Transcript Devil`s claw

New Botanical Medicinal
Breakthroughs
for the Management of Pain
Presented by:
Guy Chamberland, MSc, PhD, Master Herbalist
PARKE DAVIS & CO
Objectives of This Workshop – Learn About
• Pharmacological mechanism of action
• Traditional evidence and clinical evidence
supporting the use of herbs in the treatment of
inflammation and pain.
• Dose levels and additive effects.
• Importance of pharmacokinetics on clinical
outcome:
– Duration of response
– Minimal effective dose
– Dose level and dosing interval
Guy Chamberland, M.Sc., Ph.D.,
Master Herbalist
• B.Sc. In Agricultural Chemistry, McGill University.
• M.Sc., Ph.D. in toxicology (Biomedical sciences), University
of Montreal.
• Natural Health Practitioner & Bioenergetics Practitioner
diploma (Oriental medicine), Alternative Medicine College of
Canada.
• Proficiency in Herbal Prescription, Australian College of
Phytotherapy.
• Chartered & Master Herbalist, Dominion College of Canada.
Guy Chamberland, M.Sc., Ph.D.,
Master Herbalist
• Over 16 years developing new drugs in pharmaceutical industry
(Canada & USA).
– Drug safety & Drug development.
• Research in herbal anxiety, sleep, pain/inflammation & wound
treatments.
– Since 2007.
– Preclinical & clinical research: inflammation/pain; wound
healing.
– 2 herb-based patents (pending): inflammation/pain; wound
healing.
– Clinical research treatment anxiety, sleep and
pain/inflammation.
PAIN MEDICATION
Worried about addiction?
Do not tolerate the pain meds?
Pain meds are contraindicated?
Concerned about long-term safety?
Patient wants a natural treatment.
TRUE OR FALSE?
Botanical medicines are as
efficacious as prescription drugs in
the management of inflammation &
pain
Pain Relief: True or False?
Model acute pain – mice :
- Evaluates inflammation – 4 hours after single dose
- Results: HED based on a 154 lb (70 kg) subject
- Aspirin – 68 mg/lb (150 mg/kg) (HED = 398 mg (875 mg))
- Naprosyn – 14 mg/lb (30 mg/kg) (HED = 76 mg (168 mg))
-
-
Phenylbutazone – 14 mg/lb (30 mg/kg) (HED = 76 mg (168 mg))
Celebrex – 4.55 mg/lb (10 mg/kg) (HED = 25 mg (56 mg))
Devil’s claw – 114 mg/lb (250 mg/kg) (HED = 636 mg (1400 mg))
- Boswellia – 114 mg/lb (250 mg/kg) (HED = 636 mg (1400 mg))
36%
23%
18%
Studies that showed equivalence to a drug active control:
Osteoarthritis – knee and hip:
–57 mg harpagoside/day vs 100 mg Diacerhein
LBP:
–60 mg harpagoside/day vs 12.5 mg Vioxx
Rheumatoid arthritis:
60 mg harpagoside/day vs Phenybutazone (300mg/day D1-4; 200mg/day
D5-28)
© Guy-Chamberland-MasterHerbalist
Pain Relief: True or False?
• Based on animal & human data = TRUE!
• Caveats:
• A question of dose level & frequency of
administration.
• Realistic expectations of relief!
• Severity of pain
• Living with pain
• Time required to reduce pain in
chronic conditions
Not surprising since Drugs
activities (pharmacology!!!).
© Guy-Chamberland-MasterHerbalist
mimic
herb
Summary – Botanical Medicines
•
As efficacious as a drug in the treatment of
pain.
•
Disadvantage: bioavailability of some herbs.
•
Advantages: Safety.
•
•
•
•
Good tolerance-safety.
No negative effect on cognition or motor
coordination.
No addiction.
No rebound.
Botanical Medicines
• In many cases, should be used
as a First Line :
• When NSAID contraindicated!
• Night pain.
• Keep in mind delay to onset when treating
acute pain!
Botanical Medicines – Treating
Pain
•
Need to set realistic expectations:
•
•
•
•
Even with drugs, after many years of adjusting
drug therapy, patient may still have pain.
Define short-term pain relief goals for patient.
• 1st target main area of pain to bring some
relief to patient.
• Expand to other areas of body as progress
is made.
Focus on sleep early on.
Use complementary strategies in severe
cases.
Review of the importance
of pharmacokinetics on
clinical outcome.
Review of Key Pharmacokinetic
Concepts
•
•
•
•
•
Effective dose
Absorption & Bioavailability
Duration of response & Dosing Interval
Accumulation
Adverse Effects
© Guy-Chamberland-MasterHerbalist
Evidence behind an
effective Botanical-based
treatment?
Pain
Sleep
(Night Pain)
Choice of herb
√
√
Dose
√
√
Frequency
√
X
Review of Key Pharmacokinetic
Concepts
• Absorption & Bioavailability
– Often limited efficacy of NHP due to poor
absorption/bioavailability.
– Use of pharmaceutical formulation science to
increase absorption of active ingredient.
• Protect ingredient from acid hydrolysis.
– Effect of Food intake.
© Guy-Chamberland-MasterHerbalist
Examples: Turmeric (Curcuma longa)
• Human trials:
– Lack of quantifiable curcumin in the plasma after a dose
of 3,600 mg.
– Oral doses of 30-180mg of curcumin failed to establish
detectable plasma levels.
– Curcumin has poor bioavailability.
© Guy-Chamberland-MasterHerbalist
Absorption of Active Ingredient
Oral absorption: acid hydrolysis (enteric coating)
Plasma concentration
intravenous
Cmax
Tmax
X
Analgesia
No Analgesia
Low bioavailability of curcuminoids.
24 hour period
Oral dosing
© Guy-Chamberland-MasterHerbalist
Absorption & Bioavailability
Turmeric (Curcuma longa)
• Bioavailability:
– Formulations developed to increase bioavailability:
– BCM-95® (Biocurcumax™) curcumin vs. plain curcumin
was determined in humans:
• The peak was:
– 1600ng/g BCM-95® group & >200ng/g plain
curcumin group.
© Guy-Chamberland-MasterHerbalist
Pharmacokinetics: Dosing Interval
Efficacy Dependent on Plasma Concentration
Plasma concentration
Cmax
Tmax
Duration of response: 4-6 hours
T1/2 = 5.6 hrs
Plasma half-life
Analgesia
Tmax = 1.3-2.5 hrs
Cmin
No Analgesia
24 hour period
Oral dosing
© Guy-Chamberland-MasterHerbalist
Dosing Frequency/Interval Dependent on
Plasma Half-life
Plasma concentration
Cmax
Analgesia
Cmin
No Analgesia
Optimize dosing interval to avoid periods of no efficacy
24 hour period
Oral dosing
© Guy-Chamberland-MasterHerbalist
Accumulation & Side Effects
Plasma concentration
Half-life ranges from 24-36 hours for hypericin
Cmax
Intolerable AE
Efficacy
Cmin
No efficacy
24 hour period
Oral dosing
© Guy-Chamberland-MasterHerbalist
Minimal Effective Dose
20mg Harpagosides per dose (Devil’s claw)
2 g California poppy
4 g Scullcap
↑Pain
Maximal effective dose
Minimal effective dose
↑ Plasma Concentration of active ingredient(s)
© Guy-Chamberland-MasterHerbalist
Are there herbs that allow us
to develop a botanical
medicine that is similar in
potency to a prescription
drug?
