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Marijuana (Cannabis sativa)



Interactions

Cannabis/Drug Interactions:
  • AlcoholAlcohol: The combination of alcohol plus cannabidiol (CBD) has been reported to result in significantly lower blood alcohol levels in humans compared to alcohol given alone, though similar pharmacological effects were induced (282). In human research, the combined use of alcohol and tetrahydrocannabinol (THC) resulted in altered performance in driving and physiological state (135; 136). Daily co-users of alcohol and marijuana were found to be more likely to engage in risky behaviors and experience negative consequences (294). The authors of a systematic review cited studies which claimed that cannabinoids interact with benzodiazepines or alcohol, leading to increased sedation (295).
  • Anabolic steroidsAnabolic steroids: In female high school students in the United States reporting use of anabolic steroids, other health-compromising behaviors, such as use of cannabis, also increased (296).
  • AnalgesicsAnalgesics: A number of studies have indicated that cannabinoids have a marked analgesic effect (297; 26; 12; 31; 11; 33; 298). According to information cited in a systematic review the use of cannabinoids and opioids resulted in increased antinociception (299).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Both THC and CBD inhibited platelet aggregation in vitro (human platelets), with THC exhibiting a significantly more potent effect than CBD (137; 138).
  • AnticonvulsantsAnticonvulsants: Animal (rat) research indicates that cannabinoids may possess anticonvulsant properties (285; 286; 287). In other research, THC and CBD increased seizure threshold, except at the maximally tested shock (60Hz), whereas CBD was ineffective and THC lowered the observed threshold (300). According to the authors of a systematic review, seizures may be reduced when cannabinoids are used in combination with benzodiazepines (183). Preliminary human research has indicated that epileptic patients may experience a reduced incidence of seizures when taking CBD concomitantly with antiseizure medication (2; 3); however, one patient with dementia in a clinical trial of cannibinoids had a seizure (the effect of cannibinoids is unclear) (166).
  • AntidiabeticsAntidiabetics: Marijuana use increased blood glucose levels in humans (139). However, in animal research, CBD was reported to decrease the incidence of diabetes (43).
  • AntiemeticsAntiemetics: Cannabinoids have been shown to have antiemetic properties in cancer patients (31; 298). Similarly, THC reduced vomiting in animal research, although CBD was ineffective (301). The effects with other antiemetic agents are unclear.
  • AntihypertensivesAntihypertensives: In human research, cases of hypotension have been reported to occur (140; 158).
  • AntineoplasticsAntineoplastics: CBD has been reported to have antineoplastic activity in vitro against human leukemia cells (15; 45; 31; 46), several human cancer cell lines (302) (including U373 glioma cell lines (303; 18; 20; 304)), tumors in rodents (15; 17; 155; 25), and multidrug-resistant mouse lymphoma cells. Cannabinoid derivatives inhibited viral tumor antigen expression (305). In human studies, cannabinoids inhibited nausea and vomiting associated with chemotherapy (183; 187; 158).
  • AntipsychoticsAntipsychotics: In human research, THC and CBD had opposing effects on psychosis. In healthy human volunteers, anxiety and psychotic-like symptoms were observed to occur with THC; however, these effects were significantly reduced by CBD (37; 39; 306). Neuroimaging (38) and animal research (157) have reported similar findings for CBD. According to a systematic review, use of standard pharmacotherapy for mental illness is effective for reducing cannabis use by people with depression or psychotic disorders (307). According to a review of treatment of patients with both psychiatric disorders and evidence of substance abuse, there is some evidence to suggest the benefit of psychiatric medications for the substance abuse; however, evidence of efficacy is limited for antidepressants, and second-generation antipsychotics (clozapine, olanzapine, and risperidone) may be more effective (308). A study cited in a systematic review suggested that the antipsychotic effects of neuroleptics were reported to be antagonized by cannabinoids (309).
  • AntipyrineAntipyrine: In human research, THC and CBD inhibited the metabolism of antipyrine (142).
  • AntiretroviralsAntiretrovirals: In laboratory research, cannabinoids exacerbated HIV infections (44). However, human experimentation has indicated that neither smoked nor oral cannabinoids adversely affect HIV RNA levels, CD4+ or CD8+ cell counts, or protease inhibitor levels in the short term (310).
