Molecular Mechanisms of Methamphetamine Induced-Neurotoxicity

March 21, 2015

Methamphetamine is a stimulant that is also highly soluble in water and affects the CNS most. Categorically it fits in the group of synthetic drugs chemically related to amphetamine but it has more adverse effects on the Central nervous system than the parent compound. Abuse of these illegal psychostimulants has become an international public health problem, with an estimated 14 to 52 million amphetamine-type stimulant users worldwide, exceeding the total number of cocaine abusers and second only to the number of cannabis abusers. This number has continued to rise in spite of the fact that much has been done to publicize the adverse effects these amphetamine related stimulants are linked to. Meth or speed as known in stimulant use circles exists in different forms like powder, tablets and capsules. It can also be found in a purer crystalline form.

It’s dangerous why is it used?

Just like most stimulants or drugs that are known to induce euphoric feelings, methamphetamine is also taken for similar reasons for example; to induce euphoric feelings, increased sense of well-being, increase energy and to calm anxiety. Being a powerful drug its effects are felt immediately after the use but these effects can last for long hours. They may be accompanied by acute adverse effects such as increased blood pressure and heart rate, which may cause irreversible damage to blood vessels in the brain, resulting in cerebrovascular accidents, stroke, and death. Methamphetamine also produces hyperthermia, pupil dilation, flushing, tremors, trismus and bruxism, muscle tension, loss of appetite or anorexia, and loss of pleasure in food intake which further leads to deterioration of the user’s health.

methamphetamine

Effects of Methamphetamine

Being an addictive drug, after a prolonged use the users may develop tolerance. It’s most common symptoms after a prolonged use include; temporomandibular joint syndrome, dental erosion, and myofacial pain. Long-term use also produces lack of appetite, weight loss, accelerated aging, nose-bleeding problems, nonhealing wounds, tooth decay and fracture known as “Meth mouth”. Psychiatric symptoms include anxiety, depression, increased aggression, social isolation, psychosis, mood disturbances, and psychomotor dysfunction. Long periods of high consumption can cause paranoid psychosis. Other symptoms of chronic methamphetamine use may also include; deficits in attention, working memory, and decision making. Most addicts are stuck in the use of meth as a result of the withdrawal symptoms which include the following; irritability, fatigue, impaired social functioning, and intense craving for the drug. Researchers have given evidence that the negative neuropsychiatric consequences of methamphetamine abuse are due, at least in part, to drug-induced neuropathological changes in the brain. Although the exact molecular mechanisms of neuronal body loss are not known, there is evidence to suggest the coexistence of different types of cell death, including apoptosis and necrosis ; indicated by the morphology of neurons stained with hematoxylin-eosin. Growing evidence exhibits that methamphetamine and MDMA induce an increase in lipid peroxidation and DNA oxidation as well as increased levels of oxidative stress markers such as hydroxyl radical producing neurotoxicity. Methamphetamine increases expression of inducible nitric oxide synthase (nNOS)/ neuronal nitric oxide synthase (iNOS ) indicating increased synthesis of neuronal nitric oxide, which combines with superoxide radicals to form peroxynitrite which is a strong oxidant and a major neurotoxin . Induction of nNOS/iNOS by methamphetamine or MDMA constitutes part of the mechanism of methamphetamine damage, as selective inhibition or genetic inactivation of nNOS and overexpression of cupper zinc superoxide dismutase (CuZnSOD), an enzyme that catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide, prevent methamphetamine neurotoxicity . Even though methamphetamine increases iNOS expression in the striatum , there is no basis for supposing the involvement of glial nitric oxide in methamphetamine-induced toxicity, but it is interesting to note that mice deficient in iNOS have increased resistance to methamphetamine-induced dopamine neuron damage.

methamphetamine

The neurotoxic effects of methamphetamine on the dopaminergic system are accompanied by activation of astroglia and microglia in the same areas being strongest in the striatum, the area with biggest toxicity. Glial cells are not activated in the nucleus accumbens, which is not much damaged . In mice, glial activation in striatum and in substantia nigra occurs shortly after methamphetamine administration, as indicated by a significant increase in Mac-1 ;a marker of reactive microglia 24 hours after methamphetamine exposure and prominent increases in GFAP ; a marker of reactive gliosis in response to injury occur within a week after treatment . The extent of these glial reactions correlates with the observed severity of neurotoxicity.

