Azadirachta indica

Neem/Drug Interactions:

  • AbortifacientsAbortifacients: Abortifacient and anti-implantation effects have been noted in animal studies (24; 25; 26; 27; 28; 1).
  • AcetaminophenAcetaminophen: Concomitant use of acetaminophen and aqueous leaf extract of Azadirachta indica has been reported to induce hepatotoxicity in rats (53).
  • AntibioticsAntibiotics: Neem extracts have been shown to exert inhibitory effects on bacterial growth and secreted cholera toxin (54). In human research, toothbrushes soaked for 12 hours in a 3% neem extract had significantly decreased S. mutans colony forming units (CFUs) (30). In children treated with neem mouthwash, significant decreases in Streptococcus mutans were seen after one to two months of use (32). However, in a randomized equivalence trial in adults, significant differences in the neem extract group were lacking for reduction in plaque and gingival indices scores (13).
  • Antidiabetic agentsAntidiabetic agents: Based on animal study, neem may decrease glucose levels and caution is advised when using concomitantly with other sugar-altering herbs and supplements (17).
  • AntihypertensivesAntihypertensives: Pre-treatment with either atropine or mepyramine failed to prevent the hypotensive effect of neem leaf alcoholic extract (19).
  • AntineoplasticsAntineoplastics: In a review, all parts of the neem tree were reported to have anticancer effects including preventative, protective, tumor-suppressive, immunomodulatory, and apoptotic effects in many types of cancer (55).
  • AntiprotozoalsAntiprotozoals: Azadirachta indica is sourced as a remedy for endo- and ectoparasites (56). Both tap water and shampoo dilutions of neem seed extract have been examined as an acaricidal and insecticidal (57).
  • AntisepticsAntiseptics: Neem extracts have been shown to exert inhibitory effects on bacterial growth and secreted cholera toxin (54). In human research, toothbrushes soaked for 12 hours in a 3% neem extract had significantly decreased S. mutans colony forming units (CFUs) (30). In children treated with neem mouthwash, significant decreases in Streptococcus mutans were seen after one to two months of use (32). However, in a randomized equivalence trial in adults, significant differences in the neem extract group were lacking for reduction in plaque and gingival indices scores (13).
  • Anti-ulcer agentsAnti-ulcer agents: Protective and healing effects on gastroduodenal ulcers have been reported in a preliminary human study (10).
  • AntiviralsAntivirals: Extracts from neem have been implicated in delaying the progression of HIV (58).
  • Cardiovascular agentsCardiovascular agents: Ventricular fibrillation and cardiac arrest due to neem leaf poisoning has been reported (41; 42). A 1000mg/kg intravenous dose of an alcoholic neem leaf extract caused bradycardia and cardiac arrhythmia in rats. Doses of 100mg/kg and 300mg/kg also caused bradycardia, and the 300mg/kg dose caused alterations in cardiac rhythm. Pre-treatment with either atropine or mepyramine failed to prevent the hypotensive effect of neem leaf alcoholic extract (19).
  • ContraceptivesContraceptives: Subcutaneously administered neem oil caused luminal epithelial damage to the uterus and surrounding glands in cyclic rats and glycogen and protein depletion in the ovary and uterus (46). Abortifacient and anti-implantation effects have been noted in animal studies (24; 25; 26; 27; 28; 1).
  • Cyclophosphamide and mitomycin CCyclophosphamide and mitomycin C: Neem leaf extract may inhibit the clastogenic activity of cyclophosphamide and mitomycin C (59).
  • Cytochrome P450 metabolized agentsCytochrome P450 metabolized agents: Neem had synergistic activity with dillapiol, a cytochrome P450 3A4 inhibitor (60). Theoretically, neem may have synergistic activity with other cytochrome P450 3A4 inhibitors.
  • Dermatologic agentsDermatologic agents: Neem oil for treating alopecia resulted in contact dermatitis on the scalp and face (43). In a case series evaluating the effects of a neem seed extract shampoo on head lice (Pediculus humanus capitis), adverse effects reported included skin irritation, red spots, and a burning feeling of the scalp (44). Azadirachta indica A. juss has astringent, antiviral, discutient, stimulant, and antibacterial properties and was reported to have anti-acne effects when prepared as a combination herbal face wash gel with similar efficacy as Clindamycin gel (61). In individuals with psoriasis vulgaris, treatment with neem significantly lowered disease severity at eight and twelve weeks (31).
