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Traditional and Herbal Medication Used in the
Treatment of Depression and Anxiety
Presented at DDAP Trainers Day: 6/11/14
Craig Strickland, PhD
https://sites.google.com/site/bioedcon
[email protected]
Learning Objectives for Today
• List herbal treatments for depression
• List at least three of the most common herbal
treatments used to reduce the symptoms of anxiety
and depression
• Summarize the effects of marijuana on the central
nervous system (CNS)
• And if time permits, list the benefits of vagal nerve
stimulation (VNS) for depression
Background Information on herbals:
Natural does not necessarily mean “safe”
• Side-effects and adverse reactions
– Herbal medications are “drugs” although they are
considered supplements by the FDA
– These compounds do, for the most part,
act on the CNS
• Production of allergic reactions
• Interactions with other herbs and
with more traditional medications
Background Information on herbals:
Natural does not necessarily mean “safe”
•Dosing is somewhat more difficult
– % of active ingredients may differ across
manufacturers
– Herbs are not “pure”
– Variety of administration formulas
• Capsules (regular vs. SR vs. XR)
• The dried herb itself
• Liquid extract
• Tincture
• Transdermal application
Background Information on herbals:
Natural does not necessarily mean “safe”
• Because herbals are “supplements”:
– Labeling is not regulated
– Herbal cannot be patented
• Thus, rigorous testing may or may not be
available
• Data may be missing regarding:
– long-term safety
– dose-response curves
– Drug interactions
Some “safe” ways to go re: herbal products
• Commission E: part of the German Regulatory
Authority
• The Herbal PDR
• Nature’s Way & other companies
• Vitacost.com
• Naturopaths & pharmacists
• Peer-reviewed journals
• Cross-referencing of sources
6
Non-Pharmaceutical
Approaches to
Treating Depression:
St. John’s Wort
Saint John’s Wort
8
Herbal Treatment of Depression:
Saint John’s Wort
• Clinical effects: mild anti-depressant
– Mechanism of action: like SSRI
• Inhibits reuptake of 5-HT, NE, DA
• May cause down regulation of 5-HT2
autoreceptors (increases amount of 5-HT release)
9
Herbal Treatment of Depression:
Saint John’s Wort
• Clinical effects/uses:
–Anxiety
–Depression
–Insomnia
–Menopausal mood changes/premenstrual
syndrome
–OCD
–Social anxiety disorder
• Thus like an SSRI
10
Herbal Treatment of Depression:
Saint John’s Wort
• Other Clinical effects/uses:
– Inflammation of the skin
– Blunt injuries, wounds, burns (has
anti-bacterial properties)
– Migraine headaches
• Drug interactions:
– Anti-depressants (especially serotonergic)
– Protease inhibitors
– Contraceptives
11
Herbal Treatment of Depression:
Saint John’s Wort
•Side effects: St. John’s Wort is fairly safe
–Agitation, anxiety, irritability, restlessness
–Dry mouth
–Dizziness; headache
–GI discomfort
–Hypomania
–Fatigue
–Abnormal dreams
12
Herbal Treatment of Depression:
Saint John’s Wort
•Therapeutic dose:
–450 mg (2x/day)
– Take 4-6 weeks (trial period)
•Cost: $ 4.99/90 capsules at 450 mg strength
13
Non-Pharmaceutical
Approaches to
Treating Depression:
Ginkgo Biloba
Herbal Treatment of Depression:
Ginkgo Biloba (Ginkgo)
• Not listed in the “herbal PDR” for use as
an anti-depressant
• Clinical effects: mild anti-depressant
– Mechanism of action is not fully known
– Increase in # of 5-HT receptors
• Via increase in protein synthesis
• Via antioxidant mechanism
(decrease in free radical activity
which damages cell membranes)
15
Herbal Treatment of Depression:
Ginkgo Biloba (Ginkgo)
•Increase in vascular flow (increases nutrients/O2 to
the brain)
• Works well in persons over 50 years old (5-HT
receptors decrease with age)
16
Ginkgo Biloba (cont.)
