What physiological pathways lie behind inhalants hallucinogenic effect?

I searched through the web and surprisingly I found pretty much nothing on the physiology of hallucinogenic effects of inhalants. Any idea how people get high with inhalants (household and industrial chemicals) and what physiological pathway lies behind this mechanism?

Diagnosis: substance abuse

Substance is often taken in larger amounts or over a longer period than was intended.
There is a persistent desire or unsuccessful efforts to cut down or control substance use.
A great deal of time is spent in activities necessary to obtain substance, use substance, or recover from its effects.
Craving, or a strong desire or urge to use substance.
Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home.
Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of substance.
Important social, occupational, or recreational activities are given up or reduced because of substance use.
Recurrent substance use in situations in which it is physically hazardous.

Substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by substance.
Tolerance, as defined by either of the following:
A need for markedly increased amounts of substance to achieve intoxication or desired effect.
A markedly diminished effect with continued use of the same amount of substance.
Withdrawal, as manifested by either of the following:
The characteristic withdrawal syndrome for substance (refer to Criteria A and B of the criteria set for substance withdrawal).
substance (or a closely related substance) is taken to relieve or avoid withdrawal symptoms.

In early remission: After full criteria for substance use disorder were previously met, none of the criteria for substance use disorder have been met for at least 3 months but for less than 12 months (with the exception that Criterion A4, "Craving, or a strong desire or urge to use substance," may be met).
In sustained remission: After full criteria for substance use disorder were previously met, none of the criteria for substance use disorder have been met at any time during a period of 12 months or longer (with the exception that Criterion A4, "Craving, or a strong desire or urge to use substance," may be met).
In a controlled environment: This additional specifier is used if the individual is in an environment where access to substance is restricted.

1. Introduction

Substance-related disorders are a set of behavioral, cognitive and physiological phenomena that occur after repeated use of a substance. These typically include: A strong desire to continue using a drug, difficulties in controlling its use, persistence in using it although it has negative consequences, the use of the substance taking precedence over other activities and obligations, along with high tolerance and sometimes withdrawal (1). New developments have altered the way we define addiction. In this sense the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) (DSM-5) (2) has changed the related chapter from ‘Substance-Related Disorders’ to ‘Substance-Related and Addictive Disorders’ as well as it lists the following types of substance addictions: Alcohol caffeine tobacco cannabis hallucinogens inhalants opioids sedatives, hypnotics and anxiolytics and stimulants.

Formerly known as an impulse control disorder, gambling was introduced in the category of addictions within the DSM-5. This important change occurred because the pathogenic mechanisms behind gambling are more similar to substance use disorders (2). This approach was initially opposed by the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) (3), which included pathological gambling to impulse control disorders alongside compulsive sexual disorder, kleptomania, pyromania and intermittent explosive disorder. Introducing gambling disorder to ICD-11 was a point of contention ultimately the ICD-11 reclassified pathological gambling to gambling disorder and exchanged it from habit and impulse disorders to disorders due to substance use or addictive behaviors. More so, for the first time, gaming disorder was added to disorders due to substance use or addictive behaviors within the ICD-11, a decision challenged by video game producers (4-6).

Although addiction has been classified as a disease since the late 1800s due to its debilitating nature on both the individual and on society, to this day neuroscientists and behavioral scientists have yet to reach a common conclusion on its cause. While neuroscientists seek genetic background and neurological correlates in the reward circuitry that accompany the development of addiction, behavioral scientists, on the other hand, strive to develop and attest behavioral models of addiction (7).

Physiological actions of opiates

Opiates (e.g., morphine, codeine, and thebaine) exert their main effects on the brain and spinal cord. Their principal action is to relieve or suppress pain. The drugs also alleviate anxiety induce relaxation, drowsiness, and sedation and may impart a state of euphoria or other enhanced mood. Opiates also have important physiological effects: they slow respiration and heartbeat, suppress the cough reflex, and relax the smooth muscles of the gastrointestinal tract. Opiates are addictive drugs they produce a physical dependence and withdrawal symptoms that can only be assuaged by continued use of the drug. With chronic use, the body develops a tolerance to opiates, so that progressively larger doses are needed to achieve the same effect. The higher opiates—heroin and morphine—are more addictive than opium or codeine. Opiates are classified as narcotics because they relieve pain, induce stupor and sleep, and produce addiction. The habitual use of opium produces physical and mental deterioration and shortens life. An acute overdose of opium causes respiratory depression which can be fatal.