  • Fertility agentsFertility agents: Subcutaneously administered neem oil caused luminal epithelial damage to the uterus and surrounding glands in cyclic rats and glycogen and protein depletion in the ovary and uterus (46). Abortifacient and anti-implantation effects have been noted in animal studies (24; 25; 26; 27; 28; 1).
  • Gastrointestinal agentsGastrointestinal agents: Vomiting, loose stools, and a Reye-like syndrome with symptoms of hypercatabolism and starvation have been reported following the use of crude neem oil (45). Significant increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed in rats treated with 5mL/kg neem oil (margosa oil) intraperitoneally (17). Alkaline phosphatase levels significantly increased and total bilirubin levels significantly decreased in rats receiving 0.4% and 1.6% crude aqueous neem extract (p<0.01) (18).
  • Heart rate regulating agentsHeart rate regulating agents: Ventricular fibrillation and cardiac arrest due to neem leaf poisoning has been reported (41; 42). A 1000mg/kg intravenous dose of an alcoholic neem leaf extract caused bradycardia and cardiac arrhythmia in rats. Doses of 100mg/kg and 300mg/kg also caused bradycardia, and the 300mg/kg dose caused alterations in cardiac rhythm.
  • HematologicsHematologics: Oral administration of crude aqueous neem extract resulted in significant increases in hemoglobin, lymphocytes, MCHC, RBCs, and WBCs in rats (18). Mild transient eosinophilia and non-specific endometritis have been reported following a single intrauterine instillation of purified neem oil (47).
  • HepatotoxinsHepatotoxins: Significant increases in ammonia levels were noted in animal research (17; 18).
  • Hormonal agentsHormonal agents: According to secondary sources, neem may interact with hormonal agents. High concentrations of neem leaf extract may be inhibitory to thyroid function, particularly conversion of T3 and T4 (20). High doses decreased T3 and increased T4 concentrations in rats following 100mg/kg per day for 20 days of neem leaf extract. The mechanism of action for the abortifacient effects of neem is not known but several actions may occur. Abortion was preceded by a decrease in progesterone and chorionic gonadotrophin (CG) in monkeys administered neem, which may affect the maintenance of the endometrium and pregnancy (26).
  • Insect repellantsInsect repellants: In clinical research, 0.5-2% neem oil provided effective protection from mosquito bites (15; 29; 16).
  • MorphineMorphine: The combination of a low dose of neem leaf extract (3.12mg/kg) and a low dose of morphine (0.5mg/kg) produced an increased loss of pain sensation (62).
  • Neurologic agentsNeurologic agents: Ingestion of margosa oil causes toxic encephalopathy particularly in infants and young children (36). Drowsiness, seizures, lethargy, and extreme exhaustion followed with coma/hyporeactivity have been reported (17).
  • QuinineQuinine: Concomitant use of neem extract and quinine hydrochloride has been reported to have positive synergistic effect in the spermicidal activity of these agents (63).
  • Respiratory agentsRespiratory agents: Teeth brushing with neem twigs has been shown to cause trauma to the palate and may predispose to oral lesions with Mycobacterium tuberculosis (49).
  • Thyroid hormonesThyroid hormones: High concentrations of neem leaf extract may be inhibitory to thyroid function, particularly conversion of T3 and T4 (20). High doses decreased T3 and increased T4 concentrations in rats following 100mg/kg per day for 20 days of neem leaf extract.
  • Uterine stimulantsUterine stimulants: Subcutaneously administered neem oil caused luminal epithelial damage to the uterus and surrounding glands in cyclic rats and glycogen and protein depletion in the ovary and uterus (46). Abortifacient and anti-implantation effects have been noted in animal studies (24; 25; 26; 27; 28; 1). Mild transient eosinophilia and non-specific endometritis have been reported following a single intrauterine instillation of purified neem oil (47).

