Specificity of Drug Tolerance
Drug Tolerance is a decreased sensitivity to a drug that develops due to exposure. In short, more and more of a drug is needed to achieve the same response. It can also be shown when the same dose has effect over time. This is sown by a shift to the right in the dose-response curve.
- Cross Tolerance – Exposure to one drug can produce tolerance to other drugs that act by the same mechanism
- Drug Sensitization – Increases in the sensitivity to a drug. You can become tolerant to some effects of a drug, but not others.
- Not a unitary phenomenon – When a drug is administered at active doses, all kinds of changes can occur to reduce its effects.
How Drug Tolerance Happens
- Metabolic Tolerance – Changes that reduce the amount of the drug getting to an activation site (increasing the rate it is broken down in the liver)
- Functional Tolerance – Results from changes that reduce the reactivity of the sites of action to the drug; tolerance to psychoactive drugs (those that change your thoughts, feelings, perceptions and behaviors) is typically functional, and shown by many experiments to be the result of Pavlovian conditioning. In one experiment (Crowell, Hinson & Siegel, 1981), rats injected with alcohol only demonstrated hypothermic effects (temperature reducing) only when they were given alcohol in the same room as it was previously administered. This, and many other experiments, demonstrates the Situational Specificity of drug tolerance.
Conditioned Compensatory Responses – According to Siegal, conditional stimuli that predict drug administration elicit conditional responses opposite to the unconditional effects of the drug – ie, if someone is in a situation where previous drug use has occurred, changes in the nervous system occur to counteract the effects. The day you experience a Conditioned Compensatory Response, you have a craving or physiological need for a drug.
Physical Dependence on Drugs
Occurs when people suffer from withdrawal symptoms when they stop taking a drug, and it is eliminated from their system. Withdrawal symptoms are almost always the opposite of the initial effects of a drug, which suggests that they are produced by the same neural changes that produce drug tolerance.
Biological Theories of Drug Addiction
What is Drug Addiction?
Addicts are habitual users; however, not all habitual users are addicts. The difference is that addicts continue to use a drug despite adverse on their health/life, and repeated, failed efforts to stop using it.
Physical Dependence Theory of Addiction
The earliest models of addiction were based on a theory that suggested drug addicts are driven by an aversion to withdrawal symptoms. However, attempts to gradually curtail drug use in addicts show that nearly all detoxified addicts return to former drug-taking habits. Another piece of evidence is that some drugs, like cocaine and amphetamines, do not produce withdrawal symptoms. Finally, some drugs involve cycles of binges and detoxification, which indicated detoxification does not prevent addicts from renewing their habits.
Positive Incentive Theory
The Positive Incentive Theory suggests that addiction is caused by the anticipated pleasure of taking a drug. Robinson and Berridge’s Incentive Sensitization Theory argue that it isn’t the liking of drug taking, but the anticipated pleasure, that creates addiction, so that in cases of chronic use, the incentive value is often disproportionate to the actual pleasure derived from it. Hence, even though the drugs result in misery, addicts continue to crave them even more.
What Causes a Drug Addict to Relapse?
- Stress – The major factor in relapse.
- Priming – Users who have abstained believe that their addiction is under control; however, one use and they often plunge back into addiction;
- Environmental Cues – Anything previously associated with the drug (times, places, people, objects) associated with the drug can induce relapse.