Herbs – Anti-Inflammatory - Analgesic
• Many clinical trials.
• Main problems:
• Bioavailability & standardization.
• Not a drug development concept.
• Dose & frequency is critical for efficacy.
• Herbs used according to their pharmacology:
• mu1, COX-2, serotonine.
• Activity = ‘atypical’
• eg., mu1 + 5-HT1 / 5-HT7
Herbs – Anti-inflammatory or Analgesic
Boswellia (Boswellia sacra)
Salix (Salix alba)
Devil’s claw (Harpagophytum procumbens)
California poppy (Eschscholzia californica)
Boswellia (Boswellia serrata)
Salix (Salix alba)
NSAID
Atypical opioid
Use cautiously in patients taking drugs
metabolized by liver cytochrome P450
enzymes.
Interaction with anticoagulants (heparin,
coumarin derivatives) is of therapeutic
importance.
Devil’s claw (Harpagophytum procumbens)
California poppy (Eschscholzia californica)

Analgesic & Hypnotic
Agent
Should your practice consider sleep quality
• Pain interferes with sleep.
– 50% - 88% patients treated for chronic pain
(nonmalignant) reported sleep impairment.
– Patients with high pain intensity had less sleep time,
more delayed sleep onset, and more nighttime
wakening than patients with low pain intensity.
• Disturbed sleep lowers pain threshold.
• Whether sleep disturbance precedes or follows
pain onset is unclear.
Should your practice consider sleep quality
• Chronic pain:
– Pain initiates and exacerbates sleep disturbance.
– Disturbed sleep maintains and exacerbates chronic
pain and related dysfunction.
• Sleep disruption, fragmentation, or restriction
produces hyperalgesia (increased sensitivity to
pain) and can interfere with analgesic
treatments
involving
opiodergic
and
serotonergic mechanisms of action.
Vicious cycle!
Poor sleep
Sleep disruption
Increases pain
sensitivity
Increased pain
Association of Sleep & Pain versus NSAID
• Treatment with NSAID
– OA show significantly greater objective sleep disturbance.
• NSAID:
– Inhibition of prostaglandin synthesis during nighttime
hours induces change in sleep patterns due to a decrease
in synthesis of prostaglandin D2.
– Suppression of normal nocturnal surge in melatonin
synthesis.
• Suppression by 75% within 75 minutes after single dose
of NSAID.
• Melatonin surge important to induce sleep.
– Aspirin and Ibuprofen (significant versus placebo);
acetaminophen not significant.
Should your practice consider sleep quality
• REM sleep deprivation results in hyperalgesia
during the subsequent awake period.
• Nonrestorative sleep occurs in 73% to 76% of
fibromyalgia patients.
• Presence of restorative sleep in patients with
fibromyalgia predicted resolution of pain at 15
months.
Recommended & Current Uses
California poppy
• Night Pain:
–
–
–
–
1 or 2 capsules at night.
Analgesic & Hypnotic.
Better sleep quality.
Reduced doses of morphine at night.
• Co-analgesic (Adjuvant):
– 1 capsule bid (off-label use by physicians).
– Patients intolerant to meds such as Lyrica and/or Cymbalta.
• Reduce doses of other pain meds.
• Insomnia:
– 1 or 2 capsules 30 minutes before bedtime.
– Sedative & Hypnotic.
*1 capsule = 500-600 mg extract (standardized)
California poppy (Eschscholzia
californica)
Historical Use:
• Relaxing nervine in anxiety and nervousness
• Sedative in insomnia
• Anodyne in pain.
• A more recent usage is in the treatment of heroin addiction
and withdrawal.
Although remedies such as Opium Poppy are of great use as an
anodyne and analgesic, Felter and Lloyd considered
Eschscholzia to be an “…analgesic and soporific without the
dangers attending opiates, quieting pain and producing (a) calm
sleep” (1893).
Opioid Receptors
X
X
Morphine
X
X
X
X
X
X
California
poppy
Analgesia with
Sedation
Pharmacology - 5:1 extract of
California poppy - mice
• Sedative activity at 90.9 mg/lb (200 mg/kg) in mice
– 200 mg/kg X 5:1 extract ratio = 1000 mg dried herb per
kg.
– Conversion to Human Equivalent Dose:
• 1000 mg/kg / 12.3 = 37 mg/lb (81.3 mg/kg).
• For a 154 lb (70 kg) subject =
• 5.7 grams of dried herb (1200 mg extract (5:1)).
– partly antagonized by flumazenil.
• Equivalent to 2 capsules of a 500 mg
standardized extract.
© Guy-Chamberland-MasterHerbalist
Pharmacology - 5:1 extract of
California poppy - mice
• Sedative activity at 90.9 mg/lb (200 mg/kg) in mice
– 200 mg/kg X 5:1 extract ratio = 1000 mg dried herb per kg.
– Conversion to Human Equivalent Dose: 1000 mg/kg / 12.3 = 37 mg/lb (81.3 mg/kg).
– For a 154 lb (70 kg) subject:
• 5.7 grams of dried herb (1140 mg extract (5:1)).
• Anxiolytic effect demonstrated at 11.4 mg/lb (25 mg/kg) (125 mg
dried herb per kg).
– For a 154 lb (70 kg) subject:
• 0.7 grams of dried herb (142 mg extract (5:1)).
• Use of a 500 mg 5:1 standardized PE:
– 1 capsule too strong to be used as a calmative!
• 8-fold stronger than dose tested.
© Guy-Chamberland-MasterHerbalist
Pharmacology - 5:1 extract of
California poppy - mice
• Antidepressant: No effect against reserpine*-induced ptosis,
akinesia or hypothermia, when it was tested at 22.7, 45.5, 90.9,
181.8 and 363.6 mg/lb (50, 100, 200, 400, 800 mg/kg).
– For a 154 lb – 90.9 mg/lb (70 kg subject - 200 mg/kg):
• 5.7 grams of dried herb (1140 mg extract (5:1)).
– For a 154 lb – 363.6 mg/lb subject (70 kg - 800 mg/kg):
• 22.8 grams of dried herb (4553 mg extract (5:1)).
NO ANTIDEPRESSANT-LIKE EFFECT.
Explains in part the good tolerability in patients versus
meds!
*Reserpine irreversibly blocks the vesicular monoamine transporter. This normally transports
free intracellular norepinephrine, serotonin, and dopamine in the presynaptic nerve terminal
into presynaptic vesicles for subsequent release into the synaptic cleft.
© Guy-Chamberland-MasterHerbalist
Pharmacology - 5:1 extract of
California poppy - mice
Analgesic effect:
• 90.9, 181.8 and 363.6 mg
extract/lb (200 – 800 mg
extract/kg)
• For a 154 lb (70 kg) human
subject:
– 5.7* – 22.8 g
– 1140 – 4553 mg extract
(5:1 PE standardized).
*A safe dose level
(equivalent: 2 capsules 500
mg PE 5:1).
© Guy-Chamberland-MasterHerbalist
Peripheral pain
relief
Pharmacology - 5:1 extract of
California poppy - mice
Dose-dependent peripheral analgesic effects were
demonstrated from a dose of 90.9 mg/lb (200 mg/kg) in
the writhing test:
- Mild CNS effect with peripheral effect.
