Introduction to Addiction Medicine

Addiction Medicine is a branch of medicine involved in the diagnosis, treatment, and prevention of substance use disorders. This article will address basic concepts related to addictions, substance use disorders, and the DSM-5's conceptualization of these disorders.

• Addiction disorders are typically characterized as a biological brain disease characterized by compulsive engagement in rewarding stimuli despite adverse consequences.
  • Any substance used in excess has direct effects on the activation of the brain reward system, which is involved in reinforcing behaviours and the production of memories.
  • The intense activation of the reward system can lead to the neglect of normal activities, which results in the clinical and functional impairment seen in substance use disorders.^[1]
• Normally, the reward system in the brain rewards adaptive behaviors (e.g. - foraging for food), but drugs of abuse bypass this and directly activate the reward pathways to produce feelings of pleasure (the “high”).
• An emerging hypothesis in the last two decades involves the excitatory neurotransmitter glutamate in drug addiction, called the “glutamate homeostasis hypothesis.”^[2]
  • Within the mesolimibic pathway in the brain, there are dopaminergic projections from the ventral tegmental area (VTA) to the nucleus accumbens, which is a critical part of the reward system in the brain.
  • The nucleus accumbens also is a major input structure of the basal ganglia and integrates cortical and limbic input to mediate goal-directed behaviors.^[3]
  • Environmental cues from substance use can induce this glutamate release, which is thought to disrupt the underlying glutamate homeostasis within this pathway.^[4]
  • In addition to glutamate, the relative activity of dopamine and serotonin in the nucleus accumbens also plays a major part in the development of behavioural addiction and substance use disorders.
    • At the most basic level, dopamine promotes wanting and serotonin promotes satiation.
    • All drugs of addiction have been shown to raise dopamine levels and lower serotonin levels in the nucleus accumbens.
• It is thought that individuals with lower levels of self-control are particularly predisposed to impairments in these homeostatic and inhibitory brain mechanisms.^[5]

• Despite the considerable research and evidence for the “brain-based” and biological model of addictions, the nature and etiology of addiction remains a controversial topic.^[6]
• Like with all psychiatric disorders, addictions can (and should be) viewed through a biopsychosocial lens.
• The development of addictions and substance use disorders can also be viewed through a sociopolitical lens as well.^[7]

• There is now increasing in recognition that addictive disorders can go beyond physical substances, and that other behavioural patterns similarly activate the same reward pathways in the brain. This includes the term behavioural addiction, specifically gambling disorder, which was recently added to the DSM-5. Other excessive behavioural patterns such as Internet gaming disorder are also under investigation as a diagnostic construct.^[8]

Physiological tolerance is best understood using the example of opioids. When the brain is chronically exposed to elevated levels of opiates, two things develop:

1. Tolerance: the need to take more of the same substance to achieve the same effect
   • When morphine binds to opiate receptors, it triggers the inhibition of adenylate cyclase, which triggers cytokines to fire impulses. With repeated activation of the opiate receptor by morphine, the enzyme adapts so that morphine no longer cause changes in cell firing. Thus, the effect of a given dose of morphine or heroin is diminished.
2. Dependence: being susceptible to opioid withdrawal symptoms (you can only develop withdrawal symptoms if you develop tolerance first).^[9]

• Tolerance can also be learned or developed through environmental exposure.
• This is much like Pavlovian conditioning (Pavlov's Dogs), where environmental stimuli can trigger innate physiological responses.
• For example, for a heroin user who frequently injects in his bathroom at home, his body will adapt to develop increased tolerance to opiates at that time.
  • If, however, he decided to go rehab, and not use for several weeks, and then injected at a foreign location, his body has lost this learned tolerance, and thus this makes him more susceptible to an overdose.^[10]
• Cases have been reported of patients overdosing due to Pavlovian conditioning.^[11]

The DSM-5 describes 10 classes of drugs for which substance-related disorders can apply: alcohol, caffeine, cannabis, hallucinogens, inhalants, opioids, “sedatives, hypnotics, and anxiolytics,” stimulants, tobacco, and other (or unknown) substances. These substances are further broken down into two diagnostic groups:

1. Substance use disorders
2. Substance-induced disorders (includes intoxication, withdrawal, and other substance/medication-induced mental disorders)

Depressant intoxication generally cause mood elevation, anxiety, sedation, behavioural disinhibition, and respiratory depression during intoxication. Withdrawal symptoms generally speaking cause anxiety, tremor, seizures, insomnia.

Stimulant intoxication and use generally causes mood elevation, decreased appetite or anorexia, psychomotor agitation, insomnia, cardiac arrhythmias, tachycardia, and anxiety. Withdrawal symptoms typically include a “post-use crash” that includes symptoms such as depression, fatigue/lethargy, increased appetite, insomnia, and vivid nightmares.

Hallucinogens are substances that can cause mind and body separation (“dissociative”) effects and visual and/or auditory hallucinations. Of note, hallucinogens such as PCP and LSD do not cause withdrawal symptoms, and hence do not have a DSM-5 diagnosis for withdrawal. Other hallucinogens however, like MDMA (which is officially designated as a hallucinogen in the DSM-5, but in fact has strong stimulant properties) and cannabis, can trigger withdrawal symptoms.

A substance use disorder for any of the above substances is diagnosed when there is a problematic pattern of use leading to clinically significant impairment or distress, as manifested by at least 2 of the following, occurring within a 12-month period:

For all the DSM-5 substance use disorders, a general estimate of severity can be added:

• A mild substance use disorder is suggested by the presence of 2 to 3 symptoms
• Moderate by 4 to 5 symptoms
• Severe by 6 or more symptoms.

The criterion for substance use disorders can broadly be divided into the following categories (which can be more easily remembered!):

1. Impaired control
   • Substance used in larger amounts or longer period than intended
   • Individual has desire to cut down substance use but fails to do so
   • Spending a great deal of time obtaining/using/recovering from its effects
   • Cravings (intense desire or urge for the drug)
2. Social impairment
   • Failure to fulfill major obligations at work, school, or home
   • Continued use despite it causing persistent/recurrent social/interpersonal problems
   • Social, occupational, or recreational activities given up or reduced
3. Risky use
   • Recurrent use in physically hazardous situations
   • Continuing use despite knowing it causes a persistent/recurrent physical/psychological problem
4. Pharmacological criteria
   • Tolerance (requiring a higher doses to achieve the same desired effect or having a reduced effect when the usual dose is used)
   • Withdrawal (a cluster of physiologic symptoms that occur when the blood/tissue concentrations of the substance declines, and the individual needs the substance to relieve the symptoms)

• A important feature of substance use disorders is an underlying change in brain circuits that can persist after detoxification.
• It is important to note that symptoms that occur due to medical treatment (e.g. - tolerance and withdrawal from as prescribed opioids) should not be diagnosed as a substance use disorder!

• Cravings can be elicited by asking: “Has there ever been a time when you had such strong urges to take the drug that you could not think of anything else?”

• Different substances can induce various psychiatric symptoms (depression, psychosis, mania, sleep disturbances, sexual dysfunction, cognitive impairment, delirium, anxiety) during different phases of use (intoxication, withdrawal).
• The table below summarizes DSM-5 recognized syndromes and diagnoses.^[12]
• Some of these disorders are temporary (i.e. - during the intoxication or withdrawal phase), while others can be persistent and have long-term sequalae.^[13]