use of a drug in a manner not medically or “socially” approved.

Persistent use resulting in adaptations typically accompanied by accommodation or tolerance (causing compensatory escalation) and withdrawal (e.g., depression and cravings)

a disorder of pathologic decision-making– i.e., Expression of compulsive destructive behavior despite extreme negative consequences

Why issues of Drug Abuse are

difficult:

Neurochmical Mechanisms of Drug Abuse/Addiction 

• While each of these drugs has unique pharmacological features, they all influence monoamine systems either directly or indirectly. 
• Monoamine systems and functions most likely to be affected by drugs of abuse:
• Dopamine pathways
• Serotonin pathways

Effects of Dopamine Pathway

(4)

•  Reward (limbic system-e.g., mesolimbic pathway
• Changes in motor activity (basal ganglia-e.g., nigrostriatal pathway)
• Compulsive behavior (basal ganglia)
• Compromised decision-making and motivation (cognition) (frontal and orbitofrontal cortex)

Effects of Serotonin Pathway

(4)

• Altered mood (limbic)
• Problems with sleep
• Compromised memory (hippocampus)
• Compromised decision making (cortex)

Mechanisms of Drugs of Abuse

(3)

• Increase transmitter (e.g., monoamines) activity by increasing vesicular release
• Reverse transporters (VMAT-2 and plasmalemmal transporter such as dopamine and serotonin transporters)-can cause a greater effect than drugs that increase vesicular release, and also can cause more long-term neuronal damage
• Prevent transmitter (e.g., dopamine and serotonin) reuptake by blocking plasmalemmal transporter

Drugs of Abuse

that Increase Transmitter

(6)

• opioid narcotics (e.g., heroin, OxyContin [oxycodone])
• nicotine
• marijuana
• caffeine
• alcohol (ethanol)
• sedative-hypnotics (e.g., barbiturates and short acting benzodiazepines)

• methamphetamine
• ecstasy (MDMA-methylenedioxymethamphetamine)

Difference Between Drug Abuse and 

Addiction

• Drug abuse is self-administering a drug for nonmedicinal purposes regardless of the motivation. 
• Addiction is a learned behavior that typically comes from repeatedly engaging in the drug self-administration behavior until it becomes automatic and compulsive and biologically entrenched. This results from a literal rewiring of the brain’s behavior-related circuitry (i.e., a change in synaptic contacts and neurotransmitter dynamics). 

Long-term effects of drugs of abuse

• Drug addiction is notoriously resistant to treatment and is commonly associated with frequent episodes of relapse, even when effectively managed. Contributing to this intractability of addiction are persistent changes in neurosystems caused by the drugs themselves, such as those described below:
• Methamphetamine damages the same dopamine pathway associated with Parkinson’s disease. This affects both motor and cognitive behavior. It also damages 5HT neurons in the hippocampus (memory deficits), cortex (cognitive deficits) and caudate (motor dysfunctions). 
• Many drugs of abuse cause long-term damage to the reward system (i.e., reduced dopamine D-2 receptors of the brain)-this effect is also seen in obesity and perhaps in some other addiction phenomena

Factors contributing to the expression of drug abuse/addiction

• drug abuse/addiction development and expression is extremely complex and associated with the interplay of a myriad of biological, mental health and environmental factors. Two of the most important factors are:
• A. Genetic vulnerability in addiction/drug abuse
• B. Psychiatric and Addictive disorders frequently co-express

Genetic vulnerability in addiction/drug abuse

• ~50% of the vulnerability to drug abuse/addiction is inherited, The other 50% comes from environment. Remember, genetic vulnerability is not inevitability but affects risk.  
• Vulnerability to drug addiction involves multiple genes and is expressed as complex traits. 
• Identification of these genes may help as markers for high-risk individuals, as well as serve as potential targets for therapeutics and prevention strategies

Psychiatric and Addictive disorders frequently co-express

(6)

• ~50% persons with drug abuse disorder have a co-expressing psychiatric disease
• Psychiatric disorders most likely to increase vulnerability to drug abuse are:

• Affective disorders
• Anxiety
• Psychotic disorders (e.g., schizophrenia)
• ADHD

Therapies for Drug Addiction

• While treatment for drug addiction is difficult, requiring patience and understanding, if done properly it can be effective for both the short- and long-term. Relapse is a common part of a remission process, but should not be viewed as failure. As we learn more about the causes and consequences of drug abuse and addiction, we will improve our therapeutic approaches and outcomes, requiring less time at less cost while increasing the chances of success. Research tells us that addiction disorders are chronic (in most cases lifelong) disease states and require persistent diligence to achieve long-term success. As with other mental health-related disorders, drug abuse/addiction is best managed with a combination of behavioral and pharmacological therapy.
• Science-based behavioral therapies
• Research is demonstrating that by understanding the underlying neurobiology of addiction we may be able to predict better the risk for addiction as well as the success of treatment (i.e., likelihood for relapse)

Science-based behavioral therapies

(3)

• Cognitive Behavioral Therapy (enhance cognitive systems related to proper decision making), most likely enhances capacity and functionality of the frontal cortex 
• Contingency Management (helps to employ reward systems to sustain, or develop new,  healthy decisions that compete with or replace drug-using inclinations)  
• Motivational Enhancement Therapy (replace pathogenic motivations with healthy motivations that discourage drug use and helps restructure the orbitofrontal cortex)