Jacob Bell
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A Dramatic Response to Inhaled Cannabis in a Woman with Central Thalamic Pain and Dystonia
Avijit Chatterjee, MSc
,
Almahrezi, MB ChB, CCFP
,
Ware, MB BS, MSc, MRCP(UK)
,
Fitzcharles, MB ChB, FRCP(C)
To the Editor:
Central pain syndromes (CPS) are difficult to treat despite recent advances in pharmacological and surgical management. Therapy commonly requires multiple interventions, continuous monitoring, and adjustment. Cannabis and its derivatives (cannabinoids) have recently received much attention as potential therapeutic agents. The clinical utility of cannabinoids has been suggested on the basis of anecdotal reports and small clinical studies for a wide range of pain syndromes, including cancer pain,1 visceral pain,2 migraine3 and pain associated with spasticity.4 We report a patient with intractable CPS who experienced dramatic relief of pain and dystonia from cannabis.
Back to Article Outline
Case Report
A 42-year-old woman presented to our multidisciplinary pain center with a fifteen-year history of progressive continuous right-sided body and limb pain due to left-sided idiopathic caudate atrophy. Her initial symptom had been numbness of the right hand, suggestive of unilateral carpal tunnel syndrome, for which she underwent unsuccessful carpal tunnel release. Following surgery, she developed right-sided upper and lower limb dystonia with equinovarus foot positioning and abnormal posturing of the right hand. She experienced severe right-sided body and limb pain, characterized by continuous paresthesias and intermittent electric-type pains exacerbated by movement. She was diagnosed with right hemiplegic painful dystonia. She progressively deteriorated, and became wheelchair-bound and unable to write. She complained of continuous debilitating pain. Between 4 and 12 years after the onset of symptoms, three thalamotomies were performed. Each operation was moderately and temporarily successful in reducing pain and dystonia. Numerous additional treatments, including opioids, anticonvulsant agents, tricyclic antidepressants, muscle relaxants, botulinum toxin, physiotherapy and acupuncture, were largely unsuccessful and commonly associated with unacceptable side effects. Thirteen years after the onset of pain, a deep brain stimulator (DBS) was inserted into the left thalamus. Electrical stimulation by internalized battery subjectively reduced her pain by about 50%, and she regained the ability to write. However, she still required continuous treatment with daily low-dose morphine. Subsequent displacement of the DBS required surgical revision, but infection at the stimulator insertion site resulted in removal of the DBS two years after placement. Following removal of the DBS, she was maintained on daily long-acting morphine with breakthrough morphine, at a total daily dose of 250-300mg per day. Additional medications included the antidepressants buproprion (150 mg/day) and amitriptyline (100 mg /day) for depression and migraines, respectively.
One month prior to a recent outpatient visit, the patient self-medicated with herbal cannabis for the first time. She smoked one 'joint' in the morning once a week for three weeks. On each of these occasions, she experienced drowsiness after smoking the cannabis and slept for about two hours. On awakening, she experienced complete pain relief and marked improvement in her dystonia, an effect confirmed by her husband. This resulted in improved ability to write and to take a few steps without support. She also reported complete relief of paresthesia and electric-type pain. She did not require any analgesic medication for the following 48 hours. Her subjective pain score on a 10 cm visual analogue scale (0-none, 10-severe) without medication in previous years was 9. At best, pharmacological and/or surgical intervention reduced her pain level to 4/10. Cannabis therapy resulted in a pain score of zero. No other treatment intervention to date had resulted in such dramatic overall improvement in her condition. Despite the abrupt reduction of chronic high-dose morphine therapy, she also did not report any symptoms of opioid withdrawal.
She has been using cannabis at a dose of one joint daily over the past three months for management of her pain and dystonia, and reports continued benefit. No tolerance to the effects of smoked cannabis has been observed. The dystonia has improved remarkably and the patient now only uses her wheel chair to go outdoors. She has discontinued her opioid treatment completely. Although a neurosurgeon has recommended reimplantation of the DBS, the patient is unwilling to undergo this surgical intervention for as long as her newly-found pain control continues to provide relief.
