Category Archives: Attention-Deficit/Hyperactivity Disorder (ADHD)

The endocannabinoid system and its therapeutic exploitation.

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“The term ‘endocannabinoid’ – originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands – now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs. We explore the conditions under which the potential of targeting the endocannabinoid system might be realized in the years to come.”  http://www.ncbi.nlm.nih.gov/pubmed/15340387

http://www.nature.com/nrd/journal/v3/n9/full/nrd1495.html

From cannabis to the endocannabinoid system: refocussing attention on potential clinical benefits.

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“Cannabis sativa is one of the oldest herbal remedies known to man. Over the past four thousand years, it has been used for the treatment of numerous diseases but due to its psychoactive properties, its current medicinal usage is highly restricted. In this review, we seek to highlight advances made over the last forty years in the understanding of the mechanisms responsible for the effects of cannabis on the human body and how these can potentially be utilized in clinical practice. During this time, the primary active ingredients in cannabis have been isolated, specific cannabinoid receptors have been discovered and at least five endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified. Together, these form the framework of a complex endocannabinoid signalling system that has widespread distribution in the body and plays a role in regulating numerous physiological processes within the body. Cannabinoid ligands are therefore thought to display considerable therapeutic potential and the drive to develop compounds that can be targeted to specific neuronal systems at low enough doses so as to eliminate cognitive side effects remains the ‘holy grail’ of endocannabinoid research.”

http://www.ncbi.nlm.nih.gov/pubmed/23155985

Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.

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Philosophical Transactions of the Royal Society B: Biological Sciences: 367 (1607)

“Human tissues express cannabinoid CB(1) and CB(2) receptors that can be activated by endogenously released ‘endocannabinoids’ or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB(1)/CB(2) receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Δ(9)-tetrahydrocannabinol (Δ(9)-THC)) and Sativex (Δ(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB(2) receptors, and/or (v) adjunctive ‘multi-targeting’.”  https://www.ncbi.nlm.nih.gov/pubmed/23108552

“Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities”  http://rstb.royalsocietypublishing.org/content/367/1607/3353.long

The endocannabinoid system in peripheral lymphocytes as a mirror of neuroinflammatory diseases.

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Abstract

“During immuno-mediated attack of the brain, activation of endocannabinoids represents a protective mechanism, aimed at reducing both neurodegenerative and inflammatory damage through various and partially converging mechanisms that involve neuronal and immune cells. Here, we review the main alterations of the endocannabinoid system (ECS) within the central nervous system and in peripheral blood mononuclear cells, in order to discuss the intriguing observation that elements of the peripheral ECS mirror central dysfunctions of endocannabinoid signaling. As a consequence, elements of blood ECS might serve as novel, non-invasive diagnostic tools of several neurological disorders, and targeting the ECS might be useful for therapeutic purposes. In addition, we discuss the appealing working hypothesis that the presence of type-1 cannabinoid receptors on the luminal side, and that of type-2 cannabinoid receptors on the abluminal side of the blood-brain barrier, could drive a unidirectional transport of AEA in the luminal –> abluminal direction (i.e., from blood to brain), thus implying that blood may be a reservoir of AEA for the brain. On this basis, it can be expected that an unbalance of the endogenous tone of AEA in the blood may sustain a similar unbalance of its level within the brain, as demonstrated in Huntington’s disease, Parkinson’s disease, multiple sclerosis, attention-deficit/hyperactivity disorder, schizophrenia, depression and headache.”

http://www.ncbi.nlm.nih.gov/pubmed/18781987

Major Health Benefits of Medical Cannabis

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“The benefits of medical marijuana plant are extensive, pervasive, and long-standing. Because of the way the cannabis impacts the Autonomic Nervous System which develops the breath and relaxes the body, prospective for health and curative characteristics are huge. Some of the major health benefits of medical cannabis are explained below:

Treats Migraines

Cannabis healing has been very effective in the treatment of migraine headaches. Migraine headaches are vascular in source and are often preceded by an air characterized by nausea, flashes of light, faintness or photosensitivity.

Slows Down Tumor Growth

Studies have shown that cannabis help in slow down the facsimile and slow down the production of cancer cells in body. It is also a natural antiemetic, which makes it effectual in plummeting the nausea and vomiting related with chemo and radiation therapies. So taking marijuana slows down the tumor growth too.

Relieves Symptoms of Chronic Diseases

Marijuana is one of the best natural pain relievers that can help sufferers of chronic pain live more relaxed lives. The side effects are often much less severe than the other common pain medications.

Prevents Alzheimer’s

Cannabis reduces the occurrence of depression in Alzheimer’s patients, which can help patients to keep up a higher level of brain function. That is a powerful way to keep patients performance for a longer time after the first onset of Alzheimer’s disease.

Treats Glaucoma

Some strains of this medicinal plant have been shown that, they are potentially decreasing the force that glaucoma can place on the optic nerve; thereby the patients can easily cut the critical condition by smoking or taking the marijuana edibles or medicines.

Prevents Seizures

Seizure is a kind of epilepsy which almost affects more than 2 millions of Americans and 30 millions of people worldwide. Epilepsy is a condition when some of the brain cells become abnormally excitable. People using marijuana to control epilepsy should be alert when there is any removal of any tablets which controls seizures may leave you more susceptible to the patient. Marijuana is no exception. Patients with epilepsy are advised to exercise caution when using oral THC because there is no enough sufficient knowledge about the convulsive or anti-convulsive properties of the single compound.

For ADD and ADHD

Many people who endure with ADD and/or ADHD find that medical cannabis recovers their knack to hub and their level of recital with definite tasks. There are no clinical studies on humans but there are some beginner studies have done on animals that point to less hyperactivity and impulsivity with the use of cannabinoids (the active medicines in cannabis).

Relieve PMS

Millions of women have an illness on Premenstrual Syndrome (PMS). PMS includes the symptoms of headaches, abdominal cramps, bloating and fluid retention. Many women report that they have tried several different medications but none as give any significant relief like Medical Marijuana. Cannabis medicine has shown to give symptomatic relief from all the unpleasant symptoms of PMS.

Calm Those With Tourette’s and OCD

Several psychological disorders have been known to be related with the medical benefits of marijuana as well. Taking weed of prescribed amount on regular basis can slow down the tics for those who are suffering from Tourette’s syndrome and Obsessive Compulsive Disorder (OCD). Yes some of the qualities in marijuana plant help the patient to calm themselves when any creation of intrusive thoughts which produces fear, uneasiness and abnormal behaviors.”

http://www.herbalmission.org/major-health-benefits-of-medical-cannabis.php

The therapeutic potential of novel cannabinoid receptors.

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“Cannabinoids produce a plethora of biological effects, including the modulation of neuronal activity through the activation of CB(1) receptors and of immune responses through the activation of CB(2) receptors. The selective targeting of either of these two receptor subtypes has clear therapeutic value. Recent evidence indicates that some of the cannabinomimetic effects previously thought to be produced through CB(1) and/or CB(2) receptors, be they on neuronal activity, on the vasculature tone or immune responses, still persist despite the pharmacological blockade or genetic ablation of CB(1) and/or CB(2) receptors. This suggests that additional cannabinoid and cannabinoid-like receptors exist. Here we will review this evidence in the context of their therapeutic value and discuss their true belonging to the endocannabinoid signaling system.”  http://www.ncbi.nlm.nih.gov/pubmed/19248809

“The therapeutic potential of novel cannabinoid receptors”  http://www.sciencedirect.com/science/article/pii/S0163725809000266

Cannabinoid receptors in brain: pharmacogenetics, neuropharmacology, neurotoxicology, and potential therapeutic applications.

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“Much progress has been achieved in cannabinoid research. A major breakthrough in marijuana-cannabinoid research has been the discovery of a previously unknown but elaborate endogenous endocannabinoid system (ECS), complete with endocannabinoids and enzymes for their biosynthesis and degradation with genes encoding two distinct cannabinoid (CB1 and CB2) receptors (CBRs) that are activated by endocannabinoids, cannabinoids, and marijuana use.

