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In Brief

Summer 2016 • Volume 9 • Issue 1

Chronic Substance Use and Cognitive 

Effects on the Brain: An Introduction

Frequent use of a psychoactive substance (or 

substances) over an extended period, or chronic 

substance use, can negatively affect many aspects 

of a person’s life and well-being. Although many 

body systems may be harmed by chronic substance 

use, this In Brief addresses ways in which the brain 

may be affected, with a particular focus on cognitive 

processes.

Psychoactive substances produce their effects by 

modifying chemical signaling in the brain, affecting 

feelings, perceptions, thought processes, and 

behavior. This can produce long-lasting alterations 

in the neural circuits responsible for normal learning 

and memory processes.1

 The cognitive effects of 

chronic substance use may abate relatively quickly 

with abstinence, resolve after weeks or months of 

abstinence, abate only with extended abstinence, or 

not abate at all.

This In Brief provides information for health and 

human services practitioners who may encounter 

clients with cognitive deficits related to chronic 

substance use. Awareness of the potential cognitive 

effects of chronic substance use is important because:

■ Cognitive effects may make it more difficult for 

clients to engage in and benefit from health care 

and other services.

■ Effects on executive functions may make clients in 

recovery from substance use, mental, or medical 

disorders particularly vulnerable to relapse.

Executive functions are the cognitive processes that 

regulate, control, and manage: 

■ Planning.

■ Working memory.

■ Attention.

■ Problem-solving.

■ Verbal reasoning.

■ Inhibition.

■ Mental flexibility.

■ Task switching.

■ Initiating/monitoring actions.

■ Problems with cognitive functioning affect the 

quality of life of clients and may create additional 

social problems.

The In Brief will discuss ways in which chronic 

substance use may affect the brain, variables that 

can influence the effects, and some ways in which 

professionals can help clients who have substancerelated cognitive impairments.

Ways in Which Chronic Substance 

Use May Affect the Brain

The process of addiction

Addiction is a chronically relapsing disorder 

characterized by a compulsion to take a substance, 

loss of control in limiting intake, and the development 

of a negative emotional state when the substance 

cannot be obtained.2,3
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In Brief

The process of addiction creates profound changes 

in the brain. The process is complex, and specific 

changes to the way the brain works can vary 

depending on the substance used. Brain reward 

circuits are often mentioned when discussing the 

effects of addictive substances and substance misuse. 

Addictive substances activate these circuits, resulting 

in pleasurable effects; because of this positive 

reinforcement, a person may be motivated to use such 

substances again. However, the process of addiction 

is functionally and structurally multifaceted, and 

motivation for continuing to use an addictive 

substance involves more than positive reinforcement.

One way of looking at how brain structures and 

systems are affected as addiction develops is to 

divide addiction into three stages: 

1. Binge/intoxication 

2. Withdrawal/negative affect

3. Preoccupation/anticipation (craving)

Each stage changes the brain in specific ways, and 

these changes interact with one another as addiction 

develops.2,3 The following descriptions note the 

primary brain area or areas involved in each stage, 

but the descriptions are not exhaustive.

The first stage, binge/intoxication, is mediated in 

large part by neurocircuitry within the basal ganglia, 

a structure critical to the reward circuits.3 Addictive 

substances create artificial pleasure signals that are 

stronger and longer lasting than normal pleasure 

signals, altering neurotransmitter signaling. The 

resulting enhanced reinforcement of substance effects 

can increase an individual’s motivation to repeat use 

of the substance.3,4

The second stage, withdrawal/negative affect, 

involves two processes. First, there is continued 

disruption of reward circuits (particularly in the 

ventral striatum). Non-substance-use activities now 

have a diminished effect in activating reward circuits 

when compared with the effect they had before the 

onset of substance use. Second, the brain’s stress 

systems are recruited into the process of addiction, 

with the extended amygdala playing a key role. At 

this point, not using the substance causes stress; an 

individual’s use of the substance is now motivated 

more by negative reinforcement (avoidance of 

aversive effects of not using the substance) than by 

positive reinforcement.

