Heroin: heroin addiction, symptoms, overdose and treatment

Opioids are used mainly for the treatment of pain syndromes. Some of the mechanisms of the brain that regulate the perception of pain, can also cause a state of complacency or euphoria. In this regard, opioids are used outside medicine - to obtain a state of euphoria, or "buzz". The ability to cause euphoria turns into a danger of abuse, and numerous attempts have been made to separate the mechanism of analgesia from the mechanism of euphoria. However, until now it has not been possible to create an opioid that would cause analgesia without euphoria. Nevertheless, the search for such a drug allowed us to better understand the physiological mechanisms of pain. Preparations created in the image and likeness of endogenous opioid peptides have a more specific effect, but they are not currently 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 certain variants of the pain syndrome, especially chronic pain. Nevertheless, opioids remain the most effective treatment for intense pain.

Especially often, opioids are used to treat acute pain. Some patients experience pleasure not only in connection with pain relief, but also because of its relaxing, anxiolytic and euphorogenic effect. This is especially true in situations with a high level of anxiety, for example, with intense chest pain in patients with myocardial infarction. Healthy volunteers who did not experience pain, when opioids are administered, also report unpleasant sensations associated with the side effects of the drug-nausea, vomiting, or sedation. Patients with pain syndrome rarely develop abuse or addiction to opioids. Of course, with the continuous introduction of opioids, tolerance inevitably develops, and if the drug is suddenly discontinued, withdrawal will develop. This means having "physical dependence", but not addiction (that is, "dependence" according to official psychiatric definitions).

Do not refrain from using opioids in patients with cancer due to fear of developing addiction to them. If the patient is shown long-term therapy with opioids, it is preferable to use drugs with a slow-onset but long-acting effect, administered internally. In this case, the likelihood of developing euphoria at the onset of the dose or withdrawal symptoms decreases with a sudden discontinuation of the drug. From this point of view, the drug of choice for severe chronic pain is methadone. You can also use a morphine preparation for oral administration with sustained release (MS-kontin). Opioids with a quick but brief action (for example, hydromorphone or oxycodone) are shown primarily for short-term treatment of acute pain (for example, in the postoperative period). With the development of tolerance and physical dependence in patients, withdrawal symptoms may appear between injections with a decrease in the pain threshold for this period. Thus, if it is necessary to continuously take a preference in most patients should be given to drugs with a long-term effect.

The risk of abuse or addiction to opioids is particularly high in patients who complain of pain, with no clear physical cause, or are associated with a chronic, life-threatening disease. Examples are chronic headache, back pain, abdominal pain, or pain in peripheral neuropathies. In these cases, opioids can only be used for short-term treatment of intense pain, but long-term therapy is not recommended. In those relatively rare cases when the controlled legal use of opioids is transformed into abuse, this transition is often evidenced by the fact that the patient sooner than usual returns to his doctor to prescribe a prescription, or calls for "emergency care" in another hospital with complaints of acute pain and a request for an injection of an opioid.

From opioids, heroin is the object of abuse most often. In the US, heroin is not used in clinical practice. Some argue that heroin has unique analgesic properties and can be used to treat intense pain, but this provision has never been proven in double-blind trials that compare the effectiveness of heroin with other parenterally administered opioids. Nevertheless, heroin is widely distributed through illegal channels, and its price for one milligram dropped significantly in the 1990s. For many years, illegally distributed heroin had low activity: a dose of 100 mg contained 0 to 8 (on average 4) mg of the active substance, and the rest was made up of inert or toxic additives. In the mid-1990s, the degree of purification of heroin distributed in large cities increased to 45%, and in some samples to 85%. Accordingly, the average dose that heroin users injected into themselves increased, which led to an increase in the level of physical dependence and the development of a more severe withdrawal syndrome with the discontinuation of its regular use. If heroin previously required only intravenous administration, then preparations with a higher degree of purification could be smoked. This led to the fact that heroin began to be used by people who had previously refrained from using it because of the danger of intravenous injection.

Although it is not possible to accurately calculate the number of heroin addicts in the United States, but given the number of deaths from overdose, the number of people seeking treatment or detained for heroin use, the total number of heroin addicts can be estimated at 750 000-1 000 000 people. It is not known exactly how many people used heroin for a short time, but did not abuse it regularly. A survey of families showed that 1.5% of American adults took heroin at any given time in their lives, with 23% of cases meeting the criteria for dependence.

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Heroin dependence

After intravenous injection of a solution of heroin, many sensations arise, for example, a sensation of spilling heat, euphoria, extraordinary pleasure ("rash", or "arrival"), which is compared to sexual orgasm. There are some differences between opioids in terms of the nature of their acute effect: morphine causes a more pronounced histamine-releasing effect, and meperidine is a stronger stimulus.

Nevertheless, even experienced drug addicts were not able to distinguish the effect of heroin from hydromorphone in double-blind studies. Moreover, there is no scientific evidence that heroin is more effective than hydromorphone to relieve intense pain, although some doctors in countries where heroin is still used as an analgesic are convinced of its superiority. The popularity of heroin in the US is due to its availability in the illegal market and speed of action.

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

For example, the hypothalamo-pituitary-gonadal or hypothalamic-pituitary-adrenal axis in individuals with heroin dependence function with abnormalities. Women who are addicted to heroin are characterized by irregular menstruation, and men have different sexual problems. After injection of heroin libido decreases, and during periods of abstinence premature ejaculations and even spontaneous ejaculations are often observed. The affective state also suffers. Persons who have heroin addiction are relatively compliant and compliant, but become irritable and aggressive during periods of withdrawal.

According to patients' reports, tolerance is quickly formed to the euphorogenic effect of opioids. Tolerance develops and their ability to depress breathing, cause analgesic and sedative effects, nausea. Persons using heroin usually increase their daily dose, depending on the availability of the drug and the possibilities for its acquisition. If the drug is available, the dose is sometimes increased 100 times. Even with high tolerance, there is a danger 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 if heroin is mixed with a stronger opioid, for example, fentanyl.

How does heroin addiction manifest itself?

Heroin dependence or from other short-acting opioids causes behavioral changes and usually becomes incompatible with a full-fledged productive life. There is a certain risk of abuse and dependence on opioids in doctors and other health workers who have daily access to these drugs. Doctors often start with the assumption that they can find their dose, allowing them to improve their condition. For example, physicians suffering from back pain can prescribe hydromorphone injections themselves in order to maintain their previous level of activity and the ability to help patients. Over time, however, control over the use of the opioid is lost, and behavioral changes that can become visible to relatives and colleagues appear. Continuous use of opioids is fraught with changes in behavior and the risk of overdose, especially when the stronger drug is accidentally introduced, but usually does not lead to toxic damage to internal organs and systems.

Opioids are often used in combination with other drugs. Often used a combination of heroin and cocaine ("speedball" - literally: "fast ball").

Fans of this combination claim that it brings more intense euphoria than each of the drugs individually. Heroin is sometimes used by drug addicts to "treat" excitement and irritability, which often occur after the action of cocaine. The pharmacological effects of opioids and psychostimulants often affect each other. Cocaine increases dinorphine levels in rats, and buprenorphine, a partial agonist of mu-opioid receptors and a kappa-opioid receptor antagonist, weakens spontaneous cocaine use by animals. In addition, cocaine reduces the manifestations of opioid withdrawal syndrome in rats. The clinical significance of this interaction between opioids and cocaine or other psychostimulants remains poorly understood.

Although opioids are non-toxic in themselves, the mortality rate among people who have heroin dependence is quite high. These early deaths are often associated with accidental overdose, involvement in criminal activities, the risk of a collision with the distributors of psychoactive substances. A large number of serious infections are associated with the use of non-sterile drugs and common supplies for injections. People who abuse heroin are infected with bacterial infections, including those causing skin abscesses, pulmonary infections and endocarditis, as well as viral infections, especially HIV infection and hepatitis C. Intravenous injection of psychoactive substances has become a major factor in the spread of HIV and hepatitis C, which can be the cause of severe complications and early death.

Overdose of heroin and its treatment

Overdose of heroin is manifested by drowsiness or coma with severe respiratory depression. It is often observed in newborns born from mothers who were injected with opioid analgesics during labor. The same pattern is observed in individuals who have heroin addiction who injected a drug with a higher than usual degree of purification or a dose of a stronger opioid than heroin. This is sometimes the case when persons who distribute psychoactive substances issue fentanyl for heroin.