• Other indications (Commission E)
– Symptomatic relief of organic brain
syndrome/Alzheimer’s disease
– Intermittent claudication
– Vertigo (vascular origin)
– Tinnitus (vascular origin)
• Drug interactions
– Can take with traditional antidepressants (unlike St. John’s Wort)
– Anticoagulants/ASA (bleeding time)
– May interfere with anti-convulsants
17
Ginkgo Biloba (cont.)
•Side effects: generally a safe herb to use
– Increased bleeding time
– Mild GI complaints
– BP problems (maybe related to
reported dizziness/headaches)
– Allergic skin reactions
– Adverse effects on oocytes
18
Non-Pharmaceutical
Approaches to
Treating Depression:
Amino Acid Treatment
Depression: Amino Acid Treatment
• Amino acids used to treat depression include
phenylalanine, tyrosine, tryptophan, and
methionine
– Phenylalanine & tyrosine are precursors to DA
(converts to NE)
– Tryptophan (and 5-hydroxytrytophan) are
precursors to serotonin (5-HT)
20
Depression: Amino Acid Treatment
•Methionine gets converted to s-adenosyl-methionine
(SAM)
– The extract of this is SAMe (“sammy”)
• SAM increases levels of the monoamines
• Improves monoamine binding naturally
– SAM levels-lower in depressed persons
– Side effects include nausea/vomiting
•Dose: 400 to 1600mg/day be reached gradually
•Also used to treat osteoarthritis and fibromyalgia
21
Non-Pharmaceutical
Approaches to
Treating Depression:
Nutritional supplements
Depression: Nutritional Supplements
• Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) : found in fish oils
– Enhances levels of omega-3 fatty acids
– Omega-3 levels have been shown to be reduced
in people with depression
– Amount to take unclear although 3 grams/day
(3000mg) is of EPA/DHA not unusual
– Side effects: high cholesterol and increased
blood sugar (and fish breath…eeewwww!!!)
Depression: Nutritional Supplements
• Other supplements to consider: the “B” vitamins
including folic acid, B6 & B12
• Iron supplements
• Take note:
– Deficiencies in the levels of these supplements can
worsen mood
– Thus, such supplements
• can decrease depressive symptoms
• but will have little effect on depressed people with
normal levels of the B vitamins & iron
Treating Anxiety
The Biochemistry of Anxiety
26
The Biochemistry of Anxiety
•Important neurotransmitters
– Gamma aminobutyric acid (GABA: cortical and
limbic areas (Hippocampus, etc.)
– Norepinephrine (sympathetic nervous system)
– Serotonin
•Neurohormones: e.g. cortisol as the stress hormone
27
Anxiety
•Traditional treatment of anxiety
– Medications acting on the GABA complex
• Alcohol
• Barbiturates & non-barbiturate sedatives
• Benzodiazepines
28
Non-Pharmaceutical
Approaches to
Treating Anxiety:
Kava Kava
Kava Kava
30
Herbal Treatment of Anxiety: Kava Kava
• Clinical effects:
– Muscle relaxant, anticonvulsive, anti-spasmodic
– Hypnotic/sedative, analgesic, and anti-anxiety
– Effects are mediated via GABA system
– Compare these effects with benzodiazepines
• Other clinical effects:
– Antithrombitic, asthmatic, nervous tension, stress
and agitation
31
Herbal Treatment of Anxiety: Kava Kava
• Drug interactions:
– Can potentiate effects of most CNS
depressants
– May potentiate St. John’s Wort,
valerian & traditional anti-depressants
– Antagonizes effects of meds. designed
to increase dopamine (e.g. L-Dopa used to treat
Parkinson’s Disease)
32
Herbal Treatment of Anxiety: Kava Kava (cont.)
• Side Effects: dose dependent (occur primarily with
higher dosages)
– Yellowing of the skin, hair, nails
– AM tiredness (early in tx. phase)
– Minor movement inhibition/impaired motor
reflexes; dyskinesia (involuntary movements)
– Weight loss (only from high doses over an
extended period
– Increased risk of suicide in persons with an
endogenous depression
33
Herbal Treatment of Anxiety: Kava Kava (cont.)
• Side Effects (cont.):
–Liver damage including:
• Hepatitis
• Liver failure
• Cirrhosis
–Some European countries have banned the sale of
Kava ??????????????????????????