The final stage, preoccupation/anticipation, or 

craving, involves impairment of executive functions 

by way of prefrontal cortex circuits. Loss of executive 

function in the prefrontal cortex can have adverse 

effects on both impulsivity and compulsivity. Along 

with the gradual changes in the reward system and 

increased stress sensitivity, this loss of executive 

function can further perpetuate the addiction cycle.2,3

The process of addiction includes the development, 

over time, of tolerance, meaning that greater 

amounts of a substance are needed to get the desired 

effects. Mechanisms similar to those involved in 

the development of tolerance can eventually lead 

to profound changes in neurons and brain circuits.4

The regions and processes of the brain involved 

in addiction, particularly as the disorder becomes 

increasingly severe, significantly overlap with those 

involved in learning, memory, attention, reasoning, 

and impulse control.5 These processes are particularly 

affected by chronic substance use.4,5

Physical damage

Although intoxication effects are short-lived, 

intoxication may indirectly lead to longer lasting 

negative effects on the brain—for example, via 

physical trauma caused by intoxication-related auto 

crashes, falls, or violence. Alcohol use, particularly 

among young adults, is especially correlated with 
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Chronic Substance Use and Cognitive Effects on the Brain: An Introduction

Summer 2016, Volume 9, Issue 1

trauma.6 A review article noted that up to threequarters of patients diagnosed with traumatic brain 

injury tested positive for alcohol at the time of 

admission, and approximately half were intoxicated.7

Negative effects on the brain may also be caused 

by physical damage related to substance use (e.g., 

damage due to stroke or vitamin deficiency).

Mental disorders

Substance use, including withdrawal from substance 

use, may also induce mental disorders. Substanceinduced mental disorders may be temporary and abate 

quickly (typically within 1 month of abstinence). 

However, some substance-induced mental disorders 

are of long duration and abate only with extended 

abstinence or not at all (e.g., inhalant- or alcoholinduced neurocognitive disorder).8

 Substance-induced 

mental disorders can also negatively affect cognition.

Alcohol is especially toxic to the 

developing brain. Excessive alcohol 

use damages brain cells and the 

fibers that connect brain regions, 

shrinks certain brain regions, and 

stops new brain cells from maturing. 

Some brain regions, such as the 

ones involved in memory, continue 

to make new neurons during 

adolescence through the expansion 

of neural stem cells. But alcohol 

specifically targets neural stem cells, 

so its negative impact is magnified in 

adolescents.11

Variables That Influence the 

Effects of Chronic Substance Use

The effects of chronic substance use can vary 

considerably across individuals. A substance’s effects 

on the brain also depend to a great degree on the 

overall substance dosage, including the length of time 

a person has been using the substance, the frequency 

of use, the typical amount used, and the route of 

administration. Not surprisingly, the longer and 

heavier the use, the more likely it is that a substance 

will have negative effects on the brain.

Two additional factors appear to play significant roles 

in how and to what extent an individual’s brain will 

be affected: age of substance use onset and genetics. 

Early substance use can have particularly deleterious 

effects on the human brain. The brain continues to 

develop throughout adolescence, and particularly 

important neural pathways are established during 

this period. For example, the prefrontal cortex of 

the brain is still maturing during adolescence. This 

part of the brain is involved in assessing situations, 

making sound decisions, and keeping emotions and 

desires under control.4

 In addition, during adolescence 

the brain is particularly malleable. Substance use 

during these years may seriously affect the normal 

course of brain development in long-lasting ways.4,5

For example, a comprehensive review of the 

literature indicated that adults who routinely use 

cannabis and began using it before the age of 17 

exhibit significantly more impairment in executive 

functioning than do adults who also routinely use 

cannabis but did not begin use until after the age of 

17.9 Heavy alcohol use during adolescence is also 

associated with cognitive impairments, particularly 

in memory and visuospatial processing (the ability to 

interpret visual information about where objects are in 

space).10

Advancing age might also increase vulnerability to 

the negative cognitive effects of substance use. For 

example, a pilot study that included age-matched 

controls found that older participants (ages 51–70) 
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In Brief

