Heroin: heroin addiction, symptoms, overdose and treatment

Opioids are used primarily to treat pain syndromes. Some of the brain mechanisms that regulate pain perception are also capable of causing a state of complacency or euphoria. In this regard, opioids are also used outside of medicine - to produce a state of euphoria, or "high". The ability to cause euphoria turns into a danger of abuse, in connection with which numerous attempts have been made to separate the mechanism of analgesia from the mechanism of euphoria development. However, it has not yet been possible to create an opioid that would cause analgesia without euphoria. Nevertheless, the search for such a drug has allowed us to better understand the physiological mechanisms of pain. Drugs created in the image and likeness of endogenous opioid peptides have a more specific effect, but they are currently not available for clinical practice. Drugs that do not act on opioid receptors, for example, non-steroidal anti-inflammatory drugs (aspirin, ibuprofen, etc.) play an important role in the treatment of some types of pain syndrome, especially chronic pain. However, opioids remain the most effective treatment for severe pain.

Opioids are particularly frequently used in the treatment of acute pain. Some patients experience pleasure when the drug is administered not only due to pain relief, but also due to its relaxing, anxiolytic, and euphoriant effects. This is especially common in situations with high anxiety, such as intense chest pain in patients with myocardial infarction. Healthy volunteers who do not experience pain report unpleasant sensations associated with the drug's side effects - nausea, vomiting, or sedation - when opioids are administered. Patients with pain rarely develop opioid abuse or addiction. Of course, tolerance inevitably develops with continuous opioid administration, and if the drug is suddenly stopped, a withdrawal syndrome will develop. This means "physical dependence" but not addiction (i.e., "dependence" according to official psychiatric definitions).

Opioids should not be withheld from patients with cancer for fear of developing addiction. If long-term opioid therapy is indicated, slow-acting but long-acting drugs administered orally are preferable. This reduces the likelihood of early euphoria or withdrawal symptoms when the drug is suddenly stopped. In this regard, methadone is the drug of choice for severe chronic pain. Oral morphine with a slow release (MS-Contin) can also be used. Opioids with a rapid but short-acting action (eg, hydromorphone or oxycodone) are indicated primarily for the short-term treatment of acute pain (eg, postoperative). As tolerance and physical dependence develop, patients may experience withdrawal symptoms between doses, with a lower pain threshold for this period. Thus, when chronic administration is necessary, long-acting drugs should be preferred in most patients.

The risk of opioid abuse or addiction is particularly high in patients who complain of pain that has no clear physical cause or is associated with a chronic, non-life-threatening condition. Examples include chronic headache, back pain, abdominal pain, or pain from peripheral neuropathies. In these cases, opioids may be used for short-term treatment of severe pain, but long-term therapy is not recommended. In the relatively rare cases where controlled, legal opioid use escalates to opioid abuse, the transition is often signaled by the patient returning to their physician earlier than usual to fill a prescription or going to an “emergency room” at another hospital complaining of severe pain and requesting an opioid injection.

Heroin is the most commonly abused opioid. Heroin is not used clinically in the United States. Some claim that heroin has unique analgesic properties and can be used to treat severe pain, but this has never been proven in double-blind trials comparing heroin with other parenterally administered opioids. However, heroin is widely distributed through illicit channels, and its price per milligram dropped significantly in the 1990s. For many years, illicit heroin was low potency: a 100 mg dose contained 0 to 8 (average 4) mg of active substance, with the remainder consisting of inert or toxic additives. In the mid-1990s, the purity of heroin distributed in major cities increased to 45%, and in some samples to 85%. Accordingly, the average dose that heroin users injected into themselves became higher, leading to increased levels of physical dependence and more severe withdrawal symptoms when regular use ceased. Whereas heroin previously required intravenous administration, higher-purity preparations could be smoked. This led to heroin being used by people who had previously refrained from using it because of the dangers of intravenous administration.

Although it is impossible to accurately estimate the number of people addicted to heroin in the United States, if overdose deaths, treatment, and arrests for heroin use are taken into account, the total number of people addicted to heroin can be estimated at between 750,000 and 1,000,000. It is not known exactly how many more people are short-term heroin users who do not become regular users. A household survey found that 1.5% of American adults used heroin at some point in their lives, with 23% of those cases meeting the criteria for addiction.