Both peripheral &
central pain relief
© Guy-Chamberland-MasterHerbalist
California poppy (Eschscholzia californica)
• Pharmacological properties demonstrated:
– Dose-response effect observed for analgesia.
– Opioid & 5-HT1A & 5-HT7 serotonin activity.
– Dose-dependent sedative & anxiolytic properties.
– No antihistaminic effects.
– No anticonvulsant or myorelaxant effects.
– No anticholinergic effects.
– No muscle relaxant and antipsychotic properties.
– No antidepressant-like properties.
California poppy (Eschscholzia
californica)
• Pharmacologic Class:
– Opioid & 5-HT1A + 5-HT7
– Analgesic + Hypnotic/sedative
• Key clinical advantage:
– Safety profile:
• No addiction/physical dependence
• High tolerability versus conventional narcotics.
• 3 key alkaloids:
– At least 0.8% Isoquinoline alkaloids:
• Californidine
• Escholtzine
• Protopine
Study
Pilot study; 7-day acute Pilot study; 28-day chronic
pain
pain
Proof-of-concept; multicentre;
open-label
Subjects:
• 10 patients
•
• Patients with acute pain •
(VAS > 4)
• No drug therapy
•
10 patients
•
Patients with chronic pain •
(VAS > 4)
No drug therapy
•
20 patients
Uncontrolled, moderate-severe,
chronic pain
Fibromyalgia with/without
myofascial syndrome
• Arthritis
• NSLBP
• Neuropathic pain
Herbs:
• California poppy (1 at
night)
• Devil’s claw (tid)
• Scullcap (tid)
•
•
•
•
California poppy (1 at night)
Devil’s claw (tid)
Scullcap (tid)
Gel
Results:
•
•
•
•
•
Improved sleep
Significantly reduced pain
Significant  mobility &
flexibility
 swelling
 tenderness
 stiffness
•
•
Reference:
Improved sleep
Significantly reduced
pain
 swelling
 tenderness
Chamberland G. unpublished
•
•
•
Chamberland G. unpublished
© Guy-Chamberland-MasterHerbalist
•
•
•
•
California poppy (1 or 2 daily)
Concomitant pain meds.
Short form McGill Pain Scale
Sleep questionnaire
• Approximately 50% patient
obtained a significant clinical
benefit in pain relief or sleep.
• Delta-VAS: 2.4 (VAS <1.0 =
failure)
• Improved sleep (night pain):
67%
• Improved sleep (all): 45%
• Significant improvement pain:
55%
Chamberland G. unpublished
Summary – California poppy
•
Induces sleep & analgesia at correct dosage.
•
Clinical evidence effective treatment night pain.
•
•
•
•
No impact on cognition.
No impact on motor incoordination.
No addiction.
No rebound.
Recommended & Current Uses
California poppy (Eschscholzia californica)
• Night Pain:
–
–
–
–
1 or 2 capsules at night.
Analgesic & Hypnotic.
Better sleep quality.
Reduced doses of morphine at night.
• Co-analgesic (Adjuvant):
– 1 capsule bid (off-label use by physicians).
– Patients intolerant to meds such as Lyrica and/or Cymbalta.
• Reduce doses of other pain meds.
• Insomnia:
– 1 or 2 capsules 30 minutes before bedtime.
– Sedative & Hypnotic.
*1 capsule = 500-600 mg extract (standardized)
Natural NSAID
NSAID vs Botanical Drug
• NSAIDs used for:
– OA of knee, hip, and spine & NSLBP
associated with pain, stiffness, limitation of
function, and diminished quality of life.
– Superior to acetaminophen in majority of
trials!
NSAID vs BOTANICAL DRUG
• Treatment guidelines recommend simple
analgesics as first-line drugs.
– Because of superior efficacy, NSAIDs are
preferred despite the lower safety-margin and
the higher cost.
A critical part of an effective
pain management strategy.
NSAID vs BOTANICAL DRUG
• Consider alternatives to NSAID therapy:
–
–
–
–
High incidence of NSAID related adverse events.
GIT complications
Risks associated with cardiovascular systems
Especially in the elderly
High costs related to adverse events:
– gastrointestinal bleeding or perforation.
– additional medical attendances, diagnostic procedures,
treatments and admissions to hospital.
We need a natural
NSAID!
Which herb is an
effective & safe
choice?
Selection of an NSAID
• Herbs with Clinical Evidence for
Osteoarthritis, Rheumatoid Arthritis, Low
Back Pain (LBP):
• Boswellia
• Willow bark
• Devil’s claw
• LBP:
• Devil’s claw
–Equivalence trial vs 12.5 mg rofecoxib
• Willow bark
–Equivalence trial vs 12.5mg rofecoxib
Willow Bark
X
• Drug interactions:
• Assessment of EMA limited to documented interactions. Not
theoretical.
• EMA concluded: Interaction with oral anticoagulants
(heparin, coumarine derivatives) is plausible and of
therapeutic importance.
• Clinical trials demonstrated:
• Willow bark significantly  AA- and ADP-induced
aggregation but to a significantly lesser extent than
acetylsalicylate did.
• Statistically significant associations between the use of
willow bark and bleeding events were identified......
• EMA recommends: The combined use of Willow bark with
acetylsalicylic acid/other NSAIDS is not recommended.
Boswellia
vs
• Pharmacokinetics:
• Poor bioavailability of
boswellic acids.
• Food alters the pharmacokinetic profile.
• Meals high in fat
increased the
concentration in plasma.
• Mean elimination half-life:
5.97 hours.
• Time to Peak (Tmax): 4.5
± 0.55 hours.
Devil’s claw
• Pharmacokinetics:
• Degradation of harpagosides
in stomach.
• Food alters absorption.
• Mean elimination half-life:
5.6 hours.
• Time to Peak (Tmax): 1.3 to
2.5 hours.
Boswellia
vs
• Pharmacokinetics:
• Moderate-to-potent inhibitors of
CYP enzymes, with equal
potency for inhibiting the major
drug metabolizing enzymes 1A2,
2C8, 2C9, 2C19, 2D6, and 3A4.
• Use cautiously in patients
taking agents metabolized by
the liver's cytochrome P450
enzymes.
X
Devil’s claw
• Pharmacokinetics:
•
No
cytochrome
P450
induction or inhibition.
•
No caution statements.
Devil’s Claw
Devil’s claw known safety profile
• Anticoagulants and antiplatelets:
• One case of purpura reported in a patient taking warfarin
(Coumadin®) with devil's claw.
• Evidence is inconclusive. Could be simply due to drug.
• European Medical Agency (EMA) approved Devil’s claw as a
medicinal herb.
• Detailed assessment of the safety information to issue
warnings.
• EMA concluded: could not find any study or reported
cases suggesting an interaction with oral anticoagulants,
or sulfonylureas.
• EMA stated: no signal, even weak, has emerged from the
literature to date.
• Conclusion: Even if evidence is weak, be cautious when using
Devil’s claw on a patient taking an AC or AP.
Devil’s claw (Harpagophytum
procumbens)
• South African plant recognized for its anti-inflammatory
properties.
• Active part of the plant is the dried secondary roots.
