elJl~D)JJ 1 rJ1HJ AND CANNABINOIDS - cbd-five.com Pain and... · fibromyalgia isa syndrome of...

elJl~D)JJ 1 rJ1HJ ANDCANNABINOIDSA surveyof currentfibromyalgiatreatment approachestogether withan overviewand case studiesof a new "old"treatment approach.

By Gordon Ko, MD, CCFP(EM), FRCPCand William Wine, PhD, DSc(toxicology)

[Editor's note: Practical Pain Management recognizes the many controversies that surround cannabinoids, yet one

cannabinoid is already on the commercial market (Marinol'») and has a significant following for its FDA-labeled use of

nausea. Additionally, we are aware of a plethora of research and development activities to produce legitimate commercial,

cannabinoid products. To this end, it is appropriate to educate physicians regarding the pharmacology a~ wells as potential,

legitimate, legal uses of cannabinoids. The publication of this article on cannabinoids is not to be construed that Practical

Pain Management endorses the illegal use of marijuana, and we urge all physicians to know and follow their state and

federal laws regarding marijuana and cannabinoid products.] 'I

Characteristic Tender Points of Fibromyalgia

Eleven out of 18 tender points is required to make a diagnosis offibromyalgia according to criteria established by the AmericanCollege of Rheumatology.1

· suboccipital muscle insertions· anterior aspect of C5-7 intertransverse

spaces

· midpoint of upper trapezius muscles

· supraspinatus origin above spine ofscapula

· second rib lateral to costochondral

junction· extensor muscle: 2 cm distal to lat.

epicondyle

· gluteal: upper outer quadrant ofbuttock·posteriorto greatertrochanterprominence·medial fat pad of knee: proximal to joint line

FIGURE 1. Charesteristic tender points of fibromyalgia.

ft

I.

According to the American Collegeof Rheumatology (ACR)definition,fibromyalgia is a syndrome of wide-

spread muscle pain (over 3 months) andstiffness with 11 or more characteristic

tender points on palpation (see Figure 1).'It affects 2% of the population, predomi-nantly females, with the most common ageat presentation of 40 to 50 years! Symp-toms in the fibromyalgia syndrome (FMS)include:

1)musculoskeletal complaints: "hurt allover," stiffness, swollen feeling in tis-sues;

2) nonmusculoskeletal: fatigue, poorsleep (with reduced stages 3/4 slowwave sleep),.'5 and paresthesia; and

3) associated syndromes such as irritablebowel syndrome (IBS; 41.8% of FMSpatients),. dysmenorrhea," female ure-thral syndrome,. endometriosis,9 non-cardiac chest pain,1O plantar heelpain," migraine headache (45%),'2temporomandibular joint pain, ,. si-nusitis,'. and Sjogren's syndrome. IS Ahigher incidence of carpal tunnel syn-drome'. and raynaud's syndrome"may explain some of the paresthesiacomplaints.

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1

Chronic Pain and Cannabinoids

Higher anxiety (63.8%) and depressionhave also been reported.'8,1. The eco-nomic impact of this syndrome is signifi-cant. Chronic musculoskeletal pain is thenumber one cause of disability (under age45) in North America, the number twocause for visits to the primary care physi-cian and for workplace absences and thenumber three cause for hospitalizationswith over 250,000 spinal fusions carriedout in the USA. It is estimated that the di-rect medical cost ofFMS to the U.S. econ-

omy is in excess of $16 billion annually!ODespite such costs, effective long-termtreatment remains elusive.

