The FASEB Journal
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Research Communication
Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channelsin the brain
Arieh Moussaieff,*
,†,1
Neta Rimmerman,
‡
Tatiana Bregman,
§
Alex Straiker,
‡
Christian C. Felder,
Shai Shoham,
¶
Yoel Kashman,
#
Susan M. Huang,**Hyosang Lee,** Esther Shohami,
†
Ken Mackie,
‡
Michael J. Caterina,** J. Michael Walker,
‡
Ester Fride,
§
and Raphael Mechoulam*
,1
*Department of Medicinal Chemistry and Natural Products, Medical Faculty, and
†
Department of Pharmacology, Pharmacy School, Hebrew University of Jerusalem, Jerusalem, Israel;
‡
Gill Center forBiomolecular Science and Department of Psychological and Brain Sciences, Indiana University Bloomington, Bloomington, Indiana, USA;
§
Departments of Behavioral Sciences and of MolecularBiology, Ariel University Center of Samaria, Ariel, Israel;
Eli Lilly and Co., Neuroscience Division,Indianapolis, Indiana, USA;
¶
Research Department, Herzog Memorial Hospital, Jerusalem, Israel;
#
School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University,Ramat Aviv, Israel; and **Department of Biological Chemistry, Johns Hopkins School of Medicine,Baltimore, Maryland, USA
ABSTRACT
Burning of
Boswellia
resin as incense hasbeen part of religious and cultural ceremonies formillennia and is believed to contribute to the spiritualexaltation associated with such events. Transient recep-tor potential vanilloid (TRPV) 3 is an ion channelimplicated in the perception of warmth in the skin.TRPV3 mRNA has also been found in neurons through-out the brain; however, the role of TRPV3 channelsthere remains unknown. Here we show that incensoleacetate (IA), a
Boswellia
resin constituent, is a potent TRPV3 agonist that causes anxiolytic-like and antide- pressive-like behavioral effects in wild-type (WT) mice with concomitant changes in c-Fos activation in thebrain. These behavioral effects were not noted inTRPV3
/
mice, suggesting that they are mediated
via
TRPV3 channels. IA activated TRPV3 channels stably expressed in HEK293 cells and in keratinocytes fromTRPV3
/
mice. It had no effect on keratinocytesfrom TRPV3
/
mice and showed modest or no effect on TRPV1, TRPV2, and TRPV4, as well as on 24 otherreceptors, ion channels, and transport proteins. Ourresults imply that TRPV3 channels in the brain may play a role in emotional regulation. Furthermore, the bio-chemical and pharmacological effects of IA may pro- vide a biological basis for deeply rooted cultural andreligious traditions.—Moussaieff, A., Rimmerman, N.,Bregman, T., Straiker, A., Felder, C. C., Shoham, S.,Kashman, Y., Huang, S. M., Lee, H., Shohami, E.,Mackie, K., Caterina, M. J., Walker, J. M., Fride, E.,Mechoulam, R. Incensole acetate, an incense compo-nent, elicits psychoactivity by activating TRPV3 chan-nels in the brain.
FASEB J.
22, 000–000 (2008)
Key Words: Boswellia
frankincense
depression
anxiety
Research on plants eliciting
psychoactive effects,such as
Cannabis sativa
,
Papaver
species, and
Nicotiana tabacum
, has provided important insights into neuro-chemical processes and diseases of the central ner- vous system (CNS) (1). Psychoactive plant drugs havealso played a major role in religious customs in many ancient cultures, as they exert a profound effect onhuman consciousness, emotions and cognition. No-table examples of plants that were used in religiousrituals are the mythological Aryan soma,
Ipomoea linnaeus
(the source of South American ololiuqui),
Cannabis sativa
,
Salvia divinorum
(the source of divi-norin) (2),
Nicotiana tabacum
(3), and several
Bo- swellia
species.The resin of
Boswellia
species (Burseraceae; “frank-incense” and “olibanum”) is mentioned in numerousancient texts as incense by itself or as a majorcomponent of incense (4). In the ancient MiddleEast,
Boswellia
resin was considered a highly preciouscommodity, carried in caravans from sub-Sahara re-gions, where it is still a major export product (5). Inancient Egypt, incense burning signified a manifes-tation of the presence of the gods and a gratificationto them. In ancient Judea, it was a central ceremony in the temple. The ancient Greeks used incenseburning as an oblation. In Christendom, its use in worship has continued since the fourth or fifthcentury C.E (6). The psychoactivity of
Boswellia
wasalready recognized in ancient times. Dioscorides
1
Correspondence: Department of Medicinal Chemistry and Natural Products, Medical Faculty, Hebrew University of Jerusalem, 91120, Jerusalem, Israel. E-mail: A.M.,arieh@weizmann.ac.il; or R.M., mechou@cc.huji.ac.ildoi: 10.1096/fj.07-101865
10892-6638/08/0022-0001 © FASEB
The FASEB Journal article fj.07-101865. Published online May 20, 2008.
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