Neurology International
June 23, 2022
Islam Mohammad Shehata, Waniyah Masood, Nouran Nemr et al.
41 citations
Depression affects 3.8% of the global population, with higher rates in older adults. Evidence links depression to Alzheimer's disease (AD), but conventional antidepressants, especially SSRIs, show conflicting efficacy in AD patients. A recent systematic review and meta-analysis of 25 randomized controlled trials found no high efficacy of fourteen antidepressant medications for AD symptoms. Ketamine, a nonselective NMDA receptor antagonist, has multiple effects including neuroprotection and antidepressant properties. Esketamine nasal spray was FDA-approved in 2019 for treatment-resistant depression. NMDA receptor antagonists may treat AD by counteracting pathological glutamate receptor stimulation. Recent findings suggest ketamine could provide neuroprotection and reduce neuropsychiatric symptoms in AD. This investigation evaluates ketamine's potential role and mechanism in AD management.
Health Psychology Research
June 22, 2021
Sahar Derakhshanian, Maxine Zhou, Alexander Rath et al.
21 citations
Treatment-resistant depression (TRD) occurs when major depressive disorder (MDD) does not respond to two adequate trials of antidepressants like SSRIs or SNRIs. MDD involves genetic, pathophysiologic, and environmental factors that disrupt neurotransmitter balance, along with dysregulation of the HPA axis, BDNF, vitamin D, and pro-inflammatory markers. Core symptoms include depressed mood or anhedonia, sleep and appetite changes, worthlessness, guilt, and psychomotor retardation. In 2019, the FDA approved intranasal esketamine (Spravato), an NMDA-receptor antagonist with AMPA-receptor agonist properties, for adult TRD when used with an oral antidepressant. It provides rapid response and is effective and safe. Intravenous ketamine also shows benefits for acute suicidal ideation, depression, and substance use relapse reduction. Off-label uses for ketamine are being studied for PTSD, anxiety disorders, bipolar depression, and substance use disorders.
Neurology International
May 18, 2022
Amber N. Edinoff, Juliana M. Fort, Christina Singh et al.
15 citations
Given the risks of long-term opioid use, nonopioid analgesics are being evaluated for chronic pain. Tetrahydrocannabinol (THC) and cannabidiol (CBD) modulate pain signals and have been studied for chronic pain. Psilocybin, which acts on serotonin 5-HT2A receptors and has a tryptamine structure similar to triptans, shows promise for migraines and potentially chronic pain. However, studies of these plant-based medications have small sample sizes, which may overlook demographic or genetic differences, and it remains unclear whether their reported effects apply to the general population or are statistically significant. Further research is needed.
Health Psychology Research
October 6, 2022
Amber N. Edinoff, Natalie W. Wu, Bryce Bonin et al.
11 citations
The opioid epidemic persists despite declining prescription opioid dispensing, with increased use of illicit opioids like heroin and fentanyl. Established long-term pharmacotherapies for opioid addiction include naltrexone, buprenorphine, and methadone, while naloxone rapidly reverses overdose. Given the epidemic's severity, this narrative review explores alternative medications: ketamine, which shows promise for treating addiction to opioids, alcohol, and cocaine; cannabinoids, with dronabinol reducing withdrawal symptoms at high doses but causing adverse effects like sedation and tachycardia; and noribogaine, a weak MOR antagonist and potent KOR agonist with potential anti-addictive effects. More research is needed to assess these medications' viability for opioid use disorder and withdrawal.
Psychopharmacology Bulletin
August 12, 2025
Dustin Latimer, Michael D. Stocker, Kia Sayers et al.
10 citations
Post-traumatic stress disorder (PTSD) is common among U.S. veterans. Standard treatments include trauma-focused psychotherapies and antidepressant medications such as SSRIs and SNRIs. MDMA, a psychoactive compound classified as a Schedule I controlled substance since the 1980s, has reemerged as a potential therapy. Before prohibition, psychotherapists used it for various psychiatric conditions. Recent randomized, controlled trials support MDMA as an effective pharmacological adjunct to psychotherapy for PTSD.
