Human lung cancer A549, colon adenocarcinoma DLD-1, and skin fibroblast WS1 cell line exhibit cytotoxicity levels of 28±1, 43±3, and 24±3 µg/mL, respectively, when exposed to α-Humulene [1]

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
The main psychoactive component of cannabis, tetrahydrocannabinol (THC), is excreted into breastmilk in small quantities. The duration of detection of THC in milk has ranged from 6 days to greater than 6 weeks in various studies. A pharmacokinetic model predicted a half-life in milk of 39 hours which is consistent with a THC clearance from milk in about 8 days. Concern has been expressed regarding the possible effects of cannabis on neurotransmitters, nervous system development and endocannabinoid-related functions. A 1-year study found that daily or near daily use might retard the breastfed infant's motor development, but not growth or intellectual development. This and another study found that occasional maternal cannabis use during breastfeeding did not have any discernable effects on breastfed infants, but the studies were inadequate to rule out all long-term harm. A large registry study in New Zealand suggested that postnatal use of cannabis may increase the risk of autism spectrum disorder, with male infants affected to a greater extent than female infants.
Cannabis can affect serum prolactin variably and some evidence indicates that it might decrease milk supply and the duration of lactation. Maternal perception that their use of cannabis is harmful to their infants are likely to discontinue breastfeeding earlier than mothers who do not believe it is harmful. One preliminary study found a decrease in secretory IgA (SIgA) levels in the milk of cannabis users. Other factors to consider are the possibility of positive urine tests in breastfed infants, which might have legal implications, and the possibility of other harmful contaminants in street drugs. Cannabis seeds are reportedly used orally to increase milk production in Türkiye, but no valid scientific data exist for this use. For information on cannabidiol (CBD), see the LactMed record on Cannabidiol.
Because of insufficient long-term data on the outcome of infants exposed to cannabis via breastmilk, health professionals' opinions on the acceptability of breastfeeding by cannabis-using mothers varies. In general, professional guidelines recommend that cannabis use should be avoided by nursing mothers, and nursing mothers should be informed of possible adverse effects on infant development from exposure to cannabis compounds in breastmilk. In addition to possible adverse effects from cannabinoids in breastmilk, paternal cannabis use may also increase the risk of sudden infant death syndrome in breastfed infants. Cannabis should not be smoked by anyone in the vicinity of infants because the infants may be exposed by inhaling the smoke.
◉ Effects in Breastfed Infants
Twenty-seven mothers reported smoking marijuana during breastfeeding. Twelve of them smoked once a month or less, 9 smoked weekly, and 6 smoked daily. Six of their infants were compared at 1 year of age to the infants of mothers who did not smoke marijuana during pregnancy or breastfeeding. No differences were found in growth, or on mental and motor development.
Sixty-eight infants whose mothers reported smoking marijuana during breastfeeding were compared to 68 matched control infants whose mothers did not smoke marijuana. The duration of breastfeeding varied, but the majority of infants were breastfed for 3 months and received less than 16 fluid ounces of formula daily. Motor development of the marijuana-exposed infants was slightly reduced in a dose-dependent (i.e., number of reported joints per week) manner at 1 year of age, especially among those who reported smoking marijuana on more than 15 days/month during the first month of lactation. No effect was found on mental development.
A small, case-control study found that paternal marijuana smoking postpartum increased the risk of sudden infant death syndrome. In this study, too few nursing mothers smoked marijuana to form any conclusion.
A study of women taking buprenorphine for opiate substitution during pregnancy and lactation found that 4 of the women were also using cannabis as evidenced by positive urine screens for THC between 29 and 56 days postpartum. One was also taking unprescribed benzodiazepines. One infant was exclusively breastfed and the other 3 were mostly breastfeeding with partial supplementation. Infants had no apparent drug-related adverse effects and showed satisfactory developmental progress.
Fifty women who reported using cannabis in the prior 14 days donated milk samples for analysis of THC and its major metabolites. THC was detectable in 66% of the samples and below the limit of quantification in 32% of samples. Preliminary evidence found no differences in infant adverse reactions, postnatal growth, or neurodevelopmental outcomes were found between the groups with quantifiable and nonquantifiable THC in breastmilk.
A 6-month-old infant was exclusively breastfed by a mother who was a chronic cannabis user. She presented to the emergency department with somnolence after falling off a couch and developed seizure-like activity and minimally responsive dilated pupils. Laboratory values and a head CT scan were normal except for carboxy-THC found in urine and blood. The infant returned to baseline in 72 hours.
A 9-month-old girl was hospitalized for a first tonic-clonic seizure. Brain scan and magnetic resonance imaging showed nonspecific right focal frontal cortical hypodensity, without bleeding or traumatic lesion. The electroencephalogram was normal, and no infection was found. Delta-9-THC, delta-9-THC-COOH and 11-OH-THC were found in the infant’s blood. Diazepam and its metabolites were also found in the infant’s blood and the urine screening found cotinine. Her mother explained she smoked cannabis resin since her child was 4 months old, sometimes just before breastfeeding, and on average 5 joints daily. Since then, her child had three spasms. She did not report any cannabis or other drugs use during pregnancy. Breastfeeding was replaced by formula and 1.5 months later, the child had not had a recurrence. The infant’s symptoms were probably caused by cannabis, but direct exposure to cannabis smoke and diazepam and tobacco use could have contributed.
The infant of a woman who used cannabis edibles for anxiety during pregnancy and during breastfeeding had several episodes of apnea. At 1 week of age while undergoing treatment for a urinary tract infection, the infant required intubation because of apneic episodes. At 5 weeks of age, the mother noticed the infant was having irregular breathing and apneic episodes and took the infant to the hospital. There the infant was having more apneic episodes and a urine positive for THC, although the mother reported not using cannabis for the prior 3 days.
◉ Effects on Lactation and Breastmilk
Acute one-time marijuana smoking suppresses serum concentrations of luteinizing hormone and prolactin in nonpregnant, nonlactating women. The effects of long-term use is unclear, with some studies finding no effect on serum prolactin. However, hyperprolactinemia has been reported in some chronic cannabis users, and galactorrhea and hyperprolactinemia were reported in a woman who smoked marijuana for over 1 year. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
Of 258 mothers who reported smoking marijuana during pregnancy, 27 who had smoked marijuana during breastfeeding were followed-up at 1 year. No difference was found in the age of weaning between these mothers and 35 who reported not smoking marijuana during pregnancy or breastfeeding.
The US state of Colorado legalized medical cannabis in 2001 and recreational cannabis in 2012. A cross-sectional survey conducted in Colorado in 2014 and 2015 found that both prenatal and postnatal cannabis use were associated with a shorter duration of breastfeeding. Among women who reported using cannabis during pregnancy, 64% breastfed for 9 or more weeks compared with 78% of women who did not use cannabis during pregnancy. Among women who reported postpartum cannabis use, 58% breastfed for 9 or more weeks compared with 79% of women who did not use cannabis postpartum. Both differences were statistically significant.
A study using a database of 4969 postpartum women found that those who reported using marijuana were more likely to smoke cigarettes, experience postpartum depressive symptoms, and breastfeed for less than 8 weeks. Tobacco smoking is known to decrease the duration of breastfeeding, so the effect of marijuana is not clear. Most of the women who smoked marijuana postpartum also used it during pregnancy.
Among a group of 14 women who used cannabis postpartum by inhalation, lactose levels were higher in the milk of cannabis users compared to the milk of non-users. The milk of cannabis users had lower levels of sIgA relative to non-users; however, when adjusted for BMI, there was no difference in sIgA levels between the groups. Subjects who used both cannabis and cigarettes had lower carbohydrate levels and greater crude protein and true protein levels in their milk. Cannabis-using mothers reported lower levels of milk production in the first, second, fourth, and sixth weeks postpartum, compared to non-users.
An online survey of 1516 mothers who used cannabis during lactation found that 67% of participants were “not at all” concerned that cannabis use while breastfeeding affected their baby. Only 3% attributed symptoms in their infants to cannabis use; symptoms were perceived as positive or negative. Interestingly, 45% (n = 603) altered timing of cannabis use relative to breastfeeding to avoid exposing their infant to cannabis. Most mothers (85.8%) reported no changes in their breast milk supply.