Opium was for many centuries the principal painkiller known to medicine and was used in various forms and under various names. Laudanum, for example, was an alcoholic tincture (dilute solution) of opium that was used in European medical practice as an analgesic and sedative. Physicians relied on paregoric, a camphorated solution of opium, to treat diarrhea by relaxing the gastrointestinal tract. The narcotic effects of opium are mainly attributable to morphine, which was first isolated about 1804. In 1898 it was discovered that treating morphine with acetic anhydride yields heroin, which is four to eight times as potent as morphine in both its pain-killing properties and its addictive potential. The other alkaloids naturally present in opium are much weaker codeine, for example, is only one-sixth as potent as morphine and is used mainly for cough relief. Since the late 1930s, various synthetic drugs have been developed that possess the analgesic properties of morphine and heroin. These drugs, which include meperidine (Demerol), methadone, levorphonal, and many others, are known as synthetic opioids. They have largely replaced morphine and heroin in the treatment of severe pain.

Opiates achieve their effect on the brain because their structure closely resembles that of certain molecules called endorphins, which are naturally produced in the body. Endorphins suppress pain and enhance mood by occupying certain receptor sites on specific neurons (nerve cells) that are involved in the transmission of nervous impulses. Opiate alkaloids are able to occupy the same receptor sites, thereby mimicking the effects of endorphins in suppressing the transmission of pain impulses within the nervous system.

The Effects of Painkillers on the Brain and Body

Drug abuse of painkillers can cause harmful effects on the brain and body of the person using the substance. Painkillers can refer to a number of both over-the-counter (OTC), prescription and illicit drugs, but more often than not related to narcotic painkillers like Percocet, OxyContin and heroin. It is these narcotic painkillers that carry the highest risk of dependency and addiction.

Whether a painkiller is prescribed by a doctor or acquired on the street, these drugs can cause serious changes to the brain and body of the user. Although some damage can occur with short-term drug use, the most extreme or dangerous changes to the brain and body typically occur with long-term use and abuse of painkillers. Long-term use also increases the possibility of addiction and physical dependency on the drugs. After a while, users need these drugs just to keep away physical withdrawal symptoms and to physically feel normal. Painkillers are the second most abuse substances in the United States, ranking behind only marijuana use.

Painkillers work by blocking the brain’s perception of pain by binding to opiate receptors. This interferes with the signals transmitted by the central nervous system to the brain. Narcotic pain relievers are depressants, meaning they have a depressant effect on the central nervous system and decrease the feeling of pain while increasing a feeling of relaxation. By binding to the opiate receptors, painkillers also cause feelings of euphoria. It is these euphoric feelings that are often associated with painkiller use and the “high” that users get when abusing painkillers.

Narcotic painkillers bind to opiate receptors which are typically bound by special hormones called neurotransmitters. When painkillers are used for a long period of time, the body slows down production of these natural chemicals and makes the body less effective in relieving pain naturally. That is because narcotic painkillers fool the body into thinking it has already produced enough chemicals as there becomes an overabundance of these neurotransmitters in the body. Existing neurotransmitters have nothing to bind with, as the drugs have taken their place on the opiate receptors. Because of this occurrence, the levels of naturally occurring neurotransmitters in the body decreases and the body builds an increased tolerance to the painkillers so more of the substance is needed to produce the same effect. Many of the neurotransmitters that are decreased include natural endorphins that are considered feel-good chemicals in the brain that also help with pain. Therefore, chemical dependency increases and likelihood of addiction increases as the body is unable to produce the natural chemical needed to relieve pain.

Neurotransmitters are necessary to send signals between the nerves to complete the brain and body connections. Although painkillers take the place of neurotransmitters on the opiate receptors, they cannot fill all of the neurotransmitters roles. Painkillers also depress the central nervous system, meaning the brain and the nerves, leading to slower breathing, slurred speech, and slower bodily reactions.

Painkiller physical dependency often comes after prolonged use and abuse of the drug, but consistent daily use of painkillers over a period of several straight days can also cause a physical addiction. Once someone is physically addicted to painkillers, they will experience extreme physical withdrawal symptoms once they stop taking painkillers. These physical symptoms can occur as soon as 4-6 hours after last use. Physical withdrawal symptoms can include: agitation, restlessness, hot and cold sweats, nausea and vomiting, muscle aches, irritability, headaches, sleeplessness, bone and joint pain, emotional instability, depression and basically like the worst flu ever multiplied by one hundred. Often simply this fear of the pain of withdrawal will keep an addict using for years past the point where they’ve recognized a drug problem and a need to stop.

