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Short answer: Psychoactive drugs make one feel good, which, for some people, is addictive, so they start to overuse them. Overuse can result in increased tolerance and this in further overuse and overdose, which is the main reason why these drugs tend to be dangerous. Overdose is dangerous only if a drug has a low enough therapeutic index (or safety ratio). A specific danger with street drugs is adulteration with other drugs.

Answer: Psychoactive drugs make one feel good, which, for some people, is addictive, so they start to overuse them. Overuse can result in increased tolerance and this in further overuse and overdose, which is the main reason why these drugs tend to be dangerous.

Short answer: Psychoactive drugs make one feel good, which, for some people, is addictive, so they start to overuse them. Overuse can result in increased tolerance and this in further overuse and overdose, which is the main reason why these drugs tend to be dangerous. Overdose is dangerous only if a drug has a low enough therapeutic index (or safety ratio).

Emergency room visits due to psychoactive drugs use in the US in 2011 (ussc.gov):

Withdrawal symptoms can be expected after prolonged use of drugs that cause physical dependence: alcohol, nicotine, caffeine, opioids, barbiturates, benzodiazepines, GHB, hypnotics (zopiclone, zolpidem).

Psychoactive drug overuse is physically dangerous only if a drug has a low enough therapeutic index.

In conclusion, psychoactive drugs can become dangerous when they are overdosed. The dangers can be sometimes explained by low "margine of exposure" or "safety ratio," but long-term dependence on a drug can be harmful on its own.

Short answer: Psychoactive drugs make one feel good, which, for some people, is addictive, so they start to overuse them. Overuse can result in increased tolerance and this in further overuse and overdose, which is the main reason why these drugs tend to be dangerous. Overdose is dangerous only if a drug has a low enough therapeutic index (or safety ratio). A specific danger with street drugs is adulteration with other drugs.

Street drugs can be adulterated with other dangerous drugs: heroin can be laced with fentanyl, which can cause fatal respiratory depression; ecstasy with "bath salts, which can dangerously increase blood pressure

Emergency room visits due to psychoactive drugs use in the US in 2011 (ussc.gov):

Withdrawal symptoms can be expected after prolonged use of drugs that cause physical dependence: alcohol, nicotine, caffeine, opioids, benzodiazepines, GHB and hypnotics (barbiturates, zopiclone, zolpidem).

Psychoactive drug overdose is dangerous only if a drug has a low enough therapeutic index.

In conclusion, psychoactive drugs can become dangerous when they are overused or overdosed. The danger of a drug can be sometimes explained by its low "margin of exposure" or "safety ratio," but long-term dependence on a drug can be harmful on its own.

Question: Why is it that psychoactive or "feel good" drugs tend to be dangerous?

Answer, in short: Some of these drugs tend to be dangerous because people commonly overuse and overdose them. The focus is on "feel good" and not specifically on "illicit" psychoactive drugs.

Low therapeutic index

Some psychoactive drugs have a low therapeutic index, which is the ratio between the dose that is Toxic for 50% of population and the dose that is Effective (therapeutic) for 50% of population, so a TI = TD50/ED50. Examples of psychoactive drugs with a low therapeutic index: alcohol (TI =10), amphetamines, barbiturates, some benzodiazepines, cocaine, some opioids, especially heroin, and phenylpropanolamine.

Low margin of exposure

Another evaluation of drug danger is margin of exposure (MOE), which is the ratio between the lowest dose found to harm health and estimated drug intake in humans.

Low safety ratio

Another source Comparison of acute lethal toxicity of commonly abused psychoactive substances (RS Gable, Addiction, 2004) (pdf) mentions "safety ratio" (equivalent of therapeutic index) that "was computed for each substance for reported acute lethal dose with the dose most commonly used for non-medical purposes."

Evidence of actual dangers

1) Death by Overdose

According to Drugabuse.gov, every day, more than 130 people in the United States die after overdosing on opioids.

2) Death by Withdrawal

• Withdrawal from moderate or short-term excessive alcohol drinking is usually not dangerous, but withdrawal from long-term excessive drinking can be deadly, for example, due to seizures or arrhythmia.
• Opiate withdrawal can also be deadly.

3) Organ damage

Examples of physical complications after prolonged drug use (years):

• Alcohol: liver cirrhosis, alcoholic neuropathy, Wernicke-Korsakoff syndrome
• Cocaine: brain damage (acute effect can be gastric ischemia)
• Methamphetamine: brain damage, tooth decay (meth mouth)

4) Emergency room visits in the US (ussc.gov, 2011):

V = ER visits/year ; RR = risk ratio (total users/ER visits)

 -                          V       RR
 - PCP (phencyclidine)   75,538     2.9
 - Heroin               258,224     0.92
 - Oxycodone/oxycontin  151,218     0.39
 - Cocaine              505,224     0.37
 - Methamphetamine      102,961     0.23
 - MDMA (Ecstasy)        22,498     0.04
 - Marijuana            445,668     0.03
 - LSD                    4,819     0.03

5) Road accidents

The risk for road trauma was increased for single use of benzodiazepines (adjusted OR 5.1 (95% Cl: 1.8-14.0)) and alcohol (blood alcohol concentrations of 0.50-0.79 g/l, adjusted OR 5.5 (95% Cl: 1.3-23.2) and >or=0.8 g/l, adjusted OR 15.5 (95% Cl: 7.1-33.9)). High relative risks were estimated for drivers using combinations of drugs (adjusted OR 6.1 (95% Cl: 2.6-14.1)) and those using a combination of drugs and alcohol (OR 112.2 (95% Cl: 14.1-892)). Increased risks, although not statistically significantly, were assessed for drivers using amphetamines, cocaine, or opiates. No increased risk for road trauma was found for drivers exposed to cannabis.

