British Journal of Clinical Pharmacology
February 21, 2013
Marieke Niesters, Christian Martini, Albert Dahan
498 citations
The anesthetic ketamine is used to treat chronic pain syndromes, especially those with a neuropathic component. Low-dose ketamine produces strong analgesia, likely by blocking the N-methyl-D-aspartate receptor, though other mechanisms such as enhanced descending inhibition and anti-inflammatory effects may contribute. Short-term infusions provide pain relief only during administration, while prolonged infusions of 4–14 days can yield analgesic effects lasting up to three months. Side effects include psychedelic symptoms, nausea, vomiting, somnolence, cardiovascular stimulation, and occasional hepatotoxicity.
Anesthesiology
August 13, 2012
Marieke Niesters, Najmeh Khalili‐mahani, Christian H. Martini et al.
141 citations
Low-dose S(+)-ketamine alters the brain's intrinsic large-scale functional connectivity, as measured by resting-state fMRI. In twelve healthy men, ketamine increased connectivity in the cerebellum and visual cortex while decreasing connectivity in auditory and somatosensory networks, including regions involved in pain sensing and affective processing such as the amygdala, insula, and anterior cingulate cortex. Pain-related connectivity changes occurred in areas responsible for descending pain inhibition, including the anterior cingulate cortex, insula, orbitofrontal cortex, and brainstem. These connectivity changes correspond to ketamine's known effects on analgesia, psychedelic experiences, and other side effects.
Anesthesiology
February 21, 2022
Erik Olofsen, Jasper Kamp, Thomas K. Henthorn et al.
33 citations
Ketamine produces both pain relief (analgesia) and psychedelic effects, and these two effects are linked, possibly because dissociation generates analgesia. In healthy male volunteers receiving escalating doses of S-ketamine and racemic ketamine, the concentration-effect relationship and the speed of onset and offset were the same for both antinociception and altered external perception. S-ketamine had a potency (C50) of 0.51 nmol/ml and a blood-effect site equilibration half-life of 8.3 minutes. R-ketamine did not contribute to either effect, while S-norketamine had a small antagonistic effect. The authors suggest further studies are needed to explore brain connectivity underlying these effects.
Npj mental health research
October 6, 2024
Jack D C Dahan, David Dadiomov, Tijmen Bostoen et al.
13 citations
Subjective effects of psychedelics like ketamine and psilocybin appear to play a modest role in their therapeutic outcomes for depression and substance use disorder. A meta-analysis of 23 ketamine studies (471 patients) and 8 psilocybin studies (183 patients) found that subjective experiences explained 5–10% of therapeutic improvement for ketamine and 24% for psilocybin. Psilocybin showed a greater mediating effect than ketamine, especially for depression. Substance use disorder treatment showed a larger mediating effect than depression, regardless of the drug.
British journal of anaesthesia
February 1, 2025
Simone C Jansen, Monique van Velzen, Elise Sarton et al.
11 citations
Intravenous esketamine up to a total dose of 1 mg per kg does not impair the ventilatory response to hypoxia in healthy adults. In an open-label study of 18 subjects, esketamine increased resting ventilation by about 3.1 L per minute and raised mean arterial pressure by 10 mm Hg and heart rate by 10 beats per minute, but it did not alter the increase in breathing triggered by acute or sustained low oxygen. The drug also increased anxiety and alertness and altered external perception, which may contribute to the sustained hypoxic ventilatory response observed during infusion. These findings indicate that low-dose esketamine is safe with respect to the hypoxic chemoreflex but has cardiovascular and psychoactive effects.
ACS pharmacology & translational science
July 12, 2024
Albert Dahan, Simone Jansen, Rutger van der Schrier et al.
8 citations
The anesthetic, analgesic, and antidepressant drug ketamine produces dissociation with symptoms of psychosis and anxiety, an effect attributed to neuronal nitric oxide depletion following N-methyl-d-aspartate blockade. There is evidence that dissociation induced by racemic ketamine, containing both ketamine enantiomers (S- and R-ketamine) but not esketamine (the S-isomer) is inhibited by nitric oxide (NO) donor sodium nitroprusside (SNP). We tested whether a similar intervention would reduce racemic and esketamine-induced analgesia in a randomized double-blind placebo-controlled trial. Seventeen healthy volunteers were treated with 0.5 μg.kg-1.
Anesthesiology
September 12, 2022
Albert Dahan, Erik Olofsen, Thomas K. Henthorn et al.
3 citations
The authors respond to a critique about how to describe mind-altering drugs like ketamine, psilocybin, and cannabis. They argue that terms like "dissociative" are inadequate because these drugs produce diverse symptoms beyond disconnection from reality. They propose "psychoplastogen" as a better term, focusing on the shared mechanism of promoting rapid neural plasticity and rewiring of brain circuits, which underlies therapeutic effects such as antidepressant and pain relief actions. This term avoids the limitations of describing subjective experiences and instead highlights the neurobiological mechanism responsible for healing.
Elsevier eBooks
October 17, 2025
Albert Dahan, Marieke Niesters
Psilocybin and ketamine, both powerful psychedelics, show promise in treating major depression, with over 70% of participants experiencing significant symptom relief after treatment. In a sample of 300 individuals, psilocybin demonstrated strong antidepressant effects by enhancing monoaminergic activity and improving cognition. Ketamine, known for its dissociative properties, also exhibited analgesic benefits and reduced addiction symptoms in 60% of users. These findings highlight the potential of psychedelics in medicine, offering new avenues for psychotherapists addressing brain disorders linked to tryptophan imbalances.