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The Science of Opioid Addiction






Addiction is a powerful physiological process … not a weakness of character or lack of discipline. Doctors, lawyers, judges, pastors, star athletes, CEO's, and heads of state have all experienced the gripping reality of a personal opioid addiction. 


Opioid dependency is classified as a true medical condition and is the direct result of dramatic brain structure changes. Once these brain structure changes take hold, an individual is no longer left with an easy choice to "simply not use", but is faced with an overpowering & persistent compulsion to feed an opioid drug hunger. No one wants to become addicted.


This overpowering urge is a phenomenon that most non-addicted people have difficulty understanding. People often naively ask "Why can't they just stop?" If it were that easy, they would! For an opioid dependent individual, the overpowering urge to use is very similar to a typical person experiencing extreme hunger after not eating for a prolonged period of time. The longer one goes without food, the more intense becomes their physical discomfort, and the hungry person becomes sharply focused on finding something to eat. This is a powerful physiological drive that blocks out other goals & considerations … until the need is met.


Another illustration is a person severely dehydrated and overcome with the desire to take in fluids. When they get to water, they rapidly gulp it down trying to satisfy their extreme thirst. Yet another example is the powerful sleep mechanism which kicks in after many hours wide awake. If you have ever watched someone fight sleep, you will inevitably see them give in to sleep as the body's physiological need overcomes the individual's intention to remain awake. And such is the case with a physiological dependency on opioids. The drive to use becomes increasingly powerful and eventually overwhelms the addicted individual.


Due to structural changes within the brain, the brain begins to crave opiates like people crave food, water, and sleep. And just as someone becomes intensely symptomatic when deprived of food, water, or sleep, the opioid dependent person becomes increasingly sick from opioid withdrawal, and desperate to end their physical discomfort.


States of physical deprivation hijack normal brain circuitry and force an individual to seek relief.


This is a basic human survival mechanism driven by powerful physiological forces.


 Cocaine addict

How Addiction Begins

Addiction is a very simple process in genesis. It begins when a person decides they “like” a drug rather than need a drug.


Addiction may begin with a legitimate opioid prescription for temporary pain relief, or brief experimental use for recreational purposes (such as taking a friend's pain pill). The individual discovers that the opiate/opioid successfully controls pain or provides a sense of euphoria or pleasure. As use of the opioid continues, cell adaptation occurs and tolerance to the opioid begins to grow. This requires larger amounts of the opioid in order to achieve the same effect. For some people, a physical dependency can come about quickly. For others, it may take longer.


Once physically "hooked", a person will experience uncomfortable withdrawal symptoms as the effect of the opioid wears off. An intense drug craving develops. The person's discomfort is immediately relieved by taking more of the drug. They do this, and the addictive cycle evolves into a long term problem.



Opioid Addiction Progression


A loss of life focus occurs in opioid addiction progression. As a tolerance to opioids builds, users must take more of the drug to achieve the same effect. Preoccupation (or mental preoccupation) is a symptom of addiction progression in which thinking about opiate use and planning for opiate use begin to dominate conscious thought & waking time. Once full blown physical withdrawal emerges, mental preoccupation can become so overpowering that the individual's life becomes replaced by daily craving for opiates and the need to obtain them.





How Do Opiates Work?


The brain and body have numerous opiate receptor sites, which when activated, increase feelings of pleasure/relaxation and decrease feelings of pain. Three regions in the brain and nervous system are specifically affected by opiates:


The Limbic System (includes the hippocampus, amygdala, hypothalamus, and other structures) – Controls human emotion, behaviour, long term memory, sense of smell. Opiate effect is primarily one of producing pleasure, relaxation, and feelings of well-being.

The Brainstem (includes the medulla oblongata, pons, and midbrain) – Regulates vital functions such as breathing and cardiovascular system control, alertness, and consciousness. Opiate effect here is to slow breathing, stop coughing, and lessen feelings of pain.

