Comparacion De Dosis Agudas Letales De Drogas Comunes

Blackwell Science, LtdOxford, UKADDAddiction0965-2140© 2004 Society for the Study of Addiction
99686696
Review
Comparison of acute lethal toxicity
Robert S. Gable
REVIEW
Comparison of acute lethal toxicity of commonly
abused psychoactive substances
Robert S. Gable
School of Behavioral and Organizational Sciences, Claremont Graduate University, Claremont, CA, USA
Correspondence to:Robert S. Gable
2738 Fulton Street
Berkeley
CA 94705
USA
Tel: (510) 849 8717
E-mail: Robert.gable@cgu.edu
Submitted 15 September 2003;
initial review completed 22 November 2003;
final version accepted 12 February 2004
REVIEW
ABSTRACT
Aims To determine the acute lethal toxicity of a range of psychoactive
substances in terms of the dose customarily used as a single substance for non-medical purposes.
Design and method A structured English-language literature search was
conducted to identify experimental studies and clinical reports that docu-
mented human and non-human lethal doses of 20 abused substances that are
distributed widely in Europe and North America. Four inclusion criteria were
specified for the reports, and approximately 3000 relevant records were
retrieved fromsearch engines at Biosis, Science Citation Index, Google and the
National Library of Medicine’s Gateway. In order to account for different drug
potencies, a ‘safety ratio’ was computed for each substance by comparing its
reported acute lethal dose with the dose most commonly used for non-medical
purposes.
Findings The majority of published reports of acute lethal toxicity indicate
that thedecedent used a co-intoxicant (most often alcohol). The calculated
safety ratios varied between substances by more than a factor of 100. Intrave-
nous heroin appeared to have the greatest direct physiological toxicity; several
hallucinogens appeared to have the least direct physiological toxicity.
Conclusions Despite residual uncertainties, the substantial difference in
safety ratios suggeststhat abused substances can be rank-ordered on the basis
of their potential acute lethality.
KEYWORDS Acute toxicity, lethality, positive subjective effects, safety
ratio, therapeutic index.
INTRODUCTION
It is commonly assumed that abused substances differ
with respect to their acute physical toxicity. However,
public opinion and public policies are often based on
anecdotal reports andstatistical information that is not
adjusted for factors such as prevalence of use. The present
study addressed this issue by undertaking a comparison
of the toxicity of abused substances based on reports of
experimental human and non-human animal research
and on published toxicological analyses of overdose
fatalities.
Most substances have multiple mechanisms of
toxicity and multiple targetorgans, each with its own vul-
© 2004 Society for the Study of Addiction
nerability to the administered compound. Because
detailed toxicological evaluation is time-consuming and
expensive, drug concentrations in plasma or whole blood
are used routinely as surrogate measures in overdose
cases. Several well-known compilations of cases have
listed the lethal human blood concentrations for arange
of hazardous substances and drugs: Druid & Holmgren
(1997), Repetto & Repetto (1997) Schulz & Schmoldt
(1997), Ekwall et al. (1998), National Toxicology
Program (2001) and Baselt (2002). Blood analysis of a
decedent is not, however, without measurement compli-
cations. Different substances have varying patterns of
postmortem redistribution from organ tissue to the blood-
stream (Pounder& Jones 1990; Leikin & Watson 2003).
doi:10.1111/j.1360-0443.2004.00744.x
Addiction, 99, 686–696
Comparison of acute lethal toxicity
Furthermore, a drug such as heroin might not be detected
at all in postmortem blood samples because it has an arte-
rial half-life of only about 3 minutes (Rentsch et al. 2001)
and its metabolite morphine-3-glucuronide has a half-life
of approximately 90...