Effect of Oxytocin on Stress in Marijuana Users

Stress is commonly associated with drug craving and relapse in substance-dependent individuals. Several studies indicate that hypothalamic neuropeptides may mediate behavioral response to stress. For example, preclinical and clinical investigations have indicated that the neuropeptide oxytocin exerts anxiolytic effects in stress paradigms. Several studies have indicated that oxytocin promotes trust, social bonding, and calmness; however, little is known about the potential anxiolytic affects of oxytocin in marijuana-dependent individuals. A preclinical study investigating the effects and mechanism of lithium on cannabinoid withdrawal in rats had positive findings, with increasing oxytocin levels hypothesized to moderate this effect (Cui et al, 2001). Given the anxiolytic nature of oxytocin, it may have a therapeutic role in ameliorating the negative affect commonly observed prior to relapse in marijuana-dependent individuals, as well as the anxiety associated with marijuana withdrawal. This pilot protocol will provide important preliminary data on the effect of oxytocin on stress in marijuana-dependent individuals.

Inclusion criteria

• Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
• Subjects must meet DSM-IV criteria for current marijuana dependence (within the past three months). While individuals may also meet criteria for abuse of other substances, they must identify marijuana as their primary substance of abuse and must not meet criteria for dependence on any other substance (except nicotine) within the last 60 days.
• Subjects must consent to remain abstinent from all drugs of abuse (except nicotine and marijuana) for a three-day period immediately prior to the CTRC admission. Subjects must abstain from marijuana for 24 hours prior to testing. By restricting marijuana use as proposed, subjects should not be under the acute effects of marijuana, and also may be experiencing mild withdrawal symptoms, the measurement of which is one of the outcome variables being tested.
• Subjects must consent to random assignment.

Exclusion criteria

• Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control.
• Subjects with evidence of or a history of significant hematological, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, or neurological disease including diabetes, as these conditions may affect physiological/subjective responses.
• Subjects with Addison's disease, Cushing's disease or other diseases of the adrenal cortex likely to affect hormonal/neuroendocrine status.
• Subjects with a history of or current psychotic disorder or bipolar affective disorder as these may interfere with subjective measurements.
• Subjects with current major depressive disorder or post-traumatic stress disorder as these disorders are associated with characteristic changes in stress response.
• Subjects receiving synthetic glucocorticoid therapy, any exogenous steroid therapy, or treatment with other agents that interfere with hormonal measurements within one month of test session.
• Subjects taking any psychotropic medications, including SRI's or other antidepressants, opiates or opiate antagonists because these may affect test response.
• Subjects with any acute illness or fever. Individuals who otherwise meet study criteria will be rescheduled for evaluation for participation.
• Subjects who are obese (³ 20% over ideal weight) as this may interfere with hormonal status.
• Subjects who are unwilling or unable to maintain abstinence from alcohol and other drugs of abuse (except nicotine) for three days prior to the stress task procedure.
• Subjects meeting DSM-IV criteria for substance dependence (other than nicotine or marijuana) within the past 60 days.