brain cells to grow more branches and connections. LSD is more potent than ketamine for this. DMT (Dimethyltryptamine, a plant hallucinogen), psilocin (found in psilocybin mushrooms), and DOI (an amphetamine-class psychedelic) all produced robust increases in the number and complexity of neural connections.

The structural changes induced by psychedelics translate into functional improvements. Studies using super-resolution microscopy revealed that psychedelics increase the density of dendritic spines—the small protrusions where synapses form between neurons. In some cases, treatment with psychedelics nearly doubled the number of spines per unit length, with accompanying increases in synapse formation and neural excitability. These changes mirror those seen with ketamine, suggesting a common mechanism for promoting neural repair.

Animal studies confirmed that psychedelics produce lasting changes in brain structure. Rats treated with a single dose of DMT showed increased dendritic spine density in the prefrontal cortex 24 hours after treatment, well after the drug had been cleared from the body. This demonstrates that psychedelics, like ketamine, trigger enduring changes in brain architecture rather than producing temporary effects. The persistence of these changes explains how a single psychedelic experience can produce lasting improvements in mood and behavior.

Defining Psychoplastogens

The growing evidence that multiple compounds can rapidly promote neural plasticity led to the creation of a new therapeutic category. Researchers coined the term “psychoplastogen” from Greek roots meaning “mind” (psych), “molded” (plast), and “producing” (gen) to describe compounds capable of rapidly promoting structural and functional neural plasticity. This classification helps distinguish fast-acting plasticity enhancers from slower traditional treatments that also promote brain changes.

To qualify as a psychoplastogen, a compound must produce measurable changes in plasticity within 24-72 hours following a single administration. These changes include increases in neurite growth, dendritic spine density, synapse number, or intrinsic excitability. More importantly, psychoplastogens must produce relatively long-lasting behavioral changes that extend beyond the acute effects of the drug, indicating genuine circuit-level modifications rather than temporary chemical alterations.

The psychoplastogen category includes several established compounds with demonstrated clinical efficacy. Beyond ketamine and classical psychedelics, the list includes scopolamine (a muscarinic receptor antagonist), GLYX-13 or rapastinel (an NMDA receptor partial agonist), and potentially other compounds that activate the mTOR pathway. All of these substances produce fast-acting antidepressant effects in humans, supporting the hypothesis that rapid plasticity enhancement underlies their therapeutic benefits.

Clinical Applications and Therapeutic Uses

One of ketamine’s most promising applications is depression that has not responded to standard treatments. About 35% of people with this do not improve significantly after trying two different antidepressants.

Yoho comment: The above was paraphrased from my sources. “Standard of care” antidepressant drugs are disasters, with problems including addiction, universal therapeutic failure, and side effects including suicide and homicide. No antidepressant is “effective” as measured by double blind study, for none exist. They—like the rest of the psych drugs—are fraudulent and typically damaging. Refer to Butchered by “Healthcare” for more detail.

In 2000, researchers at Yale discovered that a single low-dose IV ketamine treatment produced significant improvement in depression symptoms within just 72 hours—much faster than the weeks typically required for standard antidepressants.

A particularly significant study from 2013 found that very low doses of ketamine given under the tongue (just 10 mg) every 2-7 days produced rapid improvement in mood, thinking ability, and sleep for 77% of patients with difficult-to-treat depression. Patients experienced only mild, temporary side effects like light-headedness, without the euphoria or dissociative experiences often associated with higher doses. Unlike traditional antidepressants that typically take weeks to work, ketamine can lift depression symptoms within hours or days. This rapid action could prove life-saving for people experiencing suicidal thoughts.

Research using very low dose sublingual ketamine provides additional evidence for the connection-restoring mechanism. Brazilian researchers found that doses as small as 10 mg administered under the tongue produced rapid and sustained effects in patients with treatment-resistant depression. This represents a dramatic reduction from the typical intravenous dose of 0.5 mg per kilogram of body weight, suggesting that even minimal amounts of ketamine can trigger the brain’s repair mechanisms.

