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Abstract

Hallucinogenic drugs were used to treat alcoholic patients in the past, and recent developments in the study of hallucinogens led to a renewal of interest regarding the application of these drugs in the treatment of addiction. In this scenario, accumulating evidence suggests that the hallucinogenic brew ayahuasca may have therapeutic effects on substance abuse problems. We investigated the effects of ayahuasca on spontaneous locomotor activity and ethanol-induced hyperlocomotion and subsequent locomotor sensitization by a two-injection protocol. Additionally, we tested the effect of ayahuasca on an 8-day counter-sensitization protocol to modify sensitized responses induced by a repeated treatment with ethanol (1.8 g/kg) for 8 alternate days. Ayahuasca showed high sensitivity in preventing the development of ethanol-induced behavioral sensitization, attenuating it without modifying spontaneous locomotor activity. At high doses, ayahuasca also showed selectivity to both acute and sensitized ethanol responses. Finally, a counter-sensitization strategy with ayahuasca for 8 consecutive days after the establishment of ethanol-induced behavioral sensitization was effective in blocking its subsequent expression on an ethanol challenge. We demonstrated that ayahuasca not only inhibits early behaviors associated with the initiation and development of ethanol addiction, but also showed effectiveness in reversing long-term drug effects expression, inhibiting the reinstatement of ethanol-induced behavioral sensitization when administered in the ethanol-associated environment.

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