question: How does tolerance (Alcohol, Marijuana, etc) build in your body and affect your interpretation of the affects?
comment: Your brain works via neuroreceptors - little links which consist of a sender and a receiver. The sender puts out little bits of chemicals, and the receiver watches for those and does something based on what they see. Suppose that you are a receiver. Your job is to make the brain feel good every time you see a light flash. Normally the light flashes once per minute - maybe 2 or 3 times per minute under special circumstances. But then drugs get involved. The drugs make the light flash *twenty* times per minute. At first you go crazy - wow, this must be important! You get hard to work making the brain feel good. But that super-quick flashing *just keeps coming*. Eventually, you get a little lazy. "Oh, it must not be important after all," you say - it's like someone who always puts the word "URGENT" in the subject of their emails. So you start treating 20 flashes per minute as the new normal. Maybe you'll work extra hard if you see *forty* flashes per minute, but until then, nah. Then when it goes back to the old one flash per minute, you think "Huh, I guess that means it's break time for me" and you don't do *any* work. That's what withdrawal is.
passages: Behavioral tolerance occurs with the use of certain psychoactive drugs, where tolerance to a behavioral effect of a drug, such as increased motor activity by methamphetamine, occurs with repeated use. It may occur through drug-independent learning or as a form of pharmacodynamic tolerance in the brain; the former mechanism of behavioral tolerance occurs when one learns how to actively overcome drug-induced impairment through practice. Behavioral tolerance is often context-dependent, meaning tolerance depends on the environment in which the drug is administered, and not on the drug itself. Behavioral sensitization describes the opposite phenomenon.
   Pharmacodynamic tolerance begins when the cellular response to a substance is reduced with repeated use. A common cause of pharmacodynamic tolerance is high concentrations of a substance constantly binding with the receptor, desensitizing it through constant interaction. Other possibilities include a reduction in receptor density (usually associated with receptor agonists), or other mechanisms leading to changes in action potential firing rate. Pharmacodynamic tolerance to a receptor antagonist involves the reverse, i.e., increased receptor firing rate, an increase in receptor density, or other mechanisms.
   While research has been conducted on the effects of addictive drugs on spatial memory, there has not been research that investigates whether chronic ethanol exposure would produce tolerance to these effects in addition to ethanol tolerance.
  
  Section::::Abnormalities.:Effects of vestibular lesioning.
   Pharmacokinetic tolerance (dispositional tolerance) occurs because of a decreased quantity of the substance reaching the site it affects. This may be caused by an increase in induction of the enzymes required for degradation of the drug e.g. CYP450 enzymes. This is most commonly seen with substances such as ethanol.
   Section::::Signs and symptoms.:Dependency.
  
  Prolonged cannabis use produces both pharmacokinetic changes (how the drug is absorbed, distributed, metabolized, and excreted) and pharmacodynamic changes (how the drug interacts with target cells) to the body. These changes require the user to consume higher doses of the drug to achieve a common desirable effect (known as a higher tolerance), reinforcing the body's metabolic systems for eliminating the drug more efficiently and further down-regulating cannabinoid receptors in the brain.
   Drug tolerance
  
  Drug tolerance is a pharmacological concept describing subjects' reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drug's effects; however, this may accelerate tolerance, further reducing the drug's effects. Drug tolerance is indicative of drug use but is not necessarily associated with drug dependence or addiction. The process of tolerance development is reversible (e.g., through a drug holiday) and can involve both physiological factors and psychological factors.
   The opposite concept to drug tolerance is drug reverse tolerance (or drug sensitization), in which case the subject's reaction or effect will increase following its repeated use. The two notions are not incompatible and tolerance may sometimes lead to reverse tolerance. For example, heavy drinkers initially develop tolerance to alcohol (requiring them to drink larger amounts to achieve a similar effect) but excessive drinking can cause liver damage, which then puts them at risk of intoxication when drinking even very small amounts of alcohol.
   Cannabis users have shown decreased reactivity to dopamine, suggesting a possible link to a dampening of the reward system of the brain and an increase in negative emotion and addiction severity.
  
  Cannabis users can develop tolerance to the effects of THC. Tolerance to the behavioral and psychological effects of THC has been demonstrated in adolescent humans and animals. The mechanisms that create this tolerance to THC are thought to involve changes in cannabinoid receptor function.
   Increased expression of AMPA receptors in nucleus accumbens MSNs is a potential mechanism of aversion produced by drug withdrawal.
  
  Section::::Biomolecular mechanisms.:Physical dependence.
   While most occurrences of pharmacodynamic tolerance occur after sustained exposure to a drug, instances of acute or instant tolerance (tachyphylaxis) can occur.
  
  Section::::Pharmacokinetic (metabolic) tolerance.
  
  Pharmacokinetics refers to the absorption, distribution, metabolism, and excretion of drugs (ADME). All psychoactive drugs are first absorbed into the bloodstream, carried in the blood to various parts of the body including the site of action (distribution), broken down in some fashion (metabolism), and ultimately removed from the body (excretion). All of these factors are very important determinants of crucial pharmacological properties of a drug, including its potency, side effects, and duration of action.
   This type of tolerance is most evident with oral ingestion, because other routes of drug administration bypass first-pass metabolism. Enzyme induction is partly responsible for the phenomenon of tolerance, in which repeated use of a drug leads to a reduction of the drug’s effect. However, it is only one of several mechanisms leading to tolerance.
  
  Section::::Behavioral tolerance.
   Section::::Book Structure.:3. Latent Variables.
  
  This chapter discusses the theory behind latent variables in psychometrics particularly with regard to item response theory. In particular Borsboom discusses issues of causality with regard to latent variables and the extent to which latent variables can be regarded as “causes” of between-subject differences and also be treated as a causal factor within a subject.
  