• An anti-inflammatory, antirheumatic and analgesic remedy.
* Doses considered safe by regulatory agencies around the world.
© Guy-Chamberland-MasterHerbalist
Pharmacology - extract of
Devil’s claw - mice
• Analgesic activity in mice
– Conversion to Human Equivalent Dose: mg/kg / 12.3.
– Corrected for a 154 lb (70 kg) subject.
Writhing test – i.p. Swiss mice
Harpagoside-HDE
154 lb or 70 kg
5 mg
10 mg
47%
20 mg
40 mg
78%
325 mg
59%
6 mg
% protection
Dose
dependent
Devil’s Claw
dose
22.7 mg/lb (50 mg/kg)
45.5 mg/lb (100 mg/kg)
90.9 mg/lb (200 mg/kg)
181.8 mg/lb (400 mg/kg)
30.9 mg/lb (68 mg/kg) ASA
0.52 mg/lb (1.15 mg/kg) morphine
Peripheral pain
relief
Lanhers M.C., Fleurentin J., Mortier F., Vinche A., Younos C. Anti-inflammatory and analgesic effects of an aqueous extract of
Harpagophytum procumbens. Planta Med 1992, 58: 117-123.
Central Effect for Pain Relief
No central pain
• Heat induced pain
relief
• Male Swiss mice
• Intraperitoneally injected:
– extract (90.9 and 181.8 mg/lb; 200 and 400 mg/kg) or
harpagoside 4.5 mg/lb (10 mg/kg).
– Acetylsalicylic acid 30.9 mg/lb (68 mg/kg) and
morphine sulphate 2.1 mg/lb (4.6 mg/kg)
Results:
- No protection: Devil’s claw, harpagoside and
acetylsalicylic acid.
- Protection: Morphine
Pain Relief: True or False?
Model acute pain – mice :
- Evaluates inflammation – 4 hours after single dose
- Results: HED expressed for 154 lb (70 kg) subject
- Aspirin – 68 mg/lb (150 mg/kg) (HED = 398 mg (875 mg))
- Naprosyn – 14 mg/lb (30 mg/kg) (HED = 76 mg (168 mg))
36%
- Phenylbutazone – 14 mg/lb (30 mg/kg) (HED = 76 mg (168 mg))
- Celebrex – 4.55 mg/lb (10 mg/kg) (HED = 25 mg (56 mg))
- Devil’s claw - 114 mg/lb (250 mg/kg) (HED = 636 mg (1400 mg))
23%
- Boswellia – 114 mg/lb (250 mg/kg) (HED = 636 mg (1400 mg))
18%
© Guy-Chamberland-MasterHerbalist
More than 23 clinical trials in patient populations of:
osteoarthritis, rheumatoid arthritis, low back pain.
– ‘Double-blind’- RCT with placebo: 13 studies.
– Studies that showed equivalence to an active control:
– Osteoarthritis – knee and hip:
– 57 mg harpagoside/day vs 100 mg Diacerhein
– LBP:
– 60 mg harpagoside/day vs 12.5 mg Vioxx
– Rheumatoid arthritis:
• 60 mg harpagoside/day vs Phenybutazone (300mg/day D1-4;
200mg/day D5-28)
• Data shows need 50-100 mg per day.
• Ideal is 20 mg tid.
• Consistent with animal data – 20 mg effective
after single dose.
*Gibofsky A et al. Comparing the efficacy of cyclooxygenase 2-specific inhibitors in treating osteoarthritis. Arthritis & Rheumatism 2003; 48(11):3102-3111.
*Laudahn D et Walper A. Efficacy and tolerance of Harpagophytum extract LI 174 in patients with chronic non-radicular back pain. Phytother. Res. 2001; 15:621-624.
Devil’s claw (Harpagophytum
procumbens)
Pharmacological uses of Devil's claw: An anti-inflammatory,
antirheumatic and analgesic remedy.
Bioenergetic uses of Devil's claw are:
Cools the exterior and dispels wind-damp-heat.
(Critical treatment for many acute and chronic painful conditions:
arthritis, musculoskeletal pain, and myalgia; especially of the winddamp-heat type.)
Prescribe for wind-damp-heat obstruction:
- muscle and joint aches and pains, swollen red joints, stiffness.
- rheumatoid, osteoarthritis, fibromyalgia, gout, low back pain,
neuralgias.
© Guy-Chamberland-MasterHerbalist
Study Design:
Double-blind, Randomized
Double-blind, Randomized, Multicentre
Multicentre, Postmarketing Surveillance
Subjects:
• 88 patients with acutely
exacerbated low back pain;
• Rx 6 weeks. DC versus 12.5
mg/day Vioxx
• 122 patients suffering from
osteoarthritis of the knee and hip.
• DC versus diacerhein 100 mg/day; 4
months treatment
• 75 patients with osteoarthritis of the hip
or knee.
• 12 weeks
Devil’s claw
(DC):
• 800 mg extract (20 mg
harpagoside) tid
• 870 mg extract (19 mg harpagoside)
tid
Method:
• 400 mg/day Tramadol rescue
allowed.
• Arhus LBP Index & Health
Assessment Questionnaire.
• Pain & functional disability on VAS;
• Severity of osteoarthritis using
Lequesne's index (LI).
• WOMAC index
• VAS pain scale
Results:
•
• Spontaneous pain: significant
improvement during study; no
difference in the efficacy.
• A progressive & significant reduction
in LI & no statistical difference was
found between treatments.
• At end of study: DC were using
significantly less NSAIDs and antalgic
drugs.
• Frequency of AE events was
significantly lower in DC.
• Improvement in WOMAC subscale : 23.8%
pain, 22.2% stiffness , 23.1% physical
function.
• WOMAC total score  22.9%.
• VAS:  25.8% actual pain, 25.2% average
pain, 22.6% worst pain , 24.5% total pain
score.
• Physicians reported a continuous
improvement in typical clinical findings
such as 45.5% for pain on palpation, 35%
for limitation of mobility and 25.4% for
joint crepitus.
Chantre P et al. Phytomedicine. 2000
Jun;7(3):177-83
Wegner et Lupke. Phytother Res. 2003
Dec;17(10):1165-72.
•
•
Reference:
Number of pain-free patients:
DC 22%,Rofecoxib 11% NS;
Percentage change Arhus
component pain: DC
30%, Rofecoxib 29%
(intention-to-treat analysis)
Chrubasik S et al.. Rheumatology
2003;42:141-148
Study Design:
8-week
4-weeks, Equivalence study
4-week, Randomized, Double-blind,
Placebo controlled
Subjects:
• 675 patients with painful
osteoarthritis,
spondylarthropathies or
fibromyalgic complaints
• bid
•
•
•
•
• 118 patients acute low back pain (nonspecific; pain for at least 6mnths).
• 2 tablets Tid
Devil’s claw
(DC):
• 480 mg extract
• 4500 and 9000 mg/day, (50 and 100
mg harpagoside per day)
• 4500 mg/day, (50 mg harpagoside per day)
Method:
• CGI score
• Reduction in symptom severity
score
• Use of NSAIDs or corticosteroids
• Pain-free without NSAIDs for 5 days at
end of study.
• Arhus low back pain index.
• Use of rescue meds (Tramadol).
• Need to use supplementary analgesic
(Tramadol) during final 3 weeks.
