Rhodiola roseaancient medicinal herb for stress,

mild to moderate depression and neuro-protection

Patricia L. Gerbarg, MDAssistant Clinical Professor in Psychiatry

New York Medical Collegeand

Richard P. Brown, MDAssociate Clinical Professor in Psychiatry

Columbia University College of physicians and Surgeons

Presenter Disclosures

• The following personal financial relationships with commercial interests relevant to this presentation existed during the past 12 months:

• No relationships to disclose.

Patricia L. Gerbarg, MDRichard P. Brown, MD

Defining Adaptogens

Adaptogens are herbal preparations used to:• Protect against physical, toxic, chemical, hypoxic, heat,

cold, radiation• Increase attention and endurance under stress• Reduce stress-induced impairments/disorders through

actions on the neuro-endocrine- immune system.

(A Panossian & G Wikman. Curr Clin Pharmacol. 2009. 4(3):198-219; AG Panossian. Psychiatric Clinics of North America. March 2013 36(1):39-64).

Molecular Mechanisms of Adaptogens

• Metabolic Regulators• Rich in antioxidants• Cellular repair: mitochondria, heat shock

proteins, neuropeptide Y, glucocorticoid receptors

• Epigenetic effects

Rhodiola Rosea

Clinical Uses for Rhodiola rosea• Antidepressant solo treatment• Enhance effects of prescription antidepressants• Relieve fatigue in medically ill patients• Improve age-related decline in memory and

cognitive function• Relieve fatigue and cognitive dysfunction caused

by antidepressants and other medications• Increase energy, motivation• Improve mental and physical and endurance

Additional Benefits of Rhodiola rosea• Improve stress tolerance and resiliency for

physical and emotional stress• Prevent/Treat Post-traumatic Stress Disorder• ADHD – helps improve mental focus• Improve cognitive recovery from neuro-lyme

disease• Prevent/relieve: high altitude sickness, jet lag• Used for sexual enhancement• Antibacterial

SHR-5 Rhodiola rosea for Depression• DBRPC 6-wk trial mild-mod depression• A - 340mg/d B – 680mg/d C – placebo

Mean drop in Scores A B C

HAMD 2516 2417 24 23 self-esteem

DBRPC = double-blind randomized placebo-controlledHAMD = Hamilton Depression Scale

(Darbinyan et al. Nordic J of Psychiatry. 2007; 61(5):343-8)

Rhodiola and Intellect

• Increases production of energy (ATP and Creatine) in mitochondria in cells of the brain, muscles, and other organs.

• Enables brain cells to function well for longer periods of time

• Fuels cellular repair mechanisms

(Saratikov AS, Krasnov EA (1987) Rhodiola rosea is a valuable medicinal plant. Tomsk. Russia Pp 91-105.)

R. Rosea Improves Mental Work Capacity Under Stress: randomized controlled studies

Improved: mental fatigue, memory, attention, errors over time, coordination, eye fatigue, well-being, physical work capacity, final exam marksRussian cosmonauts given exhausting mental tasks reading monitors for long hoursCadets at Russian Military AcademyForeign high school students Exam period fatigue/stress in college students

(Baranov VM et al. 1994; Shevtsov et al. Phytomedicine 10:95-105, 2003; Spasov AA et al. 2000, Panossian 2013; Brown, Gerbarg. The Rhodiola Revolution. Rodale. 2004)

What is the # 1 Misconception about Rhodiola rosea?

“Rhodiola acts as an MAOI and should not be combined with antidepressants.”

True False

X

Monoamine Oxidase Inhibitors (MAOIs)• One in vitro study: a solution from a R. rosea extract,

in far greater concentration that would occur with oral doses, had MAOI activity

• R. rosea extracts in therapeutic doses contain such small amounts of MAOIs that they have no clinical significance when taken by mouth

• R. rosea has been combined with all classes of antidepressants (except MAOIs) with no adverse effects.

(van Diermen D, et al. J Ethnopharmacology. 2009 Mar 18;122(2):397-401; A)

Rhodiola in Menopause

• energy and mood• memory• mental focus, “sharpness”• 3 women who had been without menses

for < 12 months resumed regular menstruation

Rhodiola & EstrogenicitySelective Estrogen Receptor Modulator (SERM)

• Tested ovariectomized rats • Strong estrogen receptor binding but not

activation of estrogen receptors• No in circulating estradiol or LH • No change in uterine size• R. rosea d excess estradiol levels from estrogen

implants

(Eagon PK, et al 2003. Evaluation of the medicinal botanical Rhodiola rosea for estrogenicity [Abstract]. In American Association of Cancer Research.)

What is the # 2 Misconception about Rhodiola rosea?

“Rhodiola rosea induces P450 enzymes and can interfere with the metabolism

of certain prescription drugs.”

True False

X

• R. rosea root extract showed in vitro inhibition of CYP3A4 isozyme and P-glycoprotein.

