Multiple sclerosis spasticity

It is mainly used in the treatment of spasticity in multiple sclerosis, spastic spinal paralysis etc. It is also used in the treatment of trigeminal neuralgia. 

Similar to opioids, the cannabinoid system appears to be intricately involved in normal physiology, specifically in the control of movement, formation of memories, and appetite control. Basic research has discovered that members of this family of compounds have the capacity to protect threatened neurons, thereby slowing neurodegenerative processes that ultimately lead to physical disability. As the function of the physiological role of endocannabinoids becomes clearer, it appears the system may be involved in the pathology of several neurological diseases, specifically multiple sclerosis, spasticity, and pain. In 1999 the German journal, Forschende Komplementar-medizin und Klassische Naturheilkunde (Research in Complementary and Classical Natural Medicine) commented ... 

Therefore, inhibition of anandamide amidohydrolase to increase the accumulation of anandamide at its sites of action is desirable as a potential therapeutic approach for the treatment or prevention of disorders such as mental diseases, inflammation and pain, including treatment or prevention of schizophrenia, mood disorders, anorexia, multiple sclerosis, spasticity and glaucoma. Source Piomelli 1999... 

Documented effects In modem medicine a decoction of the stems and leaves is used in medicine to disinfect animals. Finely ground seeds mixed with butter is used to treat pediculosis (lice infestation). Tablets of condelphine are used to treat psycho-neurological diseases. The compounds delsemine and mellictine are used as anesthesia during surgical procedures (Altimishev 1991). The alkaloid condelphine has an activity similar to curare. Physicians use tablets of 0.025 g to treat conditions of excess skeletal muscle contraction, Parkinson s disease, multiple sclerosis, spastic and traumatic paralysis, etc. This preparation cannot be used by patients with conditions of reduced muscle contraction, liver and kidney diseases, or heart decompensation (Khalmatov et al. 1984). 

A 65-year-old woman with multiple sclerosis, spastic paraparesis, and chronic pain, who had previously taken gabapentin, lamotrigine, and amitriptyline, with partial pain relief, was given pregabalin 75 mg/day after 3 days she developed slurred speech, delusions, and insomnia. Pregabalin was withdrawn, and she recovered her normal cognitive function. 

Currently, baclofen is the only clinically used GAB Ab receptor agonist. It is used as a muscle relaxant for treatment of spasticity in spinal injury and multiple sclerosis. The cloning of GABAb receptors has renewed the interest in the search for more selective diugs and novel therapeutic indications. 

There have been a number of studies to evaluate the therapeutic effect of carmabinoids against spastic disorders, including multiple sclerosis and spinal cord injury. For example, a randomised placebo-controlled trial in more than... 

Multiple sclerosis patients must be treated with agents specific for upper motor neuron spasticity. 

Baker D, Pryce G, Croxford JL. Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature 2000 404 84-87. 

Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Makriyannis A, Khanolkar A, Layward L, Fezza F, Bisogno T, Di Marzo V. Endocanna-binoids control spasticity in a multiple sclerosis model. FASEB J 2001 15 300-302. 

Metz L and Page S (2003). Oral cannabinoid for spasticity in multiple sclerosis Will attitude continue to limit use Lancet, 362, 1513. 

Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A and Thompson A (2003). Cannabinoids for the treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study) Multicentre randomised placebo-controlled trial. Lancet, 362, 1517-1526. 

Skeletal muscle relaxants may be nsed for relief of spasticity in nenromnscular diseases, snch as multiple sclerosis, as well as for spinal cord injnry and stroke. They may also be used for pain relief in minor strain injnries and control of the mnscle symptoms of tetanus. Dantrolene (Dantrium) has been nsed to prevent or treat malignant hyperthermia in surgery. 

Oral Alleviation of signs and symptoms of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus. 

Oral - For the control of clinical spasticity resulting from upper motor neuron disorders such as spinal cord injury, stroke, cerebral palsy, or multiple sclerosis. It is of particular benefit to the patient whose functional rehabilitation has been retarded by the sequelae of spasticity. Such patients must have presumably reversible spasticity where relief of spasticity will aid in restoring residual function. 

Baclofen is a GABA agonist at GABA B receptors and it has a presynaptic inhibitory function by reducing calcium influx. Its indication is increased extensor tone and clonus. Intrathecal administration may control severe spasticity pain. It is used for the treatment of spastic movement, especially in instances of spinal cord injury, spastic diplegia, multiple sclerosis and amyotrophic lateral sclerosis. Its central nervous system effects include drowsiness, somnolence and seizure activity in epileptic patients. 

