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
◉ Overview of Lactation Use
The main psychoactive component of cannabis, tetrahydrocannabinol (THC), is excreted in small amounts into breast milk. In various studies, the detection time of THC in breast milk has ranged from 6 days to over 6 weeks. Pharmacokinetic models predict a half-life of THC in breast milk of 39 hours, consistent with the approximately 8-day clearance time from breast milk. Concerns have been raised regarding the potential effects of cannabis on neurotransmitters, nervous system development, and endocannabinoid-related functions. A one-year study found that daily or near-daily cannabis use may delay motor development in breastfed infants but did not affect their growth or intellectual development. This study and another found no significant effect on breastfed infants from occasional cannabis use by mothers during lactation, but these studies are insufficient to rule out all long-term harms. A large registry study in New Zealand suggests that postpartum cannabis use may increase the risk of autism spectrum disorder, with male infants being more severely affected than female infants. The effects of cannabis on serum prolactin levels vary from person to person, and some evidence suggests it may reduce milk production and shorten breastfeeding. Mothers who believe cannabis use is harmful to their infants may stop breastfeeding earlier than mothers who do not. A preliminary study found lower levels of secretory immunoglobulin A (SIgA) in the breast milk of cannabis users. Other factors to consider include the possibility that breastfed infants may test positive for cannabis in urine (which could involve legal issues), and the potential presence of other harmful contaminants in street drugs. It has been reported that Turks ingest cannabis seeds to increase milk production, but there is currently no valid scientific data to support this practice. For information on cannabidiol (CBD), please refer to the CBD section on the LactMed website. Due to a lack of data on the long-term effects of cannabis exposure to infants through breast milk, healthcare professionals are divided on whether mothers who use cannabis can breastfeed. Generally, professional guidelines recommend that breastfeeding mothers avoid cannabis use and should be informed that cannabis compounds in breast milk may have adverse effects on infant development. In addition to the potential adverse effects of cannabinoids in breast milk, paternal marijuana use may also increase the risk of sudden infant death syndrome (SIDS) in breastfed infants. No one should smoke marijuana near an infant, as the baby may be affected by inhaling the smoke.
◉ Effects on Breastfed Infants
27 mothers reported using marijuana while breastfeeding. Of these, 12 used it once a month or less, 9 once a week, and 6 once a day. Researchers compared six infants at one year of age with infants whose mothers did not use marijuana during pregnancy or breastfeeding. The results showed no differences between the two groups in terms of growth, psychological development, and motor development.
Researchers also compared 68 infants whose mothers used marijuana while breastfeeding with 68 matched control infants whose mothers did not use marijuana. The duration of breastfeeding varied, but most infants were breastfed for 3 months and consumed less than 16 ounces (approximately 473 ml) of formula daily. Results showed that at age 1, infants exposed to cannabis experienced a slight decline in motor development, which was dose-dependent (i.e., the amount of cannabis smoked per week), particularly in infants who smoked cannabis for more than 15 days per month during the first month of breastfeeding. No effects on psychological development were found. A small case-control study found that paternal cannabis use postpartum increases the risk of sudden infant death syndrome. In this study, the number of breastfeeding mothers who smoked cannabis was too small to draw any conclusions. A study of women taking buprenorphine for opioid replacement therapy during pregnancy and breastfeeding found that four women tested positive for THC in their urine between 29 and 56 days postpartum, indicating concurrent cannabis use. One of these women also took an unprescription benzodiazepine. One infant was exclusively breastfed, and the other three were primarily breastfed with small amounts of other foods. The infants did not experience significant drug-related adverse reactions and developed well. Fifty women who reported cannabis use in the past 14 days donated breast milk samples for THC and major metabolites analysis. THC was detected in 66% of the samples, and in 32% of the samples, the THC content was below the limit of quantification. Preliminary evidence showed no difference in adverse reactions, postnatal growth, or neurodevelopmental outcomes between infants with quantifiable and non-quantifiable THC levels in breast milk. A 6-month-old infant, exclusively breastfed by a mother with a history of marijuana use, fell off a sofa and became lethargic, subsequently exhibiting seizure-like symptoms with dilated pupils and weak pupillary light reflex, and