Higher elevations can increase your dopamine

Intoxication and drugs

Thomas Koehler

To person

is professor of psychology at the University of Hamburg as well as a doctorate in medicine and a graduate mathematician. Most recently he published "The times fly by as if in a frenzy. An entertaining story of alcohol, drugs and their users" (2019). [email protected]

Drugs or psychotropic substances [1] are substances that are often taken against the express medical advice and with the disapproval of relatives and colleagues, despite expected or already occurring damage and in the knowledge that their acquisition or possession may have criminal consequences. A dependency often develops. The reasons for consumption vary in nature and can change over the course of a "drug career". The most important motive for the first use is almost always to raise the mood. The mechanism of this euphorization is the stimulation of the body's own "reward system", i.e. the reinforcement of dopaminergic (the transmitter dopamine) nerve cells that move from the midbrain to the nucleus accumbens in the distal brain. Psychostimulation, i.e. stimulation of activity, for example when taking cocaine or amphetamines, is also often desirable. Other psychotropic substances are taken to calm down, or changes in consciousness and perception are sought, i.e. hallucinogenic (psychedelic) effects.

If, after regular intake, the effect is weaker at the same dose, one speaks of tolerance. There are two variants of this: In the case of metabolic tolerance, the metabolism of the substance changes (for example, the rate of breakdown increases); functional tolerance changes in terms of effect (for example, due to reduced sensitivity of the binding sites). The result is often substance abuse at the expense of physical and psychological damage, material loss or social exclusion. If there is dependence ("addiction"), consumption cannot be given up, or only with difficulty.

Harmful use is defined in the International Classification of Mental Disorders (a chapter of the International Classification of Diseases and Allied Health Problems, or ICD-10 for short) as "a pattern of use of psychotropic substances" that "leads to damage to health". The dependency syndrome is introduced as "a group of physical, behavioral and cognitive phenomena in which the consumption of a substance (...) has priority for the person concerned over other behaviors that were previously rated higher by him". To make this diagnosis, at least three of six criteria must be met: In addition to tolerance and withdrawal syndrome, the strong, occasionally overpowering desire (compulsion) to consume substances, "reduced ability to control the beginning, the end and the amount of consumption", "progressive Neglecting "other interests in favor of substance use, ultimately continuing use" despite evidence of clear harmful consequences ". [2]

The ICD-10 distinguishes between ten types of drugs: alcohol, opioids, cannabinoids, cocaine, stimulants, hallucinogens, volatile solvents, tobacco, sleeping pills, sedatives and other psychotropic substances. In the following I will - for reasons of space - only deal with the first six of them and describe effects and side effects, i.e. benefits and dangers, as well as tolerance and withdrawal symptoms from a medical point of view.

Table: Immediate effects of the consumption of psychotropic substances. (& copy Thomas Köhler, Drugs and other psychotropic substances, Tübingen 2014.)

alcohol

Alcohol (more precisely: ethanol) is one of the most harmful psychotropic substances, if consumed in excess. It is usually taken orally as a drink and is mainly absorbed in the upper small intestine. With stronger effects and cheaper, it can also get into the bloodstream through the anal or vaginal mucosa (for example by means of tampons soaked in vodka). From there it reaches the liver via the portal vein, which already intercepts part of it and breaks it down while generating energy (presystemic elimination). Its effect can be considerable: the only non-central nervous effects to be mentioned are irritation of the mucous membranes and the expansion of skin vessels (with loss of heat and the risk of hypothermia). The neurological effects found even at low blood alcohol levels due to the strengthening of the inhibitory neurotransmitter y-aminobutyric acid (GABA) include prolonged reaction times and motor impairments, which develop into gait disorders and impaired speech motor skills at higher concentrations. When it comes to psychological effects, the first thing that should be mentioned is the relaxing, anti-anxiety effect. In higher doses it comes to sleepiness, with further intake even to coma and death. The deadly blood alcohol concentration is two to four per thousand, which is often considerably higher for long-term users. However, this level is rarely reached, as sleep or unconsciousness usually occurs beforehand.

The fact that alcohol tolerance occurs is a well-known everyday experience - one speaks in a derisive way of "drinkability". Chronic users often have an astonishingly low blood alcohol level despite ingesting large amounts. Since many behave remarkably inconspicuously despite the increased alcohol concentration, a functional tolerance can also be assumed. Withdrawal syndrome with alcohol is characterized by restlessness, anxiety, irritability, sleep disorders and noticeable tremors of the hands (tremor), plus circulatory symptoms (increased blood pressure, heartbeat), sometimes epileptic convulsions. The most severe withdrawal symptoms are delirium tremens: It begins two to three days after the last consumption, often when the drinking habits are lost during a hospital stay. This is often preceded by signs of simple withdrawal syndrome, sometimes seizures. The actual symptoms consist in hallucinations of moving objects ("white mice"), illusionary misjudgments, extreme agitation and fears with paranoia, as well as local and spatial disorientation. If left untreated, delirium lasts between four and ten days and can be fatal if left untreated. Typically, it occurs in individuals who have experienced significant abuse over several years; 15 percent of alcoholics are said to go through this disease, many several times.

Alcohol addiction syndrome and harmful use are often not differentiated, but are summarized under "alcoholism" or "alcohol sickness". About five percent of men and two percent of women in Germany are likely to meet the criteria for addiction; a much higher percentage drives at least harmful use. The familial accumulation of alcoholism is well documented, which is partly due to milieu and also has genetic causes. The physical changes in the event of abuse are only hinted at here: first, fatty deposits occur on the liver with the risk of inflammatory processes (fatty liver hepatitis), and after years or decades, connective tissue is transformed (cirrhosis of the liver). The consequences are changes in the vascular system and bypass circuits in the form of veins that run in the wall of the esophagus to the heart (esophageal varices). In addition, this results in restricted synthesis and degradation functions, disorders of blood coagulation, and the accumulation of toxic substances (e.g. ammonia) that damage the brain and can lead to hepatic encephalopathy and even hepatic coma. It can also lead to inflammation in the gastrointestinal area and the pancreas as well as an increased risk of carcinoma development in the oropharynx, larynx and esophagus (especially when consuming high-proof spirits and simultaneously consuming tobacco). Heart muscle and nerve cells are also often damaged. In terms of mental disorders, the Korsakoff syndrome should be mentioned in particular, characterized by impaired memory and confabulations (filling in the memory gaps with inventions) in generally preserved intellectual abilities. Alcohol hallucinosis can develop after prolonged consumption and is characterized by acoustic hallucinations. Alcoholic jealousy is also widespread, and frequent impotence contributes to its development.

Opioids

Opioids (Greek: "similar to opium") are all substances that have effects like opium or morphine. Opium is obtained from the unripe seed pods of the opium poppy, which contain numerous alkaloids - basic molecules with a nitrogen content that are mainly found in plants and act on animal nervous systems (as protection against being eaten). The three most important are morphine, codeine and thebaine. Through the further treatment of morphine, among other things, the much stronger diacetylmorphine / diamorphine, known as heroin, can be obtained. Synthetic opioids, on the other hand, are manufactured in the laboratory without the use of opium; Examples are methadone or fentanyl. Despite a slight structural similarity to morphine, they share all of the essential active properties with it, but are generally much stronger. When taken orally, opioids usually lose their effectiveness, as they (mostly) undergo presystemic elimination when they pass through the liver. It can be circumvented by injecting, sniffing, or smoking the substance. Since methadone is not subject to presystemic elimination, it can be taken orally without loss of effectiveness - a major advantage in substitution therapies.

Opioids are still indispensable in medical therapy: their most important effect is the analgesic (pain reliever), whereby the accumulation of receptors for endogenous (endogenous) opioids makes it difficult, among other things, to transmit excitation in the pain pathways in the spinal cord and to reduce pain perception. Euphoria makes a significant contribution to the development of opiate addiction - when injecting heroin in the form of a surge of exhilaration. Opioids also have a sedative effect and influence various vegetative functions, with the inhibitory effect on the respiratory center being the most important clinically. Opioids in low doses have an antitussive effect, while higher doses can paralyze the respiratory center; a large part of the acute deaths can be attributed to this ("golden shot"). Other effects include constriction of the pupils and increased smooth muscle contraction in the gastrointestinal area; cramping can lead to wall rigidity and thus constipation. Opiates are therefore also used to treat diarrhea.

Compared to the consequences of chronic alcohol abuse, the consequences of long-term opioid use are rather minor. The main damage is caused by improper application using dirty needles and syringes (hepatitis B and C, HIV infection, syringe abscesses). Further effects of chronic consumption are loss of appetite, weight loss, and increased susceptibility to infection. In the psychological field, cognitive deficits, decline in performance, neglect of other interests and changes in mood are described. Psychotic disorders usually do not occur, only rarely pronounced memory disorders or severe intellectual impairments.

