Psycodex #4: Addiction
Stories of Alcohol and Opioids, and the boundaries of Biology and Medicine
This is the fourth post in a series of weekly primers on what Australian medical students learn in psychiatry. “/” indicates content taught within the medical curriculum; “\” indicates content beyond. Past posts: Introduction, #1 Depression, #2 Mania, #3 Psychosis.
CW: Mentions of suicide, substance use.
A few days in any Drug & Addiction ward is enough to see how deeply addiction can affect lives. I found the stories there heart-rending, and illustrative of the social root causes of biological suffering. To detail a few -
A middle-aged gentleman with a history of chronic alcohol use. 2 years ago, his wife divorced him. A year ago, he fell while drunk and hit his head, causing a subdural haemorrhage and leading to a craniotomy of a significant portion of his frontal lobes. Today, he was homeless, showed imaging signs of Wernicke’s encephalopathy, and was struggling to have any executive function post-craniotomy. He was previously a manager; and was frustratingly confused about being put on a disability pension.
A middle-aged gentleman with a history of synthetic cannabis, heroin, and methamphetamine use. He did not want to talk to me. He was only here because his girlfriend would only stay with him if he got clean. He told me about the voices he’d hear, that he would hear what others were thinking. He mentioned his paranoia about everyone, the subsequent trouble with police. He didn’t trust the medical system; he’d been prescribed antipsychotics which he took rarely. It wasn’t clear whether there was any underlying schizophrenia, or if these symptoms were all drug-induced.
An older woman with a history of chronic alcohol use. She was sent from the orthopaedics ward; her principal medical concern was a shoulder fracture. But the reality was, her biggest issues were social. Her family has all passed away; she didn’t have children. She lives by herself; she drank to ease the loneliness. She was a kind, but incredibly anxious lady - always apologising for being a bother to the medical staff, whilst desperate for human connection.
In every one of these cases, you could find an understanding for their addiction. One patient watched their father drown while saving their uncle when they were young, who subsequently ended their life. Another watched their father and their grandfather deal with life’ s stresses with drugs, and adopted the same cursed habit. Another felt a burden to their family with their schizophrenia, struggled to keep any social connections, and found that only opioids could provide a relief to this isolation.
\ We all have our own addictions. David Foster Wallace probably knew this best - Infinite Jest, amongst other autobiographical topics, centres around the addictions of our modern age. Alcohol, opioids, and television. Some addictions are socially acceptable than others; some are more insidious rather than immediate. But they are all addictions.
He discusses the modern plight of TV addiction best, in typical DFW meandering style, in his essay: E Unibus Pluram: Television and U.S. Fiction (1993).
“Watching TV can become malignantly addictive. [...] If it’s true that many Americans are lonely, and if it’s true that many lonely people are prodigious TV-watchers, and if it’s true that lonely people find in television’s 2D images relief from the pain of their reluctance to be around real humans, then it’s also obvious that the more time spent watching TV, the less time spent in the real human world, and the less time spent in the real human world, the harder it becomes not to feel alienated from real humans, solipsistic, lonely.”
I’ll leave it up to the reader to extrapolate what this means in a world of social media, incessant short-form video, and the incoming entanglement of AI.
/ Construct and Neurobiology of Addiction
In the DSM-V, addiction lies under the label of Substance Use Disorders. Although there are discrete labels for each substance, they are all defined by four categories of behaviours, needing at least 2 symptoms for 12 months:
Impaired control: Taking large amounts of substance or longer than intended, inability to cut down, significant time spent obtaining substance, intense cravings.
Social impairment (due to substance use): Unable to fulfill roles in work/school/home, persistent interpersonal problems, reduction of social/recreational activities.
Risky use: Use of substance in physically hazardous situations, use despite physical or psychological sequelae
Pharmacological criteria: Tolerance of drug (higher dose needed to achieve same desired effect), and withdrawal symptoms.
These categories are captured by quick screening tools like CAGE, where the presence of two is highly suggestive of an alcohol use disorder:
Have you ever felt the need to Cut down?
Have others ever gotten Annoyed by you?
Have you ever felt Guilty?
Have you ever needed a drink first thing in the morning as an Eye-opener?
Along with clear social and psychological antecedents, substance use has distinct neurobiological phenomena. There are three proposed pathways which are hypothesised to influence addiction and subsequent systems:
1. Resetting reward circuitry in the mesolimbic pathway. This pathway involves the connection between the ventral tegmental area and the nucleus accumbens, and encodes “wanting” and “liking”. Prior to and during a rewarding behaviour, dopamine surges - signalling motivation to pursue the behaviour, and encoding the prediction error on how rewarding it was. Opioids encode the hedonic value during an experience, further reinforcing the behaviour. Addiction manifests as a tolerance of this system - where more dopamine and endogenous opioids are required to maintain the same motivation and reinforcing effect.
2. Pavlovian conditioning via stress in the HPA axis. Substance use generally suppresses the normal excitatory pathways through GABA or opioids - the brain then compensates through up-regulating the stress system via cortisol and noradrenaline. These substances strengthen encoding of drug-related triggers via the hippocampus and amygdala, causing any drug cues to be immediate triggers for craving (i.e. environments and smells trigger alcohol craving).
3. Impairment of salience and executive control. The deficit in the combination of these networks contribute to poor decision making and the impaired control. The salience network is used to prioritise what stimuli to pay attention to; whilst the frontal-executive networks are used to inhibit undesired behaviour. The result is a mismatch between our psychological and biological systems - one has insight over the negative consequences of addiction, but struggles from the biologically skewed competition between overstimulated motivational circuits and compromised executive regulation.
