The investigator's study will be a randomized cross-over design, in which all 40
participants receive six weeks of CBD and six weeks of placebo with a 2-week washout in
between. Participants will be seen at in-person visits at Baseline and at the end of
Weeks 2, 4, and 6 of each arm of the study for clinical evaluation and primary data
collection. Two additional telephone visits will be held with participants during Weeks 1
and 3 of each arm to collect data related to safety and drug tolerability.
Currently in the clinic, as part of routine care on a semi-annual basis, the
investigators administer the following informant-reported scales: Aberrant Behavior
Checklist (ABC, a 58-item inventory that examines presence and severity of behaviors in
the domains of hyperactivity, irritability, lethargy, stereotypies, and inappropriate
speech); Neuropsychiatric Inventory Questionnaire (NPI-Q, measures severity and caregiver
distress related to 12 different neuropsychiatric symptoms); Social Communication
Questionnaire (SCQ, a 40-item yes/no questionnaire that screens for ASD); and Waisman
Activities of Daily Living scale (17-item scale to assess level of independence in
activities of daily living). As part of this study, the investigators will also
administer the Hamilton Anxiety Rating scale (14-item clinician-clinician rated scale to
assess severity of anxiety), the Yale-Brown Obsessive Compulsive Scale (YBOCS, 10-item
clinician-rated scale to measure obsessions and compulsions), and Clinical Global
Impression (CGI, clinician-rated assessment of severity of illness compared to other
patients and measure of global improvement) scale to participants.
The investigators will obtain informed consent to administer all assessments prior to the
initiation of CBD and placebo (i.e., baseline) and administer the above clinical
assessments (listed in paragraph above) at Baseline, and at the end of Week 2, Week 4,
and Week 6 of each arm of the study. The investigators will monitor cognition, using the
Mini Mental State Exam, at Baseline, Week 2, and Week 6 of each arm.
The study intervention will be supplied as a softgel capsule containing either CBD or
inert filler (for placebo). The starting dose of CBD will be 100 mg twice daily (with
breakfast and dinner, roughly 10-12 hours apart), with a plan to increase the dose to 200
mg twice daily at Week 3. The target dose is based on studies of CBD in
children/adolescents with ASD and observational data of adults with ASD. Dose will be
reduced or stopped for participants who exhibit an exacerbation of aberrant behavior or
adverse side effects. Doses will not exceed 200 mg twice daily (400mg total daily dose).
The study physician will remain blinded to the treatment assignment. However, if, based
on clinical observation and adverse event reporting, the study physician believes that
the study intervention has led to adverse events, she has the option of reducing or
stopping the intervention "dose" (independent of whether participant is taking placebo or
CBD) at her discretion.
The investigators will monitor for medication side effects and adverse events at all
telephone and clinic visits. The investigators will use both the Drug Effect
Questionnaire (DEQ) and Medication Side-Effects Questionnaire. The DEQ determines
subjective ratings of cannabis intoxication using a visual analog scale anchored with
"not at all" at one end and "extremely" at the other end. This method is sensitive to
detecting acute effects of cannabis. There are few data reflecting the validity and
reliability of DEQ in individuals with cognitive impairment, such as intellectual
disability, and many neuropsychiatric measures in this field require the use of an
informant. Because of this, the investigators will also use an informant version of the
DEQ that is currently in use for a study of dronabinol in older adults with dementia. The
items are similar but worded to be administered to an informant rather than a cognitively
impaired adult. The investigators will also administer the Medication Side-Effects
Questionnaire and use "all evaluable data," including participant interview and
discussion with informants, if the participant has language or cognitive impairment. The
Questionnaire lists potential side effects of CBD rated on a four-point scale (none,
mild, moderate, strong). Based on the list of potential side effects from trials of CBD,
items will include diarrhea, somnolence, fever, decreased appetite, vomiting, dry mouth,
restlessness, irritability, and coughing.
As part of routine clinical care, the investigators will check vital signs (heart rate,
blood pressure, and weight) at all in-person clinic visits. Blood draws, to examine liver
function tests (hepatic function panel), will be drawn at baseline (Week 0), Week 2, and
Week 4 of each arm. If a participant is simultaneously taking lithium or valproic acid
and is experiencing adverse events that the investigators think could be due to drug-drug
interactions, then the investigators will draw lithium or valproic acid levels,
respectively. Elevation of aminotransferases three times the upper limit of normal will
result in discontinuing the dose of CBD and withdrawal from the study. The investigators
will also assess for suicidality using the Columbia Suicide Severity Rating Scale at
Baseline, Week 2, and Week 6 of each arm. If a participant endorses suicidal ideation
with intent or plan ("yes" to questions 4 or 5), then the participant will undergo
further clinician assessment to determine the safest course of action, which may include
direction to the emergency department for evaluation, safety monitoring, and planning.
The investigators hypothesize that compared to placebo, CBD treatment will be associated
with greater reduction in challenging behaviors as measured by the total score on the
Aberrant Behavior Checklist (ABC). The investigators also intend to compare the safety of
six weeks of CBD treatment to placebo and hypothesize that CBD will be well-tolerated
with adverse effects not significantly different than placebo. This study will add to the
limited knowledge base of effective interventions for psychiatric illness and behaviors
in adults with ASD, with the ultimate goal of improved patient care and quality of life.