Physical and genetic localization of the CBR genes CNR1 and CNR2 have been mapped to chromosome 6 and 1, respectively. A number of variations in CBR genes have been associated with human disorders including osteoporosis, attention deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), drug dependency, obesity, and depression. Other family of lipid receptors including vanilloid (VR1) and lysophosphatidic acid (LPA) receptors appear to be related to the CBRs at the phylogenetic level. The ubiquitous abundance and differential distribution of the ECS in the human body and brain along with the coupling to many signal transduction pathways may explain the effects in most biological system and the myriad behavioral effects associated with smoking marijuana. The neuropharmacological and neuroprotective features of phytocannabinoids and endocannabinoid associated neurogenesis have revealed roles for the use of cannabinoids in neurodegenerative pathologies with less neurotoxicity. The remarkable progress in understanding the biological actions of marijuana and cannabinoids have provided much richer results than previously appreciated cannabinoid genomics and raised a number of critical issues on the molecular mechanisms of cannabinoid induced behavioral and biochemical alterations. These advances will allow specific therapeutic targeting of the different components of the ECS in health and disease.

 This review focuses on these recent advances in cannabinoid genomics and the surprising new fundamental roles that the ECS plays in the retrograde signaling associated with cannabinoid inhibition of neurotransmitter release to the genetic basis of the effects of marijuana use and pharmacotherpeutic applications and limitations. Much evidence is provided for the complex CNR1 and CNR2 gene structures and their associated regulatory elements. Thus, understanding the ECS in the human body and brain will contribute to elucidating this natural regulatory mechanism in health and disease.”

http://www.ncbi.nlm.nih.gov/pubmed/19897083

The endocannabinoid system: physiology and pharmacology.

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Abstract

“The endogenous cannabinoid system is an ubiquitous lipid signalling system that appeared early in evolution and which has important regulatory functions throughout the body in all vertebrates. The main endocannabinoids (endogenous cannabis-like substances) are small molecules derived from arachidonic acid, anandamide (arachidonoylethanolamide) and 2-arachidonoylglycerol. They bind to a family of G-protein-coupled receptors, of which the cannabinoid CB(1) receptor is densely distributed in areas of the brain related to motor control, cognition, emotional responses, motivated behaviour and homeostasis. Outside the brain, the endocannabinoid system is one of the crucial modulators of the autonomic nervous system, the immune system and microcirculation. Endocannabinoids are released upon demand from lipid precursors in a receptor-dependent manner and serve as retrograde signalling messengers in GABAergic and glutamatergic synapses, as well as modulators of postsynaptic transmission, interacting with other neurotransmitters, including dopamine. Endocannabinoids are transported into cells by a specific uptake system and degraded by two well-characterized enzymes, the fatty acid amide hydrolase and the monoacylglycerol lipase. Recent pharmacological advances have led to the synthesis of cannabinoid receptor agonists and antagonists, anandamide uptake blockers and potent, selective inhibitors of endocannabinoid degradation. These new tools have enabled the study of the physiological roles played by the endocannabinoids and have opened up new strategies in the treatment of pain, obesity, neurological diseases including multiple sclerosis, emotional disturbances such as anxiety and other psychiatric disorders including drug addiction. Recent advances have specifically linked the endogenous cannabinoid system to alcoholism, and cannabinoid receptor antagonism now emerges as a promising therapeutic alternative for alcohol dependence and relapse.”

CONCLUSION

“Since the discovery of anandamide, the increasing information on the physiological roles played by the endogenous cannabinoid system and its contribution to pathology have led to this signalling system becoming more important in neurobiology. The intense pharmacological research based on this information has yielded, in a very short time, potent, selective drugs targeting the endogenous cannabinoid system that have opened up new avenues for the understanding and treatment of major diseases including cancer, pain, neurodegeneration, anxiety and addiction. This is a very promising starting point for a new age that takes over from the ancient use of Cannabis as a medicine. Now is the time for clinical trials aimed at evaluating the efficacy of cannabinoid drugs in disorders lacking effective therapeutic approaches, such as alcoholism.”

http://alcalc.oxfordjournals.org/content/40/1/2.long