Psychoactive natural products

If you've been working in this field for any period of time, cocktail party discussions or talks with students invariably turn to nature's greatest trove of biologically-active compounds, those that act on the central nervous system (CNS) as stimulants, euphorics, and hallucinogens.

So, over the last couple of days, I've been enjoying the posts by my relatively new compatriot here at ScienceBlogs, SciBling for short, The Molecule of the Day. I have no clue as to who he/she is or where they are other than it is written, "by a chemist who enjoys rambling about the relationship between chemistry and real life to non-chemists."

I've really enjoyed the last few posts as MotD has ventured into psychoactive natural products:

Kavain (Unlike papain, does not make you strong like Popeye) - the psychoactive anxiolytic, and potential hepatotoxin, from Kava kava supplements

Arecoline (Chew on this) - the mildly-intoxicating nicotinic agonist and carcinogen from betel nut

Salvinorin A (Houseplant or drug? You be the judge) - the hallucinogen from Salvia divinorum, NOT from the common sage, Salvia officinalis

MotD notes that the latter compound, salvinorin A, is an unusual CNS-active agent in the it is completely devoid of nitrogens, a feature common to most neurotransmitters and agents that disrupt or modulate their functioning. Although it was discovered and structurally-elucidated in the early 1980s, chemists and biologists have been very excited about salvinorin A most recently due to a 2002 paper in PNAS where it was classified pharmacologically as an agonist (stimulator) of the kappa subtype of opioid receptors.

The findings of this paper were quite notable in that salvinorin A was shown not to act at 5-HT2 serotonin receptors, the classic site of action of LSD. Moreover, its selective and potent effects at the kappa-opioid receptor raises questions that diseases of altered thought and perception, most often believed to eminate from dopamine dysfunction, might have an opioid component.

What does this jibberish mean? It means that the treatment of schizophrenia, dementia, and bipolar disorder might have other options down the road with the use of compounds that lack some of the liabilities of dopaminergic antagonists. Kappa-opioid-selective agents that act oppositely of salvinorin, namely, as blockers or antagonists, could be such drugs.

One final caveat to the recreational pharmacology enthusaists that frequent this blog: Salvinorin is not recommended as a recreational hallucinogen. First, its use is illegal in the some states, although it does not yet appear that the US DEA has issued a federal prohibition of its use (this educational blog is very particular in not promoting any illegal activites, of course.)

Moreover, respected international experts on hallucinogen use have issued strong cautions about salvinorin, noting,

"The majority of people who have had a full blown experience with salvinorin A are reluctant to ever do it again. Anyone choosing to experiment with this compound should always have an alert, clear-thinking sitter present to prevent them from injuring themselves or others."

So, pay attention to those in the know - even for those agents that are not completely illegal as of this writing.

In the meantime, if you are looking for an enriching, mind-altering experience, might I recommend a fine, award-winning North Carolina microbrew?