Subjective effects of Salvia divinorum: LSD- or marijuana-like?

Salvia divinorum is a naturally occurring psychedelic considered to be one of the most potent hallucinogens found to date. The few behavioral studies conducted conclude that Salvia's effects may be similar to traditional psychedelics, which is noteworthy because Salvia acts via a unique molecular mechanism as a kappa opioid receptor agonist. One hundred and ninety-three participants, including 34 Salvia users, were asked to fill out a series of questionnaires related to general drug use, personality characteristics, demographics and their experiences with Salvia. Salvia users were found to differ from nonusers on personality characteristics and reported consuming significantly more alcohol than nonusers. In addition, although Salvia users rated their hallucinogenic experiences as similar to those seen in previously published reports, the majority likened their experiences as most similar to marijuana instead of more traditional psychedelics. Low scores on the ARCI LSD subscale confirmed this finding and call into question the reigning theory of LSD-like subjective effects elicited by Salvia.

Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse.

Drug abuse is thought to induce long-term cellular and behavioral adaptations as a result of alterations in gene expression. Understanding the molecular consequences of addiction may contribute to the development of better treatment strategies. This study utilized high-throughput Affymetrix microarrays to identify gene expression changes in the post-mortem nucleus accumbens of chronic heroin abusers. These data were analyzed independently and in relation to our previously reported data involving human cocaine abusers, in order to determine which expression changes were drug specific and which may be common to the phenomenon of addiction. A significant decrease in the expression of numerous genes encoding proteins involved in presynaptic release of neurotransmitter was seen in heroin abusers, a finding not seen in the cocaine-abusing cohort. Conversely, the striking decrease in myelin-related genes observed in cocaine abusers was not evident in our cohort of heroin subjects. Overall, little overlap in gene expression profiles was seen between the two drug-abusing cohorts: out of the approximately 39,000 transcripts investigated, the abundance of only 25 was significantly changed in both cocaine and heroin abusers, with nearly one-half of these being altered in opposite directions. These data suggest that the profiles of nucleus accumbens gene expression associated with chronic heroin or cocaine abuse are largely unique, despite what are thought to be common effects of these drugs on dopamine neurotransmission in this brain region. A re-examination of our current assumptions about the commonality of molecular mechanisms associated with substance abuse seems warranted.

Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin.

Chronic cocaine abuse induces long-term neural adaptations as a consequence of alterations in gene expression. This study was undertaken to identify those transcripts differentially regulated in the nucleus accumbens of human cocaine abusers. Affymetrix microarrays were used to measure transcript abundance in 10 cocaine abusers and 10 control subjects matched for age, race, sex, and brain pH. As expected, gene expression of cocaine- and amphetamine-regulated transcript (CART) was increased in the nucleus accumbens of cocaine abusers. The most robust and consistent finding, however, was a decrease in the expression of a number of myelin-related genes, including myelin basic protein (MBP), proteolipid protein (PLP), and myelin-associated oligodendrocyte basic protein (MOBP). The differential expression seen by microarray for CART as well as MBP, MOBP, and PLP was verified by RT-PCR. In addition, immunohistochemical experiments revealed a decrease in the number of MBP-immunoreactive oligodendrocytes present in the nucleus accumbens and surrounding white matter of cocaine abusers. These findings suggest a dysregulation of myelin in human cocaine abusers.