Terpinolene

Terpinolene

1. Identity: Chemical and Botanical Overview

Chemical Names and Classification

Terpinolene is a monoterpene identified by CAS number 586-62-9. At its core, terpinolene is a cyclic monoterpene hydrocarbon with the molecular formula C₁₀H₁₆, whose structure is characterized by a cyclohexene ring with a methyl group and an isopropylidene group attached. It is a monocyclic monoterpene, meaning it contains a single six-membered ring structure with a branching side-chain double bond. This specific arrangement of carbon atoms and double bonds is responsible for its distinctive aroma and reactivity.

Terpinolene (also known as δ-terpinene) has been isolated from a variety of plant sources. Other synonyms include: p-Mentha-1,4(8)-diene; 1-Methyl-4-isopropylidene-1-cyclohexene; 1,4(8)-Terpadiene; and 4-Isopropylidene-1-methylcyclohexene. In the research literature it is also abbreviated as TPL or TPO. Terpinolene shares a close connection with another monoterpene named terpinene, being one of four isomers of that compound; as an isomer, terpinolene features the same atoms as terpinene but in a different arrangement.

Physical and Chemical Properties

Terpinolene carries the molecular formula C₁₀H₁₆ and a boiling point of approximately 186°C. Like its isomers, terpinolene is a colorless liquid with a turpentine-like odor. More specifically, terpinolene produces a complex aroma profile described as piney, floral, herbal, and citrus. Like all monoterpene hydrocarbons with allylic positions, terpinolene is susceptible to autoxidation upon air exposure.

Natural Sources

Terpinolene is a monoterpene that is naturally found in a variety of herbs and is widely used as a flavoring agent in the industry. It appears naturally in a wide range of botanical contexts: cannabis, tea tree, sage, lilac, rosemary, nutmeg, cumin, and apple all contain it in varying concentrations. Terpinolene is also found in high percentages (up to 10%) in some Cannabis sativa cultivars, and is found abundantly in plants such as Pastinaca sativa (parsnip), Melaleuca alternifolia (tea tree), and Myrtus communis (myrtle). It is found in plant species across diverse geographic regions, including Melaleuca alternifolia in Australia, Pistacia vera in Greece, India, and Iran, Artemisia dracunculus in Iran, and Rosmarinus officinalis in Brazil.

Terpinolene is a common constituent of certain commercial cannabis chemovars and is a distinguishing feature of "sativa" strains. It is also a cyclic monoterpene compound found in some Labiatae herbs.

Common Forms and Preparations

In commercial and research contexts, terpinolene is encountered primarily as an isolated liquid monoterpene, obtained by steam distillation or solvent extraction of plant material. It is used as a concentrated aromatic and flavor ingredient in flavor and fragrance compounds according to FEMA GRAS/FDA guidelines. Terpinolene holds FEMA GRAS designation number 3046. It also appears as a natural constituent of many commercially sold essential oils derived from its source plants, including tea tree oil and various pine-needle oils. In the context of cannabis, terpinolene is present within the whole-plant material or concentrated cannabis extracts rather than as a standalone supplement.

2. Traditional and Historical Use

Ethnobotanical Context

Terpinolene itself has not historically been isolated or used as a discrete compound. Its traditional use is embedded within the use of terpene-containing plants and their essential oils. Terpenes have been acknowledged as effective therapeutic alternatives for the treatment of various conditions in herbal medicine traditions from around the world, including in Mediterranean, Ayurvedic, and Chinese Medicine.

From an ethnotraditional point of view, Pinus mugo — one of the richest botanical sources of terpinolene — is mainly used for respiratory disorders and wound healing; its essential oils have been shown to possess antimicrobial and antioxidant activities, which can substantiate its potential therapeutic effect in pulmonary and urinary tract diseases, as well as anti-inflammatory and antitumor effects. Numerous members of the genus Pinus (Pinaceae) are used in traditional medicine in their native ranges, and several essential oils derived from the genus are commercially important for use in aromatherapy and topical therapy applications — including Scots pine (Pinus sylvestris), black pine (Pinus nigra), jack pine (Pinus banksiana), and white pine (Pinus strobus).

