• The OAD Clinic

Exploring the Mechanism of Maintenance Therapy

Updated: Jul 16, 2020

Understanding Opioids

Over the past few decades, much has been revealed about opioid dependence that has shaped our comprehension of addiction as a chronic disease. Opioid drugs activate specific opioid receptors (mu, kappa, and delta in the spinal cord and GIT system. Initially, when heroin or other opioids derivatives are consumed, activation of these receptors in the human body induces euphoric effects. Subsequent doses will quickly lead to tolerance – the need for increasingly higher doses to produce the same effect – and physical dependence. Currently, the studies reveal that tolerance is a result of a reduction in either the number or the responsivity of opioid receptor



What are Opioids?

Opioids are a class of drugs naturally occurring in the opium poppy plant and that act on the endogenous receptors in the human body to produce a variety of effects, including the relief of pain, euphoria and GIT effects.


What do opioids do?

The opioid drugs, characterised by morphine, can potentially produce profound analgesia, physical dependence, mood changes, tolerance along with a hedonic ('rewarding') effect which may lead to dependence or compulsive drug use. The receptors for opioids are found both in the central and peripheral nervous systems. Within the central nervous system, opioid receptors are widely spread in the spinal cord. In the peripheral nervous system, opioid receptors are located within the wall of the gut– responsible for the powerful constipating effects. Receptors in peripheral tissues such as joints seem to regulate inflammation.



Mechanism of Opioid Dependence

Opioid dependence is a neurobehavioral disorder characterised by a repeated, compulsive seeking or use of opioid medication. The predisposition for developing opiate addiction depends on the complex interaction between genetics, environmental factors, and the pharmacological effects of opiates. Environmental factors like availability of opiates from an early age, perceived risk of opiate use, psychosocial factors, and learned coping strategies all regulate the risk of developing an opiate addiction. Researchers also reveal an association between post-traumatic stress disorder and opiate addiction with an over-representation in the prevalence of this disorder in opiate addicts compared to the control population.

Opioid dependence is accompanied by well-described physical dependence with withdrawal syndrome and tolerance. Opiate addiction includes not only abuse of illicit heroin and other opium derivatives, but also the less commonly recognised problem of misuse and chronic abuse of prescription opioid pain relief medications, such as oxycodone, hydrocodone, codeine, etc.

Drug dependence is referred to a drug-induced clinical state in which, in which drug cessation results in physical and/or psychological withdrawal symptoms. Like many definitions, this is a blurry one.



Underpinnings of the behavioural disease state of opioid dependence

One addiction theory, including that of Robbins, Everitt, Wise, Berridge, Kalivas, Robinson, and Piazza stems from many decades of addiction research. This theory proposes the 3 steps model for the development of opioid dependence:

1st step: development of a reward learning process with drug consumption.

2nd step: escalated drug use in vulnerable individuals with hypo-dopaminergic systems and impaired prefrontal cortex inhibitory control.

3rd step: This step leads to the addiction phenotype, is described as a result of allostatic drug-induced changes in reward circuitry in your neurons which result in a strong desire for drugs (incentive-sensitisation).

This model emphasises positive reinforcement. The driver for addiction seems to be the modified reward circuitry and loss of inhibitory control, with the inference of altered plasticity of synapses in cortical-striatal neuronal circuits and switching from goal-directed to habitual circuitry.


Opioid withdrawal syndrome – What are the symptoms?

Short-acting opioids (e.g. heroin): withdrawal symptoms ensue within 8-24 hours after last use; the phase lasts for 4-10 days.

Long-acting opioids (e.g. methadone): withdrawal symptoms ensue within 12-48 hours after last use; the phase lasts for 10-20 days.


Symptoms include:

  • Nausea and vomiting

  • Anxiety

  • Insomnia

  • Hot and cold flushes

  • Perspiration

  • Muscle cramps

  • Watery discharge from eyes and nose

  • Diarrhoea


What is Opioid Maintenance Therapy?

The primary driver of ongoing drug use is the negative reinforcement of withdrawal symptoms. Several strategies to relieve opiate withdrawal symptoms have been evaluated. An integrated global therapeutic approach towards pharmacotherapeutic decisions for opioid dependence should be adopted. This will include psychosocial support, focusing on the individual’s functional recovery. In this respect, Opioid Maintenance Treatments (OMTs) remains the gold standard medication for opioid dependence. While opioid medications are generally indicated for treating pain, when used as OMTs, they have their specific indication and their particular criteria of use. Methadone, buprenorphine, and naltrexone are each approved for the long-term treatment of opiate addiction.