Table 1.
Summary of Studies Published in Last 5 Years Reporting on Cannabis and Alcohol Co-use and Neurocognitive Function, Brain Structure and Brain Function.
| Author and Year | Age Range (yrs) | Sample Size (N) | Sample Characteristics | Substance Use Groups or Variables for Analysis | Task/Outcome | Main Findings |
|---|---|---|---|---|---|---|
| Concurrent Alcohol and Cannabis Episodes | ||||||
| 33Wade N et al., 2020* | 15–26 | 232 | Community sample of adolescents and adults with a range of substance use from none to weekly (<50 lifetime use episodes of any other illicit substances). Alcohol breath analysis and urinalysis verified abstinence from all substances, other than nicotine, at study sessions. | Total number of past month BD episodes [episodes >4 or more drinks (female), >5 or more drinks (male)] Total number of past month CA episodes. Total number of past month BD+CA episodes. |
CVLT-II, D-KEFS, RCFT, Ruff 2&7, WAIS-III. | More past month BD+CA episodes associated with poorer selective attention accuracy (Ruff 2&7). Co-use not associated with executive function, verbal fluency, learning and memory, and delayed recall. |
| 15Wade N et al., 2020* | 16–26 | 75 | Community sample of adolescents and adults with a range of substance use from none to weekly (<50 lifetime use episodes of any other illicit substances). Alcohol breath analysis and urinalysis verified abstinence from all substances, other than nicotine, at study sessions. | Total number of past month BD episodes [episodes >4 or more drinks (female), >5 or more drinks (male)] Past month CA use (total grams) Total number of past month BD+CA episodes. |
WM integrity (AD, FA, MD, RD). | More past month BD+CA episodes associated with lower AD (left inferior longitudinal fasciculus) and lower FA (left inferior longitudinal fasciculus, right anterior thalamic radiation, left cingulum cingulate gyrus). Co-use not associated with MD and RD in any tract. |
| Recent Alcohol and Cannabis Co-use (e.g., past 2 months) | ||||||
| 60Feldstein Ewing S et al., 2015** | 14–18 | 95 | Community sample of high-risk youth (involved in justice day-program) (97.9% had both alcohol and cannabis use in past month). Abstinence prior to study session not reported. | Sum of alcohol use days + sum of cannabis use days in past month. | Go/No-Go fMRI Task | Significant negative correlations between past month alcohol and cannabis use days and response inhibition (left IFG, right insula BOLD activation). |
| 37Karoly HC et al., 2015 | 14–18 | 132 | Community sample of adolescents from larger study focused on HIV/STI risk reduction, included those with no current substance use in addition to more frequent substance users. Abstinent from any substances (including tobacco) at least 3 hours prior to study session. | ALC users (≥2 ALC days in past month). CA users (≥10 CA days in past month). TOB users (≥27 TOB days in past month). CA+TOB users (≥10 CA days, ≥27 TOB days in past month). CA+ALC+TOB users (≥10 CA days, ≥27 TOB days, ≥2 ALC days in past month). CON (0 ALC, CA, TOB days in past month). |
ImpSS, Monetary Incentive Delay Task (Reward, Loss, Neutral trials) | No differences in impulsivity/sensation seeking or reaction time and percentage of hits for reward, loss, neutral trials between ALC, CA, TOB, CA+TOB, CA+ALC+TOB, CON. TOB less activation in left NAcc compared to CA+ALC+TOB across all Reward-Neutral contrasts. No differences in NAcc activation between CA+ALC+TOB and CA+TOB or between CA+ALC+TOB and CON on all Reward-Neutral contrast. |
| 12Claus E et al., 2018** | 14–18 | 189 | Community sample of high-risk youth (involved in justice day-program). Abstinence verified by self-report 24 hours prior to study session. | ALC users (>1 ALC use episode in past month). CA users (>1 CA use episode in past month). CA+ALC users (>1 CA use episode, >1 ALC use episode in past month). CON (≤1 ALC or CA use episode in past month). |