  Section::::Book Structure.:4. Scales.
   One may also develop drug tolerance to side effects, in which case tolerance is a desirable characteristic. A medical intervention that has an objective to increase tolerance (e.g., allergen immunotherapy, in which one is exposed to larger and larger amounts of allergen to decrease one's allergic reactions) is called drug desensitization.
   Section::::Research.:"Developing Pharmacotherapies for Cannabis and Cocaine Use Disorders".
   In recent years his research focus has shifted more to the examination of how environmental events, including drugs, stress, hormones, and learning differentially affect brain and behavior at different developmental ages by altering neuronal morphology, gene expression, and ultimately behavior. His work on the effects of drugs on neuronal morphology, in collaboration with Terry Robinson (University of Michigan), was the first to show that the physical structure of neurons becomes altered by addictive drugs, thus showing that drugs physically alter brain systems.
  
  Section::::Awards/honors.
   Section::::Research.:Increased tolerance.
   Finally, a link has been found between ethanol use and histone acetylation during development. After ethanol exposure, adolescent rats showed increased H3 and H4 acetylation in reward centers of the brain, such as the frontal cortex and nucleus accumbens. This effect was not seen in adult rats. Thus, brain chromatin remodeling that increases gene expression in reward centers of developing brains may contribute to an increased propensity toward alcoholism upon and after ethanol exposure.
  
  Section::::Tolerance.
   Tolerance is a lessened response to ethanol after repeated or prolonged ethanol exposure or consumption. In mammals, tolerance can form within minutes or over longer periods of time. Ghezzi et al. (2014) speculated that tolerance occurs due to a homeostatic mechanism that resists environmental changes. However, homeostatis does not explain how tolerance influences alcohol addiction in many cases. Epigenetic alterations, including phosphorylation, methylation, acetylation, miRNA, and chromatin remodeling, may help explain the cases not explained by homeostatic mechanisms.
   In the study of malleable intelligence, behavioral factors are often the most intriguing because these are factors humans can seek to control. There are numerous behavioral factors that affect intellectual development and neural plasticity. The key is plasticity, which is caused by experience-driven electrical activation of neurons. This experience-driven activation causes axons to sprout new branches and develop new presynaptic terminals. These new branches often lead to greater mental processing in different areas.
  
  Section::::Behavioral factors.:Taking advantage of the critical period.
  
  As previously discussed, the critical period is a time of neural pruning and great intellectual development.
  
  Section::::External links.
   Section::::Reducing LFT.
  
  In REBT, reducing irrational beliefs and increasing rational beliefs can reduce LFT. This cognitive restructuring allows a modification of dysfunctional thinking and acting, and allows people to change thoughts of great distress like:
  
  · “Existing conditions must be changed to give me what I like, otherwise I can't stand it and I can't be happy at all!”
  
  · "I must have immediate gratification and have to have it, or else I can't stand it and my life is awful"
  
  · "I can't stand hassles"
  
  Into more rational and less exaggerated thoughts like:
  
  · "I don't like existing conditions"
   Section::::Drug induced.
  
  Neural adaptation can occur for other than natural means. Antidepressant drugs, such as those that cause down regulation of β-adrenergic receptors, can cause rapid neural adaptations in the brain. By creating a quick adaptation in the regulation of these receptors, it is possible for drugs to reduce the effects of stress on those taking the medication.
  
  Section::::Post-injury.
   The example of someone having a positive experience with a drug is easy to see how drug dependence and the law of effect works. The tolerance for a drug goes up as one continues to use it after having a positive experience with a certain amount the first time. It will take more and more to get that same feeling. This is when the controlled substance in an experiment would have to be modified and the experiment would really begin. The law of work for psychologist B. F. Skinner almost half a century later on the principles of operant conditioning, "a learning process by which the effect, or consequence, of a response influences the future rate of production of that response.
   BULLET::::- Donaldson, Stewart I. (1995). Peer influence on adolescent drug use: A perspective from the trenches of experimental evaluation research. American Psychologist, 50, 801-802.
  
  BULLET::::- Donaldson, Stewart I., Graham, John W., Piccinin, Andrea M., & Hansen, William B. (1995). Resistance-skills training and onset of alcohol use: Evidence for beneficial and potentially harmful effects in public schools and in private Catholic schools. Health Psychology, 14, 291-300.
  
  BULLET::::- Donaldson, Stewart I., Graham, John W., & Hansen, William B. (1994). Testing the generalizability of intervening mechanism theories: Understanding the effects of school-based substance use prevention interventions. Journal of Behavioral Medicine, 17, 195-216.
   Alcohol tolerance
  
  Alcohol tolerance refers to the bodily responses to the functional effects of ethanol in alcoholic beverages. This includes direct tolerance, speed of recovery from insobriety and resistance to the development of alcoholism.
  
  Section::::Consumption-induced tolerance.
  
  Alcohol tolerance is increased by regular drinking. This reduced sensitivity requires that higher quantities of alcohol be consumed in order to achieve the same effects as before tolerance was established. Alcohol tolerance may lead to (or be a sign of) alcohol dependency.
   Prospective epidemiological studies do not support the hypotheses that comorbidity of substance use disorders with other psychiatric illnesses is primarily a consequence of substance abuse or dependence or that increasing comorbidity is largely attributable to increasing use of substances. Yet emphasis is often on the effects of substances on the brain creating the impression that dual disorders are a natural consequence of these substances. However addictive drugs or exposure to gambling will not lead to addictive behaviors or drug dependence in most individuals but only in vulnerable ones, although, according to some researchers, neuroadaptation or regulation of neuronal plasticity, and molecular changes, may alter gene expression in some cases and subsequently lead to substance use disorders.
  