• Number of patients pain-free at end.
• Arhus low back pain index.
Results:
• CGI scores rated good or very
good in 82% of cases.
• Symptom score for painful
motion decreased by 53% from
2.23 (indicating moderate pain)
to 1.04 (indicating slight pain)
after eight weeks.
• Co-medication doses were
reduced or discontinued in 60%
of the 464 patients taking
NSAIDs and 56% of the 50
patients taking corticosteroids.
• Pain-free patients : 9% DC1; 15%
DC2; 5% PL (p=0.027).
• Overall median Arhus index scores: 
55% at baseline to 20% by week 4,
but no statistically significant
difference between both treatment
groups & PL.
• Greater effectiveness of DC2 seen
only in subgroups with more severe
pain radiating to the leg, the smaller
dose did not seem to have much
effect on them.
• Non-radiating pain, DC2 was more
effective.
• DC group tended to use fewer analgesics
(p=0.44).
• A non-significant improvement in median
Arhus low back pain index scores was seen
(20% vs. 8%; p<0.059).
• Significantly more pain-free patients at the
end of the trial (9/51 vs. 1/54; p=0.008).
• Percentage change Arhus component pain:
DC 34%, PL 6% (p=0.016)
Reference:
Ribbat NaturaMed 2001;16:23-30
Chrubasik et al. Eur.J Anaesthesiol.
1999;16(2):118-129.
Chrubasik et al. Phytomedicine 1996;3(1):1-10.
197 patients, tid
65 received 200 mg tablets
66 received 400 mg tablets
66 placebo
Study Design:
• 20-week, Randomized, Placebo
controlled trial
• 4-month, Randomized, Double-blind,
Parallel-group study
• 8-weeks, Multicentre, Postmarketing study
Subjects:
• 46 patients with osteoarthritis of
the hip
• Rx DC vs PL (placebo); bid
• 122 patients with hip and knee
osteoarthritis
• Rx DC vs 100 mg Diacerhein
• 104 patients with low back pain, 85 patients
with arthritic knee pain, and 61 patients with
arthritic hip pain
Devil’s claw (DC):
• 4500 mg/day, (< 30 mg
harpagoside per day
• DC 2610 mg (57mg of
harpagoside)/day
• 800 mg extract (20 mg harpagoside) tid
Method:
• Efficacy using WOMAC.
• Stepwise-reduced daily doses of
ibuprofen: 800mg daily for the
first eight weeks, 400mg daily for
a further eight weeks, and none
during the
• Spontaneous pain using VAS
• Lequesne Index, functional disability
of movement assessed on a VAS,
amount of taken rescue medication
(acetaminophen-caffeine with or
without diclofenac).
•
•
•
•
Results:
• WOMAC scores  both groups
despite the reduced dose of
ibuprofen.
• Stiffness, pain & dysfunction
both groups.
• Ibuprofen-free period, 20% or
less in the pain score considered
clinically relevant response rate:
71% DC vs 41% PL met criteria
(p=0.04).
• 52% DC vs 36% PL completed
without using rescue during
Ibuprofen-free period..
• 65.3% DC & 60% Diacerhein had
considerable improvements in OA
symptoms both groups.
• No significant differences for pain,
functional disability, or Lequesne
score.
• DC found to be using statistically
significantly less analgesic
medications (p=0.01).
• Adverse effects (mainly diarrhea) that
were considered to be due to
treatment were reported in 8.1% and
26.7% of Harpadol®and Diacerhein
patients, respectively (p=0.017).
• Improvement tended to be more when the
initial pain and disability score was more: older
patients tended to improve less than younger,
the hip group tended to improve convincingly
more than the back group, whereas the
improvement in the knee group was less
readily differentiated from that in the back
group. The subgroup of patients with back
pain who required NSAIDs during the eight
weeks used significantly more per patient than
patients in the other two groups, but that
requirement also declined more with time.
About 10% of the patients suffered from
minor adverse events that could possibly have
been attributable to Doloteffin. Between 50%
and 70% of the patients benefitted from
Doloteffin with few adverse effects (primarily
gastrointestinal).
Reference:
Frerick et al. Stufenschema bei
Coxarthrose. Der Kassenarzt
2001;5(34):41.
Chantre et al. Phytomedicine
2000;7(3):177-183
Chrubasik et al. Phytomedicine 2002;9(3):181194.
Arhus low back pain index.
WOMAC index.
HAQ
Unvalidated measures (total pain index, three
score index, the patient's global assessment of
the effectiveness of treatment.
Devil’s claw (Harpagophytum
procumbens)
• According to UpToDate
(www.uptodate.com):
– "Devil's claw reportedly improves joint mobility
and reduces pain and swelling in arthritis."
– "It may be more effective for osteoarthritis as
compared to rheumatoid arthritis."
– "It may be more effective for chronic, rather than
acute, arthritis symptoms."
*UpToDate® is an evidence-based clinical decision support system authored by physicians
Devil’s claw (Harpagophytum
procumbens)
• "There is a growing body of scientific evidence
suggesting that devil's claw is safe and beneficial
in the short-term management of pain related to
degenerative joint disease or osteoarthritis. It may
be equally effective as drug therapies, such as
non-steroidal anti inflammatory drugs (or may
allow for dose reductions or cessation of these
drugs in some patients).“ – Natural Standard
database*
*Natural Standard is impartial; not supported by any interest group, professional organization or product
manufacturer.
Devil’s claw (Harpagophytum
procumbens)
• Enteric coating required:
– Studies demonstrated loss of anti-inflammatory
effects by oral administration
– Dose-dependent effects observed with
intraperitoneal and intraduodenal administration
– Enteric coating - protection of efficacy
demonstrated
Importance of enteric coated formulations…
Devil’s claw (Harpagophytum
procumbens)
• The iridoid glycoside, harpagoside, linked to its antiinflammatory and analgesic benefits.
• PD & PK - 3 studies in human volunteers*:
– Relation between serum harpagoside levels and the
inhibition of leukotriene biosynthesis.
– Maximum levels of plasma harpagoside reached after
1.3 to 2.5 hours.
– Harpagoside elimination half-life has been reported as
5.6 hours.
*Clin Pharmacol Ther. 2001 May;69(5):356-64.
Devil’s claw (Harpagophytum
procumbens)
Inhibition of Cyclo Oxygenase 2
Assists the extracellular matrix
construction (synthesis of GAGs)
Synthesis of hyaluronic acid
(human chondrocytes)
Iridoids (harpagosides) interact with Arachidonic Acid metabolism pathways:
• Action on eicosanoids synthesis
• Action on cyclo-oxygenase, lipoxygenase and NO synthetase
• Action on TNFa liberation
• Action on Cys-LT synthetis
• Action on enzymes responsible for collagen degradation
Explanation for absence of renal & cardiovascular toxicity: Potent cytokine
release inhibitor & weak inhibitor of COX-2 mediated prostaglandin E2
biosynthesis.
Systematic Review - Conclusions
• No efficacy when less than <30 mg harpagoside per
day in the treatment of knee and hip osteoarthritis.
• Moderate evidence when 60 mg harpagoside per day
in the treatment of osteoarthritis of the spine, hip
and knee.
• Moderate evidence (57 mg harpagoside per day) for
non-inferiority to diacerhein (inhibitor of IL-1) in
treatment of acute exacerbations of osteoarthritis in
the hip and knee.