With opioids, habituation occurs quickly, which is probably a consequence of the reduced sensitivity of the receptors actually intended for endogenous opioids. With abstinence, tolerance quickly recedes, with the consequence that addicts who inject their last usual dose after withdrawal run the risk of fatal overdosing. The opiate withdrawal syndrome is very impressive and uncomfortable, but rarely a deadly threat - some addicts self-subject to "cold withdrawal" to counteract the development of tolerance. It corresponds to an activation of the sympathetic nervous system with an acceleration of the pulse, an increase in blood pressure, dilated pupils, and sweating. In addition, there are vomiting and diarrhea, muscle cramps, lacrimation and flu-like symptoms. Increased sensitivity to pain and severe itching are often reported. In contrast to alcohol withdrawal, there are typically neither seizures nor delirious symptoms. Withdrawal syndrome occurs a few hours after the last dose and reaches its peak after about one to two days; then the symptoms subside, only to go away after about a week.

In contrast to the USA, where there is a real opiate epidemic, which can be traced back not least to the overly generous medical prescription of legal opioid-containing tablets over the years, the frequency of abuse is lower in this country - but on the rise. The "classic" (injecting) heroin addict has become rarer. In the meantime, there has often been a transition to orally consumed, snuffed or inhaled opioids (mostly when other psychotropic substances are consumed). A complete elimination of the addiction rarely succeeds, so that substitution therapies, for example with methadone, often remain the means of choice. As pharmaceutical products - in contrast to the products sold on the street (containing more or less toxic substances) such as heroin - these have a precisely defined composition and therefore pose less of a risk of overdosing and other poisoning. In addition, there is no risk of infection. However, since the flooding experience, which is highly valued with intravenous injection, is omitted, substitution drugs are often not accepted, or, if they are, heroin is often also consumed.

Cocaine and psychostimulants

Cocaine is a psychostimulating (drive-increasing) substance and is similar to amphetamines in this regard. It is the main alkaloid of the coca plant, which grows mainly at medium altitudes in South America. The highest cocaine content is found in the leaves that have been chewed there for thousands of years and have a performance-enhancing effect, and are also used therapeutically (for example against headaches or to treat "altitude problems"). To obtain "coke", coca leaves are processed into a paste, from which a white crystalline powder emerges through chemical treatment; it consists of cocaine hydrochloride, the alkaloid present in salt form. The expensive product can be applied in various forms, is usually sniffed or placed on other mucous membranes, and often injected. Pure cocaine, which is stronger than the hydrochloride compound, can be recovered through simple processes, such as heating with solvents and lye. In a less dangerous procedure, it is heated with sodium bicarbonate and smoked as dry lumps (crack); this is considerably cheaper and, due to its rapid influx, leads to extremely strong effects. Cocaine leads to increased alertness, euphoria, increased drive and disinhibition; consumers are unusually active, talkative and self-confident, hardly need any sleep; Feelings of hunger stay away for a long time. At higher doses, psychotic reactions in the form of hallucinations and delusions can occur, as can extreme fears and aggression. The activation of the sympathetic nervous system leads to an accelerated pulse rate and rise in blood pressure, increased respiratory rate, dilated pupils; seizures are also described. The not uncommon deaths in cocaine intoxication are primarily due to cardiovascular complications such as arrhythmias or heart attacks, often also to blockages and bleeding of the cerebral vessels; coma can occur at high doses. In addition - especially among crack smokers - accidents and acts of violence are not uncommon causes of death.

Psychostimulants also include caffeine, khat, which is widespread in Yemen and parts of north-east Africa, and the group of amphetamines (e.g. amphetamine and methamphetamine). The methylphenidate used to treat ADHD (e.g. Ritalin) is also a psychostimulant. Amphetamine is a substance related to the hormone adrenaline, which was first synthesized in the 1930s and used to treat asthma. During the Second World War, German soldiers were given pervitin with the active ingredient methamphetamine as "tank chocolate" to prevent symptoms of fatigue. Amphetamines are used as doping agents in sport. Because of the pronounced dampening of hunger, the substances were also used as appetite suppressants. Amphetamines were readily available until around 1980, but were largely withdrawn from the market later on. Today in Germany essentially only methylphenidate and amphetamine are approved as psychostimulants. They play a significant role in the illegal market. They are usually taken in tablet form, sometimes injected. Methamphetamine (obtained via simple processes from ephedrine / pseudoephedrine and then acquired as crystal meth in the form of sharp, small crystal fragments) is usually absorbed through the nasal mucosa and can also be smoked in pure preparation. Amphetamines are similar to cocaine in terms of their effects and mechanisms of action.The intake often happens cyclically with extreme consumption and euphoric overactivity, also of a sexual nature, followed by fatigue, cravings and depressive mood. Intoxications are not without risk, among other things because of severe cardiovascular reactions, but also because of the often violent behavior; Psychotic states are feared, especially after consuming crystal meth.