Etiologyof FibromyalgiaPostulated risk factors for the develop-ment of FMS include a family history ofthis condition,21 a family history of de-pression and/or alcoholism in first degreerelatives,22childhood physical and sexualabuse, eating disorders, drug abuse,2'.2'hypermobile joint syndrome.25 FMS hasalso been documented after physical trau-ma26,27and whiplash,28 but the causal rela-tionship has not been established in a con-

sensus report on FMS and disability.2. Areview on psychosocial aspects concludedthat the view that FMS is caused by stressor abuse is unproven and that there is noevidence that communicating such a di-agnosis causes iatrogenic consequences.'o

It has also been postulated that viral in-fections may play an etiologic role." 70%of FMSpatients meet the Centers for Dis-ease Control and Prevention criteria for

chronic fatigue syndrome (CFS)32and 70%of CFS patients meet the ACR criteria forFMS." The usual routine laboratory testssuch as basic hematology, ESR, muscle en-zymes, rheumatoid factor and ANAare allnormal. 34 CFS researchers suggest thatderegulation of the 2.5A synthetase RnaseL antiviral pathway may be the patho-physiological reason." Muscle biopsy'6and MRI spectroscopy" studies which arecontrolled have proven to be non-diag-nostic. More recent electron microscopysuggests ultra-structural changes includ-ing increased DNAfragmentation (possi-bly due to persistent focal muscle con-tractions).'8 Reduced growth hormone se-cretion;'. and elevated CSF substance p"o

Amitriptyline 10-50mg effective for first 2 months, but not significant

compared to placebo at 6 months 52

Effects may be augmented with the addition of Fluoxetine53

Cyclobenzaprine 10mg qhs as effective as 10mg tid but with less side-

effects.54Combined with ibuprofen is helpful for morningstiffness55

Dothiepin tricyclic similar to amitriptyline56

Human growth hormone57 Nine month study of 50 FMS females with lowIGF-1 levels

0.3mg/kg Lv. drip in prescreened responders

Lv. drip

norepinephrine serotonin reuptake inhibitor""

a 5-Hydroxytryptamine type 3 receptor antagonist"'

antidiencephalon immune serum62

commercial form of gammahydroxybutyrate63

carisoprodol, paracetamol, caffeine64

Paroxetine,65 Venlafaxine (uncontrolled study)66

Tizanidine (Zanaflex)67

Topical camphor, methyl salicylate, menthol lotion (uncontrolled study for a

duration 20 minutes)68

Topical capsaicin 35% of neck pain group with FMS69

Tramadol Lv. drip single dose treatment; 12 patients with 20.6%

reduction in VAS pain70

5-HT3 receptor antagonist"

5 hydroxytryptophan 100mg tid72,73

Ketamine58

Lignocaine5.MilnacipranOdansetronSER282

Sodium oxybateSomadrilSSRI's:

TropisetronTryptophan

TABLE1. Medicationspublished in randomized trials and reponed to be effective for pain in FMS.

2 Practical PAIN MANAGEMENT, May 2005Reprintedwithpermission,PPMCommunications,Inc,

homocysteine," nerve growth factor lev-els'2 as well as abnormal neuroendocrine

challenge tests"'" and abnormal func-tional MRI studies.6.5osuggest a centralpain mechanism but no reliable diagnos-tic test has yet to be established. The mostrecent research suggests a clinical endo-cannabinoid deficiency as an etiologicalcause.51

Surveyof FibromyalgiaTreatmentsThe most studied medications to date are

the tricyclic derivatives such as amitripty-line and cyclobenzaprine. Randomizedtrials (RCT)of these and other treatmentsas outlined in Tables 1 and 2, below, onlydemonstrate short-term improvement insymptoms. Only the most recent or mostcomprehensive RCTs are referenced.

One recent review on pharmacologicaltherapies concluded that the best sup-ported medications to date are the lowdose tricyclic antidepressants, but that thebenefits are short-term and have not been

shown to be superior to placebo at 6months of study.",75

FMS patients are high consumers ofnonphysician and complementary alter-native medical (CAM) interventions. One

study comparing those using such servic-es found no differences in level of painand functional impairment. 76 Anotherstudy of III FMS subjects found that 98%had used at least one complementarymedical strategy in the preceding 6months and that such use was correlated

with lower age, higher pain and higherdisability." Use of complementary thera-pies was seen in patients of a higher so-cioeconomic status and a longer durationof fibromyalgia. The most popular ther-apy was oral supplementation and themost popular source of advice was frommagazines (40%).78Table 2 presents al-ternative medicine therapies reported as

being helpful for FMS pain.In the first author's survey of 116 physi-

atrists (rehabilitation medicine special-ists) in Ontario, Canada, 55% of respon-dents agreed that FMS is a "real disablingcondition." When asked what type of al-

ternative therapy works, 14 differenttypes were mentioned with the top threebeing acupuncture, biofeedback and chi-ropractic.128 It would appear that there ispresently no standard therapy that ishighly effective for treating niS. Perhaps,this is the reason why so many ofthese pa-

tients pursue CAM modalities.Promising new studies indicate that an

Chronic Pain and Cannabinoids

effective treatment of FMS may beachieved with cannabinoids. Following isan overview of cannabinoids followed bycase studies of treatment outcomes.

