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.
Picture: Margin of exposure for daily drug use estimated using probabilistic analysis; red bar = average user ; error bar = standard deviation ; gray bar = tolerant user (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.
Low safety ratio
Another source Comparison of acute lethal toxicity of commonly abused psychoactive substances (RS Gable, Addiction, 2004) 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."
- Heroin: 6
- Gamma hydroxybutyrate (GHB): 8
- Isobutyl nitrite: 8
- Methamphetamine: 10
- Alcohol: 10
- Cocaine: 15
- MDMA (ecstasy): 16
- Codeine: 20
- Methadone: 20
- Mescaline (peyote cactus): 24
- Flunitrazepam (a benzodiazepin): 30
- Ketamine: 38
- Phenobarbital: 50
- Dimethyltryptamine: 50
- Fluoxetine (Prozac): 100
- Nitrous oxide: >150
- LSD: 1,000
- Psilocybin (mushrooms): 1,000
- Marijuana: >1,000
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. Overuse of alcohol, but not likely moderate alcohol drinking (~2 drinks/day), can result in physical addiction Alcohol dependence and withdrawal.
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.
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.