Salvinorin A and Related Compounds as Therapeutic Drugs for Psychostimulant-Related Disorders

Abstract

Pharmacological treatments are available for alcohol, nicotine, and opioid dependence, and several drugs for cannabis-related disorders are currently under investigation. On the other hand, psychostimulant abuse and dependence lacks pharmacological treatment. Mesolimbic dopaminergic neurons mediate the motivation to use drugs and drug-induced euphoria, and psychostimulants (cocaine, amphetamine, and methamphetamine) produce their effects in these neurons, which may be modulated by the opioid system. Salvinorin A is a κ-opioid receptor agonist extracted from Salvia divinorum, a hallucinogenic plant used in magico-ritual contexts by Mazateca Indians in México. Salvinorin A and its analogues have demonstrated anti-addiction effects in animal models using psychostimulants by attenuating dopamine release, sensitization, and other neurochemical and behavioral alterations associated with acute and prolonged administration of these drugs. The objective of the present article is to present an overview of the preclinical evidence suggesting anti-addictive effects of salvinorin A and its analogues.

Plant based assisted therapy for the treatment of substance use disorders - part 1. The case of takiwasi center and other similar experiences

“…An interdisciplinary group of professionals led by psychologist Sacha Domenech founded in 2001 the civil association Runa Wasi (http://runawasi.blogspot.pe/), in Buenos Aires, Argentina. The initiative follows the experience of the community Ayllu Tinkuy created in the 90s by Domenech (1996), who has been trained as socio-therapeutic operator in therapeutic communities by the "Progetto Uomo", and as practitioner of traditional Peruvian medicine.…”

Molecular Signaling Pathways Behind the Biological Effects ofSalviaSpecies Diterpenes in Neuropharmacology and Cardiology

“…Because salvinorin A has agonistic activity on KOR, it possess many different properties such as effects on behavioral and neurobiological endpoints, effects on KOR/dynorphin system during stress, or in addictive states, neuroendocrine effects, and its effects for the treatment of neuropsychiatric diseases (Butelman and Kreek, ; dos Santos et al, ).…”

Dynorphin/kappa opioid receptor system regulation on amygdaloid circuitry: Implications for neuropsychiatric disorders

“…It has been speculated that over short periods, Dynmediated agonism of KOR may act as an acute punisher to reduce the seeking for other drugs and reinforcers (Freeman et al, 2014;Butelman and Kreek, 2015;Heinsbroek et al, 2018), but over the long term, it may act as a negative reinforcer of such behaviors (Bruchas et al, 2010;Wee and Koob, 2010;Walker et al, 2012;Chartoff et al, 2016;Escobar et al, 2020). Consistent with effects produced by synthetic KOR agonists, the recreational drug salvinorin A promotes similar behavioral effects and blocks the reinforcing effects of other drugs, most notably psychostimulants (Gonzalez et al, 2006;dos Santos et al, 2014;Brito-da-Costa et al, 2021). Salvinorin A, unlike other hallucinogens, does not bind the 5-HT2A receptor (Sheffler and Roth, 2003).…”