The proposed protocol is a double-blind, placebo-controlled outpatient study of the safety and benefit of Extended-release mixed amphetamine salt (Adderall-XR, MAS-XR) in the treatment of individuals with Cannabis Use Disorder (CUD) and Attention-deficit/Hyperactivity Disorder (ADHD). The investigators plan to enroll 50 and randomize 40 of these patients in the trial. The primary objective of the study is to determine the efficacy of MAS-XR in promoting cannabis abstinence among individuals with CUD and in promoting a decrease of ADHD symptoms.

ADHD is common in substance use disorder patients in general and cannabis use disorder (CUD) in particular, occurring at rates substantially greater than in the general population. A meta-analysis found that approximately 23% of substance abusers seeking treatment have childhood and/or adult ADHD. Moreover, ADHD was overrepresented in adults with CUD compared to other substance use disorder patients seeking treatment. The importance in treating CUD individuals who also have ADHD is underscored by findings demonstrating that individuals with co-occurring ADHD and substance use disorders are a particularly intractable group: they exhibit earlier onset of use, more severe use, a more complicated pattern of remission/relapse, and poorer treatment outcomes relative to those without ADHD. Yet, to date, ADHD individuals with CUD have not been adequately studied. The investigators have found that in their treatment research studies targeting cannabis dependence that a substantial percentage (35%) have screened positive for adult ADHD, rates that are higher than participants in their cocaine use disorder clinical trial and almost 8x greater than rates found in the general population. Thus, this appears to be a sizable cannabis-abusing group warranting much greater clinical attention than they are currently receiving.

The goal is to demonstrate feasibility, tolerability, and estimate effect size for purposes of planning future more definitive trials. Because of the research team's extensive experience in working with stimulant medication in treating ADHD in cocaine-dependent populations, the large effect size of amphetamine in treating adult ADHD, and notable reduction in cocaine use and ADHD symptoms in cocaine-dependent ADHD adults, the investigators will explore the efficacy of Adderall-XR (MAS-XR) for the treatment of cannabis use disorder and ADHD. The study is a 12 week placebo controlled double-blind trial. The maximum maintained dose will be 80 mg of MAS-XR daily.

Inclusion Criteria:

• Individuals who meet criteria for cannabis use disorder (CUD) and report that marijuana is their primary drug of abuse
• Individuals must report using marijuana at least 5 days a week over the past 28 days and have a positive urine test for tetrahydrocannabinol (THC) on the day of study entry
• Individuals must meet Diagnostic and Statistical Manual 5th ed. (DSM-5) criteria for adult ADHD
• Individuals who score > 22 on the adult ADHD Investigator Symptom Rating Scale (AISRS)
• Individuals between the ages of 18-65 capable of giving informed consent and capable of complying with study procedures
• Women of child-bearing age will be included if they: a) are not pregnant, b) agree to use an effective method of contraception, c) agree not to become pregnant during the study and d) are not breastfeeding. To confirm this, urine pregnancy tests will be repeated every month after screening. Women will be provided a full explanation of the potential dangers of pregnancy while taking MAS-XR. If a woman becomes pregnant, she will be taken off medication and continue standard treatment. At the end of the study, patients will be offered treatment until an appropriate referral can be made to a community clinic.

Exclusion Criteria:

• Individuals meeting DSM-5 criteria for schizophrenia, schizoaffective illness, psychotic disorder other than transient psychosis due to drug abuse, current major depression, bipolar illness or psychiatric disorders (other than substance abuse) which require psychiatric intervention or would interfere with study participation
• Individuals who are medically unstable based on laboratory tests, electrocardiogram, medical history, physical examination that would make participation hazardous
• Use of synthetic cannabinoids in the past month and meeting CUD diagnosis based on synthetic cannabinoids use alone in the past year
• Individuals with liver enzyme function tests greater than 3 times normal
• Individuals with significant current suicidal risk
• Individuals with systolic blood pressure > 140; diastolic blood pressure >90; pulse >100
• Individuals who are cognitively impaired to impede study participation
• Nursing mothers and pregnant women
• Individuals who are physiologically dependent on any other drugs (excluding nicotine) that would require a medical intervention
• Individuals with known sensitivity/allergy to MAS-XR or amphetamine analogs
• Individuals currently being prescribed psychotropic medication (including sleep medication)
• Individuals with history of seizures
• Individuals who are mandated to treatment
• Individuals with a history of amphetamine use disorders, including amphetamines such as methamphetamine and methylenedioxymethamphetamine (MDMA).
• Individuals with a current cocaine use disorder

Randomized participants

12 weeks of trial or length of participation.