who were dependent on cocaine demonstrated 

greater impairment in psychomotor speed, attention, 

and short-term memory compared with younger 

participants (ages 21–39) who were dependent on 

cocaine.12

Genetic factors also play a role in how a substance 

will affect an individual. For example, according to a 

2010 review article, several studies have found that 

certain variations in a particular gene (SLC6A3) are 

associated with increased risk of cocaine-induced 

paranoia and methamphetamine-induced psychosis.13

Another example is the finding of increased risk 

of psychosis among adults who used marijuana 

in adolescence, but only among those who also 

carry a specific variant of the gene for catechol-Omethyltransferase.14

Clinical Implications of 

Neurological Effects of Chronic 

Substance Use

The neurological effects of chronic substance use 

may significantly affect a client’s ability to remain 

abstinent and to manage other aspects of his or 

her life, such as developing a healthy lifestyle or 

recovering from a co-occurring medical or mental 

disorder. Deficits in information processing and other 

learning issues interfere with acquiring and applying 

coping and other skills needed for ongoing recovery 

from substance use, mental, or medical disorders.9,15,16

Other cognitive issues that can further complicate 

recovery include:17

■ Difficulties understanding complex instructions.

■ Distractibility.

■ Disorganized behavior.

■ Lack of insight.

How Practitioners Can Help

Educate clients with cognitive deficits 

and teach life skills

Practitioners can talk with clients about the possibility 

of substance-use-related impairment and explain 

the ways in which it might interfere with treatment 

for substance use or mental disorders, health care, 

case management, or life goals.9 When appropriate, 

practitioners can offer realistic reassurance that the 

impairment will be temporary and that there are ways 

of compensating for it.

Practitioners can further help clients with cognitive 

deficits better manage their lives by encouraging and 

teaching them to:

■ Allow ample time to complete tasks.

■ Check and recheck their work.

■ Use memory aids such as calendars, diaries, 

pill containers, watches that beep, and sticky 

notepaper.

■ Take advantage of smartphone features like 

alarms, voice recorders, calculators, and notepads.

■ Establish and use cues to help remember skills 

and information.9

■ Take some time before responding to situations; 

make lists and carefully weigh costs and benefits 

of actions instead of reflexively responding.9

■ Develop routines for daily living.

■ Ask for help when needed.

Provide or refer clients for treatment of 

co-occurring mental disorders

Mental disorders may bring their own cognitive 

deficits, which may exacerbate the deficits caused 

by chronic substance use. If a client shows signs of 

a mental disorder, such as depressive symptoms, 

suicidal thoughts or attempts, anxiety, paranoia, 

or auditory hallucinations, the client should be 

referred for psychological assessment. A qualified 
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Chronic Substance Use and Cognitive Effects on the Brain: An Introduction

Summer 2016, Volume 9, Issue 1

mental health practitioner can monitor the course 

of the mental disorder over time and provide useful 

feedback to other service practitioners.

Adjust behavioral interventions to help 

compensate for deficits

Practitioners can help clients learn new information 

and skills in ways that can at least partially 

compensate for cognitive deficits. For example, 

practitioners can:

■ Schedule shorter but more frequent sessions.18

■ Use more than one modality (oral, graphic, 

video) to convey information;18 provide written 

information in addition to verbal explanations.

■ Use feedback-based learning approaches (e.g., 

frequent in-session rehearsal of skills);17,18 provide 

specific, immediate, direct, and positive feedback.

■ Repeat information frequently, in short and 

concise segments.

■ Ask the client to repeat or paraphrase what he or 

she heard.

■ Support a client’s positive coping styles (e.g., 

actively addressing life problems as they arise, 

using humor to counteract stress, making time for 

enjoyable activities).

Refer clients for cognitive rehabilitation

Although cognitive rehabilitation programs may not 

be available or financially realistic, they can be very 

helpful for clients, particularly when the cognitive 

effects of substance use are likely to be long lasting. 

Practitioners should be aware of such programs 

where they are available and know the eligibility 

requirements, costs, and coverage options.

One such program is Goal Management Training 

(GMT), a validated, structured program for 

rehabilitating executive functions.19 A pilot study 

examined the efficacy of a combination of GMT and 

mindfulness meditation with individuals with alcohol 

and polysubstance dependence along with deficits in 

executive functioning.20 Clients who participated in a 

7-week program that included GMT and mindfulness 

meditation significantly improved their performance 

on measures of working memory, response inhibition, 

and decision making. A matched control group of 

clients who did not receive the GMT and mindfulness 

program showed no significant improvement in 

executive functioning.

