Nerolidol in the pharmacy list: two studies on mice and six strains

What is nerolidol and where is it found besides hemp?

Nerolidol is a sesquiterpene alcohol with the formula C15H26O and a molecular weight of 222.37, occurring in two geometric forms. Plants produce it far beyond hemp: it can be found in the essential oils of cardamom and pepper plants of the genus Piper, and it is named after neroli oil, pressed from the flower of the bitter orange.

The difference from myrcene or limonene is not just a naming detail. The former are hydrocarbons, while this compound has a hydroxyl group in its molecule and half again as many carbon atoms, making it an oily liquid with distinctly lower volatility. The PubChem record number 5284507 provides the systematic name for the trans form as (6E)-3,7,11-trimethyl-1,6,10-dodecatrien-3-ol; the second form differs in the arrangement of substituents at one double bond.

The physical description in the same record comes from the FAO and WHO committee on food additives: a colorless or very pale, straw-colored liquid with an oily consistency and a faint woody-floral scent with a hint of rose apple. The fact that this particular committee described the compound is not a coincidence. The substance has served for decades as a fragrance component in cosmetics and is an approved food flavoring, so most of the physicochemical data we have about it comes from evaluations for food, not from studies on inhaling hot vapor. This circumstance recurs in the two subsequent sections.

In how many pharmacy positions does this terpene appear at all?

In the database budcare.pl, it appears in 52 out of 146 described registered positions, while in the medweed.pl database, it is found in 8 out of 65. On the side of cultivars, the same range is visible: the pharmacy list indicates this compound as predominant for six strains, while profile databases list it in the composition of twenty-five.

These two measures do not count the same thing. The pharmacy list assigns one leading terpene to each position, while the profile database lists a whole set, so a strain with our compound in fourth place enters the second set but not the first. Merging both lists into one gives a number that does not answer either the question about the label or the question about the composition.

This is also where our refusal to provide percentage shares for terpene names comes from. We calculated the sums of all shares declared for a single position in the budcare.pl database, considering those 52 records in which nerolidol is present at all. The range was from 14 to 102 with a median of 82.5, and two records exceeded one hundred. Since the complete composition sometimes gives a dozen and sometimes over a hundred, the denominator is different in each record, and a single number pulled from such a table does not measure anything verifiable.

This is most clearly seen in Pink Kush. Seven positions of this strain have a total of 14 in the database, while two positions of Aurora sum to 87 and 91, with a completely different hierarchy of components at the top. One trade name, two irreconcilable declarations.

The contradictions are not only between databases. For Galaxy Walker OG, one profile source describes a position produced by S-LAB solely with myrcene, while a position from Tilray opens with nerolidol, even though it concerns the same cultivar. For Wedding Pie, one database places this substance at the top of the weight list, while another does not mention it at all; with Northern Berry, the roles are reversed. Farm Gas has a record in one of the sources consisting of a single ingredient, and that is precisely this substance.

How long does it take for this terpene to reach the body and how long does it stay there?

It is unknown. No study from the evidence base of this project measured the concentration of nerolidol in human blood after vaporizing dried flower or after ingestion. Only what depends on the route of administration and concerns the entire raw material can be described honestly, not a single component taken from the terpene profile.

The route of administration determines the course more than the variety itself. After vaporization, the substance passes from the lungs to the blood almost immediately, so the first sensations appear after a few minutes, the intensity increases for another ten to thirty minutes, and the whole effect lasts for two to four hours. After ingestion, the raw material first passes through the intestine and liver, so the first sensations are awaited from half an hour to two hours, and the episode can last six, sometimes eight hours. Hence the most common mistake with oral administration: anyone who thinks nothing is happening after thirty minutes and takes another dose will receive both doses at once. The above ranges describe the route of administration, not this variety; pharmacokinetic studies for a single cultivar have not been published.

It has not been calculated how much of this compound passes from the plant material to the vapor when heated. What is known is that it is a substance significantly less volatile than monoterpenes, so attributing the above temporal distribution to it would be a guess, not a reading from measurement. Where the data ends, so does this paragraph.

