Effects of ketamine in normal and schizophrenic volunteers - PubMed (original) (raw)
Clinical Trial
Effects of ketamine in normal and schizophrenic volunteers
A C Lahti et al. Neuropsychopharmacology. 2001 Oct.
Abstract
This study evaluates the effects of ketamine on healthy and schizophrenic volunteers (SVs) in an effort to define the detailed behavioral effects of the drug in a psychosis model. We compared the effects of ketamine on normal and SVs to establish the comparability of their responses and the extent to which normal subjects might be used experimentally as a model. Eighteen normal volunteers (NVs) and 17 SVs participated in ketamine interviews. Some (n = 7 NVs; n = 9 SVs) had four sessions with a 0.1-0.5 mg/kg of ketamine and a placebo; others (n = 11 NVs; n = 8 SVs) had two sessions with one dose of ketamine (0.3 mg/kg) and a placebo. Experienced research clinicians used the BPRS to assess any change in mental status over time and documented the specifics in a timely way. In both volunteer groups, ketamine induced a dose-related, short (<30 min) increase in psychotic symptoms. The scores of NVs increased on both the Brief Psychiatric Rating Scale (BPRS) psychosis subscale (p =.0001) and the BPRS withdrawal subscale (p =.0001), whereas SVs experienced an increase only in positive symptoms (p =.0001). Seventy percent of the patients reported an increase (i.e., exacerbation) of previously experienced positive symptoms. Normal and schizophrenic groups differed only on the BPRS withdrawal score. The magnitude of ketamine-induced changes in positive symptoms was similar, although the psychosis baseline differed, and the dose-response profiles over time were superimposable across the two populations. The similarity between ketamine-induced symptoms in SVs and their own positive symptoms suggests that ketamine provides a unique model of psychosis in human volunteers. The data suggest that the phencyclidine (PCP) model of schizophrenia maybe a more valid human psychosis/schizophrenia drug model than the amphetamine model, with a broader range of psychotic symptoms. This study indicates that NVs could be used for many informative experimental psychosis studies involving ketamine interviews.
Similar articles
- Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers.
Gouzoulis-Mayfrank E, Heekeren K, Neukirch A, Stoll M, Stock C, Obradovic M, Kovar KA. Gouzoulis-Mayfrank E, et al. Pharmacopsychiatry. 2005 Nov;38(6):301-11. doi: 10.1055/s-2005-916185. Pharmacopsychiatry. 2005. PMID: 16342002 Clinical Trial. - Optimizing the glutamatergic challenge model for psychosis, using S+ -ketamine to induce psychomimetic symptoms in healthy volunteers.
Kleinloog D, Uit den Boogaard A, Dahan A, Mooren R, Klaassen E, Stevens J, Freijer J, van Gerven J. Kleinloog D, et al. J Psychopharmacol. 2015 Apr;29(4):401-13. doi: 10.1177/0269881115570082. Epub 2015 Feb 17. J Psychopharmacol. 2015. PMID: 25693889 Clinical Trial. - [Effects of a subanaesthetic dose of ketamine on emotional and behavioral state in healthy subjects].
Micallef J, Tardieu S, Gentile S, Fakra E, Jouve E, Sambuc R, Blin O. Micallef J, et al. Neurophysiol Clin. 2003 Jun;33(3):138-47. doi: 10.1016/s0987-7053(03)00028-5. Neurophysiol Clin. 2003. PMID: 12909392 Clinical Trial. French. - [Glutaminergic hypothesis of schizophrenia: clinical research studies with ketamine].
Mechri A, Saoud M, Khiari G, d'Amato T, Dalery J, Gaha L. Mechri A, et al. Encephale. 2001 Jan-Feb;27(1):53-9. Encephale. 2001. PMID: 11294039 Review. French. - Do NMDA receptor antagonist models of schizophrenia predict the clinical efficacy of antipsychotic drugs?
Large CH. Large CH. J Psychopharmacol. 2007 May;21(3):283-301. doi: 10.1177/0269881107077712. J Psychopharmacol. 2007. PMID: 17591656 Review.
Cited by
- Persistent deficits in hippocampal synaptic plasticity accompany losses of hippocampus-dependent memory in a rodent model of psychosis.
Wiescholleck V, Manahan-Vaughan D. Wiescholleck V, et al. Front Integr Neurosci. 2013 Mar 15;7:12. doi: 10.3389/fnint.2013.00012. eCollection 2013. Front Integr Neurosci. 2013. PMID: 23508474 Free PMC article. - Altered neuronal excitability underlies impaired hippocampal function in an animal model of psychosis.
Grüter T, Wiescholleck V, Dubovyk V, Aliane V, Manahan-Vaughan D. Grüter T, et al. Front Behav Neurosci. 2015 May 20;9:117. doi: 10.3389/fnbeh.2015.00117. eCollection 2015. Front Behav Neurosci. 2015. PMID: 26042007 Free PMC article. - Glutamatergic dysbalance and oxidative stress in in vivo and in vitro models of psychosis based on chronic NMDA receptor antagonism.
Genius J, Geiger J, Dölzer AL, Benninghoff J, Giegling I, Hartmann AM, Möller HJ, Rujescu D. Genius J, et al. PLoS One. 2013 Jul 15;8(7):e59395. doi: 10.1371/journal.pone.0059395. Print 2013. PLoS One. 2013. PMID: 23869202 Free PMC article. - Discordant behavioral effects of psychotomimetic drugs in mice with altered NMDA receptor function.
Benneyworth MA, Basu AC, Coyle JT. Benneyworth MA, et al. Psychopharmacology (Berl). 2011 Jan;213(1):143-53. doi: 10.1007/s00213-010-2023-4. Epub 2010 Sep 24. Psychopharmacology (Berl). 2011. PMID: 20865248 Free PMC article. - Reduced d-serine levels drive enhanced non-ionotropic NMDA receptor signaling and destabilization of dendritic spines in a mouse model for studying schizophrenia.
Park DK, Petshow S, Anisimova M, Barragan EV, Gray JA, Stein IS, Zito K. Park DK, et al. Neurobiol Dis. 2022 Aug;170:105772. doi: 10.1016/j.nbd.2022.105772. Epub 2022 May 20. Neurobiol Dis. 2022. PMID: 35605760 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical