ISOL-IsoDerm-Direct Effect Therapy. POTENTIAL OF DIRECT EFFECTSTM TOPICAL CANNABINOID THERAPY
A major shortcoming in cannabinoid therapy is its potential for undesirable side effects. Of particular concern is in children with intractable epilepsy, exposing developing brains to unknown long-term effects of systemic cannabinoids. Direct Effects Topical Drug Delivery provides a potential solution.17-19
In view of the beneficial effects of CBD in various neuropathic and psychiatric conditions, studies were performed with Direct Effects topical delivery of CBD applied as cream to the back of the neck (BON) and other areas of the spine and peripheral nerves, as appropriate. Intent is modulating neural afferents to affect efferents as relief of pathologic symptoms. BON is unique considering the magnitude of available afferent input available through skin-free nerve-endings.
Direct Effects is a means to deliver CNS-active drugs, including cannabinoids, through activating neurochemical receptors existing on free nerve-endings. There exist hundreds of thousands to millions of free nerve-endings below the skin surface (stratum corneum) at the upper posterior cervical region, BON. Cervical nerve roots, C1-C4, and occasionally C5 provide direct neural connections to afferent components of the trigeminal, vagal, and cervical sympathetic nerve systems inputting CNS. No other location has such a magnitude of afferent neural input accessible through skin nerve-endings.
Modulated CNS efferents responding to afferent activation results in improvement of symptoms of brain and spinal cord dysfunction. In using direct nerve pathways without restrictions of blood flow and the blood-brain-barrier, therapeutic onset is greatly reduced, and systemic side effects are avoided.
Direct Effects therapy has rapid therapeutic onset of action of less than 10 to 15 minutes, and maximal benefit within 30 minutes. Therapeutic effect is 4 to 12 hours or more, depending on condition and severity.
Direct Effects drug delivery has been used with success with sumatriptan in migraines, apomorphine in Parkinson’s disease and related movement disorders, and tizanidine in muscle spasm and tension headache. US and international patents have been granted in these areas. In view of superiority of topical delivery as compared to systemic use as oral tablet, injection, nasal spray, or transdermal patch, it was believed cannabinoids could be similarly applied as a cream to treat symptoms of neuropathic conditions. This was of particular interest in view of known systemic side effects of inhaled and ingested cannabinoids.
CLINICAL RESULTS WITH TOPICAL CBD
In a study of 88 patients, topical CBD was found effective in treating the symptoms of the following conditions:
-Seizures
-Encephalopathy, including lethargy, inattention, and cognition
-Spasticity
-Weakness
-Pain, including radiculopathy and shingles
-Numbness
-Anxiety and other mood disorders, including PTSD
-Hypertension
-Parkinsons disease
-Insomnia
-Bells palsy and facial nerve dysfunction
-Trigeminal Neuralgia
-Hemi-facial spasm
-Autism/Asperger’s
-Attention Deficit Disorder & Hyperactivity
-Social Isolation
-Occipital Neuralgia
-TMJ dysfunction-related symptoms
-Cognitive problems, including memory disturbance
-Peripheral Neuropathy
-Essential Tremor
Breakdown of major clinical categories:
-34 subjects with seizures, encephalopathy, and spasticity responded to topical CBD therapy at BON
-13 subjects with headaches and neck pain benefitted from topical CBD application to BON
-16 subjects with back/spin and extremity pain, fibromyalgia achieved relief with topical CBD applied at BON and at other appropriate spinal and extremity/peripheral locations
-6 subjects with Parkinson’s, tremors, movement disorders responded to topical CBD treatment at the BON
-Dosing frequency ranged from once daily to 3x/day depending on chronicity andseverity of condition; and individual response to topical CBD therapy (each 1-g dose
contained 1.5 to 3% CBD)
-Duration of treatment with topical CBD ranged from several days to as needed/prn for relief of episodically symptomatic disease states; to months of continued daily therapy for chronic conditions, such as epilepsy, Parkinsons/movement disorders, and spasticity with permanent symptoms or impairments
-The longest continuous use period in the aforementioned patients was 6 months of 2x/day for a 7-year-old male with absence seizures; however, the longest period of continued use for any patient with topical CBD is18 months for intractable epilepsy (refer to Figures 5a and 5b showing attenuation of absence seizure focus, 3/second spike and slow wave complexes, with topical CBD therapy at BON)
-No systemic side-effects were observed or reported in any subject exposed to topical CBD. Several patients (less than 10%) reported itching or slight rash at CBD cream application site. The formulation was changed in these cases.
-In some patients on long-term medications, some previous medications were lowered or discontinued as a result of clinical improvement from topical CBD
CONCLUSION
Topical CBD is beneficial in treating symptoms of a number of neuropathic and psychiatric conditions. Individual clinical response varied depending on condition treated and on severity and longevity of symptoms. Topical CBD therapy was overall well tolerated.
In a few instances, topical CBD treatments rendered subjects free of symptoms that had been present for some time. This suggests “neural reprograming” and re-establishment of homeostasis. This possibility of disease modification and pathologic process reversal deserves further investigation. It places cannabinoids in a unique category of therapeutic compounds. Studies in rat models of MS have suggested such phenomena with remyelination of de-myelinated areas with CBD therapy.
Some conditions were more responsive to topical cannabinoid therapy than others. Seizure disorders and epilepsy responded most robustly to topical CBD application at BON. Complete seizure freedom was achieved in a number of patients with previous intractable epilepsy on multiple drug regimen.
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Ronald Aung-Din, MD, practices General Neurology and Neuropsychiatry in Sarasota, FL. Through affiliation with Lovelace Research Institute, Albuquerque, NM, he has functioned as Principal Neurology Investigator in over 60 clinical trials, helping bring to market drugs in Epilepsy, Multiple Sclerosis, Neuropathic Pain, and Parkinson's Disease. In May 2009, Dr. Aung-Din founded AfGin Pharma, LLC, a research and development biopharmaceutical company dedicated to Direct Effects Topical Neuro-Affective Therapy, a novel non-systemic delivery of neuro-active compounds he discovered useful in treating neurological and neuropsychiatric conditions. The therapy is unique in that rapid (within 10-30 mins) therapeutic results are achieved without usual systemic side effects and drug interactions. To date, 7 patents relating to the technology have been granted by USPTO and the EU and Australian patent offices, with others filed and pending.