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

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

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.

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

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Image source: Scientific Reports, Nature.com, Open Access

Image explanation:

For individual exposure the four substances alcohol, nicotine, cocaine and heroin fall into the “high risk” category with MOE < 10, the rest of the compounds except THC fall into the “risk” category with MOE < 100.

Most dangers of psychoactive drugs stem from overuse:

1) Overdose

Opioids, such as heroin, in high doses can cause respiratory depression. According to Drugabuse.gov: "Every day, more than 130 people in the United States die after overdosing on opioids" and "Roughly 21 to 29 percent of patients prescribed opioids for chronic pain misuse them."

2) Addiction

Moderate alcohol drinking (1-2 drinks/day) does not likely make you addicted, but higher amounts drunk for several months/years can. Alcohol dependence and withdrawal.

3) Withdrawal

4) Organ damage

Physical complications after prolonged use (years):

In conclusion, many "feel good" psychoactive drugs are dangerous mainly because they can be easily overdosed. Most of them have a "narrow therapeutic index:" alcohol, benzodiazepines, cocaine, opioids.

"Emergency room visits due to "feel good" drugs

Emergency room visits ratios in the US, 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

If you evaluate danger by ER visits, the relative risks (RR) may not appear high, but number of ER visits does.

Road accidents associated with "feel good" drugs

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.

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