Back to Article Outline
Comment
Our case raises three interesting points. First, inhaled cannabis has provided a prolonged period of complete pain relief in a patient who was cannabis-naı̈ve and who previously required high doses of opioids, as well as neurosurgical interventions for control of intractable central thalamic pain. Second, the patient exhibited a marked reduction in limb dystonia in response to cannabis. Third, the patient did not experience any opioid withdrawal symptoms for the 48 hours without opioids, and has been subsequently able to completely discontinue opioid use. While her dramatic response may be attributable to a profound placebo effect, recent advances in our understanding of cannabinoid neuropharmacology permit an explanation of these results on scientific grounds.
Specific cannabinoid (CB) receptors have been identified in the central (CB1) and peripheral (CB2) nervous system in areas known to be involved in pain modulation and motor control, including the rostral ventromedial medulla and the periaqueductal gray matter (PAG),5 and basal ganglia.6 Agonists at the CB1 receptors, including delta-9-tetrahydrocannabinol (THC), the principal active component of smoked cannabis, and other synthetic CB1 agonists have been shown to have analgesic properties in animal models of chronic neuropathic pain.5 Cannabinoids also have been reported in the treatment of movement disorders, including tics in Tourette's syndrome, levodopa-induced dyskinesia in Parkinson's disease, and muscle spasm in multiple sclerosis.7 Animal studies have also demonstrated functional interactions between cannabinoids and opioids. In animal models of neuropathic pain, the analgesic effects of cannabinoids are reduced by opioid receptor antagonists and potentiated by morphine, suggesting overlapping signalling cascades and potential synergistic interactions.8 Opioid-sparing effects of cannabinoids were demonstrated in an N-of-1 study of a patient with abdominal pain due to familial Mediterranean fever.2
There are many unanswered questions regarding the safety and efficacy of prolonged use of cannabis for medical purposes. Although anecdotal reports in both the medical and lay literature describe outstanding success with cannabinoid use, it is not known what percentage of individuals respond favorably, which diseases are likely to respond, whether tolerance may develop, and what quantity of drug is required. Our case report illustrates improvement in control of central pain and dystonia, and discontinuation of other treatments following cannabis use, suggesting a role for cannabinoids in the management of central pain syndromes with dystonia. Further research is required into the mechanisms of action, and the safety and efficacy of cannabinoid treatment in this and other chronic pain syndromes. The possibility that cannabinoids may have opioid-sparing effects and may ameliorate opioid withdrawal should also be further investigated.
Back to Article Outline
References
Noyes R, Brunk SF, Avery DAH, Canter AC. The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Clin Pharmacol Ther. 1975;18:84—89
View In Article
MEDLINE
Holdcroft A, Smith M, Jacklin A, et al. Pain relief with oral cannabinoids in familial Mediterranean fever. Anaesthesia. 1997;52:483—486
View In Article
MEDLINE
Russo E. Cannabis for migraine treatment (the once and future prescription? An historical and scientific review). Pain. 1998;76:3—8
View In Article
Abstract
Full Text
Full-Text PDF (54 KB)
CrossRef
Consroe P, Musty R, Rein J, Tillery W, Pertwee R. The perceived effects of smoked cannabis on patients with multiple sclerosis. Eur Neurol. 1997;38:44—48
View In Article
MEDLINE
CrossRef
Meng ID, Manning BH, Martin WJ, Fields HL. An analgesia circuit activated by cannabinoids. Nature. 1998;395:381—383
View In Article
MEDLINE
CrossRef
Sanudo-Pena MC, Tsou K, Walker JM. Motor actions of cannabinoids in the basal ganglia output nuclei. Life Sci. 1999;65:703—713
View In Article
MEDLINE
CrossRef
Muller-Vahl KR, Kolbe H, Schneider U, Emrich HM. Cannabis in movement disorders. Forsch Komplementarmed. 1999;6(Suppl 3):23—27
View In Article
Reche I, Fuentes JA, Ruiz-Gayo M. Potentiation of delta 9-tetrahydrocannabinol-induced analgesia by morphine in mice (involvement of mu- and kappa-opioid receptors). Eur J Pharmacol. 1996;318:11—16
Source: A Dramatic Response to Inhaled Cannabis in a Woman with Central Thalamic Pain and Dystonia
Avijit Chatterjee, MSc
,
Almahrezi, MB ChB, CCFP
,
Ware, MB BS, MSc, MRCP(UK)
,
Fitzcharles, MB ChB, FRCP(C)
To the Editor:
Central pain syndromes (CPS) are difficult to treat despite recent advances in pharmacological and surgical management. Therapy commonly requires multiple interventions, continuous monitoring, and adjustment. Cannabis and its derivatives (cannabinoids) have recently received much attention as potential therapeutic agents. The clinical utility of cannabinoids has been suggested on the basis of anecdotal reports and small clinical studies for a wide range of pain syndromes, including cancer pain,1 visceral pain,2 migraine3 and pain associated with spasticity.4 We report a patient with intractable CPS who experienced dramatic relief of pain and dystonia from cannabis.