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Heroin addiction

After intravenous administration of a heroin solution, a variety of sensations arise, such as a feeling of spreading warmth, euphoria, and extraordinary pleasure (the "rush" or "high"), which have been compared to a sexual orgasm. There are some differences between opioids in the nature of their acute effect: morphine causes a more pronounced histamine-releasing effect, and meperidine causes a stronger excitation.

However, even experienced addicts have been unable to differentiate between the effects of heroin and hydromorphone in double-blind studies. Moreover, there is no scientific evidence that heroin is more effective than hydromorphone in relieving severe pain, although some doctors in countries where heroin is still used as an analgesic believe it is superior. Heroin's popularity in the United States is due to its availability on the illegal market and its rapid onset of action.

After intravenous administration of heroin, the reaction occurs within 1 minute. Heroin is highly lipid soluble and therefore quickly penetrates the blood-brain barrier, after which it is deacetylated to form the active metabolites 6-monoacetylmorphine and morphine. After intense euphoria, lasting from 45 seconds to several minutes, there follows a period of sedation and tranquility ("hang-up") lasting about an hour. Depending on the dose, heroin acts from 3 to 5 hours. People suffering from a disease such as heroin addiction can inject it 2 to 4 times a day, thus balancing between euphoria and the unpleasant sensations associated with early withdrawal syndrome. This causes numerous disorders, at least in the part controlled by endogenous opioids.

For example, the hypothalamic-pituitary-gonadal or hypothalamic-pituitary-adrenal axis functions abnormally in people with heroin addiction. Women addicted to heroin experience irregular periods, and men experience various sexual problems. After injecting heroin, libido decreases, and during periods of abstinence, premature ejaculations and even spontaneous ejaculations are often observed. The affective state also suffers. People who are addicted to heroin are relatively docile and compliant, but during periods of abstinence they become irritable and aggressive.

Patients report that tolerance to the euphoric effects of opioids develops quickly. Tolerance also develops to their ability to depress respiration, cause analgesic and sedative effects, and cause nausea. Heroin users typically increase their daily dose depending on the availability of the drug and the ability to purchase it. If the drug is available, the dose is sometimes increased by 100 times. Even with high tolerance, there is still a risk of overdose if the dose exceeds the tolerance threshold. Overdose is likely to occur when the effect of the acquired dose is unexpectedly stronger or when heroin is mixed with a stronger opioid, such as fentanyl.

How does heroin addiction manifest itself?

Heroin or other short-acting opioid addiction causes behavioral changes and is usually incompatible with full and productive life. There is some risk of opioid abuse and dependence among physicians and other health care workers who have daily access to these drugs. Physicians often begin with the assumption that they can find a dose that will improve their condition. For example, physicians with back pain may prescribe themselves hydromorphone injections to maintain their level of activity and ability to care for patients. Over time, however, control over opioid use is lost, and behavioral changes occur that may become noticeable to family and colleagues. Chronic opioid use primarily involves behavioral changes and the risk of overdose, especially if a stronger drug is accidentally injected, but it does not usually result in toxicity to internal organs or systems.

Opioids are often used in combination with other drugs. A common combination is heroin and cocaine ("speedball").

Fans of this combination claim that it produces a more intense euphoria than either drug alone. Heroin is sometimes used by addicts to "treat" the agitation and irritability that often follow cocaine. The pharmacological effects of opioids and psychostimulants often interfere with each other. Cocaine increases dynorphin levels in rats, and buprenorphine, a partial mu-opioid receptor agonist and kappa-opioid receptor antagonist, reduces the animals' spontaneous cocaine use. Cocaine also reduces opioid withdrawal symptoms in rats. The clinical significance of this interaction between opioids and cocaine or other psychostimulants remains poorly understood.

Although opioids themselves are nontoxic, the mortality rate among heroin addicts is high. These early deaths are often attributed to accidental overdose, involvement in criminal activity, and exposure to drug dealers. Many serious infections are associated with the use of unsterile drugs and shared injection equipment. Bacterial infections, including those causing skin abscesses, lung infections, and endocarditis, and viral infections, especially HIV and hepatitis C, are common among heroin abusers. Intravenous drug use has become a major factor in the spread of HIV and hepatitis C, which can cause severe complications and early death.

Heroin Overdose and Its Treatment

Heroin overdose results in drowsiness or coma with severe respiratory depression. It is common in newborns born to mothers who were given opioid analgesics during labor. The same pattern is seen in heroin addicts who have injected themselves with a higher-than-normal purity of the drug or a stronger opioid than heroin. This sometimes occurs when drug dealers pass off fentanyl as heroin.