Coordinate with other care providers

Collaborative care teams can be particularly important 

for clients with cognitive deficits and/or substanceinduced mental disorders. Teams can include 

physicians as well as practitioners who specialize in 

areas such as physical and neurological rehabilitation, 

substance-induced or co-occurring mental disorders, 

vocational rehabilitation, employment services, and 

family support services. Close collaboration among 

providers can help ensure consistent communication 

and facilitate meeting a client’s complex needs in a 

coordinated and effective manner.

Summary

Chronic psychoactive substance use can affect 

the brain in a number of ways, both directly and 

indirectly. The effects depend in part on the type and 

quantity of substances used and the duration of their 

use. Individual factors such as genetics and the age 

of first use play a substantial role in determining the 

effects of chronic substance use on an individual’s 

brain.

Cognitive effects of chronic substance use may make 

it more difficult for clients to engage in and benefit 

from treatment; make relapse to substance use, mental 

disorders, and physical disorders more likely; and 

make everyday life for clients more difficult.

Although most cognitive effects related to chronic 

substance use abate fairly quickly with abstinence, 
Behavioral Health Is Essential To Health • Prevention Works • Treatment Is Effective • People Recover

6

In Brief

others may take more time. Practitioners can help by 

understanding that cognitive deficits are common in 

clients who have substance use disorders, assessing 

clients for cognitive deficits, adapting behavioral 

interventions to help clients gain maximum benefit 

from treatment, teaching clients skills to help 

them navigate everyday life more efficiently, and, 

when appropriate and feasible, referring clients for 

cognitive rehabilitation.

Relevant Publications From 

SAMHSA

Substance Abuse Treatment Advisory: Treating 

Clients With Traumatic Brain Injury

http://store.samhsa.gov/product/Treating-Clients

-With-Traumatic-Brain-Injury/SMA10-4591

Treatment Improvement Protocol (TIP) 29: Substance 

Use Disorder Treatment for People With Physical and 

Cognitive Disabilities

http://store.samhsa.gov/product/TIP-29-Substance

-Use-Disorder-Treatment-for-People-With-Physical

-and-Cognitive-Disabilities/SMA12-4078

Other Resources

National Institute of Neurological Disorders and 

Stroke

www.ninds.nih.gov

National Institute on Drug Abuse

www.drugabuse.gov

Society for Cognitive Rehabilitation

www.societyforcognitiverehab.org

Notes

1 Torregrossa, M. M., Corlett, P. R., & Taylor, J. R. (2011). 

Aberrant learning and memory in addiction. Neurobiology 

of Learning and Memory, 96(4), 609–623.

2 Koob, G. F. (2015). Alcohol use disorders: Tracts, twins, 

and trajectories. American Journal of Psychiatry, 172(6), 

499–501.

3 Koob, G. F., & Volkow, N. D. (2010). Neurocircuitry of 

addiction. Neuropsychopharmacology Reviews, 35, 217–

238.

4 National Institute on Drug Abuse. (2010 revision). Drugs, 

brains, and behavior: The science of addiction. NIH 

Publication No. 10-5605. Bethesda, MD: National Institutes 

of Health.

5 Gould, T. J. (2010). Addiction and cognition. Addiction Science 

and Clinical Practice, 5(2), 4–14.

6 Goforth, H. W., Murtaugh, R., & Fernandez, F. (2010). 

Neurologic aspects of drug abuse. Neurologic Clinics, 28,

199–215.

7 Taylor, L. A., Kreutzer, J. S., Demm, S. R., & Meade, M. A. 

(2003). Traumatic brain injury and substance abuse: A 

review and analysis of the literature. Neuropsychological 

Rehabilitation, 13(1–2), 165–188.

8 American Psychiatric Association. (2013). Diagnostic and 

statistical manual of mental disorders (5th ed.). Arlington, 

VA: American Psychiatric Publishing.

9 Crean, R. D., Crane, N. A., & Mason, B. J. (2011). An 

evidence-based review of acute and long-term effects of 

cannabis use on executive cognitive functions. Journal of 

Addiction Medicine, 5(1), 1–8.

10 Hanson, K. L., Medina, K. L., Padula, C. B., Tapert, S. F., & 

Brown, S. A. (2011). Impact of adolescent alcohol and drug 

use on neuropsychological functioning in young adulthood: 

10-year outcomes. Journal of Child and Adolescent 

Substance Abuse, 20(2), 135–154.

