Herbal supplement & marijuana use pre- & post …...HERBAL SUPPLEMENT & MARIJUANA USE PRE- & POST-TRANSPLANT Mariesa Cote, PharmD Clinical Pharmacist – Sold i Organ Transpalnt Massachusetts

HERBAL SUPPLEMENT & MARIJUANA USE PRE- & POST-TRANSPLANT

Mariesa Cote, PharmD

Clinical Pharmacist – Solid Organ Transplant

Massachusetts General Hospital

October 4th, 2018

STATEMENT OF DISCLOSURE

I have no conflicts of interest

OBJECTIVES

Identify the risks associated with herbal supplement use pre-transplant

Identify major drug interactions with herbal supplements

Explain the risks of marijuana use post-transplant

ALTERNATIVE MEDICINE

Form of medical therapy used as a substitute for conventional medicine

Naturopathic medicine

Homeopathic medicine

Chinese medicine

Aromatherapy

Massage therapy

Use of a special diet or herbal remedy to cure or alleviate the symptoms of a condition

Kaye, et al. Anesthesiology Clin Am. 2004

HISTORY OF HERBAL THERAPY

Ancient middle-eastern civilizations used herbal therapy extensively

Herbal gardens were created to grow medicinal plants for medical schools

Early colonial days relied on herbal therapy to provide medical care in the home

Herbal therapy re-emerged in the U.S. in the 1960s

The Office of Alternative Medicines by the National Institutes of Health was established in 1992


REGULATIONS

Dietary Supplement Health and Education Act (DSHEA) of 1994

Defines dietary supplements as “a product to supplement the diet”

Considered food, not drugs

No requirements for safety & efficacy testing

Food and Drug Administration (FDA)

Included in the “supplement” category, not classified as a drug

Manufacturers exempt from approval by FDA

No protocol for standardization of these herbal supplements

Lack of standard regulations and good manufacturing practice (GMP) leads to products available of variable quality and content

Kaye, et al. Anesthesiology Clin Am. 2004Gabardi S, et al. Clin J Am Soc Nephrol. 2007.

Ang-Lee MK, et al. JAMA. 2001.

DIETARY SUPPLEMENTS

Vitamins Minerals Herbs

Amino acids Enzymes Organ

tissues

Metabolites


FORMULATIONS

Extracts Concentrates Tablets

Capsules Gelcaps Liquids

Powders Oils


HERBAL THERAPY & DIETARY SUPPLEMENTS

There are >20,000 nutraceuticals available in the United States

Approximately 36% of the population use nutraceuticals in conjunction with prescription drugs

Majority of patients report utilizing these products to “cure” chronic conditions

Misconception that these products are “natural” so they must be safe

Only 12% of supplement users seek care from a physician or licensed complementary and alternative medicine provider

Kaye, et al. Anesthesiology Clin Am. 2004Gabardi S, et al. Clin J Am Soc Nephrol. 2007.

HERBAL THERAPY & DIETARY SUPPLEMENTS

70% of patients failed to disclose their herbal supplement use

Rationale:

Thoughts that physicians are not knowledgeable about herbal supplements

Patient’s fear admitting to providers their use of non-standard therapy

Thoughts that herbal supplement use is unrelated to their medical care

Herbal supplements not considered medications that require reporting

Providers should seek out a history of herbal supplement use!

Ang-Lee MK, et al. JAMA. 2001

TOP 10 BEST SELLING HERBAL PRODUCTS

Cranberry

Saw palmetto

Soy

Garlic

Gingko

Echinacea

Milk Thistle

Black cohosh

St. John's Wort

Ginseng

https://www.takingcharge.csh.umn.edu/explore-healing-practices/botanical-medicine/10-top-best-selling-botanicals-what-they-do

PERI-OPERATIVE USE

SURGICAL CONCERNS

Applicable to both organ donors and recipients

Decreased platelet aggregation or inhibition of clotting Bleeding

Central nervous system (CNS) depression Potentiation of anesthesia

American Society of Anesthesiologists recommends that patients discontinue use of herbal supplements 2-3 weeks before surgery


BLEEDING RISK

Herbal Indication Perioperative considerations

Recommendation

Garlic (Allium sativum)

Vasodilatory effect↓cholesterol

↑ bleeding risk through platelet dysfunction & ↑ fibrinolytic activity

D/C 7 days prior to surgery

Ginger (Zingiber offcinale)

