Substance dependence

The human body can turn against its own owner, creating a biological trap that makes stopping a drug feel physically impossible. This phenomenon, known as substance dependence, is not merely a lack of willpower but a biopsychological state where functionality becomes dependent on the re-consumption of a psychoactive substance. When an individual develops this adaptive state, the discontinuation of the drug results in withdrawal symptoms that range from physical somatic distress to emotional and motivational turmoil. The body, having adapted to the constant presence of the substance, reacts with chemical and hormonal imbalances if the drug is not reintroduced, creating a cycle where the drug is used to escape the very state the drug created. This mechanism of negative reinforcement ensures that the user continues to consume the substance not necessarily for pleasure, but to avoid the unpleasant state of withdrawal. Infants are not immune to this biological reality, as neonatal abstinence syndrome can cause severe and life-threatening effects in babies born to mothers dependent on substances like alcohol. The dependence potential of a drug varies from substance to substance and from individual to individual, influenced by dose, frequency, pharmacokinetics, route of administration, and time. A study published in The Lancet compared the harm and dependence liability of twenty drugs, using a scale from zero to three to measure physical dependence, psychological dependence, and pleasure. Heroin and morphine scored a perfect 3.0 across all categories, while tobacco showed a mean score of 2.21 with a psychological dependence score of 2.6. The capture rates, which enumerate the percentage of users who reported becoming dependent, revealed that 31.9% of tobacco users became dependent, compared to 23.1% of heroin users and 15.4% of alcohol users. These statistics highlight that the most rewarding drugs are not always the most addictive, and the most addictive drugs are not always the most rewarding in terms of pleasure.

The Brain's Rewiring

Beneath the surface of behavior lies a complex biological machinery that rewires the brain to ensure survival of the addiction. Two factors have been identified as playing pivotal roles in psychological dependence: the neuropeptide corticotropin-releasing factor and the gene transcription factor cAMP response element binding protein. The nucleus accumbens, a specific brain structure, is implicated in the psychological component of drug dependence. In this region, CREB is activated by cyclic adenosine monophosphate immediately after a high, triggering changes in gene expression that affect proteins such as dynorphin. These dynorphin peptides reduce dopamine release into the nucleus accumbens by temporarily inhibiting the reward pathway. A sustained activation of CREB thus forces a larger dose to be taken to reach the same effect, while leaving the user feeling generally depressed and dissatisfied, and unable to find pleasure in previously enjoyable activities. This state often leads to a return to the drug for another dose, creating a self-perpetuating cycle of dependence. In addition to CREB, it is hypothesized that stress mechanisms play a significant role in dependence. Koob and Kreek hypothesized that during drug use, the activation of the hypothalamic-pituitary-adrenal axis and other stress systems in the extended amygdala influences the dysregulated emotional state associated with psychological dependence. They found that as drug use escalates, so does the presence of CRF in human cerebrospinal fluid. In rat models, the separate use of CRF inhibitors and CRF receptor antagonists both decreased self-administration of the drug of study. Other studies in this review showed dysregulation of other neuropeptides that affect the HPA axis, including enkephalin which is an endogenous opioid peptide that regulates pain. It also appears that mu-opioid receptors, which enkephalin acts upon, is influential in the reward system and can regulate the expression of stress hormones. Increased expression of AMPA receptors in nucleus accumbens medium spiny neurons is a potential mechanism of aversion produced by drug withdrawal. Physical dependence involves the upregulation of the signal transduction pathway in the locus coeruleus, which has been implicated as the mechanism responsible for certain aspects of opioid-induced physical dependence. The temporal course of withdrawal correlates with locus coeruleus firing, and administration of alpha-2 agonists into the locus coeruleus leads to a decrease in locus coeruleus firing and norepinephrine release during withdrawal. A possible mechanism involves upregulation of NMDA receptors, which is supported by the attenuation of withdrawal by NMDA receptor antagonists. Physical dependence on opioids has been observed to produce an elevation of extracellular glutamate, an increase in NMDA receptor subunits NR1 and NR2A, phosphorylated CaMKII, and c-fos. Expression of CaMKII and c-fos is attenuated by NMDA receptor antagonists, which is associated with blunted withdrawal in adult rats, but not neonatal rats. While acute administration of opioids decreases AMPA receptor expression and depresses both NMDA and non-NMDA excitatory postsynaptic potentials in the nucleus accumbens, withdrawal involves a lowered threshold for long-term potentiation and an increase in spontaneous firing in the nucleus accumbens.

