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Plavka R. Professor Antonín Dolezal, MUDr., DrSc.--an outstanding Prague obstetrician. The 75th birthday anniversary (* January 20, 1929). Neuro Endocrinol Lett. 2004 Apr; 25(1-2): 50-51
: The benign essential blepharospasm is a subliminal form of primary torsion dystonia with still uncertain aetiology. It is characterized by involuntary convulsive muscle contractions of the M. orbicularis occuli, accompanied by unbearable pain of the cornea, eye bulb and the muscle itself. It has been suggested that blepharospasm is neurobiologically based on a dysfunction of the basal ganglia and an impairment of the dopamine neurotransmitter system. Therefore, therapy of blepharospasm contains administration of anticholinergic- and tranquillizing drugs as well as botulinum toxin as neuromuscular blocking agent. However serious side effects can be observed as well as failure of therapy. In the brain a dense co-localisation of cannabinoid (CB1) and dopamine (D2)-receptor was identified which had been associated with the influence of cannabinoids on the dopaminergic reward system. Additionally, it has been demonstrated that cannabinoids may have an impact on the central GABAergic and glutaminergic transmitter system and thus might be involved in the influence of movement control. In the present case we administered the cannabinoid receptor agonist Dronabinol (Delta-9-Tetrahydrocannabinol) to a woman suffering from severe blepharospasm. Multiple treatments with botulinum toxin did not reveal a long-lasting beneficial effect. By contrast, treatment with 25 mg Dronabinol for several weeks improved the patients' social life and attenuated pain perception remarkably. This case study demonstrates that the therapy with a cannabinoid agonist may provide a novel tool in the treatment of blepharospasm and maybe of other multifactorial related movement disorders....
Gauter B, Rukwied R, Konrad C. Cannabinoid agonists in the treatment of blepharospasm--a case report study. Neuro Endocrinol Lett. 2004 Apr; 25(1-2): 45-48
: An initial report on the therapeutic application of delta 9-THC (THC) (Dronabinol, Marinol) in 8 children resp. adolescents suffering from the following conditions, is given: neurodegenerative disease, mitochondriopathy, posthypoxic state, epilepsy, posttraumatic reaction. THC effected reduced spasticity, improved dystonia, increased initiative (with low dose), increased interest in the surroundings, and anticonvulsive action. The doses ranged from 0.04 to 0.12 mg/kg body weight a day. The medication was given as an oily solution orally in 7 patients, via percutaneous gastroenterostomy tube in one patient. At higher doses disinhibition and increased restlessness were observed. In several cases treatment was discontinued and in none of them discontinuing resulted in any problems. The possibility that THC-induced effects on ion channels and transmitters may explain its therapeutic activity seen in epileptic patients is discussed....
Lorenz R. On the application of cannabis in paediatrics and epileptology. Neuro Endocrinol Lett. 2004 Apr; 25(1-2): 40-44
OBJECTIVES: This study examines the concept of clinical endocannabinoid deficiency (CECD), and the prospect that it could underlie the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis.
METHODS: Available literature was reviewed, and literature searches pursued via the National Library of Medicine database and other resources.
RESULTS: Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is now conceived as a central sensitization state with secondary hyperalgesia. Cannabinoids have similarly demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS and related disorders. The past and potential clinical utility of cannabis-based medicines in their treatment is discussed, as are further suggestions for experimental investigation of CECD via CSF examination and neuro-imaging.
CONCLUSION: Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines....
Russo E. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 2004 Apr; 25(1-2): 31-39
: Endogenous cannabinoids (endocannabinoids) and their cannabinoid CB1 and CB2 receptors, are present from the early stages of gestation and play a number of vital roles for the developing organism. Although most of these data are collected from animal studies, a role for cannabinoid receptors in the developing human brain has been suggested, based on the detection of "atypically" distributed CB1 receptors in several neural pathways of the fetal brain. In addition, a role for the endocannabinoid system for the human infant is likely, since the endocannabinoid 2-arachidonoyl glycerol has been detected in human milk. Animal research indicates that the Endocannabinoid-CB1 Receptor ('ECBR') system fulfills a number of roles in the developing organism: 1. embryonal implantation (requires a temporary and localized reduction in anandamide); 2. in neural development (by the transient presence of CB1 receptors in white matter areas of the nervous system); 3. as a neuroprotectant (anandamide protects the developing brain from trauma-induced neuronal loss); 4. in the initiation of suckling in the newborn (where activation of the CB1 receptors in the neonatal brain is critical for survival). 5. In addition, subtle but definite deficiencies have been described in memory, motor and addictive behaviors and in higher cognitive ('executive') function in the human offspring as result of prenatal exposure to marihuana. Therefore, the endocanabinoid-CB1 receptor system may play a role in the development of structures which control these functions, including the nigrostriatal pathway and the prefrontal cortex. From the multitude of roles of the endocannabinoids and their receptors in the developing organism, there are two distinct stages of development, during which proper functioning of the endocannabinoid system seems to be critical for survival: embryonal implantation and neonatal milk sucking. We propose that a dysfunctional Endocannabinoid-CB1 Receptor system in infants with growth failure resulting from an inability to ingest food, may resolve the enigma of "non-organic failure-to-thrive" (NOFTT). Developmental observations suggest further that CB1 receptors develop only gradually during the postnatal period, which correlates with an insensitivity to the psychoactive effects of cannabinoid treatment in the young organism. Therefore, it is suggested that children may respond positively to medicinal applications of cannabinoids without undesirable central effects. Excellent clinical results have previously been reported in pediatric oncology and in case studies of children with severe neurological disease or brain trauma. We suggest cannabinoid treatment for children or young adults with cystic fibrosis in order to achieve an improvement of their health condition including improved food intake and reduced inflammatory exacerbations....
Fride E. The endocannabinoid-CB receptor system: Importance for development and in pediatric disease. Neuro Endocrinol Lett. 2004 Apr; 25(1-2): 24-30
: Dronabinol (Delta 9-tetrahydocannabinol, THC), the main source of the pharmacological effects caused by the use of cannabis, is an agonist to both the CB1 and the CB2 subtype of cannabinoid receptors. It is available on prescription in several countries. The non-psychotropic cannabidiol (CBD), some analogues of natural cannabinoids and their metabolites, antagonists at the cannabinoid receptors and modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoid receptors are distributed in the central nervous system and many peripheral tissues including spleen, leukocytes; reproductive, urinary and gastrointestinal tracts; endocrine glands, arteries and heart. Five endogenous cannabinoids have been detected so far, of whom anandamide and 2-arachidonylglycerol are best characterized. There is evidence that besides the two cannabinoid receptor subtypes cloned so far additional cannabinoid receptor subtypes and vanilloid receptors are involved in the complex physiological functions of the cannabinoid system that include motor coordination, memory procession, control of appetite, pain modulation and neuroprotection. Strategies to modulate their activity include inhibition of re-uptake into cells and inhibition of their degradation to increase concentration and duration of action. Properties of cannabinoids that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, anti-inflammation, anti-allergic effects, sedation, improvement of mood, stimulation of appetite, anti-emesis, lowering of intraocular pressure, bronchodilation, neuroprotection and antineoplastic effects....
Grotenhermen F. Pharmacology of cannabinoids. Neuro Endocrinol Lett. 2004 Apr; 25(1-2): 14-23
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Mechoulam R. The promise of advances in the field of endocannabinoids. Neuro Endocrinol Lett. 2004 Apr; 25(1-2): 11-12
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Ruttkay-Nedecký I. A concise survey of L. Dérer's work on biorhythmicity. Neuro Endocrinol Lett. 2003 Dec; 24(6): 11-12