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Stimulants: Caffeine, Cocaine, Amphetamine, and Other Stimulants

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Absolute Addiction Psychiatry Review

Abstract

The term stimulant refers to a diverse array of natural and synthetic compounds whose use results in varying degrees of euphoria, as well as heightened attention, wakefulness, and libido, in addition to sympathomimetic effects. Certain stimulants are FDA approved for various medical and psychiatric conditions and are therefore available via prescription. While some stimulants have relatively benign physiological profiles, such as caffeine, use of other stimulants such as amphetamines or cocaine can result in significant negative physiological and/or psychiatric consequences such as stroke or myocardial infarction, psychosis, and movement disorders, and also carry a high risk for physiological dependence and the development of use disorders (addiction). As a result of their non-medical and abuse potential, a robust illicit stimulant trade remains active worldwide. There are no pharmacotherapies that are FDA approved for the treatment of any stimulant use disorder, but several behavioral therapies, such as contingency management, have demonstrated promise. This chapter reviews the mechanisms of action of various stimulants, diagnostic features of different stimulant intoxication/withdrawal/use disorders, and evidence-based treatment modalities for these diagnostic entities. The stimulants of particular focus in this chapter will be caffeine, cocaine, as well as amphetamine and amphetamine-type (AAT) stimulants.

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Notes

  1. 1.

    Windows of detection are dependent on a number of factors, including the relative cut-off levels of the individual tests. For example, a test with a lower cut-off level could potentially detect both a smaller amount of substance used as well as detect the presence of a substance for a longer period of time following exposure.

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Author information

Authors and Affiliations

  1. Behavioral Health and Recovery Services; Marin County California Department of Health and Human Services, San Rafael, CA, USA

    Jeffrey J. DeVido

  2. Partnership HealthPlan of California, Fairfield, CA, USA

    Jeffrey J. DeVido

  3. University of California, San Francisco, Department of Psychiatry, San Francisco, CA, USA

    Jeffrey J. DeVido

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  1. Jeffrey J. DeVido
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Corresponding author

Correspondence to Jeffrey J. DeVido .

Editor information

Editors and Affiliations

  1. University of California, San Diego, La Jolla, CA, USA

    Carla Marienfeld

Review Questions

Review Questions

  1. 1.

    A 29-year-old male medical resident is studying for his licensing examination. To help stay awake, he has been consuming caffeine-containing “energy” drinks on a nightly basis. The wakefulness-enhancing effects experienced by this resident from caffeine are attributable to its _________ of central ___________ receptors, a system which is implicated in the experience of escalating sleepiness during periods of prolonged wakefulness.

    1. A.

      Agonism, dopamine

    2. B.

      Antagonism, adenosine

    3. C.

      Agonism, adenosine

    4. D.

      Antagonism, dopamine

    5. E.

      Partial agonism, mu-opioid

    Answer: B.

    Explanation: Endogenous adenosine agonizes central A1 and A2A adenosine receptors, which leads to the experience of increased sleepiness. Caffeine’s psychomotor-reinforcing effects and hyperarousal are the result of the antagonism of central A1 and A2A adenosine receptors.

  2. 2.

    A 37-year-old female intravenous heroin and cocaine user has entered treatment at an opioid treatment program. With initiation of methadone maintenance, the patient achieved abstinence from use of heroin, but she continues to struggle with cocaine use. To address this, the opioid treatment program enrolls the patient in a program that provides specific reinforcements and sanctions for providing toxicology screens that are negative or positive, respectively, for cocaine. This behavioral strategy of providing environmental reinforcements has been shown to be effective in the treatment of cocaine use disorder, and is known as:

    1. A.

      Cognitive behavioral therapy

    2. B.

      Motivational enhancement therapy

    3. C.

      Acceptance and commitment therapy

    4. D.

      Contingency management

    5. E.

      Mindfulness-based stress reduction

    Answer: D.

