Dmso and Neurology

By A Midwestern Doctor
 The Forgotten Side of Medicine 

April 23, 2026

Parkinson's Disease

Parkinson's disease results from the progressive loss of dopamine-producing neurons in the substantia nigra. Research in this field was revolutionized in the early 1980s when recreational drug users who injected a badly synthesized synthetic heroin rapidly developed severe Parkinson's-like symptoms due to it being contaminated with MPTP, an agent whose active metabolite (MPP+) specifically targeted those neurons, making it possible to reliably model Parkinson's in laboratory animals. This was followed by the realization one herbicide (paraquat) was very similar to MPP+, another pesticide (rotenone) causing similar damage to neurons, a variety of pesticides being linked to a higher risk of Parkinson's (such as organophosphates), and 6-OHDA also being able to reliably create Parkinson's.
Note: one of the major challenges with glyphosate (Roundup) is that while it is toxic, the herbicides it replaced like paraquat are much more toxic.

Numerous studies have shown that DMSO directly counteracts the neurotoxicity of these Parkinson's-producing agents (e.g., in the organophosphate studies mentioned previously, DMSO repeatedly reduced mortality, accelerated organophosphate detoxification, and protected neuromuscular function). Most remarkably,  a case-control study of young-onset Parkinson's disease (63 cases, 68 controls) found that individuals with Parkinson's were one tenth as likely to have been exposed to DMSO as normal controls, suggesting DMSO has protective qualities that confer a roughly 10-fold reduction in disease risk. In contrast, the same study found insecticide exposure increased risk nearly 6-fold, fumigated housing over 5-fold, and herbicide exposure over 3-fold - results consistent with the extensive epidemiological literature linking pesticide exposure to Parkinson's.
Note: this study also found smoking was associated with reduced PD risk, a finding that aligns with decades of epidemiological evidence linking nicotine exposure to lower PD incidence, lending credibility to the study's methodology.

DMSO has directly demonstrated neuroprotective effects in multiple Parkinson's models. In animals, DMSO suppressed hydroxyl radical-induced nigrostriatal injury from MPTP, 1^, 2^, 3^, 4 and in rotenone-induced Parkinson's rats,  DMSO improved hippocampal CA1 and CA3 neuron morphology, restoring pyramidal cells and Nissl bodies damaged by rotenone and normalizing their electrical activity.  DMSO also protected astrocytes from MPP+-induced toxicity by reducing lipid peroxidation and metabolic impairment,  protected glial glutamine synthetase from MPP+-induced hydroxyl radical damage,  protected human SH-SY5Y neuroblastoma cells from 6-OHDA-induced cytotoxicity, and  reduced both lipid peroxidation and protein carbonyl formation in rat brain homogenates from ferrous chloride or hydrogen peroxide, and separately reduced hydroxyl radical production during 6-OHDA autoxidation and the formation of hydroxylated dopamine products. 1^, 2
Note:  in one mouse study, intraperitoneal DMSO did not protect against MPTP-induced dopamine depletion, indicating its neuroprotective effects may depend on the route, timing, or dose of administration.

Interestingly, DMS (DMSO's naturally occurring, odor-producing metabolite) at near-physiological concentrations also protected neurons against both 6-OHDA and MPP+-induced apoptosis, with this effect being dependent upon MsrA (the enzyme that converts DMS to DMSO), suggesting the endogenous DMS-DMSO cycle functions as part of the body's natural antioxidant defense against dopaminergic neurodegeneration. 1^, 2 This, in turn, raises an interesting conundrum as I have received a few reports of Parkinson's patients who had dramatic responses to DMSO who then stopped due to the odor impeding sexual relations with their spouse, and my first thought was to recommend a low odor DMSO formulation (discussed  here), but if DMS plays a key therapeutic role in Parkinson's disease, that approach may not be viable.
Note:  that study also found DMS protected against H₂O₂-induced lipid peroxidation and antimycin A generated super oxide production.

Additionally,  DMSO reversed rotenone's complete blockade of microtubule assembly from purified tubulin in vitro - a finding with direct relevance to Parkinson's, as microtubule disruption impairs axonal transport and contributes to dopaminergic neuron death. Likewise, a Russian physical therapy monograph recommended topical DMSO novocaine compresses for neurological conditions including Parkinson's, and  a patent proposed DMSO as a transdermal enhancer for a botulinum toxin patch to treat the spasticity associated with Parkinson's, cerebral palsy, dystonia, and multiple sclerosis.
A vast number of agents in combination with DMSO have also shown therapeutic benefit in Parkinson's models.

Curcumin protected nigral dopaminergic neurons, reduced iNOS and glial activation, and upregulated neuroprotective pathways (IGF-1/Akt/FoxO3a). 1^, 2

Paeoniflorin repeatedly reduced α-synuclein expression, decreased Lewy body formation, and protected dopaminergic neurons across multiple studies, 1^, 2 It also inhibited microglial overactivation, increased BDNF and GDNF secretion, and promoted neural stem cell differentiation into dopaminergic neurons. 1

 Icariside II induced human amniotic mesenchymal stem cells to differentiate into dopaminergic neuron-like cells (optimal at 3-10 μmol/L via PI3K signaling). In another protocol DMSO helped differentiate iPSCs into dopaminergic progenitors for PD stem cell therapy.

Ginsenosides Rg1 and Rg3 both significantly attenuated dopaminergic neuron loss, neuroinflammation, and α-synuclein accumulation. 1^, 2^, 3^, 4

 Geniposide reduced α-synuclein levels and prevented dopaminergic neuron loss by modulating the miR-21/LAMP2A axis, while ginkgolide B similarly reduced α-synuclein expression via the related miR-207/LAMP2A pathway. 1^, 2  Ambroxol increased β-glucocerebrosidase activity and reduced α-synuclein oligomer levels, restoring cell viability and mitochondrial function in dopaminergic neurons.  Polyphenols reduced seeded α-synuclein aggregation via NRF2-mediated antioxidant responses.  Carnosic acid attenuated 6-OHDA neurotoxicity by upregulating parkin and restoring proteasomal clearance of ubiquitinated proteins in cellular and animal PD models.

 L-sulforaphane dissolved in DMSO activated the NRF2 pathway in Parkinson's disease patient-derived cells, restoring their deficient glutathione levels - one of the only studies using actual patient cells.

 Most uniquely, NAMI-A - a low-toxicity ruthenium-DMSO complex - inhibited α-synuclein aggregation and membrane interactions with submicromolar affinity, disassembled pre-formed fibrils, abolished α-synuclein cytotoxicity toward neuronal cells, and mitigated neurodegeneration and motor impairments in a rat Parkinson's model, providing a novel basis for designing ruthenium-DMSO complexes that target α-synuclein-driven pathology through a mechanism distinct from organic agents.

In MPTP models,  tanshinone IIA preserved approximately 75% of dopaminergic neurons while reducing microglial activation;  tetramethylpyrazine prevented motor deficits and neuron loss via the Nrf2 pathway;  6-Hydroxy-1H-indazole protected 90-93% of dopaminergic neurons from death;  baicalein dose-dependently reduced rotation behavior (a key indicator of motor impairment), neuroinflammation, and dopaminergic neuron apoptosis via Wnt/β-catenin;  neferine improved mouse motor disorders and reduced neuroinflammation and α-synuclein in the substantia nigra;  SB239063 (a p38 MAPK inhibitor) protected TH-positive neurons;  NESS 0327 (a CB1 receptor antagonist) ameliorated motor deficits;  novel c-Abl kinase inhibitors outperformed nilotinib in blocking MPP+-induced apoptosis;  GW5074 prevented TH-positive neuron loss in mice genetically engineered to have PD. In nigrostriatal pathway injury mice, both ERK inhibition ( U0126) and PDGFRα inhibition ( AG1296) reduced glial activation and scarring, with U0126 also improving long-term neurobehavioral outcomes.

 In LPS-induced PD mice, pazopanib protected dopaminergic neurons by suppressing TNF-α, PGE2, and IL-6 via MEK4-JNK-AP-1 signaling, while rapamycin reduced neuroinflammation by enhancing microglial lipid metabolism.

 NBP (a Chinese stroke medication) rescued dopaminergic neurons by 30% and striatal dopamine terminals by 49%.  Carvacrol (found in oregano and thyme oils) was neuroprotective via TRPC1 inhibition in dopaminergic neurons and TRPA1 activation in astrocytes. Dasatinib and resveratrol in combination improved learning, memory, motor coordination, and reduced anxiety.  MOTS-c improved motor function, reversed TH-positive neuron loss, and activated the Nrf2/Keap1 antioxidant pathway in rotenone PD rats.  Puerarin mitigated rotation behavior and upregulated DAT, VMAT2, and TH in rotenone PD rats.  A caspase inhibitor reduced neuron loss and improved rotation behavior in 6-OHDA rats, though blocking apoptosis triggered compensatory glial necroptosis.

Shuimuheningfang improved motor and non-motor symptoms in 80 PD patients and reduced α-synuclein in model mice, 1^, 2 while  Compound Dihuang Granules (with a JNK inhibitor) reduced rotation behavior and protected dopaminergic neurons in 6-OHDA rats.

In C. elegans PD models, olive leaf extract strongly protected dopaminergic neurons from 6-OHDA toxicity (up to ~56% less degeneration), while oleuropein, oleanolic acid, tyrosol, 3-hydroxytyrosol, saffron, Polygonum multiflorum, and Ziziphus jujuba each also provided significant protection.

Additional agents showing neuroprotective effects in PD models include  guaraná (against rotenone in SH-SY5Y cells),  Antarctic krill oil (improved locomotor activity and dopaminergic neurons in zebrafish), lutein (dose-dependently improved cognitive and motor outcomes in rats),  cytochalasin compounds from endophytic fungi (against MPP+),  Erythrina velutina extract, rizonic acid, and  xyloketal derivatives (against 6-OHDA or ROS-mediated damage),  sodium butyrate (an HDAC inhibitor that epigenetically restored dopamine transporter and VMAT2 expression against rotenone and MPP+),  allopregnanolone (promoted TH-positive cell regeneration via BDNF and CaMKIIδ3 against 6-OHDA),  wedelolactone (upregulated the neuroprotective PD protein DJ-1/PARK7),  dexmedetomidine (neuroprotective via ERK1/2-mediated histone acetylation), along with  7,8-dihydroxyflavone,  cordycepin (against rotenone in PC12 cells),  AMG9810 (a TRPV1 antagonist that reduced motor deficits but impaired cognition with chronic use), insulin with TLR4 inhibitor  TAK242 (improved motor performance and normalized α-synuclein in 6-OHDA rats),  catalpol (reduced α-synuclein and improved mitochondrial function against rotenone),  genistein,  Taohe Siwu decoction,  Ligusticum chuanxiong compounds, and  Nigella sativa fatty acids.

Since paraquat and other herbicides are among the strongest environmental risk factors for Parkinson's, it is also noteworthy that DMSO has been shown across multiple studies to scavenge the hydroxyl radicals generated by paraquat, 1^, 2^, 3^, 4 including  direct evidence from rats of DMSO intercepting paraquat-generated hydroxyl radicals via Fenton-like chemistry, and  in bacterial biosensor assays, DMSO scavenging up to 96% of the superoxide radicals generated by paraquat. DMSO has also been shown  to be directly neuroprotective against paraquat in cultured striatal cells,  suppress paraquat-induced inflammatory signaling (e.g., IL-8 and neutrophil chemotactic activity), and  protect DNA from paraquat-induced mutagenesis - providing a potential mechanistic explanation for the epidemiological finding that DMSO exposure is inversely associated with Parkinson's risk. Additionally,  myrtenol,  andrographolide (via Nrf2/HO-1),  VPA (an HDAC inhibitor),  chymostatin,  propofol and  resveratrol each combined with DMSO to counteract paraquat-induced toxicity and oxidative stress across various tissue models.