N/V, motion sickness, vertigo

Potent inhibitor of thromboxane; ↑ bleeding risk


Avoid w/ use of antiplatelets, anticoagulants & NSAIDs

Gingko biloba Antioxidant, circulatory stimulant, dementia

Inhibits platelet activating factor; ↑ bleeding risk; gingko toxin



Avoid with anticonvulsants

Kaye, et al. Anesthesiology Clin Am. 2004Wong A, et al. Continuing Education in Anaesthesia, Critical Care & Pain. 2011

BLEEDING RISK


Recommendation

Ginseng Mood enhancer,Immunomodulation,Hypoglycemic activity

Irreversible platelet inhibition ↑bleeding

↓blood glucose

↑blood pressure



Turmeric Anti-infective, analgesic, anti-inflammatory and anti-oxidant effects

Antiplatelet effects D/C 14 days prior to surgery


Natural Medicines Database

DRUG-DRUG INTERACTIONS


Recommendation

St. John’s Wort (Hypericum perforatum)

Antidepressant Inducer of CYP3A4 & 2C9

Sedative effects


Drug interactions!

Echinacea Immunostimulatoryproperties

Potential for anaphylaxis

Inhibits CYP3A4


Drug interactions!


SEDATIVE EFFECTS

Herbal Indication Perioperative Complications

Recommendation

Kava kava (Piper methysticum)

Anxiolytic/sedative Potentiation of the effects of anesthesia/sedatives

D/C 24 hours prior to surgery

Valerian Anxiolytic/sedative Potentiation of the effects of anesthesia/sedatives

D/C 2 weeks prior to surgery

Melatonin Sedative Potentiation of the effects of anesthesia/sedatives

No general consensus for when to D/C -recommend D/C 7-14 days prior to surgery



RECOMMENDATION

Providers should seek out a history of herbal supplement use

Patients utilizing herbal supplements can be referred to pharmacy for consult

All herbal supplements should be held at least 2 weeks prior to surgery

POST-TRANSPLANT USE

POST-TRANSPLANT CONSIDERATIONS

Modulation of the immune system through “boosting” of the immune system

Drug-drug interactions through alterations in cytochrome P450 metabolism and P-glycoprotein (P-gp) transporter function

Direct toxic effects on the transplanted organ

IMMUNOMODULATION

Herbal Indication Post-Transplant Concerns Recommendation

Ginseng Mood enhancer,Immunomodulation,Hypoglycemic activity

Stimulates the immune function by increasing T cell proliferation that may interfere with immunosuppressive therapy.

AVOID

Echinacea Immunostimulatory properties

Stimulates immune function through activation of complement pathway increasing activity of T cells potentially interfering immunosuppressive therapy

AVOID

Melatonin Sedative Stimulates immune function through secretion of cytokines potentially interfering immunosuppressive therapy

Case reports of autoimmune hepatitis

AVOID


Natural Medicines DatabaseKang S, et al. J Ginseng Res. 2012.

Carrillo-Vico A, et alInternational Journal of Molecular Sciences. 2013.


Herbal Indication Post-Transplant Concerns

Recommendation

St. John’s Wort (Hypericum perforatum)

Antidepressant Inducer of CYP3A4 & 2C9

Sedative effects

AVOIDDrug interactions!

↓immunosuppression levels rejection

Echinacea Immunostimulatory properties

Inhibits CYP3A4 AVOIDDrug interactions!

↑immunosuppression levels toxicity

Turmeric Anti-infective, analgesic, anti-inflammatory and anti-oxidant effects

Inhibits CYP3A4 AVOID

↑immunosuppression levels toxicity



FRUIT JUICES

Fruit Juice Post-Transplant Concerns Recommendation

Pomegranate Case report of elevated tacrolimus levels in a heart transplant patient consuming 1-2 pomegranate popsicles per day (51g each)

CAUTION – may result in increased tacrolimus levels

Clementine Case report of elevated tacrolimus levels in a renal transplant patient consuming >1 kg/day of clementines; tacrolimus levels returned to normal with discontinuation

Recommend use in moderation

Grapefruit Case report of elevated tacrolimus levels in a liver transplant patient consuming 250ml of grapefruit juice four times per day for 3 days

CAUTION – effect on tacrolimus level was delayed, peaking ~1 week after grapefruit ingestion

Cranberry No significant difference in cyclosporine levels when 1 glass of cranberry juice consumed.

