Sapiens: A Brief History of Humankind.

Addiction is a chronic, relapsing disorder involving changes in brain reward, motivation, learning, stress and executive control systems. While different substances (and behaviours) act through distinct primary mechanisms, they converge on common neurobiological pathways — particularly the mesocorticolimbic dopamine system.

Below is an overview in Australian English of the core mechanisms and then substance-specific and behavioural addiction processes.

Core Neurobiological Pathways in Addiction

1. The Mesocorticolimbic Dopamine System

The central pathway implicated in addiction is the mesocorticolimbic circuit, involving:

• Ventral tegmental area (VTA)
• Nucleus accumbens (NAc)
• Prefrontal cortex (PFC)
• Amygdala
• Hippocampus

All addictive drugs increase dopamine transmission in the nucleus accumbens, either directly or indirectly. Dopamine does not simply produce pleasure — it encodes reward prediction, salience and learning. With repeated exposure:

• Drug-related cues gain exaggerated salience
• Natural rewards become less reinforcing
• Behaviour becomes increasingly habitual and compulsive

2. Neuroadaptation and Allostasis

Repeated substance exposure produces:

Tolerance — Reduced response due to receptor downregulation or neurotransmitter depletion.

Dependence — Neuroadaptations that produce withdrawal when the substance is removed.

Allostatic shift — The brain’s reward set point shifts downward, mediated by stress systems (e.g. corticotropin-releasing factor), resulting in dysphoria during abstinence.

3. Habit Formation and Loss of Control

With repeated use:

• Control shifts from ventral striatum (goal-directed) to dorsal striatum (habit-based)
• Prefrontal cortex regulation weakens
• Impulsivity and compulsivity increase

Substance-Specific Mechanisms

Alcohol

Alcohol acts on multiple neurotransmitter systems:

• Enhances GABA-A receptor function (inhibitory)
• Inhibits NMDA glutamate receptors (excitatory)
• Increases dopamine release in nucleus accumbens
• Affects endogenous opioid systems

Chronic exposure leads to:

• GABA downregulation
• NMDA upregulation
• Hyperexcitable state during withdrawal (risk of seizures, delirium tremens)

Alcohol dependence also involves stress system activation and impaired frontal cortical control.

Methamphetamine

Methamphetamine is a potent psychostimulant that:

• Enters presynaptic terminals
• Reverses the dopamine transporter (DAT), causing carrier-mediated dopamine efflux
• Inhibits vesicular monoamine transporter 2 (VMAT2), releasing dopamine from synaptic vesicles into the cytoplasm
• Causes massive dopamine release into the synapse

It also increases noradrenaline and serotonin.

Chronic use causes:

• Dopamine neurotoxicity (particularly to dopaminergic terminals)
• Reduced dopamine transporter availability
• Structural changes in striatum and PFC
• Persistent cognitive deficits

Methamphetamine produces particularly strong sensitisation of cue-driven craving.

Cocaine

Cocaine:

• Blocks the dopamine transporter (DAT), preventing reuptake
• Increases synaptic dopamine concentration

Unlike methamphetamine, cocaine acts by blocking DAT rather than reversing it, and does not cause large presynaptic vesicular release — the elevation in synaptic dopamine arises from impaired clearance.

Repeated use leads to:

• Dopamine receptor downregulation
• Enhanced cue reactivity
• Rapid cycling between intoxication and crash
• Strong psychological dependence

Opioids (e.g. heroin, morphine, oxycodone)

Opioids act primarily at mu-opioid receptors (MORs), which are expressed throughout the brain, including in the VTA. Their dopaminergic effects arise through multiple mechanisms:

• MORs on GABAergic interneurons in the VTA suppress inhibitory tone, thereby disinhibiting dopamine neurons (the classical disinhibition mechanism)
• MORs are also expressed on VTA dopamine neurons and projection targets directly, contributing additional excitatory drive beyond the disinhibition pathway

They also act in brainstem respiratory centres, which underlies the risk of respiratory depression in overdose.