Tolerance development is well documented with cocaine and amphetamines; In order to achieve constant effects, an increase in dose is often necessary soon, mainly because the binding sites on the transporter proteins or the receptors respond less and less. With regard to some effects, there is sometimes an increase in effectiveness (sensitization). Withdrawal symptoms by no means occur in all users and are mainly characterized by an anxious, depressed and easily irritable mood, as well as a change in the level of activity, which can be increased (insomnia, agitation) or decreased (need for sleep, psychomotor inhibition). Most of the symptoms after consumption, especially the subsequent fatigue, can be explained as rebound effects for the regulation of neglected body needs.

Cocaine addiction develops rapidly especially when the substance is smoked or administered intravenously; Crack smokers are particularly at risk. In addition to the frequent damage to the nasal mucous membrane, the consequences of long-term consumption are particularly evident in the cardiovascular system (heart attacks, strokes). Real dependence on amphetamines develops particularly quickly when the substances are smoked, snorted or injected; abuse without strict dependency is likely to be more frequent (exception: crystal meth). Damage after chronic use is similar to cocaine. Noticeable changes can be found among crystal meth users; The rapid decay of carious teeth is attributed to reduced salivation (together with teeth grinding and a one-sided diet with sugar supplements). The changes in the skin, which "age" the consumer at a terrifying rate, are likely to be damage caused by the crystals (in the case of poor wound healing due to vasoconstriction), as well as effects of the substances used for production. Cognitive impairments are also well documented.

Cannabinoids

The hemp plant is one of the oldest cultivated plants in the world. Some of their varieties contain around a hundred psychotropic substances, of which tetrahydrocannabinol (THC) is the most important for intoxication ("booming") and various other effects; There is increasing interest in other ingredients, especially cannabidiol (CBD), the effects of which are (at least in part) contrary to those of THC. Marijuana refers to the dried leaves and shoot tips of the hemp plant, hashish refers to the THC-rich resin. Marijuana is mostly smoked, but it is also absorbed after ingestion. Hashish is commonly smoked in pipes; it can also be consumed orally, for example processed into biscuits. Compared to earlier cannabis products, those consumed today are about ten to twenty times stronger due to the higher THC content.

THC binds to specific receptors, of which two types are known: the CB1 receptor, which is mainly located in the central nervous system, and the CB2 receptor, which can be detected in lymphatic organs such as the spleen and lymph nodes. In this way, it intervenes indirectly in various transmitter systems. The effects depend heavily on the experiences and psychological initial situation of the consumer as well as the ambient atmosphere, also on the amount consumed and the ratio of the THC concentration to that of other cannabinoids, especially CBD. Mostly they are described as euphoric and peaceful-relaxing, which is based on the activation of the dopaminergic reward system, and also on the stimulation of the endogenous opioid system. Some feel stimulated to talk, others prefer to pursue their own thoughts. Psychedelic effects are often described, such as a sensation of higher color intensity, as well as a changed passage of time (time intervals appear considerably longer, movements correspondingly slower); hallucinations may occur at higher doses. The reactions are slowed down. Sometimes there are also unpleasant effects such as irritability and anxiety. The actual intoxication lasts for about three to six hours, limitations of the ability to react much longer. The THC stored in adipose tissue is only broken down slowly.

Of the various positive effects that have been reported, several can be used therapeutically: These include suppressing nausea and increasing appetite, as well as relieving spasticity and neuropathic pain, such as those that occur in particular in multiple sclerosis (MS). In the meantime, cannabis analogues and extracts of the hemp plant are approved for the treatment of pain and spasticity in MS or to combat nausea in chemotherapy, and recently cannabis flowers ("medicinal hemp"). Cannabis products with a very low content of THC (but higher levels of CBD) are now freely available for sale in many places.