Traditional terpinolene uses include natural antiseptic, antifungal, and antibacterial applications, as well as use as a mild central nervous system depressant exhibiting sedative effects, mainly when combined with linalool. The herb Microtoena patchoulii, a Labiatae species whose inhaled essential oil was found to contain terpinolene as an active sedative ingredient, has an established history of use in traditional Asian medicine systems. Studies have shown that the production of terpene compounds is influenced by both genetic factors and the environmental conditions to which the plant is exposed. Evidence has suggested that the fact that terpenes are produced as part of the defense mechanism of plants in response to stressful stimuli contributes significantly to their wide variety of biological effects.

3. Key Constituents, Active Compounds, and Mechanisms of Action

Nature as an Active Compound

Terpinolene is itself the active moiety under investigation rather than a mixture; however, it is typically encountered in nature as one component among many terpenes within essential oils. Terpenes are the largest group of natural bioactive compounds, and among them, monoterpenes are widely used flavoring agents with significant biological activity.

Computational Targets (In Silico Evidence)

An in silico analysis showed that the most likely targets for terpinolene interaction belong to the following categories: (1) Family A G protein-coupled receptors including Cannabinoid receptor 2, Adenosine A1 receptor, Prostanoid EP4 receptor, and Acetylcholine receptor; (2) Nuclear receptors including Peroxisome proliferator-activated receptor alpha (PPAR-α), Estrogen and Androgen Receptors; (3) Arachidonate oxidoreductase enzymes including 5-lipoxygenase and Cyclooxygenase-1; (4) Orphan receptor tyrosine kinase (RTK) including Proto-oncogene tyrosine-protein kinase ROS; and (5) Other enzymes including Alkaline phosphatase, Adenosine deaminase, and Aminopeptidase N.

Computational predictions indicate terpinolene has significant predicted activity at several biological targets, including Muscarinic acetylcholine receptor M1, Prostanoid EP4 receptor, Serotonin 3a (5-HT3a) receptor, and Proto-oncogene tyrosine-protein kinase ROS. These computational findings provide a plausible mechanistic scaffold, but must be understood as hypothesis-generating rather than established pharmacology.

Antioxidant Mechanism

The essential oil of Pinus mugo and the contained monoterpene terpinolene effectively prevent LDL oxidation. In order to test the mechanism by which terpinolene protects LDL from oxidation, LDL from human blood plasma enriched in terpinolene was isolated; in this preparation not only the lipid part of LDL is protected against copper-induced oxidation — as proven by following the formation of conjugated dienes — but also the oxidation of the protein part is inhibited, since loss of tryptophan fluorescence is strongly delayed. This inhibition is due to a retarded oxidation of intrinsic carotenoids of LDL, and not, as in the case of some flavonoids, attributable to a protection of intrinsic alpha-tocopherol.

Anti-inflammatory and Antinociceptive Mechanism

Terpinolene shows anticancer, antioxidant, and anti-inflammatory properties along with efficiency against LDL oxidation, sedative features, and is anti-nociceptive via the 5-HT2A receptor. Terpinolene has been recognized for its anti-inflammatory and pain-reducing effects, possibly through modulation of serotonergic mechanisms within the central nervous system.

Anticancer Mechanisms

Studies have found terpinolene effective at reducing the expression of a protein kinase known as AKT (protein kinase B), which contributes to cancer progression by mediating cell proliferation and survival signals. Inhibition of cell proliferation via down-regulation of Akt1 expression in K562 cells has been reported at terpinolene concentrations as low as 50 µg/mL.

Sedative Mechanism

In research evaluating the sedative effect of the inhaled essential oil of Microtoena patchoulii leaves in mice, terpinolene was isolated as the active ingredient. Investigation of the structure–activity relationships found that a double bond in the side-chain or pi bonds in the six-membered ring play important roles in the sedative effect; in experiments using olfactory-impaired mice, inhaled terpinolene was further shown to exert its effect after nasal absorption into the body.

Acetylcholinesterase Inhibition

Molecular docking studies revealed that terpinolene has hydrophobic and polar favourable interactions with key residues in the catalytic site of cholinesterase, thereby inhibiting acetylcholinesterase (AChE). A pharmacological cholinesterase inhibition effect has been measured with an IC₅₀ at 156.4 µg/mL.

Antifungal Mechanism

A 2020 study published in Letters in Applied Microbiology demonstrated that terpinolene enhanced the antifungal activity of terbinafine against dermatophyte species including Microsporum canis and Trichophyton interdigitale, with synergistic results when the compounds were combined; the proposed mechanism involved disruption of plasma membrane functionality in fungal cells.