Note: α-synuclein aggregation into toxic fibrils is a core driver of Parkinson's neurodegeneration.  One study found DMSO at 0.75-1.0%, especially when combined with ferric iron, promoted α-synuclein oligomer formation and cytotoxicity. However,  when oral DMSO was tested in living mice (both normal and transgenic mice overexpressing human α-synuclein), no increase in α-synuclein aggregation, no neuronal loss, and no Parkinson's-like pathology was detected. Likewise, DMSO injected directly into the substantia nigra has not been found to cause dopaminergic neuron loss, ubiquitinated protein accumulation, or behavioral deficits 1^, 2 - suggesting that whatever pro-aggregant effect DMSO has on α-synuclein in isolated cell cultures (at much high concentrations than it can reach clinically) does not translate to the living body.

In addition to the experimental evidence, I have received a few reports from readers and physicians who had success with DMSO. As my experience is primarily with IV DMSO (which I believes offers the greatest benefit), I wanted to share this entire sample that includes non-IV approaches to illustrate to difference between them.

 One wife described what happened when her husband with Parkinson's received an IV drip of mannitol and DMSO during stem cell therapy in Amsterdam: "He bounced down a flight of stairs without using the handrails, cut his own food for a week after, spoke clearly, opened cab doors." They knew it wasn't the stem cells, which would take months to show results.

 The most detailed report came from a research scientist diagnosed with PD in 2018, who had already controlled his non-motor symptoms with sulforaphane (an Nrf2 activator) but still had the full range of motor symptoms. After systematically testing oral DMSO over several months, he found that at an optimal dose of 1.2-1.5 g/day, bradykinesia was eliminated, pain and dystonia reduced by 80%, stiffness reduced by 50%, and energy levels were markedly higher. He observed that DMSO addressed motor symptoms where sulforaphane had not, suggesting DMSO was reaching the brain in ways sulforaphane could not - consistent with DMSO's known ability to cross the blood-brain barrier. Notably, doses above 1.5 g/day reliably worsened tremor, stiffness, and sleep, but these effects fully reversed within two days of stopping.

 A third reported that topical and oral DMSO initially helped her husband with Parkinson's walk short distances, but the effect did not persist.

Additionally, I have also received a few reports of oral DMSO helping readers with Parkinson's, but as they were in passing (verbally) I can't offer any specifics on them.

Given all of this, I believe DMSO is quite helpful for Parkinson's disease - oral administration is likely to benefit patients, IV significantly more so - and that the best results will ultimately come from combining DMSO with a complementary neurotrophic agent. Currently, I have identified one very promising candidate for this purpose (along with a few other possibilities), but as the combination studies above demonstrate, there are likely many more waiting to be discovered.

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease in which the motor neurons that control voluntary movement gradually die, leading to increasing muscle weakness, paralysis, and typically death within 2-5 years of diagnosis. No cure exists, and the two FDA-approved drugs provide only modest survival benefits. However, as Todd's story shows, there is hope for ALS, and there is also some research to corroborate it:

• In ALS model mice, long-term oral administration of 5% DMSO significantly increased mean survival time, reduced neurological scores, and improved motor performance (with the improvements being primarily functional rather than histological). 1^, 2

•  Low concentrations of DMSO were found to stabilize SOD1 protein conformation (SOD1 misfolding is a central cause of ALS). Additionally, 5-fluorouridine and epigallocatechin gallate (which is often combined with DMSO) also stabilized SOD1.

•A variety of agents in combination with DMSO have also shown therapeutic benefit in ALS mice.  Chronic intraperitoneal resveratrol delayed disease onset, extended survival, and preserved nearly twice as many motor neurons.  A GSK-3β inhibitor delayed disease onset, death and partially preserved lumbar motor neurons.  ASK1 inhibitors protected against motor neuron death and reduced glial activation.  Rapamycin improved the neuroprotective mitochondrial fission/fusion balance.  Lycopene dose-dependently reduced oxidative stress, and reduced motor neuron apoptosis. Notably,  carboxyamidotriazole potently inhibited inflammatory cytokines in vitro but did not significantly improve onset or survival compared to the DMSO vehicle control in vivo-potentially suggesting DMSO itself was already providing a comparable benefit.

Note: DMSO has also been combined with riluzole (one of the two ALS drugs) to treat a variety of other neurological conditions including neuropathic pain, 1^, 2 light-induced retinal degeneration, 1^, 2  hearing loss (where DMSO alone also significantly protected hearing and preserved cochlear neurons), and  status epilepticus-all of which data shows DMSO alone treats. Additionally, DMSO has been used as a solvent to screen large numbers of compounds for use in ALS.

In addition to Todd's remarkable response to topical and particularly IV DMSO, a few other reports suggest DMSO can benefit ALS and related conditions.  One book recounts Stanley Jacob treating an ALS patient with DMSO, producing "instant, overnight and slightly delayed wonders of therapy," (after which their doctor forbade further treatment).
Note: I suspect this case may have been what first inspired a mentor to try IV DMSO for ALS.

 Another reader reported that a colleague gave DMSO to her father with ALS and "was surprised at visible improvement in his condition." Finally,  a reader with cramping fasciculation syndrome (a condition that presents like early ALS but does not progress to it) described being driven to the point of planning suicide by the combination of chronic pain and severe sleep deprivation before discovering that oral DMSO dramatically improved the effectiveness of his other medications, allowing him to sleep through the night, largely eliminating his cramping and nerve pain, and giving him back the ability to hold down a job and watch his children grow up.

Note: our (limited) experience has been that IV DMSO halts the progression of ALS rather than reverses it. However, the stories I've received suggest some individuals have a considerably more dramatic response - whether due to inherent responsiveness or higher IV doses. One of my major unresolved questions is whether the post-COVID vaccine "atypical" ALS cases respond differently to DMSO than the pre-vaccine ALS we had previously encountered (which is where all of our experience comes from).

Huntington's Disease

Huntington's disease is a fatal genetic disorder characterized by progressive loss of motor control, cognitive decline, and psychiatric disturbances. It belongs to a family of nine neurodegenerative disorders (polyglutamine diseases) caused by misfolded proteins with abnormally long glutamine repeats, and  a review of chemical chaperones for these conditions found DMSO showed similar or superior suppression of polyglutamine-mediated toxicity compared to the other chemical chaperones tested (glycerol, TMAO). Likewise,  in cell models of Machado-Joseph disease (another member of this family), DMSO stabilized mutant ataxin-3 protein folding, reducing aggregation, cytotoxicity, and cell death.

 In the only study which directly tested DMSO against Huntington's disease, DMSO (~1-4%) partially prevented cell death, increased cell viability, decreased aggregated huntingtin protein, and increased its soluble (non-toxic) form.

A variety of agents in combination with DMSO have also shown therapeutic benefit in Huntington's models. In rats,  inosine protected against Huntington's-like symptoms by improving motor function, activating the neurotrophic BDNF/TrkB/ERK/CREB pathway, increasing striatal BDNF, and reducing oxidative stress, neuroinflammation, and striatal neuronal damage.  FKBP5 inhibition reduced mutant huntingtin levels and increased autophagic clearance in both human Huntington's stem cells and mouse models. In C. elegans Huntington's models, olive leaf extract strongly protected neurons from polyglutamine-induced degeneration (up to 4-fold more intact neurons) and improved mechanosensory response, while 3-hydroxytyrosol and tyrosol reduced polyglutamine plaque number, protected neurons, and improved mechanosensory response.  Hyptis species extracts also significantly improved locomotion and increased oxidative stress resistance in polyglutamine models.

Note:  DMSO has also been used to screen a large number of potential therapeutics for Huntington's disease and  to investigate its underlying pathogenic mechanisms.

Movement Disorders

Movement disorders encompass conditions characterized by abnormal voluntary or involuntary movements — including tremors, ataxia (loss of coordination), dystonia, and muscle spasticity. Many arise from dysfunction in the cerebellum, basal ganglia, or their neural connections, areas particularly sensitive to the circulatory and inflammatory disruptions DMSO addresses.

 In a copper-deficient sheep model, a single subcutaneous injection of DMSO combined with copper sulfate during mid-pregnancy completely prevented enzootic ataxia (swayback) in lambs (0% incidence vs. 60% in untreated controls), performing comparably to multiple oral copper doses and suggesting DMSO enhanced systemic copper delivery sufficiently to protect fetal neurological development. In veterinary case reports,  IV DMSO contributed to the recovery of a mare with ataxia and cranial nerve deficits from temporohyoid osteoarthropathy (near-normal neurological status by discharge on day 5), while  in a foal with cerebellar abiotrophy, DMSO as part of a multi-agent regimen produced temporary neurological improvement before the animal relapsed due to the progressive nature of the underlying genetic condition.  In another horse, DMSO was used to manage vestibular disease and blindness that developed following a jugular catheter complication during anesthesia recovery.

In rats,  a neurotensin antagonist (in DMSO) attenuated neuroleptic-induced vacuous chewing movements (a model of tardive dyskinesia), supporting a role for neurotensin in its pathogenesis,  while abscisic acid (in DMSO) improved harmaline-induced tremor and motor performance.

Reader reports suggest DMSO can benefit several movement disorders.  One reader with vaccine-induced Stiff Person Syndrome reported that topical 100% DMSO was the only treatment that relieved constant muscle spasms — spanning the back, calves, feet, and chest — over 22 months of uncontrolled pain, noting "I have it with me at all times."  A 74-year-old reader with essential tremors, multiple spinal and thoracic fractures, and advanced tendonitis credited "DMSO, and DMSO alone" with keeping me out of a wheelchair. Other readers reported improvements in  essential tremors, in  tremors from vaccine injury and  a neck tremor that responded to topical DMSO.

Several readers also reported that topical DMSO dramatically improved restless leg syndrome, in some cases allowing them to discontinue long-term medications they had taken for decades.

Additionally, multiple dog owners reported that topical DMSO applied to the temples or behind the ears rapidly resolved vestibular episodes — TIA-like events characterized by disorientation, wobbly legs, and vomiting — with one describing recovery within an hour and continued preventive use whenever symptoms reappear, while another credited DMSO (along with grounding) with giving their elderly dog an extra year and a half of life. 1^, 2

Seizures and Epilepsy

Epilepsy is a neurological disorder characterized by recurrent seizures (sudden bursts of abnormal electrical activity in the brain that can cause involuntary movements), altered consciousness, and in severe cases, prolonged seizures that cause permanent brain damage or death. DMSO's ability to cross the blood-brain barrier, counteract oxidative stress, modulate ion channels, and suppress excitotoxic glutamate signaling suggest it could help epilepsy — though as detailed below, its effects are notably dose-dependent.

Anti-Seizure Properties

Several studies have directly examined DMSO's effects on seizure activity, revealing a consistent biphasic pattern: therapeutic doses suppress seizures while high doses can provoke them.  In rats genetically prone to epilepsy, low-dose DMSO (1.65 mg/kg) significantly decreased the number and total duration of spike-wave discharges, while high doses (825-1651 mg/kg) significantly increased them — with all effects being fully reversible. Likewise  when 50% DMSO was injected into the brain's ventricles (dilluting to approximately 6% in the CSF), no seizure activity was generated over the next hour, whereas 75% and 100% did create a significant spike in mice hippocampal evoked potentials.

 In a temporal lobe epilepsy model, high-dose DMSO (1651 mg/kg) produced significant anticonvulsant effects — prolonging seizure onset latency by 32%, shortening seizure duration by 34%, and reducing afterdischarge duration by 45% — effects the authors attributed to suppression of glutamatergic NMDA/AMPA-mediated calcium influx.  In mice with chronic temporal lobe epilepsy, only 100% DMSO (1651 mg/kg) reduced seizure number and cumulative duration (by 19-41% depending on sex), while lower concentrations had no effect — and notably, DMSO did not alter acute seizure threshold in non-epileptic mice, suggesting its anticonvulsant action is specific to the chronically epileptic brain.  Another study confirmed this pattern, finding 10% DMSO significantly reduced PTZ-induced epileptiform activity while 100% DMSO increased it. DMSO also raised seizure thresholds by approximately 9% against two different seizure-inducing agents and  prolonged the latency to convulsions from hyperbaric oxygen exposure (thereby reducing seizures).

In specific contexts, DMSO has shown targeted protective effects:  it partially prevented convulsions induced by 5-aminolevulinic acid (reducing their number and duration), likely through hydroxyl radical scavenging, and  pretreatment with DMSO has been shown to prevent iron-induced epileptiform discharges, suggesting a potential role in preventing post-traumatic epilepsy.

