RESEARCH ON PLANTS ELICITING psychoactive effects, such as Cannabis sativa, Papaver species, and Nicotiana tabacum, has provided important insights into neurochemical processes and diseases of the central nervous system (CNS) (1). Psychoactive plant drugs have also played a major role in religious customs in many ancient cultures, as they exert a profound effect on human consciousness, emotions and cognition. Notable examples of plants that were used in religious rituals are the mythological Aryan soma, Ipomoea linnaeus (the source of South American ololiuqui), Cannabis sativa, Salvia divinorum (the source of divinorin) (2), Nicotiana tabacum (3), and several Boswellia species.

The resin of Boswellia species (Burseraceae; “frankincense” and “olibanum”) is mentioned in numerous ancient texts as incense by itself or as a major component of incense (4). In the ancient Middle East, Boswellia resin was considered a highly precious commodity, carried in caravans from sub‐Sahara regions, where it is still a major export product (5). In ancient Egypt, incense burning signified a manifestation of the presence of the gods and a gratification to them. In ancient Judea, it was a central ceremony in the temple. The ancient Greeks used incense burning as an oblation. In Christendom, its use in worship has continued since the fourth or fifth century C.E (6). The psychoactivity of Boswellia was already recognized in ancient times. Dioscorides (first century C.E.) writes that it causes madness (7). In the Jewish Talmud (300–600 C.E.), Boswellia resin is mentioned as a potion (in wine) given to prisoners condemned to death to “benumb the senses” (8). In Ethiopia, where Boswellia trees are indigenous, it is believed to have a tranquilizing effect (9). For additional data on the cultural and religious customs associated with Boswellia, see Supplemental Material.

In view of the prolonged use of Boswellia, its historical importance, and its significance in cultural and religious rituals along with its purported pharmacological effects, we investigated the biochemical profile and psychoactivity of purified components of Boswellia resin. We assumed that the spiritual exaltation caused by incense burning in religious ceremonies would be enhanced by putative pharmacological effects of its constituents, particularly on the conductors of the ceremonies, who presumably inhale large amounts of smoke. We are unaware of any attempt to identify constituents with an effect on sensation or emotion. Menon and Kar (10) have reported that an ether extract of Boswellia serrata resin produces analgesic and sedative effects in rats, but the compounds causing these effects have not been isolated.

We examined Boswellia extract for the presence of novel bioactive components and isolated incensole acetate (IA) as a major active constituent of Boswellia resin. IA showed an antiinflammatory action, as recently reported by us (11, 12), as well as several CNS‐associated activities, described below. It is known as a macrocyclic diterpenoid (13), considered to be a biomarker of Boswellia species (14), but has not been previously evaluated for its psychoactivity.

To evaluate the activity profile of IA, we used behavioral, pharmacological, and physiological assays. They included standard behavioral mice models for the evaluation of anxiolytic and antidepressive drugs (elevated plus maze, Porsolt's forced swimming test, open field behavior, and a test for catalepsy), c‐Fos immunostaining, various receptor binding assays, and physiological measurements.

Transient receptor potential (TRP) channels are activated by multiple stimuli in expression systems and mediate transmembrane flux of cations (15). The TRP vanilloid (TRPV) channel subfamily consists of six members; TRPV1‐TRPV4 comprise the so‐called thermo‐TRPVs and are activated by temperature and chemical stimuli. Although thermo‐sensitive, TRPV channels are also expressed in tissues such as the brain, in which thermoregulatory homeostasis precludes dramatic temperature swings (15).

TRPV3 has a threshold for temperatures in the 31–39°C range, and it is highly expressed in epithelial cells of the skin and oropharynx (16–18), where its activation causes a feeling of warmth. mRNA encoding this channel has also been detected in the brain (17, 18). Owing to the recent identification of TRPV3 ion channel, relatively few agonists are known for it. The first chemical agonist identified for TRPV3 was the synthetic broad spectrum TRP modulator 2‐aminoethoxydiphenyl borate (2‐APB; ref. 19). Shortly afterward, the monoterpene camphor was found to be an agonist (20). In addition, carvacrol, thymol, and eugenol have recently been described to activate TRPV3 (21). The function of TRPV3 in the CNS remains to be elucidated.