Important to give 50 -100 mg
harpagosides per day.
Joel J Gagnier et al. Harpgophytum procumbens for osteoarthritis and low back pain: A systematic review. BMC Complementary and
Alternative Medicine 2004, 4:13.
Systematic Review - Conclusions
• Moderate evidence for a daily dose of 100 mg harpagoside
in the treatment of acute exacerbations of chronic nonspecific low back pain.
– subgroup with neurological deficits (e.g. radiation into
the leg) responded well.
• 60 mg harpagoside being non-inferior to 12.5 mg rofecoxib
(VIOXX) per day for chronic non-specific low back pain
(NSLBP) in the short term.
• Strong evidence for 50 mg harpagoside in the treatment of
acute exacerbations of chronic NSLBP.
Important to give 50 -100 mg
harpagosides per day.
Joel J Gagnier et al. Harpgophytum procumbens for osteoarthritis and low back pain: A systematic review. BMC Complementary and
Alternative Medicine 2004, 4:13.
Laudahn D and Walper A. Efficacy and Tolerance of Harpagophytum Extract LI 174 in Patients with Chronic Non-radicular Back
Pain. Phytother. Res. 15, 621–624 (2001)
Laudahn D and Walper A. Efficacy and Tolerance of Harpagophytum Extract LI 174 in Patients with Chronic Non-radicular Back
Pain. Phytother. Res. 15, 621–624 (2001)
Using Schober’s sign, a significant improvement in
the evaluation of mobility of the spinal column.
Laudahn D and Walper A. Efficacy and Tolerance of Harpagophytum Extract LI 174 in Patients with Chronic Non-radicular Back
Pain. Phytother. Res. 15, 621–624 (2001)
The mobility of the spinal column increased significantly during
treatment.
There was a significant reduction (p 0.001) in the average finger–floor
distance (FFD) from 15.1 cm initially to 10.2 cm at the end of treatment (Fig.
4).
Laudahn D and Walper A. Efficacy and Tolerance of Harpagophytum Extract LI 174 in Patients with Chronic Non-radicular Back
Pain. Phytother. Res. 15, 621–624 (2001)
Study - Conclusions
• The drug was slow in taking effect (about 14 days).
– "Does not seem to have immediate analgesic potency.
More a question of a myotonolytic effect which may be
combined with an antiinflammatory effect as a result of
an increased blood supply to the affected regions".
• Patient should be told about the slow onset of
action so that treatment is not stopped prematurely.
A question of dose. Consider a
loading dose!
Laudahn D and Walper A. Efficacy and Tolerance of Harpagophytum Extract LI 174 in Patients with Chronic Non-radicular Back
Pain. Phytother. Res. 15, 621–624 (2001)
Study - Conclusions
• Treatment costs:
– no need for gastric protection treatment or
secondary treatment for gastrointestinal
ulcers.
• Can be used in patients with known sensitivity
to NSAIDs
– high-dose Harpagophytum extract.
Laudahn D and Walper A. Efficacy and Tolerance of Harpagophytum Extract LI 174 in Patients with Chronic Non-radicular Back
Pain. Phytother. Res. 15, 621–624 (2001)
Recommended & Current Uses
Devil’s claw (Harpagophytum procumbens)
• Chronic Pain:
– 1 tablet bid or tid.
– Half-life 5.6 hours; 4-6 hrs prn.
• Fibromyalgia:
– 1 tablet tid.
• Acute Pain (sporadic):
– 2 tablets single dose.
• No contraindications:
– Hypertension, cardiovascular risk, no risk of GI bleeds.
*1 tablet = 23.4 mg harpagoside (3.74 g dried secondary root)
Natural
Antispasmodic
Skullcap (Scutellaria lateriflora)
(also known as Virginia Skullcap)
• Used as a nerve tonic, sedative and nervous conditions.
• Used as antispasmodic medicine in the early 1900’s
and the Manual of Materia Medica lists the following pain
associated conditions where it was used: spasms,
muscular twitching, and neuralgia.
• Today it is widely used for treating tension, anxiety and
insomnia as well as a visceral relaxant / antispasmodic
for muscular cramps.
Skullcap (Scutellaria lateriflora)
(also known as Virginia Skullcap)
• Scutellarin:
• Shown protective effect for cerebral injury via regulating
expression of NOS isoforms & angiogenic molecules (Hu XM et al)
• Protection against ConA-induced immunological liver injury in
mice; mechanism: effect on pro-inflammatory cytokines (inhibition
NF-kappaB-TNF-alpha-iNOS transduction pathway) (Tan ZH et al)
• Study showed neuroprotective effects on brain ischemic injuryiinhibition of the apoptosis-inducing factor pathway in rats (Zhang
HF et al)
• Anti-inflammatory activity in microglial cell (Wang S et al)
Skullcap (Scutellaria lateriflora)
Bioenergetic uses of Scullcap are:
Relaxes constraint. Tonifies the Yin, clears empty heat.
Relieves Heart Qi constraint (Liver-Yang rising) or Kidney/adrenal Qi constraint).
Treats conditions of heart and kidney Yin deficiency:
- insomnia, anxiety.
Treats conditions of stomach or kidney Qi stagnation:
- nervousness, stress.
Treats conditions of kidney /adrenal Qi constraint:
- mental/nervous tension from chronic stress or pain or mental/physical exhaustion,
unrest, stress-related conditions, anxiety, panic attacks.
- tension headache, neuralgia, neuritis, uterine pain, muscle spasms/cramps
(e.g.,
lower leg, back).
Should be used to treat conditions with patterns of constrained Qi arising from
deficiency; empty tense conditions. Not for conditions arising from excess.
Indicated for chronic and not acute stages.
Recognized as a nervine tonic.
Considered to have trophorestorative effect on nerves.
Systemic relaxant: very effective for spasms-cramps.
Muscle Relaxants
•
•
Clinical trials:
• Insufficient evidence to determine whether skeletal muscle
relaxants are effective for subacute or chronic LBP.
• No difference in short-term reduction of muscle spasm
between cyclobenzaprine and placebo.
Benzodiazepines:
• Used as skeletal muscle relaxants.
• Two trials: more effective than placebo for short-term
pain intensity and overall improvement.
• One trial: no difference between diazepam and placebo
for muscle spasm.
• Short term use to avoid addiction.
Natural Topical
Analgesic
Adjuvant for Chronic Pain
•
•
Topical agents:
• Several advantages over systemic drugs:
• Local action
• Lower systemic absorption
• Fewer systemic effects
• Patient preference.
Topical NSAIDs:
• Acute & widespread musculoskeletal pain.
• Chronic LBP.
• Peripheral neuropathic pain.
Uses of essential oils: aches and pains of muscles and joints associated
with backache, bursitis, lumbago, strains, bruises, sprains and arthritic or
rheumatic pain, pain of tendons and ligaments. Tired, aching muscles.
© Guy-Chamberland-MasterHerbalist
Adjuvant for Chronic Pain
Menthol, camphor, clove & eucalyptus = topical analgesic.
•
•
•
Inhibit TRPA1:
• Topical analgesic.
TRPA1: Transient receptor potential cation channel, subfamily A, member 1
• Acute & chronic (neuropathic) pain & inflammation.