4. Scientific Evidence by Area of Use

Overview of the Evidence Base

Although it is well established in the literature that terpinolene is an important component of plant extracts, the biological properties and the potential therapeutic use of this compound remain poorly explored. Analysis of the literature reveals that most studies addressing the biological activities of terpinolene were conducted using in vitro tests. Few preclinical studies have investigated these activities through in silico (computational), in vitro, and in vivo studies, and no clinical trials have been conducted to demonstrate the therapeutic potential of terpinolene.

The most comprehensive synthesis of the existing evidence is a systematic review published in Phytomedicine in 2021. The review was carried out in four electronic databases (Embase, Web of Science, Scopus, and PubMed) according to PRISMA guidelines. The initial search found a total of 2,449 articles; however, only 57 of them met the inclusion criteria. The analysis indicated that terpinolene presents a series of biological effects, from which the antioxidant, larvicide, and insecticide activities stand out. Despite the evidence demonstrating pharmacological potential, the mechanisms underlying its cellular and molecular effects remain to be better elucidated, and the in vivo efficacy and safety of the administration of this compound have been poorly evaluated through either preclinical or clinical trials.

Antioxidant Activity

Evidence Level: Preliminary — in vitro and limited ex vivo; no clinical trials.

Terpenoids are a class of naturally occurring antioxidants found in essential oils, and the essential oil of Pinus mugo and the contained monoterpene terpinolene effectively prevent LDL oxidation. The key study here is the 2005 work by Grassmann et al. published in Phytomedicine (Vol. 12, pp. 416–423), which used an ex vivo model: concentrations of 0.025% and higher were reported to have a protective role against the oxidation of lipophilic and proteinaceous parts of LDL molecules when terpinolene was incubated with human blood plasma.

Research published in the journal Cytotechnology tested the effects of terpinolene on human lymphocytes — a subtype of white blood cells — exposing the cells to the terpene for periods of 24 and 48 hours; researchers found antioxidant activity along with no genotoxic effects, concluding that terpinolene could be a "new resource of therapeutics" due to its antioxidant activities.

Terpinolene increased total antioxidant capacity and total oxidative stress without a genotoxic effect in both primary rat neurons and N2a neuroblastoma cell lines in a dose-dependent manner. The antioxidant activity of terpinolene could be useful in preventing cell damage caused by oxidative stress, and may potentially be useful for neurodegenerative diseases such as Alzheimer's. No human clinical trials on terpinolene's antioxidant effects have been published.

Anticancer and Antiproliferative Activity

Evidence Level: Preliminary — in vitro and animal studies only; no clinical trials.

A 2011 study published in Oncology Letters (cited as Okumura et al., 2011) examined terpinolene's effect on K562 leukemia cells. Terpinolene, described as a component of herbal sage, was found to downregulate AKT1 expression in K562 cells. Researchers found the terpene to produce significant effects when administered to neuroblastoma cells and concluded that terpinolene produces potent antiproliferative effects and may have potential use as an anticancer agent.

A separate study from Aydin, Türkez, and Taşdemir (2013), published in Archives of Industrial Hygiene and Toxicology (64[3]:415–424), studied terpinolene in rat brain cells. While efficacy was dose-dependent, the researchers stated that terpinolene is a potent antiproliferative agent for brain tumor cells and may have potential as an anticancer agent, which needs to be further studied.

Consistent evidence has demonstrated antiviral properties of this monoterpene against influenza A virus (PR8, subtype H1N1), Herpes simplex virus types 1 and 2, Echovirus 9, Poliovirus 1 (Sabin strain), Coxsackievirus B1, and Adenovirus 2. For influenza A/PR/8 virus subtype H1N1, terpinolene showed antiproliferative effects, without however inhibiting neuraminidase expression or virus fixation in the cells.

Research suggests that terpinolene might have anticancer properties and be effective in inhibiting the growth of cancer cells; however, these studies are not yet conclusive, and proof is lacking when it comes to the efficacy of terpinolene as a cancer treatment option.

Sedative and CNS Effects

Evidence Level: Animal studies only (mice); no human clinical trials.

