Pilot study of ketamine in phobic participants using virtual reality stimuli

INTERVENTION: Participants with DSM V specific spider phobia will receive one of 3 randomized study treatments at weekly intervals ‐ over a period of 3 weeks. Participants will be administered single oral doses of 0.5 mg/kg ketamine, 1.5mg/kg ketamine, 0.05mg/kg of midazolam (the psychoactive control) liquid added to 50 mls of orange juice. The order of the doses are randomized. One hour after dosing the participants will be exposed to images of spiders using a virtual reality headset. We are using commercially‐available spider exposure software (https://store.steampowered.com/app/485270/Arachnophobia/), which has 5 levels. Lower levels have fewer spiders, and these are contained in a glass jar. Higher levels have more spiders, more movement, and are uncontained. Progression from lower to higher levels is under control of the participant, who can stop the simulation at any time. We will monitor ratings of anxiety using a 100 mm Visual Analog Scale (0mm= no anxiety; 100mm = worst anxiety ever), and physiological measures of anxiety including heart rate and galvanic skin response. Galvanic skin response is measured using an E4 wristband which is a wearable wireless device, galvanic skin response is changes in the electrical resistance of the skin caused by emotional stress. Participants will also complete the Fear Questionnaire item 18 ‐ which measures level of phobic avoidance. CONDITION: Mental Health ‐ Anxiety spider phobia; ; spider phobia PRIMARY OUTCOME: Change in anxiety ratings[After each virtual reality headset spider presentation (which occurs 60 minutes post dose using 5 exposure levels of approximately 2 minutes each) plus 30 minutes post dose ‐ measured by Fear Questionnaire item 18, visual analog scale of anxiety intensity(0mm = no anxiety, 100mm = most anxiety ever), Heart rate and Galvanic skin response measured using an E4 wristband. The E4 wristband is a wearable wireless device which measures galvanic skin response i.e. measures changes in the electrical resistance of the skin caused by emotional stress. ] SECONDARY OUTCOME: Completion of Fear Questionnaire item 18 phobic avoidance.[Predose and 30 minutes postdose plus after the virtual reality headset spider presentations which occur after 60 minutes.] How many of the 5 exposure levels using the virtual reality headset participants are able to complete. ; Assessed by clinical observations of anxiety ‐ recording heart rate and galvanic skin response. PLus participants will use 100 mm visual analog scale to self rate their anxiety intensity.[One hour after dosing participants will be exposed to images of spiders for approximately 2 minutes at a time using a virtual reality headset. ] INCLUSION CRITERIA: 1. Capable of understanding and signing an informed consent 2. Aged 18 years or over on the day of consent 3.Must meet criteria for DSM 5 specific phobia and have a Fear of Spiders Questionnaire score > 95 to participate.