–Those at risk for or with known liver disease
should not take Kava
34
Herbal Treatment of Anxiety: Kava Kava (cont.)
•Therapeutic doses:
– Anxiety: 50-70 mg kavalactones 3x/day
– Insomnia: 150-210 mg kavalactones in a single
dose before bed
35
Non-Pharmaceutical
Approaches to
Treating Anxiety:
Valerian
Herbal Treatment of Anxiety: Valerian
• Clinical effects:
– CNS depressant, hypnotic/sedative, anti-anxiety
and muscle relaxant
– Humans: reduces sleep induction time
– Similar to Kava Kava and/or benzodiazepines
– Increase GABA activity by binding to GABA
receptors
– Valerian also contain glutamine (which the brain
converts into GABA)
37
Herbal Treatment of Anxiety: Valerian
•Other effects: anti-spasmodic & anti-ulcerogenic
– Re: the latter reduces stress related hormone
production
– Perhaps through the hypothalamicpituitary-adrenal axis (HPA)
• Drug interactions:
– Can potentiate the effects of the CNS
depressants (like Kava Kava)
– No hard evidence regarding potentiation of
alcohol, however
38
Herbal Treatment of Anxiety: Valerian (cont.)
• Side effects:
– Long term use: headaches, restless states,
sleeplessness, disorders of cardiac function
– Not recommended during pregnancy nor in
nursing mothers
• Therapeutic doses
– Restlessness: 220mg extract 3x/day (dosage for
anxiety would be similar)
– Sleep aid: 300mg to 900mg extract 30-45
minutes before bed
– Cost: $5.89 (180 capsules, 3 capsules HS)
39
Other Herbal Products for Reducing Anxiety
(recommended by Commission E)
•
•
•
•
•
•
•
Bugleweed
Camphor Tree
English Lavender
Hops
Lemon Balm
Lily of the Valley
Passion Flower (taken in
combination with Valerian)
Passion Flower
Treating Anxiety by
Reducing Lactic Acid
41
Anxiety and Lactic Acid
• Normal metabolic processes (involved with producing
energy) are as follows:
1. Glucose  Pyruvic acid + energy
2. Pyruvic acid + 02  H20 + C02
If no 02 is available (which occurs during
strenuous exercise) then:
3. Pyruvic acid  H20 +C02 + lactic acid
• In people who suffer from panic attacks:
– High lactic acid/pyruvic acid ratio
– Lactate (soluble lactic acid) sensitivity
42
Anxiety and Lactic Acid
• Methods of reducing anxiety by reducing lactic acid
levels:
– Reduce caffeine, alcohol and sugar intake
– Increase intake of B-vitamins, niacin,
pyridoxine, thiamin, calcium and magnesium
43
OK, What is this?
44
Marijuana
• A unique sedative-euphoriant-psychedelic drug
• Major psychoactive ingredient: delta-9-tetrahyrdocannabinol (delta-9-THC or just THC)
• Effects include:
– Motor (movement disruption)
– Cognitive
– Psychedelic
– Analgesic
45
Pharmacologic Effects of THC
•
•
•
•
•
•
•
Disruption in attention
Impairment in short-term memory
Altered sensory awareness
Analgesia
Altered control of motor movements
Immunosuppressive actions
Appetite increases (the munchies!)
46
How does THC work?
• THC binds to the cannabinoid receptor
• Two main types of receptors: CB1 and CB2
– CB1
• Found in the brain
– Substantia nigra
– Cerebellum
– Cortex
– Limbic system e.g. hippocampus,
amygdala
– Hypothalamus
– Other
47
Cannabinoid receptors
• CB1 (cont.)
– Substantia nigra:
– Cerebellum:
– Cortex:
– Limbic system:
– Hypothalamus:
movement
coordination
cognitive functioning
memory, emotion
munchies
48
Cannabinoid Receptors
• CB2 receptors
– Found mostly within the immune system
including T-cells
• Accounts for immunosuppressive effects
– Also found in the peripheral nervous system
which is most probably associated with relief
from pain
49
Pharmacological Effects in Humans
• Central Nervous System (CNS)
– Effects vary based on dose, route of
administration, experience of the user,
vulnerability to psychoactive effects and
setting of use
• Senses may be enhanced
• Perception of time is altered
• Increased sense of well-being
• Mild euphoria; relaxation
• Relief from anxiety
50
Pharmacological Effects in Humans
• Why do some experience anxiety?