Common questions

What is substance dependence and how does it affect the body?

Substance dependence is a biopsychological state where functionality becomes dependent on the re-consumption of a psychoactive substance. When an individual develops this adaptive state, the discontinuation of the drug results in withdrawal symptoms that range from physical somatic distress to emotional and motivational turmoil.

Which drugs scored the highest on dependence and harm scales in The Lancet study?

Heroin and morphine scored a perfect 3.0 across all categories of physical dependence, psychological dependence, and pleasure. Tobacco showed a mean score of 2.21 with a psychological dependence score of 2.6.

How did the DSM-5 change the classification of substance dependence compared to the DSM-IV?

The Diagnostic and Statistical Manual of Mental Disorders released in 2013 eliminated the distinction between substance abuse and substance dependence, replacing them with the single diagnosis of substance use disorders. This change was implemented because the tolerance and withdrawal that previously defined dependence are actually very normal responses to prescribed medications that affect the central nervous system.

What are the differences between treatment goals in the United States and Europe for substance dependence?

In the United States and many developing countries, the goal of commissioners of treatment for drug dependence is generally total abstinence from all drugs. Other countries, particularly in Europe, argue the aims of treatment for drug dependence are more complex, with treatment aims including reduction in use to the point that drug use no longer interferes with normal activities such as work and family commitments.

When was morphine isolated and how did it impact addiction history in the United States?

Morphine was isolated in the early 19th century and came to be prescribed commonly by doctors, both as a painkiller and as an intended cure for opium addiction. Addiction to opium became widespread among soldiers fighting in the Civil War, who very often required painkillers and thus were very often prescribed morphine.

The Shifting Diagnosis

The medical understanding of substance dependence has undergone a radical transformation, moving from a rigid classification system to a more nuanced view of human behavior and biology. The International Classification of Diseases classifies substance dependence as a mental and behavioural disorder, yet the Diagnostic and Statistical Manual of Mental Disorders released in 2013 eliminated the distinction between substance abuse and substance dependence, replacing them with the single diagnosis of substance use disorders. This change was implemented because the tolerance and withdrawal that previously defined dependence are actually very normal responses to prescribed medications that affect the central nervous system and do not necessarily indicate the presence of an addiction. The DSM-IV defined substance dependence with physiological dependence, evidence of tolerance or withdrawal, or without physiological dependence, listing specific codes for alcohol dependence, opioid dependence, sedative dependence, cocaine dependence, cannabis dependence, amphetamine dependence, hallucinogen dependence, inhalant dependence, polysubstance dependence, phencyclidine dependence, and other substance dependence. The DSM-5 removed these distinctions to reflect the reality that tolerance and withdrawal are expected physiological responses to many medications, not just signs of addiction. This shift in terminology reflects a deeper understanding of the difference between dependence and addiction. Substance dependence is a biopsychological situation whereby an individual's functionality is dependent on the necessitated re-consumption of a psychoactive substance because of an adaptive state that has developed within the individual from psychoactive substance consumption that results in the experience of withdrawal. An addictive drug is a drug which is both rewarding and reinforcing, but drug addiction is defined as compulsive, out-of-control drug use, despite negative consequences. Delta FosB, a gene transcription factor, is now known to be a critical component and common factor in the development of virtually all forms of behavioral and drug addictions, but not dependence. This distinction highlights that while dependence is a physiological adaptation, addiction involves a deeper, more complex psychological and behavioral compulsion. The DSM-5 change was driven by the realization that the presence of tolerance and withdrawal does not automatically equate to addiction, as these are normal responses to many prescribed medications that affect the central nervous system. This reclassification has had profound implications for how patients are treated and how society views the nature of substance use disorders.