Painkillers cause chemical changes to the brain and also kills brain cells. The most affected areas of the brain are those areas that deal with cognition, learning and memory. Painkiller use and abuse also can affect nerve cells. Additionally, based on the manner in which the drug is used, painkiller abuse can cause long-term heart damage and increase the likelihood of a heart attack. Crushing and snorting the drug can cause damage to the nose and lungs and crushing and injecting the drug increases the risk of infection.

If you or someone you know is suffering from a drug and alcohol addiction and needs treatment please call us for help. Maryland Addiction Recovery Center offers the most comprehensive addiction treatment in the area. If we aren’t the best fit, we will work with you to find a treatment center that fits your needs. Please call us at (888) 491-8447 or email our team at [email protected] For more information on all of our alcohol and addiction treatment services and resources, please visit the web site at

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Anabolic steroids are synthetically produced variants of the naturally occurring male hormone testosterone. They are often abused to promote muscle growth, enhance athletic ability or physical performance, improve physical appearance or increase strength. Some of the most abused anabolic steroids are testosterone, nandrolone, methandienone, boldenone&hellip

Alcohol, ethyl alcohol, or ethanol, is an intoxicating ingredient found in beer, wine, and liquor. Alcohol is produced by the fermentation of yeast, sugars, and starches. Alcohol is a powerfully intoxicating substance, sometimes even causing a physical dependence for the user and is a central nervous&hellip

Cocaine, a powerfully addictive, psychoactive, stimulant drug, is derived from the processed leaves of the cocoa plant. Cocaine can be used by being snorted, smoked or injected. Cocaine does not produce a physical dependence like heroin or benzodiazepines but it can be very&hellip

Marijuana has been headlining the news recently. From the Colorado to Maryland to California to Washington State, everyone is weighing in on the marijuana debate. Should it be legal? Should it only be used for medicinal purposes? Is there a governmental agenda? Should it stay&hellip

Zachary Snitzer

Zach Snitzer is the Corporate Director of Marketing at Maryland Addiction Recovery Center and is responsible for the business development, marketing, branding, public relations and social media strategies of the organization.


The percentage of laboratory animals that show addictive-like behaviors, or of people that become addicted to a drug after repeated exposure, varies as a function of the drug, being higher for drugs like heroin or methamphetamine and lower for drugs like alcohol or cannabis. For example, only between 15 and 20% of rats chronically exposed to cocaine will continue to compulsively prefer cocaine over other rewarding options (52), whereas the percentage of heroin-preferring rats can go as high as 50% under similar experimental conditions (198). These percentages, however, do vary across different rat strains, highlighting the role of genetics in modulating drugs’ effects. Epidemiological data are generally consistent with this picture. According to the best available estimates, the odds, in lifetime drug users, of ever becoming addicted to alcohol, cannabis, cocaine, or opioids (heroin) are

1.5, 9, 17, and 23%, respectively (7). As of now, it is not clear what determines the transition from drug experimentation to addiction, which emerges when individuals lose their ability to overcome the strong urge to take the drug despite a conscious awareness of not wanting to do so and the recognition of their potentially catastrophic consequences. However, we do know this transition is associated with measurable disruptions in several brain circuits including those involved with conditioning, reward sensitivity, incentive motivation, self-monitoring/regulation, mood, and interoception. In this review, we use the term addiction in correspondence with the dimensional definition of moderate to severe SUD as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (TABLE 2).

Table 2. Diagnostic criteria for substance use disorder based on DSM-5

A mild substance use disorder (SUD) is diagnosed with 2–3 criteria, moderate with 4–5, and severe 6–7 criteria (147). DSM-5, Diagnostic and Statistical Manual of Mental Disorders.

Myths About Addiction

The processes that give rise to addictive behavior resist a simplistic explanation. There is not just one cause: Although genetic or other biological factors can contribute to a person’s vulnerability to the condition, many social, psychological, and environmental factors also have a powerful influence on substance use.

Some characteristics, such as a lack of ability to tolerate distress or other strong feelings, have been associated with addiction, but there is no one “addictive personality” type that clearly predicts whether a person will face problems with addiction.

Cocaine Research Report What are some ways that cocaine changes the brain?

