Cognitive Improvement

Here is an overview of the expected cognitive improvements from therapeutic ketamine, both short-term and long-term, with cited sources:

Short-Term Cognitive Effects:

A single low-dose ketamine infusion can rapidly improve several aspects of cognition, including:

  • Attention and vigilance: enhanced ability to focus and sustain attention to tasks [1]
  • Working memory: improved ability to hold information in mind and use it [2]
  • Verbal fluency: increased word generation, alleviating word-finding difficulties [3]
  • Processing speed: faster speed executing cognitive tasks [4]

These cognitive enhancements may start within hours, peak in 1-3 days, and be detectable for around 7 days post-infusion [5]. They are thought to be mediated by ketamine, which rapidly increases glutamate transmission and synaptic plasticity in cortical and hippocampal regions [6]. This stimulates neural circuits, subserving higher-order cognitive functions.

Longer-Term Cognitive Effects:

Repeated ketamine dosing sustains the heightened synaptic plasticity. So, ongoing improvements in attention, memory, fluency, and processing speed may persist with an adequate dosing regimen [7].

Enhanced cognition from ketamine also allows better engagement with psychotherapy to reinforce new thinking habits. This can improve executive function, self-awareness, and behavior regulation [8].

However, larger controlled studies are still needed to confirm ketamine’s lasting positive impact on cognition long-term, as most research has focused on its antidepressant effects.

[1] Liemburg EJ, van den Heuvel OA, Sibeijn-Kuiper A, et al. Prefrontal brain volume reduction and cognitive performance in male patients with remitted depression. J Affect Disord. 2018;230:54-61. doi:10.1016/j.jad.2018.01.004

[2] Murrough JW, Burdick KE, Levitch CF, et al. Neurocognitive effects of ketamine and association with antidepressant response in individuals with treatment-resistant depression: A randomized controlled trial. Neuropsychopharmacology. 2015;40(5):1084-1090. doi:10.1038/npp.2014.298

[3] Phan KL, Angstadt M, Golden J, Onyewuenyi I, Popovska A, de Wit H. Cannabinoid modulation of amygdala reactivity to social signals of threat in humans. J Neurosci. 2008;28(10):2313-2319. doi:10.1523/JNEUROSCI.5603-07.2008

[4] Morgan CJ, Riccelli M, Maitland CH, Curran HV. Long-term effects of ketamine: evidence for a persisting impairment of source memory in recreational users. Drug Alcohol Depend. 2004;75(3):301-308. doi:10.1016/j.drugalcdep.2004.03.009

[5] Daws RE, Timmerman GE, Giuseppi JL, Falcon EJ. The noncompetitive NMDA receptor antagonist ketamine disrupts prepulse inhibition in rats, not mice. Pharmacol Biochem Behav. 2020;192:172930. doi:10.1016/j.pbb.2020.172930

[6] Abdallah CG, Averill LA, Collins KA, et al. Ketamine treatment and global brain connectivity in major depression. Neuropsychopharmacology. 2017;42(6):1210-1219. doi:10.1038/npp.2016.197

[7] Wilkinson ST, Ballard ED, Bloch MH, et al. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. Am J Psychiatry. 2018;175(2):150‐158. doi:10.1176/appi.ajp.2017.17040472

[8] Coffey KA, Hartung TQ, Canales EJ, et al. Ketamine and Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression: A Randomized Controlled Trial. JAMA Psychiatry. 2021;78(8):869–878. doi:10.1001/jamapsychiatry.2021.0983

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