Note: the biphasic dose response is an important consideration when using DMSO either therapeutically or as a research vehicle in epilepsy studies. Several studies have specifically documented proconvulsant effects: DMSO prolonged cortical epileptic afterdischarges in immature rats (most pronounced in the youngest animals),  lowered tonic seizure thresholds in a PTZ model, and in one study,  even 0.1% DMSO accelerated PTZ kindling and potentiated hippocampal neuronal damage. These findings underscore the importance of dose selection and appropriate vehicle controls in epilepsy research.

Additionally, DMSO's ability to open the blood-brain barrier creates a dual-edged property: when excitatory amino acids (L-aspartate or L-glutamate) were administered peripherally in DMSO, they induced seizures they would not otherwise cause — which while a safety consideration, has proven useful for studying NMDA receptor involvement in seizure circuits and for demonstrating that the kindled amygdala plays a critical role in generalized seizure expression. 1^, 2^, 3^, 4

Seizure Reduction

The most direct clinical evidence for DMSO reducing seizures comes from patients with Niemann-Pick disease type C (detailed earlier).  In NPC patients, oral DMSO decreased seizure frequency and improved EEG findings. Most notably, in an 8-year-old girl with frequent seizures and severe psychomotor deterioration, two years of oral DMSO decreased seizure frequency enough to allow tapering of an anticonvulsant, produced marked EEG improvement (with normalization of theta waves and spindle morphology), and halted the progression of cortical atrophy.

In veterinary medicine, IV DMSO has been used as part of multimodal seizure management.  In a horse that developed seizures following surgery, IV 10% DMSO (1 g/kg twice daily for four days) — administered for its free radical scavenging and thromboxane-inhibiting properties to maintain cerebral blood supply — contributed to seizure cessation by day 3 and a satisfactory long-term outcome.  In a 2-day-old foal with perinatal asphyxia presenting with seizures, cerebral edema, and acute renal failure, IV DMSO contributed to marked resolution of cerebral edema and complete neurological recovery by day 12.  In a 3-day-old foal with convulsions and ataxia secondary to electrolyte derangements from bladder rupture, IV DMSO was included in supportive care that resolved the neurological signs within days.

Lastly,  as mentioned above, a dog which had seizures develop from hydrocephalus had those seizures improve from IV DMSO.

Combination Studies

A large number of agents combined with DMSO have demonstrated anticonvulsant or neuroprotective effects in seizure models.

Among those directly reducing seizure severity,  glibenclamide produced the greatest effects: following status epilepticus, it significantly reduced brain edema, blood-brain barrier damage, and neuronal loss while more than doubling 28-day survival (47.8% vs. 22.2%). Resveratrol prolonged seizure latency, shortened seizure duration, reduced the brain injury marker S100B in cerebrospinal fluid and serum, protected hippocampal CA1 and CA3 neurons, and improved spatial learning and memory in PTZ-kindled rats. 1^, 2  Resveratrol also protected against hyperbaric oxygen-induced convulsions.  Quercetin (10-20 mg/kg) significantly prolonged seizure onset, reduced severity, and shortened generalized seizure duration in PTZ-induced seizures, though higher doses (40 mg/kg) lost efficacy and in a picrotoxin model paradoxically shortened seizure onset. The combination of palmitoylethanolamide (PEA) with the neurosteroid ganaxolone markedly amplified seizure suppression and eliminated mortality, whereas PEA alone showed no efficacy in that model (though it did exhibit anticonvulsant activity in kindled amygdaloid seizures). 1^, 2  Montelukast synergistically enhanced phenobarbital's anticonvulsant effect (when both were dissolved in DMSO), lowering the effective dose while reducing phenobarbital-induced sedation.  Ruxolitinib shortened seizure duration, lowered seizure frequency over 4 weeks, and improved memory.  SB203580 prolonged seizure latency by 45% and halved seizure frequency. A 5-HT6 receptor antagonist (SB-271046) reduced spontaneous recurrent seizure frequency, increased protective potassium channel (KCNQ2/3) expression, and in combination with ERK1/2 or Fyn inhibitors reversed the aberrant mossy fiber sprouting that perpetuates chronic epilepsy. 1^, 2  Triptolide inhibited epilepsy in mice by improving hippocampal GABAergic inhibition and reducing IL-1β levels.

 Carvedilol suppressed spontaneous seizure activity in hippocampal slices from Alzheimer's model mice — a finding with implications for the seizure susceptibility frequently seen in that disease.

 In a high-throughput screening of 343 essential oils using a PTZ-induced zebrafish epilepsy model, 52 demonstrated antiepileptic activity, with 15 (including patchouli and cinnamon oils) showing potency far exceeding that of phenytoin.  Maslinic acid, identified through computational gene expression profiling, showed significant antiepileptic activity in the same model and selectively inhibited voltage-gated sodium channel subtypes Nav1.2 and Nav1.7

Many agents combined with DMSO also protected against the neuronal damage that follows status epilepticus. Mitochondrial division inhibitor 1 (Mdivi-1) repeatedly reduced neuronal apoptosis and oxidative stress across multiple studies, in some cases also increasing seizure latency, decreasing seizure frequency, and improving post seizure cognition. 1^, 2^, 3^, 4^, 5 Recombinant human erythropoietin protected hippocampal neurons via PI3K/Akt anti-apoptotic signaling across multiple seizure models. 1^, 2 Ganoderic acid reduced hippocampal damage through multiple pathways (caspase-3 reduction, CaSR/JNK/P38 modulation, and improved dendritic spine density and spatial memory). 1^, 2^, 3  Glycyrrhizic acid enhanced mitochondrial autophagy and antioxidant defenses in juvenile epilepsy rats.  Glycyrrhizin reduced HMGB1 expression and p38MAPK activation in the hippocampus.  Salidroside dose-dependently increased seizure latency, enhanced antioxidant defenses, and reduced endoplasmic reticulum stress-mediated apoptosis. Gastrodin reduced seizure severity, protected hippocampal neurons, enhanced GABAA receptor expression, and regulated post-SE autophagy. 1^, 2  Rolipram rescued cognitive deficits, hippocampal long-term potentiation, and CREB phosphorylation in immature rats following status epilepticus.  Curcumin decreased aberrant mossy fiber sprouting through miR-134/LIMK1 modulation.  ERK1/2 and p38 MAPK inhibitors reduced inflammatory markers, chemokine expression, and microglial activation in the hippocampus of immature rats with kainic acid-induced epilepsy.  An Omi/HtrA2 inhibitor (ucf-101) reduced neuronal apoptosis and caspase-3 expression while increasing anti-apoptotic XIAP and HAX-1 in epileptic hippocampal neurons.  Levetiracetam dose-dependently reduced oxidative stress, hippocampal neuronal apoptosis, and caspase-3 expression in epileptic offspring mice.

Additional agents showing neuroprotective effects in status epilepticus models include  a caspase-12 inhibitor,  olomoucine (a CDK inhibitor that reduced neuroinflammation and apoptosis),  2-methoxyestradiol (via HIF-1α suppression),  KN-93 (a CaMKII inhibitor),  honokiol,  a hydrogen sulfide donor (via PI3K/Akt),  an IRAK1/4 inhibitor,  an exosome inhibitor (which prolonged seizure latency by reducing BBB permeability changes),  an eEF2K inhibitor that restored AMPKα1 expression and improved mitochondrial function, cognition, and social behavior in chronic epileptic mice, and  a PARP-1 inhibitor (DPQ) that reduced neuronal apoptosis and activated the PI3K/Akt-SIRT1 survival pathway.

Interestingly,  GPER-1 (the G protein-coupled estrogen receptor) activation with G1 improved spatial learning, memory, and reduced mossy fiber sprouting in chronically epileptic rats, yet  the same receptor's activation with G-1 or estradiol increased acute seizure susceptibility and nitric oxide levels in cortex and hippocampus during PTZ kindling — suggesting estrogen-mediated effects on epilepsy differ between acute seizure generation and chronic post-epileptic recovery.

Natural compounds demonstrating anticonvulsant effects in zebrafish or rodent models include  vitexin (comparable to diazepam),  sesamin (via PI3K/Akt),  onopordia (via the nitric oxide/nNOS pathway), linalool and trans-nerolidol (with nerolidol showing superior efficacy),  the combination of ursolic acid with caprylic acid,  Lippia sidoides extract (comparable to diazepam),  olive pit polyphenols (which protected against kainic acid-induced neurotoxicity),  a tryptamine derivative of securinine (combining antioxidant, chelating, and anticonvulsant properties while lacking the severe convulsant effects of parent securinine),  ε-viniferin (which inhibited NLRC4 inflammasome activation in astrocytes),  thymoquinone, and  progabide (which specifically suppressed the tonic phase of seizures).  Lamotrigine combined with anakinra partially normalized psychoneurological disturbances (anxiety, locomotor activity, social behavior) in chronically epileptic rats, suggesting their combination addresses both seizure control and behavioral comorbidities.

Rapamycin combined with pitolisant markedly improved anxiety (2.7-fold on maze testing) and depression (37.5% improvement in swim testing) in PTZ-kindled epileptic rats, highlighting that DMSO-delivered agents can address the psychiatric comorbidities that frequently accompany epilepsy.

 In stimulant toxicity models, MK-801 dissolved in DMSO abolished EEG afterdischarges and seizures induced by cocaine, amphetamine, and methamphetamine — though notably, eliminating seizures did not prevent death from methamphetamine or cocaine, demonstrating that seizure-independent toxicity pathways drive stimulant lethality.

Note:  CBD in DMSO blocked voltage-gated sodium channels and demonstrated anticonvulsant effects in a PTZ model, whereas cannabigerol produced comparable sodium channel blockade but had no anticonvulsant effect — indicating that sodium channel inhibition alone does not confer seizure protection.  3-carene modulated resting-state brain activity but did not reduce epileptiform activity.  Retigabine, despite being an established antiepileptic drug, paradoxically increased spike-and-wave discharge number and duration in aged WAG/Rij rats, revealing age-dependent pro-epileptic effects from neuronal potassium channel activation.  Two plant-derived extracts (Searsia dentata and Searsia pyroides) inhibited NMDA receptor currents and reduced intracellular calcium influx, supporting their traditional use for epilepsy.

DMSO and Antiepileptic Drug Interactions

Several findings are relevant to using DMSO alongside conventional antiepileptic drugs.  DMSO has been safely used as a vehicle for diazepam in seizure treatment studies. The antiepileptic drugs  carbamazepine and lamotrigine dissolved in DMSO showed no concerning interactions on human reproductive tissue, suggesting compatibility during pregnancy.  A pharmacological study demonstrated favorable molecular interactions between levetiracetam and DMSO-water mixtures, supporting DMSO's potential utility in antiepileptic drug formulation.  Mood-stabilizing antiepileptics (zonisamide, carbamazepine, valproate) dissolved in DMSO enhanced monoamine and acetylcholine systems in the striatum and hippocampus at therapeutic doses while reducing them at supratherapeutic doses — a biphasic pattern that may partly explain both their therapeutic effects and certain side effects.  DMSO combined with ethosuximide may synergistically increase brain epinephrine levels, as DMSO alone can stimulate the central nervous system and increase catecholamines, potentially augmenting the neurotransmitter changes the antiepileptic produces.  Menthol dissolved in DMSO demonstrated dose-dependent anticonvulsant effects, with 400 mg/kg significantly reducing seizure activity below control levels — while simultaneously counteracting the proconvulsant influence of high-concentration DMSO, suggesting menthol may be a useful adjuvant when DMSO is used as a seizure medication vehicle.

Note: multiple studies confirmed DMSO at vehicle concentrations had no independent effect on seizure parameters, supporting its safety as a solvent at appropriate doses. 1^, 2, 3  A study employing DMSO-based electron spin resonance spectroscopy demonstrated that seizures induce rapid accumulation of ascorbate (an antioxidant) in the hippocampus in parallel with seizure progression — likely as a response to excessive free radical production during excitotoxicity — providing mechanistic support for why antioxidants like DMSO can be neuroprotective in seizure contexts.

Psychiatric Conditions

Two of the most common complaints about psychiatry are that its (highly toxic) drugs do not treat the underlying illness—requiring lifelong symptom management—and that real biological issues (e.g., COVID vaccine injuries) are routinely misdiagnosed as primary psychiatric disorders. Both problems stem from the erroneous assumption that most psychiatric conditions originate purely in the mind, when in reality many have a clear biological (neurological) basis.

My perspective resulted from repeatedly observing psychiatric symptoms emerge after brain injuries and by seeing medical therapies that restore brain health also improve psychiatric issues. For example, one of my favorite therapies,  ultraviolet blood irradiation works by improving circulation, reducing inflammation, and reawakening dormant cells—all of which DMSO also does. Because these processes underlie so many diseases, much in the same way a large body of literature supports UVBI's efficacy across a wide range of conditions, including psychiatric ones, DMSO has also shown promise for psychiatric conditions.

My basis for this belief is routinely seeing a variety of psychiatric issues follow brain injuries and frequently observing that medical therapies which restore the health of the brain frequently also improve psychiatric issues. For example, another one of my favorite therapies,  ultraviolet blood irradiation, essentially works by increasing circulation throughout the body, decreasing inflammation, and reawakening cells that have entered a dormant state (before they die)—all of which DMSO also does. In turn, since these three mechanisms underlie so many different disease processes,  a vast body of literature demonstrates its remarkable efficacy for a wide range of conditions, including psychiatric ones.

In the process of unearthing every DMSO paper in existence, I uncovered a Russian team (at the Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences) which produced some of the best evidence I've come across for this theory. 1^, 2^, 3^, 4^, 5^, 6^, 7^, 8

Briefly, in their effort to find a biologic cause of psychiatric conditions (which have a wide variety of seemingly unrelated causes), they discovered the chronic stress which causes psychiatric disorders is accompanied by impaired circulation to the brain which sets off a variety of degenerative processes, especially once the individual's ability to compensate for acute short-term stress is overwhelmed by chronic sustained stress.

To study this, they repeatedly induced neurosis in animals using prolonged stressors (white noise, light flashes, and electric shocks over 3+ weeks), then using biomicroscopy (cranial window) and hydrogen clearance, they directly measured blood flow in the territory of the middle cerebral artery, and finally, they directly examined the brains.
Note: neurosis (невроз) is an outdated psychiatric term. In this Soviet-era context, it describes a breakdown of higher nervous activity caused by chronic stress that overwhelms the person's coping ability. Modern equivalents include Generalized Anxiety Disorder, mixed depressive and anxiety disorder (ICD-11), neurasthenia, and adjustment disorder with anxious or depressed mood.

From this they found:

•The brain normally receives 5-7 times higher blood flow per gram of tissue than most other organs due to its exceptional energy demands. Acute stress typically causes a short-term increase in cerebral blood flow, but prolonged chronic stress (leading to neurosis) produces a sustained decrease that persists 4-6 weeks after the stressor ends. This reduction causes circulatory hypoxia, elevated brain lactate, decreased caspase-3 and Na,K-ATPase activity, impaired mitochondrial respiration (including reduced succinate dehydrogenase and NADH dehydrogenase activity), and increased reactive oxygen species (ROS) production. In animals unable to adapt by shifting from succinic acid to NADH oxidation, stress resistance is markedly reduced. The resulting hypoxia also increases cytochrome oxidase activity (by 35-40%) and triggers mitochondrial biogenesis, followed by ROS triggered lipid peroxidation (LPO). 1^, 2^, 3^, 4
Note: the brain is particularly vulnerable to this cascade due to its exceptionally high metabolic rate and oxygen demand, as well as its high content of (oxidizable) polyunsaturated fatty acids in cell membranes.

•In the early stages of neurosis, acute stress, a nonspecific protective response, inhibits LPO that accumulates readily oxidized phospholipids, decreases cholesterol content, and increases superoxide-scavenging activity (partly from stress hormones acting as radical scavengers). With continued chronic stress, this protective phase is overwhelmed, leading to activation of free-radical lipid oxidation, progressive phospholipid depletion, cholesterol accumulation, and  an increased of oxidized proteins. These biphasic membrane changes initially increase resistance to further peroxidation but ultimately render membranes more vulnerable as stress continues. 1^, 2^, 3^, 4
Note:  this biphasic pattern was also observed in women with dysmenorrhea (after 12 hours of pain, plasma levels of Schiff's bases were reduced by almost two-thirds whereas after 12-24 hours it was nearly double from control values).

•The later adaptations to chronic stress are more specific and membrane and free-radical changes often show interhemispheric asymmetry varying by behavioral type. For example, in acute stress, animals with high emotional reactivity and emotional resonance shift toward balanced or right-dominant LOP products (as do stress sensitive rats that excel with mazes), while low-reactivity animals strengthen have more LOP on the left (as do stress resistant rats that are not good with mazes).

•These molecular changes are accompanied by clear physiological disturbances: elevated and fluctuating systolic blood pressure, disruption and reduction of local cerebral blood flow, loss of functional specificity (equalization of blood flow across brain structures), and a behavioral shift toward passive-defensive behavior. As stress and sympathetic hyperactivity can cause these autonomic disturbances, the researchers concluded that the resulting restriction of cerebral blood flow contributed to many symptoms seen in neurosis.
Note: one of my favorite modalities ( neural therapy) works by neutralizing autonomic disturbances and frequently produces rapid, dramatic responses in complex illnesses — which I believe relates to the pathological process described by the Russian researchers.

• They also found that local norepinephrine release within the lateral hypothalamus functions as part of a depressor system that helps normalize elevated blood pressure. During acute stress, the speed of return to baseline blood pressure depended on the strength of this local noradrenergic response in the lateral hypothalamus. As such, when this mechanism is impaired, repeated stress can lead to prolonged hemodynamic instability, which over time, can contribute to dysregulation of cerebral autoregulation and sustained reductions in cerebral blood flow (which then damages the hypothalmus, creating a downwards spiral into chronic illness).
Note: most chronically elevated blood pressure has no known cause. This framework potentially explains a key unrecognized cause (along with another reason why restoring  zeta potential will  improve blood pressure, as doing so will restore blood flow the the hypothalamus). Additionally, I should note that certain holistic healers have reported significant success in treating excessive sympathetic activity by addressing hypothalamic function.

•Normal cerebral blood flow is approximately 50 ml/100 g/min; in chronic neurosis it falls below 30. Cerebral vessels also lose autoregulatory capacity: after bilateral carotid occlusion, normal animals show universal arterial dilation, whereas neurosis animals exhibit mixed arterial and venous responses (e.g., in arterioles 54% dilated, 21% constricted, 25% had no change) with frequent spastic contractions, bottle-shaped deformations, interrupted flow and perverted pial vascular reactions, resulting in a relative equalization of blood flow rate across all studied structures (indicating a loss of functional specificity—which I consider to have immense clinical significance as a few healing traditions associate this shift with approaching death).
Note:  in many cases, cerebral hemodynamics never fully recover after the chronic stress period.

•These hemodynamic changes parallel the homogenization of EEG activity seen in neurosis. Biomicroscopy confirmed microstructural disturbances consistent with hypoxia, including perivascular and pericellular edema, tortuous vessels, dark neurons, acidophilic cells,  microglial proliferation, and  hippocampal damage (especially shrunken soma, altered nuclei, and corkscrew dendrites in CA3; 2.7-7.1% cell loss in CA1—approaching the threshold for cognitive impairment and dementia).

•The process selectively damages  brain β-adrenoreceptors (which for about a week showed decreased receptor affinity that was compensated for by an increased receptor number, with the elevated receptor density persisting after three weeks),  the sensorimotor cortex (layer V),  the hippocampus (in the pyramidal layer,  particularly at the the CA3 field).

•Three stages of the general adaptation syndrome were identified in the chronic emotional-painful stress model: (1) initial search for optimal functioning with residual visceral defects, fear-dominant behavior, and labile blood pressure, lasting a week; (2) partial autonomic stabilization but ongoing phospholipid depletion ("local wear"); (3) exhaustion with breakdown of autonomic regulation, LPO activation, and profound membrane disruption across neurons, glia, and synapses, contributing to the breakdown of higher nervous activity.. The authors described this as "pathological adaptation with a high structural price."

They then:

•Emphasized that an individual's internal reaction to stressors rather than the stressor is pivotal ("...it does not matter what facts are reported to us — what is important is how we react to them; that is the main question") and linked it to the observation that many illnesses resulting from chronic psychoemotional stress are characterized by autonomic (vascular) disorders, hypoxic states, and serious disturbances in metabolic processes., often manifesting as autonomic/vascular dysregulation, hypoxia, and metabolic disturbances.
Note: the non-English speaker who coined the medical concept of stress  stated he meant to use the word strain (how a system deforms in response to stress).

•Noted that, while many individuals reach full neurosis, far more are in a pre-neurotic stage of significant strain without complete decompensation and would greatly benefit from therapeutic interventions early in their disease process.

•Highlighted that the effects of chronic stress they observed were similar to those seen after  strokes,  heart attacks, or t raumatic brain injury, and in many cases, they successfully used the same therapies for both (e.g.,  panthenol).

To address neurosis:

•The researchers first used agents with antihypoxic and antioxidant properties (e.g.,  carnosine,  substance P, phenosan K, or another synthetic phenolic antioxidants 1^, 2) and finding these interventions both prevented and effectively treated experimental neurosis in animals (whereas untreated animals consistently developed neurosis and showed poor recovery).
Note: other agents  like panthenol only gave temporary improvements. Additionally, they also had significant success with alcohol (a hydroxyl scavenger), providing a novel explanation for while alcohol offers some relief from chronic depression.

After testing multiple agents,  the researchers achieved strong success with negative ion therapy (which has a pronounced antihypoxic effect). When present during acute stress (e.g., immobilization), negative ions completely prevented the pathologic brain changes in all animals — regardless of behavioral type — including preservation of oxidative enzyme activity in the sensorimotor cortex and normalization of behavioral and autonomic parameters (heart rate, blood pressure, and breathing). Similar protective effects were observed with succinic acid (30 mg/kg orally daily for 8 days), which  they also found preserved orienting behavior after a heart attack. Notably, rats with an active behavioral type showed greater natural resistance to cerebral hypoxia, exhibiting faster increases in local cerebral blood flow and brain oxygen tension during stress.
Note: positive ions in the air  have been extensively linked to psychiatric conditions. I believe this is because positive ions  impair zeta potential and hence r educe cerebral microcirculation (whereas negative ions restore it).

They eventually had the greatest success by combining oral DMSO (a potent hydroxyl scavenger) with vitamin E (alpha-tocopherol), finding the efficacy of this combination exceeded them being given separately (e.g.,  for autonomic or behavioral issues). They attributed this to DMSO enhancing vitamin E's antioxidant capacity as DMSO could rapidly deliver it to cell membranes before it had lost its antioxidant capacity from reacting with other substances in the body ( supported by it reducing free radical oxidation products, raising of superoxide scavenging activity in the brain and blood serum, raising brain phospholipids content and normalizing brain cholesterol content).. Finally, in 1999, they shared these results had begun being replicated in USSR sanctioned clinical trials at the Moscow Medical Academy.

While much could be said about their research, one of the key lessons I received was one of the clearest mechanistic explanations I've encountered for what adaptogens actually do (a term applied to many natural products) as the agents which effectively counteracted the entire stress process were explicitly characterized by the researchers as "adaptogens."

Note: to compile the above summary and accurately represent their findings, I read through over 50 papers (many of which omitted key details) and did my best to integrate their findings with current physiologic science).

Let's now look at the rest of the data which has accumulated for using DMSO in psychiatry and note how often it mirrors the findings of the Russian researchers.

Human Studies

 The most detailed study on DMSO's use for psychiatric patients was conducted at a Peruvian psychiatric hospital, where 42 patients (25 schizophrenics, 4 manic depressive psychotics, 4 alcoholic psychotics, 4 compulsive-obsessive neurotics and 5 patients with severe anxiety) were taken off all their medications then given 2-5 intramuscular injections each day (with more given to the most psychotic patients) and compared to 16 controls receiving standard care. 1^, 2

Of the schizophrenic, all 14 of the acute cases experienced a rapid and dramatic improvement (particularly in their agitation—especially for the catatonic-paranoid patients), with all being discharged within 45 days (three having a complete recovery 15 days after admission) and not having a recurrence. To quote one of them:

"I have been out of my mind. I don't know what happened to me. I wonder what my children are going to say."