  • Appetite stimulantsAppetite stimulants: In available clinical research, benefit from cannabis-based therapies for cancer-related anorexia-cachexia syndrome was lacking (236); however, early research suggests a benefit of dronabinol on weight gain in patients with cystic fibrosis (238) and on appetite and weight in patients with AIDS (311). In patients with eating disorders, THC had a lack of effect on weight, caloric intake, and psychiatric assessment (312).
  • BarbituratesBarbiturates: According to human research, THC and CBD may inhibit the metabolism of barbiturates (142), although other human experimentation has reported that CBD does not appear to inhibit secobarbital metabolism (283). CBD has been reported to inhibit hexobarbital clearance; however, the effects of hexobarbital were not affected by CBD (143).
  • BenzodiazepinesBenzodiazepines: According to the authors of a systematic review, seizures may be reduced when cannabinoids are used in combination with benzodiazepines (183). The authors of a systematic review cited studies which claimed that cannabinoids interact with benzodiazepines or alcohol, leading to increased sedation (295).
  • Bromo-dragonFLYBromo-dragonFLY: In a case report, toxicity (severe agitation and seizures) was associated with the recreational use of Bromo-dragonFLY (1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-aminopropane), as well as cannabis and ketamine (253).
  • BronchodilatorsBronchodilators: In a human study, THC was found to have acute bronchodilator activity; however, this effect was lacking with cannabinol and CBD (313).
  • Cannabinoid CB1 receptor antagonistsCannabinoid CB1 receptor antagonists: According to a review, cannabinoid CB1 receptor antagonists are of interest for the cessation of cannabis dependence (314).
  • Cardiovascular agentsCardiovascular agents: Cases of myocardial infarction following marijuana use (167; 168; 169), as well as a case of ventricular bigeminy and circulatory collapse following self-titration of Sativex® oromucosal spray (144), have been reported.
  • CNS depressantsCNS depressants: Dizziness, sleepiness, fatigue, disturbances in attention, and headache have been the most common reported adverse effects in patients using cannabis-based drugs, according to reviews and clinical trials (8; 4; 144; 145; 146; 140; 147; 148).
  • CocaineCocaine: Renal and spleen infarction occurred after use of a large amount of cannabis and cocaine in a case report of a young man (170).
  • CorticosteroidsCorticosteroids: CBD has been reported to interfere with cortisol secretion in humans (315).
  • Cytochrome P450-modifying agentsCytochrome P450-modifying agents: In animal research, cannabis induced the expression of CYP 2E1, which may alter the therapeutic action and metabolism of various types of drugs, including N-nitrosamines and aromatic hydrocarbons (150). In vitro and in vivo, CBD slowed cocaine N-demethylation and metabolism-related hepatotoxicity by inhibition of P450 3A (47).
  • Dermatologic agentsDermatologic agents: In human research, ingestion of hemp seed oil reduced the symptoms of atopic dermatitis, including skin dryness and itchiness (1). Cannabinoids inhibited keratinocyte proliferation in vitro (14).
  • Dopamine antagonistsDopamine antagonists: According to a review, dopamine D3 receptor antagonists are of interest for the cessation of cannabis dependence (314).
  • EcstasyEcstasy: According to a study of adverse effects associated with ecstasy, the authors indicated that visual memory was affected more by concurrent cannabis use (316).
  • EstrogensEstrogens: In laboratory research, a marijuana smoke condensate was found to have an antiestrogenic effect, while this effect was lacking with three major cannabinoids, THC, CBD, and cannabinol (284).
  • Gastrointestinal agentsGastrointestinal agents: In animal research, THC suppressed defecation (266). According to human research, hemp seed oil may have caused gastrointestinal disorders (178). Intravenous usage of marijuana caused fulminant gastroenteritis in humans (141).
  • HepatotoxinsHepatotoxins: In human research, intravenous usage of marijuana caused toxic hepatosis (141).