/ Alcohol: The Legal Drug
It is this biological aspect of addiction where medicine has a role to play. Medicine can help acutely reduce withdrawal symptoms (AKA detox programs), manage the medical sequelae of chronic drug use, and offer some medications - for alcohol and opioid addiction - which can help with the process of abstinence. But it is this final aspect which is the most difficult, the most necessary, and where the efficacy of medicine is most limited. Nevertheless, we can try.
Alcohol is the most abused legal drug in Australia, with around 75% of adults having tried it at some point in their lives, and estimated around 25% of adults are risky drinkers (more than 5 drinks on any given day, and more than 10 drinks in a week monthly). In the most extreme cases, this has led to around 80,000 hospitalisations across 2022-23, around ~0.3% of the population.
The acute withdrawal symptoms of alcohol manifest in the first 5 days. The most major complication are seizures, which occur within the first 2 days. Mild withdrawal symptoms include tremors, anxiety, nausea, agitation, sweating. More severe symptoms are characterised by the clinical syndrome delirium tremens (peaking at 48 - 72hrs), which includes auditory and visual hallucinations, autonomic changes, and a confused, altered mental state. These symptoms are all monitored and graded in alcohol withdrawal scales, like the CIWA.
Chronically, delirium tremens share parallels to the main neurological complication of alcohol, known as Wernicke-Korsakoff Syndrome. This is a disease of Thiamine deficiency, which alcohol reduces the metabolic uptake and storage of. Wernicke’s encephalopathy is an earlier complication, described by the triad of ophthalmoplegia, ataxia, and altered mental state. Korsakoff syndrome is the later manifestation, which includes anterograde and retrograde amnesia, along with confabulations. Oliver Sacks, a neurologist and author, provides a movingly detailed example in the case The Lost Mariner.
The acute management of alcohol withdrawal is as follows:
Thiamine (for acute management of Wernicke’s and prevention of Korsakoff’s): 300mg oral for low risk, IV for moderate risk. If Wernicke’s present or high risk, 500mg TDS for 3 days, and continue 300mg daily. After withdrawal, 300mg daily for 6 months.
Benzodiazepines (for withdrawal): Diazepam 5mg PRN (/Chlordiazepoxide), or Lorazepam if liver disease.
The medical options for alcohol use prevention are:
Naltrexone (50mg daily): Also used in opioid addiction, it reduces the reward of alcohol via opioid antagonism. Not suitable in liver dysfunction (if LFTS > 5x normal) or opioids already.
Acamprosate (666mg TDS daily): Reduces cravings via GABA and NMDA modulation. Also contraindicated in liver failure. Aside: I couldn’t find any clear articles around why the dosing HAS to be 666mg (as opposed to 665), beyond just regulatory proliferation. Probably worth revisiting in a historical deep-dive!
Disulfiram (200mg daily): Acts to associate alcohol with negative symptoms of nausea, flushing, and headache, caused by the inhibition of acetaldehyde dehydrogenase - essentially maintaining a toxic alcohol breakdown product, acetaldehyde.
Finally, long term sequelae of alcohol use include alcoholic fatty liver disease, dilated cardiomyopathy, nutritional deficiencies, and increased cancer risk to name a few. The liver is monitored via ultrasound fibroscans, the heart through transthoracic echocardiograms, and otherwise routine bloods for vitamin monitoring. These monitoring systems act as another information point to stress the problematic use of alcohol, and inform treatment of liver transplants, steroids, or antiarrhythmics.
/ Opioids and others
Opioids are the other drugs where biomedical tools exist - ranging from low-potency like codeine or low-dose oxycodone, to high-potency compounds such as fentanyl and heroin. They differ in potency (amount needed for effect), onset and duration of action, and lipid solubility, which affects how quickly they reach the brain and produce their effects.
The main goal of opioid treatment is to give supervised doses of opioid agonist to prevent withdrawal symptoms, while supporting long term maintenance or tapering. This can be done using either methadone (which has a long half life and can be better controlled), or buprenorphine, a partial μ-opioid agonist sometimes combined with naloxone (AKA suboxone). Suboxone is generally preferred over methadone, since it has two key properties:
Ceiling effect: Partial agonism of buprenorphine limits the maximal opioid effect - even if you take more, you don’t get more opioid agonism, reducing the overdose side effects such as respiratory depression.
Overdose prevention: Naloxone is an opioid antagonist (same as Naltrexone) that has poor sublingual absorption, but good intravenous absorption. Thus, if Suboxone is misused (i.e. injected), the naloxone kicks in and causes withdrawal effects, discouraging abuse.
Other highly addictive illicit substances include nicotine, methamphetamine, and cocaine. Benzodiazepines and cannabis then are moderately addictive, and the psychedelic substances (like LSD, psilocybin) have less addictive properties but with alternate side effect risk profiles. For most of these other substances, the main pharmacological treatment are benzodiazepines to manage the acute severe symptoms.
Ultimately, biological management of addiction is limited. Like most psychiatric disorders, addiction is complex, shaped by psychological, social, and environmental factors. The expertise of medicine lies in shaping this biology - providing a salve to suffering in the face of slow societal change. Society is fixed, biology is mutable. Until enough political will exists to address these sociological determinants, medicine will have to do its best with the tools that we have.
P.S. I’d love to hear what you found interesting, and what you’d like more of in the comments.