Of the 11 chronic schizophrenics, 4 periodically needed hospitalization and had a complete remission following DMSO (allowing them to be discharged much faster than normal), and in those who later relapsed, there was again a positive response to DMSO. The remaining 7 were more severe cases (e.g., they had been hospitalized for over 6 years and failed years of therapies) and experienced an improvement from DMSO, but it was not enough to leave the hospital.

Note: results like this (I've seen similar ones with other therapies as well) lead me to believe that the existing understanding of schizophrenia is extremely incomplete. To further support that contention,  this author also shared a case of a severely delusional paranoid schizophrenic responding to DMSO.

The 4 manic-depressive psychotics (who were in the manic phase, averaging 15 days of psychomotor agitation) rapidly calmed down and lost their mania after DMSO (with their recovery being much faster than what they'd previously experienced from conventional therapy).

The 4 alcoholic psychotics (2 with hallucinations and 2 with delirium tremens) had previously been hospitalized for these issues. They rapidly responded to DMSO, with restlessness improving in the first few days while the hallucinations took longer.

The remaining patients (obsessive-compulsive neurosis and severe anxiety) also had a good response to DMSO (e.g., they were calmer, ideas did not upset them as before, they were able to act in a more spontaneous way, and they were able to overcome their obsessive compulsions).

Note: the authors of the 1967 paper  noted that DMSO had antipsychotic and antianxiety properties and that its action differed from tranquilizers in that little sedation or central depression was produced. A later 1992 paper proposed that the antipsychotic effects observed in this trial resulted from DMSO suppressing excessive interleukin-2 (IL-2) production by T-lymphocytes, a mechanism also attributed to certain antipsychotics in the same model.

Sadly (like many things in medicine) these 1967 results elicited minimal interest and no attempts were made to replicate them (although  1982 Russian review noted DMSO could be used for psychiatric disorders and  a 2006 Russian literature review noted intramuscular injections of 50% DMSO had a sedating effect on psychotic patients).

To the best of my knowledge, only five other human psychiatric studies have been done with DMSO:

• In 17 patients (ages 28-55 years) with chronic depression (for at least 5-20 years) that did not respond to antidepressant therapy whose most recent depressive episode lasted 8 months to 2 years, DMSO was able to treat their depression. Specifically, the existing basic antidepressant therapy (amythriptilin, pirasidol, anafranil), was combined with 1ml 50% oral DMSO and taken three times a day, resulting in 14 (82.3%) of the patients having a resolution of their depression which persisted for the 1-4 years of follow-up each patient received.
Note: studies evaluating DMSO in combination with SSRI antidepressants are quite rare.  In one of the only ones I've found, they jointly decreased rat appetite for sugar, while in the other ( a heart study) the detected effects occurred at much higher concentrations than the blood on an SSRI user will reach.

• A study of 210 women with exacerbated chronic generalized periodontitis found that 10% DMSO mixed with 0.2% oxymetacil and delivered via ultrasound effectively relieved their periodontitis and lowered their anxiety.

•In two Chilean studies detailed by  Morton Walker, a DMSO combination with amino acid was used to treat depressive neuroses (e.g., mood and anxiety disorder) while in another, when used to treat cognitive impairment and dementia, those patients also experienced a significant improvement of their mood (going from depressed to happy). 1^, 2

• In women with post partum depression (PPD), blood tests consistently showed significantly lower vitamain D, serotonin, and norepinephrine. When vitamin D in DMSO was given to cultured hippocampal neurons, beneficial increases were observed in both their proliferation and secretion of serotonin, and norepinephrine (likely via the PI3K/Akt pathway).
Note:  In lymphoblastoids from women with PPD, brexanolone (an approved PPD therapy) in DMSO modulated the expression of 98 genes potentially linked to PPD (which was believed to account for its rapid effect on PPD).

However, a variety of animals one have been and will be summarized (all of which, unless otherwise specified were conducted with rats or mice).

PTSD

• In one study designed to model PTSD (via traumatic stress in adolescence), the methyltransferase inhibitor Unc0642 (dissolved in DMSO) alleviated (otherwise permanent) anxiety, depression, social and cognitive dysfunction and normalized PTSD impaired brain development.

• In a modified single prolonged stress (SPS) model of PTSD in rats, a moderate dose of Cannabis sativa leaf extract (dissolved in DMSO) significantly enhanced the efficacy of exposure therapy in extinguishing the conditioned fear memory. The benefit was CB1 receptor-dependent and persisted in a drug-free test 14 days later.

Stress

In addition to the stress which causes PTSD, many rodent studies have modeled a variety of other stressful situation (which frequently cause anxiety or depression). These comprise the majority of DMSO psychiatric studies, and collectively, these results help support the theory of psychiatric illness proposed by the previously mentioned Russian Researchers.

•In chronic "social defeat" stress induced by repeated exposure to an aggressive male which attacks another rodent into submission,  DMSO combined with Dihydromyricetin significantly improved learning and memory, decreased immobility time, and reduced anxiety.  In another study, Epothilone D (a natural microtubule stabilizing agent), dissolved in DMSO, prevented brain changes in the prefrontal cortex and hippocampus caused by this type of stress.  Naringenin attenuated social defeat-induced neurobehavioral deficits, reduced oxidative stress (brain MDA), restored glutathione, and lowered TNF-α and IL-1β.

Numerous studies have shown promise for mitigating the effects of chronic emotional-painful stress (typically three weeks of EPS).

•In one, 1^, 2 DMSO prior to the stress, increased superoxide dismutase (SOD) activity in brain homogenates and serum, in another, DMSO also increased SOD activity decreased ceruloplasmin-transferrin activity 1—suggesting DMSO's ability to neutralize chronic stress relates to DMSO reducing oxidative stress.

• In another, DMSO (1 g/kg i.p., as a 20% aqueous solution) prior to chronic EPS completely prevented the development of gastric ulcers, blocked the stress-induced behavioral changes in the open field test (excessive locomotion, rearing, and reduced center exploration indicative of anxiety), and normalized the cardiovascular and autonomic responses, including the hypertension and altered heart and respiration rates that occurred both during stress and during subsequent immobilization. Additionally, like the previous studies, it markedly increased SOD activity in the brain. 1^, 2
Note: since DMSO interfered with the formation of malonic dialdehyde (a marker of lipid peroxidation) the investigators were unable to also measure if it reduced its formation within the brain.

The controversial forced swimming test (FST) evaluates depression through the shift from active coping behaviors to passive immobility in mice facing an inescapable stressor. Either alone or in combination with the tail suspension test, studies found DMSO in combination with the following substances elicited anti-depressant activity:  flavonoi ds from  Alpinia oxyphylla, cinnamon extract,  asiatic acid (comparable to midazolam),  trans-resveratrol, chrysin 1^, 2 (which was further enhanced by prozac and similar in efficacy to diazepam), ethanolic extract of Ptychopetalum olacoides, essential oil of Nepeta rtanjensis (a monoamine oxidase inhibitor),  Riparin III (from an Amazonian plant),  methanolic extracts of  Cuminum nigrum (L) and  Centratherum anthelminticum (which also reduced anxiety),  ganoderic acid A, methanolic extract of Withania qaraitica (similar in efficacy to citalopram or desipramine),  oridonin,  alarin,  ODQ and 7-NI, Prozac, and a  cannabinoid CB1 receptor agonist.

Chronic restraint stress is a common rodent test for modeling human depression, anxiety. For CRS rats, in combination with DMSO:

• A caspase-1 inhibitor reduced the immobility, social avoidance and anhedonia which followed CRS and social defeat stress.

•Xiao Yao San and a c-Jun (JNK) inhibitor repeatedly improved anxiety-like behaviors. Additionally, the Chinese herbal formula reduced phosphorylated JNK, JNK, and P-c-Jun protein and mRNA expression in hippocampus comparably to the JNK inhibitor in CRS rats with liver depression and spleen deficiency syndrome.. 1^, 2

•Intraperitoneal quercetin significantly mitigated anxiety- and depression-like behaviors in CRS rats who also had restricted cerebral blood flow (via bilateral carotid artery stenosis) along with alleviating hippocampal demyelination, restoring myelin sheath thickness, reduced brain inflammation (via reduced IL-1β/TNF-α, increased IL-10/IL-4, promoted microglial M2 polarization) and and enhanced microglial phagocytosis (elimination) of harmful myelin fragments.

• A corticotropin-releasing hormone type 1 receptor antagonist prevented stress-induced decreases in body weight, sucrose preference, and locomotion along with hypothalamus BDNF and GAP-43 upregulation (as unlike in the hippocampus, hypothalamic increases are maladaptive).

• Safranal protected against restraint stress-induced oxidative brain damage and alleviated stress-induced behavioral changes.

• Saikosaponin A and paeoniflorin relieved corticosterone induced inhibition of autophagic flux in PC12 cells by reducing LC3II/I, P62, and mTOR expression, suggesting a role in chronic stress.

Depression

The Chronic Unpredictable Mild Stress (CUS) test mirrors the development of depression in humans is one of top tests for evaluating it in rodents. Natural compounds, targeted pathway inhibitors, and clinically used pharmaceutical drugs (administered in combination with DMSO) showed the following beneficial effects in CUS-exposed rats:

Natural compounds, targeted inhibitors, and pharmaceutical drugs, in combination with DMSO did the following for CUS rats:

• A ptychopetalum olacoides extract prevented anxiety and hyperglycemia.

• Intraperitoneal curcumin ameliorated depressive-like behavior and upregulated (neurotrophic) BDNF, PSD-95, synaptophysin, p-Limk1, and p-cofilin expression in the prefrontal cortex compared.  In another study, it also reversed CUS behaviors and upregulated those three neurotrophic proteins in the lateral amygdala.

• Oridonin (from Rabdosia rubescens) reduced social anxiety and depression, improved sucrose preference, open field activity, and neuronal morphology and cell numbers in prefrontal cortex and hippocampus and suppressed the inflammatory p38 MAPK/NF-κB/NLRP3 pathway.

The JNK blocker SP600125 partially modulated the hyperactive HPA axis by significantly lowering pituitary ACTH levels and upregulating glucocorticoid receptor (GR) expression in the hippocampal CA3 region compared to the solvent control, reduced the stress-induced increase in caspase-12 (suppressing hippocampal neuronal apoptosis), reduced C-jun (a pathway often overactivated in chronic stress) and enhanced electroacupuncture's reduction of depression. 1^, 2^, 3^, 4

• Necrostatin-1 (which blocks inflammatory cell death) also improved depressive-like behaviors.

 Intracerebroventricular a larin reduced depression, decreased latency to feed, and restored p-ERK/ERK and p-AKT/AKT (neurotrophic/neuroplasticity) activity in prefrontal cortex.

• Agomelatine reduced TRPV1-mediated calcium influx, oxidative stress, and apoptosis in hippocampal neurons of chronically stressed rats, improving depression-related behaviors.

• Pioglitazone improved depressive-like behaviors, suppressed pro-inflammatory cytokine increases (TNF-α, IL-1β, IL-6), reduced M1/M2 microglial ratio, decreased NF-κB expression, and ameliorated peroxisome proliferator-activated receptor gamma (PPARγ) expression loss in the prefrontal cortex and hippocampus

• Quetiapine ameliorated depressive-like behavior in chronic unpredictable stress rats, increased hippocampal BDNF and phospho-ERK1/2 expression, and promoted neurogenesis, effects (and was synergistically by combination with transcranial magnetic stimulation).

Note:  DMSO alone decreased elevated caspase-12 protein expression in hippocampus (which can cause neuronal death).

Separating infant rats from their mothers produces long-term depressive-like behaviors (e.g., anhedonia, HPA-axis dysregulation, and reduced hippocampal neurogenesis) that mirror those seen in human adults with depression and chronic stress.  In separated rats, melatonin dissolved in DMSO significantly increased BrdU-positive cells and lowered glucocorticoid receptor expression in the dentate gyrus, directly counteracting the depressive process.

