Collybolide is a chemical constituent of the ''
Rhodocollybia maculata
''Rhodocollybia maculata'', commonly known as the spotted toughshank, is a species of Basidiomycota#:~:text=Basidiomycota are filamentous fungi composed,specialized spores are called basidiospores., basidiomycete fungus in the family Omphalota ...
'' mushroom, a fungus that grows on rotting conifer wood. It is potentially a potent and selective
K-opioid receptor agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
, like
salvinorin A.
No total syntheses of this compound have been reported, and research is inconclusive as to whether collybolide is a K-opioid receptor agonist, and it still remains unknown whether collybolide is a
hallucinogen;
however, anecdotal reports suggest it is possible.
If it is active in humans, collybolide will be the only non-salvinorin selective K-opioid receptor agonist psychedelic.
Research
Gupta ''et al.''
found collybolide to exhibit biased K-opioid agonist activity. K-opioid receptor agonists are under research for their potential in
addiction treatment: and along with an easily modifiable structure (in contrast to salvinorin A), collybolide has attracted attention for the development of next-generation K-opioid receptor agonist
analgesic
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
s,
antipruritic
Antipruritics, abirritants, or anti-itch drugs, are medications that inhibit the itching (Latin: ''pruritus'') often associated with sunburns, allergic reactions, eczema, psoriasis, chickenpox, fungal infections, insect bites and stings like those ...
s, and
antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
s.
However, this is contested by Shevick ''et al.'', who, after synthesizing collybolide, could not find K-opioid agonist activity of either
enantiomer
In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...
. Shevick ''et al.'' fault the 2016 assay and suggest: an unidentified contaminant in the ''C. maculata'' extract, degradation during storage, or degradation during handling, produced a derivative of collybolide that is the true, but still unknown K-opioid receptor agonist.
[{{cite journal , last1=Shevick , first1=Sophia L. , last2=Freeman , first2=Stephan M. , last3=Tong , first3=Guanghu , last4=Russo , first4=Robin J. , last5=Bohn , first5=Laura M. , last6=Shenvi , first6=Ryan A. , title=Asymmetric Syntheses of (+)- and (−)-Collybolide Enable Reevaluation of kappa -Opioid Receptor Agonism , journal=ACS Central Science , date=27 July 2022 , volume=8 , issue=7 , pages=948–954 , doi=10.1021/acscentsci.2c00442 , pmid=35912357 , pmc=9335922 ]
References
3-Furyl compounds
Benzoate esters
Heterocyclic compounds with 3 rings
Lactones
Rhodocollybia