Borderline Personality Disorder

Borderline personality disorder affects about 1.35% of people and causes emotional instability, troubled relationships, identity confusion, and a high risk of suicide (8-10%). Despite its severity, no medication has been specifically approved to treat BPD. Recent research suggests ketamine may help people with BPD. A study from the Canadian Rapid Treatment Center of Excellence examined 100 people with treatment-resistant depression and BPD who received four ketamine infusions over two weeks. Not only did their depression improve, but 34.3% also showed significant improvement in their BPD symptoms, with another 22.9% showing partial improvement. Suicidal thoughts decreased in these patients.

A remarkable case report describes a 60-year-old woman with a 34-year history of BPD, recurrent depression, daily suicidal thoughts, and anxiety disorders who showed dramatic improvement with low-dose sublingual ketamine (25 mg daily). After 10 months of treatment, her depression was nearly gone, she was working two jobs, and she no longer met the criteria for BPD diagnosis. Even her chronic pain from fibromyalgia had largely resolved.

PTSD Treatment and Treating Fears

The therapeutic applications of psychoplastogens extend beyond simple depression treatment to encompass a broad range of psychiatric and neurological conditions. Curing chronic fear is an example of how these compounds can rewire neural circuits. Giving a psychoplastogen shortly before talk therapy can improve fears more effectively than the training alone.

MDMA exemplifies this approach in clinical practice. The compound has shown remarkable success in treating post-traumatic stress disorder through a treatment method best described as pharmaceutical-enhanced psychotherapy. Clinical trials demonstrate that MDMA-assisted therapy produces sustained improvements in PTSD symptoms, leading to a breakthrough therapy designation from the Food and Drug Administration. This success stems from MDMA’s ability to promote fear extinction learning while reducing anxiety during therapeutic sessions.

Spinal Cord Injury (SCI)

This affects approximately 40 million people worldwide each year, with devastating consequences including paralysis and sensory loss. Currently, no effective medicine exists to help the spinal cord heal after injury.

Researchers speculate that ketamine might help with SCI recovery for several reasons: it blocks excessive glutamate activity, which can damage nerve cells after injury; it promotes the growth of new neurons and connections between neurons; it helps with remyelination (rebuilding the protective covering around nerve fibers); and it reduces inflammation in the nervous system.

Animal studies have shown that ketamine’s ability to block NMDA receptors protects against cellular damage after spinal cord injury and improves recovery. Other substances with similar neuroplasticity-promoting properties, including LSD and certain medicinal mushrooms, have shown promise in SCI models. While clinical trials in humans with SCI have not yet been conducted, the existing evidence suggests daily low-dose ketamine might assist in recovery from spinal cord injury by promoting neural repair and reducing secondary damage.

Yoho comment: Intravenous DMSO is the first step to treat spinal cord injury, although ketamine may be the second. See my DMSO posts.

Anti-Parasitic Properties

In a surprising discovery, researchers found that ketamine can effectively kill parasitic worms that infect humans and animals. A 2020 study showed that ketamine was effective against three types. When tested in hamsters and mice, ketamine was as effective as standard anti-parasitic medications at reducing worm infections. This discovery could have significant implications for human health, livestock management, and agriculture, as parasitic worm infections affect millions worldwide and cause substantial economic losses.

Administration

Yoho note: this is important. Ketamine’s bioavailability varies significantly by administration route. Intravenous administration provides nearly 100% bioavailability, while intramuscular injection reaches about 93%. Intranasal administration achieves approximately 45% absorption, sublingual (under the tongue) reaches 29-32%, and oral swallowing only provides 17-24% absorption with high conversion to norketamine, a lower potency metabolite.

