THC and Ketamine Effects in Humans: Relation to Neural Oscillations and Psychosis

An Electrophysiological Examination of CB1 and NMDA Receptors in Humans

The aim of the research protocol is to evaluate cannabinoid-glutamate interactions in humans. As part of this aim the investigators will assess the safety and tolerability of the combination of NMDA antagonist, ketamine, and the cannabinoid, delta-9-tetrahydrocannabinol (THC), in healthy adult subjects, and characterize the interactive effects of ketamine and THC on various electrophysiological (EEG), cognitive, and behavioral outcomes.

The investigators will examine the contributions of the cannabinoid receptor (CB1R) and N-methyl D-aspartate receptor (NMDAR) systems to psychosis in healthy humans beings using THC and ketamine respectively (both alone and in combination). Healthy subjects (n=21) will receive THC (active or placebo) followed by ketamine (active or placebo) in a double blind, randomized, crossover (2x2) design. Psychotomimetic effects will be assessed before and at various time points after the drug infusions. EEG indices of information processing, specifically neural oscillations, will be assessed during peak drug effects.

Inclusion Criteria:

1. 18 to approximately 45 years old
2. Good physical and mental health as determined by history, the Structured Clinical Interview for DSM-5 TR (SCID-NP) and collateral information, physical and laboratory examinations, ECG and vital signs.
3. Weight of 100 kg (220.46 lbs.) or less (inclusive).

Exclusion Criteria:

1. Unstable serious medical conditions. At the discretion of the investigator, subjects with unstable medical conditions that may necessitate changes in medical treatment and hence influence study outcomes will be excluded.
2. Uncontrolled hypertension, long QT syndrome, and seriously abnormal EKG results. EKG abnormalities will be reviewed by the PI and eligibility decisions will be made at the discretion of the PI.
3. A hearing deficit in greater than one band in an ear detected using a Welch-Allyn audioscope (500, 1000, 2000 and 4000 Hz threshold will be evaluated)
4. Positive pregnancy test