Back to Article Outline
Case Report
A 42-year-old woman presented to our multidisciplinary pain center with a fifteen-year history of progressive continuous right-sided body and limb pain due to left-sided idiopathic caudate atrophy. Her initial symptom had been numbness of the right hand, suggestive of unilateral carpal tunnel syndrome, for which she underwent unsuccessful carpal tunnel release. Following surgery, she developed right-sided upper and lower limb dystonia with equinovarus foot positioning and abnormal posturing of the right hand. She experienced severe right-sided body and limb pain, characterized by continuous paresthesias and intermittent electric-type pains exacerbated by movement. She was diagnosed with right hemiplegic painful dystonia. She progressively deteriorated, and became wheelchair-bound and unable to write. She complained of continuous debilitating pain. Between 4 and 12 years after the onset of symptoms, three thalamotomies were performed. Each operation was moderately and temporarily successful in reducing pain and dystonia. Numerous additional treatments, including opioids, anticonvulsant agents, tricyclic antidepressants, muscle relaxants, botulinum toxin, physiotherapy and acupuncture, were largely unsuccessful and commonly associated with unacceptable side effects. Thirteen years after the onset of pain, a deep brain stimulator (DBS) was inserted into the left thalamus. Electrical stimulation by internalized battery subjectively reduced her pain by about 50%, and she regained the ability to write. However, she still required continuous treatment with daily low-dose morphine. Subsequent displacement of the DBS required surgical revision, but infection at the stimulator insertion site resulted in removal of the DBS two years after placement. Following removal of the DBS, she was maintained on daily long-acting morphine with breakthrough morphine, at a total daily dose of 250-300mg per day. Additional medications included the antidepressants buproprion (150 mg/day) and amitriptyline (100 mg /day) for depression and migraines, respectively.
One month prior to a recent outpatient visit, the patient self-medicated with herbal cannabis for the first time. She smoked one 'joint' in the morning once a week for three weeks. On each of these occasions, she experienced drowsiness after smoking the cannabis and slept for about two hours. On awakening, she experienced complete pain relief and marked improvement in her dystonia, an effect confirmed by her husband. This resulted in improved ability to write and to take a few steps without support. She also reported complete relief of paresthesia and electric-type pain. She did not require any analgesic medication for the following 48 hours. Her subjective pain score on a 10 cm visual analogue scale (0-none, 10-severe) without medication in previous years was 9. At best, pharmacological and/or surgical intervention reduced her pain level to 4/10. Cannabis therapy resulted in a pain score of zero. No other treatment intervention to date had resulted in such dramatic overall improvement in her condition. Despite the abrupt reduction of chronic high-dose morphine therapy, she also did not report any symptoms of opioid withdrawal.
She has been using cannabis at a dose of one joint daily over the past three months for management of her pain and dystonia, and reports continued benefit. No tolerance to the effects of smoked cannabis has been observed. The dystonia has improved remarkably and the patient now only uses her wheel chair to go outdoors. She has discontinued her opioid treatment completely. Although a neurosurgeon has recommended reimplantation of the DBS, the patient is unwilling to undergo this surgical intervention for as long as her newly-found pain control continues to provide relief.