Balloon Analogue Risk Task (fMRI), ImpSS. | CA+ALC decreased activation in insula, striatum, and thalamus during risky decision making and stronger correlation between risk probability and activity in dACC compared to CON. CA+ALC significantly greater levels of impulsive sensation seeking compared to CA and CON. |
| 64Vergara V et al., 2019 | 18–55 | 534 | Community sample of adults who had varying ranges of substance use confirmed by interview self-report and urinalysis. Abstinence prior to study session not reported. | ALC users (>8 AUDIT-C). CA users (≥15 days 60-day TLFB). TOB users (≥7 FTQ). ALC+TOB users (>8 AUDIT-C, ≥7 FTQ). CA+ALC (≥15 days 60-day TLFB, >8 AUDIT-C). CA+TOB (≥15 days 60-day TLFB, ≥7 FTQ). CA+ALC+TOB (≥15 days 60-day TLFB, >8 AUDIT-C, ≥7 FTQ). CON [no CA or TOB use, did not assess AUDIT-C scores, but did not meet criteria for ALC abuse/dependence (DSM-IV)]. |
Dynamic Functional Network Connectivity | CA+ALC lower occupancy rates in state 2 (supplementary motor area-6 and right fusiform/lingual) than CON. CA+ALC higher connectivity in state 1 (between postcentral and inferior frontal gyrus) and 4 (left putamen/caudate and postcentral) than ALC. CA+ALC no differences in connectivity compared to CA. |
| 36Tong T et al., 2020 | 18.7 (SD=0.66) | 221 | Freshmen and sophomore college students. Participants who had a positive drug screen for other substances, except cannabis, or met criteria for SUD (DSM-IV), other than AUD, were excluded. Abstinence prior to study session not reported. | sBinge users [2+sBinge episodes (4 (female)/5(male) drinks within 2-hour drinking session) in past month, <3 CA use & no more than 30 occasions of lifetime CA use]. eBinge users [2+eBinge episodes (>4 (female)/5(male) drinks within 2-hour drinking session) in past month, <3 CA use & no more than 30 occasions of lifetime CA use]. CA+sBinge users (sBinge criteria, 4+ episodes CA use). CA+eBinge users (eBinge criteria, 4+episodes CA use). CON (no history of CA use or sBinge/eBinge, but ALC use consisting of 1–2 drinks per occasion). |
Monetary Incentive Delay (Reward, Loss trials), Stop-Signal | sBinge, eBinge, CA+sBinge, CA+eBinge CON showed strong brain activation, but no group differences were observed in behavioral performance or neural correlates of monetary incentive delay and stop-signal tasks. |
| 35Petker T et al., 2021 | 19.5–23 | 730 | Community sample of emerging adults reporting high risk drinking, widely varying cannabis use, and minimal tobacco use. Abstinence prior to study session not reported. | HRD [≥2 instances of high-risk drinking (>4(male)/3(female) standard drinks) in past month]. HRD + monthly/weekly CA (one high-risking drinking instance in past month, monthly/weekly CA). HRD + daily/multiple times daily CA (one high-risking drinking instance in past month, daily/multiple times daily CA). |
Delay and Probability Discounting, Digit Span Task, Go/No-Go Task, Shipley Verbal Scale. | HRD + daily/multiple times daily group significantly greater impulsive delay discounting than HRD and HRD + weekly/monthly CA. No differences observed between HRD, HRD+weekly/monthly CA, and HRD+daily/multiple times daily CA for any other neurocognitive measures. |
| Lifetime Alcohol and Cannabis Co-use | ||||||
| 16Jacobus J, Squeglia L, Infante A et al., 2015† | 16–19 baseline, 1.5 & 3-year follow up | 108 | Adolescents/Young adults from local high schools and colleges. Participants with history of lifetime SUD (DSM-IV) other than alcohol or cannabis abuse/dependence were excluded. Substance using participants abstained for at least 3 weeks on average prior to completing the protocol. | CA+ALC (≥60 lifetime CA episodes, concomitant ALC use). CON (≤9 lifetime CA episodes, minimal ALC use). |
CVLT-II, D-KEFS, PASAT, WAIS-III, WASI, WMS-III. | CA+ALC significantly worse performance, across time points (baseline, 1.5-year, 3 year), in the domains of complex attention, memory, and visuospatial functioning compared to CON. No differences were observed between CA+ALC and CON for processing speed or executive function. |
