Writer: Chengzu Maxwell Xiang

The first time you take heroin will be the greatest moment of your life, perhaps only because everything else will be downhill from that moment. Heroin belongs to a class of drugs known as opioids, a class of natural, semi-synthetic, and synthetic drugs that include both prescription medications and illegal drugs. Natural opioids, such as morphine, codeine, opium, and thebaine are all made from the seed pods of the opium poppy plant. These natural substances are also known as opiates. Semi-synthetic opioids, such as heroin, oxycodone, hydrocodone, and oxymorphone, are made in laboratories by chemically processing natural opioids. Synthetic opioids, such as fentanyl, methadone, meperidine, and tramadol, are manufactured entirely in laboratories, with no natural ingredients. Opioids wildly differ in strength, or potency. For example, fentanyl is 50 to 100 times more potent than morphine, capable of causing deaths even in tiny doses. People take opioids for a wide variety of reasons, ranging from painkillers to recreational uses, making them invaluable for people suffering from chronic pain, being the only thing capable of giving them a semblance of a regular life. Yet at the same time, opioids incredibly addictive if misused, being found in the blood of over 80% of those who died from drug abuse in America in 2023 alone, making it over 338% deadlier than homicides and 103% deadlier than suicides. So how does opioid addiction develop, and why is it so hard to overcome?

Opioids are taken orally, via skin patch, under the tongue, or by infection, where it enters the bloodstream and travels throughout the body to the brain. Opioids bind to specific molecules called opioid receptors, also known as mu-opioid receptors (MORs). These receptors mediate the human body’s response to most hormones, neurotransmitters, drugs, and are involved in sensory perception of vision, taste, and smell. These receptors normally interact with naturally occurring molecules in the body to regulate essential functions, controlling pain, regulating breathing, and managing stress responses. Opioid receptors are found on nerve cells that send pain signals from the body to the brain, and when opioid drugs bind to these receptors, they trigger changes in nerve cells that can stop the transmission of pain signals in the spinal cord, dulling the perception of pain in the brain, making them highly effective pain medications. Additionally, opioid receptors are also found in the brain regions collectively known as the reward system. The body’s own opioid-like signaling molecules bind to those receptors in response to natural rewards, making us feel good in response to natural rewards, which encourages us to repeat the healthy behaviours that help us survive.

Opioids from both inside your body, endogenous, and outside your body, exogenous, both act upon opioid receptors, making you less aware of pain and slowing down your bodily functions, leading to slower heart and breathing rate, drowsiness, sedation, dry skin, and pinpoint pupils. However, endogenous opioids such as endorphins, are only released locally and act only in specific sites, leading to a more mild and localized response, while exogenous opioids act upon any cell they can bind to in the central nervous system, leading to a much stronger effect. In other words, exogenous opioids completely overpower the reward function of endogenous opioids, encouraging dramatic change within the brain, and combined with the negative feedback from withdrawal, people can become rapidly conditioned to opioids, increasing their desire and motivation to consume the drug. Long-term use of opioids causes many problems, including: depression, trouble concentrating and sleeping, sexual problems, serious constipation, lowered endorphin levels, and if used with other drugs, may also cause stomach bleeding or kidney and liver damage. 

In general, opioid administration causes a four-phase subjective effect. The first phase is the rush or rapid onset of euphoria that occurs seconds after injection. This is followed by the high, which causes feelings of joy and ease. The third phase is called the nod, which is characterized by feelings of calm and disinterest. During this phase, the user may feel no anxiety and engage in light sleep. The final phase is the straight phase, which is a period of normalcy. Once absorbed, opioids are capable of crossing the blood-brain barrier, and with the varying lipid solubilities of different opioids, some cross the blood-brain barrier faster than others. A prime example is heroin, which has greater lipid solubility than morphine, achieving peak concentrations in 5 minutes, while morphine peaks occur in about 20. The rapid onset of action is a large contributor to why opioids have the highest potential for addiction. Certain synthetic opioids such as fentanyl have a rapid onset combined with a potency hundreds of times greater than morphine. Prescription opioids, which are normally taken orally, tend to have a slower rate of absorption and longer onset of action. As users make the switch to heroin and fentanyl, the rush of euphoria increased alongside the potency, creating a stronger dependence on the drug and increasing the risk of overdose.

