Cureus
April 8, 2026
Christian David Galindo, Victor Agudelo, Ivan Ramirez Blanco et al.
A young woman with no prior psychiatric history experienced a 12-hour episode of visual and auditory hallucinations, disorganized speech, and aggressive behavior requiring emergency restraint. Her symptoms began with unusual noises and a sense of external presence, which her partner also reported, leading to a religious consultation. She later described a trance-like state with loss of self and partial amnesia. Managed with antipsychotic and benzodiazepine treatment, she stabilized. The case illustrates the diagnostic complexity of trance and possession disorder, especially its overlap with acute psychosis, and underscores the need for a biopsychosocial approach that accounts for cultural context.
Cureus
April 1, 2026
Juan Pablo Berlin Viniegra
Treatment-resistant depression (TRD) is defined as failing to achieve remission after at least two adequate antidepressant trials. It causes persistent functional impairment, higher morbidity, and greater healthcare use. This narrative review covers conventional pharmacological strategies, augmentation approaches, ketamine and esketamine, and neuromodulatory interventions including electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), theta burst stimulation (TBS), transcranial direct current stimulation (tDCS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS). Emerging psychedelic-assisted treatments are also discussed. While new modalities expand options for severe cases, limitations remain in cost, accessibility, response durability, and long-term outcomes. Individualized treatment selection and sequencing based on patient history and illness severity are emphasized.
Cureus
April 1, 2026
Samantha Siu, Peter Hsin, Sarah Simon et al.
A systematic review and meta-analysis of six randomized controlled trials found that perioperative ketamine or esketamine, given during elective cesarean section, significantly reduced early postpartum depressive symptoms measured by the Edinburgh Postnatal Depression Scale between postoperative days 3 and 14. The pooled effect showed a standardized mean difference of -0.36, with moderate heterogeneity. The direction of effect consistently favored ketamine over control. The findings suggest a potential benefit for reducing early postpartum depressive symptom burden, but further research is needed to determine optimal dosing, timing, and long-term clinical impact.
Cureus
March 14, 2026
Suneha Shelke, Rusheeth Thummalapally
Treatment-resistant depression (TRD) affects up to a third of people with major depressive disorder who do not respond to standard antidepressants. Esketamine, a nasal spray approved for TRD in 2019, blocks NMDA receptors and may also reduce compulsive and addictive behaviors in patients whose depression and substance use disorders are linked. This review of randomized trials, cohort studies, systematic reviews, and animal research suggests that esketamine can reduce drug-seeking behavior, lessen cravings, and improve outcomes when paired with behavioral therapies like mindfulness. In rodent studies, esketamine reduced cocaine-seeking after abstinence, and clinical data hint at benefits for alcohol misuse. Esketamine may offer a dual treatment for depression and addiction, but larger studies are needed to confirm its effects and safety.
Cureus
January 31, 2026
Lukasz Siwek, Marta Nowocien, Barbara Balajewicz et al.
Psilocybin, a psychoactive compound from Psilocybe mushrooms that activates serotonergic receptors, is being investigated as a treatment for depression, a psychiatric disorder with rising global prevalence projected to become the leading cause of disability by 2030. This narrative review presents recent reports on psilocybin-assisted therapy, which, based on promising results showing higher therapeutic efficacy compared to conventional treatments, offers hope for a modern approach with sustained clinical effects and minimal or no adverse effects.
Cureus
January 25, 2026
Hana Abbasian
Psychedelic-assisted psychotherapy is emerging as a promising mental health treatment that may foster emotional processing, self-understanding, and personal growth through transformative experiences. This article examines ethical considerations through narrative ethics, which focuses on patients' lived experiences and cultural contexts, and virtue ethics, which highlights clinicians' moral character and relational presence. Integrating these frameworks supports holistic, patient-centered care addressing psychological, social, and cultural dimensions of recovery. Ethical practice requires building trust and inclusivity to ensure these interventions promote resilience, empowerment, and well-being across diverse communities. The discussion offers guidance for clinicians, researchers, and policymakers navigating ethical complexities in integrating psychedelics into mental health care.