CannabinoidsOverviewCannabinoids are derived from the

cannabis sativa plant (marijuana) andhave been used over the past three thou-sand years to treat many physical condi-tions, including pain (see Table 3).

Scientific research (see Table 4) hasbegun to elucidate the mechanisms ofaction of THC (tetrahydrocannabinol,the main psychoactive component). Todate, two important cannabinoid re-ceptors have been identified in thehuman body: CBl and CB2. The formeris mainly confined to the central nerv-ous system (CNS) and the latter in theperipheral immune system (tonsils,spleen, mast cells, lymphocytes). Im-portantly, few CBl receptors are foundin the cardiorespiratory area of thebrainstem which makes cannabinoidssafe in overdose. 129.130Further laborato-

ry studies have demonstrated effectson several endogenous systems includ-mg:

1)Endorphinergic (specifically the pe-riaqueductal gray matter).131.133

2)Serotonergic (stimulates 5-HT syn-thesis and inhibits 5-HT3 receptorsthat mediate pain, nausea).134

3) Dopaminergic (inhibit dopamine Dlreceptors and activate dopamine D2receptors, both via CBl recep-tors). 135.136

4) Glutamatergic (act presynapticallyvia CBl receptor to reduce glutamatetransmission via NMDA receptorswithout blockade.'37 Glutamate is an

important mediator of neurogenicinflammation (neuropathic pain).

5)Anti-inflammatory (inhibit prosta-glandin E-2synthesis'>"and may bindand activate a not-yet characterizedCB2-like receptorI39).

6) Increases corticosteroid secretion.l40Its effect on inhibiting neuronal in-jury was recently shown to be inde-pendent of this.141

7) Improves sleep: In humans, Delta9-THC increase stage 4, or deep, sleepand reduce the duration of REM it-

self. 142.146Delta9-THC was found to sig-

nificantly decrease the time it takesto fall asleep in physically healthy in-somniacs. It also tended to be asso-ciated with some decrease in awak-

PHYSICAL THERAPIES

Aerobic exercise79-82 when combined with flexibility and strength training,

is superior to relaxation83Pool exercise84.85

Hydrotherapy"6-BB

Low power laser therapy"9.90

Strengthening exercise9'.92

TENS ( uncontrolled study)93

PSYCHOLOGICALTHERAPIES

Cognitive Behavioral therapy94,95Group therapy,96 including relaxation and cognitive behavioral training97Hypnotherapy98Meditation-based stress reduction program99

ALTERNATIVEMEDICINETREATMENTSWITH POSITIVECLINICAL TRIALS

Biochemical:DHEAsupplementation'OO .Dietary indole supplementation (ascorbigen and broccoli powder)'O'Dietary supplementation of coenzyme Q10 combined with Ginkgo bilobaextract'02

Homeopathy'03.'04Multimodality approach including nutrition and hormone repiacement'05024 essential oils'06

SAMe Lv.'07p.o (improved VAS pain, not TPI during last week of 6 weekstudy)'08

Super Malic (malic acid 200mg and magnesium 50mg: 6 tablets bid)'09Vegan diet"O

Electromagnetic (autonomic nervous system):Acupuncture'''.''3Copper wire bedsheet"4Cranial electrotherapy stimulation"5Static electromagnetic fields"8Thermoflow garments'17

Psychoemotional:Biofeedback - relaxation (combined with exercise best across years)"8Biofeedback - EMG'1!J.'22EEG-driven'23Mind-body therapies'24

Structural:Chiropractic therapy (4 weeks of spinal manipulation, soft tissue therapy,passive stretching)'25Osteopathy'26Prolotherapy (75% pain improvement; unblinded study)'27

TABLE 2. Xon-physician therapies reponed helPful for pain in FMS.

enings in the first half of the night. 147

A direct effect stimulation of mela-

tonin secretion by Delta9-THC mayplaya role.'4'

At the recent Canadian/American Pain

Society meeting in Vancouver (May 2004),over 20 clinical papers on cannabinoidswere presented. Several were N of 1 tri-als. Larger randomized trials are de-scribed in Table 5.