The Spinal Cord (a thin, tubular column of nerves which extend downward from the medulla oblongata) – Serves as a conduit for motor and sensory messages and a centre for coordinating reflexes. Opiate effect here is to decrease feelings of pain.







Opiate Receptors


There are three identified types of opiate receptors found in the body. They are the mu, delta, and kappa receptors primarily located in the brain, spinal cord, and digestive tract. Each of the receptor varieties serve specific functions with the mu receptors predominantly responsible for pleasure effects and pain relief (analgesia) when activated.


As opiates enter the bloodstream, they bind with opiate receptors in the brain, leading to euphoric effects and pain reduction. For the opiate dependent person, uncomfortable withdrawal symptoms begin to subside and the individual experiences both physical and emotional relief.


Methadone, compared with other opioids of addiction, is a long lasting medication that remains present in the body much longer than heroin or other commonly prescribed pain pills. This means that methadone is available to bind with opiate receptors for a longer duration thus producing extended relief from painful withdrawal symptoms. This relief from withdrawal sickness allows the individual to resume normal daily activities and responsibilities.


An added benefit of methadone is that it blocks the effects of other opiates and consequently discourages opiate misuse. Since methadone occupies the opiate receptor sites for an extended period of time, using other opiates becomes pointless because there are no available opiate receptors to be activated. This "blocking" effect is most effective once a client is on a stable methadone dose, and is a recovery-enhancing benefit of methadone maintenance treatment (MMT).



The Opioid Maintenance Treatment Program:
Methadone, Suboxone, Subutex




“Addiction is defined as a chronic, relapsing disease that is characterized by compulsive drug seeking and use, despite harmful consequences.


It is considered a disease because drugs change the brain - they change its structure and how it works.


These changes can be long lasting, and can lead to the harmful behaviours seen in people who abuse drugs.



Addiction is similar to other diseases, such as heart disease. Both disrupt the normal, healthy functioning of the underlying organ, have serious harmful consequences, are preventable, treatable, and if left untreated, can last a lifetime.”

Source: National Institute on Drug Abuse (NIDA)







Methadone / Suboxone Maintenance Treatment Programs are available worldwide. The governments of many countries try to help their citizens recover from one of teh most dangerous, destructive and lethal diseases on the planet by providing medicines such as Suboxone, Subutes and Methadone.


For example, they exist even in bastions of conservatism such as the USA. The Mount Sinai Beth Israel Program is the largest non-profit methadone clinic in the United States, has been in operation for more than 40 years, with 18 clinics throughout Manhattan and Brooklyn.


Methadone maintenance has proven to be an invaluable tool for the effective treatment and rehabilitation of opioid-addicted individuals.


Breaking an opioid addiction can be extremely difficult. Methadone / Suboxone maintenance is not a cure, but a treatment that can be very effective if taken properly. Methadone / Suboxone are a long-acting, synthetic medication which, when used in maintenance treatment, will:



There are multiple chemical dependency programs such as:

Outpatient Programmes :such as that available through the Toombul clinic.

Inpatient detoxification,

Inpatient rehabilitation and

Outpatient programs such as ambulatory detoxification services.



The Mission for All Governments is to provide the highest quality addiction services to opioid-addicted individuals with an emphasis to good relationships, sympathetic staff encouraging patient's self-reliance and supporting their dignity.






help addiction



Benzodiazepines: it's time to return to the evidence
Published online by Cambridge University Press:  12 October 2020

We propose that discussions of benzodiazepines in the current psychiatric literature have become negatively biased and have strayed from the scientific evidence base. We advocate returning to the evidence in discussing benzodiazepines and adhering to clear definitions and conceptual rigour in commentary about them.

When benzodiazepine anxiolytics were first introduced in the 1960s they were viewed as a liability-free alternative to barbiturates and meprobamate and were prescribed widely to patients with complaints of anxiety. After a decade of experience, it had become clear that benzodiazepines could be abused, and the pendulum began to swing towards suspicion of them. It is now commonly believed that they are dangerous drugs, prone to abuse and addiction. Treatment guidelines caution against their use as first-line or long-term therapy. It has become almost standard for clinical publications about benzodiazepines to issue warnings about dependence, abuse, addiction, tolerance or dangerousness, even when their central topic is an unrelated matter. Clinicians who advocate use of benzodiazepines may risk opprobrium from peers and institutions.
The literature and diagnostic classifications such as the DSM and ICD use varying terminology when describing substance-use disorders. Here we differentiate between abuse (taking a drug to achieve an appetitive effect, or ‘high') and misuse (any use that deviates from the way a medication has been prescribed).
A reminder of what the evidence tells us
The bulk of scientific literature on benzodiazepine safety, dependence and misuse tells a different story. Although demonstrating a range of potential liabilities, including cognitive and psychomotor impairment, possible risk in pregnancy and severe and/or prolonged withdrawal syndromes, it does not confirm that these medications are primary drugs of abuse or gateway drugs leading to other substance abuse. The database was scrutinised in the 1980s and 1990s in a series of extensive reviews, including a volume commissioned and published by the American Psychiatric Association. In aggregate, they comprise over 2000 literature citations, dealing with both animal and human studies bearing on abuse, misuse and dangerousness of benzodiazepines.13 Their authors conclude that benzodiazepines ‘do not strongly reinforce their own use and are not widely abused drugs. When abuse does occur, it is almost always among persons who are also abusing alcohol, opiates or other sedative hypnotics’2 and that ‘epidemiological studies of various populations of drug abusers have often found rates of nonmedical use of benzodiazepines that exceed those found in the general population [but] the preponderance of the extensive use of benzodiazepines is directed by physicians for disorders in which these drugs have proven therapeutic effect’.3 Although co-abuse of benzodiazepines has risen in the context of the opioid epidemic, there has been no newer evidence suggesting that either benzodiazepine abuse or any other substance abuse has its genesis in prescribed treatment for general (i.e. non-substance-abusing) patients. In his 2005 review of benzodiazepine abuse and dependence, O'Brien states, ‘benzodiazepines are usually a secondary drug of abuse – used mainly to augment the high received from another drug or to offset the adverse effects of other drugs. Few cases of addiction arise from the legitimate use of benzodiazepines’.4 Although most of the literature on this topic is not recent, neither is it outdated; it is simply ignored.
Reasons for the bias against benzodiazepines
Why bias against a safe and useful class of medications has become so entrenched is not entirely clear and is itself a subject worthy of investigation. One factor may be that major pharmaceutical companies long ago abandoned benzodiazepines in favour of antidepressants, which we believe has had a substantial influence on practitioners and has left benzodiazepines with few people to speak up for them. Concern about co-abuse of benzodiazepines by opioid abusers, with potentially lethal consequences, may be another factor motivating physicians to avoid them. In this climate of opinion, discussions about benzodiazepines often blur important distinctions about their clinical pharmacology or describe them in inaccurately pejorative terms. We discuss below

five instances of unfounded beliefs about benzodiazepines that we believe have been especially detrimental.

  1. (a) Benzodiazepines prescribed for anxiety disorders are likely to be abused. Benzodiazepines have a short latency of onset to calming or sedating effects, which may make them attractive to people who abuse substances. However, they are not prone to being abused by those with no such history. Conflating risk in these two populations stigmatises people with anxiety disorders and deprives them of treatment that might restore them to more functional lives.
  2. (b) Patients who misuse benzodiazepines are on a spectrum of drug abuse and are at risk of proceeding to frank abuse or addiction. Misuse is defined as any use of a medication that deviates from the way it has been prescribed by a clinician – including taking extra doses or taking less medication than prescribed.5 Addiction (called dependence in ICD-10) is defined by a cluster of behaviours that includes drug-taking to achieve appetitive effects (i.e. a high), preoccupation with the substance in question, temporary satiation, loss of control and persistent use despite negative consequences. Misuse of benzodiazepines is common, estimated at 17% of overall use.5 However, the great majority of people who deviate from doctors’ prescriptions of them are trying to control symptomatic distress, not to get high,5 and there is no evidence that misuse is likely to lead to abuse. Abuse and addiction should be addressed by substance abuse treatment; misuse is a more heterogeneous phenomenon that may involve suboptimal prescribing, poor doctor–patient communication, and patients inappropriately attempting to eradicate all negative affect with medication. However, alarmed clinicians who automatically view patients who deviate from their instructions as medication abusers may demand that they taper off benzodiazepines, with detrimental consequences.
  3. (c) Patients prescribed benzodiazepines tend to escalate their doses, which should preclude long-term use. There is a common belief that long-term benzodiazepine treatment is associated with tolerance to their anxiolytic effects and consequent dose escalation. The accumulated evidence is to the contrary: long-term treatment is associated with maintenance of therapeutic benefits, and no dose escalation. Tolerance does develop to the sedating and psychomotor effects of benzodiazepines, however.2 Failure to make this distinction may be the basis for withholding benzodiazepines, or for withdrawing them from patients who have been doing well on them during acute treatment.

  4. (d) Benzodiazepines are dangerous in overdose. Benzodiazepines alone are among the safest of psychotropic medications, with lethal dose LD50 estimates for most in the range of thousands of mg/kg. Even alprazolam, which may be more toxic, has an estimated LD50 range of 300–2000 mg/kg. Taken in conjunction with alcohol or opioids, they markedly raise the lethality of these already dangerous substances. That benzodiazepines are safe for the vast majority of people with anxiety disorders for whom they are prescribed is obscured by commonly used phrases such as ‘benzodiazepine-related death’ to describe a lethal combination of opioids and benzodiazepines ingested by a polysubstance-abusing person.
  5. (e) Taking benzodiazepines long-term leads to dependence. The word ‘dependence’ almost invariably has pejorative connotation and may unfairly characterise patients when applied vaguely or inconsistently. As used in ICD-10, ‘drug dependence’ is essentially a syndrome of addiction. ‘Dependence’ may also be used to describe a physiological withdrawal syndrome, an entirely different phenomenon that occurs with many medications, and is not in itself a sign of addiction.4 People with anxiety disorders discontinuing chronic benzodiazepines may experience a syndrome that includes rebound anxiety, which clinicians may take as a reason to withhold long-term treatment. Dependence is commonly applied, without clear definition, to patients in long-term treatment with benzodiazepines who lack any of the behavioural characteristics of substance abuse. They may be labelled as dependent (or addicted or hooked) because of the potential for a withdrawal syndrome and told that they must deal with it by getting off their medication. It is not surprising that anxious patients summarily told that they are drug dependent and deprived of an effective medication have difficulty tapering off it. But their doctors may interpret their struggles as evidence that a benzodiazepine prescription was problematic to begin with.

A call to clinicians
It's time to return to the evidence about benzodiazepines and to conceptual rigour in interpreting it. Benzodiazepines are highly effective for treatment of anxiety disorders, but are not for everyone, have potential liabilities and are best used in conjunction with targeted psychotherapies. That polysubstance abuse often includes benzodiazepines, however, should not blind us to their appropriate use.

Distinctions between abuse, addiction/dependence, misuse and physiological dependence may be challenging, but they are supported by the evidence and are clinically important. Conflating these phenomena will perpetuate stigma against benzodiazepines, the clinicians who prescribe them and the patients who take them. We invite colleagues to engage in evidence-based reappraisal of the benefits and risks of these medications and to abandon aspects of conventional wisdom that do not stand up to such scrutiny.
This manuscript arose out of discussions among the members of the International Taskforce on Benzodiazepines, an informal collaborative group of academic clinicians (including the authors) who are interested in disseminating accurate information about and fostering appropriate use of these medications.
Author contributions
E.S. prepared the first draft and subsequent revisions; all other authors reviewed the drafts, commented, made editorial suggestions, and reviewed and approved the final draft.
Declaration of interest
The authors are members of the International Taskforce on Benzodiazepines. C.Z. was Chair of the American Psychiatric Association Task Force on Benzodiazepine Dependency and author of its report.
ICMJE forms are in the supplementary material, available online at https://doi.org/10.1192/bjp.2020.164.