  • Hormonal agentsHormonal agents: In other research, THC stimulated prolactin and luteinizing hormone levels in vitro (317), though the prolactin-stimulating effect of THC may be rapidly diminished by successive exposures to the drug (318). In laboratory research, a marijuana smoke condensate was found to have an antiestrogenic effect on human breast cancer cells, while effects of three major cannabinoids, THC, CBD, and cannabinol, were lacking (284).
  • ImmunosuppressantsImmunosuppressants: In an in vivo study, CBD was reported to have the potential to clinically affect the metabolism of the immunosuppressive drug cyclosporine, suggesting the possibility of an increase in cyclosporine blood levels and its toxic side effects (154). In human and laboratory research, constituents of marijuana (THC, CBD) were found to be immunomodulating (151; 152; 153). Laboratory studies have also demonstrated that cannabinoids possess immunosuppressive properties (152; 153).
  • Neurologic agentsNeurologic agents: In limited available human research, a potential benefit of dronabinol for weight gain and behavior was presented in individuals with dementia (166).
  • NicotineNicotine: According to a clinical report cited (319) by authors of a systematic review, the effects of cannabinoids may be potentiated by nicotine (183).
  • Nonsteroidal anti-inflammatoriesNonsteroidal anti-inflammatories: According to reports cited (309; 320; 321; 322) by authors of a systematic review (183), the subjective "high," tachycardia, and antiglaucoma effects of cannabinoids are antagonized by indomethacin and nonsteroidal anti-inflammatory agents.
  • Opioid receptor antagonistsOpioid receptor antagonists: According to a review, opioid receptor antagonists are of interest for the cessation of cannabis dependence (314).
  • P-glycoprotein regulated agentsP-glycoprotein regulated agents: According to laboratory research, cannabinol may affect the absorption and disposition of coadministered compounds that are P-glycoprotein (P-gp) substrates (P-gp plays a significant role in the transport of many compounds) (155).
  • ProchlorperazineProchlorperazine: According to a systematic review, when THC is combined with prochlorperazine, chemotherapy side effects may be reduced further (183).
  • Reproductive agentsReproductive agents: Exposure to the three active marijuana components (THC, CBD, and cannabinol) has been reported to adversely affect spermatogenesis in both humans and rodents (267).
  • Respiratory agentsRespiratory agents: In a human study, THC was found to have acute bronchodilator activity; however, effects of cannabinol and CBD were lacking (313).
  • SedativesSedatives: Dizziness, sleepiness, fatigue, disturbances in attention, and headache have been the most common reported adverse effects in patients using cannabis-based drugs, according to reviews and clinical trials (8; 4; 144; 145; 146; 140; 147; 148). Theoretically, concurrent use of cannabis-based agents and central nervous system (CNS) depressants may increase the risk of CNS adverse effects. According to information cited in a systematic review, cannabinoids may interact with benzodiazepines or alcohol, leading to increased sedation (295). According to the authors of a systematic review, seizures may be reduced when cannabinoids are used in combination with benzodiazepines (183). In human insomniacs, CBD improved sleep quality (2).
  • Synthetic cannabinoidsSynthetic cannabinoids: According to a systematic review, although anecdotally there may be overlapping effects between marijuana and so-called herbal products containing synthetic cannabinoid agonists, such as Spice and K2, actual known clinical effects are lacking in the available literature (133). In three regular cannabis users, the effects of these agents were well tolerated and similar to marijuana, according to the authors. According to the three users, cannabis withdrawal was alleviated by use of the cannabinoid agonists.
  • VasodilatorsVasodilators: In animal and laboratory research, CBD produced vasodilation (323; 29; 30).

Cannabis/Herb/Supplement Interactions:
  • Anabolic steroidsAnabolic steroids: In female high school students in the United States reporting use of anabolic steroids, other health-compromising behaviors, such as use of cannabis, were also increased (296).
  • AnalgesicsAnalgesics: A number of studies have indicated that cannabinoids have a marked analgesic effect (297; 26; 12; 31; 11; 33; 298). According to information cited in a systematic review, the use of cannabinoids and opioids resulted in increased antinociception (299).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Both THC and CBD inhibited platelet aggregation in vitro (human platelets), with THC exhibiting a significantly more potent effect than CBD (137; 138).
