Novel psychoactive substances are newly used
designer drugs ("internet drugs", "research chemicals", "legal highs") potentially posing similar health risks to classic illicit substances. Chemically, many novel psychoactive substances can be classified as
phenethylamines,
amphetamines,
synthetic cathinones,
piperazines, pipradrols/
piperidines, aminoindanes
benzofurans, and
tryptamines. Pharmacologically, these substances interact with various monoaminergic targets. Typically, stimulants inhibit the transport of
dopamine and
noradrenaline (pipradrols,
pyrovalerone cathinones) or induce the release of these monoamines (
amphetamines and
methamphetamine-like cathinones), entactogens predominantly enhance
serotonin release (phenylpiperazines, aminoindanes, para-substituted
amphetamines, and
MDMA-like cathinones) similar to
MDMA (ecstasy), and
hallucinogens (
tryptamines, hallucinogenic
phenethylamines) are direct agonists at serotonergic 5-HT2A receptors. Synthetic
cannabinoids are another group of novel substances which all act as agonists at the
cannabinoid CB1 receptor similar to
THC but are chemically diverse. In particular, the relative serotonergic vs dopaminergic activity (determined by the
dopamine/
serotonin transporter inhibition ratio in vitro) can be helpful to predict the desired psychotropic but also the toxic effects of novel substances as well as their potential for addiction. Although the use of novel psychoactive substances mostly produces minor or moderate
poisonings, serious complications occur.
Serotonergic drugs (entactogens and
hallucinogens) are associated with acute
serotonin syndrome,
hyperthermia,
seizures, and
hyponatremia.
Dopaminergic drugs are highly addictive and acute toxicity includes prolonged stimulation,
insomnia, agitation, and
psychosis. Agitation, anxiety,
paranoia,
hypertension, and rarely
myocardial infarction and
renal failure are seen with synthetic
cannabinoids. Treatment is supportive.