Use of cocaine, like other drugs of abuse, induces long-term changes in the brain. Animal studies show that cocaine exposure can cause significant neuroadaptations in neurons that release the excitatory neurotransmitter glutamate. 9,10 Animals chronically exposed to cocaine demonstrate profound changes in glutamate neurotransmission—including how much is released and the level of receptor proteins—in the reward pathway, particularly the nucleus accumbens. The glutamate system may be an opportune target for anti-addiction medication development, with the goal of reversing the cocaine-induced neuroadaptations that contribute to the drive to use the drug. 9

Although addiction researchers have focused on adaptations in the brain’s reward system, drugs also affect the brain pathways that respond to stress. Stress can contribute to cocaine relapse, and cocaine use disorders frequently co-occur with stress-related disorders. 11 The stress circuits of the brain are distinct from the reward pathway, but research indicates that there are important ways that they overlap. The ventral tegmental area seems to act as a critical integration site in the brain that relays information about both stress and drug cues to other areas of the brain, including ones that drive cocaine seeking. 11 Animals that have received cocaine repeatedly are more likely to seek the drug in response to stress, and the more of the drug they have taken, the more stress affects this behavior. 11 Research suggests that cocaine elevates stress hormones, inducing neuroadaptations that further increase sensitivity to the drug and cues associated with it. 11

Chronic cocaine exposure affects many other areas of the brain too. For example, animal research indicates that cocaine diminishes functioning in the orbitofrontal cortex (OFC), which appears to underlie the poor decision-making, inability to adapt to negative consequences of drug use, and lack of self-insight shown by people addicted to cocaine. 12 A study using optogenetic technology, which uses light to activate specific, genetically-modified neurons, found that stimulating the OFC restores adaptive learning in animals. This intriguing result suggests that strengthening OFC activity may be a good therapeutic approach to improve insight and awareness of the consequences of drug use among people addicted to cocaine. 13

Cocaine Research Report How does cocaine produce its effects?

The brain’s mesolimbic dopamine system, its reward pathway, is stimulated by all types of reinforcing stimuli, such as food, sex, and many drugs of abuse, including cocaine. 8 This pathway originates in a region of the midbrain called the ventral tegmental area and extends to the nucleus accumbens, one of the brain’s key reward areas. 8 Besides reward, this circuit also regulates emotions and motivation.

In the normal communication process, dopamine is released by a neuron into the synapse (the small gap between two neurons), where it binds to specialized proteins called dopamine receptors on the neighboring neuron. By this process, dopamine acts as a chemical messenger, carrying a signal from neuron to neuron. Another specialized protein called a transporter removes dopamine from the synapse to be recycled for further use. 8

Drugs of abuse can interfere with this normal communication process. For example, cocaine acts by binding to the dopamine transporter, blocking the removal of dopamine from the synapse. Dopamine then accumulates in the synapse to produce an amplified signal to the receiving neurons. This is what causes the euphoria commonly experienced immediately after taking the drug (see the video "Brain Reward: Understanding How the Brain Responds to Natural Rewards and Drugs of Abuse").

Ch. 1: Introduction to Psychological Models of Addiction

Over the years, psychological principles have contributed to the development of many theories about substance use disorders and addiction. Learning theories represent one set of psychological principles that have had a strong influence on our understanding of the causes of addiction, as well as informing some of our intervention strategies. Relevant learning theories include both operant and classical conditioning principles.

The classical conditioning process helps explain why stimuli in the environment or sensations originating from inside the body often trigger a person’s craving for a substance. Certain areas of the brain may be triggered just by seeing the paraphernalia used to administer a drug, inducing an intense craving for the drug. This is no different, really, from Pavlov’s dogs learning to associate food with the ringing of a bell through classical conditioning, and drooling over the previously irrelevant sound. The craving trigger stimulus from the environment might involve any of the five senses: hearing, seeing, touching, smelling, or tasting. Or, craving may be triggered by familiar internal states (like anxiety, depression, loneliness) that were previously alleviated by taking drugs.

Operant conditioning is all about rewards and punishments. A person might use a drug for the first time and enjoy the feelings it creates, which is a positive reinforcement for the behavior. Similarly, the person might find that the drug decreases a negative feeling like pain, low mood, or anxiety. This, too, would be reinforcing—what we call negative reinforcement. These basic learning theories are taken a step further with an understanding of social learning theory. A person does not necessarily have to experience the rewards and punishments themselves learning also happens by watching others engage in the behavior and seeing what happens to them.

Through observational learning, we learn to imitate both the precise behaviors and general classes of behavior modeled by others in our social environment. In other words, a person might not imitate a parent who uses alcohol for relaxation from stress (the specific or precise behavior) but imitates the general class of behavior being modeled by using marijuana this way.

This concept leads to another set of psychological principles in addiction: drug or alcohol expectancies. Expectancies are the set of beliefs individuals develop regarding how using these substances might affect them. A person develops expectancies from many sources: other people, television, movies, music, news, social media, and others, including their own personal prior experiences with the drug.

Even young children have been shown to develop both positive and negative expectancies about the outcomes of drinking alcohol (Donovan, Molina, & Kelly, 2009).

