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Tolerance to a medication or illicit drug represents a very complex concept that consists of both physiological and psychological mechanisms. A basic definition of tolerance is simply the need to administer more of the medication (drug) to get the same effect that was once achieved at a lower dosage or getting less of a response to a drug at the usual dosage (the amount of the drug that one typically takes).
Tolerance can be a sign of the development of a substance use disorder, but simply developing tolerance to a substance is not sufficient for anyone to be diagnosed with a substance abuse issue or for anyone to develop physical dependence on a drug or medication. In fact, tolerance is quite common in individuals who use drugs medicinally, and physicians often must adjust doses of medications to account for this aspect of treatment.
Tolerance is not a singular concept. There are multiple facets to tolerance that include:
As stated above, tolerance to drugs like cocaine is most often described in terms of the physiological type of tolerance that occurs due to changes in neurotransmitters, hormones, and other substances in the body as a result of using drugs. All psychoactive drugs like cocaine, alcohol, heroin, etc., result in stimulation of the neurotransmitter dopamine. The production and availability of other neurotransmitters and hormones are also stimulated depending on the specific drug. In the case of cocaine, excitatory neurotransmitters like norepinephrine and glutamate are also activated. The overstimulation of the neurons that produce these neurotransmitters results in changes in the neuroanatomy of an individual’s brain that can be long-lasting.
Recently, there has been quite a bit of attention given to neuroplasticity, a concept that is actually far older than many people believe. Neuroplasticity refers to the notion that there are physiological changes in the brain that occur as a result of experience. For example, simply reading this article results in changes in an individual’s brain. Individuals using drugs like cocaine also induce physiological changes to the brain that affect numerous areas of their functioning, including the response to the drugs they take.
The use of cocaine and other psychoactive drugs activates dopamine in the brain, resulting in changes in what is often referred to as the reward system of the brain (better referred to as the limbic system). Cocaine directly activates dopamine in areas of the brain as well. This overstimulation of dopamine leads to the physiological changes in the brain.
First, the activation of dopamine results in significant changes in neurons as a result of the person’s system attempting to maintain balance. Dopamine neurons (and the neurons of other neurotransmitters that are stimulated as result of using cocaine) become downregulated over time, meaning that the central nervous system reduces them in number and in their effectiveness. The massive activation of neurotransmitters as a result of cocaine use also leads to a massive depletion of these neurotransmitters once the person stops using cocaine.
The down regulation of neurons as a result of continued use of a drug means that a person will need to take more of the drug to get the same effect that lower amounts of the drug once produced. However, these are not the only changes that occur.
Because our bodies, including our brains, attempt to maintain a system of balance when they function, a person who regularly uses cocaine experiences a significant imbalance of neurotransmitters, hormones, and other substances in the body. In addition to downregulating neurons that are associated with the increases in these substances, the body upregulates (increases) the number of neurons that produce effects that are in opposition to the effects of the drug; this is an attempt to maintain a level of balance, or homeostasis, in the system. This change also results in the person needing more of the substance to get the same type of euphoria they got at lower doses, as well as creating a state of imbalance in the system when the person stops using the cocaine. This imbalance eventually leads to a withdrawal syndrome once the person stops using a drug and its levels in the system are decreased as a result of normal metabolic functioning.
The more often a person uses cocaine, and as they use it for longer and longer periods of time, the more permanent these changes in the brain become. Over the long run, using cocaine makes the brain less efficient in experiencing the effects of cocaine, even though the person finds that they desire cocaine more in an attempt to maintain the state of balance they have artificially produced. In addition, other neural pathways are also altered that can affect a person’s ability to experience pleasure, to experience satisfaction, to concentrate, to make judgments, to remember new information, etc.
When physiological tolerance is combined with other types of tolerance (behavioral types of tolerance), individuals begin to binge on the drug when it is available to them, accelerating the process. Continuing to use cocaine results in massive releases of neurotransmitters followed by massive depletions of neurotransmitters that further exacerbate the situation and physically change the person’s brain. Some researchers have used animal models and neuroimaging studies of people to show that even after long-term abstinence following chronic use of cocaine, the changes that occur as a result of the development of significant tolerance never fully resolve even after the person has been abstinent from cocaine for years, making an individual more susceptible to the effects of cocaine and similar drugs for the rest of their life. Thus, the development of tolerance also plays a significant role in susceptibility to relapse for people in recovery.
According to the formal diagnostic criteria for substance use disorders presented by the American Psychiatric Association (APA), tolerance to a drug is a symptom of substance use disorders; however, having tolerance to a drug does not guarantee that an individual has developed a substance use disorder (an abuse problem or addiction). Instead, the person’s use of drugs must also produce significant distress, impairment, and/or dysfunction in their life, and they must have at least one other symptom from the list before they can be considered to have a formal diagnosis of any substance abuse issue.
This indicates that individuals who use drugs for medicinal reasons can develop tolerance (and even physical dependence), but they are not considered to have an addiction by clinicians as long as they use the medication under the supervision of their doctor and according to its prescribed instructions.
Tolerance to cocaine develops rapidly, and even individuals who occasionally use the drug will find that they develop some level of tolerance to it. Moreover, the development of tolerance is also subject to the method that the person uses to administer the drug. Individuals who snort cocaine will develop tolerance far more slowly than individuals who smoke or inject it.
However, cocaine is not a drug that is prescribed medicinally; it is only used in very circumscribed clinical conditions. Anyone who uses cocaine and begins to notice that they have developed significant tolerance to the drug is very likely on the way to developing a substance use disorder if they have not already developed an abuse issue.
Thus, any person who uses cocaine and begins notice that they need a greater amount of the drug to feel its psychoactive effects is most likely experiencing a potential issue with addiction.
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The development of tolerance to cocaine is a serious issue that could lead to numerous other physical, emotional, and behavioral issues. Anyone who believes that they are developing tolerance to cocaine and using more of the drug should discuss their situation and concerns with a licensed mental health professional who specializes in the assessment and treatment of addictive behavior. Only a licensed mental health professional can diagnose a substance use disorder, and this diagnosis represents a serious issue.
Individuals who are diagnosed with a substance use disorder as result of cocaine use/abuse should get professional treatment. This disorder would technically be referred to as a stimulant use disorder because cocaine is a powerful stimulant drug.
The overall approach to treatment would be to first assess the individual’s situation, including their use of cocaine and the other drugs, develop a treatment plan to fit their needs, and then implement the plan. The treatment plan will follow the general principles of effective treatment for substance use disorders, but would be adjusted to fit the specific needs of the person being treated.
The overall treatment plan would include:
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