Humulene: present in 48 strain profiles, absent from the pharmacy list

What is humulene and where does it occur outside of hemp?

Humulene is a sesquiterpene with the formula C15H24, consisting of a single eleven-membered ring with three double bonds. PubChem lists it under number 5281520 and the name alpha-humulene, with the synonym alpha-caryophyllene. The name comes from common hop, Humulus lupulus, in whose essential oil this compound is described as one of the main sesquiterpenes.

The same molecular formula and the same molecular weight of 204.35 link it to beta-caryophyllene, but the structure is different: caryophyllene has two connected rings, including a strained four-membered one, while humulene has only one large ring. Hence the old name alpha-caryophyllene, which can be misleading for readers expecting a caryophyllene variant. In our data, both compounds are paired: the budcare.pl database lists them together in 88 out of 93 records containing humulene, and when narrowed down to cultivars, in 45 out of 48.

Outside of hemp and hops, sesquiterpenes of this group are common components of essential oils of plants, and in brewing, the oxidation products of humulene contribute to part of the hop aroma. For readers of the pharmacy list, what matters is something else: the presence of the compound in the plant is a chemical feature, not information about the dose that the patient will take. This difference recurs in every subsequent section of this text, as it determines what can be written about a position from the pharmacy list and what remains a description of the molecule.

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

It is unknown, as it has not been measured in humans. The only measurement in the evidence base of this cluster concerns mice after oral administration and refers to minutes, not hours. For the inhalation route, there is not a single value, and our data do not even provide the boiling point under room conditions.

The measurement comes from the work of Chaves JS, Leal PC, Pianowisky L, Calixto JB from 2008 in Planta Medica (PMID:18951339), conducted on a rodent model (mouse). The authors state: "After oral administration of 150 mg/kg, the concentration of alpha-humulene in the plasma of mice peaked after 15 minutes, and its bioavailability was 18%; the half-life was 16.8 minutes after oral administration, and the compound was practically undetectable two hours after intravenous administration."

The boiling point describes the pure compound in a flask, not the setup of the equipment or the amount that passes into vapor. Our collection of temperatures has only one source record for alpha-humulene, 99-100 °C at a pressure of 3 mmHg, attributed to the HMDB database with the PubChem record 5281520. Atmospheric pressure is about 760 mmHg, so this number cannot be compared with measurements under room conditions. The scale of divergence is evident for caryophyllene, for which we have both types of records.

The same substance appears in the record once at 257.5 °C and once at 130 °C, with the difference being solely the pressure. How much humulene remains in the dried flower after heating is unknown, so we do not provide any device settings.

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.

What have studies shown about the effects of humulene?

Two studies, both on rodents. The first describes a reduction in paw swelling and inhibition of two cytokines in mice and rats, the second measures the fate of the compound in the body of mice. Neither included humans, and neither was an in vitro study, so the conclusion about its effects on patients has no basis here.

The work of Fernandes ES, Passos GF, Medeiros R, da Cunha FM, Ferreira J, Campos MM, Pianowski LF, Calixto JB from 2007 in the European Journal of Pharmacology (PMID:17559833) was conducted on a rodent model (mouse and rat). The result states: "Oral alpha-humulene reduced paw swelling in mice and rats induced by platelet-activating factor, bradykinin, ovalbumin, and carrageenan, and as the only one of the two studied compounds also reduced swelling after histamine; systemic administration inhibited the production of tumor necrosis factor alpha and interleukin 1 beta in rats."

The second entry is the pharmacokinetic measurement discussed above (PMID:18951339), also on mice. The proportions of the entire evidence base look modest: eleven terpenes in this cluster have a total of 22 works, none involving humans, and two do not involve a mammalian model, as one concerns a transgenic radish with aphids, and the other is a review of entomological literature. For humulene, both entries are rodent studies, so there is not even an in vitro study that could be referenced when describing the mechanism.

The model determines what can be written. Paw swelling induced experimentally is a measure of the inflammatory response in an animal, not a symptom that a patient presents to a doctor. The doses given to rodents are measured in milligrams per kilogram of body weight and are not converted to a portion of dried flower. Therefore, this text will not include a statement about what humulene does to humans.

What has not been shown about humulene?

Nothing has been demonstrated in humans. There is a lack of measurement of blood concentration after inhalation, measurement of bioavailability from dried flower, and data on the dose at which anything happens. The following sentence from the evidence base of this cluster describes this gap more accurately than any commercial description of the strain.

In humans, neither the bioavailability of humulene from dried flower nor its concentration after inhalation has been measured. Measurements in mice show an 18% bioavailability and a half-life of less than twenty minutes after oral administration, so the percentage in the strain profile says nothing about how much of the compound reaches the blood.

Let's break this down. Eighteen percent was measured after administering a dose of 150 mg/kg to mice via the stomach, a route not used for pharmaceutical raw materials, and in a species whose liver functions differently than that of humans. A half-life shorter than twenty minutes means that in mice, the compound disappeared from plasma faster than a single vaporization session lasts. Neither of these two numbers can be transferred to humans.

What else is missing? There is no measurement of how much of the compound passes from dried flower to vapor during heating, so it cannot be said what portion of the profile record actually leaves the plant material. There is no dose-response relationship in humans, no threshold at which anything begins to happen, and no data on interactions with medications. The phrase 'strain rich in humulene' thus describes the profile label, not the dose that anyone receives.