Current Pain and Headache Reports
January 14, 2025
Alan D. Kaye, Brynne E Tynes, Coplen D Johnson et al.
6 citations
Complex Regional Pain Syndrome (CRPS) is a chronic pain condition where pain is much greater than expected from the initial injury and lasts a long time. Many standard treatments have been unsatisfactory. Ketamine, a drug that blocks NMDA receptors and is normally used for anesthesia and pain relief, shows promise for CRPS patients who do not respond to usual therapies. Multiple studies report significant improvements in pain severity, limb mobility, and other measures after ketamine infusion. Side effects such as nausea, vomiting, headache, or psychotropic symptoms were uncommon and reversible by stopping the drug. More research is needed on optimal dosing and duration, but ketamine appears safe and effective for difficult CRPS cases. This review summarizes current knowledge on ketamine infusions for CRPS to help physicians weigh benefits and risks.
Neurology International
March 28, 2023
Amber N. Edinoff, Saveen Sall, Colby B. Koontz et al.
5 citations
Ketamine, derived from phencyclidine and used to treat conditions like treatment-resistant depression, impairs driving-related abilities. A study comparing ketamine with a similar drug, rapasitnel, found that ketamine caused more sleepiness and reduced self-reported motivation and confidence in driving. Effects vary depending on acute versus persistent use and anesthetic versus subanesthetic doses, complicating clinical decisions. This review describes ketamine's clinical uses and the risks of driving under its influence, aiming to guide patient counseling and protect public safety.
Current Pain and Headache Reports
December 15, 2025
Alan D. Kaye, Madison C Wolf, Sarah I Dufour et al.
2 citations
Ketamine, an NMDA receptor antagonist, shows promise as an adjunctive treatment for patients with both chronic pain and opioid use disorder. It blocks NMDA receptors, reducing neural excitability and promoting neuroplastic changes that may help manage pain and reduce opioid dependence. Clinical studies suggest ketamine can reduce pain severity, decrease opioid consumption, and alleviate withdrawal symptoms in select populations. However, evidence is limited by small sample sizes, non-standardized protocols, and short follow-up periods. Side effects include dissociative symptoms, sympathomimetic activity, and potential for misuse, requiring careful patient selection and monitoring. Ketamine is a promising option in multimodal care when conventional therapies fail, but further research is needed.
Current Pain and Headache Reports
April 21, 2026
Navy C Coggins, Hanson A Chokr, Tricia A Meyer et al.
Ketamine, originally developed as a dissociative anesthetic, has expanded beyond procedural sedation to pain management and psychiatry. In pain medicine, its therapeutic rationale is grounded in noncompetitive antagonism of the NMDA receptor and modulation of central sensitization, key mechanisms underlying refractory neuropathic and centralized pain states. Evidence from preclinical studies and randomized clinical trials suggests intravenous ketamine may provide short-term analgesic benefit for resistant neuropathic pain, phantom limb pain, and complex regional pain syndrome. Low-dose perioperative administration has demonstrated opioid-sparing effects as part of multimodal analgesia.
Pain Medicine
December 10, 2024
Christopher L. Robinson, Pawan Solanki, S Snyder et al.
Psychedelics such as LSD and psilocybin primarily act as 5HT2A receptor partial agonists, influencing mood, perception, and decision-making. Research suggests they can promote synaptic growth, release oxytocin, and exhibit anti-inflammatory effects. MRI studies indicate psilocybin disrupts connections between the anterior hippocampus and the default mode network, potentially explaining therapeutic effects. From 2015 to 2020, psychedelic use among people over age 12 in the United States increased by over 40%, with over 7.1 million reporting use between 2019 and 2020. Despite this, formal training on psychedelics in medical education remains limited. The report outlines a proposed curriculum to prepare future clinicians for integrating psychedelics into practice, emphasizing the need for education on mechanisms, therapeutic uses, risks, and legal considerations.