CaseStudies Of CannabinoidTreatment Of FMS

Case #1. A 50 year old public healthnurse, divorced mother of two, presentedwith longstanding FMS. This includedneck pain x 26 years, low back pain x 23years, migraines x 13 years. Predisposingchildhood factors included: growingpains, eating disorders, depression (fa-ther died of Hodgkin's). Associated syn-

Practical PAIN MANAGEMENT, May 2005Reprintedwithpermission.PPMCommunications.Inc.

3

Chronic Pain and Cannabinoids

dromes: costocondritis, plantar fascitis,tendonitis, menopause. Non-helpfultreatments included mobicox, amitripty-line, glucosamine, fish oil, guaifenesin(naturopathy), massage, pool exercise,cognitive behavioral therapy and relax-ation therapy. Temporary relief withtoradol, robaxacet, acetaminophen, topi-cal rubs, heating pad, chiropractic, os-teopathy. She was allergic to meperdine,and codeine. Cold made her worse.

She declined acupuncture and injec-tions. For migraines, she used migranal,zomig, fiorinal. L-tryptophan helpedwith sleep only. Physical exam revealed aBody Mass Index 38 (5'7" 240 Ibs). BP120/80 mmHg. 18/18 tender points. Pos-itive tinel's with no neuropathic deficitnor signs of connective tissue disease.Bone Scan: degenerative changes: shoul-ders, ankles, feet, TlO-12, L3-L5 facets.Ultrasound suggested borderline rightCTS but EMGstudy was normal. NegativeTOS Doppler study. Beck depressionscore: 9/63.

She was started on Nabilone Img QHS.Her pain and stiffness were reduced. Sideeffects included dizziness x 2 days, drymouth x 1 week. After 2 weeks, the dosewas increased to Img BID. By 1 month,the pain and headaches were further de-creased (see Table 6).

She returned 23 weeks later and ratedNabilone as most effective on a 5 pointlikert scale. With it, she reported that shewas able to discontinue mobicox onemonth earlier. It was the only treatmentamong pharmaceuticals and alternativetherapies that rated so high.

Case #2. A 45 year old bank employee,married mother of three, presented withlongstanding FMS(>5 years) and Crohn'sdisease. Her worse pain areas includedupper shoulders, low back pain, R elbow,forearm, and 2nd, 4th fingers. There wasshooting pain and tingling. Contributingfactors included sleep apnea, dysfunc-tional uterine bleeding, anxiety. Non-suc-cessful treatments included physiothera-py, massage therapy, muscle relaxants in-cluding Flexeri!, Zanaflex, cortisone in-jections. Botox injections provided somepain relief. Anti-inflammatories andamitriptyline were not tolerated. Oxycon-tin caused tremors. Hydromorph continwas helpful but then caused GI discomfort,so she was switched over to the Duragesicpatch (75uglhr q3days). When prednisonehad to be used for a Crohn's flare-up, she

4

gained 451b in weight and this aggravat-ed her FMS even more. Physical Exam:BMI 32 (5'6" 1951bs) BP 135/ 75mmHg.18/18 tender points to light touch. She wasstarted on Nabilone Img QHS. Her painand nausea were reduced. Side effects in-cluded mild somnolence. After 2 weeks,the dose was increased to Img BID. By 1month, the pain and headaches were fur-ther decreased.