The Treatment Divide

The global response to substance dependence has fractured into two distinct philosophies, each with its own goals and outcomes. In the United States and many developing countries, the goal of commissioners of treatment for drug dependence is generally total abstinence from all drugs. Other countries, particularly in Europe, argue the aims of treatment for drug dependence are more complex, with treatment aims including reduction in use to the point that drug use no longer interferes with normal activities such as work and family commitments. These European approaches also focus on shifting the addict away from more dangerous routes of drug administration such as injecting to safer routes such as oral administration, reduction in crime committed by drug addicts, and treatment of other comorbid conditions such as AIDS, hepatitis and mental health disorders. These kinds of outcomes can be achieved without eliminating drug use completely. Drug treatment programs in Europe often report more favorable outcomes than those in the US because the criteria for measuring success are functional rather than abstinence-based. The supporters of programs with total abstinence from drugs as a goal believe that enabling further drug use means prolonged drug use and risks an increase in addiction and complications from addiction. Residential drug treatment can be broadly divided into two camps: 12-step programs and therapeutic communities. 12-step programs are a nonclinical support-group and spiritual-based approach to treating addiction, with prominent examples including Alcoholics Anonymous, Narcotics Anonymous, and Pills Anonymous. Therapy typically involves the use of cognitive-behavioral therapy, an approach that looks at the relationship between thoughts, feelings and behaviors, addressing the root cause of maladaptive behavior. Cognitive-behavioral therapy treats addiction as a behavior rather than a disease, and so is subsequently curable, or rather, unlearnable. Cognitive-behavioral therapy programs recognize that, for some individuals, controlled use is a more realistic possibility. One of many recovery methods are 12-step recovery programs, with prominent examples including Alcoholics Anonymous, Narcotics Anonymous, and Pills Anonymous. They are commonly known and used for a variety of addictions for the individual addicted and the family of the individual. Substance-abuse rehabilitation centers offer a residential treatment program for some of the more seriously addicted, in order to isolate the patient from drugs and interactions with other users and dealers. Outpatient clinics usually offer a combination of individual counseling and group counseling. Frequently, a physician or psychiatrist will prescribe medications in order to help patients cope with the side effects of their addiction. Medications can help immensely with anxiety and insomnia, can treat underlying mental disorders such as depression, and can help reduce or eliminate withdrawal symptomology when withdrawing from physiologically addictive drugs. Some examples are using benzodiazepines for alcohol detoxification, which prevents delirium tremens and complications; using a slow taper of benzodiazepines or a taper of phenobarbital, sometimes including another antiepileptic agent such as gabapentin, pregabalin, or valproate, for withdrawal from barbiturates or benzodiazepines; using drugs such as baclofen to reduce cravings and propensity for relapse amongst addicts to any drug, especially effective in stimulant users, and alcoholics; using clonidine, an alpha-agonist, and loperamide for opioid detoxification, for first-time users or those who wish to attempt an abstinence-based recovery; or replacing an opioid that is interfering with or destructive to a user's life, such as illicitly-obtained heroin, dilaudid, or oxycodone, with an opioid that can be administered legally, reduces or eliminates drug cravings, and does not produce a high, such as methadone or buprenorphine. Opioid replacement therapy is the gold standard for treatment of opioid dependence in developed countries, reducing the risk and cost to both user and society more effectively than any other treatment modality for opioid dependence, and shows the best short-term and long-term gains for the user, with the greatest longevity, least risk of fatality, greatest quality of life, and lowest risk of relapse and legal issues including arrest and incarceration. In a survey of treatment providers from three separate institutions, the National Association of Alcoholism and Drug Abuse Counselors, Rational Recovery Systems and the Society of Psychologists in Addictive Behaviors, measuring the treatment provider's responses on the Spiritual Belief Scale, the scores were found to explain 41% of the variance in the treatment provider's responses on the Addiction Belief Scale. Behavioral programming is considered critical in helping those with addictions