The toxicity was long considered low; severe addictions or deaths were rarely observed even at high doses. However, this has changed, probably as a result of consumed synthetic cannabinoids, which are increasingly coming onto the market and which bind particularly strongly to CB receptors. A (moderate) development of tolerance is given and can be attributed to the adaptation of the cannabinoid receptors. The withdrawal symptoms mentioned earlier were not very noticeable: flu-like symptoms, diarrhea, poor appetite, sleep disorders. With a higher THC content of newer varieties and especially when consuming synthetic cannabinoids, there are more pronounced withdrawal symptoms such as severe nausea, stomach pain, and sometimes seizures. When there is abuse is controversial. In contrast to reading earlier, addiction does occur, and regular consumption over the years is by no means harmless, especially if you started early. Often the "amotivational syndrome" is described, an increasing lack of interest and drive; there has been evidence of deterioration in memory performance and attention. In addition, cannabis smokers are much more likely to develop schizophrenia, often immediately following acute intoxication. In addition, there is damage to the oropharynx and the bronchial system, because more toxic products are created when the marijuana leaves are burned than with tobacco.

Hallucinogens

Hallucinogens (psychedelics) are substances that change perception and consciousness ("mind-expanding" drugs). The best known is LSD (lysergic acid diethylamide). There are also numerous psychedelic substances contained in mushrooms or plants (including animal secretions). MDMA (Ecstasy) would also be best classified in this group. In addition, new substances with a similar effect are constantly being synthesized in laboratories ("designer drugs").

LSD was produced from ergot alkaloids by the chemist Albert Hofmann in 1943 and examined in bold self-experiments; it was used at times in scientific experiments. Mescaline, the main alkaloid of the peyote cactus, has been known as an intoxicant in Mexico for centuries. Another hallucinogen is psilocybin in mushrooms of the genus Psilocybe ("magic mushrooms"); like the dimethyltryptamine (DMT) contained in the drug ayahuasca and the bufotenin secreted by toads, it belongs to the tryptamines and is therefore (like LSD) structurally related to the neurotransmitter serotonin; the hallucinogenic effect is explained by the stimulation of certain serotonin receptors. The hallucinogens also include the anticholinergics atropine and scopolamine contained in nightshade plants (for example angel's trumpet, thorn apple, deadly nightshade). They block acetylcholine receptors and thus indirectly increase the effect of other transmitter systems (such as the dopaminergic and serotonergic). Physical reactions are the result of activation of the sympathetic nervous system (pulse acceleration, widening of the pupils). Occasionally there are (temporary) neurological symptoms; Irreversible damage to the central nervous system has also been documented, especially after taking scopalamin-containing herbal products with unknown substance content. Even after using ecstasy, severe neurological impairments (cerebral edema) can sometimes be seen, as well as acute internal symptoms such as clotting or cardiac arrhythmias.

The individual hallucinogens (at least the "classic" ones) have a similar effect in principle. Sharpened sensations, for example for colors or tones, are typical; Synaesthesias such as colored vision of sounds are also reported. Real hallucinations (perception of what is not there) occur rather rarely, at least in the usual doses; if they occur, consumers usually recognize them as substance effects. Further effects are a changed perception of space and time, feelings of unreality, as well as the (deceptive) feeling of having gained deep insights. The drive is typically increased, the mood is usually elevated; however, "bad trips" are also described. Misjudgments of reality (such as the feeling of being able to fly) often lead to self-harm. Immediate transitions into hallucinatory psychoses occur. Anticholinergics are more likely to produce delirious states. The effect of ecstasy is primarily "entactogenic": the environment and fellow human beings appear in a "positive light". Whether the desired effects of psychedelics can be used medically - for example in psychotherapy to treat the most severe depression - is the subject of current research, but so far it is still controversial.

Tolerance develops rapidly, presumably due to reduced receptor sensitivity. Severe withdrawal syndromes are not described in classic hallucinogens, and real dependencies are hardly observed. The same applies to ecstasy. However, abuse in the sense of regular consumption is not uncommon. Consequential damage such as transitions into psychosis, self-harm while intoxicated or changes in the central nervous system are not uncommon. In the meantime, cognitive disorders, especially memory, have been documented after (even occasional) use of ecstasy.

Conclusion

As this overview of the most common psychotropic substances shows, the medical benefits and physical harm of their use are often closely related - with the exception of the opioids or the sedatives (tranquilizers) not discussed here, the latter is typically greater. The dose makes the poison, goes a well-known proverb, and every excessive use or abuse of psychotropic substances has its price - often a high one. The glass of wine is part of the culture of the West; Heavy drinking bouts with their terrible consequences, on the other hand, are detrimental to culture, and the habitual abuse of alcohol can ruin the livelihood of entire families. Or as the journalist Alexander Wendt puts it: "Every drug consumption is based on a counter-deal. Those who engage in it offer a natural function of their body (...) in order to exchange an extraordinary ability. A good skin, for example, can become an object of exchange, an unproblematic one Liver function, a reliable memory. Possibly also lifetime. Possibly life itself. "[3]