When considering the safety of a substance, we might also want to know how likely a fatal overdose is. As is well known, any substance, including water, can cause death at high enough doses. In order to estimate the safety of a substance and a given dose, the median lethal dose (LD50) is often used as the first estimate of toxicity, which is established in pre-clinical research within a rodent population. Specifically, the doseresponse relationship is documented by plotting the number of deaths occurring among the group of experimental animals against the range of drug doses administered. The LD50 is simply the dosage at which 50% of the animals die within a specified interval of time.
While this can give an indication as to at what point the drug may become dangerous, another very important factor is the steepness of the dose-response curve - which plots the dose against intensity of effects. If the curve is very steep, meaning that the difference in dose between mild effects and strong effects is very small, then the difference between an active dose and a fatal dose will also be small, making accidental over-
doses much more likely. To quantify this, the so called safety ratio is used. This is the ratio of a usual active dose and a usual fatal dose. A low ratio means a steep curve and thus more danger of a lethal overdose, while a high ratio means a flat curve and less danger.
The doses indicated in the table below are the estimated quantity for an average, healthy 70-kg adult human who has not developed tolerance to the substance, and who does not have residual amounts of the substance present in their body from previous administrations. Note, however, that individuals vary greatly in terms of physical and psychological vulnerability; therefore, the information in this table should not be used as a dosage guide.
Abbreviations used: im = intramuscular, inh = inhaled, in = intranasal, ip = intraperitoneal, iv = intravenous, or = oral, sm = smoked.
|Substance||LD50 (mg/kg)||# fatal human cases selected||Usual lethal concen- tration in blood (mg/l)||Usual lethal dose re- portedly adminis- tered||Usual effective dose (and range)||Safety ratio|
|Alcohol (or)b||mouse (or) 6800; rat (or) 10300||894||3600 (2200- 5000)||330g (276-455)||33g (22-40)||10|
|DMT (or)||mouse (or) 280; mouse (ip) 47||0||-||-||40 mg (34-70)||50|
|LSD (or)||mouse (iv) 46; rat (iv) 17||2||4.8 (–)||100 mg (extrapo- lated)||100μ g (25-200)||1000|
|Marijuana (sm)||mouse (or) 22; monkey (iv) 130||2||(180315)||> 15 g (extrapo- lated)||15 mg (12-22)||>1000|
|MDMA (or)||rat (or) 160; guinea pig (ip) 26||27||3 (0.04-8.5)||2g (150- 1250)||125 mg (15-150)||16|
|Mescaline (or)||mouse (or) 880; rat (im) 330||1||0.48 (–)||8.4g (extrapo- lated)||350mg (200-450)||24|
|Psilocybin (or)||mouse (ip) 285; rat (ip) 280||1||4 (–)||6g (extrapo- lated)||6 mg (–)||1000|