Recommend use in moderation

Khuu T, et al. The Journal of Heart and Lung Transplantation 2013.Theile D, et al. European Journal of Pharmaceutical Sciences. 2017.

Julie G, et al. Clinical Pharmacology & Therapeutics. 2006.Fukatsu S et al. Drug Metabolism and Pharmacokinetics. 2006.

HEPATOTOXIC DIETARY SUPPLEMENTS

Bee pollen

Birch oil

Blessed thistle

Borage

Butterbur

Cascara Sagrada

Celandine

Chaparral

DHEA

Echinacea

Ephedra

Green tea

Kava

Mistletoe

Periwinkle

Sassafras

Turmeric

Valerian

Vitamin EGabardi S, et al. Clin J Am Soc Nephrol. 2007.


Echinacea

Used as an immunostimulant to fight a variety of infections

Multiple case reports of acute cholestatic hepatitis

Consumption of echinacea root extract 600mg-1500mg daily for 5-14 days

Green Tea

Polyphenols are thought to be associated with the anti-oxidant properties of green tea

Data in animals showing acute tubular necrosis & hepatotoxicity with green tea supplement use

Natural Medicines DatabaseGabardi S, et al. Clin J Am Soc Nephrol. 2007.


Valerian

Used to manage insomnia and restlessness

Multiple case reports of hepatotoxicity with a variety of doses utilized

Long-term effect of valerian on liver function is unknown

Vitamin E

Used for cancer prevention and wound healing

Immunostimulatory properties are undesirable post-transplant

Deleterious effects seen in patients taking more than 1000mg per day

Natural Medicines DatabaseGabardi S, et al. Clin J Am Soc Nephrol. 2007.

Neff GW, et al. Liver Transpl. 2004.


Turmeric

Multiple case reports of autoimmune hepatitis in a patients taking turmeric dietary supplements

LFT abnormalities resolved with discontinuation of supplements

Ramelteon/Melatonin

Case reports of autoimmune hepatitis

Immunostimulatory effects of melatonin through T-cell and B-cell modulation, potentiating autoimmune hepatitis

Funk J, et al. The FASEB Journal. 2017Lulefahr AL, et al. BMF Case Reports. 2018.

Fourman LT, et al. J Clin Gastroenterol. 2013.Hong YG, et al. J Clin Gastroenterol. 1997.

NEPHROTOXIC DIETARY SUPPLEMENTS

Direct Nephrotoxicity

• Chromium• Creatine• L-Lysine• Yohimbe• Willow Bark• Cat's Claw• Turmeric• Ginger• Green Tea

Nephrolithiasis

• Vitamin C• Ephedra• Cranberry

Rhabdomyolysis

• Wormwood Oil• Creatine• Licorice• Red Yeast Rice

Gabardi S, et al. Clin J Am Soc Nephrol. 2007.


Chromium

Used for weight loss, glucose control and hyperlipidemia

Multiple case reports of ATN related to chromium use

Amount consumed varied from 600mcg/day to 2400mcg/day for 2 weeks to 6 months

Creatine

Used for muscle enhancement or “body building”

Two case reports of ATN & 5 cases of rhabdomyolysis following creatine use

One patient ingested 5g/day for 4 weeks and the second ingested 15g/day for 1 week followed by 2g/day for 12 weeks

After stopping creatine, serum creatinine normalized



L-Lysine

Used to promote wound healing/treat oral ulcers/cold sores

Reported to cause Fanconi Syndrome and tubulointerstitial nephritis

Single case report of patient consuming 3000mg/day for 5 years

Ginger

Theoretical risk based on known mechanisms

Used to treat inflammation and inhibit cyclooxygenase (COX)

Inhibition of prostaglandins leading to vasoconstriction & renal failure



Turmeric

Theoretical risk based on known mechanisms

Used to treat inflammation and inhibit cyclooxygenase (COX)

Inhibition of prostaglandins leading to vasoconstriction & renal failure

Green Tea

Polyphenols are thought to be associated with the anti-oxidant properties of green tea

Data in animals showing acute tubular necrosis & hepatotoxicity with green tea supplement use

Gabardi S, et al. Clin J Am Soc Nephrol. 2007.Lambet JD, et al. Chem Res Toxicol. 2007.