achieve abstinence. From the applied behavior analysis literature and the behavioral psychology literature, several evidence based intervention programs have emerged: behavioral marital therapy, community reinforcement approach, cue exposure therapy, and contingency management strategies. In addition, the same author suggests that social skills training adjunctive to inpatient treatment of alcohol dependence is probably efficacious. Community reinforcement has both efficacy and effectiveness data. In addition, behavioral treatment such as community reinforcement and family training have helped family members to get their loved ones into treatment. Motivational intervention has also shown to be an effective treatment for substance dependence. Alternative therapies, such as acupuncture, are used by some practitioners to alleviate the symptoms of drug addiction. In 1997, the American Medical Association adopted, as policy, the following statement after a report on a number of alternative therapies including acupuncture. In addition, new research surrounding the effects of psilocybin on smokers revealed that 80% of smokers quit for six months following the treatment, and 60% remained smoking free for 5 years following the treatment. Medical professionals need to apply many techniques and approaches to help patients with substance related disorders. Using a psychodynamic approach is one of the techniques that psychologists use to solve addiction problems. In psychodynamic therapy, psychologists need to understand the conflicts and the needs of the addicted person, and also need to locate the defects of their ego and defense mechanisms. Using this approach alone has proven to be ineffective in solving addiction problems. Cognitive and behavioral techniques should be integrated with psychodynamic approaches to achieve effective treatment for substance related disorders. Cognitive treatment requires psychologists to think deeply about what is happening in the brain of an addicted person. Cognitive psychologists should zoom in to neural functions of the brain and understand that drugs have been manipulating the dopamine reward center of the brain. From this particular state of thinking, cognitive psychologists need to find ways to change the thought process of the addicted person. There are two routes typically applied to a cognitive approach to substance abuse: tracking the thoughts that pull patients to addiction and tracking the thoughts that prevent them if so from relapsing. Behavioral techniques have the widest application in treating substance related disorders. Behavioral psychologists can use the techniques of aversion therapy, based on the findings of Pavlov's classical conditioning. It uses the principle of pairing abused substances with unpleasant stimuli or conditions; for example, pairing pain, electrical shock, or nausea with alcohol consumption. The use of medications may also be used in this approach, such as using disulfiram to pair unpleasant effects with the thought of alcohol use. Psychologists tend to use an integration of all these approaches to produce reliable and effective treatment. With the advanced clinical use of medications, biological treatment is now considered to be one of the most efficient interventions that psychologists may use as treatment for those with substance dependence. Another approach is to use medicines that interfere with the functions of the drugs in the brain. Similarly, one can also substitute the misused substance with a weaker, safer version to slowly taper the patient off of their dependence. Such is the case with Suboxone in the context of opioid dependence. These approaches are aimed at the process of detoxification. Medical professionals weigh the consequences of withdrawal symptoms against the risk of staying dependent on these substances. These withdrawal symptoms can be very difficult and painful at times for patients. Most will have steps in place to handle severe withdrawal symptoms, either through behavioral therapy or other medications. Biological intervention should be combined with behavioral therapy approaches and other non-pharmacological techniques. Group therapies including anonymity, teamwork and sharing concerns of daily life among people who also have substance dependence issues can have a great impact on outcomes. However, these programs proved to be more effective and influential on persons who did not reach levels of serious dependence. Vaccines are also being developed to combat addiction. TA-CD is an active vaccine developed by the Xenova Group which is used to negate the effects of cocaine, making it suitable for use in treatment of addiction. It is created by combining norcocaine with inactivated cholera toxin. TA-NIC is a proprietary vaccine in development similar to TA-CD but being used to create human anti-nicotine antibodies in a person to destroy nicotine in the human body so that it is no longer effective.

