The Effect of Glutamatergic Modulation on Cocaine Self-administration
Repeated drug consumption may progress to problematic use by triggering neuroplastic adaptations that attenuate sensitivity to natural rewards while increasing reactivity to craving and drug cues. Converging evidence suggests that glutamate modulation may work to correct these adaptations and rapidly restore motivation for delayed non-drug rewards relative to immediate drug use. Using an established laboratory model aimed at evaluating behavioral shifts in the salience of cocaine now vs. money later, the investigators will test the effect of CI-581a on cocaine self-administration as compared to the active control.
Study Arms & Interventions
Ketamine
experimental52-min sub-anesthetic intravenous infusion of ketamine hydrochloride
Interventions
- Ketamine0.71 mg/kgvia IV• single dose• 1 doses total
administered as 0.11 mg/kg 2-min bolus followed by 0.60 mg/kg in saline over 50 min
Midazolam
active comparator52-min sub-anesthetic intravenous infusion of midazolam
Interventions
- Placebo0.025 mg/kgvia IV• single dose• 1 doses total
administered as 2-min saline bolus followed by 0.025 mg/kg in saline infused over 50 min
Saline
placebo52-min saline infusion during the first hospitalization to identify and exclude non-responders
Interventions
- Placebovia IV• single dose• 1 doses total
used as a sham infusion in Inpatient Phase 1
Primary Results(2 publications)
Participants
Global Improvement Score
Score at Timepoint
Response Rates
maintained abstinence
Adverse Events (from all publications)
| Arm / Group | n | Any TEAE | Severe | Serious | Discont. |
|---|---|---|---|---|---|
| Ketamineexperimental | 10 | — | — | 0(0.0%) | — |
| Midazolamactive_comparator | 10 | — | — | 0(0.0%) | — |
| Salineplacebo | 20 | — | — | 0(0.0%) | — |
| Ketamineexperimental | 18 | — | — | 0(0.0%) | — |
| Midazolamactive_comparator | 18 | — | — | 0(0.0%) | — |
| Salineplacebo | 18 | — | — | 0(0.0%) | — |
* Participants tolerated study procedures without notable adverse effects. Ketamine led to acute dissociation (CADSS) which resolved within 30 min post infusion; no persistent dissociative or other adverse effects reported.
* Participants tolerated study procedures without notable adverse effects. Midazolam led to greater acute dissociation than saline, but no persistent adverse effects reported.
* Saline (sham) infusion used for baseline; no notable adverse effects reported.
* The paper states 'All participants tolerated study procedures without adverse events, including unexpected psychiatric disturbances and initiation of ketamine or benzodiazepine misuse.'