Baclofen is an agent of choice for treating spinal spasticity and spasticity associated with multiple sclerosis. It is not useful for treating spasticity of supraspinal origin. Doses should be increased gradually to a maximum of 100 to 150 mg per day, divided into four doses. 

Benzodiazepines also possess muscle relaxant activity. Their pharmacology is discussed in Chapter 30. Diazepam Valium) has been used for control of flexor and extensor spasms, spinal spasticity, and multiple sclerosis. The muscle relaxant effect of the benzodiazepines may be mediated by an action on the primary afferents in the spinal cord, resulting in an increased level of presynaptic inhibition of muscle tone. Polysynaptic reflexes are inhibited. The most troublesome side effect is drowsiness, which is dose dependent. Tolerance to both the therapeutic effects and the side effects develops. 

P. Jobin, et al. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis a randomized, double-blind, placebo-controlled, crossover study. 

Luo, J., J. H. Yin, H. Z. Wu, and Q. Wei. Extract from Fructus cannabis activating calcineurin improved learning and memory in mice with chemical drug-induced dysmnesia. Acta Pharmacol Sin 2003 24(11) 1137-1142. Degenhardt, L., W. Hall, and M. Lynskey. Exploring the association between cannabis use and depression. Addiction 2003 98(11) 1493-1504. Zajicek, J., P. Pox, H. Sanders, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study) multicentre randomised placebo-controlled trial. Lancet 2003 362(9395) 1517-1526. 

Unlabeled Uses Low back pain, spasticity associated with multiple sclerosis or spinal cord injury, tension headaches, trigeminal neuralgia... 

The safety and efficacy of gabapentin as adjunctive therapy to CBZ and/or phenytoin has been assessed in adults, adolescents (Bruni, 1998), and children (Khur-ana et ah, 1996) with partial seizures. A decrease of 50% or more in frequency of complex partial -I- secondary generalized seizures was reported in 71% of patients on a mean maintenance dose of gabapentin of 1600 mg/day (Bruni, 1998). It has also been used in the treatment of spasticity in adolescents with multiple sclerosis (Cutter et al., 2000) and in adults and adolescents with neuropathic pain (Rosenberg et al.,... 

Cutter, N.C., Scott, D.D., Johnson, J.C., and Whiteneck, G. (2000) Gabapentin effect on spasticity in multiple sclerosis a placebo-controlled, randomized trial. Arch Phys Med Rehabil 81 164-169. 

It is indicated in spasticity due to neurological disorders e.g., multiple sclerosis, chronic myelopathy, degenerative diseases of the spinal cord, cerebrovascular accidents and cerebral palsy painful muscle spasm associated with static and functional disorders of the spine (cervical and lumbar syndromes) painful muscle spasm following surgery e.g., for herniated intervertebral disc or for osteoarthritis of the hip. 

A9-THC is marketed as marinol or dronabinol for the treatment of chemotherapy-induced nausea and vomiting in Australia, Canada, Israel, South Africa and the USA. It was granted orphan drug status in the US for the stimulation of appetite and prevention of weight loss in patients with a confirmed diagnosis of AIDS. A9-THC is in phase I trials for spasticity, multiple sclerosis and postoperative pain. Several small clinical studies have confirmed the effectiveness of A9-THC as an analgesic, with doses of 15 to 20 mg being comparable to 60 to 120 mg of codeine (Williamson and Evans, 2000). 

Gabapentin [Neurontin] Adult initially, 300 mg TID. Can be gradually increased up to 3600 mg/d based on desired response. Children (3-12 years of age] Initially, 10-15 mg/kg body weight in 3 divided dosages increase over 3 days until desired effect or a maximum of 50 mg/kg/d. Developed originally as an anticonvulsant may also be helpful as an adjunct to other drugs in treating spasticity associated with spinal cord injury and multiple sclerosis. 

Uses. Gabapentin is effective in decreasing the spasticity associated with spinal cord injury102 and multiple sclerosis.29 Additional research should clarify how this drug can be used alone or with other agents to provide optimal benefits in spasticity resulting from various spinal, and possibly cerebral, injuries. 

A long list of potential therapeutic effects was recorded for THC, including analgesic, bron-chodilatory, antiemetic, anticonvulsant, and anti-inflammatory action, reduction of intraocular pressure, and alleviation of some neurological conditions (such as seizure disorders, spasticity associated with spinal cord injuries, and multiple sclerosis) (Mechoulam et al., 1994). 

At present, there is no approved medical use for cannabis in patients with neurological disorders. However, it is illegally used for spasticity and ataxia in patients with multiple sclerosis and spinal cord injury, and for the treatment of trigeminal nerve pain and, to a lesser extent, attention deficit hyperactivity disorder. Individuals with spinal cord injury have reported a reduction in spasticity after cannabis use. 

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