The Historical Epidemic

The phenomenon of drug addiction has occurred to some degree throughout recorded history, yet modern agricultural practices, improvements in access to drugs, advancements in biochemistry, and dramatic increases in the recommendation of drug usage by clinical practitioners have exacerbated the problem significantly in the 20th century. Improved means of active biological agent manufacture and the introduction of synthetic compounds, such as fentanyl and methamphetamine, are also factors contributing to drug addiction. For the entirety of US history, drugs have been used by some members of the population. In the country's early years, most drug use by the settlers was of alcohol or tobacco. The 19th century saw opium usage in the US become much more common and popular. Morphine was isolated in the early 19th century, and came to be prescribed commonly by doctors, both as a painkiller and as an intended cure for opium addiction. At the time, the prevailing medical opinion was that the addiction process occurred in the stomach, and thus it was hypothesized that patients would not become addicted to morphine if it was injected into them via a hypodermic needle, and it was further hypothesized that this might potentially be able to cure opium addiction. However, many people did become addicted to morphine. In particular, addiction to opium became widespread among soldiers fighting in the Civil War, who very often required painkillers and thus were very often prescribed morphine. Women were also very frequently prescribed opiates, and opiates were advertised as being able to relieve female troubles. Many soldiers in the Vietnam War were introduced to heroin and developed a dependency on the substance which survived even when they returned to the US. Technological advances in travel meant that this increased demand for heroin in the US could now be met. Furthermore, as technology advanced, more drugs were synthesized and discovered, opening up new avenues to substance dependency. The history of drug addiction is a story of medical progress turning into public health crisis, as the very tools designed to heal humanity became the instruments of its destruction. The isolation of morphine in the early 19th century marked a turning point in medical history, as doctors began to prescribe it widely for pain relief and even as a cure for opium addiction. The prevailing medical opinion at the time was that the addiction process occurred in the stomach, and thus it was hypothesized that patients would not become addicted to morphine if it was injected into them via a hypodermic needle. This hypothesis proved to be catastrophically wrong, as many people did become addicted to morphine. Addiction to opium became widespread among soldiers fighting in the Civil War, who very often required painkillers and thus were very often prescribed morphine. Women were also very frequently prescribed opiates, and opiates were advertised as being able to relieve female troubles. The Vietnam War era saw another surge in addiction, as many soldiers were introduced to heroin and developed a dependency on the substance which survived even when they returned to the US. Technological advances in travel meant that this increased demand for heroin in the US could now be met. Furthermore, as technology advanced, more drugs were synthesized and discovered, opening up new avenues to substance dependency. The history of drug addiction is a testament to the power of human ingenuity and the unintended consequences of medical progress.

The Demographic Divide

Internationally, the U.S. and Eastern Europe contain the countries with the highest substance abuse disorder occurrence, ranging from 5 to 6 percent, while Africa, Asia, and the Middle East contain countries with the lowest worldwide occurrence, ranging from 1 to 2 percent. Across the globe, those that tended to have a higher prevalence of substance dependence were in their twenties, unemployed, and men. The National Survey on Drug Use and Health reports on substance dependence/abuse rates in various population demographics across the U.S. When surveying populations based on race and ethnicity in those ages 12 and older, it was observed that American Indian/Alaskan Natives were among the highest rates and Asians were among the lowest rates in comparison to other racial/ethnic groups. When surveying populations based on gender in those ages 12 and older, it was observed that males had a higher substance dependence rate than females. However, the difference in the rates are not apparent until after age 17. Alcohol dependence or abuse rates were shown to have no correspondence with any person's education level when populations were surveyed in varying degrees of education from ages 26 and older. However, when it came to illicit drug use there was a correlation, in which those that graduated from college had the lowest rates. Furthermore, dependence rates were greater in unemployed populations ages 18 and older and in metropolitan-residing populations ages 12 and older. The National Opinion Research Center at the University of Chicago reported an analysis on disparities within admissions for substance abuse treatment in the Appalachian region, which comprises 13 states and 410 counties in the Eastern part of the U.S. While their findings for most demographic categories were similar to the national findings by NSDUH, they had different results for racial/ethnic groups which varied by sub-regions. Overall, Whites were the demographic with the largest admission rate, at 83 percent, while Alaskan Native, American Indian, Pacific Islander, and Asian populations had the lowest admissions, at 1.8 percent. The data reveals a complex web of social, economic, and demographic factors that influence substance dependence. The rates of substance dependence vary significantly across different racial and ethnic groups, with American Indian/Alaskan Natives having the highest rates and Asians having the lowest rates. The rates also vary by age, with males having a higher substance dependence rate than females, but the difference in the rates are not apparent until after age 17. The rates also vary by education level, with those that graduated from college having the lowest rates of illicit drug use. The rates also vary by employment status, with unemployed populations having higher dependence rates than employed populations. The rates also vary by region, with metropolitan-residing populations having higher dependence rates than non-metropolitan populations. The data also reveals disparities within admissions for substance abuse treatment, with Whites having the largest admission rate and Alaskan Native, American Indian, Pacific Islander, and Asian populations having the lowest admissions. These disparities highlight the need for targeted interventions that address the specific needs of different demographic groups. The data also reveals the importance of addressing the social and economic factors that contribute to substance dependence, such as unemployment and lack of access to education. The data also highlights the need for more research into the factors that contribute to substance dependence, particularly in underrepresented populations. The data also highlights the need for more effective treatment programs that address the specific needs of different demographic groups. The data also highlights the need for more research into the factors that contribute to substance dependence, particularly in underrepresented populations. The data also highlights the need for more effective treatment programs that address the specific needs of different demographic groups.