Fortunately, there is an antidote that is effective against heroin overdose. Naloxone has a high affinity for the mu-opioid receptor, the site of action of morphine and other strong opioid agonists. Naloxone displaces opioids from the receptor, thereby reversing the symptoms of overdose. When administered intravenously, the effect occurs in less than 1 minute, but additional injections may be needed if a very large dose of opioid is administered. It is important to remember that naloxone is very short-acting. If the overdose is caused by a long-acting opioid, naloxone will awaken the patient, but within 45 minutes the symptoms of heroin overdose will return.

Treatment for heroin addiction

As with other forms of addiction, the first stage of treatment is aimed at eliminating physical dependence and consists of detoxification. Heroin withdrawal is subjectively extremely unpleasant, but rarely life-threatening. It develops 6-12 hours after the last administration of a short-acting opioid or 72-84 hours after the administration of a long-acting opioid. People who are addicted to heroin often go through an early phase of heroin withdrawal when they are unable to obtain another dose. Some drug support groups deliberately do not alleviate withdrawal symptoms - so that the addict can experience them against the background of group support. The duration and intensity of the syndrome is determined by the pharmacokinetics of the drug used. Heroin withdrawal is intense, short-term and lasts 5-10 days. Methadone withdrawal develops more slowly and lasts longer. The second stage of withdrawal, the so-called protracted withdrawal syndrome, is also likely to be longer lasting with methadone use.

How to relieve heroin withdrawal?

Detoxification should be performed if the patient is planned to completely abstain from the drug in the future with his participation in one of the psychological rehabilitation programs for people who have given up drugs (in mutual aid groups or as part of outpatient treatment). In the absence of an effective relapse prevention program, in most cases a relapse occurs after the detoxification procedure. Detoxification should also be performed if the patient is planned to be prescribed the long-acting opioid receptor antagonist naltrexone. However, if the patient is prescribed opioid maintenance therapy and he prefers this method of treatment, then detoxification is not performed. In this case, the patient can immediately be transferred from heroin to methadone or L-alpha-acetylmethadol (L-AAM).

The most commonly used method of reversing opioid withdrawal is based on the phenomenon of cross-tolerance and consists of switching to a legal opioid drug and then gradually reducing the dose. The principles of detoxification for opioids are the same as for other psychoactive substances that cause physical dependence. It is recommended to replace a short-acting opioid, such as heroin, with a long-acting drug, such as methadone. The initial dose of methadone is usually 20 mg. This is a test dose that allows one to predict the dose required to reverse heroin withdrawal. The total dose on the first day of treatment can be determined taking into account the response to this initial dose of methadone. If 20 mg of methadone does not produce a clinically obvious effect, the dose can be increased. Usually, 20 mg methadone twice daily provides sufficient relief of withdrawal symptoms, with a 20% reduction per day during subsequent detoxification. If the heroin dose was higher, the initial methadone dose should also be higher.

A second approach to detoxification is based on the use of clonidine, which is commonly used as an antihypertensive agent. Clonidine is an alpha2-adrenergic receptor agonist that activates presynaptic autoreceptors in the locus coeruleus, thereby inhibiting the activity of adrenergic systems in the brain and periphery. Many of the autonomic symptoms of opioid withdrawal (e.g., nausea, vomiting, painful muscle spasms, sweating, tachycardia, hypertension) arise from the loss of the inhibitory effect of opioids, including on adrenergic systems. Thus, clonidine, although a non-opioid drug, can relieve many of the symptoms of heroin withdrawal. However, because clonidine does not reduce the diffuse pain or craving for opioids characteristic of withdrawal, patients often continue to experience some discomfort when treated with this drug. A disadvantage of this approach is that the dose of clonidine that suppresses withdrawal symptoms often also causes arterial hypotension and dizziness.

The third treatment regimen for opioid withdrawal syndrome has theoretical significance but is not used in practice. It is based on the activation of the endogenous opioid system without the use of drugs. This method involves the use of acupuncture and various methods of activating the central nervous system using transcutaneous electrical stimulation. An experiment showed that electrical stimulation can block withdrawal symptoms in rats and increase the activity of the endogenous opioid system.