Simply put, alcohol or other drug use is more likely if positive outcomes are expected than if negative outcomes are expected. Results from the 2016 Monitoring the Future study of middle and high school students are informative here. The students were asked to rate the harmfulness of various substance use behaviors in terms of how much they believed a person risks self-harm (physical or other ways) by using specific substances. Figure 1 shows a portion of the results from the 8 th , 10 th , and 12 th graders. As you can see, the students expected less potential harm with an experimental trial of these substances (once or twice) compared to occasional or regular use. They also distinguished between the potential harm of using different types of substances, especially they viewed alcohol and marijuana as being less harmful than the other substances. This estimate of harmfulness represents an expectancy related to using these substances in the described patterns.

Figure 1. Percent reporting “great risk” if a person…

Try one or two drinks of an alcoholic beverage

Take one or two drinks nearly every day

Have five or more drinks once or twice each weekend

Try marijuana once or twice

Smoke marijuana occasionally

Smoke marijuana regularly

Try heroin once or twice without using a needle

Take heroin occasionally without using a needle

Try cocaine once or twice

Take cocaine occasionally

Try any narcotic other than heroin (codeine, Vicodin, OxyContin, Percocet, etc.) once or twice

Take any narcotic other than heroin occasionally

Take any narcotic other than heroin regularly

Yet another set of psychological theories address human information processing. This area of cognitive psychology explains how substance use can affect the way that a person takes in (perceives) information from the environment, stores the information as a short-term memory, moves information into long-term memory, and later retrieves information in order to influence behavior.

Research suggests that when a person learns something while under the influence of a drug, it is possible that they will not be able to retrieve what they learned later, when the person is in a sober state—there simply will not be enough retrieval cues available to trigger the recall. This information processing framework not only has tremendous implications for how individuals function when taking psychotropic substances, but also how they often have to re-learn many things once they enter into recovery or quit using after a period of regular use.

Past clinical literature includes discussions about the “addictive personality.” This concept presumes the existence of specific personality traits that characterize individuals who develop substance use or addiction disorders. The idea is that people are predisposed to developing addiction based on specific personality traits (in much the same way we might theorize a predisposition based on genetics). While there may be some characteristics commonly observed in the population of individuals with substance use disorders, the evidence does not support there being a universal set of personality traits or a personality type associated with addiction—evidence for the existence of an “addictive personality” type does not really exist (per Szalavitz, 2016 citing an interview with George Koob, director of the National Institute on Alcohol Abuse and Alcoholism). An argument discussed by Szalavitz (2016) is the observation that 18% of persons with an addiction also have “a personality disorder characterized by lying, stealing, lack of conscience, and manipulative antisocial behavior.” While this rate of 18% is more than four times the rate seen across the general population, it still means the 82% of people experiencing addiction do not fit that characteristic. This is the case with study after study of personality traits. The population of people experiencing addiction is tremendously diverse and heterogeneous on all fronts: demographics and personality alike. This also means that pretty much anyone, regardless of personality type, could potentially develop an addiction if the right (or wrong) combination of factors come together.

There are psychodynamic, attachment theory, and self-medication perspectives about addiction to consider, as well. These psychological approaches suggest that a person uses drugs to fill a terrific void in their emotional lives or as a means of quieting voices of inner conflict. A person might be using the drugs to find relief from physical or emotional pain.

These are called self-medication theories. In this line of thinking, a person uses substances to avoid or blunt their negative or disturbing feelings, as in the Pink Floyd song lyrics: “I have become comfortably numb.” The underlying basis for the pain that is being medicated is usually attributed to trauma—adverse childhood experiences (ACES), sexual or violence trauma as an adult, or other experiences associated with post-traumatic stress. We do know that trauma experiences and post-traumatic stress disorder (PTSD) are commonly reported among women and men with substance use disorders (we will learn more about this in Module 14 when we talk about co-occurring problems). However, it is a gross oversimplification to attribute this association to self-medication efforts. The aftermath of trauma is complex and variable, involving changes in (1) neurological pathways–especially the amygdala that we studied in Module 3, that keeps signally the presence of threat long after the threat is past, (2) changes in biology, and (3) changes in how a person interfaces with the social environment. Furthermore, trauma is often a consequence of substance misuse, not only an antecedent. Regardless, practitioners are now very aware of how important it is to screen and assess for both PTSD and substance use disorders, and to treat both issues together if they co-occur.

The remaining readings in this module elaborate further about these psychological models and theories.

Watch the video: Ich bin dann mal weg! Die Pharmakologie der Injektionsnarkotika! (January 2022).