The pivotal study on terpinolene's sedative properties was conducted by Ito and Ito and published in the Journal of Natural Medicines (67[4]:833–837, 2013). Terpinolene is a cyclic monoterpene compound found in some Labiatae herbs. In the study, the sedative effect of inhaled essential oils of Microtoena patchoulii leaves in mice was evaluated and terpinolene was isolated as an active ingredient. The structure–activity relationships were investigated to identify the structural part essential to its sedative effect; comparison of terpinolene analog activities showed that a double bond in the side-chain or pi bonds in the six-membered ring play important roles in the sedative effect. In another experiment using olfactory-impaired mice, the study revealed that inhaled terpinolene exerted the effect after nasal absorption into the body.

It was sedative in mice at 0.1 mg, reducing motor activity to 67.8%. In a related data point, terpinolene was sedative in mice at 0.04 mg in air, reducing motor activity to 47.3% of baseline.

Subjective reports in humans suggest greater stimulation in terpinolene-rich cannabis chemovars, possibly attributable to cholinesterase inhibition effects in the presence of THC. This apparent paradox between isolated terpinolene sedation in animal models and perceived stimulation in terpinolene-rich whole-plant preparations highlights the complexity of multi-compound interactions and the entourage effect hypothesis. No controlled human trials have been conducted.

Anti-inflammatory and Analgesic Activity

Evidence Level: Animal studies only; no human clinical trials.

The main clinical-preclinical evidence comes from Macedo et al. (2016), published in the Brazilian Journal of Medical and Biological Research (49[7]) as a freely accessible PMC article (PMC4918787). The association of ineffective doses of terpinolene (TPL) and diclofenac (DCF) (3.125 and 1.25 mg/kg p.o., respectively) presented antinociceptive and anti-inflammatory effects in both acute (0, 1, 2, 3, 4, 5 and 6 hours after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170–230 g, n=6–8). Mechanical hyperalgesia was assessed by the Randall-Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethysmography. The TPL/DCF association reduced neutrophils, macrophages, and lymphocytes in the histological analysis of the paw.

Studies have shown that the combination of NSAIDs with monoterpenes can produce synergistic analgesic and anti-inflammatory effects with fewer gastric side effects. This synergistic effect is considered particularly noteworthy; however, all data derive from a rat model, and translation to human medicine remains unvalidated.

Antifungal and Antimicrobial Activity

Evidence Level: In vitro only; no clinical trials.

According to the consulted literature, terpinolene has antimicrobial activities as a parasite, antifungal, antibacterial, virucide, and trypanocide. Terpinolene showed activity against Trypanosoma brucei with an EC₅₀ of 0.035 µg/mL (0.26 µM). Its fungicidal effects were demonstrated in studies with Leptographium abietinum, Candida tropicalis (32 mg/mL), C. utilis (8 mg/mL), C. albicans (at concentrations above 32 mg/mL), Botrytis cinerea, and Sclerotium cepivorum.

A 2018 study identified terpinolene (5.36%) among terpenoid derivatives of Cupressus torulosa essential oil; the compounds were effective against pathogens including B. subtilis, Pseudomonas alcaligenes, M. luteus, and B. cereus. All antimicrobial results to date are in vitro, and no clinical application for terpinolene as a standalone antimicrobial has been established.

Cardiovascular — LDL Oxidation Inhibition

Evidence Level: In vitro / ex vivo only; no clinical outcomes data.

Terpinolene has demonstrated the ability to inhibit LDL oxidation, which holds significance in the treatment of atherogenesis and coronary artery disease. Antioxidants such as vitamin E, beta-carotene, and flavonoids inhibit the oxidative modification of low-density lipoproteins; this protective effect could possibly retard atherogenesis and in consequence avoid coronary heart diseases, and some studies have shown a positive effect of those antioxidants on cardiovascular disease. Terpinolene's inhibition of LDL oxidation, demonstrated by the Grassmann et al. (2005) study, places it in this class of terpenoid antioxidants, though no cardiovascular outcome data in humans exist.

Insecticidal and Larvicidal Activity

Evidence Level: Multiple in vitro and in vivo (insect) studies; most researched activity.

The 2021 PRISMA systematic review highlights terpinolene's insecticidal and antioxidant effects as the most promising activities demonstrated through preclinical studies. Studies have demonstrated the effectiveness of terpinolene in the elimination of disease vectors due to both its insecticide and larvicide properties. Literature data regarding the biological activities of other non-oxygenated monocyclic monoterpenes presenting the same molecular mass as terpinolene indicate that they share comparable insecticidal activities, as demonstrated for limonene. The insecticidal evidence is the most extensive in terpinolene's research profile, though this is primarily of environmental and agricultural relevance rather than direct human supplementation.