• R. rosea (SHR-5) extract fed to rats (in vivo) showed no significant effect on 2 CYP450 substrates or on warfarin anticoagulant activity.

• Adverse interactions of R. rosea with prescription medications have not been reported in humans.

(Hellum et al., Planta Med.2010. 76(4):331-8; Panossian, et al. Planta Med. 2009.; Kennedy, DA, and D Seely. 2010. Expert Opin Drug Saf; Francis Brinker. 2010. Herbal Contraindications and Drug interactions.)

In Vitro, In Vivo, or In Human?

R. Rosea helps kill cancer cells and protect against side effects of chemotherapy

• Rodents with transplants of human cancers: Lewis lung sarcoma, Pliss lymphosarcoma, Ehrlich’s sarcoma, NKY/LY tumor, and melanoma B16

• Given adriamycin or cyclophosphamide • R. rosea increased chemotherapy effectiveness• Protected liver and bone marrow stem cells from

toxic effects of the chemotherapy

(Brown, Gerbarg, Muskin. How to Use Herbs, Nutrients, and Yoga in Mental Health. NY: WW Norton, 2009)

Breast Cancer and Ovarian Cancer• Human Breast Cancer grafts in mice. Rhodiola

crenulata slowed growth, prevented metastasis, induced death of breast cancer cells but not normal human mammary epithelial cells.

• 28 women stage III-IV ovarian cancer after surgery and 1st Rx cisplatin + cyclophosphamide. 9 pts given AdMax (L.carthemoides, R.rosea, E.senticosus, S.chinesis) had:

CD3,4,5,8 lymphocytes, IgG, IgM fatigue and depression• 2 R. rosea compounds killed prostate cancer cells(Y. Tu et al. J Med food. 2008; Vinalathan et al. Phytotherapy Res

2005; Kormosh et al Phytother Res 2006)

Rhodiola rosea Potential Side Effects• Stimulative effects can be additive

– Caffeine in coffee, sports drinks– Mild anti-platelet at higher doses (above 800 mg/day)

in some people can cause increased bruising• Patients susceptible to stimulative effects

– Anxiety disorder, Bipolar disorder, Elderly– Patients with underlying cardiac arrhythmia

(Panossian AG. Adaptogens in mental and behavioral disorders. Psych Clin NA. 2013:49-64; Gerbarg & Brown. Phytomedicines for prevention and treatment of mental health disorders. Psych Clin NA. 2013:37-47)

R. Rosea Daily Dosages• Healthy people to physical and cognitive function: 50-

400 mg/day• Augment antidepressants: 300-900 mg/day• Elderly, medically ill, anxious: start 25-50 mg, titrate

slowly as tolerated• Response may take 1 week to 2 months• Take most of the dose in the morning on an empty

stomach at least 20 min before a meal for best absorption. A second dose can be taken midday as needed

• Do not take in late afternoon or evening, as it may impair sleep

Quality is Important• R. rosea extracts contain hundreds of

bioactive compounds that can be destroyed or volatilized during extraction.

• The quality of cultivated R. rosea varies depending on climate and soil conditions

• The quality of supplements varies greatly.• It is particularly important to use highest

quality brands to get the full benefits and minimize side effects

Alaska Rhodiola rosea 3-Year-Old Plant

Summary and Future Directions• Educate consumers and doctors regarding

benefits, HDIs, side effects, and quality products• interest and support for human studies:

– firmer evidence base of safety and efficacy– Enable clinicians to extend therapeutic benefits to

patients– new treatments for depression, fatigue, stress,

mental and physical performance, cognitive and memory decline, cancer, space exploration

– Possible selective estrogen receptor modulator (SERM)

“We consider ourselves phytopharmaceuticals!”

BIG PHARMA

Key References -1

• Alexander Panossian. Adaptogens in Mental and Behavioural Disorders. Psych Clin NA. 2013, 36(1): 39-64.

• Brown RP, Gerbarg PL. The Rhodiola Revolution. Rodale press. 2009.

• Gerbarg PL, Brown RP. Phytomedicines for Prevention and Treatment of Mental Health Disorders. Psych Clin NA. 2013, 36(1): 37-47.

• A Panossian & G Wikman. Evidence-based efficacy of adaptogens in fatigue and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol. 2009. 4(3):198-219.

• Francis Brinker 2010. Herbal Contraindications and Drug Interactions plus Herbal Adjuncts with Medicines. 4th ed. Sandy, Oregon: Eclectic Medical Publications.

• Kennedy DA, Seely D. 2010. Clinically based evidence of drug-herb interactions: a systematic review. Expert Opin Drug Saf . 9 (1):79-124.

• Jerome Sarris, Panossian A, Schweitzer I, et al. Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. Eur Neuropsychopharmacol. 2011,21(12):841-60.

• Gurley BJ. Pharmacokinetic herb-drug interactions (Part 1): origins, mechanisms, and the impact of botanical dietary supplements. Planta Med. 2012; 78:1478-89