Vitamin C

Used to promote wound healing & prevent cancer and heart disease

Metabolized to oxalate leading nephrolithiasis secondary to oxaluria

Immunostimulatory properties are undesirable post-transplant

Seen in patients utilizing 60g/day of Vitamin C

Cranberry

Used to acidify the urine and prevent urinary tract infections

Contains oxalate leading to nephrolithiasis secondary to oxaluria

Case reports of nephrolithiasis following administration of cranberry concentrate tablets and >1L of juice per day



Licorice

Potent diuretic associated with severe hypokalemia

FDA Warning in October 2017 regarding risk of arrhythmia associated with black licorice use

Age 40 or older and consuming 2 ounces per day for at least two weeks

Gabardi S, et al. Clin J Am Soc Nephrol. 2007.https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm277152.htm

https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm277152.htm

RESOURCES

Natural Medicines https://naturalmedicines-therapeuticresearch-com.ezproxymcp.flo.org/

National Center for Complementary and Integrative Health https://nccih.nih.gov/

https://naturalmedicines-therapeuticresearch-com.ezproxymcp.flo.org/

https://nccih.nih.gov/

MARIJUANA USE

MARIJUANA

Extract of Cannabis sativa (Indian hemp) plant

Classified as a Schedule 1 containing substances with high abuse potential

Consists of 60 pharmacologically active cannabinoids

Two most described cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)

Oberbarnscheidt, T. J Addict Res Ther. 2016.

MECHANISM OF ACTION

Cannabinoid receptors are present in the brain and spinal cord

CB1 receptors are primarily in the nervous system Antagonism of these receptors leads to mental & behavioral effects

Alters perceptions & mood, affects memory and learning

Leads to impaired judgement

CB2 receptors primarily in the periphery on cells in the immune system Possible immunosuppressive activity of cannabis

Inhibition of neurotransmitter release (acetylcholine & glutamate)Oberbarnscheidt, T. J Addict Res Ther. 2016.

MECHANISM OF ACTION

CBD does not have psychoactive effects & appears to block the effects of THC through antagonism at the CBD receptor

Marijuana has become significantly more potent

Newer forms of marijuana available with higher THC content

Oberbarnscheidt, T. J Addict Res Ther. 2016.ElSohly MA, et al. Biol Psychiatry. 2016.

FORMULATIONS

Natural Form

Consists of THC & CBD

Active component is THC which is sought after for psychoactive effects

Marijuana or “Medical Marijuana”


FORMULATIONS

Synthetic Forms

Consist of THC

Two FDA-approved forms: Marinol (Dronabinol) & Cesamet (Nabilone)

Street Forms: K2, Spice, Joker, Black Mamba, Kush, and Kronic

Oberbarnscheidt, T. J Addict Res Ther. 2016.Synthetic Cannabinoids. NIDA. 2018.

FORMULATIONS

Marinol (dronabinol) Cesamet (nabilone)Schedule CIII substance CII substanceIndication Indicated for the treatment of:

Anorexia in AIDS patientsN/V associated with cancer chemotherapy

Indicated for the treatment of:N/V associated with cancer chemotherapy

Dosing Initial dose: 2.5mg BID Initial dose: 1-2mg BID, 1-3 hours prior to chemotherapy

Adverse Effects May cause psychiatric and cognitive effects and impair mentation

May cause psychiatric and cognitive effects and impair mentation

Dose adjustment NoneMay increase LFTs (≤1%)

None

Drug Interactions Substrate of 2C9 & 3A4**Cyclosporine/Tacrolimus

None

Marinol. FDA. 2017.Cesamet. FDA. 2013.

FORMULATIONS

Semi-Synthetic Forms

Combination of THC & CBD

Sativex (Nabiximols) – Not available in U.S.


FORMULATIONS

Epidiolex (cannabidiol) was approved by the FDA in June 2018

CBD oral solution for management of Lennox-Gastaut syndrome and Dravetsyndrome

Three randomized, controlled trials showed significantly greater reductions in seizure activity compared to placebo

Mild increases in liver transaminases were noted but raising the possibility of more severe injury

https://www.thecannabist.co/2018/04/18/gw-pharmaceuticals-epidiolex-cbd-justin-grover/103667/Epidiolex (Cannabidiol) in Treatment Resisntant Epilepsy.

https://www.thecannabist.co/2018/04/18/gw-pharmaceuticals-epidiolex-cbd-justin-grover/103667/