[1]. Anti-Inflammatory, Antioxidant, Antibiotic, and Cytotoxic Activities of Tanacetum vulgare L. Essential Oil and Its Constituents. Medicines (Basel). 2017 May 25;4(2). pii: E34.

(1E,4E,8E)-alpha-humulene is the (1E,4E,8E)-isomer of alpha-humulene.
Humulene has been reported in Trichogonia grazielae, Callilepis laureola, and other organisms with data available.
See also: Caryophyllene (related); Hemp (annotation moved to).

C₁₅H₂₄

204.35

204.188

6753-98-6

5281520

Colorless to light yellow liquid

0.889 g/mL at 20 °C(lit.)

166-168 °C(lit.)

< 25 °C

90°C

n20/D 1.503(lit.)

5.035

0

0

0

15

287

0

C/C/1=C\CC(/C=C/C/C(=C/CC1)/C)(C)C

FAMPSKZZVDUYOS-HRGUGZIWSA-N

InChI=1S/C15H24/c1-13-7-5-8-14(2)10-12-15(3,4)11-6-9-13/h6-7,10-11H,5,8-9,12H2,1-4H3/b11-6+,13-7+,14-10+

(1E,4E,8E)-2,6,6,9-tetramethylcycloundeca-1,4,8-triene

Humulene α-Caryophyllene

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~33.33 mg/mL (~163.10 mM)

Solubility in Formulation 1: 2.5 mg/mL (12.23 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (12.23 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (12.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)