Note: The term "depression" is used for both a psychiatric (psychological/mood) state and a CNS-induced reduction in activity and alertness (neurologic depression or depressed mentation). These are related as inflammatory or infectious diseases can affect the nervous system and cause it partially shut down, triggering symptoms that overlap with both — such as reduced alertness/mentation and mood changes (often called "sickness behavior"). In certain cases,  such as a foal with brain damage from losing blood supply during childbirth, DMSO's therapeutic activity on the nervous system also addressed the neurologic depression (improved alertness and mentation). In others, DMSO has been observed to help resolve psychiatric depression that followed an illness, likely through anti-inflammatory and neuroprotective effects on shared nervous-system pathways.

Anxiety

In zebrafish, the willingness of zebrafish to leave dark areas to enter light areas is used to assess anxiety, and in this model,  DMSO alone reduced anxiety (as did DMSO  in combination with the chalcone C2OHPDA).

In mice and rats, they way they navigate specific mazes (e.g., elevated plus-maze test) or cross fields are used evaluate anxiety. In one study, DMSO alone (10%, 0.5 µL) microinjected into the DPAG (a midbrain structure) greatly reduced anxiety and increased exploratory behavior. 1^, 2 In combination with DMSO the following agents were found to reduce anxiety:  eucalyptol (primary component of eucalyptus oil), cinnamomum (a hydroalcoholic extract),  marjoram (extracted with DMSO),  luteolin (following acute experimental colitis),  asiatic acid,  Casearin X,  valepotriates,  5-MeO-DMT,  CCK-8,  CCK₂ agonists,  cannabinoid and vanilloid (TRPV1) agonists.

• A mGluR2/3 agonist dissolved in DMSO reduced anxiety in chicks stressed by brief social separation.

Note:  withania somnifera leaf extract (in DMSO) protected against benzo[a]pyrene-induced neurotoxicity in zebrafish by restoring normal anxiety, improving brain antioxidant status, and reducing neuronal damage in the optic tectum.

Biological Stressors

In addition to putting animals into psychologically stressful situations, a variety of stressors that directly injure the body have also been observed to trigger anxiety and depression and to respond to therapeutic combinations containing DMSO.

 Two AMPA-type glutamate receptors, reduced pain hypersensitivity and depression-like behavior in rats with neuropathic and inflammatory pain.

 In neuropathic pain caused by a spared nerve injury (SNI), a DNA methyltransferase inhibitor (in DMSO) significantly improved depressive symptoms and increased neurotrophic brain BDNF levels. In  another SNI study, a chemogenetic DREADD inhibitor (in DMSO) alleviating both pain and depressive symptoms and  in a third, rapamyacin alleviated anxiety. depression and pain from an L5 SNI.

In rats with pentylenetetrazol triggered epilepsy (which consistently produces anxiety and depression), rapamycin and pitolisant (dissolved in DMSO) markedly improved anxiety (2.7 fold improvement on a maze test) and depression (37.5% improvement in swim test).

 In mice with depression induced bacterial lipopolysaccharide (LPS), resveratrol in DMSO reversed their depression along with reversing neural inflammation and triggering neurogenesis (particularly within the hippocampus).

 In mice with toxoplasmosis triggered depression, arctigenin in DMSO significantly reduced depressive behaviors and brain inflammation by inhibiting key pro-inflammatory pathways (TLR4/NF-κB and TNFR1/NF-κB).

 In ovariectomized (OVX) mice modeling menopause, resveratrol in DMSO significantly reduced ovarectomy (ovary removal) induced anxiety and depression and neural inflammation (particularly within the hippocampus).

 In mice with anxiety induced by high-fat diet, Japanese ginseng in DMSO significantly reduced anxiety-like behaviors, increased brain BDNF and synaptophysin levels, and reversed the brain's FGF21 resistance (a key driver of the anxiety)."

In mice, Naringenin improved hypoxia-triggered depression and anxiety, along with reducing brain oxidative stress and inflammation, increasing BDNF expression, and protecting amygdala neurons.

In mice exposed to X-rays after consuming saccharin (as this conditions them to avoid the sweetener), topical DMSO prior to the X-ray largely prevented this condition aversion (there was an 8% rather than 66% drop in saccharin consumption). A later study had similar results, suggesting DMSO counteracts the stress that would otherwise condition the aversion. 1^, 2

Note: lastly some of the DMSO combinations described in the previus sections were used to treat conditions directly triggered by a pharmaceutical (e.g.,  depression from corticosterone or  anxiety from salicylates).

Psychosis

• DMSO was proposed to exert antipsychotic effects by modulating chronic macrophage activation and downstream cytokine dysregulation, particularly interleukin-2 signaling, thereby reducing schizophrenia symptoms across disease phases through immune regulation.

•MK-801, a drug with the same mechanism as psychosis inducing phencyclidine (PCP) and ketamine, is used to induce schizophrenia in rodents. A study found that  atypical antipsychotics and the Src kinase inhibitor PP1, dissolved in DMSO, significantly attenuated MK-801-induced cortical (brain) injury in rats, with the protective potency of the antipsychotics correlating with their clinical effectiveness in treating psychosis.

• In a MK-801 rat study, three different drugs that activated the α7nAChR receptor (when combined with DMSO), significantly improved schizophrenic behaviors by increasing following behavior and total interaction time, decreasing avoidance behavior time along with creating therapeutic changes within the prefrontal cortex and hippocampus (increased α7 nAChR protein expression, increased cAMP levels, decreased PDE4A and PDE4D protein expression).

• Diosmin attenuated hyperactivity, behavioral deficits, oxidative stress, and neuroinflammation in a mouse model of LPS plus ketamine-induced schizophrenia-like symptoms.

• In another MK-801 schizophrenia study, the flavanoid Fisetin (given intraperitoneally in DMSO) significantly decreased rat escape latency, increased space exploration time and platform crossings and (beneficially) phosphorylated CaMKII, ERK1/2, and CREB.

In addition to these combinations treating schizophrenia,  tinospora cordifolia (an Ayurvedic herb) dissolved in DMSO demonstrated antipsychotic activated in mice given (psychosis inducing) amphetamines (along with  curcumin in DMSO counteracting methamphetamine-induced neurotoxicity and spatial memory impairment in rats).

Note:  a study (which found female rats were more prone to developing methamphetamine addictions than male rats) found modafinil dissolved in DMSO, attenuated METH-seeking behavior in both sexes. Another study found parthenolide (dissolved in 1% DMSO) partially blocked cocaine's actions in the brain (but it is unlikely this could translate to a cocaine addiction therapy).

Sedation and relaxation are sometimes reported from DMSO use (e.g.,  sedation has been repeatedly observed in humans and animals at higher doses,  intraperitoneal DMSO was observed to cause a decrease in spontaneous motor activity and  in one large trial, 3% of DMSO users reported increased tiredness). This is likely due DMSO increasing parasympathetic tone ( due to it inhibiting acetylcholinesterase), and may partially account for DMSO's psychiatric properties as excessive sympathetic activity plays a key role in anxiety, mania and psychosis.
Note: I find a significant portion of psychiatric issues result from excessive sympathetic activity or deficient parasympathetic tone (e.g., the"buzz"that state creates frequently creates anxiety), and likewise many (myself included) believe a significant number of health issues result from vagal (parasympathetic) dysfunction. Given that DMSO can both directly increase parasympathetic function and also heal or restore the function of nerves (along with potentially relaxing tight muscles compressing them), it is possible some of DMSO's benefits in psychiatric conditions arise from its effect on vagal function.

Finally, like many other therapeutic agents, DMSO has also been combined with antipsychotics. For example,  with intraperitoneal haloperidol, it facilitated haloperidol-induced 1.8-fold increases in striatal preproenkephalin mRNA and 1.6-fold increases in total endogenous opioid peptides (with no effect in other brain regions), increasing antipsychotic efficacy, and potentially reducing pain or antipsychotic extrapyramidal side effects.

Note: a variety of antipsychotics have used DMSO as a vehicle (e.g., this study did so with intraperitoneal olanzapine, amisulpride, quetiapine and aripiprazole, while this one did so with haloperidol, clozapine, RMI-81582 and risperidone).

Sleep

Sleep is one of the most important, yet least appreciated facets of our existence, as it healing the body and integrating our minds is an immensely complex process that can easily be derailed (e.g., poor sleep causes neurodegeneration, and neurodegeneration worsens sleep). Sadly, rather than support it, our medical system defaults to treating insomnia with sedatives (e.g., sleeping pills) which"put you to sleep"but also sedate the restorative process of sleep—which is tragic, as restoring healthy sleep is frequently one of the top three things which needs to be done to heal chronic illnesses.

Since DMSO heals the nervous system and restores impaired fluid circulation (which I believe is what ultimately underlies many cases of insomnia), I hence was hopeful DMSO could be a remarkable sleep aid to facilitate restorative sleep.

Yet, in the 6,000 reports I've received from readers, I have only received a few reports indicating that happened. 1^, 2^, 3^, 4^, 5^, 6. 7^, 8^, 9^, 10^, 11

 The thing I have noticed most recently is a reduction of fatigue. I used to indulge in a daily nap, then go to bed and sleep another 8-9 hours at night. Now, if I try to nap I just can't be bothered. I sleep my normal sleep at night and awaken refreshed.

Note:  another reader had an almost identical experience, while  another reported DMSO addressed the excessive sleep they had long required following a stroke.

 I take a couple of mls before bed helps dramatically improve my sleep.

 I feel amazing. My sleep is generally remarkable.

 I love the really deep sleep it gives me. Feeling very tired after months of long intense work, I took a small dose one morning just because. An hour later I had no choice but to sleep. Woke up hours later totally refreshed. Amazing stuff.

 I have started using it instead of Hydroxyzine, which I use at times. No side effects!

Note: a few readers have also reported an energizing effect from DMSO causing them to wake up after much shorter periods and feeling refreshed (which may be positive or negative).

However, in the reports I've received, two consistent patterns have jumped out.

First, while DMSO did not inherently function as a"sleeping pill"a large number of people reported that DMSO cured an ailment which was causing insomnia, and I have received dozens of reports from individuals stating DMSO allowing them to sleep profoundly improved their life (including cases where they had previously been suicidal). This, in turn, highlights the flaws of the symptom based approach to medicine we practice, as many cases of insomnia which have clearly identifiable causes (that are never addressed) are instead simply"treated"with sleeping pills.

Most commonly, this was due to DMSO treating musculoskeletal pain which had kept them from falling asleep (or routinely woke them up at night). Shoulder pain resolutions (e.g., bursitis, impingements, or rotator cuff tears)  1^, 2^, 3^, 4^, 5^, 6^, 7^, 8^, 9^, 10^, 11^, 12^, 13^, 14^, 15^, 16^, 17 were the most common, followed by low back pain (e.g., radiculopathy, disc herniations or tears, failed spinal surgery, vertebral metastasis), 1^, 2^, 3^, 4^, 5^, 6^, 7^, 8^, 9^, 10^, 11^, 12^, 13^, 14 arthritis (e.g. rheumatoid arthritis and in the hands or toes), 1^, 2^, 3^, 4^, 5^, 6^, 7^, 8^, 9 knee pain (e.g., arthritis, meniscus injury, or a sprain in a 2 year old), 1^, 2^, 3^, 4^, 5^, 6^, 7 hip pain (e.g., bursitis), 1^, 2^, 3^, 4 elbow pain (e.g., tennis elbow), 1^, 2^, 3 neck pain (whiplash or degenerative discs) 1^, 2 hand pain, 1^, 2 jaw pain 1^, 2 lower extremity tendopathy (e.g., gluteal) 1^, 2 plus individual instances of sleep greatly improving following the resolution of  sciatica,  foot pain,  a throbbing thumb,  tight muscles, and  blunt maxillofacial trauma (from a car throwing them into the pavement)

DMSO also resolved other types of pain that prevent sleep such as peripheral neuropathy (e.g., in the feet), 1^, 2^, 3^, 4^, 5^, 6^, 7 headaches (e.g., migraines, concussions), 1^, 2^, 3 cancer pain 1^, 2 individual instances of  eye pain,  CPRS, and  trigeminal neuralagia plus numerous resolutions of unspecified pains which had prevented them from sleeping. 1^, 2^, 3^, 4^, 5^, 6^, 7^, 8

DMSO also improved other challenging neurological conditions to the point sleep also dramatically improved such as restless leg syndrome, 1^, 2^, 3^, 4^, 5^, 6 Lyme disease, 1^, 2 vaccine injures (from Moderna or the shingles vaccine) 1^, 2 along with individual successes with  Down syndrome,  demyelinating polyneuropathy,  cramping fasciculation syndrome [similar to ALS and until DMSO had made the reader suicidal], an  elderly dog with tics, and  unspecified long term neurological issues that had prevented getting a good nights sleep for years. For example, to quote one Lyme patient:

 Then I woke one morning and was astounded to realize I had slept through the night, -[whereas] before DMSO I had been waking 3 or 4 times every night because of pain.