Fortunately, there is an antidote that is effective in heroin overdoses. Naloxone has a high affinity for mu-opioid receptors, the site of action of morphine and other strong opioid agonists. Naloxone displaces opioids from the receptor and thus overcomes the symptoms of overdose. With intravenous administration, the effect occurs less than 1 minute, but additional injections may be required if a very large dose of opioid is administered. It is important to remember that naloxone has a very short action. If the overdose is caused by a long-acting opioid, the patient will awaken under the action of naloxone, but after 45 minutes the symptoms of a heroin overdose will arise again.

Treatment of heroin addiction

As with other forms of dependence, the first stage of treatment is aimed at eliminating physical dependence and consists in detoxification. Heroin withdrawal is subjectively extremely unpleasant, but rarely threatens life. It develops 6-12 hours after the last injection of a short-acting opioid or 72-84 hours after the administration of a long-acting opioid. Persons who have heroin dependence often go through the early phase of heroin withdrawal when it is impossible to get the next dose. In some groups of support for drug addicts, it is not customary to ease the withdrawal syndrome - so that the addict survives it against the backdrop of group support. The duration and intensity of the syndrome is determined by the pharmacokinetics of the drug used. Heroin withdrawal is intensive, short-term and lasts 5-10 days. The methadone withdrawal syndrome develops more slowly and lasts longer. The second stage of the withdrawal syndrome - the so-called protracted withdrawal syndrome - is also probably more prolonged with the use of methadone.

How to remove heroin withdrawal?

Detoxification should be carried out if in the future it is planned that the patient will completely abandon the drug with his participation in one of the psychological rehabilitation programs for people who refused drugs (in self-help groups or in outpatient treatment). In the absence of an effective program for the prevention of recurrence, in most cases a relapse occurs after the detoxification procedure. Detoxification should also be performed if a long-acting antagonist of opioid naltrexone receptors is scheduled for the patient. But if the patient is shown supporting opioid therapy, and he prefers this particular method of treatment, detoxification is not carried out. In this case, the patient can immediately be transferred from heroin to methadone or L-alpha-acetylmetadol (L-AAM).

The most commonly used method of cupping opioid withdrawal syndrome is based on the phenomenon of cross tolerance and consists in switching to a legal opioid drug followed by a gradual dose reduction. Principles of detoxification for opioids are the same as for other psychoactive substances that cause physical dependence. It is recommended to replace the short-acting opioid, such as heroin, with a long-acting drug, for example, methadone. The initial dose of methadone is usually 20 mg. This is a trial dose, which allows to predict the dose necessary for the relief of heroin withdrawal. The total dose on the first day of treatment can be determined by taking into account the response to this initial dose of methadone. If 20 mg of methadone did not cause a clinically apparent effect, the dose may be increased. Usually a sufficient weakening of withdrawal symptoms ensures the intake of 20 mg of methadone 2 times per day with a 20% reduction in dose at the day of subsequent detoxification. If the dose of heroin was higher, then the initial dose of methadone should also be higher.

The second approach to detoxification is based on the use of clonidine, which is usually used as an antihypertensive agent. Clonidine is an α2-adrenoreceptor agonist that activates presynaptic autoreceptors in a blue spot, thus inhibiting the activity of adrenergic systems in the brain and periphery. Many vegetative symptoms of opioid withdrawal syndrome (for example, nausea, vomiting, painful muscle spasms, sweating, tachycardia, arterial hypertension) arise due to the loss of inhibitory effect of opioids, including adrenergic systems. Thus, clonidine, although it is a non-opioid drug, can alleviate many of the symptoms of heroin withdrawal. But since clonidine does not relieve the diffuse pain or craving for opioids that are characteristic of the withdrawal syndrome, patients often experience discomfort when treating withdrawal with this drug. The drawback of this approach is that the dose of clonidine, which suppresses withdrawal symptoms, often also causes arterial hypotension and dizziness.

The third treatment regimen of opioid withdrawal syndrome is of theoretical importance, but is not applied in practice. It is based on the activation of an endogenous opioid system without the use of medications. This technique involves the use of acupuncture and various methods of CNS activation through percutaneous electrical stimulation. The experiment showed that electrostimulation can block withdrawal symptoms in rats and increase the activity of the endogenous opioid system.