  • AnticonvulsantsAnticonvulsants: Animal (rat) research indicates that cannabinoids may possess anticonvulsant properties (285; 286; 287). In other research, THC and CBD increased seizure threshold, except at the maximally tested shock (60Hz), whereas CBD was ineffective and THC lowered the observed threshold (300). According to the authors of a systematic review, seizures may be reduced when cannabinoids are used in combination with benzodiazepines (183). Preliminary human research has indicated that epileptic patients may experience a reduced incidence of seizures when taking CBD concomitantly with antiseizure medication (2; 3); however, one patient with dementia in a clinical trial of cannibinoids had a seizure (the effect of cannibinoids is unclear) (166).
  • AntiemeticsAntiemetics: Cannabinoids have been shown to have antiemetic properties in cancer patients (31; 298). Similarly, THC reduced vomiting in animal research, although CBD was ineffective (301). The effects with other antiemetic agents are unclear.
  • AntineoplasticsAntineoplastics: CBD has been reported to have antineoplastic activity in vitro against human leukemia cells (15; 45; 31; 46), several human cancer cell lines (302) (including U373 glioma cell lines (303; 18; 20; 304)), tumors in rodents (15; 17; 155; 25), and multidrug-resistant mouse lymphoma cells. Cannabinoid derivatives inhibited viral tumor antigen expression (305). In human studies, cannabinoids inhibited nausea and vomiting associated with chemotherapy (183; 187; 158).
  • AntioxidantsAntioxidants: THC has been reported to act as an antioxidant in vitro (24; 324).
  • AntipsychoticsAntipsychotics: In human research, THC and CBD had opposing effects in psychosis. In healthy human volunteers, anxiety and psychotic-like symptoms were observed to occur with THC; however, these effects were significantly reduced by CBD (37; 39; 306). Neuroimaging (38) and animal research (157) have reported similar findings for CBD. According to a systematic review, use of standard pharmacotherapy for mental illness is effective for reducing cannabis use by people with depression or psychotic disorders (307). According to a review of treatment of patients with both psychiatric disorders and evidence of substance abuse, there is some evidence to suggest the benefit of psychiatric medications for the substance abuse; however, evidence of efficacy is limited for antidepressants, and second-generation antipsychotics (clozapine, olanzapine, and risperidone) may be more effective (308). A study cited in a systematic review suggested that the antipsychotic effects of neuroleptics were reported to be antagonized by cannabinoids (309).
  • Antiretroviral agentsAntiretroviral agents: In laboratory research, cannabinoids exacerbated HIV infections (44). However, human experimentation has indicated that neither smoked nor oral cannabinoids adversely affect HIV RNA levels, CD4+ or CD8+ cell counts, or protease inhibitor levels in the short term (310).
  • Appetite stimulantsAppetite stimulants: In available clinical research, benefit of cannabis-based therapies in cancer-related anorexia-cachexia syndrome was lacking (236); however, early research suggests a benefit of dronabinol on weight gain in patients with cystic fibrosis (238) and on appetite and weight in patients with AIDS (311). In patients with eating disorders, THC had a lack of effect on weight, caloric intake, and psychiatric assessment (312).
  • BarbituratesBarbiturates: According to human research, THC and CBD may inhibit the metabolism of barbiturates (142), although other human experimentation has reported that CBD does not appear to inhibit secobarbital metabolism (283). CBD inhibited hexobarbital clearance; however, the effects of hexobarbital were not affected by CBD (143).
  • BenzodiazepinesBenzodiazepines: According to the authors of a systematic review, seizures may be reduced when cannabinoids are used in combination with benzodiazepines (183). The authors of a systematic review cited studies which claimed that cannabinoids interact with benzodiazepines or alcohol, leading to increased sedation (295).
  • BronchodilatorsBronchodilators: In a human study, THC was found to have acute bronchodilator activity; however, cannabinol and CBD did not (313).
  • Cardiovascular agentsCardiovascular agents: Cases of myocardial infarction following marijuana use (167; 168; 169), as well as a case of ventricular bigeminy and circulatory collapse following self-titration of Sativex® oromucosal spray (144), have been reported.
