Drug addiction, dependence, and tolerance describe a variety of ways drugs affect a person’s body and brain.

Tolerance

Tolerance happens when a person no longer responds to a drug in the way they did at first. So it takes a higher dose of the drug to achieve the same effect as when the person first used it. This is why people with substance use disorders use more and more of a drug to get the “high” they seek.

Dependence

Dependence means that when a person stops using a drug, their body goes through “withdrawal”: a group of physical and mental symptoms that can range from mild (if the drug is caffeine) to life-threatening (such as alcohol or opioids, including heroin and prescription pain relievers). Many people who take a prescription medicine every day over a long period of time can become dependent; when they go off the drug, they need to do it gradually, to avoid withdrawal discomfort. But people who are dependent on a drug or medicine aren’t necessarily addicted.

Addiction

Unlike tolerance and dependence, addiction is a disease; but like tolerance and dependence, addiction can result from taking drugs or alcohol repeatedly. If a person keeps using a drug and can’t stop, despite negative consequences from using the drug, they have an addiction (also called a severe substance use disorder). But again, a person can be dependent on a drug, or have a high tolerance to it, without being addicted to it.

Drug Tolerance is a condition that occurs when the body gets used to a drug so that either more drug is needed or different combination of drugs is needed to created the desired effect.

Let's take a look at opioids and how tolerance develops with this class of drugs.

• Opioids are a class of drugs naturally found in the opium poppy plant and that work in the brain to produce a variety of effects, including the relief of pain with many of these drugs. Opioids can be prescription medications often referred to as painkillers, or they can be so-called street drugs, such as heroin.

• Watch the following video to learn more about opioids.

When someone takes a drug for the first time, they experience its full effect. But if they keep taking it, their body adjusts and it takes more of the drug to produce the same effect. This is known as tolerance. 

When an opioid drug is used on a regular basis, the brain adjusts so the effects of the same amount of the drug become less over time. A person developing tolerance to opioid drugs may: 

• Need larger amounts of the drug to get the same effect or “high”. 

• Experience reduced effects when taking the same amount of a drug.

Tolerance happens through changes at the cellular level. It’s the result of the brain restoring balance after it’s repeatedly overstimulated by a drug. As balance is restored, neurons, synapses, and entire brain regions start to work differently. The brain sets a new normal that includes effects of the drug.

supply of the drug to maintain its fragile state of chemical equilibrium. When that supply is cut off, the brain finds itself with a shortage and goes into a state of withdrawal, creating a variety of physical symptoms. 

Withdrawal symptoms are related to this chemical imbalance. Some of these symptoms can easily be observed by others, while some are felt acutely by the user but are not readily observed. withdrawal encompasses a broad spectrum of observable and non-observable symptoms, and the experiences of those going through detox vary wildly.The brain will re-adjust itself with time.

With regular, frequent use of the drug, both physical psychological dependence on the substance is likely.  Over time, a person's ability to choose not to take drugs is compromised. This, in large part, a result of the effects of prolonged drug use on brain circuits, and that prime drug seeking cravings and behavior.  Addiction, therefore, is characterized by compulsive drug craving, seeking, and use that persists even in the face of negative consequences. 

Let's take a look at these graphics depicting the six stages of drug addiction:

The reward pathway of the brain is connected to areas of the brain that control behavior and memory. It begins in the ventral tegmental area, where neurons release dopamine to make you feel pleasure. The brain begins to make connections between the activity and feeling pleasure, storing the memory of that experience in the hippocampus, and thus ensuring that we will repeat the behavior.  

Dopamine increases with food, sex, play, sports, and reaching an important goal. This dopamine rush is often termed a "natural high".  

You will observe in the upcoming mouse party simulation that there are two major ways that drugs of abuse facilitate this dopamine high:

1. Increase synaptic dopamine levels: nicotine, cocaine, amphetamines.

2. Increase dopamine by stopping the release of inhibitory neurotransmitters (e.g., GABA): alcohol and opiates.

Many drugs can alter a person’s thinking and judgment, and can lead to health risks, including addiction, drugged driving, infectious disease, and adverse effects on pregnancy. Information on commonly used drugs with the potential for misuse or addiction can be found at the National Institute of Health. This site offers valid and reliable information on commonly abused street and prescription drugs; as well as, withdrawal symptoms.

The most common drugs of abuse stimulate the release of dopamine, which creates their rewarding effects. Compulsive drug-taking behaviors are a result of the permanent structural and functional changes in the dopamine system arising from repetitive dopamine stimulation. Cocaine, alcohol, opioids, nicotine, cannabinoids, and amphetamine (and their analogs) alter the influence of dopamine or by stimulating the activation of neurons:

(1) Dopamine synthesis increases, and

(2) Neurons in the reward pathway become more responsive to dopamine. 

These alterations are responsible for a decrease in signals to not use the drug, and a decrease in decision making abilities.

Withdrawal occurs when there is a decrease in neuron activation and dopamine activity. This change creates physiologic distress, wherein the drugs become necessary in order for the user to feel and function normally. 

Research has shown that even after withdrawal has passed, drug-seeking/use behavior can be instantly restored if exposed to the drug or drug-related stimuli. 

REVIEW QUESTIONS

After completing the Mouse Party simulation complete these review questions: [google form]

1. List three points in the neurotransmission pathway that can be affected by drugs of abuse.

2. How are the mechanisms of different drugs of abuse alike? 

3. How might drug use alter teen brain development [both growth and pruning]?  Think about what is getting wired up in your brain, and what are you practicing?

Stigma involves the negative or discriminatory attitudes that others have about addiction. Negative stereotypes and prejudices regarding drug addiction can result in discrimination and violence against people struggling with addiction. People experiencing societal stigma are more likely to feel shame. Stigma and shame are barriers to seeking drug abuse treatment and hinder recovery efforts.

Everyone has days and even weeks or months when life is hard. Stress levels are high, confidence levels are low, and solutions to problems are tough to find. Sometimes the negative feelings are overwhelming and painful. Sometimes people try to escape the pain by using drugs, or they think about hurting themselves. Everyone can get help dealing with the pain.

Substance use and mental health disorders sometimes occur together. This is because:

• Some drugs can cause people with an addiction to experience one or more symptoms of a mental health problem.

• Mental health problems can sometimes lead to alcohol or drug use, as some people with a mental health problem may misuse these substances as a form of self-medication.

• Substance use and mental health disorders share some underlying causes, including changes in brain composition, genetic vulnerabilities, and early exposure to stress or trauma

More than one in four adults living with serious mental health problems also has a substance use problem (Source: mentalhealth.gov). Substance use problems occur more frequently with certain mental health problems, including:

• Depression

• Anxiety Disorders

• Schizophrenia

• Personality Disorders

REFERENCES

Above the Influence

Andrew Huberman  (2019).  "Self Directed, Adaptive Neuroplasticity". Stanford University. Huberman Lab.

The Science of Addiction: Genetics and the Brain

Maine Youth Drug and Alcohol Use Survey (MYDAUS)

Drug Use in High School

From Drug Use To Drug Abuse: The Stages Of Addiction. 

Natural Highs

Project Aware, Inc. Falling - A powerful short movie by teens about the dangers of prescription drug abuse. 

Rethinking Drinking

SAMHSA