6) Dependence

Drug dependence by itself is harmful, because it takes control over someone's life and prolongs the eventual physical harm of a drug.

Psychoactive drugs that can cause physical dependence: alcohol, nicotine, caffeine, opioids, barbiturates, benzodiazepines, GHB, hypnotics (zopiclone, zolpidem). Physical dependence means that stopping using a drug causes withdrawal symptoms (Drugabuse.gov).

In summary, the dangers of psychoactive drugs stem from overdose and overuse; examples of drugs with low safety ratios are: opioids, isobutyl nitrite (poppers), gamma hydroxybutyrate (GHB), methamphetamine, alcohol, cocaine, methamphetamine, ecstasy and nicotine.

Question: Why is it that psychoactive ("feel good") drugs tend to be dangerous?

The question implies that psychoactive drugs are 1) dangerous and that 2) the reason is in their low therapeutic indices.

Short answer: Psychoactive drugs make one feel good, which, for some people, is addictive, so they start to overuse them. Overuse can result in increased tolerance and this in further overuse and overdose, which is the main reason why these drugs tend to be dangerous. Overdose is dangerous only if a drug has a low enough therapeutic index (or safety ratio).

DANGERS

ACUTE DANGERS

Overdose can result in acute sickness, for example, gastric ischemia with cocaine overdose, or death, mainly due to opioids (130/day in US), but also alcohol (6/day in US).

Emergency room visits due to psychoactive drugs use in the US in 2011 (ussc.gov):

V = ER visits/year ; RR = risk ratio (total users/ER visits)

 -                          V       RR
 - PCP (phencyclidine)   75,538     2.9
 - Heroin               258,224     0.92
 - Oxycodone/oxycontin  151,218     0.39
 - Cocaine              505,224     0.37
 - Methamphetamine      102,961     0.23
 - MDMA (Ecstasy)        22,498     0.04
 - Marijuana            445,668     0.03
 - LSD                    4,819     0.03

Road accidents

In one 2004 study in Netherlands, the risk of road trauma was strongly associated with a single use of benzodiazepines (5.1), alcohol (5.5), combination of drugs (6.1) and combination of drugs and alcohol (112.2). The values in brackets are adjusted odd ratios.

CHRONIC DANGERS

Examples of chronic physical damage due to psychoactive drugs, usually after years of overuse:

• Tobacco smoking: chronic bronchitis, arteriosclerosis (ischemic heart disease, peripheral vascular diseases), throat and lung cancer
• Alcohol: liver cirrhosis, alcoholic neuropathy, Wernicke-Korsakoff syndrome, fetal alcohol syndrome
• Cocaine: brain damage
• Methamphetamine: brain damage, tooth decay (meth mouth)

Withdrawal

Abrupt withdrawal after prolonged use of certain drugs can be deadly:

• Alcohol withdrawal can be deadly due to seizures or arrhythmia.
• Opiate withdrawal can also be deadly.

Withdrawal symptoms can be expected after prolonged use of drugs that cause physical dependence: alcohol, nicotine, caffeine, opioids, barbiturates, benzodiazepines, GHB, hypnotics (zopiclone, zolpidem).

THERAPEUTIC INDEX

Psychoactive drug overuse is physically dangerous only if a drug has a low enough therapeutic index.

Therapeutic index is the ratio between the dose that is Toxic for 50% of population and the dose that is Effective (therapeutic or "feel good") for 50% of population, so a TI = TD50/ED50. 

Examples of psychoactive drugs with low therapeutic indices: alcohol, amphetamines, barbiturates, some benzodiazepines, cocaine, some opioids (especially heroin), and phenylpropanolamine.

When psychoactive drugs are not used for therapy, we can't speak about therapeutic indices, so comparable indices, such as "margin of exposure" and "safety ratio" have been developed for these cases.

Margin of exposure (MOE) is the ratio between the lowest dose found to harm health and estimated drug intake in humans.

Another source: RS Gable, Addiction, 2004 (pdf) mentions "safety ratio" that "was computed for each substance for reported acute lethal dose with the dose most commonly used for non-medical purposes."

In conclusion, psychoactive drugs can become dangerous when they are overdosed. The dangers can be sometimes explained by low "margine of exposure" or "safety ratio," but long-term dependence on a drug can be harmful on its own.