Experimental Medicine in ADHD - Cannabinoids (EMA-C)

The Effects of Sativex on Neurocognitive and Behavioural Function in Adults With Attention-deficit/Hyperactivity Disorder; The EMA-C Study (Experimental Medicine in ADHD - Cannabinoids)

Adult patients with ADHD commonly report an improvement in behavioural symptoms when using cannabis with some reporting a preference towards cannabis over their ADHD stimulant medication. The EMA-C study aims to investigate the effects of a cannabis based medication, Sativex Oromucosal Spray on behaviour and cognition in adults with ADHD.

This will be carried out by conducting a placebo controlled trial. 30 adults with ADHD will take Sativex or a dummy medication (a placebo) every day for 6 weeks. There is a 50% chance of receiving the Sativex or Placebo. Measures of behaviour and cognition will be taken before and after 6 weeks of treatment. We hypothesise that treatment with Sativex will result in improvements in behaviour and cognition above that of the placebo group.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
• Intervention / Treatment: Drug: Placebo; Drug: Sativex Oromucosal Spray

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 8AF
    • Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The study is open for both men and women aged 18-55 who meet DSM 5 criteria for ADHD (N= 30). Subjects will be either unmedicated or medicated with stimulant medication only and be willing to come of this medication for 1 week before and for the duration of the study. To ensure that this does not disadvantage patients we will only include those on stimulant medication who do not take medication on a regular basis and where short periods of medication are not thought by both the patient and psychiatrist to represent a clinical problem in the overall control of the symptoms and impairments. For example, by including patients who are considering a "stimulant drug holiday", which is a common clinical procedure in ADHD. Subjects must not use other prescription and non-prescription medication or recreational drugs during the study.

Exclusion Criteria:

• Exclusion criteria will include autism spectrum disorders and other psychiatric disorders including recurrent major depression, bipolar I disorder, any psychotic disorder and obsessive compulsive disorder and learning difficulties defined as an IQ < 70. Neurological problems and known or suspected history of a drug or alcohol dependence disorder. Subjects who are using or have used cannabis or cannabis based medications in the 30 day period prior to study entry. Concurrent history of renal, hepatic, cardiovascular or convulsive disorders. Females who are pregnant or breastfeeding. Female subjects of child bearing potential and male subjects whose partner is of child bearing potential, unless willing to ensure that they or their partner use two effective forms of contraception, for example, oral contraception, double barrier, intra-uterine device, during the study and for three months thereafter (Note: a male condom should not be used in conjunction with a female condom).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sativex Oromucosal Spray; Participants will titrate onto Sativex during the first two weeks of the study, carried out according to a standardised dosing schedule. After 2 weeks the clinician and participant will decide on the optimal dose for the remainder of the 4 week trial	Drug: Sativex Oromucosal Spray; Sativex Oromucosal Spray (GW Pharma Ltd, Salisbury. UK). Each 100 microlitre spray contains: 2.7 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD).; Other Names: Sativex
Placebo Comparator: Placebo; Participants will titrate onto the placebo during the first two weeks of the study, carried out according to a standardised dosing schedule. After 2 weeks the clinician and participant will decide on the optimal dose for the remainder of the 4 week trial	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in performance on the QB Test using the average of 3 weighted indexes: 'activity' 'inattention' and 'impulsivity'	QbTest: The Qb test is a computer administered attention test. An infrared camera monitors patient movement and measures activity; attention and impulsivity are calculated based on the task performance and activity level. The data is processed and compared with a normative group.	6 weeks (baseline (day 1)-follow-up (day 42))

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADHD symptoms of inattention, hyperactivity-impulsivity and emotional lability	This will be assessed using the Conners' Adult ADHD Rating Scales (CAARS) and Wender-Reimher Adult Attention Deficit Disorder Scale (WRAADS) combined (investigator rated): Both measure ADHD symptom severity.	6 weeks (baseline (day 1) - follow-up (day 42))
Self-report behavioural questionnaire	Executive function measured with: The Brief-A.	6 weeks (baseline (day 1) - follow-up (day 42)
Self-report behavioural questionnaire	Common psychopathology measured with: The Symptom Check-List (SCL-90)	6 weeks (baseline (day 1) - follow-up (day 42)
Self-report behavioural questionnaire	Mood will be measured using: The Centre for Neurologic Studies-Lability Scale (CNS-LS)	6 weeks (baseline (day 1) - follow-up (day 42)
Self-report behavioural questionnaire	Mood measured with: The Affective Lability Scale (ALS-SF)	6 weeks (baseline (day 1) - follow-up (day 42)
Self-report behavioural questionnaires	Sleep measured with: The Pittsburgh Sleep Quality Index (PSQI)	6 weeks (baseline (day 1) - follow-up (day 42)
Self-report behavioural questionnaire	Level of depressive thoughts: The Depressive Thoughts Questionnaire (DTQ)	6 weeks (baseline (day 1) - follow-up (day 42)
Self-report behavioural questionnaire	Control over thoughts: Cognitive Control Questionnaire	6 weeks (baseline (day 1) - follow-up (day 42)
Self-report behavioural questionnaire	The Brief COPE assesses how participants are coping with stressful life events	6 weeks (baseline (day 1) - follow-up (day 42)
Self-report behavioural questionnaire	The Brief Life Events Questionnaire (BLEQ) assesses the occurrence of stressful life events.	6 weeks (baseline (day 1) - follow-up (day 42)
Self-report behavioural questionnaires	Functional Impairment: The Weiss Functional Impairment Rating Scale Self Report (WFIRS-S)	6 weeks (baseline (day 1) - follow-up (day 42)
Self-report behavioural questionnaires	The Adult ADHD Quality of Life Scales (AAQoL)	6 weeks (baseline (day 1) - follow-up (day 42)
Change in cognitive performance	SART: The SART is a computerised go/no go task measuring both response inhibition and sustained attention	6 weeks (baseline (day 1)-follow-up (day 42))

Collaborators and Investigators

• Sponsor: King's College London
• Collaborators: South London and Maudsley NHS Foundation Trust
• Investigators: Principal Investigator: Philip Asherson, MD, PhD, Institute of Psychiatry, King's College London

Publications and helpful links

General Publications

• Cooper RE, Williams E, Seegobin S, Tye C, Kuntsi J, Asherson P. Cannabinoids in attention-deficit/hyperactivity disorder: A randomised-controlled trial. Eur Neuropsychopharmacol. 2017 Aug;27(8):795-808. doi: 10.1016/j.euroneuro.2017.05.005. Epub 2017 May 30.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: September 3, 2014
• First Submitted That Met QC Criteria: September 23, 2014
• First Posted (Estimate): September 25, 2014

Study Record Updates

• Last Update Posted (Actual): December 4, 2020
• Last Update Submitted That Met QC Criteria: December 3, 2020
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Cognition; ADHD,; Cannabis,; Sativex,; Endocannabinoid,
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Nabiximols
• Other Study ID Numbers: EMA-C