| 13Jacobus J, Squeglia L, Meruelo A et al., 2015† | 16–19 baseline, 1.5 & 3-year follow up | 68 | Adolescents/Young adults from local high schools and colleges. Participants with history of lifetime SUD (DSM-IV) other than alcohol or cannabis abuse/dependence were excluded. Substance using participants abstained for at least 3 weeks on average prior to completing the protocol. | CA+ALC (≥120 lifetime CA episodes, ≥22 lifetime alcohol episodes). CON (≤9 lifetime CA episodes, ≤20 lifetime AC episodes, on average). |
Cortical Thickness. | CA+ALC greater cortical thickness estimates in all four lobes of brain (frontal, parietal, temporal, occipital) than CON across time points. 18 of 23 regions in which differences observed were in frontal and parietal cortex. |
| 14Jacobus J et al., 2016†† | 12–14 baseline, 18–21 by 6–8 year follow-up | 69 | Adolescents from local schools. Participants with history of lifetime SUD (DSM-IV) other than alcohol or cannabis abuse/dependence were excluded. Abstinence prior to study session not reported. | ALC (<40 cumulative CA episodes, similar lifetime ALC use by follow up). CA+ALC (>50 cumulative CA episodes by follow-up). CON (<3 lifetime ALC episodes, no cannabis episodes by follow-up). |
CVLT-Children, CVLT-II, D-KEFS, WAIS-III, WASI, WISC-III. Cortical Thickness. |
ALC and CON performed better on complex attention than CA+ALC. ALC and CON demonstrate greater cortical thickness at baseline and more substantial decrease by follow-up compared to CA+ALC. |
| 40Infante A et al., 2017†† | 12–14 baseline, 17–21 by ~6-year follow up | 69 | Adolescents from local schools. Participants with history of lifetime SUD (DSM-IV) other than alcohol or cannabis abuse/dependence were excluded. Abstinence prior to study session not reported. | ALC (>20 cumulative lifetime ALC episodes, <40 cumulative CA episodes by follow-up). CA+ALC (>50 cumulative CA days, >20 cumulative lifetime ALC episodes by follow-up). CON (<3 lifetime ALC episodes, no cannabis or other substance use episodes by follow up). |
GM Surface Area. | CA+ALC and CON greater surface area at baseline and follow-up than ALC. ALC more substantial decrease in bilateral medial orbitofrontal cortex and right insula than CON and CA+ALC. ALC greater decrease in right medial orbitofrontal cortex surface area than CA+ALC. |
| 22Cookey J et al., 2018 | 19–35 | 21 | Early phase psychosis patients typically <5 years from diagnosis. Participants with lifetime history of SUD (DSM-IV) for any other substances, other than alcohol, cannabis, or tobacco were excluded. Abstinence prior to study session not reported. | Cannabis*alcohol lifetime occasions. | WM integrity (FA). | No significant interaction effect of lifetime alcohol and cannabis use on FA values. |
*, **, †, ††
Studies with matching superscripts derived participants from the same overall sample. Note: Main findings reported are relevant to the co-use of alcohol and cannabis. ALC-alcohol, AUDIT-C-Alcohol Use Disorder Identification Test-Consumption, AD-axial diffusivity, BD-binge-drinking, BD+CA-binge drinking and cannabis, BOLD-blood oxygen level dependent, CA-cannabis, CA+ALC-cannabis and alcohol, CA+TOB-cannabis and tobacco, CON-control, CVLT-II California Verbal Learning Test-Second Edition, dACC-dorsal anterior cingulate cortex, D-KEFS-Delis-Kaplan Executive Function System, DSM-IV-fourth edition of the diagnostic and statistical manual of mental disorders, eBinge-extreme binge-drinking, fMRI-functional magnetic resonance imaging, FTQ-fagerstrom tolerance questionnaire, FA-fractional anisotropy, GM-gray matter, HRD-high-risk drinking, ImpSS-impulsivity and sensation seeking scale, MD-mean diffusivity, MID-monetary incentive delay task, OFC-orbitofrontal cortex, RCFT-Rey Complex Figure Task, RD-radial diffusivity, sBinge-standard binge-drinking, SUD-substance use disorder, TLFB-timeline followback, TOB-tobacco, WAIS-III-Weschler Adult Intelligence Scale-Third Edition, WM-white matter.