PHARMACOKINETICS - ABSORPTION

Route Absorption Peak Concentration Bioavailability

Inhalation/smoking Rapid drug delivery to the brain

22 min Varies, 2-56%

Oral Slow 1-2hr but can be delayed to 8hr

10-20%

Sublingual Fast 30 min 10-20%

Rectal Fast 15min 20-40%

Transdermal Slow 2hr; maintained for 48hr

10%


PHARMACOKINETICS - DISTRIBUTION

Highly lipophilic which allows it to be easily taken up into the tissues

THC and metabolites are formed with prolonged exposure, allowing for accumulation of these substances in tissues

Half-life varies based on frequency of use

Infrequent users: 1.3 days

Frequent users: 5-13 days

THC has a large volume of distribution (Vd) with slow elimination from the body

Crosses the placenta & accumulates in breast milkOberbarnscheidt, T. J Addict Res Ther. 2016.

PHARMACOKINETICS - METABOLISM

THC is metabolized in the liver by hydroxylation and oxidation by CYP450 enzymes

CYP2C9, 2C19, 3A4

Certain metabolizing enzymes are decreased in cirrhosis

CYP1A and CYP3A are reduced

CYP2C, 2A and 2B are unaltered

Equipotent active metabolite of THC is 11-OH-THC

Possible extra-hepatic sites in the brain, intestine and lung

Oberbarnscheidt, T. J Addict Res Ther. 2016.Elbekai RH, er al. Curr Drug Metab. 2004.

PHARMACOKINETICS - ELIMINATION

Rate of excretion varies based on gender

Women - clearance rate: 11.8 ±3 L/hr

Men - clearance rate: 14.9 ±3.7 L/hr

65% feces; 20% urine


USE PRE-TRANSPLANT

USE PRE-TRANSPLANT

Over 25 states have legalized medical marijuana with another 4 states legalizing recreational use

Marijuana use has been considered a relative contraindication to transplant listing in some centers

Transplant guidelines do not provide a recommendation regarding marijuana use pre-transplant

There are 7 states with current laws that prohibit transplant centers from denying transplant listing based solely on a patient’s use of medical marijuana

Allen LA, et al. Circ Heart Fail. 2016.

CURRENT LAWS

Current legislature includes the following statement regarding marijuana use and transplant listing:

“For the purposes of medical care, including organ transplants, a registered qualifying patient's authorized use of cannabis in accordance with this Act is considered the equivalent of the authorized use of any other medication used at the direction of a physician, and may not constitute the use of an illicit substance or otherwise disqualify a qualifying patient from needed medical care.”

Wash. Rev. Code. § 69.51A.110 (2011). 410 Ill. Comp. Stat. § 130/40(a)(2) (2015).Del. Code. Ann. tit. 16, § 4905A(a)(2) (2015). Ariz. Rev. Stat. § 36–2813(c) (2015). R.I. Gen. Laws § 21-28.6-4(p) (2015). N.H. Rev. Stat. Ann. § 126-X:2VII (2013).Minn. Stat. § 152.32(b) (2014).AB 258 (Act to add Cal. Health & Safety Code Section 7151.36) Feb. 9, 2015

CONCERNS POST-TRANSPLANT

1. Infection risk

2. Bleeding risk

3. Drug interactions

4. Cannabinoid Hyperemesis Syndrome

5. Impaired cognition

6. Cardiovascular effects

7. Abuse/Addiction potential

INFECTION

Aspergillus species found in soil, air and vegetable matter, including tobacco

Marijuana smoking may subject immunocompromised patients to serious & lethal opportunistic fungal infections

Multiple case reports and at least 2 cases at BIDMC of invasive fungal infections related to smoking marijuana

Hamadeh R, et al. CHEST. 1988Marks WH, et al. Transplantation. 1996.

INFECTION

Use of a water pipe has been associated with severe infection

Case report of Pseudomonas aeruginosa necrotizing pneumonia secondary to water pipe usage

Heating of cannabis buds is not sufficient for sterilization

Vaping does not reach high enough temperatures to kill fungal spores

Autoclaves have been used to sterilize marijuana

Temperatures as high as 150ºC/300ºF were utilized

Kumar AN, et al. Respirol Case Rep. 2018.

BLEEDING

Synthetic cannabinoids have been recently linked to serious, unexplained bleeding in numerous states

Over 94 people presented to the hospital with life-threatening coagulopathy secondary to brodifacoum

Brodifacoum is used in a commercial product used for killing rodents and pests

Synthetic cannabinoid product samples tested positive for brodifacoum

Synthetic Cannabis Laced With Poison Linked to Severe Bleeding, CDC Warns. Medscape. 2018.