Cureus
January 1, 2026
Sebastian Hernandez Mejia, Aishwarya Ashwinee, Ranwa Aldaker
A 45-year-old man without prior health problems developed severe rhabdomyolysis (creatine kinase 160,000 U/L) and acute kidney injury requiring dialysis after taking 1.5 grams of pure MDMA, despite never having a fever. This is the first reported case of severe MDMA-associated rhabdomyolysis without hyperthermia and the third-highest creatine kinase values documented. He was later diagnosed with Crohn's disease, suggesting that underlying inflammatory bowel disease-related muscle inflammation may have made him more susceptible to muscle injury. The case indicates a non-hyperthermic mechanism of MDMA toxicity involving direct mitochondrial and oxidative damage to skeletal muscle, potentially worsened by occult Crohn's disease, and underscores that MDMA toxicity should be considered even in afebrile patients with severe rhabdomyolysis.
Cureus
January 1, 2026
Mohsin Raza, Jasleen Kaur
Psychedelic-assisted therapies are gaining renewed scientific and clinical interest in psychiatry, especially for treatment-resistant depression, post-traumatic stress disorder, and substance use disorders. Compounds like psilocybin and MDMA show promising therapeutic effects in controlled clinical trials when used within structured psychotherapeutic frameworks. Neurobiological evidence suggests these agents may promote neural plasticity and enhance cognitive and emotional flexibility, potentially leading to durable clinical improvement. However, significant challenges remain, including regulatory uncertainty, methodological limitations in trials, ethical concerns about patient vulnerability, and equitable access. The editorial highlights both the therapeutic potential and critical considerations for responsible integration into mental health care.
Cureus
December 20, 2025
Marcus Vinícius de Aragão Batista, Miguel Barbosa, José Casimiro et al.
A previously healthy 22-year-old man developed seizures, hyperthermia (43 °C), and cardiovascular collapse one hour after ingesting MDMA. Laboratory results showed severe metabolic acidosis, rhabdomyolysis with creatine kinase over 360,000 U/L, acute kidney injury, disseminated intravascular coagulation, and rapidly progressive hepatic necrosis with aspartate aminotransferase/alanine aminotransferase over 3000 U/L and factor V below 5%. Despite aggressive resuscitation, continuous renal replacement therapy, N-acetylcysteine, plasma exchange, and hemoadsorption, hepatic failure progressed. On day 5, urgent orthotopic liver transplantation was performed, and the patient gradually stabilized. The case illustrates that MDMA can cause catastrophic systemic toxicity and that timely liver transplantation can be lifesaving.
Cureus
December 1, 2025
Demetra Solomos, Aggeliki Bairaktari, Theodoros Xanthos et al.
Adding ketamine to ropivacaine, either intravenously or regionally, speeds the onset of sensory and motor blockade and reduces rebound pain after axillary brachial plexus block for below-elbow surgery. In a randomized trial of 81 patients, both routes of ketamine administration led to faster block onset and lower pain scores on the numerical rating scale at 16, 20, and 24 hours after surgery compared with ropivacaine alone. Motor block scores and the need for postoperative opioid rescue did not differ among groups. The findings suggest that ketamine as an adjuvant improves early postoperative analgesia without increasing opioid use.
Cureus
December 1, 2025
Paweł Liszka, Agata Ogórek, Klaudia M Olejnik-Chlewicka et al.
Classic psychedelics and MDMA are being revisited as potential psychiatric treatments. They work primarily by stimulating 5-HT2A receptors, inducing neuroplastic changes, and modifying functional brain networks, which may help shift entrenched cognitive and emotional patterns. Randomized trials with psilocybin show rapid and sustained reduction of depressive symptoms in treatment-resistant depression and cancer patients, as well as promise for alcohol use disorders. MDMA combined with psychotherapy shows substantial potential for PTSD. Caution is needed due to risks of adverse reactions and drug interactions, especially with serotonergic agents and MAOIs. Further multicenter studies with greater statistical power and longer follow-up are required before routine clinical use.
Cureus
December 1, 2025
Kamran Nazir, Waqas Ahmed, Salman Rafi et al.
Chronic ketamine use can damage both the liver and urinary tract. A 55-year-old woman with recurrent hemorrhagic cystitis and long-term recreational ketamine use had abnormal liver enzymes without symptoms. Imaging showed fatty liver and a beaded pattern of bile duct narrowing, while tests ruled out autoimmune or infectious causes. Bladder biopsy confirmed ketamine-induced cystitis. After stopping ketamine, her liver enzymes improved. This case illustrates that ketamine toxicity can cause cholangiopathy alongside cystitis, an emerging cause of cholestasis and urinary injury.