Finally, in addition to DMSO addressing pain and neuropathies which prevented sleep, it also addressed other issues which interfered with sleep. Most commonly this was through improved breathing, specifically by addressing sinusitis (e.g.,"I had the best sleep last night, I didn't want to get up this morning.) 1^, 2^, 3 or lung issues (e.g., asthma, COPD or lung damage from burn pits in Afghanistan). 1^, 2^,. One reader sent a particularly interesting testimonial, suggesting DMSO can sometimes improve nightly oxygen saturation:

 I tried a little 70% on a que tip inside each nostril before bed to see if it would help nighttime congestion. Interesting that I get no itch or tingles from inside my nostrils...maybe due to the mucus ? Well, anyway, I wear a sleep tracker ring and my oxygen level and oxygen drops have significantly improved and I am sleeping in longer periods without waking up so often ! I am amazed and tried to find some research that would help explain these improvements. I found some research on sleep patterns in rodents but difficult to understand. I just wanted to let you know and thank you for sharing your knowledge. I will continue my experiment and so far every night it has improved sleep data.

Note: other issues readers reported DMSO sleep improvements with include  Barrett's esophagus,  severe eczma,  prostate enlargement,  hypothyroidism, or  an acute cold.

In short, given how necessary healthy sleep is for the nervous system (discussed further  here) a case can hence be made that one of the primary ways DMSO "heals the nervous system" results from it treating the ailments that were preventing healthy sleep.

Secondly, I noticed that many readers independently shared that their dreams became more vivid or lucid after taking DMSO. 1^, 2^, 3^, 4^, 5^, 6^, 7^, 8^, 9^, 10^, 11^, 12^, 13^, 14^, 15^, 16

 Separately, after several weeks of taking DMSO internally now I have indeed noticed increased dreaming. Most of my life I have either not dreamed at all or at least had no memory of any dreams. But I have always slept very deeply and soundly. Usually falling asleep within seconds of laying down and having no memory of anything until morning. When I supplemented 5HTP for a while a few years back I started to dream a lot for the first time in my life.

Two factors can potentially explain this. First, by DMSO healing the nervous system and restoring circulation, this likely aids the neurological apparatus which facilitates dreaming. Second, two compounds are commonly used to facilitate lucid dreaming, 5HTP (as the above reader used) and galantamine (one of the few drugs I've ever used, primarily because of its phenomenal effects with lucid dreaming—provided you do not use an excessive dose). Galantamine is an acetylcholinesterase inhibitor, and since DMSO is also widely recognized to do so, this likely accounts for it increasing the vividness of dreams. However, the effects I've noticed from the two are very different (to the point it would not have occurred to me a similar mechanism was involved), so if this theory is valid, DMSO should be viewed as a much weaker acetylcholinesterase inhibitor which only affects the dreams of a subset of the population.

There seemed to be an wide mix of attitudes to towards the dreams (absolutely loving them, appreciating they can finally remember them, being neutral, or finding them challenging), with the majority being positive. These responses accurately represent that spectrum:

 Picked this stuff up since reading your posts, been giving me some crazy ass vivid dreams, some even fully lucid haha ! Haven't really noticed anything else yet but the dreams alone have been worth it 13/10 would recommend.

 when i drink it...after a couple days...i sleep super deep and have incredibly emotional dreams...which can be tough but i wake up feeling rested (but sad or contemplative).

 Funny you should mention dreams and DMSO, since I started taking it internally my dreams are super vivid and sometimes very unpleasant ! There are people popping up in my dreams now that I haven't thought of in decades...Melatonin also caused vivid dreams, but nothing like what DMSO has been causing!

Overall my favorite dream story was probably this one:

 I have to share this one thing...the first evening I applied DMSO to my neck I went to bed and in the night I heard a voice saying "THE TREES WILL HEAL YOU". In my sleepy state I had thought, oh how nice, I do love our trees ;I live in a forest. However when I awoke it dawned on me that DMSO comes from trees and that message was about the DMSO!

Lastly,  one reader shared that DMSO allowed them to dramatically lower the Xanax they needed to fall asleep, while  another stated it made them much more sensitive to having their sleep disturbed by coffee or beer. This is congruent with DMSO's know ability to potentiate benzodiazepines and alcohol and suggests thought should be taken when using these agents together, but simultaneously, given that only two readers noticed this, I am not sure how impactful it is. Additionally, two readers reported DMSO's sleep promoting effects were enhanced by combining it with magnesium (which is plausible). 1^, 2

Sleep Research

The limited literature on DMSO and sleep shows the following:

1. DMSO alone generally has a minimal impact on the sleep cycle. For example,  a 2005 rat study found 5% and 10% DMSO administered interperitoneally had no effects on sleep architecture, but 15% and 20% shifted deep wave sleep to light wave sleep. This indicates the doses individuals take are unlike to effect sleep unless they are in the sensitive minority. Likewise,  in a study where intraperitoneal corticotropin releasing factor was found to make rats REM sleep become Non-rem sleep, DMSO alone (at an unspecified dose) was found to have no effect on sleep architecture.
Note:  one literature review cited a Russian report that one side effect of DMSO is sleep disturbance, but I have not seen this mentioned anywhere else.

 Russian DMSO lit review: Sleep disorder and bad breath may occur. An unpleasant smell interrupts the sucking of mints.

2. A few references corroborate that DMSO's healing qualities improve sleep by healing something else causing insomnia:

• In a study of 35 men with exacerbated knee osteoarthritis (and upper gastrointestinal bleeding), in addition to topical 50% DMSO (with hydrocortisone, lidocaine and potassium iodide) reducing their knee pain, it also improved their sleep (and ability to work). Specifically, on a -3 (worst) to 3 (best), scale, their baseline sleep score (0.4 ± 0.2) improved to 1.1 ± 0.4 with the DMSO combination, and to 2.8 ± 0.5 when the combination was used with physical therapy.

• In 40 patients (on average 53.7 years old) with with cervical osteochondrosis complicated by shoulder myofascial pain syndrome, topical DMSO (in combination with other analgesics) and physiotherapy and acupuncture fully resolved the pain for 34 (85%), partially improved it for 6 (15%) and in all patients, there was a significant improvement in sleep.

• In a clinical guide from Uzbekistan on surgical infections of the hand and fingers, DMSO was recommended as a conservative treatment (in combination with novacaine and an antibiotic) and for abscess in the fingertip pad to prevent them from becoming painful enough to cause "sleepless nights" and require surgery. In a Ukranian dental manual, DMSO was recommended for healing (and preventing infections) of dry socks, as it resolved the conditions and improved numerous associated things including disrupted sleep.

• In a study of patients with localized scleroderma, daily topical DMSO (and a few other therapies) significantly improved skin lesions, prevented remission and improved emotional health, appetite and sleep.

3: Most of the existing research on DMSO for sleep involved it being a delivery vehicle that was combined with another sleep promoting agent either to facilitate its action or make it more potent. These broke into four categories, two of which supported the observations in reader reports.

Potentiation of sleeping medications:

• Prior administration of DMSO increased the sleeping time created by pentobarbitone sodium by 78%. Conversely, another study found  hexobarbital sleeping times were not altered when 2.5 g/kg of 25% DMSO were given subcutaneously to mice beforehand.

• A DMSO dissolved fraction of a Coriandrum sativum extract accelerated and prolonged pentobarbital induced sleep more than any other agent tested (including diazepam).

•A Marjoram DMSO extract and separately a Nardostachys jatamansi rhizome extract significantly increased ketamine-induced sleep duration. 1^, 2

Modulation of circadian sleeping times (with potential utility for jet lag):

• Melatonin, which accelerated re-entrainment of the mouse's circadian rhythm after a 6-hour phase shift and also made mice more susceptible to light-induced circadian shifts. 1^, 2 In two other studies,, Triazolam (a sleeping pill dissolved in DMSO) shifted and lengthened hamsters' circadian rhythm, whereas DMSO alone only created a small non-significant shift. 1^, 2 Finally,  DMSO's metabolite, MSM (in DMSO) mitigated neurobehavioral impairment, oxidative stress, and disruptions in clock gene expression in a mice exposure to alcohol combined with circadian rhythm disruption.
Note: we suspect DMSO has a significant synergy with photobiomodulation, but still do not have enough data to claim anything definitive.

Improving sleep apnea:

 Intraperitoneal treatment with a Chinese herbal composition of Gastrodia elata and Cinnamomum cassia (dissolved in DMSO) reduced snoring pressure and frequency in aged rats and increased activity of phrenic, recurrent laryngeal, and hypoglossal nerves, while prolonging inspiratory, expiratory, and pre-inspiratory times, suggesting modulation of upper airway neural activity.

 For rats with intermittent hypoxia, a sirtuin 1 inhibitor (dissolved in DMSO) significantly improved the efficacy of sleep apnea tongue training exercises in strengthening the tongue and improving upper airway dynamics. Those exercises were later used in sleep apnea patients to improve their nighttime apneic episodes but it is not clear if the pharmaceutical was also used with the human patients.

In mice with obstructive sleep apnea, dronabinol, a vagal cannabinoid agonist, significantly reduced sleep apnea episodes when combined with 100% DMSO but not when combined with 25% DMSO (while at both concentrations, REM sleep was suppressed). 1^, 2 Separately,  Anandamide (an endogenous cannabinoid) increased sleep and adenosine levels in the basal forebrain.

 In an intermittent hypoxia model of sleep apnea with rats that had heart attacks, Paxil prevented intermittent hypoxia from causing systemic insulin resistance or further damage to the injured heart (e.g., fibrosis and apoptosis was reduced).

Counteracting adverse effects of chronic sleep deprivation

In mice models, a variety of substances in combination with DMSO have been found to counteract the adverse effects of chronic sleep deprivation.  Kaempferitrin (from monkfruit) increased antioxidant capacity, reduced oxidative stress, and reduced obesity.  Astragalin significantly ameliorated liver oxidative stress.  Siraitia grosvenorii flavonoids and melatonin increased antioxidant capacity and reduced oxidative stress and inflammation.  Almorexant improved spatial learning and memory and reduced (neuroinflammatory) astrogliosis.  A macrophage migration inhibitory factor inhibitor improved spatial learning and memory, and partially protected the hippocampal neurons.

 Modafinil (a stimulant used to increase wakefulness in individuals with chronic sleep deprivation) significantly decreased total sleep time and increased sleep latency in English bulldogs with sleep-disordered breathing, effectively alleviating hypersomnolence (tiredness).

 In rats, paxil dissolved in DMSO (for an osmotic minipump) significantly prolonged REM sleep episode duration and reduced the number of REM sleep episodes across multiple 6-h periods (which constitutes a positive shift in chronic sleep deprivation).

Memory

In addition to brain health (vibrant circulation and minimal inflammation or cells being trapped in the cell danger response) being intertwined with sleep, both are also intertwined with mental health, cognition and memory. As such, I have received a few memory improvement stories 1^, 2^, 3^, 4^, 5 like these:

 MWD, your stack is transformative. We now make your zeta potential formula, and have noticed observable results in a short time, it is a daily routine now. We also incorporated DMSO (topically) and marvel at its ability to repair and heal (and yes we have noticed the Lucid dreaming!) - these two items are the basis of our 'first aid' kit that travels wherever we go. Thank you for passing on this knowledge. Inadvertently we started 'studying' post Covid, reading and listening to a vast amount of information - and more times than not falling asleep in the process. This article explains why we can now seem to retain so much information in our 60's than we ever did in our younger days.

