Efficacy Study of Quetiapine Plus Topiramate for Reducing Cannabis Consumption and Bipolar Mania

Inclusion/Exclusion Criteria Inclusion Criteria: To be included, all subjects must… * have an authorized parent/legal guardian who understands the nature of the study and who provides written informed consent if the study subject is younger than 18 years of age. Additionally, each subject must provide assent to the study; * be fluent in English; * be 12 to 21 years of age, inclusive; * be using a medically accepted means of contraception (i.e., oral contraceptives and barrier methods (diaphragm or condom), medroxyprogesterone acetate injectable suspension, abstinence) if female and of menarche. Oral contraceptives alone are not acceptable means of contraception because concomitant use of topiramate and low estrogen oral contraceptive pills may lead to oral contraceptive failure; * have a diagnosis of bipolar I disorder in a current manic or mixed episode, in addition to a cannabis use disorder (which includes abuse or dependence) within 28 days prior to screening, as determined by the WASH-U-KSADS; * have an initial YMRS total score of \>16 at screening and baselines; * use cannabis a minimum of twice per week on average during the 28 days prior to screening. Exclusion Criteria: Subjects will not be eligible for participation if they… * have a known history of mental retardation; * are acutely intoxicated, and thus impaired; * have manic or depressive symptoms resulting entirely from acute medical illness or acute intoxication or withdrawal from drugs or alcohol, as determined by medical evaluation and rapid symptom resolution; * have clinically significant alcohol or other drug withdrawal symptoms, as determined by vital signs, The Clinical Institute Withdrawal Assessment for Alcohol Scale - Revised (CIWA-Ar)24, and physician interview; * have any unstable medical or neurological illness as determined by a study physician; * have laboratory abnormalities \>3 times upper limits of established normal values; * as females, have a positive serum (screening and week 16) or urine pregnancy test (at baseline and weeks 1-16), are lactating, or are not practicing a reliable form of birth control; * have a history of nephrolithiasis, since topiramate has been associated with an elevated risk of kidney stones; * require concurrent treatment with mood stabilizers, anticonvulsants, or antidepressants * require concurrent treatment with carbonic anhydrase inhibitors. * have significant suicidal ideation * have been treated for a substance use disorder during 28 days prior to screening or are court-ordered to treatment for substance use to ensure that, if we detect a change in use with topiramate treatment, it is likely not due to these other confounding factors that might influence substance use. Peer support groups are not considered treatment for substance use. \*\*Patients can be enrolled into the study that are already enrolled in a court ordered substance treatment, for at least 1 month prior to study enrollment, if they still meet the minimum cannabis use criterion.\*\* * have been diagnosed or treated for an eating disorder, to make sure any weight loss does not contribute to an already underlying condition * have a family history of glaucoma, since topiramate has been associated with an elevated risk of glaucoma; * have a history of non-response or hypersensitivity to quetiapine or topiramate; * if scanning, have claustrophobia and/or contraindicated for magnetic resonance scanning (i.e. intraocular metallic objects, braces, cochlear implants, pacemakers, or other electrical, mechanical, or magnetically activated implants); and * if scanning, have a history of significant head trauma (i.e. injury resulting in loss of consciousness for greater than five minutes).