    • Neem/Herb/Supplement Interactions:

  • AbortifacientsAbortifacients: Abortifacient and anti-implantation effects have been noted in animal studies (24; 25; 26; 27; 28; 1).
  • AntibacterialsAntibacterials: Neem extracts have been shown to exert inhibitory effects on bacterial growth and secreted cholera toxin (54). In human research, toothbrushes soaked for 12 hours in a 3% neem extract had significantly decreased S. mutans colony forming units (CFUs) (30). In children treated with neem mouthwash, significant decreases in Streptococcus mutans were seen after one to two months of use (32). However, in a randomized equivalence trial in adults, significant differences in the neem extract group were lacking for reduction in plaque and gingival indices scores (13).
  • AntineoplasticsAntineoplastics: In a review, all parts of the neem tree were reported to have anticancer effects including preventative, protective, tumor-suppressive, immunomodulatory, and apoptotic effects in many types of cancer (55).
  • AntiparasiticsAntiparasitics: Azadirachta indica is sourced as a remedy for endo- and ectoparasites (56). Both tap water and shampoo dilutions of neem seed extract have been examined as an acaricidal and insecticidal (57).
  • AntisepticsAntiseptics: Neem extracts have been shown to exert inhibitory effects on bacterial growth and secreted cholera toxin (54). In human research, toothbrushes soaked for 12 hours in 3% neem extract had significantly decreased S. mutans colony forming units (CFUs) (30). In children treated with neem mouthwash, significant decreases in Streptococcus mutans were seen after one to two months of use (32). However, in a randomized equivalence trial in adults, significant differences in the neem extract group were lacking for reduction in plaque and gingival indices scores (13).
  • Anti-ulcer agentsAnti-ulcer agents: Protective and healing effects on gastroduodenal ulcers have been reported in a preliminary human study (10).
  • AntiviralsAntivirals: Extracts from neem have been implicated in delaying the progression of HIV (58).
  • Cardiovascular agentsCardiovascular agents: Ventricular fibrillation and cardiac arrest due to neem leaf poisoning has been reported (41; 42). A 1000mg/kg intravenous dose of an alcoholic neem leaf extract caused bradycardia and cardiac arrhythmia in rats. Doses of 100mg/kg and 300mg/kg also caused bradycardia, and the 300mg/kg dose caused alterations in cardiac rhythm. Pre-treatment with either atropine or mepyramine failed to prevent the hypotensive effect of neem leaf alcoholic extract (19).
  • ContraceptivesContraceptives: Subcutaneously administered neem oil caused luminal epithelial damage to the uterus and surrounding glands in cyclic rats and glycogen and protein depletion in the ovary and uterus (46). Abortifacient and anti-implantation effects have been noted in animal studies (24; 25; 26; 27; 28; 1).
  • Cytochrome P450 metabolized herbs and supplementsCytochrome P450 metabolized herbs and supplements: Neem had synergistic activity with dillapiol, a cytochrome P450 3A4 inhibitor (60). Theoretically, neem may have synergistic activity with other cytochrome P450 3A4 inhibitors.
  • Dermatologic agentsDermatologic agents: Neem oil for treating alopecia resulted in contact dermatitis on the scalp and face (43). In a case series evaluating the effects of a neem seed extract shampoo on head lice (Pediculus humanus capitis), adverse effects reported included skin irritation, red spots, and a burning feeling of the scalp (44). Azadirachta indica A. juss has astringent, antiviral, discutient, stimulant, and antibacterial properties and was reported to have anti-acne effects when prepared as a combination herbal face wash gel with similar efficacy as Clindamycin gel (61). In individuals with psoriasis vulgaris, treatment with neem significantly lowered disease severity at eight and twelve weeks (31).
  • Fertility agentsFertility agents: Subcutaneously administered neem oil caused luminal epithelial damage to the uterus and surrounding glands in cyclic rats and glycogen and protein depletion in the ovary and uterus (46). Abortifacient and anti-implantation effects have been noted in animal studies (24; 25; 26; 27; 28; 1).
  • GarlicGarlic: Administration of garlic and neem leaf extracts significantly decreased the formation of lipid peroxides and enhanced the levels of antioxidants and detoxifying enzymes in stomach, as well as in the liver and circulation (64).
  • Gastrointestinal agentsGastrointestinal agents: Vomiting, loose stools, and a Reye-like syndrome with symptoms of hypercatabolism and starvation have been reported following the use of crude neem oil (45). Significant increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed in rats treated with 5mL/kg neem oil (margosa oil) intraperitoneally (17). Alkaline phosphatase levels significantly increased and total bilirubin levels significantly decreased in rats receiving 0.4% and 1.6% crude aqueous neem extract (p<0.01) (18).
  • Heart rate regulating agentsHeart rate regulating agents: Ventricular fibrillation and cardiac arrest due to neem leaf poisoning has been reported (41; 42). A 1000mg/kg intravenous dose of an alcoholic neem leaf extract caused bradycardia and cardiac arrhythmia in rats. Doses of 100mg/kg and 300mg/kg also caused bradycardia, and the 300mg/kg dose caused alterations in cardiac rhythm.
  • HematologicsHematologics: Oral administration of crude aqueous neem extract resulted in significant increases in hemoglobin, lymphocytes, MCHC, RBCs, and WBCs in rats (18). Mild transient eosinophilia and non-specific endometritis have been reported following a single intrauterine instillation of purified neem oil (47).
  • HepatotoxinsHepatotoxins: Significant increases in ammonia levels were noted in animal research (17; 18).
  • Hormonal agentsHormonal agents: According to secondary sources, neem may interact with hormonal agents. High concentrations of neem leaf extract may be inhibitory to thyroid function, particularly conversion of T3 and T4 (20). High doses decreased T3 and increased T4 concentrations in rats following 100mg/kg per day for 20 days of neem leaf extract. Abortion was preceded by a decrease in progesterone and chorionic gonadotrophin (CG) in monkeys administered neem, which may affect the maintenance of the endometrium and pregnancy (26).
  • HypoglycemicsHypoglycemics: Based on animal study, neem may decrease glucose levels and caution is advised when using concomitantly with other sugar-altering herbs and supplements (17).
  • HypotensivesHypotensives: Pre-treatment with either atropine or mepyramine failed to prevent the hypotensive effect of neem leaf alcoholic extract (19).
  • Insect repellantsInsect repellants: In clinical research, 0.5-2% neem oil provided effective protection from mosquito bites (15; 29; 16).
  • Neurologic agentsNeurologic agents: Ingestion of margosa oil causes toxic encephalopathy particularly in infants and young children (36). Drowsiness, seizures, lethargy, and extreme exhaustion followed with coma/hyporeactivity have been reported (17).
  • Respiratory agentsRespiratory agents: Teeth brushing with neem twigs has been shown to cause trauma to the palate and may predispose to oral lesions with Mycobacterium tuberculosis (49).
  • Thyroid agentsThyroid agents: High concentrations of neem leaf extract may be inhibitory to thyroid function, particularly conversion of T3 and T4 (20). High doses decreased T3 and increased T4 concentrations in rats following 100mg/kg per day for 20 days of neem leaf extract.
  • Uterine stimulantsUterine stimulants: Subcutaneously administered neem oil caused luminal epithelial damage to the uterus and surrounding glands in cyclic rats and glycogen and protein depletion in the ovary and uterus (46). Abortifacient and anti-implantation effects have been noted in animal studies (24; 25; 26; 27; 28; 1). Mild transient eosinophilia and non-specific endometritis have been reported following a single intrauterine instillation of purified neem oil (47).