Exogenous cannabinoids are potent inhibitors of CYP3A and P-gptransporter

CYP2C9, 3A4 and 2C19 inhibitors increase plasma concentration of THC & CBD

Multiple case reports of elevated CNI levels Tacrolimus level of 45.8ng/mL when

previously at goal – patient using marijuana gummies

Cyclosporine level of 500ng/mL following marijuana brownie use

Hauser N, et al. Case Reports in Transplantation. 2016Horn JR, et al. Pharmacy Times. 2014.

CANNABINOID HYPEREMESIS SYNDROME

Cyclical vomiting without other identifiable cause seen in patients with chronic cannabis use

Most commonly seen in patients with prolonged, high-dose cannabis use

Most cases are refractory to usual antiemetic agents with patients reporting relief only from long, hot showers

Concerning post-transplant if patients are unable to take immunosuppression consistently

Hickey JL, Witsil JC, Mycyk MB. Am J Emerg Med. 2013.

IMPAIRED COGNITION

Classified as a hallucinogen

Impairs coordination, perception of time/surroundings, comprehension and cognition

Develop psychotic symptoms including hallucinations, paranoia and delusions

Post-transplant medication regimen consists of 15+ medications

Patient must be able to make frequent dose adjustments, administer medications multiple times per day and ensure timing of administration is accurate


CARDIOVASCULAR EFFECTS

Dose dependent tachycardia and increase cardiac workload

Evidence suggest marijuana users are at a 5-fold increased risk of an acute cardiac event

Increased risk of ischemia due to a reduction in blood flow to the brain

Marijuana use can lead to vasodilation of peripheral blood vessels leading to orthostatic hypotension & syncope


ABUSE/ADDICTION POTENTIAL

High potential for abuse, affecting the same reward system in the brain as alcohol and opioids

Tolerance can develop over time, requiring an increase in the amount of cannabis to produce the same effect

With discontinuation of use or between uses, withdrawal symptoms can occur including anxiety, depression, irritability and insomnia

Withdrawal can occur within 1-3 days, peaks within 2-6 days and can last up to 4-14 days depending on frequency of use


CONCLUSION

Marijuana consists of 60 pharmacologically active cannabinoids and is available as many formulations

Some centers consider marijuana use a relative contraindication to transplant listing

There is a potential for drug interactions with immunosuppression and marijuana may increase the risk for post-transplant complications, including infection

Patients utilizing marijuana should be educated on the risks of marijuana use pre- & post-transplant

QUESTION 1

ST is scheduled for kidney donation in 3 weeks. When reviewing her medications, she reports taking gingko biloba and ginseng supplements daily at home. Which of the following is the correct recommendation in regards to herbal supplement use prior to surgery?

a) She should hold gingko biloba & ginseng 1 week prior to surgery

b) She does not need to hold gingko biloba & ginseng prior to surgery

c) She should hold gingko biloba & ginseng 2 weeks prior to surgery

QUESTION 2

MJ is s/p liver transplant 2 months prior and is maintained on tacrolimus, mycophenolate and prednisone. He is inquiring about turmeric supplements given their anti-infective and anti-oxidant properties and wants to know if they interact with his transplant medications. Which of the following is correct?

a) Turmeric is a CYP3A4 inducer, potential leading to a reduction in immunosuppression levels

b) Turmeric is a CYP3A4 inhibitor, leading to an increase in immunosuppression levels

c) Turmeric does not impact CYP3A4 and is safe to take post-transplant

QUESTION 3

Which of the following risks may be associated with marijuana use post-transplant?

a) Infection

b) Cardiovascular effects

c) Bleeding

d) A&B only

e) All of the above

QUESTIONS?EMAIL : [email protected]

REFERENCES

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16. Lambert JD, Sang S, Yang CS. Possible Controversy over Dietary Polyphenols: Benefits vs Risks. Chem Res Toxicol. 2007 04/01;20(4):583-5.

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http://www.pharmacytimes.com/publications/issue/2014/december2014/drug-interactions-with-marijuana

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Herbal supplement & marijuana use pre- & post …...HERBAL SUPPLEMENT & MARIJUANA USE PRE- & POST-TRANSPLANT Mariesa Cote, PharmD Clinical Pharmacist – Sold i Organ Transpalnt Massachusetts