11 Brey, R. L. (2011). The adolescent brain: What neurology can 

teach us about protecting teens. Neurology Now, 7(6), 9.

12 Kalapatapu, R. K., Vadhan, N. P., Rubin, E., Bedi, G., 

Cheng, W. Y., Sullivan, M. A., et al. (2011). A pilot study 

of neurocognitive function in older and younger cocaine 

abusers and controls. American Journal on Addictions, 20,

228–239.
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Chronic Substance Use and Cognitive Effects on the Brain: An Introduction

Summer 2016, Volume 9, Issue 1

13 Mroziewicz, M., & Tyndale, R. F. (2010). Pharmacogenetics: 

A tool for identifying genetic factors in drug dependence 

and response to treatment. Addiction Science and Clinical 

Practice, 5(2), 17–29.

14 Caspi, A., Moffitt, T. E., Cannon, M., McClay, J., Murray, 

R., Harrington, H., et al. (2005). Moderation of the effect 

of adolescent-onset cannabis use on adult psychosis 

by a functional polymorphism in the catechol-Omethyltransferase gene: Longitudinal evidence of a gene 

X environment interaction. Biological Psychiatry, 57(10), 

1117–1127.

15 Fox, H. C., Jackson, E. D., & Sinha, R. (2009). Elevated 

cortisol and learning and memory deficits in cocaine 

dependent individuals: Relationship to relapse outcomes. 

Psychoneuroendocrinology, 34, 1198–1207.

16 Kiluk, B. D., Nich, C., & Carroll, K. M. (2011). Relationship 

of cognitive function and the acquisition of coping skills 

in computer assisted treatment for substance use disorders. 

Drug and Alcohol Dependence, 114, 169–176.

17 Verdejo-García, A. (2011). Novel therapies for cognitive 

dysfunction secondary to substance abuse: Brief screening, 

referral, and cognitive rehabilitation. Psychiatric Times, 

28(6).

18 Aharonovich, E., Hasin, D. S., Brooks, A. C., Liu, X., Bisaga, 

A., & Nunes, E. V. (2006). Cognitive deficits predict low 

treatment retention in cocaine dependent patients. Drug and 

Alcohol Dependence, 81, 313–322.

19 Rotman Research Institute at Baycrest, Centre for Brain 

Fitness. (n.d.). Goal management training. Retrieved 

June 27, 2016, from www.baycrest.org/research/rotman

-research-institute/centre-for-brain-fitness

20 Alfonso, J. P., Caracuel, A., Delgado-Pastor, L. C., & VerdejoGarcía, A. (2011). Combined goal management training and 

mindfulness meditation improve executive functions and 

decision-making performance in abstinent polysubstance 

abusers. Drug and Alcohol Dependence, 117, 78–81.
In Brief

In Brief, Chronic Substance Use and Cognitive Effects on the Brain: An Introduction

In Brief

In Brief 

This In Brief was written and produced under contract numbers 270-09-0307 and 270-14-0445 by the Knowledge Application 

Program (KAP), a Joint Venture of JBS International, Inc., and The CDM Group, Inc., for the Substance Abuse and Mental 

Health Services Administration (SAMHSA), U.S. Department of Health and Human Services (HHS). Christina Currier and 

Suzanne Wise served as the Contracting Officer’s Representatives, and Candi Byrne served as KAP Project Coordinator.

Disclaimer: The views, opinions, and content of this publication are those of the authors and do not necessarily reflect the 

views, opinions, or policies of SAMHSA or HHS.

Public Domain Notice: All materials appearing in this publication except those taken from copyrighted sources are in 

the public domain and may be reproduced or copied without permission from SAMHSA or the authors. Citation of the 

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Electronic Access and Copies of Publication: This publication may be ordered or downloaded from SAMHSA’s 

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Recommended Citation: Substance Abuse and Mental Health Services Administration. (2016). Chronic Substance Use and 

Cognitive Effects on the Brain: An Introduction. In Brief, Volume 9, Issue 1.

Originating Office: Quality Improvement and Workforce Development Branch, Division of Services Improvement, Center 

for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, 5600 Fishers Lane, Rockville, 

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HHS Publication No. (SMA) 16-4973

Printed 2016