The Legal Paradox

Depending on the jurisdiction, addictive drugs may be legal, legal only as part of a government sponsored study, illegal to use for any purpose, illegal to sell, or even illegal to merely possess. Most countries have legislation which brings various drugs and drug-like substances under the control of licensing systems. Typically this legislation covers any or all of the opiates, amphetamines, cannabinoids, cocaine, barbiturates, benzodiazepines, anesthetics, hallucinogenics, derivatives and a variety of more modern synthetic drugs. Unlicensed production, supply or possession is a criminal offence. Although the legislation may be justifiable on moral or public health grounds, it can make addiction or dependency a much more serious issue for the individual: reliable supplies of a drug become difficult to secure, and the individual becomes vulnerable to both criminal abuse and legal punishment. It is unclear whether laws against illegal drug use do anything to stem usage and dependency. In jurisdictions where addictive drugs are illegal, they are generally supplied by drug dealers, who are often involved with organized crime. Even though the cost of producing most illegal addictive substances is very low, their illegality combined with the addict's need permits the seller to command a premium price, often hundreds of times the production cost. As a result, addicts sometimes turn to crime to support their habit. In the United States, drug policy is primarily controlled by the federal government. The Department of Justice's Drug Enforcement Administration enforces controlled substances laws and regulations. The Department of Health and Human Services' Food and Drug Administration serve to protect and promote public health by controlling the manufacturing, marketing, and distribution of products, like medications. The United States' approach to substance abuse has shifted over the last decade, and is continuing to change. The federal government was minimally involved in the 19th century. The federal government transitioned from using taxation of drugs in the early 20th century to criminalizing drug abuse with legislations and agencies like the Federal Bureau of Narcotics mid-20th century in response to the nation's growing substance abuse issue. These strict punishments for drug offenses shined light on the fact that drug abuse was a multi-faceted problem. The President's Advisory Commission on Narcotics and Drug Abuse of 1963 addressed the need for a medical solution to drug abuse. However, drug abuse continued to be enforced by the federal government through agencies such as the DEA and further legislations such as The Controlled Substances Act, the Comprehensive Crime Control Act of 1984, and Anti-Drug Abuse Acts. In the past decade, there have been growing efforts through state and local legislations to shift from criminalizing drug abuse to treating it as a health condition requiring medical intervention. 28 states currently allow for the establishment of needle exchanges. Florida, Iowa, Missouri and Arizona all introduced bills to allow for the establishment of needle exchanges in 2019. These bills have grown in popularity across party lines since needle exchanges were first introduced in Amsterdam in 1983. In addition, AB-186 Controlled substances: overdose prevention program was introduced to operate safe injection sites in the City and County of San Francisco. The bill was vetoed on the 30th of September 2018, by California Governor Jerry Brown. The legality of these sites are still in discussion, so there are no such sites in the United States yet. However, there is growing international evidence for successful safe injection facilities. The legal landscape of drug addiction is a complex and evolving field, with different jurisdictions taking different approaches to the issue. The legislation covers any or all of the opiates, amphetamines, cannabinoids, cocaine, barbiturates, benzodiazepines, anesthetics, hallucinogenics, derivatives and a variety of more modern synthetic drugs. Unlicensed production, supply or possession is a criminal offence. Although the legislation may be justifiable on moral or public health grounds, it can make addiction or dependency a much more serious issue for the individual. The illegality of drugs combined with the addict's need permits the seller to command a premium price, often hundreds of times the production cost. As a result, addicts sometimes turn to crime to support their habit. The