Facts About Commonly Used Drugs
Tobacco and alcohol have much larger negative health effects on Americans than marijuana, cocaine and heroin
- Nicotine is the major psychoactive ingredient
- Responsible for over 3 million deaths per year worldwide (about 450,000 in the US, and about 20% of all deaths in Western countries)
- High tolerance develops
- 70% of experimenters become addicted versus 10% for alcohol and 30% for heroin
- Only 20% of attempts to quit are successful for 2 years or more
- Nicotine addiction has a genetic component with 65% heritability
- Smokers are actually more tense than non-smokers; stress level increase between cigarettes
- Buerger’s Disease – Blood vessels in the legs constrict when nicotine enters the system, leads to gangrene and amputation
- Smoking during pregnancy increases the risk of miscarriage, stillbirth and early death of a child; levels of nicotine in breastfed infants is nearly as high as in the blood of their smoking mothers
- 100,000 Americans die each year from alcohol-related diseases and accidents, and is involved in about 3% of all deaths in the US
- Alcohol is classified as a depressant because it decreases neural firing; at low doses, it can stimulate neural firing and sociability
- Alcohol has a major genetic component; 55% heritability
- Blood levels at 0.5% causes risk of death from respiratory depression
- A hangover is actually alcohol withdrawal
- Delirium tremens (DTs) – third phase of withdrawal which starts about 1 to 2 days after cessation, and lasts 3 to 4 days, causes hallucinations, delusions, agitation, confusion, high temperature, and increased heart rate
- Chronic alcohol consumption is associated with extensive brain damage
- Korsakoff’s Syndrome – neuropsychological disorder characterized by severe memory loss, sensory and motor dysfunction, and dementia
Marijuana (Cannabis Sativa)
- Psychoactive ingredient is THC (delta-9-tetrahydrocannabinol) which are in the form of a sticky resin on the leaves and flowering part of the plant; when extracted, this is called hashish
Can be smoked, or baked into an oil-rich substrate and ingested orally
- Usage goes back 6,000 to China
- George Washington grew cannabis for rope
- Some laws classify marijuana as a narcotic; however, the structures of the active ingredients, physiological and behavior effects bear no resemblance to other narcotics
- High doses impair psychological functioning – short term memory impairment and ability to perform multi-step tasks, slurred speech, limited ability to have a meaningful conversation
- Seems to curb aggressive behavior
- Low addiction potential, but tolerance does develop, no obvious withdrawal symptoms
- Most scientists agree that small amounts have few, if any, permanent adverse effects, and long-term adverse effects are fewer than legal drugs like alcohol and nicotine
- Respiratory problems are common, as is elevated heart rate
- Anadamide is a clone of the THC-like chemical that binds to the receptor, but function is still unknown; it may protect the brain from excitotoxicity; mice without these receptors are more susceptible to seizures
Cocaine & Stimulants
- Stimulants increase neural and behavioral activity
- Coca-Cola is a mild stimulant that uses caffeine, but originally contained small amounts of cocaine
- Cocaine is derived primarily in Peru and Bolivia from the coca bush
- Cocaine hydrochlorida is the white powder most people are familiar with, and it is usually snorted or injected
- Crack is an impure form of cocaine residue that is usually smoked
- 1.5 million Americans used cocaine or crack in the last month
- Often consumed in binges, like alcohol
- Cocaine psychosis is similar to paranoid schizophrenia
- Extremely addictive, but mild withdrawal symptoms
- Blocks the reuptake of catecholamines (dopamine, norepinephrine, and epinephrine)
- Amphetamines (speed) has effects similar to cocaine; methamphetimines (METH) and MDMA/Esctacy are other popular forms of amphetamines
- Stimulants are neurotoxins and a large cause for concern; MDMA has been shown to have toxic effects on serotonergic and dopaminergic neurons, and has been shown to cause brain damage
- Women who use stimulants while pregnant often have children with lower IQs
Opiates: Heroin & Morphine
- Opium contains morphine and codeine, a weaker derivative
- Unmatched at painkillers, and can be used to treat coughs
- Also highly addictive
- Practice of eating opium became popular in the Middle East around 4000 B.C.
- Harrison Narcotics Act 1914 made it illegal to sell or use opium, morphine or cocaine, but not heroin, which can penetrate the blood-brain barrier
- In 1989, Bayer Drug Company marketed heroin, which was available without a prescription, as a non-addictive super-aspirin; it became illegal in 1942
- About 130,000 Americans currently use heroin
- Direct health hazards of chronic exposure are fairly minor
- Dr. William Stewart Halsted, one of the founders of John Hopkins, is rumored to have regularly used opiates
- Moderate withdrawal symptoms comparable to the flu; sometimes exaggerated in media; not as dangerous or terrifying as withdrawal from barbiturates or alcohol
- Treatment programs report about a 10% rate
Addictions: Neural Mechanisms of Motivation
Drug Self-Administration Paradigm – Laboratory rats and primates can learn to self-administer addictive drugs, just like humans do
Conditioned Place Preference Paradigm – Drug-free rats will prefer the less comfortable compartment in which drugs were previously administered; importance is that they are tested while drug-free to avoid effects of drugs on behavior
Dopamine & Drug Addiction
Mesotelencephalic Dopamine System – The neurons which compose the brain’s dopamine system are the substantia nigra and ventral tegmental areas in the brain. Most of the axons of dopaminergic neurons have cell bodies in the substantia nigra and project into the dorsal striatum (nigrostriatal pathway). The degeneration of this pathway is associated with Parkinson’s disease.
Get Help for Drug Addiction
If you, or someone you know, suffers from Drug Addiction, get help from a professional. Each drug addiction counseling session an addict undergoes is a step towards building a brighter future without drugs.