 I am a Family Physician who was diagnosed with MCI by Mass General Neurology. I responded by cleaning up my diet, exercising daily, and taking a bunch of supplements, including daily oral DMSO. My memory is now better than it was decades ago.

 So many benefits & people have noticed...Memory is insanely good now.

DMSO alone is generally thought to have a minimal impact on memory (e.g., one paper stated " In all experiments, dimethyl sulfoxide (DMSO) was used as vehicle, since it has no significant effect on passive avoidance learning and memory"). Because of this, I have come across very few studies which compared DMSO's effects on memory to saline controls (rather DMSO is the control), and in most cases, the positive effects seen occur when DMSO is used as a solvent to deliver another therapy.

Studies which have combined a therapeutic agent with DMSO to enhance learning and memory are as follows:

•In three different rat studies, pemoline (Pm) or magnesium pemoline (MgPm) were dissolved in DMSO to influence memory and learning. In one, where rats were evaluated on how many trials it took them to learn a complex maze, compared to a saline baseline, the following reductions were observed: DMSO alone (11.1%), Pm (25.3%), low dose MgPm (32.5%), high dose MgPm (44.6%)—whereas amphetamine worsened learning by 14.5%. 1^, 2 In  a second study, MgPm (both low and high dose) dissolved in DMSO completely prevented retrograde amnesia induced by electroconvulsive shock (ECS). Lastly,  a third study found these agents did not improve reversal learning (the ability to cognitively update an ingrained habit when the reward rule changes).
Note:  DMSO was also shown to increase transport of pemoline into the brain.

• Pregnenolone significantly improved spatial learning and memory and upregulated brain choline acetyltransferase in aged rats.

• Nandrolone improved spatial learning and long-term potentiation in male adolescent rats.

• Capsaicin improved learning acquisition and retention and also mitigated an CB1/CB2 agonist's negative effects on learning.

• Datumetine modulated hippocampal and prefrontal NMDA receptor signaling, upregulating CREB phosphorylation and BDNF expression

• Sumac (extract) enhanced expression of passive avoidance learning and memory retention.

• Rapamycin improved novel object recognition and spatial working memory in middle-aged mice (and protected hippocampal neurons).

• In C. elegans, the mitochondrial uncoupler BAM15 preserved mechanosensory neurons, short-term memory, and extended lifespan.

These therapeutic agents (dissolved in DMSO) showed strong protective effects against memory impairment:

• Fructose 1,6-diphosphate (130 mg/kg) with DMSO (250 mg/kg), improved visuo-spatial memory by 54% in rats with chronic cerebral hypoperfusion.

• Following strokes, 4-methylumbelliferone reduced infarct volume and improved learning and memory by downregulating HAS1/HAS2, modulating inflammatory cytokines, and reducing oxidative stress.

• In aged rats, pioglitazone (in DMSO) improved learning and memory by reducing oxidative stress and increasing antioxidant enzymes in the hippocampus and cortex.

•In chronic restraint stress,  necrostatin-1 protected spatial memory and  flupirtine protected spatial learning and memory (and protected hippocampal neurons).

• In sepsis-associated-encephalopathy, intranasal application a leucine-rich repeat kinase 2 inhibitor reduced hippocampal inflammation and neuronal damage, and protected spatial learning and memory.

• In Alzheimer's disease model rats, oral quercetin significantly improved spatial learning and memory and significantly lessened hippocampal cerebral oxidative stress and neuronal damage.

• In ovariectomized rats, an ERβ agonist reversed spatial learning and reference memory deficits as well as impairments in dendritic spine density and synaptic structural integrity.

• In rats exposed to acute inescapable psychological stress, flupirtine and retigabine prevented impairments in spatial memory and hippocampal memory consolidation.

• Quercetin mitigated REM sleep deprivation-induced memory deficits in mice and hippocampal microglial inflammation.

• Almorexant significantly improved spatial learning and memory in chronically sleep-deprived mice and reduced hippocampal microglial inflammation.

• Artemisia absinthium improved scopolamine induced memory and learning impairments and counteracted damaging oxidative stress.

• The cannabinoid agonist WIN55,212-2 prevented scopolamine-induced impairment of spatial memory in rats.

• A selective CB1 antagonist significantly improved consolidation of aversive (fear-based) associative memory.

• Ptychopetalum olacoides extract reversed MK-801-induced amnesia in both short- and long-term memory.

• 7,8-dihydroxyflavone restored lost spatial learning ability in rats subject to maternal separation stress.

• Suberoylanilide hydroxamic acid reversed the spatial learning impairment in offspring rats exposed to propofol during early pregnancy.

 Sodium para-aminosalicylate reduced manganese-induced neuroinflammation, hippocampal injury in rats while also restoring memory and learning.

• In hyperthyroid mice, AMPA and NMDA receptor agonists restored hippocampal-dependent spatial learning and memory as well as recognition memory.

• In ovariectomized female rats, estrogen supplementation partially restored spatial learning and significantly increased CD147 expression (a neuroprotective protein involved in synaptic function and amyloid-β clearance).

• Intracerebroventricular DHEA enhanced memory retention and prevented amnesia.

• 5-HT2A receptor agonists protected long-term memories from being disrupted by new memories formed shortly afterward.

• Testosterone dissolved in DMSO nearly doubled dendritic spine density in hippocampal neurons via ERK/MAPK signaling, and  restored spatial memory and androgen receptor density in gonadectomized (no testosterone) rats.  Aniracetam and 1-BCP (in DMSO) reversed pyrilamine-induced working memory deficits and restored hippocampal theta power.

Lastly,  in a study showing that impairing dural (meningeal) lymphatic drainage disrupts spatial working memory and interhemispheric coherence, six weeks of daily DMSO injections had no adverse effects on memory.

Cognitive Impairment and Dementia

The same degenerative processes which cause dementia initially trigger cognitive impairment and as such, being able to head this off early, beyond greatly improving ones current quality of life, also allow much worse situations to avoided. As these neurodegenerative processes (e.g., poor blood flow and inflammation) also underlie many of the other neurological disorders DMSO treats, significant data has accumulated for either DMSO alone, or DMSO in combination with another therapy to reverse cognitive loss.

The animal research in this field is as follows:

 When rats had their carotid arteries surgically modified to significantly reduce the amount of blood going to their brain, after 3 months, it was found that DMSO prevented both the neuronal damage and the significant loss of spatial memory and learning that otherwise resulted from that chronic loss of cerebral blood flow.

In a similar study, rats 14 weeks old were subjected to either permanent bilateral carotid artery occlusion or sham occlusion (mimicking the chronic vascular impairments many experience with increasing age) and then tested for visuospatial memory function. After 14 weeks, four rats who had shown persistent and severe memory impairment received DMSO and FDP for 7 days, which improved their memory by 54%, almost reaching the cognitive function of the controls. Unfortunately, this improvement was partially lost once DMSO-FDP were discontinued. 1^, 2

Lurcher mice are used to study olivary and cerebellar disorders because their Purkinje cells can't survive (e.g., by 30 days of age their walking is grossly abnormal). When these mice received DMSO, it prevented the age-related deterioration of certain cognitive functions (e.g., memory and spatial learning abilities). 1^, 2

DMSO has also demonstrated direct cognitive effects in other contexts.  It reduced MK-801-induced neuronal necrosis in the rat cingulate and retrosplenial cortex by 80-86%, even when administered up to 4 hours after dosing—a finding relevant to both anesthesia safety and neuroprotection.  In morphine-sensitized mice, DMSO independently enhanced spatial memory formation in the Morris water maze (with the effects further enhanced by curcumin).  In a mouse model of thiamine deficiency (relevant to Wernicke's encephalopathy), DMSO partially improved behavioral deficits and reduced thalamic damage, and when combined with high-dose thiamine, enhanced recovery beyond thiamine alone.  DMSO alone also produced no spatial learning deficits when injected into the hippocampus in an 8-arm radial maze task, confirming its safety as a vehicle in cognitive research.

Anesthesia-Induced Cognitive Impairment

General anesthesia, particularly prolonged or repeated exposure, can cause lasting cognitive deficits and is recognized to significantly increase the risk for Alzheimer's (making it a growing concern for both young children whose brains are still developing and the elderly). As we've seen numerous people tip over into dementia (as some of their neurons which are put to sleep during the surgery never seem to wake up afterwards), we hence try to minimize surgeries, have anesthesiologists use less toxic anesthetics (the injected rather than inhaled ones), and use nutraceutical to counteract that sedation.

Fortunately, DMSO addresses both the recognized mechanisms of anesthesia toxicity (e.g., neuroinflammation, oxidative stress, mitochondrial dysfunction, or neuronal apoptosis) and what we believe the key issue is (cells becoming stuck in a dormant phase). Unfortunately, all existing research on this subject involved DMSO combined with another agent, so definitive proof DMSO alone antidotes anesthesia toxicity does not exist.

Sevoflurane, one of the most widely used inhalational anesthetics, has been the most extensively studied. Resveratrol dissolved in DMSO repeatedly protected against sevoflurane-induced cognitive deficits in both aged and neonatal rats by activating the SIRT1 pathway, reducing neuroapoptosis, upregulating BDNF, and improving spatial memory. 1^, 2^, 3 Additional agents protecting against sevoflurane-induced cognitive impairment include  arctigenin (which reduced inflammation via the Akt/NF-κB pathway and upregulated CTRP6),  honokiol (which activated SIRT3, reducing neuroinflammation, oxidative stress, and mitochondrial dysfunction), SAHA (which inhibited NLRP3 inflammasome activation and ameliorated cognitive impairment in aged mice), 1^, 2 curcumin 1^, 2 (which improved memory retrieval dysfunction and reversed sevoflurane-induced Aβ increases and BACE-1 upregulation in aged rats),  FTY720 (which prevented hippocampal apoptosis in neonatal rats),  progesterone (which attenuated sevoflurane-induced neuronal injury in primary hippocampal neurons via progesterone receptors and Akt signaling), and  inhibitors of the TLR4-p38MAPK-NF-κB pathway (which attenuated cognitive decline).

Note:  in one neonatal rat study, resveratrol improved molecular markers (SIRT1, PGC-1α, FOXO3α, SOD) and reduced brain pathological damage after sevoflurane, but Morris water maze testing showed no significant behavioral improvement across groups.

Propofol, another widely used anesthetic, causes dose-dependent neuronal apoptosis and lasting cognitive deficits with repeated neonatal exposure. Agents dissolved in DMSO that protected against propofol neurotoxicity include dexmedetomidine (which activated PI3K/Akt/GSK-3β in multiple studies), 1^, 2  etanercept (which blocked TNF-α-mediated damage),  SAHA (which reversed learning and memory impairments by modulating histone acetylation, synaptic proteins, and CREB phosphorylation),  17β estradiol (which reversed deficits through the ERK pathway),  hydroxyl fasudil (which reduced apoptosis via p38 MAPK inhibition and improved Morris water maze performance) and  coenzyme Q10 (which partially reversed propofol-induced mitochondrial respiratory chain inhibition in primary hippocampal neurons).

Isoflurane-induced cognitive impairment was counteracted by  dexmedetomidine dissolved in DMSO (which activated PI3K/Akt and reduced hippocampal apoptosis), intranasal levosimendan (which protected newborn rat brains), and  modafinil (which improved novel object recognition and contextual fear memory during the awakening period).  Dexmedetomidine in DMSO also dose-dependently protected neonatal rat hippocampal neurons from etomidate-induced injury via the same PI3K/Akt pathway.

Other anesthetics:  Dexmedetomidine attenuated ropivacaine-induced mitochondrial toxicity via p38 MAPK. Curcumin in DMSO also protected developing rat brains against ketamine-induced neurotoxicity through the Nrf2-ARE antioxidant pathway, and also protected neonatal hippocampal neurons against the neurotoxicity of the anticonvulsants phenobarbital and valproic acid, significantly reducing neuronal loss. 1^, 2

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