    • Neem/Food Interactions:

  • Insufficient available evidence.

    • Neem/Lab Interactions:

  • AmmoniaAmmonia: Significant increases in ammonia were observed in rats treated with 5mL/kg neem oil (margosa oil) intraperitoneally. Ammonia levels increased from 367+/-89mcg NH3N/dL to 716+/-167mcg NH3N/dL (p<0.02 compared to corn oil control and nonsignificant compared to baseline) (17).
  • Bilirubin, potassium, testosteroneBilirubin, potassium, testosterone: Oral administration of crude aqueous neem extract resulted in significant decreases in total bilirubin, serum potassium, and testosterone in rats (18).
  • Blood pressureBlood pressure: Pre-treatment with either atropine or mepyramine failed to prevent the hypotensive effect of neem leaf alcoholic extract (19).
  • GlucoseGlucose: Based on animal study, neem may decrease glucose levels. Glucose levels were decreased in rats from 128+/-3mg/dL to 73+/-7mg/dL (p<0.001 compared to corn oil control and p<0.01 compared to baseline) (17).
  • Heart rateHeart rate: Ventricular fibrillation and cardiac arrest due to neem leaf poisoning has been reported (41; 42). A 1000mg/kg intravenous dose of an alcoholic neem leaf extract caused bradycardia and cardiac arrhythmia in rats. Doses of 100mg/kg and 300mg/kg also caused bradycardia, and the 300mg/kg dose caused alterations in cardiac rhythm.
  • Hemoglobin, lymphocytes, mean corpuscular hemoglobin concentration (MCHC), red blood cells (RBC), white blood cell (WBC)Hemoglobin, lymphocytes, mean corpuscular hemoglobin concentration (MCHC), red blood cells (RBC), white blood cell (WBC): Oral administration of crude aqueous neem extract resulted in significant increases in hemoglobin, lymphocytes, MCHC, RBCs, and WBCs in rats (18).
  • Thyroid functionThyroid function: High concentrations of neem leaf extract may be inhibitory to thyroid function, particularly conversion of T3 and T4 (20). High doses decreased T3 and increased T4 concentrations in rats following 100mg/kg per day for 20 days of neem leaf extract.