Opioid tolerance is established very quickly as well, with people building tolerance after just 2 to 3 doses. This leads to people needing more drugs to get the same high, increasing their chance of overdose and accelerating their journey to a street corner. Tolerance happens through changes at the cellular level. It is the result of the brain restoring balance after repeated overstimulation by a drug. As the balance is restored, neurons, synapses, and entire brain regions start to work differently. The brain has set a new normal, one that includes the effects of the drugs. And with this new normal, dependence quickly sets in, and you can no longer live independently without opioids. Not all effects develop tolerance at the same rate. Tolerance to pain relief and euphoria tends to develop at lower doses than respiratory depression. As users will typically escalate opioid use to achieve similar effects, long-term users often begin to develop a tolerance for respiratory depression as well. 

Opioid dependence is more likely to occur in people with a history of alcohol or other substance use, and opioid dependence while being pregnant may cause the baby to go through withdrawal symptoms after they’re born. Opioid dependence is characterized by an overwhelming need to acquire and use opioids. Addiction is easily developed as compulsive drug use will persist despite negative consequences. Opioid dependence is common and difficult to escape once established. Relapse is common. Heroin is the most notorious of abused opioids, although fentanyl and its derivatives have likely surpassed it. One of the reasons why opioid dependence is so strong is because withdrawal symptoms are unpleasant and often severe. Withdrawal symptoms are the inverse of drug effects, and the most notable symptom is hyperalgesia, or increased pain sensitivity. Long-term use of opioids can lead to opioid-induced hyperalgesia, where opioid pain medications increase pain instead of providing relief. 

Withdrawal symptoms also include dilated pupils, sweating, nausea and vomiting, diarrhea, aches and pains, low blood pressure and heart rate, insomnia, anxiety, hyperactivity, and depression. These symptoms occur at different times and can last for weeks or months, although peak withdrawal symptoms occur within the first 72 hours. An exception to this is precipitated withdrawal or withdrawal caused by the administration of an opioid antagonist such as naloxone. In this case, maximum withdrawal can occur within minutes.

Opioid overdose is severe and comes with many signs, most of which mimic the typical effects of the drug. Respiratory depression, pinpoint pupils, stomach and intestine spasms, drowsiness, disorientation, and loss of consciousness are all signs of an overdose, as well as a dry mouth, low blood pressure, and bluish-coloured lips and nails. When opioids are combined with other depressants, respiratory depression is intensified. Most deaths from opioid overdose are caused by respiratory failure. To reverse an opioid overdose, an opioid antagonist such as naloxone or naltrexone is administered. These drugs have a high affinity for opioid receptors and bind to them, displacing the opioid and reversing its effects. Opioid antagonists are commonly injected, although a naloxone nasal spray has been developed and approved by the FDA for emergency overdose treatment. Nasal sprays are easier to use and reduce the risk of emergency responders contracting bloodborne illnesses. Different opioids have different rates of overdose. An overdose on fentanyl can occur with as little as 2mg of the drug, and within seconds to minutes, reducing the window for emergency treatment. This has made fentanyl one of the most dangerous drugs in the recent opioid epidemic, not including the fact that many other drugs such as heroin and cocaine may be laced with lethal amounts of the drug, with over 42% of tested pills testing positive for 0.2mg to 5.1mg of fentanyl, which is over twice the lethal dose.

There are numerous methods for combating opioid dependence. One form of prevention strategy is to reformulate prescription opioids to make them harder to misuse. In the wake of the opioid epidemic, the manufacturers of OxyContinⓇ changed the dosage form to be harder to crush or dissolve. Most approaches involve treatment and relapse prevention, which can be done through a combination of drug therapies and psychotherapies. Psychotherapy is always required for the treatment of opioid use disorder. Dependence is more than just physical dependence, there remains a potent psychological and social triggers that can increase the risk of relapse. These complex conditions are best addressed by cognitive-behavioral therapy, contingency management, and family counseling. 

The most common form of drug therapy for opioid use disorder is drug replacement, which involves administering a safer opioid with weaker effects to mitigate withdrawal. One such drug is methadone (DolophineⓇ). It is slower-acting and longer lasting compared to heroin and morphine, and can be administered once a day. Methadone does not cause a rush, nor does it cause drowsiness or impairment of thinking, emotions, or sensations, yet despite these differences, there is still some potential for misuse, as higher doses can reproduce the desired effects. Alternatives include buprenorphine (BuprenexⓇ). Compared to methadone, which is a full opioid agonist, which causes the cell to produce the maximum opioid effect, buprenorphine is a partial agonist, which can only produce certain or limited effects, lowering potential for misuse, all while remaining effective at mitigating withdrawal symptoms. If the patient is already opioid-free and wants to prevent relapse, naltrexone (VivitrolⓇ) is another option. However, naltrexone is an opioid antagonist, meaning that it cannot be administered to patients who have recently used opioids, otherwise, it will precipitate withdrawal. Naltrexone is orally active and can be taken daily as a pill or injected once a month. And because it is an antagonist, it is not used to mitigate withdrawal symptoms, instead being used to prevent the pleasurable effects of future opioid use. Compared to methadone or buprenorphine drug replacements, there is no risk of misuse.