Case #3. A 55 year old informationtechnology manager presented with a his-tory of diffuse chronic pain following aMVAin Oct. 2000. This was most severein the head, neck and upper shoulders.MRI scan revealed cervical multi-level de-

generative disc disease worse at C5-6 withan osteocartilaginous bar and mild flat-tening of the anterior spinal cord. Ep-worth Sleepiness Scale score: 14/24 indi-cated heavy sleep debt. Anxiety and panicattacks were reported. Non-helpful treat-ments included physiotherapy, chiro-practic, acupuncture, massage, gym exer-cise. He underwent cervical facet jointmedial branch rhizotomies. He used 2

Mersyndol and Tylenol#3 every morn-ing. NSAIDs were not helpful. Physicalexam: BMI28 (5'8 V2"185Ibs). BP 148/97.Neurologic exam revealed no evidence ofcervical radiculopathy or myelopathy. Hehad 12118 tender points on manual pal-pation. Average VASpain was 9110. Dura-gesic patch (up to 75ug/hr q3days) andBotox injections (7 sessions) provided fur-ther pain control VAS:511O.He was start-ed on Nabilone Img QHS and notedmuch less nausea and even better paincontrol VAS: 2110. 0118 tender points onalgometry noted. His sleep was also im-proved. When he tried to increase thedose to BID, he described "feeling like azombie." He continues to be maintainedwell on the lower dose.

Case #4. A 59-year-old former ultra-sound technician presented with a 10yearhistory of fibromyalgia, irritable bowelsyndrome, hypoglycemia. She describedher worst area of pain in her low back withMRI evidence of severe degenerativechanges, L4-5 bulging disc with moder-ate thecal sac compression. EMG testingrevealed chronic neurogenic changes inthe right L3-4 myotomes. She underwentextensive physiotherapy, massage, twoepidurals and a series of lumbar facetblocks. She also saw a neurosurgeon whodid not recommend surgery. Hypnosis,

Practical PAIN MANAGEMENT, May 2005Reprintedwithpermission.PPMCommunications,Inc.

acupuncture, aquatic exercise were nothelpful. Medications included celebrex200mg BID, amitriptyline 10mg QHS,oxycontin 10mg BID, oxycodone PRN,imovane, losec, estrogel. Physical examrevealed a BMI of 24 (5'3," 138 Ibs), BP117!74mmHg. She had 15/18 FMStenderpoints. Neurologic exam revealed painfulright straight-leg-raise test but no motor,sensory or reflex deficit. Grade 1 insta-bility noted in the right sacroiliac jointwith tight piriformis and tender triggerpoints. Gluteals were weak. Initial treat-ment with Botox helped with the piri-formis and gluteal pain. Prolotherapy re-quired she stop celebrex and aggravatedthe sacroiliac pains. Further trigger pointinjections with sensorcaine providedshort-term relief. She inquired aboutmedical marijuana and was started onNabilone 1/2capsule at night.

With the Nabilone, she was able to wean

off amitriptyline and oxycontin QHS com-pletely as she was able to go back to sleepif she woke up with pain. After 2 weeks,she tried to increase to 1 capsule at nightbut felt too dizzy. She continues on the V2capsule and rates it as markedly helpful.

Other Observations

In general, it was noted that responders(to cannabinoid therapy) scored lower de-pression ratings (Beck score < 21), had noprevious adverse reaction (paranoia, psy-chosis) to marijuana use, and were em-ployed or retired. It appeared also to workwell in combination with opioids by am-plifying analgesia and reducing nausea.The latter effect also helped in FMS pa-tients with GI problems (irritable bowel,Crohn's). Poor responders included thosewith unstable psychiatric states, multiplechemical sensitivities, nondermatomalsomatosensory deficits (conversion disor-der), and those actively seeking disabilityclaims.

Patient Screening and AdvisingThe use of Nabilone is contraindicated in

patients with known sensitivity to mari-juana or other cannabinoid agents, andin those with a history of psychotic reac-tions. Since Nabilone can elevate heart

rates and cause postural hypotension, itshould be used with caution in the elder-

ly and in patients with hypertension orheart disease. Nabilone is metabolized in

the liver by the GYP 2G9 pathway andshould be used with caution in patientswith liver dysfunction. Due to the addi-

.