Numerous clinical trials:
• Peripheral & central neuropathic pain:
• menthol was analgesic
• Long-term CIPN (chemotherapy-induced peripheral neuropathy (CIPN):
• Improvement in pain and function - topical menthol.
• Well tolerated, have minimal side effects.
• Works relatively quickly.
© Guy-Chamberland-MasterHerbalist
Adjuvant for Chronic Pain
• Essential oils are often used in alternative medicine as analgesic
and anti-inflammatory remedies.
• TRPM8 is a thermosensitive receptor that detects cool
temperatures and menthol whereas TRPA1 is a sensor of
noxious cold. Ideally, an effective analgesic compound would
activate TRPM8 and inhibit TRPA1.’ (Takaishi et al)
• TRPA1 (Transient receptor potential cation channel, subfamily A,
member 1) is involved in acute & chronic (neuropathic) pain &
inflammation. TRPA1 antagonists are used to help reduce pain
caused by inflammation.
© Guy-Chamberland-MasterHerbalist
Adjuvant for Chronic Pain
•
Antagonists/Inhibitors of TRPA1 include: Camphor, clove oil and menthol. They
act as a topical analgesic.
•
Study shows that Clove oil helps reduce pain via peripheral action (Alqareer et
al).
•
Eugenol, the main constituent of Clove oil, shown to provide analgesia in rat
monoiodoacetate-induced osteoarthritis (Ferland et al).
•
1,8-cineole (Eucalyptus oil) is an antagonist of human TRPA1 that has analgesic
and anti-inflammatory activity via inhibition of TRPA1.
•
Menthol also activates heat-activated TRPV3 & TRPM8 -a cold-activated
thermo TRP ion channel.
•
Explains sensations of cold and/or heat reported after application of product.
Menthol is a natural compound of plant origin that induces a cool sensation via
the activation of the TRPM8 channel. Research indicates that voltage-gated
Na(+) channels are critical for experiencing pain sensation. (Gaudioso)
© Guy-Chamberland-MasterHerbalist
Can we effectively reduce
moderate-severe pain
with a combination of
Devil’s claw, California
poppy and Skullcap?
Pain Medications –
Visual Analog Scale
• The clinical goal in the treatment of pain is to suppress the feeling
of pain until it is tolerable (or gone) by the patient.
• One of the primary endpoints is the measure of the sensation of
pain by the patient using a Visual Analog Scale (VAS).
– An effective dose of an analgesic must lower VAS by 2.0 or
more.
Pain Medications –
Visual Analog Scale
• The clinical goal in the treatment of pain is to suppress the feeling
of pain until it is tolerable (or gone) by the patient.
• One of the primary endpoints is the measure of the sensation of
pain by the patient using a Visual Analog Scale (VAS).
– The patient scores the level of the feeling of pain using a 0
to 10 scale. For example, a patient taking acetaminophen
+ ibuprofen that is in chronic severe pain has a VAS of 9.
The physician will begin by adding 2 mg of
hydromorphone. This can reduce the feeling of pain by
30% (VAS = 6). The physician will then increase the
dosage of hydromorphone to 4 mg which is still clinically
acceptable. If the VAS does not decrease to a level that is
tolerable for the patient, the physician will then begin
adding or analgesics and or switching to stronger
narcotics.
INDEPENDENT CLINICAL DATA –
Acute Pain Protocol
• Analgesic:
– California poppy – single dose (2 grams Dried Herb
Equivalent (DHE) per day) at night.
• Anti-inflammatory:
– Devil’s claw – 2 tablets twice (4 grams DHE bid) a
day.
• Anti-Spasmodic:
– Scullcap – 2 tablets three times (4 grams DHE tid) a
day
• Topical gel:
– 3 – 4 times a day on affected area
INDEPENDENT CLINICAL DATA –
Chronic Pain Protocol
• Anti-Inflammatory:
– 2 capsules TID; each equivalent to 1000 mg. Daily
dose = 6000 mg DHE.
• Analgesic-Anti-Inflammatory:
– 1 capsule of 2500 mg dried herb top California poppy
at night + 1000 mg Devil’s claw.
• Topical gel:
– 3 to 4 times a day on affected
Study
Pilot study; 7-day acute pain
Subjects:
• 10 patients
• 10 patients
• Patients with acute pain (VAS > • Patients with chronic pain (VAS > 4)
4)
• No drug therapy
• No drug therapy
Herbs:
• California poppy (1 at night)
• Devil’s claw (tid)
• Scullcap (tid)
•
•
•
•
Results:
•
•
•
•
•
•
•
•
•
•
Reference:
Chamberland G. unpublished
Improved sleep
Significantly reduced pain
 swelling
 tenderness
Pilot study; 28-day chronic pain
California poppy (1 at night)
Devil’s claw (tid)
Scullcap (tid)
Gel
Improved sleep
Significantly reduced pain
Significant  mobility & flexibility
 swelling
 tenderness
 stiffness
Chamberland G. unpublished
© Guy-Chamberland-MasterHerbalist
Initial Pharmacological intervention
Examples of Analgesic-NSAID Choices
acetaminophen
ibuprofen
Devil’s claw
NSAID
contraindicated
500 mg q 4 hrs po
MDD 4000 mg
400 mg q 4-6 hrs po
MDD 3200 mg
20 mg harpagoside q 6 hrs po
Reassessment?
Second Pharmacological intervention.
Upward titration?
Need co-analgesic--adjuvant meds?
Devil’s claw
© Guy-Chamberland-MasterHerbalist
Relief
obtained
Second Pharmacological intervention - Reassessment
Non-opioid analgesics (acetaminophen, NSAIDs, COX-2 Inhibitors);
Tramadol;
Opioids;
Alpha 2 adrenergic agonists;
Antidepressants (tricyclics and SNRIs);
Antiepileptic drugs (gabapentin, pregabalin);
Muscle relaxants;
N-methyl-d-aspartate (NMDA) receptor antagonists;
Topical analgesic agents
+
Upward titration?
Need co-analgesic--adjuvant meds?
© Guy-Chamberland-MasterHerbalist
COMPLEMENTARY ACTIVITIES –
Pain Management examples
Natural NSAID: enteric coated Devil’s claw (20 mg harpagosides).
Goal: 50 – 100 mg harpagosides per day.
1st 48 hours: loading dose to rapidly decrease inflammation.
468 mg PE 8:1 standardized 5% harpagosides (23.4 mg)
Or 500 mg PE 4:1 standardized 5% harpagosides (25 mg)
Natural analgesic: California poppy (3 g DHE; 5:1 extract; standardized to
0.8% isoquinoline alkaloids).
Night pain – critical part of therapy.
Co-analgesic – adjuvant to natural NSAID.
Antispasmodic: enteric coated Scullcap (2 g DHE).
Spasms and cramps.
Anxiety. Nervine tonic.
Tablet of 500 mg PE 4:1 = 2 g DHE
© Guy-Chamberland-MasterHerbalist
Natural – NSAID: Enteric Coated Devil’s
Claw (20 mg harpagosides)
Goal: 50 – 100 mg harpagosides per day.
1st 48 hours: loading dose to rapidly decrease inflammation.
468 mg PE 8:1 standardized 5% hapragosides (23.4 mg)
Loading dose for 48 hrs = 2 tablets tid = 250% of dose.