Chronic use produces:

• Receptor desensitisation and internalisation
• Reduced endogenous opioid production
• Severe physical withdrawal mediated by noradrenergic rebound in the locus coeruleus
• Strong negative reinforcement (use to avoid withdrawal)

Cannabis

Δ9-tetrahydrocannabinol (THC):

• Activates CB1 receptors (the primary psychoactive cannabinoid receptor)
• Modulates GABA and glutamate release at presynaptic terminals
• Indirectly increases dopamine in NAc via disinhibitory mechanisms

Cannabis produces:

• Altered endocannabinoid system function
• CB1 receptor downregulation with chronic use
• A mild to moderate withdrawal syndrome (irritability, sleep disturbance, appetite changes)
• Effects on hippocampal memory circuits

While addiction risk is generally considered lower than for opioids or stimulants, it remains clinically significant and may be underestimated, particularly given the widespread availability of high-potency THC products (e.g. concentrates and high-THC flower), which are associated with greater dependence risk and more severe withdrawal.

MDMA (Ecstasy)

MDMA:

• Reverses the serotonin transporter (SERT), causing massive serotonin efflux — this is its primary mechanism
• Also increases dopamine and noradrenaline

Neurobiological consequences include:

• Acute empathogenic and entactogenic effects driven by serotonin release
• Post-use serotonin depletion, which may contribute to dysphoria in the days following use
• Potential serotonergic neurotoxicity, though this evidence comes largely from high-dose or repeated animal studies; the clinical significance in typical human recreational use remains under debate and is not definitively established
• Moderate addictive potential relative to psychostimulants, partly because dopaminergic effects are less prominent than with cocaine or methamphetamine

Prescription Psychoactive Medications

Certain prescribed medications also have addictive potential:

Benzodiazepines — Enhance GABA-A receptor activity. Cause tolerance via receptor downregulation. Dependence is primarily a GABAergic adaptation. Withdrawal can be protracted and, in cases of high-dose or long-term use, may produce seizures.

Prescription stimulants — Act via similar mechanisms to amphetamine, increasing dopamine and noradrenaline. Risk of misuse exists in susceptible individuals, though therapeutic doses in appropriately diagnosed patients are associated with substantially lower addiction risk than recreational use.

Behavioural (Process) Addictions

Gambling Disorder

Gambling disorder is recognised in DSM-5-TR as a non-substance-related addictive disorder. Although no substance is ingested, similar neurobiological mechanisms are involved.

Dopamine and reward prediction error — Near misses activate the nucleus accumbens similarly to wins. Variable ratio reinforcement schedules (as in poker machines) generate strong, unpredictable dopamine prediction error signalling that powerfully drives continued behaviour.

Cue reactivity — Gambling-related cues activate the same mesocorticolimbic circuitry as drug cues, with increased striatal activation and reduced prefrontal inhibitory control.

Habit circuitry — A shift from ventral to dorsal striatal control contributes to compulsive betting despite continued losses.

Other Emerging Behavioural Addictions

Conditions such as internet gaming disorder, compulsive sexual behaviour disorder, and problematic social media use share overlapping neurobiological features including:

• Dopamine dysregulation and sensitisation to cue salience
• Reduced executive control
• Stress system activation

However, the evidence base for most of these conditions is still developing, and their classification as formal addictive disorders remains an area of active research and debate. Internet gaming disorder is currently listed in DSM-5-TR as a condition for further study.