Cureus
November 23, 2025
A 75-year-old man with chronic exploding head syndrome—loud internal noises, lightning-like sensations, and sleep paralysis for over five years—failed multiple standard medications. Sublingual ketamine, starting at 25 mg every third night and increasing to nightly, reduced episodes from 3-4 times weekly to once every two weeks after one month, monthly by three months, and resolved completely by six months, with only occasional sleep paralysis remaining. The treatment improved quality of life. Ketamine may work through NMDA receptor modulation and neuroplasticity. This case suggests a potential new approach for this difficult-to-treat sleep disorder.
Cureus
November 12, 2025
Aung Phyo Oo, Sarah Tseu, Arvind Ponnusamy
A middle-aged man with past cocaine use developed severe anuric acute kidney injury requiring dialysis after magic mushroom poisoning. He also experienced supraventricular tachycardia, elevated troponin T, and severe left ventricular dysfunction, attributed to possible myocarditis from the mushrooms. Imaging showed extensive thrombosis in the abdominal aorta, superior mesenteric artery, and bilateral iliac arteries, causing right kidney infarction and a pulmonary embolism. While psilocybin may theoretically induce vasoconstriction, direct evidence linking it to thrombosis remains limited.
Cureus
October 1, 2025
Abdelazim Ali, Nahida Ahmed, Sona Varghese
A 41-year-old man with treatment-resistant depression and polysubstance use (daily opioids and intermittent methamphetamine) received intranasal esketamine alongside his existing antidepressant. Depressive symptoms and craving markedly improved within one month. By two months he had stopped using opioids and methamphetamine. At six months he remained in remission and abstinent, with PHQ-9 scores dropping from 24 to 4. Side effects were transient dizziness and mild dissociation. The authors suggest esketamine may reduce craving through glutamatergic modulation and synaptic plasticity, offering dual benefits for depression and substance use, but note that controlled studies are needed.
Cureus
August 1, 2025
Brett Hughes, Soz Mirza, Manasi Ponamala et al.
The COVID-19 pandemic highlighted pre-existing needs for rapid-acting therapies in pediatric psychiatry. This narrative review examined ketamine and psilocybin for treatment-resistant depression, mood disorders, and PTSD in children and adolescents, comparing them to standard treatments. Ketamine, an NMDA receptor antagonist, provided rapid relief for depression and was well tolerated for mood disorders. Psilocybin, a 5-HT2A agonist, decreased symptoms in refractory depression and fostered emotional processing. For PTSD, ketamine-assisted psychotherapy reduced symptom severity, though outcomes varied; psilocybin enhanced neural plasticity, allowing memory reframing. Both drugs modulate glutamate pathways. Ethical considerations for using dissociative and hallucinogenic therapies in youth are discussed.
Cureus
July 1, 2025
Amy Avakian
The psychedelic N,N-Dimethyltryptamine (DMT) rapidly alters consciousness by disrupting the default mode network (DMN) and increasing global brain integration. fMRI and EEG-fMRI studies show that under DMT, the brain becomes hyperconnected and less modular, with heightened activity in the thalamus, amygdala, and hippocampus—regions involved in memory, emotion, and sensory salience—while cortical areas for self-referential processing lose organizing control. This temporary collapse of hierarchical brain structure is linked to vivid imagery, emotional release, and loosened self-boundaries. Rather than merely distorting perception, DMT reveals the brain's capacity to restructure consciousness, suggesting consciousness is a flexible process shaped by context, neurochemistry, and meaning.
Cureus
July 1, 2025
Akshita Suleria, Sakshi Verma, Khanij Arya et al.
LSD acts primarily on 5-HT2A receptors in the brain and periphery, producing psychedelic effects. Although acute ingestion raises heart rate and blood pressure, and large recreational doses can cause cardiovascular or cerebrovascular events, chronic peripheral antagonism of 5-HT2A receptors may reduce atherosclerosis and thrombosis by decreasing platelet aggregation and vascular smooth muscle cell proliferation. Central sympathetic stimulation from microdosing LSD may also reduce chronic inflammation, a contributor to cardiovascular disease, through anti-inflammatory effects and increased cortical synaptogenesis.
Cureus
June 24, 2025
Alfred Mathew, Roshan Dongre, Seo Hee Kim et al.