Chronic Pain and Cannabinoids

First recorded use for medicinal purposes: Chinese

medical compendium 2737 B.C. ( Emperor Shen Nung)

Indian Hindu Vedas sang of it as one of the divine

nectars able to give man good health and visions of

the gods.

o Tibetans considered it sacred. Buddha, prior to his

enlightenment, reportedly lived on one hemp seed a day.

o 500 A.D. : European use after Napolean invadedEgypt and brought back to France.

Physicians published on using it: Aubert-Roche,

Moreau de Tours. William B. O'Shaughnessy MD 1840.

1840 to 1860: more than 100 articles published inmedicine.

1860 Ohio State Medical Society convention of the

Committee on Cannabis Indica: therapeutic applications

in mania, whooping cough, asthma, chronic bronchitis,

tetanus, epilepsy and withdrawl from alcohol.

o 1923 Marijuana first banned in Canada under theOpium and Drug act.

o 1937 Marijuana TaxAct in USA makes it difficult toobtain for medical purposes.

o Listed in US Pharmacopoeia until 1941

TABLE3. History of cannabinoid use.

tive effects, Nabilone should be used with caution in patientstaking sedatives such as benzodiazepines, barbiturates, or ex-cessive alcohol. When prescribing Nabilone, begin at a low doseand titrate up slowly.

Patients should be counseled on the most common adversereactions:

Drowsiness (reported in 66% of patients and therefore havethem take initial doses prior to sleeping at night)Dysphoria/Euphoria - Mood alteration (reported in 39%of patients)Dry Mouth (reported in 22% of patients). Encourage pa-tients with the knowledge that the adverse effects ofNabilone will decrease in 4-7 days.

DosingThe recommended starting dose is O.5mg QHS at bedtime. Mter1-2 weeks the dose may be increased to Img QHS to enhancefurther analgesia. Some nls patients are very sensitive to med-ications and may need to start at a lower dose ofO.25mg (in sus-pension).

Long-Term Management ofFibromyalgiaThere is no universal "magic bullet'" for the treatment ofFMS. Itis a syndrome and not a specific pathological disease entity. Di-agnosis is made be exclusion (the usual lab tests are all negative).Symptoms may last on average 15 years. 154 Review papers sug-gest that positive outcomes occur not only with age'" but also withan adequate physical activity level'56and coping skills.'57Excessmajor negative life events and permanent disability pensions wereassociated with a negative outcome.'58 Younger age of onset and

1964 Delta 9THC identified as the main psycho

active ingredient of cannabis (Gaoni &

Mechoulam)

Synthetic Cannabinoids

CB1 Receptor identified (Devane et aL)

CB1 Receptor cloned (Matsuda et aL)

CB2 Receptor (Kaminski et aL) + Endogenous

Ligands (anandamide) (Mechoulam et al) iden-tified

CB2 Receptor cloned (Munro et aL)

Cannabinoid Receptor Antagonists developed.

(SR141716A) (Rinaldi-Carmona et aL)

Endogenous Ligands proven analgesics

'Knock out' receptor modified mice CB1 (Ledent

et aL, Zimmer aL)

'Knock out' receptor modified mice CB2

(Buckley et aL)Clinical use of cannabis initiated Canada is first

industrialized nation to legalize the use of

medicinal marijuana (Allan Rock, federal minis-

ter of health).

1980

1988

1990

1992

1993

1994-7

1998

1999

2000

2000-1

TABLE 4. Medical cannabinoid key discoveries.

less sleep disturbance were associated with a more favorable out-come.'59 Effective management is best with an interdisciplinaryapproach'GO.'.2emphasizing lifestyle improvement ("TENSQ":Toxin elimination,'63 Exercise, Nutrition, Sleep hygiene, Quiet"de-stress" time) and pain control. Perhaps oral and sublingualcannabinoids'64 (without the stigma or pulmonary adverse effectsof inhaled marijuana), used in an integrated approach will be-come an effective well-accepted standard therapy. These casestudies backed by laboratory and clinical research indicated thatit helps not only with pain but also with anxiety, irritable boweland abnormal sleep.

