Cannabis Use Disorder, Attention-deficit/Hyperactivity Disorder
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGAdderall-XR
DRUGMatched placebo
matched placebo provided for placebo arm
Sponsors
National Institute on Drug Abuse (NIDA)
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Marijuana Abstinence | Change from baseline compared to last 2 weeks of the 12 week study on maintained dose (weeks 10 and 11 for completers) or last 2 weeks of participants' participation during the study for participants who drop out of the study before weeks 10 and 11 | Number of participants who achieve abstinence from marijuana during the last two weeks of the trial as recorded by the Timeline Followback method and confirmed by urine toxicology. |
| Reduction in ADHD Symptoms | Change from baseline compared to last week of trial on maintained dose during the 12 week trial (week 11 for completers) or last week of participants' participation during the 12 week trial for those who drop out of study prior to week 11. | The primary ADHD outcome measure will be the number of individuals who achieve at least a 30% reduction in symptom severity as measured by the Adult ADHD Interview Rating Scale (AISRS). |
Countries
United States
Participant flow
Pre-assignment details
The study contained a one week placebo lead-in prior to randomization. Three participants were excluded due to being a placebo-responder and two participants were lost to follow-up during this lead-in week.
Participants by arm
| Arm | Count |
|---|---|
| Placebo matched Placebo arm
Matched placebo: matched placebo provided for placebo arm | 15 |
| Adderall-XR Adderall-XR (MAS-XR) 80 mg/day maximum maintenance dose
Adderall-XR | 13 |
| Total | 28 |
Baseline characteristics
| Characteristic | Placebo | Adderall-XR | Total |
|---|---|---|---|
| Age, Continuous | 33.3 years STANDARD_DEVIATION 9.5 | 32.4 years STANDARD_DEVIATION 11.2 | 32.9 years STANDARD_DEVIATION 10.2 |
| baseline cannabis use | 26.9 days STANDARD_DEVIATION 1.7 | 27.3 days STANDARD_DEVIATION 1.1 | 27.1 days STANDARD_DEVIATION 1.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 6 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 7 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 5 Participants | 13 Participants |
| Region of Enrollment United States | 15 participants | 13 participants | 28 participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 10 Participants | 12 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 13 |
| other Total, other adverse events | 5 / 15 | 7 / 13 |
| serious Total, serious adverse events | 0 / 15 | 1 / 13 |
Outcome results
Primary
Marijuana Abstinence
Number of participants who achieve abstinence from marijuana during the last two weeks of the trial as recorded by the Timeline Followback method and confirmed by urine toxicology.
Time frame: Change from baseline compared to last 2 weeks of the 12 week study on maintained dose (weeks 10 and 11 for completers) or last 2 weeks of participants' participation during the study for participants who drop out of the study before weeks 10 and 11
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Marijuana Abstinence | 0 Participants |
| Adderall-XR | Marijuana Abstinence | 2 Participants |
Primary
Reduction in ADHD Symptoms
The primary ADHD outcome measure will be the number of individuals who achieve at least a 30% reduction in symptom severity as measured by the Adult ADHD Interview Rating Scale (AISRS).
Time frame: Change from baseline compared to last week of trial on maintained dose during the 12 week trial (week 11 for completers) or last week of participants' participation during the 12 week trial for those who drop out of study prior to week 11.
Population: One participant in each arm did not have any follow-up AISRS scores, so they were not included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Reduction in ADHD Symptoms | 10 Participants |
| Adderall-XR | Reduction in ADHD Symptoms | 10 Participants |