Back to Article Outline
Comment
Our case raises three interesting points. First, inhaled cannabis has provided a prolonged period of complete pain relief in a patient who was cannabis-naı̈ve and who previously required high doses of opioids, as well as neurosurgical interventions for control of intractable central thalamic pain. Second, the patient exhibited a marked reduction in limb dystonia in response to cannabis. Third, the patient did not experience any opioid withdrawal symptoms for the 48 hours without opioids, and has been subsequently able to completely discontinue opioid use. While her dramatic response may be attributable to a profound placebo effect, recent advances in our understanding of cannabinoid neuropharmacology permit an explanation of these results on scientific grounds.
Specific cannabinoid (CB) receptors have been identified in the central (CB1) and peripheral (CB2) nervous system in areas known to be involved in pain modulation and motor control, including the rostral ventromedial medulla and the periaqueductal gray matter (PAG),5 and basal ganglia.6 Agonists at the CB1 receptors, including delta-9-tetrahydrocannabinol (THC), the principal active component of smoked cannabis, and other synthetic CB1 agonists have been shown to have analgesic properties in animal models of chronic neuropathic pain.5 Cannabinoids also have been reported in the treatment of movement disorders, including tics in Tourette's syndrome, levodopa-induced dyskinesia in Parkinson's disease, and muscle spasm in multiple sclerosis.7 Animal studies have also demonstrated functional interactions between cannabinoids and opioids. In animal models of neuropathic pain, the analgesic effects of cannabinoids are reduced by opioid receptor antagonists and potentiated by morphine, suggesting overlapping signalling cascades and potential synergistic interactions.8 Opioid-sparing effects of cannabinoids were demonstrated in an N-of-1 study of a patient with abdominal pain due to familial Mediterranean fever.2
There are many unanswered questions regarding the safety and efficacy of prolonged use of cannabis for medical purposes. Although anecdotal reports in both the medical and lay literature describe outstanding success with cannabinoid use, it is not known what percentage of individuals respond favorably, which diseases are likely to respond, whether tolerance may develop, and what quantity of drug is required. Our case report illustrates improvement in control of central pain and dystonia, and discontinuation of other treatments following cannabis use, suggesting a role for cannabinoids in the management of central pain syndromes with dystonia. Further research is required into the mechanisms of action, and the safety and efficacy of cannabinoid treatment in this and other chronic pain syndromes. The possibility that cannabinoids may have opioid-sparing effects and may ameliorate opioid withdrawal should also be further investigated.
Back to Article Outline
References
Noyes R, Brunk SF, Avery DAH, Canter AC. The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Clin Pharmacol Ther. 1975;18:84—89
View In Article
MEDLINE
Holdcroft A, Smith M, Jacklin A, et al. Pain relief with oral cannabinoids in familial Mediterranean fever. Anaesthesia. 1997;52:483—486
View In Article
MEDLINE
Russo E. Cannabis for migraine treatment (the once and future prescription? An historical and scientific review). Pain. 1998;76:3—8
View In Article
Abstract
Full Text
Full-Text PDF (54 KB)
CrossRef
Consroe P, Musty R, Rein J, Tillery W, Pertwee R. The perceived effects of smoked cannabis on patients with multiple sclerosis. Eur Neurol. 1997;38:44—48
View In Article
MEDLINE
CrossRef
Meng ID, Manning BH, Martin WJ, Fields HL. An analgesia circuit activated by cannabinoids. Nature. 1998;395:381—383
View In Article
MEDLINE
CrossRef
Sanudo-Pena MC, Tsou K, Walker JM. Motor actions of cannabinoids in the basal ganglia output nuclei. Life Sci. 1999;65:703—713
View In Article
MEDLINE
CrossRef
Muller-Vahl KR, Kolbe H, Schneider U, Emrich HM. Cannabis in movement disorders. Forsch Komplementarmed. 1999;6(Suppl 3):23—27
View In Article
Reche I, Fuentes JA, Ruiz-Gayo M. Potentiation of delta 9-tetrahydrocannabinol-induced analgesia by morphine in mice (involvement of mu- and kappa-opioid receptors). Eur J Pharmacol. 1996;318:11—16
Source: A Dramatic Response to Inhaled Cannabis in a Woman with Central Thalamic Pain and Dystonia