This section weighs more than a list of presumed properties. Descriptions of strains circulating online present the actions of terpenes as if they were derived from measurements in patients. In our evidence base, there is no such measurement for humulene, and we state this directly instead of burying the gap in generalities.

What side effects have been reported after humulene?

None, because no one collects them under the name of the terpene. The records include finished medication from a specific batch, so there is no entry in public compilations that could be attributed to the compound itself. Below is the state of knowledge about the raw material from which humulene is one of many molecules.

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.

A separate property of the entire group is that concentrated terpenes can irritate the respiratory tract and skin, which is more related to working with oils and concentrates than to the content in dried flower. We do not have a measurement that would link such a reaction to inhaled humulene with vapor, and we do not replace it with assumptions.

The conclusion is modest. Symptoms described after dried flower are attributed to the raw material as a whole, so the choice of strain based on the profile record does not change anything here. A report of an adverse effect should be directed to a doctor or to the monitoring system, and that is the proper route; the strain description is not a tool for this.

Which strains from Polish pharmacies have humulene as the leading terpene?

None. In our pharmacy data, no entry has this compound indicated as leading, although it appears in the composition of 48 strain profiles. The list assigns one leading terpene to each entry and uses only six names, and humulene is not among them.

The numbers look like this. Pharmacy data includes 141 commercial entries spread across 85 cultivars, and the field for the leading terpene accepts six values: caryophyllene in 30 cultivars, myrcene in 20, limonene in 16, terpinolene in 7, nerolidol in 6, and pinene in 6. The total sums to 85, so it is not about gaps in filling the field, but rather a closed dictionary.

An empty list is therefore a statement about the source, not about the plant. The pharmacy list indicates one compound per entry, while profile databases list several, and it is they that show humulene. If indicating the leading terpene were to mean 'the most', a quantitative measurement with a known denominator would be needed, and such measurements are not published by Polish pharmacy sources.

We maintain a complete list of positions available in pharmacies in the strain hub. The store catalog has a separate category for dried flower, which is not a pharmacy list and does not include items dispensed by prescription, as such items are not dispensed outside of pharmacies.

Which profile databases mention humulene in the strain composition at all?

Practically one. Budcare.pl mentions this compound in 48 cultivars from our list, medweed.pl in five, and there is not a single strain that would be indicated exclusively by medweed. The discrepancy is not a detail: for 43 out of 48 names, the entire record of humulene's presence is based on one source.

In raw numbers, it looks like this: the budcare.pl database has 146 registration records and humulene is present in 93 of them, while the medweed.pl database has 65 records and humulene is present in 5. After reducing the records to cultivars, there are 48 names out of 85 described in this cluster.

What is more interesting is what happens where both databases describe the same strain. We have 19 such entries with humulene: both sources consistently mention it in 5, while in 14 it is mentioned exclusively by budcare.pl. The direction is one-sided and never occurs the other way around. Additionally, all three strains for which both databases provide identical compositions have humulene on the list.

For the reader, this means one thing: the record of content can be a feature of the database, not the strain. The table below shows for each name which source mentions this compound and whether the composition descriptions agree at all.

What does the share of humulene provided by profile bases mean?

Less than it seems. Shares provided by the profile base do not sum up to one hundred: in 93 records with this compound, they yield 35 different sums, ranging from 14 to 116, with a median of 84. The denominator is therefore unknown and different in each record, which is why we provide the composition as is, without numbers next to the names.

The variability is easy to check. Four records close exactly at one hundred, three exceed one hundred, and the poorest collects barely fourteen. The number of listed ingredients also varies, from four to nine per record. With such material, the value placed next to the name looks like a measurement, but it is a share in a set whose boundaries no one provides.

The order speaks for itself. In 93 records on budcare.pl, this ingredient has the highest share only twice, and most often lands in the fourth, fifth, or sixth position on the list. Medweed.pl provides only the order, without numbers, and in five of its records places it once in second, twice in third, and twice in fifth position. Not a single entry in this database places it first.

Hence the principle of this cluster: next to the name of the terpene, we do not place a number. A share without a denominator in a text about a prescription drug looks like a measurement, but it is not, and it is this apparent precision that can be the reason why a patient chooses a position from the pharmacy based on one value from the description.

Frequently asked questions about humulene

Is humulene the same as alpha-caryophyllene?

Yes. Alpha-caryophyllene is an older name for the same compound with the formula C15H24, listed in PubChem under number 5281520. Beta-caryophyllene is a separate substance with the same molecular formula but a different ring structure.

Does humulene from dried flower reach the bloodstream after vaporization?

Unknown. In humans, neither the concentration after inhalation nor how much of the compound passes from dried flower to vapor has been measured. The only measurement of bioavailability in the evidence base of this cluster concerns mice after oral administration.

At what temperature does humulene boil?

Our data carries one record: 99-100 °C at a pressure of 3 mmHg, thus a measurement under reduced pressure. This value is not comparable to temperatures measured at 760 mmHg and is not a setting of any device.

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

Not one. The pharmacy list in our data uses only six names of leading terpenes, and humulene is not among them, although it is mentioned in the composition of 48 out of 85 described cultivars.

Why don't you provide how much humulene is in the strain?

Because the denominator is unknown. Shares from the profile base give in 93 records 35 different sums, from 14 to 116, so the value placed next to the name would look like a measurement, but it is not.

Do the results of studies on mice say anything about the action of humulene in patients?

No. Both studies on this compound in the evidence base of the cluster were conducted on rodents, and the doses given to mice are measured in milligrams per kilogram of body weight. Transferring such a result to humans has no basis in data.

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