ConclusionsOne recent extensive FMSreview paper listed 433 references.'.5Out of this, there was no mention of cannabinoids. Our presentreview has summarized not only up-to-date published studieson chronic FMS pain management but also presented the first-ever reported case series of effective FMS treatment withcannabinoids.

The evidence suggests that Nabilone (Cesamet), titrated inlow dosages is an extremely safe and effective pain medicationfor FMSpatients. It also exhibits very little or no adverse druginteraction effects with concurrent analgesic or psychiatric med-ications. In fact. it appears to potentiate opioid medications, sothat patients can taper doses to safer levels. All of this wouldsupport the contention that perhaps the most promising emerg-ing treatment to date for pain control is the use of cannabinoids.

From an evidence-based perspective, there is an obvious needto do a randomized controlled double-blinded study forcannabinoids in FMS.It is hoped that this review will stimulatefurther research in this area and enhance the well-being and

Practical PAIN MANAGEMENT, May 2005Reprintedwithpermission.PPMCommunications,Inc.

5

Chronic Pain and Cannabinoids

care of our chronic pain patients.

TABLE5. Summary of randomized trials of cannabinoids.

Additional comments:Please note that the oral cannabinoid Ce-

samet (Valeant pharmaceuticals) has beenapproved for use in Canada since theearly 1980's for the on-label use of severenausea/vomiting associated with cancerchemotherapy. It will be available in theUnited States for the first time in July2005. The sublingual cannabinoid spraySativexl64 (marketed by Bayer pharma-ceuticals) will be launched in Canada inJune 2005. Its on-label indication is forneuropathic pain associated with multiplesclerosis..

Dr. Gordon Ko, MD, CCFP (EM), FRCPC is

a Consultant Physiatrist and Lecturer at Sun-

nybrook & Women's College Health Sciences

Centre, University of Toronto. Further infor-mation and resources are available on Dr. Ko's

education website at www.MusclePainReliefca.

Dr. Kn is also Dean of the School of Integrative

Medicine, Rutherford University (Wyomingand Wlncouver, BC). For those interested in the

one-year PhDprogram in Integrative Medicine,

please contact registrar@rutheiford.edu.

Dr. William Wine, PhD, DSc (toxicology) is

a Psychopharmacologist at the Canadian Cen-

tre for Integrative Medicine, Markham, On-tario, Canada.

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6

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I CONDITIONS .... ....r.. #"I[C--BIN! SU DRUG .. :ii' I

Postoperative pain 56 Levonantradol Significant analgesic effects ofor trauma pain14. 1.5 to 3mg each dose of levonantradol as

Lm. compared to placebo

Chronic refractory 60 Nabilone 30% obtained significant reliefpain (esp. MS 0.25mg to and beyond that, a decreasedand neuropathic 3mg use of other analgesics andpain)'SO psychotropic medications

Neuropathic 24 THC & CBO Pain relief significantly superiorpain's' (Cannabidiol) to placebo. Impaired bladder

control, muscle spasms andspasticity were improved.

Chronic pain'52 34 THC; CBO; Extracts which contained THCTHC:CBO 1:1 proved most effective in symp-mixture tom control

Neuropathic 21 CT-3 Effective in reducing chronicpain,s3 neuropathic pain compared with

placebo

Chronic Pain and Cannabinoids

VAS pain (best to worse)

Fibromyalgia Impact Questionnaire (FIQ)

Average tender point pain threshold (APT)

Number of tender points:

Pre-treatment

5-8/10

24.3/100

2.18kg18/18

Two months later

4-5/1019.3/100

2.6kg16/18

TABLE6. CaseStudy #1 Outcomes.

VAS pain (average)FIQAPT

Pre-treatment

9/1086.0

0.6 kg (18/18)

Two months later6/1061.9

1.3 kg (18/18)

TABLE7. CaseStudy #2 Outcomes.

VAS pain (average)FIQAPT

Pre-treatment9/1077.4

1.98 kg (15/18)

Six weeks later5/1063.0

2.82 kg (10/18)

TABLE8. CaseStudy#4 Outcomes.

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