Wound Healing

Evidence Level: In vitro only.

A 2019 study by de Christo Scherer et al. published in the Journal of Tissue Viability (28[2]:94–99) examined wound healing activity. The study evaluated wound healing activity of terpinolene and α-phellandrene by attenuating inflammation and oxidative stress in vitro. No in vivo wound healing trials have been published.

Cholinesterase Inhibition and Potential Neuroprotection

Evidence Level: In silico and in vitro only.

Although terpinolene demonstrates a variety of biological effects (antioxidant, antifungal, bacteriostatic, antispasmodic, cytoprotective, and anti-inflammatory), only few studies present its potential as an Alzheimer's disease (AD) treatment. Molecular docking studies revealed that terpinolene has hydrophobic and polar favorable interactions with key residues in the catalytic site of cholinesterase, thereby inhibiting AChE. These findings remain at the computational stage.

5. Body Systems and Health Areas Associated with Terpinolene

• Cardiovascular system: Inhibition of LDL oxidation holds significance in the treatment of atherogenesis and coronary artery disease.
• Central nervous system / sedation: Terpinolene is known for its sedative effects through oral administration, as well as through nasal absorption.
• Oncology / antiproliferative: Evidence has placed terpinolene as a bioactive compound with significant pharmacological activities, among which the antifungal, antioxidant, and insecticide activities are highlighted. Antiproliferative activity in cancer cell lines has been reported, though only in vitro.
• Pain and inflammation: Collectively, articles analyzed in the systematic review reported that terpinolene has several pharmacological activities, including anti-cholinesterase, sedative, cytotoxic, cytoprotective, anti-inflammatory, antispasmodic, antiproliferative, antinociceptive, lysozyme ligand, n-nitrosamine inhibitor, and P-glycoprotein effects.
• Immune/antimicrobial: Consistent evidence has demonstrated antiviral properties against influenza A virus, HSV-1 and HSV-2, Echovirus 9, Poliovirus 1, Coxsackievirus B1, and Adenovirus 2.
• Skin (dermal): Wound healing and antifungal properties relevant to dermatophytes have been identified in vitro. Terpinolene is a recognized phytoconstituent of tea tree oil (Melaleuca alternifolia), which contains a wide array of terpene compounds with antimicrobial action.
• Neurology: The antioxidant activity of terpinolene could be useful in preventing cell damage caused by oxidative stress, with potential relevance to neurodegenerative diseases such as Alzheimer's.

6. Dosage Forms and Dosages Reported in Studies

There is no established human clinical dosage for terpinolene as a dietary supplement. The following dosages are reported in the specific preclinical studies cited and should not be construed as clinical recommendations.

• LDL oxidation (ex vivo, human plasma): Concentrations of 0.025% and higher terpinolene were reported to have a protective role against the oxidation of lipophilic and proteinaceous parts of LDL molecules when terpinolene was incubated with human blood plasma.
• Sedation (inhalation, mouse): Terpinolene was sedative in mice at 0.1 mg, reducing motor activity to 67.8%. A separate report found sedation at 0.04 mg in air, reducing motor activity to 47.3% of baseline.
• Anti-inflammatory / analgesic (oral, rat): Ineffective doses of terpinolene (3.125 mg/kg p.o.) in combination with diclofenac (1.25 mg/kg p.o.) presented antinociceptive and anti-inflammatory effects in female Wistar rats.
• Anticancer / antiproliferative (in vitro, cell lines): Inhibition of cell proliferation via downregulation of Akt1 expression in K562 cells was reported even at 50 µg/mL terpinolene concentration.
• Antifungal (in vitro): Fungicidal effects against Candida tropicalis were demonstrated at 32 mg/mL; against C. utilis at 8 mg/mL; and against C. albicans at concentrations above 32 mg/mL.

Although some studies have mentioned the possibility of using terpinolene in the production of food, insecticides, and medicines, given the lack of scientific data proving its effectiveness, this theme deserves further investigation through in vivo and clinical studies.

7. Safety Considerations and Toxicology

Regulatory Status

Terpinolene is recognized as a concentrated aromatic and flavor ingredient used in flavor and fragrance compounds according to legal IFRA or FEMA GRAS/FDA guidelines. It holds FEMA GRAS designation number 3046. The Flavor and Extract Manufacturers Association (FEMA) GRAS assessment of aliphatic and aromatic terpene hydrocarbons, published in Food and Chemical Toxicology in 2011, provides a key reference for its safety as a food flavoring agent.