Although stimulation of the endogenous opioid system appears to be the most natural way to treat opioid withdrawal symptoms, its effectiveness is difficult to confirm in controlled trials. The fundamental problem is that opioid withdrawal patients are highly suggestible, making it difficult to rule out a placebo effect caused by being placed in a mystery chamber or having needles inserted under the skin.

Long-term treatment for heroin addiction

If patients are simply discharged from the hospital after the withdrawal syndrome has been relieved, there is a high probability of relapse into compulsive opioid use. Addiction is a chronic disease that requires long-term treatment. Various factors predetermine the development of a relapse. One of these factors is that the withdrawal syndrome does not regress after 5-7 days. Its mild manifestations are often referred to as "protracted withdrawal syndrome" and can persist for up to 6 months. These persistent changes tend to fluctuate as a new reference point is established, although the mechanism for this process is not known. After the detoxification procedure, outpatient treatment with complete drug withdrawal is rarely successful. Even after an intensive detoxification procedure and with long-term treatment in special mutual aid groups, the relapse rate is very high.

The most successful treatment for heroin addiction is methadone stabilization. If a patient who has completely given up the drug relapses, he or she can be immediately transferred to methadone without detoxification. The methadone dose should be sufficient to prevent withdrawal symptoms for at least 24 hours. L-AAM is another drug approved by the FDA for maintenance therapy and blocks withdrawal symptoms for 72 hours. Thus, stable patients can be prescribed L-AAM 2-3 times a week, eliminating the need for daily clinical monitoring, which can interfere with the rehabilitation procedure. Due to data on the possibility of prolongation of the QT interval during treatment with L-AAM, the use of this drug in some European countries is currently suspended.

Opioid agonist maintenance therapy

Patients taking methadone or L-AAM do not experience the “highs” and “lows” that occur with heroin. The craving for the drug decreases and may disappear. Neuroendocrine rhythms are gradually restored. Due to cross-tolerance (between methadone and heroin), patients who inject heroin during treatment report a decrease in the effect of its usual dose. This cross-tolerance is a dose-dependent effect. Therefore, the higher the maintenance dose of methadone, the more effective it is in preventing the use of illicit opioids, as evidenced by urine testing. Over time, patients develop a tolerance to the sedative effect of methadone, so they can attend school or cope with their work. In addition, opioids also cause a mild but constant stimulant effect, which becomes noticeable after tolerance to the sedative effect has developed, so reaction speed and activity increase with a stable methadone dose. Recent studies have shown that methadone is not only a selective mu-opioid receptor agonist but also a moderate NMDA receptor antagonist, which may explain, at least in part, the lack of tolerance to the effects of methadone, which persist for many years.

Treatment with opioid receptor antagonists

Another treatment option is the use of opioid receptor antagonists. Naltrexone, like naloxone, is an opioid receptor antagonist but has a longer duration of action. It has a high affinity for the mu-opioid receptor and thus completely blocks the effects of heroin and other mu-receptor agonists. However, naltrexone has almost no agonist properties, does not reduce drug craving, and does not alleviate the manifestations of protracted withdrawal symptoms. For these reasons, naltrexone treatment is generally not attractive to drug addicts. However, the drug can be used after detoxification in patients who are highly motivated to abstain from opioids. This method is especially indicated for physicians, nurses, and pharmacists who have access to opioid medications. Although naltrexone was originally intended to treat opioid dependence, it is now more widely used worldwide to treat alcoholism.

New Treatments for Heroin Addiction

Currently, there is great interest in new drugs that are potentially effective in various forms of addiction. One such drug is buprenorphine, a partial agonist of mu-opioid receptors. It is characterized by a slow onset and significant duration of action, mild withdrawal symptoms during cancellation, and a low risk of overdose. At the same time, its ability to block the action of heroin is comparable to naltrexone. Buprenorphine is used both as monotherapy and in combination with naloxone. In combination therapy, the ratio of doses of the two drugs should be such that naloxone does not significantly block the ability of buprenorphine to stimulate mu-opioid receptors if both drugs are taken sublingually as prescribed, but if someone tries to inject this combination intravenously to get euphoria, naloxone, which has a higher activity when administered intravenously, would block this ability. It is possible that, because of its relative safety and low abuse potential when combined with naloxone, buprenorphine will be less strictly regulated than other opioids. This could make treatment for opioid addiction more like any other medical condition, with patients given the choice of being treated in private practices or in larger, less comfortable, “methadone” clinics.