Is 275-277 degrees Celsius the vaporizer setting?

No. This is the only recorded boiling point of pure nerolidol that we have in the data, coming from one source and given without measurement pressure. The boiling point indicates when the entire liquid in the vessel evaporates, not how to set the device, and we do not derive any setting range from it.

Two rows of this table show why comparing such numbers directly can be misleading. Humulene has the only record made at a pressure of three millimeters of mercury and comes out at less than one hundred degrees, which is lower than for limonene, even though the molecule is heavier. Caryophyllene has both types of measurements at once, and the difference between them exceeds one hundred twenty-five degrees. The record for nerolidol does not specify the pressure at all, so it cannot be determined which of these two groups it belongs to, and comparing it with the rest of the column is therefore risky.

There is something even more serious than pressure. The dried flower is not a pure reagent: in the chamber of the device, the plant material is heated, in which the substance is embedded in glands along with dozens of others, so the value measured for the test tube does not directly translate to the device. Therefore, you will not find a single recommended temperature setting or administration instructions here: these are established by the attending physician together with the patient, not by the description of the chemical compound.

What have studies shown about the effects of this terpene?

Two things, both in mice. The first study described a weaker pain response along with a decrease in two pro-inflammatory cytokines, while the second noted a longer time to seizure along with lower markers of oxidative stress in the brain. Neither of them included humans, and none studied inhalation.

The model here is part of the result, not a footnote. Both studies administered pure substance calculated per kilogram of body weight, the first intraperitoneally, the second via the gastrointestinal tract. A person inhaling vapor from dried flower does not receive either such a form or such a quantity, so transferring the conclusion to them is an abuse, not a shortcut. A decade separates the two studies, and neither worked with plant material: mice received a reagent, not dried flower, so it is even unknown how the same effect would behave in a mixture with a hundred other components of the flower.

This is better seen against the backdrop of the entire literature gathered for these pages. It contains twenty-two studies spread over eleven terpenes. None of them involved humans. Two entries do not concern any mammal at all, as one describes an experimental plant along with an aphid, and the other is a review of insect literature. Our compound is not an exception here, but a typical case: the literature cited in commercial descriptions as evidence of effects on humans ends with rodents, cell cultures, or insects.

What has not been shown about this terpene?

It has not been shown that nerolidol alleviates anxiety or insomnia in humans; both available studies concern rodents and describe analgesic, anticonvulsant, and antioxidant effects, not sleep or mood. This statement is the most important in the entire text and does not constitute a legal disclaimer, but rather a description of what has been measured and published so far.

Descriptions of strains circulating online attribute calming and sleep-inducing effects to this substance. Neither study included such a measurement or endpoint: the first counted abdominal contractions after acetic acid administration, the second the time to seizures induced by pentylene tetrazole. None studied sleep, mood, or anxiety, and least of all in humans.

Three further things that patients most often ask about have also not been shown. First, no one has measured how much of this compound enters the bloodstream after vaporization, so even if the effect in mice could be transferred, there is a missing link regarding exposure. Second, it has not been checked whether the substance alters the effects of THC or other components of the dried flower; the popular hypothesis about the mutual enhancement of plant components has not been tested for this pair. Third, no dose for humans has been established, as this requires a study involving them, and none exists.

A fair answer is therefore this: two signals from animals and zero measurements in humans. A service that states otherwise does not have newer data, only less caution. The question of what has not been shown receives a separate section on these pages precisely because the lack of evidence can be more valuable to the patient than another paragraph about aroma.

What adverse effects have been reported after this terpene?

None, because no one collects them in this way. Safety oversight covers the medicinal product, not a single component of the oil, so reports after dried flower cannot be attributed to the terpene. The evidence base for this project has no studies on adverse effects for nerolidol.

Reports of adverse effects are collected for medicinal products with a batch number, not for the strain name, so the following pertains to hemp dried flower as a group of raw materials. The most frequently reported symptoms are dry mouth, red eyes, and increased heart rate. Dizziness upon rapid standing, daytime drowsiness, and temporary worsening of short-term memory are less frequently described, as well as anxiety that increases with dosage. A separate issue is medications taken concurrently, especially sedatives and those affecting coagulation: their assessment requires knowledge of the entire list of preparations, not just the description of the plant. We do not provide the frequency of these symptoms numerically, as public compilations for hemp dried flower in Poland do not separate them by individual products.

