Ketamine's Actions on Rumination Mechanisms as an Antidepressant

Inclusion Criteria:

* Right-handed male and female volunteers with a history of depression between the ages of 18 and 50 years.
* Good command of the English language.
* Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of and agrees to comply with all aspects of the study.
* Willing and able to comply with scheduled visits, dosing plan, laboratory trials and any other necessary procedures.
* Are willing for data to be shared and disseminated after being anonymised.

Exclusion Criteria:

* Have a current or previously diagnosed psychiatric disorder except depression.
* Have one or more immediate family members with a current or previously diagnosed psychotic disorder.
* Have a medically significant condition which renders them unsuitable for the study (e.g., diabetes, severe cardiovascular disease, hepatic or renal failure etc.).
* Show MR contraindications (e.g., metal implants, pacemakers, claustrophobia etc.) which would render them unsuitable for the study.
* Have previously experienced an adverse response to ketamine.
* Have excessive use of alcohol (in excess of 28 units a week), caffeine (\>6 cups of coffee a day), or other drugs.
* Have taken any other medication during the course of the study that has not been discussed - this should be documented by the investigators. (As an exception, 1g paracetamol/24 hours may be taken up to 24 hours prior to any MRI scan).
* Have taken illicit drugs 7 days prior to admission, have consumed alcohol or caffeine within 24 hours prior to admission or have consumed nicotine within 4 hours prior to admission.
* Have taken grapefruit juice- or Seville orange-containing products 24 hours prior to admission.
* Use of any prescribed medication in the 3 weeks prior to enrolment or non-prescription medication (other than paracetamol) or herbal preparations in the previous 7 days.
* Have a significant history of drugs of abuse (including benzodiazepines) or positive drugs of abuse test.
* Had acute illness within 2 weeks before the start of study.
* Have clinically significant abnormalities in clinical chemistry (including liver function tests), haematology or urinalysis results.
* Have a history or presence of gastrointestinal, hepatic or renal disease or other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
* Have been diagnosed hypertension, or supine systolic BP outside of the range of 90 to 140 mmHg and a supine diastolic BP outside the range of 40 to 90 mmHg, after a period of acclimatisation
* Have a decrease in systolic BP of \> 25 mmHg or a decrease in diastolic BP of \> 15 mmHg when going from resting in bed to standing position, with or without symptoms such as dizziness or light-headedness. (For determination of orthostatic hypotension, lying and standing BP will be recorded after the subject has rested for 10 minutes and has had resting BP recorded followed by measurements taken at 1, 2 and 5 minutes after standing)
* Had treatment in the previous 3 months with any drug known to have a well-defined potential for hepatotoxicity (e.g., halothane)
* Subjects who, in the opinion of the investigator, should not participate in the study for reasons of safety