For depression treatment, ketamine has been traditionally given as an IV infusion at a dose of 0.5 mg/kg over 40 minutes. However, much smaller doses given under the tongue (sublingual) can also be effective. When taken this way, ketamine is typically held under the tongue for several minutes and then swallowed or spit out. Ketamine has a half-life of about 2-2.5 hours—half of the drug is cleared from the body in that timeframe.

Yoho: The significance of this is:

1. You get the most activity per milligram in intramuscular or intravenous use. When used under the tongue, only a third of the drug is absorbed.

2. The troches and holding ketamine in the mouth are efforts to increase absorption, but it does not work as well as 1). For example, if you are told to take 25 mg sublingually, you might only get 30 %—8 mg—because of poor absorption. Troches for sublingual use must be manufactured from the liquid at additional cost.

3. IV use is a scam to get people into formal care where more can be charged and limit access to this wonderful treatment. Doses of IV ketamine of 50 mg and above can cause side effects and occasional hazards. I know—I worked with it for years. Download my paper for more.

4. Spravato is a costly patented ketamine knockoff nasal spray drug with a special applicator. Other patents were obtained for nasal use.

5. Intramuscular seems impractical for daily use.

6. Subcutaneous is reasonable, but I never saw it mentioned. It is easy to learn, the absorption is good, and since tiny needles are used, it is nearly painless.

7. Ketamine is 50 mg/cc, so the equivalent subcutaneous or intramuscular dose to 25 mg sublingually is about 8 mg, which is .16 of a cc. One cc luer-lock syringes work best.

Safety Profile and Side Effects

At the low doses used for depression and other mental health conditions, ketamine is generally well-tolerated. The most common side effects of low-dose sublingual ketamine include mild dizziness, temporary sedation, and temporary changes in thinking or perception. These effects typically last from 5 to 60 minutes and resolve on their own. At higher doses, ketamine can cause dissociative effects—a feeling of detachment from one’s surroundings or self—but these are rarely problematic at the lower doses used for depression treatment. Yoho: I never saw this when I used 25 mg IV in thousands of cases.

Long-term safety data from patients treated for pain show that ketamine is generally safe when used at appropriate doses under medical supervision.

People with certain heart conditions, untreated high blood pressure, or a history of psychosis should avoid ketamine or use it only with caution.

Advantages of Sublingual Administration

Cost-effectiveness is a major benefit, with sublingual ketamine costing approximately $15-30 per month, compared to hundreds or thousands of dollars for IV ketamine treatment.

Yoho: “Facility fees,” an invention of medical billing departments, can be charged. This is a charge for simply stepping into a healthcare facility. These would never be tolerated by consumers in any other industry.

Patients can take the medication at home without needing to visit a clinic for each dose. Lower blood levels mean a reduced risk of hallucination or confusion side effects, and flexible dosing permits daily administration if needed, allowing for more consistent treatment effects.

Sublingual ketamine must be prepared by a compounding pharmacy since it is not produced by pharmaceutical companies. This requires a prescription.

Real-World Clinical Outcomes

Studies of at-home ketamine treatment with telehealth support show promising results. In one study of 1,247 patients who received ketamine treatment through a telehealth platform, about 62.8% showed at least a 50% improvement in depression symptoms, and 62.9% showed similar improvement in anxiety symptoms. Only about 1% of patients experienced worsening symptoms, and fewer than 1% dropped out due to side effects or adverse events, suggesting the treatment is generally well-tolerated when patients are properly screened and monitored.

The combination of at-home administration with telehealth support from healthcare providers appears to provide a safe and effective approach that increases access to treatment while maintaining appropriate oversight.

Future Research

The potential applications for psychoplastogens span numerous conditions beyond mood and anxiety disorders. The compounds show promise for treating substance use disorders. Stroke recovery, brain trauma rehabilitation, and neurodegenerative disease treatment are additional areas where plasticity enhancement could provide therapeutic benefits. Traditional plasticity-promoting compounds like fluoxetine have already demonstrated utility in promoting functional recovery after brain injuries, suggesting broader applications for more potent psychoplastogens. Yoho: this is quoting my sources, but if you believe it you are likely also fooled by Steve Kirsch’s ridiculous trial of fluoxetine as a Covid cure (!). This drug is an SSRI antidepressant, a failed, ineffective class of medications that is addictive and has side effects ranging up to suicide. See Butchered by “Healthcare.”

The Brazilian study of very low dose sublingual ketamine demonstrates that effective treatment requires much smaller amounts than initially assumed. This finding has important implications for safety, cost, and accessibility of treatment. Similar dose-optimization studies for psychedelics could lead to protocols that maximize therapeutic benefits while minimizing unwanted effects.

Conclusion

Psychoplastogens shift psychiatric medicine from symptom management toward circuit repair. These compounds—led by ketamine and followed by classical psychedelics—work by restoring neural connections that depression and other mental health disorders damage or destroy. The evidence demonstrates that structural brain changes occur within hours of treatment and persist for days or weeks, providing a biological explanation for the sustained therapeutic effects observed in clinical studies.

Animal studies, human clinical trials, cellular research, and mechanistic investigations all support this approach.

As researchers develop safer and more selective psychoplastogens, these treatments could address a wide range of neurological and psychiatric conditions.

Yoho: Again, this viewpoint is from my references. We already have a drug that works. Researchers are looking under the patent money tree rather than studying cheap, natural products like ketamine.

This revolution in brain treatment moves psychiatry beyond discredited theories of chemical rebalancing. The identification of psychoplastogens as a therapeutic class provides a framework for understanding and developing treatments that promote the brain’s natural capacity for renewal and repair. These advances offer hope for recovery and lasting improvement for treatment-resistant conditions.

Comment: It is heartening to see some of the shrinks jump ship from the pharma companies into the ketamine pirate craft. However, few of them will admit to completely abandoning SSRIs, benzodiazepines, and atypical antipsychotics, citing their experience that these “sometimes work.” Again, NONE of them have been confirmed effective using placebo controlled trials. They are toxic scams and psychiatrists have allowed themselves to be repeatedly duped.

Respected Counterpoints:

• I am leery of ketamine because of its connection to mind control programs. —Martha Carlin

• Ketamine promotion may be another psy-op just like marajuana and the psychedelics. —Kat Lewis, MD

• Legalizing pot was a really dumb thing to do without warning how strong it is. Seeing young people with stoned eyes is disheartening. —Elizabeth Cronin

Yoho: Every other drug or surgery psychiatrists have promoted is damaging and ineffective, and I fear this is yet another disaster.

References

• Ferreira, N.R., et al. “Ketamine Can Be Produced By Pochonia Chlamydosporia: An Old Molecule And A New Anthelmintic.” Journal of Helminthology, 2020.

• Hull, T.D., et al. “At Home: Sublingual Ketamine Telehealth Is A Safe And Effective Treatment For Moderate To Severe Anxiety And Depression: Findings From A Large Prospective Open Label Effectiveness Trial.” Journal of Affective Disorders, 2022.

• Lara, Diogo R., et al. “Antidepressant, mood stabilizing and procognitive effects of very low dose sublingual ketamine.” International Journal of Neuropsychopharmacology, 2013.

• Ly, Calvin, et al. “Psychedelics Promote Structural and Functional Neural Plasticity.” Cell Reports, June 12, 2018.

• NPR Health. “Ketamine Relieves Depression By Restoring Brain Connections.” October 4, 2012.

• Olson, David E. “Psychoplastogens: A Promising Class of Plasticity-Promoting Neurotherapeutics.” Journal of Experimental Neuroscience, 2018.

• Rodriguez, C.I., et al. “Very Low Dose Sublingual Ketamine For Borderline Personality Disorder And Treatment Resistant Depression.” Journal of Clinical Psychiatry, 2021.