What is known about the substance itself is as much as is known about fragrance components in general: at high concentrations, they can irritate the respiratory tract and skin. The safety assessment that the compound underwent as a food flavoring concerns the ingestion of flavoring amounts, not the inhalation of hot vapor over an extended period. These two routes of administration differ in what they encounter in the respiratory epithelium, so we do not transfer conclusions from the first to the second. If someone wanted to describe the inhalation risk for the terpene itself, they would have to start with a study that no one has done so far.

Which strains from Polish pharmacies have this terpene as dominant?

Six: Galaxy Walker OG, Headband, Pink Certz, Pink Kush, Rockstar, and Strawberry OG. This is the number of entries in the pharmacy list that have this compound indicated as the leading terpene, out of eighty-five cultivars in the entire compilation. They correspond to twenty-one catalog numbers out of one hundred forty-one that we collected for these strains.

The list is short and quite uneven. Pink Kush occupies eight numbers from five producers, Strawberry OG one from one, and the rest fall between these extremes. On the producers' side, the same concentration is visible: S-LAB supplies five of these six strains, Tilray four, and the remaining entities have one each.

The table describes the indication from the label, not the composition. Profile databases list nerolidol in the composition of twenty-five cultivars in this set, which is a group more than four times larger. Besides the six from the table, these are: Beach Crasher, Black Tuna, Chemango Kush, Electric Honeydew, Farm Gas, Island Sweet Skunk, Jack Herer, Jean Guy, King Sherb, Mango, Master Kush, Northern Berry, Purple Octane, Purps, Sherbert Scotti, Sirius, Tilray Sirius, Wedding Pie, White Widow.

The difference between both lists is not a formality. A patient looking for a strain described by a specific terpene usually encounters an indication from the label, which is derived from a single manufacturer declaration for one batch, rather than an average from measurements. The composition provided by profile databases, in turn, comes from commercial descriptions exchanged between parties without specifying the method. Therefore, we present both lists separately and do not represent either as a measurement of content.

The availability of each of these items changes from month to month, as it depends on batch releases and wholesale orders, which is why we maintain the current status in the list of strains available in Polish pharmacies, and not in this text. A separate issue is the nomenclature: dried flower dispensed from a pharmacy on prescription in the Rpw category and dried hemp sold without a prescription in the store section are two different legal categories that should not be confused.

Frequently Asked Questions about nerolidol

Does nerolidol induce sleep?

It is unknown. Both studies from the evidence base of this project concern mice and did not measure sleep with any endpoint, so the description of sedative action is not supported by them.

Does nerolidol have anxiolytic effects in humans?

This has not been demonstrated. Neither of the two studies included humans, and neither had anxiety among the measured endpoints.

At what temperature does nerolidol evaporate?

The only record in our data mentions 275-277 degrees Celsius for the pure compound, without specifying the measurement pressure. This is not the device setting, and we do not derive any of these numbers.

How many strains from Polish pharmacies have nerolidol as the leading terpene?

Six out of eighty-five cultivars in our list, totaling twenty-one catalog entries out of one hundred forty-one.

Why don't you provide how much of this terpene is in the strain?

Because the denominator is unknown. The declared share totals for one entry range in the profile database from 14 to 102, and two records exceed one hundred.

Does nerolidol occur only in hemp?

No. It is found in the essential oils of many plants, including cardamom and pepper plants of the genus Piper, and its name comes from the neroli oil from the bitter orange flower.

Have there been reports of adverse effects from nerolidol alone?

There are no such reports in our database. Safety monitoring is conducted for the medicinal product with a batch number, not for a single component of the oil.

Dried hemp is a pharmaceutical raw material dispensed by a doctor's prescription in the Rpw category. The material is informational in nature and describes the state of evidence; it does not replace the advice of a doctor or pharmacist. The editorial text was prepared by redakcja ubucha.pl.