United States' approach to substance abuse has shifted over the last decade, and is continuing to change. The federal government was minimally involved in the 19th century. The federal government transitioned from using taxation of drugs in the early 20th century to criminalizing drug abuse with legislations and agencies like the Federal Bureau of Narcotics mid-20th century in response to the nation's growing substance abuse issue. These strict punishments for drug offenses shined light on the fact that drug abuse was a multi-faceted problem. The President's Advisory Commission on Narcotics and Drug Abuse of 1963 addressed the need for a medical solution to drug abuse. However, drug abuse continued to be enforced by the federal government through agencies such as the DEA and further legislations such as The Controlled Substances Act, the Comprehensive Crime Control Act of 1984, and Anti-Drug Abuse Acts. In the past decade, there have been growing efforts through state and local legislations to shift from criminalizing drug abuse to treating it as a health condition requiring medical intervention. 28 states currently allow for the establishment of needle exchanges. Florida, Iowa, Missouri and Arizona all introduced bills to allow for the establishment of needle exchanges in 2019. These bills have grown in popularity across party lines since needle exchanges were first introduced in Amsterdam in 1983. In addition, AB-186 Controlled substances: overdose prevention program was introduced to operate safe injection sites in the City and County of San Francisco. The bill was vetoed on the 30th of September 2018, by California Governor Jerry Brown. The legality of these sites are still in discussion, so there are no such sites in the United States yet. However, there is growing international evidence for successful safe injection facilities. The legal landscape of drug addiction is a complex and evolving field, with different jurisdictions taking different approaches to the issue. The legislation covers any or all of the opiates, amphetamines, cannabinoids, cocaine, barbiturates, benzodiazepines, anesthetics, hallucinogenics, derivatives and a variety of more modern synthetic drugs. Unlicensed production, supply or possession is a criminal offence. Although the legislation may be justifiable on moral or public health grounds, it can make addiction or dependency a much more serious issue for the individual. The illegality of drugs combined with the addict's need permits the seller to command a premium price, often hundreds of times the production cost. As a result, addicts sometimes turn to crime to support their habit. The United States' approach to substance abuse has shifted over the last decade, and is continuing to change. The federal government was minimally involved in the 19th century. The federal government transitioned from using taxation of drugs in the early 20th century to criminalizing drug abuse with legislations and agencies like the Federal Bureau of Narcotics mid-20th century in response to the nation's growing substance abuse issue. These strict punishments for drug offenses shined light on the fact that drug abuse was a multi-faceted problem. The President's Advisory Commission on Narcotics and Drug Abuse of 1963 addressed the need for a medical solution to drug abuse. However, drug abuse continued to be enforced by the federal government through agencies such as the DEA and further legislations such as The Controlled Substances Act, the Comprehensive Crime Control Act of 1984, and Anti-Drug Abuse Acts. In the past decade, there have been growing efforts through state and local legislations to shift from criminalizing drug abuse to treating it as a health condition requiring medical intervention. 28 states currently allow for the establishment of needle exchanges. Florida, Iowa, Missouri and Arizona all introduced bills to allow for the establishment of needle exchanges in 2019. These bills have grown in popularity across party lines since needle exchanges were first introduced in Amsterdam in 1983. In addition, AB-186 Controlled substances: overdose prevention program was introduced to operate safe injection sites in the City and County of San Francisco. The bill was vetoed on the 30th of September 2018, by California Governor Jerry Brown. The legality of these sites are still in discussion, so there are no such sites in the United States yet. However, there is growing international evidence for successful safe injection facilities.