• Stevens, Calvin L. “Ketamine Review And Hypothesis For Potential Use In Spinal Cord Injury.” Spinal Cord Medicine, 2020.

Here are five of the papers I summarized above for you to download and preserve:

• Very Low Dose Sublingual Ketamine For Borderline Personality Disorder And Treatment Resistant Depression

Download

Download

• Lara: Antidepressant Mood Stabilizing And Procognitive Effects Of Very Low Dose Sublingual Ketamine In Refractory Unipolar And Bipolar Depression

Download

Download

• Ketamine Review And Hypothesis For Potential Use In Spinal Cord Injury

Download

Download

• Hull At Home: Sublingual Ketamine Telehealth Is A Safe And Effective Treatment For Moderate To Severe Anxiety And Depression Findings From A Large Prospective Open Label Effectiveness Trial

Download

Download

• Ferreira: Ketamine Can Be Produced By Pochonia Chlamydosporia An Old Molecule And A New Anthelmintic

Download

Download

Other references

• Scott Marsland about ketamine on his Lightening Bug Substack HERE and HERE.

• Ari Whitten’s podcast, “Breakthroughs for Depression, “Ketamine-assisted psychotherapy” is HERE.

• Low-Dose Sublingual Ketamine for the Treatment of Raynaud’s Phenomenon is HERE

Yoho: are ketamine’s potential rewards worth it for me?

I hate being stoned or hung over, but I see little other risk. Nothing else I have found for Parkinson’s shows much promise, and since I already have neurological damage, my answer is yes. I will try to tolerate the long wait for improvement, but I am not a patient dude.

My brilliant friend Margaret Aranda, MD, adds a few pearls:

She writes The Rebel Patient Substack.

• Nandrolone, an injectable anabolic steroid, has neuroregenerative effects.

• Human Growth Hormone also has potential.

• I prescribed ketamine with oxytocin and believe the combination fosters healthy thinking and long term attitude improvement. Yoho comment: Oxytocin is a hormone that promotes social bonding that is sometimes referred to as the “love hormone” or “cuddle hormone” due to its association with positive social interactions and feelings of trust and connection.

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• Editing credit: Elizabeth Cronin, Jim Arnold.

Appendix: An abridged Perplexity search on ketamine and Parkinson’s:

Ketamine is promising for both motor and non-motor symptoms in Parkinson’s disease (PD).

• Clinical Trials: A phase 2 trial (NCT06231563) is evaluating ketamine’s safety and efficacy in PD patients with levodopa-induced dyskinesia (LID). Early results indicate weeks-long benefits after a single infusion. Comment: This is a common issue with levodopa therapy that typically develops after 2-5 years as involuntary, jerky movements. LID is irreversible in most cases, which killed my interest in levodopa.

• Long-Term Reduction of Dyskinesia: Preclinical studies show that low-dose ketamine infusions (5–20 mg/kg) in rodent models lead to a dose-dependent, long-term reduction in abnormal involuntary movements associated with levodopa-induced dyskinesia (LID). Effects lasted up to 55 days post-treatment, suggesting neuroplastic changes rather than transient pharmacological action. Comment: these are far larger doses than those for humans.

• Mechanism: Ketamine disrupts pathological oscillations in the motor cortex, restoring cortical control over movement. This is coupled with enhanced neuroplasticity, allowing neurons to reestablish functional connections.

• Rapid Antidepressant Effects: Ketamine’s ability to alleviate treatment-resistant depression within 24 hours is being tested in PD-specific trials. The Yale PD Ketamine Trial (Phase II) and UCSF’s VA-focused study are investigating repeated low-dose infusions, with preliminary data suggesting sustained mood improvements.

• Yale’s imaging studies (PET/fMRI) are mapping ketamine-induced improvements in synaptic density and functional connectivity.

• Safety Profile: Early trials report tolerability, with no worsening of Parkinsonism or acute pro-dyskinetic effects.