Cocaine Use Disorders Clinical Trial
Official title:
Lorcaserin Effects on Cocaine Craving and Drug-Reinforced Behavior
This is a randomized, cross-over, single-blind, placebo-controlled, single-center, multiple-panel evaluation of the potential for oral lorcaserin to modify cocaine self-administration in a laboratory setting. To prevent unauthorized drug use, study medications will be administered as participants are confined during overnight stays at the Medical Center. Non-treatment-seeking, regular cocaine users will receive oral treatment with single doses of placebo, lorcaserin 10 mg (Panel 1), or lorcaserin 20 mg (Panel 2). Afterwards, the subjective and reinforcing effects of intravenous cocaine will be measured in a laboratory setting.
Background
Serotonin (5-HT) is one of three brain monoamines that are widely distributed in the brain
and play important roles in affect and goal-directed behaviors. Limbic structures that
underlie behavior motivated by palatable food and drugs of abuse receive dense projections
from brainstem serotonergic nuclei. In rats, light and sound cues associated with access to
cocaine strongly stimulate drug-seeking behavior. Agonists for the type 2C serotonergic
receptor (5-HT₂cR) attenuate this responding.8 Drug taking (cocaine self-administration) is
also attenuated at 5-HT₂cR agonist doses similar to those that decrease food-reinforced
responding and cause reductions in locomotor activity.
Lorcaserin is a novel and selective agonist of the 5-HT₂cR recently approved by the FDA for
weight loss therapy. It acts selectively at this receptor subtype with minimal activation of
5-HT₂ᴀR or 5-HT₂ᴃR receptors. Based on initial clinical studies leading to its approval,
lorcaserin is well tolerated and probably does not cause cardiac valve disease or other
serious side effects. Even so, given the potential for serious adverse events, the FDA has
limited its use to patients who are either obese or overweight with a medical complication
such as hypertension. Whether or not lorcaserin will become generally accepted as a
long-term treatment for obesity will depend on the results of ongoing post-marketing studies
of cardiovascular outcome data.
Rationale In preclinical studies, agonists for the 5-HT₂cR potently attenuate
cocaine-seeking behavior. Lorcaserin is a recently approved selective 5-HT₂cR agonist with
an acceptable safety profile in humans. No published studies have reported its effects on
cocaine-induced craving or drug-reinforced responding in humans.
Specific Aims:
1. Evaluate whether lorcaserin treatment attenuates the positive subjective effects of
cocaine and drug-reinforced behavior.
2. Determine whether active treatment modifies cocaine- or script- induced craving.
Methods This is a randomized, cross-over, double-blind, placebo-controlled, single-center,
multiple-panel evaluation of the potential for oral lorcaserin to modify cocaine
self-administration in a laboratory setting. Up to 32 non-treatment-seeking, regular cocaine
users will receive treatment with single doses of oral placebo, lorcaserin 10 mg (Panel 1),
or lorcaserin 20 mg (Panel 2). Script-guided imagery of autobiographical memories will be
developed based on experiences related to cocaine use, anger, and a neutral event. Following
treatment with lorcaserin, script-induced emotional states will be assayed. Sampling doses
of cocaine (0.0, 0.23, and 0.46 mg/kg) will be administered, and participants will choose
between self-administering additional intravenous doses or receiving monetary alternatives.
Detailed measures of the negative and positive subjective effects of intravenous infusions
will also be made. As noncontingent infusions of cocaine are administered, the
pharmacokinetics of cocaine and lorcaserin will be determined.
;
Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment
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