Drug therapies are usually paired with some form of psychotherapy, due to the fact that even with treatment of physical dependence, there are still psychological cues and triggers that can induce relapse. Cognitive-behavioural therapy (CBT) can reduce cravings and provide the patient with coping strategies to reduce the need for drugs. Contingency management programs reward opioid abstinence with vouchers or other redeemable prizes. Finally family counseling is often used to help educate friends and family about opioid use disorder and provide a social support network.

In conclusion, opioids are a highly addictive group of drugs responsible for hundreds of thousands of deaths worldwide every year, and that number continues to grow. Opioid addiction develops rapidly, forcing you into a vicious cycle of needing more and more to not even feel good, but merely normal. Relapse is common, with over 50% of all heroin addicts relapsing, and even reporting cravings years after treatment. But it is not unbeatable, and the longer you go without falling back into those old habits, the more likely you are to remain clean as your brain slowly resets to its old normal. 

Bibliography

DEA. “Facts About Fentanyl.” DEA, 29 Apr. 2021, https://www.dea.gov/resources/facts-about-fentanyl. Accessed 16 July 2026.

Dhaliwal, Armaan, and Mohit Gupta. “Physiology, Opioid Receptor.” PubMed, StatPearls Publishing, 2023, https://www.ncbi.nlm.nih.gov/books/NBK546642/. Accessed 15 July 2026.

Fentanyl, Sources . “Sources – Fentanyl.” Google.Com, 2020, https://sites.google.com/view/sources-fentanyl/. Accessed 15 July 2026.

Gillette, Hope. “Partial Opioid Agonists: What They Are and How They Work.” Healthline, 12 June 2023, https://www.healthline.com/health/partial-opioid-agonist. Accessed 16 July 2026.

Johns Hopkins Medicine. “Opioids.” Www.Hopkinsmedicine.Org, John Hopkins Medicine, 19 Oct. 2022, https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/opioids. Accessed 15 July 2026.

Koob, George F. “Neurobiology of Opioid Addiction: Opponent Process, Hyperkatifeia, and Negative Reinforcement.” Biological Psychiatry, vol. 87, no. 1, June 2019, 10.1016/j.biopsych.2019.05.023.

Le Roy, Chloé, et al. “Endogenous Opioids Released During Non-Nociceptive Environmental Stress Induce Latent Pain Sensitization via a NMDA-Dependent Process.” The Journal of Pain, vol. 12, no. 10, Oct. 2011, pp. 1069–1079, 10.1016/j.jpain.2011.04.011.

National Center for Drug Abuse Statistics. “Drug Overdose Death Statistics: Fentanyl, Opioids, Heroin & More.” National Center for Drug Abuse Statistics, 2019, https://drugabusestatistics.org/drug-overdose-deaths/. Accessed 15 July 2026.

National Institute on Drug Abuse. “Opioids.” National Institute on Drug Abuse, 2022, https://nida.nih.gov/research-topics/opioids. Accessed 15 July 2026.

—. “Prescription Opioids Drug Facts.” National Institute on Drug Abuse, June 2021, https://nida.nih.gov/publications/drugfacts/prescription-opioids. Accessed 15 July 2026.

Quock, Raymond. “Chapter 12: Opioids.” Drugs and Behavior, Washington State University, 19 Jan. 2021, https://wsu.pressbooks.pub/biopsychological-effects-alcohol-drugs/chapter/chapter-12-opioids/#12.1. Accessed 16 July 2026.

Volkow, Nora D., et al. “Prevention and Treatment of Opioid Misuse and Addiction.” JAMA Psychiatry, vol. 76, no. 2, 2019, p. 208, https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2716982, 10.1001/jamapsychiatry.2018.3126. Accessed 15 July 2026.

World Health Organization. “Opioid Overdose.” World Health Organization, 29 Aug. 2025, https://www.who.int/news-room/fact-sheets/detail/opioid-overdose. Accessed 15 July 2026.“Opioids and the Physiology of Tolerance.” Learn.Genetics.Utah.Edu, https://learn.genetics.utah.edu/content/addiction/tolerance/. Accessed 15 July 202