Acute Toxicity

The oral LD₅₀ in rats is 4,390 mg/kg. The dermal LD₅₀ in rabbits exceeds 5,000 mg/kg. The acute oral LD₅₀ value in rats has been reported as 4.39 mL/kg, and similarly that in mice and rats was reported to be 4.4 mL/kg. These values indicate low acute oral and dermal toxicity in rodents at dietary exposure levels. Terpinolene is classified under GHS hazard categories as a flammable liquid (Category 3), with acute oral toxicity (Category 5), skin sensitization potential (Category 1), and aspiration hazard (Category 1).

Genotoxicity and Mutagenicity

Terpinolene was evaluated in an Ames test with Salmonella typhimurium and returned a negative result for mutagenicity. In a micronucleus test using human lymphocytes, the result was also negative; no ingredient is identified as a probable, possible, or confirmed human carcinogen by IARC. Under the conditions of the study, terpinolene was not mutagenic in the Ames test. The U.S. National Toxicology Program (NTP) Report on Carcinogens does not list terpinolene.

Skin and Contact Sensitization

Terpinolene was not irritating to human skin when applied at a concentration of 20% in petrolatum for 48 hours under a closed patch in 24 volunteers, and it was not a sensitizer in the maximization test. However, in a case report, a 49-year-old woman developed eczematous lesions of the hands and forearms while using a machine cleaner containing terpinolene; upon patch testing, terpinolene gave a positive reaction.

Like all monoterpene hydrocarbons with allylic positions, terpinolene is susceptible to autoxidation upon air exposure. The resulting hydroperoxides and aldehydes can act as contact sensitizers — a concern shared with limonene, linalool, and alpha-terpinene. Fresh, properly stored material (sealed, cool, less than 24 months) shows no irritation or sensitization in human patch testing at 10% concentration. This strongly suggests that oxidized or degraded terpinolene carries a meaningfully different risk profile than fresh material.

Aspiration Hazard

Terpinolene may be fatal if swallowed and enters airways; if accidentally swallowed, the product may enter the lungs due to its low viscosity. This is a standard risk class for liquid monoterpene hydrocarbons.

Aquatic Toxicity

Terpinolene is classified as very toxic to aquatic life. Toxicity to fish (semi-static test) shows an LC₅₀ in zebrafish (Danio rerio) of 0.805 mg/L over 96 hours.

Thermal Degradation

Research published in Nature Scientific Reports on monoterpene thermal behavior at vape coil temperatures (100–300°C) identified 29 reaction byproducts specifically from terpinolene under those conditions, with the unchanged portion of the parent compound varying from just 11–28% at higher temperatures — a dramatic degradation rate compared to more stable terpenes like myrcene, which preserved 97–98% of its parent compound under comparable conditions. This is relevant to inhalation-based delivery of terpinolene.

Interactions and Drug Combination Data

There are few studies on terpinolene's pharmacological activity, including as one of the major components of essential oils that showed anti-inflammatory, antibacterial, and anticancer actions. The rat study by Macedo et al. (2016) specifically examined a drug interaction: studies have shown that the combination of NSAIDs with monoterpenes can have synergistic analgesic and anti-inflammatory effects with fewer gastric side effects. This finding was made only in animals; whether a similar interaction profile applies in humans, and whether it extends to other NSAIDs or classes of drugs, is unknown.

There are insufficient toxicity data on terpinolene (CAS # 586-62-9) to draw comprehensive conclusions about interactions, long-term safety, or systemic effects from ingested or inhaled exposures beyond those described in the studies above.

Overall Evidence Limitations

Most studies included in the 2021 systematic review provide a superficial characterization of terpinolene's biological effects, and therefore further research elucidating its mechanism of action and potential therapeutic benefits through preclinical and clinical trials are required. Nevertheless, due to its wide range of different biological activities, terpinolene will certainly attract the interest of scientific research, which could significantly contribute to the development of new products with both therapeutic and environmental applications.

References

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• Ito K, Ito M. (2013). The sedative effect of inhaled terpinolene in mice and its structure-activity relationships. Journal of Natural Medicines 67(4):833–837. PubMed.
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