If we’re honest with ourselves, we know if a relationship isn’t working, if it is abusive or hurtful, or if it has run it’s course. We can ask trusted family and friends for their opinion if we’re confused or unsure.

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.

What is meant by self-harm?

Self-harm is any behaviour that involves the deliberate causing of pain or injury to oneself without the intention to end your life. Self-harm can include behaviours such as cutting, burning or hitting oneself, binge-eating or starvation, or repeatedly putting oneself in dangerous situations. It can also involve abuse of drugs or alcohol, including overdosing on prescription medications. Self-harm is usually a response to distress, whether it be from mental illness, trauma, or psychological pain. Some people find that the physical pain of self-harm helps provide temporary relief from emotional pain (extract from Self harm (lifeline.org.au)).

People who engage in self-harm will profess that they have no intention of dying and that their self-harming behaviour is a coping strategy, however, there are incidents of accidental suicide. The act of self-harm can develop into an obsessive-compulsion experience which can be very difficult to stop, like addiction, without outside intervention. This can result in feelings of hopelessness and possible suicidal thinking. Like building a tolerance to a drug, when self-injury does not relieve the tension or help control negative thoughts and feelings, the person may injure themselves more severely or may start to believe they can no longer control their pain and may consider suicide.

The following extract by Tracy Alderman Ph.D explains the physiological response to physical pain:

“Physiologically, endorphins are released when we are injured or stressed. Endorphins are neurotransmitters that act similarly to morphine and reduce the amount of pain we experience when we are hurt. Joggers often report experiencing a “runners high” when reaching a physically stressful period. This “high” is the physiological reaction to the release of endorphins – the masking of pain by a substance that mimics morphine. When people self-injure, the same process takes place. Endorphins are released which limit or block the amount of physical pain that’s experienced. Sometimes people who intentionally hurt themselves will even say that they felt a “rush” or “high” from the act. Given the role of endorphins, this makes perfect sense” (Oct 22, 2009).

Please click on the link for the full article Myths and Misconceptions of Self-Injury: Part II | Psychology Today Australia

The first step is to distinguish between self-harming and suicidal behaviour by paying attention to a person’s underlying motivation. When working with self-harming behaviour it is important to remember that this behaviour serves a purpose. In collaboration with the client, try to identify what problem self-harm solves for the client. For example, from the client’s perspective:

• To make me feel real (counteracts dissociation)
• To punish me (temporarily lessens guilt or shame)
• To stop me from feeling (when strong feelings are too dangerous)
• To mark the body (to show externally the internal scars)
• To let something bad out (symbolic way to try to get rid of shame, pain, etc.)
• To remember
• To keep from hurting someone else (to control my behaviour and my anger)
• To communicate (to let someone know how bad the pain is)
• To express anger indirectly (to punish someone without getting them angry at me)
• To reclaim control of the body (this time I’m in charge)
• To feel better

Tips for helping yourself in the moment
It can be hard for people who self-harm to stop it by themselves. That’s why it’s important to get further help if needed; however, the ideas below may be helpful to start relieving some distress:

• Intense exercise for 30 seconds, 30 second break, repeat, up to 15 minutes – Exercising intensely will help your body mitigate unpleasant energy that can sometimes be stored from strong emotions. Transfer this energy by running, walking at a fast pace, doing jumping jacks, etc. Exercise naturally releases endorphins which will help combat any negative emotions like anger, anxiety, or sadness.
• Delay — put off self-harming behaviours until you have spoken to someone.
• Distract — do some exercise, go for a walk, play a game, do something kind for yourself, play loud music or use positive coping strategies.
• Deep breathing — or other relaxation methods.
• Cool your body temperature – Cooler temperatures decrease your heart rate (which is usually faster when we are emotionally overwhelmed). You can either splash your face with cold water, take a cold (but not too cold) shower, or if the weather outside is chilly you can go outside for a walk. Another idea is to take an ice cube and hold it in your hand or rub your face with it.
• Listen to loud music
• Call someone you trust or one of the services available like LifeLine 13 11 14, MensLine Australia 1300 78 99 78 and BeyondBlue 1300 22 4636 [see below].
• You could write an email to yourself to express your emotions, or journal your feelings, if that’s something that might be effective for you.
• Watch humorous Youtube clips

New, healthier coping strategies may not be as effective as the one you’re trying to replace so it may take practice. Bring lots of compassion to yourself, okay.

You may find that some of these strategies work in some situations but not others, or you may find that you need to use a combination of these. It’s important to find what works for you. Also, remember that these are not long-term solutions to self-harm but rather, useful short-term alternatives for relieving distress.