was taken to the emergency department. Laboratory tests and a head CT scan were normal, with carboxyl-THC detected only in urine and blood. The infant recovered after 72 hours. A 9-month-old girl was admitted for her first tonic-clonic seizure. Brain scans and MRI showed a nonspecific focal low-density lesion in the right frontal cortex, without hemorrhage or traumatic lesions. Electroencephalography was normal, and no infection was detected. Δ-9-THC, Δ-9-THC-COOH, and 11-OH-THC were detected in the infant's blood. Diazepam and its metabolites were detected in the infant's blood, and cotinine was found in the urine. The infant's mother explained that she had been smoking cannabis resin since the child was 4 months old, sometimes even before breastfeeding, averaging 5 cannabis cigarettes a day. Since then, her child had experienced three seizures. She did not report using cannabis or other drugs during pregnancy. After switching from breastfeeding to formula feeding, the child stopped experiencing seizures after 1.5 months. The infant's symptoms were most likely caused by cannabis, but direct exposure to cannabis smoke and the use of diazepam and tobacco may have also played a role. A mother who consumed cannabis edibles during pregnancy and breastfeeding to relieve anxiety gave birth to an infant who experienced several episodes of apnea. One week after birth, while receiving treatment for a urinary tract infection, the infant required intubation due to an apnea episode. At 5 weeks old, the mother noticed the infant's irregular breathing and apnea and took the infant to the hospital. The infant experienced an increased frequency of apnea episodes and tested positive for THC in urine, despite the mother reporting no cannabis use in the previous 3 days.
◉ Effects on Lactation and Breast Milk
Acute single cannabis use suppresses serum luteinizing hormone (LH) and prolactin levels in non-pregnant, non-lactating women. The effects of long-term use are unclear; some studies have found no effect on serum prolactin. However, some long-term cannabis users have been reported to have hyperprolactinemia, and one woman who used cannabis for more than one year was also reported to have galactorrhea and hyperprolactinemia. Prolactin levels in established lactating mothers may not affect their ability to breastfeed.
Of the 258 mothers who reported cannabis use during pregnancy, 27 who used cannabis while breastfeeding were followed up for one year. The study found no difference in weaning age between these mothers and 35 mothers who reported not using cannabis during pregnancy or breastfeeding.
Colorado legalized medical and recreational marijuana in 2001 and 2012, respectively. A cross-sectional survey conducted in Colorado in 2014 and 2015 found that marijuana use during pregnancy and postpartum was associated with shorter breastfeeding duration. Among women who reported marijuana use during pregnancy, 64% breastfed for nine weeks or longer, compared to 78% among women who did not use marijuana during pregnancy. Among women who reported marijuana use postpartum, 58% breastfed for nine weeks or longer, compared to 79% among women who did not use marijuana postpartum. Both differences were statistically significant.
A study using a database of 4,969 postpartum women found that women who reported marijuana use were more likely to smoke, experience postpartum depression symptoms, and breastfeed for less than eight weeks. Smoking is known to shorten breastfeeding duration, so the effect of marijuana is unclear. Most women who used marijuana postpartum also used marijuana during pregnancy. In a group of 14 women who inhaled cannabis postpartum, the lactose content in the breast milk of cannabis users was higher than that of non-users. The level of secretory immunoglobulin A (sIgA) in the breast milk of cannabis users was lower than that of non-users; however, after adjusting for body mass index (BMI), there was no difference in sIgA levels between the two groups. Subjects who simultaneously smoked cannabis and cigarettes had lower carbohydrate content and higher levels of crude protein and true protein in their breast milk. Compared to mothers who did not smoke cannabis, mothers who smoked cannabis had lower milk production in the first, second, fourth, and sixth weeks postpartum. An online survey of 1516 breastfeeding mothers who smoked cannabis found that 67% of participants were “not at all” worried about the effects of cannabis use on their infants. Only 3% of mothers believed that their infants’ symptoms were related to cannabis use; these symptoms were categorized as positive and negative. Notably, 45% of mothers (n=603) adjusted the timing of their cannabis use to avoid exposing their infants to cannabis. The majority of mothers (85.8%) reported no change in their breast milk production.

[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)-α-Humulene is the (1E,4E,8E)-isomer of α-humulene. Humulene has been reported in buttercups (Trichogonia grazielae), laurel buttercups (Callilepis laureola), and other organisms with relevant data. See also: caryophyllene (related); cannabis (note 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.)