(Very effective speed of onset for pain reduction but consider safety –
risk-to-benefit.)
Therapeutic dose of 1 tablet tid = 125% of dose.
Maintenance dose of 1 tablet bid = 85% of dose.
(Both are safe if no contraindications. Always aim for lowest systemic
exposure long-term.)
Safe daily dose:
9 g/day DHE
© Guy-Chamberland-MasterHerbalist
Natural – NSAID: Enteric Coated Devil’s
Claw (20 mg harpagosides).
Goal: 50 – 100 mg harpagosides per day.
1st 48 hours: loading dose to rapidly decrease inflammation.
500 mg PE 4:1 standardized 5% hapragosides (25 mg)
Loading dose for 48 hrs = 2 tablets tid = 133% of dose.
(Safer than previous because of lower total herb exposure. Draw back: some
efficacy associated with other ingredients that are now at lower dose
than harpagoside content.)
Therapeutic dose of 1 tablet tid = 67% of dose.
Maintenance dose of 1 tablet bid = 44% of dose.
(Both are safe if no contraindications. Always aim for lowest systemic
exposure long-term.)
Safe daily dose:
9 g/day DHE
© Guy-Chamberland-MasterHerbalist
Natural Analgesic
Natural analgesic: California poppy (3 g DHE; 5:1 extract);
standardized to 0.8% isoquinoline alkaloids.
Night pain – critical part of therapy. (100% of dose)
(Safe if no contraindications.)
Co-analgesic – adjuvant to natural NSAID. (200% of dose)
(If no contraindications, this approach is safe. Consider
dosing interval and assess effect on drowsiness.)
Safe daily dose:
3 g/day DHE
© Guy-Chamberland-MasterHerbalist
Antispasmodic
Enteric coated Scullcap (2 g DHE).
Spasms and cramps. Anxiety. Nervine tonic.
Tablet of 500 mg PE 4:1 = 2 g DHE
(each tablet equivalent to 17% of dose)
1 Tablet of 500 mg PE 4:1 given tid = 50% additive intake
(Very safe if no contraindications.)
2 Tablets of 500 mg PE 4:1 given tid = 100% additive intake
(Very safe if no contraindications.)
3 Tablets of 500 mg PE 4:1 given tid = 150% additive intake
(Safe if no contraindications. However, consider impact on
drowsiness.)
Safe daily dose:
12 g/day DHE
© Guy-Chamberland-MasterHerbalist
A Simple View of Herbs & Pain
Management
Combination therapy for acute or chronic pain:
enteric coated Devil’s claw + California poppy + enteric coated Scullcap.
Edema and/or
inflammation
Rheumatic
condition
+++
inflammation
Enteric coated
Figwort
Black cohosh
Feverfew
Local
pain
Topical gel
Complementary therapeutic activity – no additive effect
© Guy-Chamberland-MasterHerbalist
Case Study – Low Back Pain
50 year old male with history of chronic back pain due to lumbar disc hernia.
Complains of low back and limb muscle spasms. Patient refuses to take
narcotics because of negative impact on his ability to concentrate and opioids
make him aggressive. Epidural injections of steroids and anesthetic do not
provide adequate benefit and patient has severe hypertension due to steroids.
Initial intervention:
- 2 tablets (enteric coated) of 23.4 mg harpagoside three times a day for first
48-hours. Reduced to 1 tablet three times a day for 2 weeks (next visit).
- 1 tablet (2 g DHE; enteric coated) of Scullcap three times a day for first week.
Reduced to 1 tablet p.r.n. every 4-6 hours as needed for spasms.
Second intervention:
- Maintain 1 tablet 23.4 mg harpagoside three times a day for one month.
Explained increase to 2 tablets three times a day for 24 hours when flare-up
due to false movement or exertion.
- 1 tablet of Scullcap p.r.n. every 4-6 hours as needed for spasms.
- Night pain: 1 tablet Devil’s claw & 3 tablets Scullcap 30 minutes before
bedtime.
Case Study– Low Back Pain
50 year old male with history of chronic back pain due to lumbar disc hernia.
Complains of low back and limb muscle spasms. Patient refuses to take
narcotics because of negative impact on his ability to concentrate and opioids
make him aggressive. Epidural injections of steroids and anesthetic do not
provide adequate benefit and patient has severe hypertension due to steroids.
Initial intervention:
- 2 tablets of 23.4 mg
harpagoside three times a
day
for
first
48-hours.
Reduced to 1 tablet three
times a day for 2 weeks (next
visit).
- 1 tablet of Scullcap three
times a day for first week.
Reduced to 1 tablet p.r.n.
every 4-6 hours as needed for
spasms.
Devil’s
claw
–
standardized
harpagoside:
1) Acute pain: use three times a day for
first 48-hours.
a) Do not exceed 48-hours.
b) TID important based on half-life.
2) Reduce to 1 tablet three times a day for
2 weeks.
3) Reduce to 1 tablet twice a day for
longer.
RAPID PAIN REDUCTION: LOADING DOSE
FOLLOWED
BY
OPTIMIZED
DOSE
FREQUENCY.
Case Study – Low Back Pain
Initial intervention:
- 2 tablets of 23.4 mg
harpagoside three times a
day
for
first
48-hours.
Reduced to 1 tablet three
times a day for 2 weeks (next
visit).
- 1 tablet (2 g DHE) of
Scullcap three times a day
for first week. Reduced to 1
tablet p.r.n. every 4-6 hours
as needed for spasms.
Enteric coated Scullcap:
1) Spasms-cramps:
a) Depending on severity, 1 tablet
every 4-6 hours as needed.
b) Beware of tranquilizing effect drowsiness.
2) Maintain lower dose during day.
3) If no sleep aid, use 2-3 tablets at
bedtime.
BALANCE SPASM/CRAMP REDUCTION
VERSUS
TRANQUILIZING
EFFECT
DURING DAYTIME!.
Case Study – Low Back Pain
Second intervention:
- Maintain 1 tablet 23.4 mg
harpagoside three times a day
for one month. Explained
increase to 2 tablets three times a
day for 24 hours when flare-up
due to false movement or
exertion.
- 1 tablet of (2g DHE) Scullcap
p.r.n. every 4-6 hours as needed
for spasms.
- Night pain: 1 tablet Devil’s claw &
3 tablets Scullcap 30 minutes
before bedtime.
Devil’s claw :
1) Flare-ups: important to rapidly reduce
sudden increase in pain.
a) Do not exceed 48-hours.
b) TID important based on half-life.
2) Reduce to maintenance dosing or stop
if no longer taking.
Case Study – Low Back Pain
Second intervention:
- Maintain 1 tablet 23.4 mg
harpagoside three times a day
for one month. Explained
increase to 2 tablets three
times a day for 24 hours when
flare-up due to false
movement or exertion.
- 1 tablet (2 g DHE) of Scullcap
p.r.n. every 4-6 hours as needed
for spasms.
- Night pain: 1 tablet Devil’s
claw & 3 tablets Scullcap 30
minutes before bedtime.
Night Pain:
1) Important to add sedative-hypnotic
PLUS anti-inflammatory-analgesic.
2) Skullcap is good choice because of
antispasmodic effect. Lemon balmPassion flower can also be used for
night pain in combinations with natural
NSAID.