  • CNS depressantsCNS depressants: Dizziness, sleepiness, fatigue, disturbances in attention, and headache have been the most common reported adverse effects in patients using cannabis-based drugs, according to reviews and based on clinical trials (8; 4; 144; 145; 146; 140; 147; 148).
  • CorticosteroidsCorticosteroids: CBD has been reported to interfere with cortisol secretion in humans (315).
  • Cytochrome P450-modifying agentsCytochrome P450-modifying agents: In animal research, cannabis induced the expression of CYP 2E1, which may alter the therapeutic action and metabolism of various types of drugs, including N-nitrosamines and aromatic hydrocarbons (150). In vitro and invivo, CBD slowed cocaine N-demethylation and metabolism-related hepatotoxicity by inhibition of P450 3A (47).
  • Dermatologic agentsDermatologic agents: In human research, ingestion of hemp seed oil reduced the symptoms of atopic dermatitis, including skin dryness and itchiness (1). Cannabinoids inhibited keratinocyte proliferation in vitro (14).
  • Dopamine antagonistsDopamine antagonists: According to a review, dopamine D3 receptor antagonists are of interest for the cessation of cannabis dependence (314).
  • Gastrointestinal agentsGastrointestinal agents: In animal research, THC suppressed defecation (266). According to human research, hemp seed oil may have caused gastrointestinal disorders (178). Intravenous usage of marijuana caused fulminant gastroenteritis in humans (141).
  • Hepatotoxic agentsHepatotoxic agents: In human research, intravenous usage of marijuana caused toxic hepatosis (141).
  • Hormonal agentsHormonal agents: CBD interfered with cortisol secretion in humans (315). In other research, THC stimulated prolactin and luteinizing hormone levels in vitro (317), though the prolactin-stimulating effect of THC may be rapidly diminished by successive exposures to the drug (318).
  • HypoglycemicsHypoglycemics: Marijuana use increased blood glucose levels in humans (139). However, in animal research, CBD decreased the incidence of diabetes (43).
  • HypotensivesHypotensives: In human research, cases of hypotension have been reported to occur (140; 158).
  • ImmunosuppressantsImmunosuppressants: In an in vivo study, CBD was reported to have the potential to clinically affect the metabolism of the immunosuppressive drug cyclosporine, suggesting the possibility of an increase in cyclosporine blood levels and its toxic side effects (154). In human and laboratory research, constituents of marijuana (THC, CBD) were found to be immunomodulating (151; 152; 153).
  • Neurologic agentsNeurologic agents: In limited available human research, a potential benefit of dronabinol for weight gain and behavior was presented in individuals with dementia (166).
  • NicotineNicotine: According to a clinical report cited (319) by authors of a systematic review, the effects of cannabinoids may be potentiated by nicotine (183).
  • Nonsteroidal anti-inflammatoriesNonsteroidal anti-inflammatories: According to reports cited (309; 320; 321; 322) by authors of a systematic review (183), the subjective "high," tachycardia, and antiglaucoma effects of cannabinoids are antagonized by indomethacin and nonsteroidal anti-inflammatory agents.
  • Opioid receptor antagonistsOpioid receptor antagonists: According to a review, opioid receptor antagonists are of interest for the cessation of cannabis dependence (314).
  • P-glycoprotein regulated agentsP-glycoprotein regulated agents: According to laboratory research, cannabinol may affect the absorption and disposition of coadministered compounds that are p-glycoprotein (P-gp) substrates (P-gp plays a significant role in the transport of many compounds) (155).
  • PhytoestrogensPhytoestrogens: In laboratory research, a marijuana smoke condensate was found to have an antiestrogenic effect, while this effect was lacking with three major cannabinoids, THC, CBD, and cannabinol (284).
  • Reproductive agentsReproductive agents: Exposure to the three active marijuana components (THC, CBD, and cannabinol) has been reported to adversely affect spermatogenesis in both humans and rodents (267).
  • Respiratory agentsRespiratory agents: In a human study, THC was found to have acute bronchodilator activity; however, effects of cannabinol and CBD were lacking (313).
