Pilot Study: Effect of electrical brain stimulation on mental skills of individuals with long-term cannabis use

INTERVENTION: Individuals will be screened for eligibility using an online survey. This will include customised questions as well as published measures such as the 21‐item Depression, Anxiety, and Stress Scale and Alcohol Use Disorder Identification test. Using a randomised, double‐blind and sham‐controlled design, we will compare cognitive outcomes following one session of transcranial Direct Current Stimulation (tDCS; HDCStim, Newronika s.r.l Italy), a brain stimulation paradigm, between individuals who use cannabis and a control group of non‐drug using individuals. Participants will receive either active or sham/placebo tDCS on one occasion. Active, anodal tDCS will be provided at 1.5mA for 20 minutes. Anodal stimulation will be used to stimulate cortical excitability of the left dorsolateral prefrontal cortex (DLPFC) while cathodal stimulation will be applied to the right DLPFC. Sham stimulation will involve stimulation for 20 seconds and then will automatically switch off. The study also involves: 1) Paired Pulse Transcranial Magnetic Stimulation (TMS). ppTMS (120%) will be applied to the primary motor cortex (M1) once prior to and once after tDCS (within approximately 10 minutes after brain stimulation has been terminated). The pre‐tDCS TMS session will take approximately 40 minutes including paradigm set‐up. The post‐tDCS TMS session will take approximately 20 minutes. During paired pulse TMS two consecutive pulses are applied to the skull with a variable inter‐stimulus interval (ISI). Short Interval Intracortical Inhibition (SICI) occurs when a sub‐threshold conditioning TMS pulse is given one to five milliseconds before a supra‐threshold test pulse. SICI provides a measure of GABA‐a (inhibitory neurotransmitter). 2) Urinary biomarker analysis. A urine sample will be collected from participants prior to and shortly after tDCS. 3) Objective cognitive measures. Cognitive function will be measured pre‐tDCS and post‐tDCS using compu CONDITION: Cognition; ; Cognition Neurological ‐ Other neurological disorders PRIMARY OUTCOME: Cognitive functioning: Decision making, measured by the Iowa Gambling Task[Cognitive functioning (decision making) will be measured pre‐ and post‐ tDCS intervention] Cognitive functioning: Inhibitory control, measured by the Go/No‐Go Task[Cognitive functioning (inhibitory control) will be measured pre‐ and post‐ tDCS intervention] SECONDARY OUTCOME: Composite secondary outcome ‐ Urinary amino acid biomarkers: ; 1. Gamma y‐aminobutyric acid ; 2. L‐glutamine ; 3. Succinic acid ; 4. Alpha‐ketoglutaric acid ; 5. Catecholaminergic (norepinephrine, epinephrine) ; 6. Dopamine ; 7. D,L‐tryptophan ; 8. L‐tyrosine ; 9. p‐tyramine ; 10. Serotonergic ; 11. L‐kynurenine ; 12. L‐ornithine ; ; [Urine samples will be obtained pre‐ and post‐ tDCS intervention] INCLUSION CRITERIA: General INCLUSION CRITERIA: 18‐40 years old, right‐handed, male and female, English‐speakers, normal or corrected‐to‐normal vision Cannabis group INCLUSION CRITERIA: Individuals who have regularly (4+ days per week) used cannabis for 2+ years. We are not specifically recruiting individuals with cannabis use disorder (CUD); however, participants may meet criteria for CUD. Cannabis users will be asked to refrain from cannabis use 24 hours + prior to the Research Session. Control group: No history of cannabis use or minimal (<50 lifetime uses) history of cannabis use