Woods, JH, Katz, JL, Winger, G. Abuse liability of benzodiazepines. Pharmacol Rev 1987; 39: 251–413.Google ScholarPubMed

American Psychiatric Association Task Force on Benzodiazepine Dependency. Benzodiazepine Dependence, Toxicity, and Abuse: A Task Force Report of the American Psychiatric Association. APA, 1990.Google Scholar

Woods, JH, Katz, JL, Winger, G. Benzodiazepines: Use, abuse, and consequences. Pharmacol Rev 1992; 44: 151–347.Google ScholarPubMed

O'Brien, CP. Benzodiazepine use, abuse, and dependence. J Clin Psychiatry 2005; 66(suppl 2): 28–33.Google ScholarPubMed

Maust, DT, Lin, LL, Blow, FC. Benzodiazepine use and misuse among adults in the United States. Psych Services 2019; 70: 97–106.CrossRefGoogle ScholarPubMed


Anti-anxiety drugsanxiety disorderscomorbiditydrug interactions and side-effectsdrugs of dependence

The British Journal of Psychiatry , Volume 218 , Issue 3 , March 2021 , pp. 125 - 127
DOI: https://doi.org/10.1192/bjp.2020.164[Opens in a new window]
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Copyright © The Author(s), 2020. Published by Cambridge University Press on behalf of the Royal College of Psychiatrists.


Edward Silberman
Richard Balon,
Vladan Starcevic,
Richard Shader,
Fiammetta Cosci,
Giovanni A. Fava,
Antonio E. Nardi
Carl Salzman and
Nicoletta Sonino








Opioid substitution therapy and HIV



Correspondence to Michelle Kermode
Bulletin of the World Health Organization 2011; 89:243-243. doi: 10.2471/BLT.11.086850



Michelle Kermode a, Nick Crofts a, M Suresh Kumar b & Jimmy Dorabjee c

a. Nossal Institute for Global Health, University of Melbourne, 161 Barry Street, Carlton, Vic., 3010, Australia.

b. Chennai, India.

c. Asian Network of People Who Use Drugs, Centre for Harm Reduction, Melbourne, Australia.




Approximately 10% of new HIV infections worldwide are attributable to injecting drug use, often of an opiate such as heroin.

Despite the evidence of effectiveness, it is estimated that only 8% of injecting drug users globally currently receive opioid substitution therapy – even less in developing countries.


There is substantial global inequity in access – for example, 90% of injecting drug users in the United Kingdom of Great Britain and Northern Ireland and 69% in Australia are receiving such therapy; compared with 3% in China and India, and none in the Russian Federation, where opioid substitution therapy is not available.

  • Opioid substitution therapy is endorsed by the Joint United Nations Programme on HIV/AIDS, the United Nations Office on Drugs and Crime and the World Health Organization
  • Methadone and buprenorphine are on its Essential Medicines list.


stop addiction

Even among those involved in HIV prevention and care there is often limited understanding of addiction and of the role of opioid substitution therapy as treatment. Opiate dependence is a chronic relapsing condition with sometimes catastrophic effects for individuals, families and communities. This is only amplified in resource-poor settings. Opioid substitution therapy is not a cure for drug dependence – it is a therapy for management of a chronic condition. Some clients may need therapy for years and some for their entire life. One of the most consistent findings in both high-income and resource-poor settings is that the more time injecting drug users spend on opioid substitution therapy, the better the outcomes and the less they are likely to engage in high risk behaviours.












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