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There is compelling evidence to the theory that the 5-HT2B receptor plays a direct and crucial role in the mechanisms of actions of methamphetamine (METH) and of 3,4-methylenedioxy- methamphetamine (MDMA) leading to addiction. The involvement of 5-HT1A receptors in all of the biochemical and behavioural consequences such as anxiety, depression, memory impairment, and cognitive dysfunction, resulting from long-term METH/MDMA abuse, has also been unequivocally established. On the basis of these facts, a dual receptor hypothesis based on postsynaptic 5-HT2B receptor antagonist and 5-HT1A receptor agonist activities in the central nervous system (CNS), is proposed.

Dual, Postsynaptic 5-HT2B Antagonist and 5-HT1A Agonist Approach to the Treatment of METH/MDMA Addiction and Related Problems. Part 1. The Hypothesis.