– Occurs mostly at higher doses (and can also
produce acute depressive reactions)
– 50 to 60 percent of users experienced at least 1
episode of anxiety
• Naïve versus experienced users
• Loss of mental control
• THC concentration and/or impurities
• Personality characteristics &/or genetics
• Social/drug use environmental context
51
Tolerance/Withdrawal
• Tolerance
– Occurs at the level of the brain
– Occur rapidly, dissipates rapidly
• Withdrawal
– Includes restlessness, irritability, mild
agitation, insomnia, sleep disturbances, nausea,
cramping and drug craving
– Withdrawal is considered mild
– Lasts four to six days
52
Dependence
• Animals do not self-administer THC…hmmm…
• And THC does not substitute for drugs with
strong reinforcing properties
– Suggests limited potential for development of
physical dependence
– Limited psychological dependence given weak
reinforcing properties of THC
53
Therapeutic Uses
• Dronabinol: used as appetite stimulant in
people with AIDS
• Treat nausea/vomiting for those undergoing
chemotherapy
• Reduce muscle spasms/pain for those with MS
• Reduce intraocular pressure associated with
glaucoma
54
Vagal Nerve Stimulation (VNS)
The Vagus Nerve
Picture provided by
Peter Jurek, MA, MS
http://www.peterjurek.com
What is vagal nerve stimulation (VNS)?
• Note: this is an FDA approved technique (2005)
for refractory depression; also approved (1997) as
adjunctive therapy for partial-onset epilepsy
• A pulse generator is surgically implanted in the
left chest area under the clavicle
• The leads from the generator are “wrapped”
around the left vagus nerve branch; the right
branch is avoided since it controls some aspects of
cardiac function
• Intermittent pulses are delivered to the nerve
How does VNS work?
• Exact anti-depressant mechanism unknown
– Stimulation does affect blood flow in various
regions of the brain
– As a result, neurotransmitter activity increases,
including 5-HT and NE which would have an
anti-depressant affect
• Side-effects: alteration of voice quality & loudness
(during pulses only), hoarseness, throat pain,
dyspnea (shortness of breath) & paresthesia
Other uses for VNS?
•
•
•
•
Various anxiety disorders
Alzheimer’s disease
Migraines
Fibromyalgia
OK, so all is said and done…or is it?
What questions should you and the
client be asking? What information
do you and your client need
regarding neutraceuticals?
Decision making
• Why am I taking this medication?
• What symptoms do I wish to decrease? Will the
alternative treatment do this? What symptoms can I
live with? Are the symptoms more of an issue for me
or for those around me?
• Am I wanting to try something new because my
medication is not working the way I want it to?
• Have I given my current medication enough time to
work? Would another pharmaceutical be a better
choice?
Decision making (cont.)
• What are my beliefs about herbal medications?
– Do I think they are safer?
– Do I think natural is better?
– Do I want to take an herbal medication because
I do not trust big pharmaceutical companies?
Decision making (cont.)
• Will the herbs interact (either positively or
negatively) with my current medications?
• Will I need to stop/decrease/increase my current
meds if I start taking herbal meds.?
• What about non-prescription substances?
– Over the counter (OTC)?
– Nicotine?
– Caffeine?
Needed Information
• What are the side effects of the herbals? Where
can I get herbal medications? Which companies
are trust worthy?
• What do these herbal products cost? Does my
insurance cover the cost of these substances?
• How much is known about the herbal medication?
Are there any head-to-head studies between herbal
medications and pharmaceuticals?
• Where can I get reliable information?
• How long will the herbs take before they start
working?
Needed Information (cont.)
• Will the herbs interfere with any medical conditions I
have?
– Cardiovascular
– Liver
– Gastrointestinal (GI)
– Endocrine (diabetes, other endocrine disorders)
• Does my doctor/pharmacist have the proper training
to help me? If not, where can I get access to properly
trained individuals?
• Are there non-medicine alternatives?
http://www.nlm.nih.gov/medlineplus/druginformation.ht
ml
Whooo hooo!!!
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