Although stimulation of the endogenous opioid system seems to be the most natural way of treating the symptoms of opioid withdrawal, the effectiveness of this technique is difficult to confirm in controlled trials. The fundamental problem is that patients with opioid withdrawal syndrome have increased suggestibility, and therefore it is difficult to exclude a placebo effect caused by placement in a mysterious chamber or by injecting a needle under the skin.

Long-term treatment of heroin addiction

If patients are simply discharged from the hospital after relief of the withdrawal syndrome, then the probability of renewal of compulsive use of opioids is high. Dependence is a chronic disease requiring long-term treatment. Various factors predetermine the development of 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 "depressed abstinence syndrome" and can persist for up to 6 months. These persistent changes tend to oscillate as the new reference point is established, although the mechanism of this process is not established. After the procedure of detoxification, out-patient treatment with complete discontinuation of the drug rarely leads to success. Even after an intensive detoxification procedure and with prolonged treatment in special care groups, the frequency of relapse is very high.

The most successful treatment for heroin dependence is to stabilize the condition with methadone. If a patient who completely abandoned the drug has a relapse, it can be immediately transferred to methadone without detoxification. The dose of methadone should be sufficient to prevent abstinence symptoms for at least 24 hours. L-AAM is another drug approved by the FDA for maintenance therapy and blocking withdrawal symptoms for 72 hours. Thus, a stable L-AAM patient can be given 2- 3 times a week, which eliminates the need for daily clinical monitoring, which may interfere with the rehabilitation procedure. In connection with the data on the possibility of prolonging the QT interval against the background of L-AAM treatment, the use of this drug in some European countries is currently suspended.

Supportive therapy with an opioid receptor agonist

Patients taking methadone or L-AAM do not experience "ups and downs", as when taking 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 against the background of 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 to prevent the use of illegal opioids, as evidenced by the results of urine testing. Over time, patients develop tolerance to the sedative effect of methadone, so they can attend educational institutions or cope with their work. In addition, opioids also cause a slight but constant stimulating effect, which becomes apparent after the appearance of tolerance to sedation, so against the background of a stable dose of methadone, the reaction rate and activity increase. Recent studies have shown that methadone is not only a selective agonist of mu-opioid receptors, but also a moderate antagonist of NMDA receptors, which can explain, at least in part, the lack of development of tolerance to the methadone effect that persists for many years.

Treatment with opioid receptor antagonists

Another therapeutic option is the use of opioid receptor antagonists. Naltrexone, like naloxone, is an antagonist of opioid receptors, but has a longer action. It has a high affinity for mu-opioid receptors and thus completely blocks the action of heroin and other mu receptor agonists. However, naltrexone almost does not have the properties of an agonist, it does not reduce cravings for the narcotic and does not facilitate manifestations of the abstinent withdrawal syndrome. For these reasons, naltrexone treatment, as a rule, does not attract drug addicts. However, this drug can be used after detoxification in patients with high motivation for abstinence from opiodides. This method is especially indicated in physicians, nurses and pharmacists who have access to opioid drugs. Although naltrexone was originally intended for the treatment of opioid dependence, it is now more widely used worldwide for the treatment of alcoholism.

New methods of treating heroin dependence

Currently, new drugs that are potentially effective in various forms of dependence are of great interest. One such drug is buprenorphine, a partial agonist of mu-opioid receptors. It is characterized by a slow onset and a significant duration of action, a mild abstinence syndrome upon cancellation, a low risk of overdose. At the same time, by its ability to block the action of heroin, it is comparable to naltrexone. Buprenorphine is used both as a monotherapy and in combination with naloxone. In combination therapy, the dose ratio 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 in accordance with the prescription, sublingually, but if someone tries to use this combination intravenously to get euphoria, then naloxone, which has a higher activity when administered intravenously, would block this possibility. It is possible that due to the relative safety and low probability of abuse in combination with naloxone, the distribution of buprenorphine will be regulated less strictly than the spread of other opioids. Due to this, treatment of opioid dependence can become similar to the treatment of any other disease, in particular, the patient will have the opportunity to choose - to be treated under the supervision of private practitioners or in large, but less comfortable "methadone" clinics.