  • SedativesSedatives: Dizziness, sleepiness, fatigue, disturbances in attention, and headache have been the most common reported adverse effects in patients using cannabis-based drugs, according to reviews and based on clinical trials (8; 4; 144; 145; 146; 140; 147; 148). Theoretically, concurrent use of cannabis-based agents and CNS depressants may increase the risk of CNS adverse effects. According to information cited in a systematic review, cannabinoids may interact with benzodiazepines or alcohol, leading to increased sedation (295). According to the authors of a systematic review, seizures may be reduced when cannabinoids are used in combination with benzodiazepines (183). In humans, CBD improved sleep quality in insomniacs (2).
  • Synthetic cannabinoidsSynthetic cannabinoids: According to a systematic review, although anecdotally, there may be overlapping effects between marijuana and so-called herbal products containing synthetic cannabinoid agonists; actual known clinical effects are lacking in the available literature (133). In three regular cannabis users, the effects of these agents were well tolerated and similar to marijuana, according to the authors. According to the three users, cannabis withdrawal was alleviated by use of the cannabinoid agonists.
  • VasodilatorsVasodilators: CBD has been reported to produce vasodilation in rodents and in vitro (323; 29; 30).

Cannabis/Treatment Interactions:
  • Cognitive-behavioral treatmentCognitive-behavioral treatment: According to a meta-analysis, cognitive-behavioral treatment was useful in marijuana studies (325). According to a review, motivational interviewing and Contingency Management may be effective for treatment of comorbid psychiatric disorders and evidence of substance abuse (308).

Cannabis/Food Interactions:
  • GeneralGeneral: In available clinical research, benefit of cannabis-based therapies in cancer-related anorexia-cachexia syndrome was lacking (236); however, early research suggests a benefit of dronabinol on weight gain in patients with cystic fibrosis (238) and on appetite and weight in patients with AIDS (311). In patients with eating disorders, THC had a lack of effect on weight or caloric intake (312).

Cannabis/Lab Interactions:
  • Blood alcoholBlood alcohol: The combination of alcohol plus CBD has been reported to result in significantly lower blood alcohol levels in humans compared to alcohol given alone, though similar pharmacological effects were induced (282).
  • Blood glucoseBlood glucose: Marijuana use increased blood glucose levels in humans (139). However, in animal research, CBD decreased the incidence of diabetes (43).
  • Blood pressureBlood pressure: In human research, cases of hypotension have been reported to occur (140; 158).
  • CD4/CD8 cell countsCD4/CD8 cell counts: In laboratory research, cannabinoids exacerbated HIV infections (44). However, human experimentation has indicated that neither smoked nor oral cannabinoids adversely affect HIV RNA levels, CD4+ or CD8+ cell counts, or protease inhibitor levels in the short term (310).
  • Coagulation panelCoagulation panel: Both THC and CBD inhibited platelet aggregation in vitro (human platelets), with THC exhibiting a significantly more potent effect than CBD (137; 138).
  • CortisolCortisol: CBD interfered with cortisol secretion in humans (315).
  • Drug screenDrug screen: Foods or supplements containing cannabis seeds or oil may contain a concentration of THC high enough to trigger a positive drug screen (160; 161). However, other research has reported that ingestion of foods containing cannabis seeds or oil did not induce a level high enough register as positive on drug tests (50ng/mL) (162; 163; 164; 165).
  • EstrogenEstrogen: In laboratory research, a marijuana smoke condensate was found to have an antiestrogenic effect; however, this effect was lacking with the cannabinoids THC, CBD, and cannabinol (284).
  • ProlactinProlactin: In in vitro research, THC stimulated prolactin levels (317).
  • Luteinizing hormone (LH)Luteinizing hormone (LH): THC stimulated prolactin and luteinizing hormone levels in vitro (317), though the prolactin-stimulating effect of THC may be rapidly diminished by successive exposures to the drug (318).
  • Radiation therapyRadiation therapy: Cannabinoids, CBD, and CBD-dimethylheptyl (CBD-DMH) induced apoptosis in a human acute myeloid leukemia (AML) HL-60 cell line, with prior exposure of the cells to gamma-irradiation (800cGy) markedly enhancing apoptosis (304).
  • Semen analysisSemen analysis: Exposure to the three active marijuana components (THC, CBD, and cannabinol) has been reported to adversely affect spermatogenesis in both humans and rodents (267).

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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