Shared Neurobiological Themes Across Addictions

Across substances and behaviours, addiction involves:

• Dopamine sensitisation to cues
• Reduced sensitivity to natural rewards
• Impaired prefrontal inhibitory control
• Stress system overactivation (particularly corticotropin-releasing factor)
• Habit circuitry dominance (dorsal striatum)
• Neuroplastic changes in glutamatergic signalling

Why Some Substances Are More Addictive

Addictive potential is influenced by multiple interacting factors. The speed of dopamine rise is one of the most studied — faster onset of dopamine elevation (e.g. via smoking or intravenous administration) is associated with stronger reinforcement. This framework, developed largely through the work of Volkow and colleagues, has strong empirical support, though it represents a mechanistic model rather than an established universal law. Other important factors include:

• Intensity of dopamine release
• Pharmacokinetics (e.g. route of administration)
• Withdrawal severity (which drives negative reinforcement)
• Social and environmental context
• Genetic vulnerability (heritability of addiction is estimated at 40–60% across substances)

Conclusion

Addiction is not simply about pleasure seeking. It reflects maladaptive neuroplasticity in reward, stress, learning and executive control circuits. While alcohol, methamphetamine, cannabis, opioids, cocaine and MDMA each act through different primary molecular mechanisms, they converge on common neural pathways that drive craving, tolerance, withdrawal and compulsive use. Behavioural addictions such as gambling engage these same circuits despite the absence of an ingested substance.

The neurobiological understanding of addiction continues to evolve, and where evidence is still emerging — particularly regarding emerging behavioural addictions and the long-term neurotoxic effects of substances like MDMA — clinical interpretation should be appropriately cautious.

When to Fake It Till You Make It (and When You Shouldn’t)

Faking it for the right reasons can change you for the better. Here’s why.

Posted Jun 27, 2016By Amy Morin

One day, a client came to see me because she felt socially awkward. She knew that her inability to make small talk was holding her back both personally and professionally. As a shy person, she hated going to networking events. But making connections was vital to her career.I asked, “What do you usually do when you go to a networking event?” She said, “I stand awkwardly off to the side and wait to see if anyone will come talk to me.” I asked her, “What would you do differently if you felt confident?” and she said, “I’d initiate conversation and introduce myself to people.”

Right then and there, she discovered the solution to her problem: If she wanted to feel more confident, she had to act more confident. That wasn’t quite what she wanted to hear. She’d hoped for a solution that would immediately make her feel more confident. But the key to becoming more comfortable in social situations is practice.Her instinct was to wait until she felt more confident, but that confidence wasn’t going to magically appear out of thin air—especially if she was standing around by herself. However, if she started talking to people like a confident person, she’d have an opportunity to experience successful social interactions, and each of these would boost her confidence.

Acting “As If”

Acting “as if” is a common prescription in psychotherapy. It’s based on the idea that if you behave like the person you want to become, you’ll become like this in reality:

1. If you want to feel happier, do what happy people do—smile.

2. If you want to get more work done, act as if you are a productive person.

3. If you want to have more friends, behave like a friendly person.

4. If you want to improve your relationship, practice being a good partner.Too often we hesitate to spring into action. Instead, we wait until everything feels just right or until we think we’re ready. But research shows that changing your behavior first can change the way you think and feel.

The Biggest Mistake Most People Make

Faking it until you make it only works when you correctly identify something within yourself that’s holding you back. Behaving like the person you want to become is about changing the way you feel and the way you think.If your motives are to prove your worth to other people, however, your efforts won’t be successful, and research shows that this approach actually backfires. A study published in the Journal of Consumer Research found that people who tried to prove their worth to others were more likely to dwell on their shortcomings. Ambitious professionals who wore luxury clothing in an effort to appear successful, and MBA students who wore Rolex watches to increase their self-worth just ended up feeling like bigger failures. Even worse, their attempts to project an image of success impaired their self-control. They struggled to resist temptation when they tried to prove that they were successful. Putting so much effort into faking it used up their mental resources and interfered with their ability to make good choices.

How to “Fake It” the Right Way

Acting “as if” doesn’t mean being phony or inauthentic. It’s about changing your behavior first and trusting the feelings will follow. As long as your motivation is in the right place, faking it until you make it can effectively make your goals become reality. Just make sure you’re interested in changing yourself on the inside, not simply trying to change other people’s perceptions of you.