A review of literature from 2020 to 2024 examined psilocybin's use in clinical practice before and after the COVID-19 pandemic. Psilocybin, a compound found in certain mushrooms, shows evidence of reducing symptoms of depression, anxiety, and post-traumatic stress disorder, with relatively safe outcomes under medical supervision. The review notes potential for treating long-haul COVID-19 symptoms, including a pharmacological basis for inhibiting the SARS-CoV-2 protease, though in vitro validation is needed. Barriers to therapeutic use exist, and more robust clinical trials comparing psilocybin to standard care are required to draw definitive conclusions.
Cureus
May 1, 2025
Hafiza Wajeeha Waheed, Muhammad R Ashraf, Talha Sajjad et al.
Ketamine use can harm the liver and bile ducts, causing problems from mild lab abnormalities to serious conditions needing medical care. The review of human studies found that ketamine may disrupt bile flow, cause oxidative stress, and directly damage liver cells. Stopping ketamine often leads to improvement, and treatments like supportive care and medications can help. The exact biological mechanisms are still unclear, and more research is needed to identify who is most at risk and to ensure safer use in medical and nonmedical settings.
Cureus
May 1, 2025
Cassidy Chau, Anthony Q Dang, Thong Nguyen
Toxic epidermal necrolysis (TEN) is a rare, life-threatening skin condition causing widespread skin detachment and mucous membrane damage. A six-month-old male with atypical TEN was transferred from a hospital in Mexico to a US facility, presenting with widespread full-thickness necrotic wounds but no bullae or sloughing. The unclear diagnosis made anesthetic planning challenging due to the need for prolonged intubation after extensive burn debridement and grafting. This case report emphasizes perioperative assessment, induction strategy, airway management, resuscitation, and pain control for atypical TEN patients.
Cureus
April 1, 2025
Alison Muñoz, Marai Roque, Marco Valladares et al.
A 33-year-old man with a four-day history of worsening confusion, restlessness, and visual hallucinations was hospitalized. He had been misusing pregabalin (Lyrica) for pain relief and also using recreational ketamine. The patient developed toxic-metabolic encephalopathy (brain dysfunction) and acute kidney injury, requiring treatment for confusion, acidosis, and electrolyte imbalances. The severe presentation warns against self-medicating with neuromodulators like pregabalin, especially when combined with other neuroactive substances. The case underscores the need to quickly identify both clinical symptoms and psychiatric risk factors to effectively diagnose and treat dangerous pregabalin intoxication.
Cureus
February 19, 2025
A 60-year-old female veteran with chronic PTSD and no prior psychiatric hospitalizations developed persistent delusions of parasitic infestation after 18 months of recreational intravenous DMT use. Her delusions that worms were coming out of her skin persisted despite haloperidol treatment but improved after 15 days of hospitalization following substance clearance and psychoeducation. The timing of hallucinogen use and symptom onset was not fully consistent, raising concern for a primary delusional disorder exacerbated by substance use. This novel case suggests a potential link between prolonged DMT use and delusional parasitosis, highlighting the need for further research.
Cureus
February 1, 2025
Eric Boccio, Jason Haidar, Michael Thiefault et al.
Chronic, high-dose ketamine use can cause a cluster of symptoms—severe abdominal pain, nausea, vomiting, and painful urination—known as K-cramps. A 25-year-old woman who used 500–1000 milligrams of ketamine weekly presented with these symptoms; lab tests were normal, and she was diagnosed with K-cramps after ruling out other causes. Treatment with intravenous fluids, antiemetics, and benzodiazepines resolved her symptoms. The condition is underrecognized by emergency physicians, leading to delayed diagnosis and unnecessary testing. Awareness and proper management, including harm reduction counseling and addiction medicine referral, are important for acute care.
Cureus
January 1, 2025
Sorcha O'Connor, Kate Godfrey, Sara Reed et al.
correction
A protocol describes a planned study testing whether a low-moderate dose of psilocybin (10 mg), combined with non-interventional therapy, can improve cognitive flexibility and neuroplasticity in people with obsessive-compulsive disorder (OCD). Twenty blinded participants will receive an active placebo (1 mg psilocybin) in a first session and 10 mg in a second session four weeks later. Cognitive flexibility will be measured with the intradimensional-extradimensional shift task two days after each session, and neuroplasticity will be assessed via electroencephalography immediately after each session. Secondary outcomes include OCD symptom severity and patient-reported measures. The results are expected to clarify neural mechanisms and guide a future randomized controlled trial.