    Explanation: Contingency management is an evidence-based behavioral therapy that has been shown to be effective in the treatment of various stimulant use disorders, but cocaine use disorder in particular. In this treatment, individuals are given the opportunity to receive behavioral incentives such as gift cards in the event that they adhere to some predetermined and agreed upon desirable behavior (e.g., attendance at counseling sessions, providing a negative toxicology screen). Correspondingly, individuals receive sanctions (e.g., no gift card, reduction in number of take-home methadone doses provided) should they not adhere to the predetermined and agreed upon desirable behavior.

  3. 3.

    A 35-year-old male who has a history of using illicit opioids has achieved 2 years abstinence from opioids while on buprenorphine-naloxone sublingual therapy. He’s at a party where a friend offers him methamphetamine, which he has never used before. Afterwards, he reports to his counselor that the experience of methamphetamine was more rewarding than any other substance he’s ever taken, including cocaine. One pharmacological explanation for why methamphetamine was even more reinforcing than cocaine in this individual is:

    1. A.

      Methamphetamine potently stimulates serotonin receptors, whereas cocaine does not.

    2. B.

      Methamphetamine blocks the effects of the most widespread inhibitory neurotransmitter in the brain, gamma-aminobutyric acid (GABA), leading to a potent stimulatory effect.

    3. C.

      Cocaine’s ability to block neuronal sodium channels lessens its pleasurable effect relative to methamphetamine which has no effect on neuronal sodium channels.

    4. D.

      Methamphetamine not only blocks reuptake of dopamine in the synapse, but also causes vesicular release of dopamine into the synaptic cleft. This results in a surge in dopamine that accounts for methamphetamine’s intensely rewarding experience relative to most other drugs of abuse.

    5. E.

      The patient must have also used a sedative medication or alcohol with the methamphetamine in order to produce an intensely pleasurable “speedball” effect, since methamphetamine alone is not very reinforcing or rewarding.

    Answer: D.

    Explanation: Much of cocaine’s psychostimulatory effects are mediated through its ability to increase synaptic dopamine levels by inhibiting dopamine reuptake. By contrast, methamphetamine (and amphetamine) produce their psychostimulatory effects by both blocking dopamine (and other catecholamine) reuptake, as well as disrupting monoamine vesicular storage causing an intracellular release of catecholamine stores with consequent increased release of synaptic catecholamines.

  4. 4.

    A 46-year-old female methamphetamine user is talking with her physician at a residential treatment program. She says to her physician: “I’ve heard of people with heroin addiction taking methadone or buprenorphine to treat their heroin addiction. I want to learn more about medications to treatment my methamphetamine addiction.” Her addiction medicine-boarded physician most accurately responds:

    1. A.

      “That’s fantastic. There is a great new option of a methamphetamine vaccine that just got approved for use in the U.S.”

    2. B.

      “Methadone and buprenorphine are just replacing one addiction for another, so I would not recommend thinking about any medications for your addiction, or any addiction for that matter.”

    3. C.

      “Researchers have tried many different kinds of medications to treat methamphetamine use disorder, and unfortunately none of them have shown a strong enough positive effect to warrant widespread use.”

    4. D.

      “I’ll get you started today with a prescription for amphetamine that you can take instead of taking methamphetamine.”

    5. E.

      “Several large-scale studies have demonstrated that topiramate is effective in treating methamphetamine addiction. I recommend that we start that today.”

    Answer: C.

    Explanation: Small studies have demonstrated some possible effect of mirtazapine and risperidone on the use of methamphetamine. However, larger studies have not demonstrated large enough beneficial effects for any medication in the treatment of methamphetamine use disorder to warrant widespread use in treatment.

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DeVido, J.J. (2020). Stimulants: Caffeine, Cocaine, Amphetamine, and Other Stimulants. In: Marienfeld, C. (eds) Absolute Addiction Psychiatry Review. Springer, Cham. https://doi.org/10.1007/978-3-030-33404-8_12

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