The dopaminergic system is also involved in this toxicity, as demonstrated in various mutant mice in which inactivation of dopamine transport, dopamine D1 receptors or D2 receptors affords a significant protection against methamphetamine toxicity. Administration of THC prevents dopaminergic toxicity after MDMA, a similar amphetamine derivative to methamphetamine, by CB1 receptor stimulation which is present in striatal medium spiny neurons. All these receptors are involved in different aspects of learning processes that became affected by the chronic use of methamphetamine or MDMA.

Finally, Drug abuse, addiction and independence are problems that people grapple with every day. These problems need to be treated effectively through integrative medicine. Dr. Dalal Akoury (MD) is an expert at this. Call her on (843) 213-1480 for help.

Molecular Mechanisms of Methamphetamine Induced-Neurotoxicity

Vitamin C and K3 in Cancer Treatment

August 19, 2014

Research Shows That Vitamin C and K3 Are Effective In Fighting Cancer

Cancer has put doctors on ‘motion’ never resting always trying to come up with better ways of cancer treatment. Maybe the more alternatives the better the treatment! Integrative cancer doctors have had much more alternatives to cancer treatments and some alternatives are added every now and then and this situation is not about to end as doctors are still working day and night to give us the best cancer treatment alternatives. The availability of many cancer treatment alternatives therefore requires that every cancer patient should know the kind of treatment that suits his case but of course with help from an integrative cancer doctor. There are naturopathic cancer treatments that have gained recognition for their whole person healing intent and while chemotherapy has been negatively thought of by many patients some improvements have been done to improve the effectiveness of chemotherapy by improving drug uptake by the cancerous cells while reducing chemotherapy drug resistance by the cancer cells which is normally a problem. With these improvements like the use of IPT among others, even the patients are not afraid of it anymore as the side effects are minimal. Some of the cancer treatment alternatives that we have today include the use of vitamin C and vitamin k3 in cancer treatment.

Vitamin C in treating cancer? I know it might be a problem to accept that vitamin C can be used in cancer treatment because you might have been told never to use vitamin C while undergoing chemotherapy. This is because vitamin C is an antioxidant which to many cancer doctors is supposed to interfere with chemotherapy treatment but what most doctors have not known is that vitamin C when used in high doses and given intravenously can be very helpful in cancer treatment as it becomes a pro-oxidant which leads to cancer cell death.

There are studies that have supported the use vitamin c in high doses and given intravenously in cancer treatment. In two Scottish studies, terminal cancer patients given intravenous vitamin C at 10 g per day showed longer survival times than historical controls. Apparently this is not the only study that has been done on vitamin C and its ability to kill cancerous cell. Another study; A Japanese study showed similar results and this are very encouraging. However at mayo clinic a double blinded study of the same using oral vitamin C supplementation did not show any benefit in fighting cancer.

Researchers have shown that oral vitamin C supplementation cannot work well in fighting cancer as it doesn’t produce plasma ascorbate levels that are sufficient enough to kill tumor cells directly. This is the reason why doctors recommend the use of vitamin C intravenously.

When vitamin C is given intravenously, they turn into hydrogen peroxide inside the cancerous cells which then causes the cells to die by poisoning them. This does not affect the healthy body cells negatively since unlike the cancerous cells the healthy body cells have the ability to fight the damage that is caused by the hydrogen peroxide. This allows for selective killing of the cancerous cells while the healthy body cells are left without harm.

Currently there is an ongoing study of Vitamin C by the National Institutes of Health (NIH) as an adjunctive therapy for cancer. In their 2008 report, the National Institutes of Health stated that the vitamin C when used in high doses reduced the rate of tumor growth by 50 percent in mice that were infected with brain cancer, ovarian cancer and pancreatic cancer. The researchers revealed that Vitamin C got its high anticancer effect from its ability to produce hydrogen peroxide inside the cancer cells killing them outright. Even in this experiment the healthy body cells were not affected by the poisonous effect of the vitamin C.

Vitamin C More effective when Combined with Vitamin K3 in Cancer

Researchers have proved that the cell killing abilities of sodium ascorbate or other vitamin C and combination of 2-methyl-1, 4-naphthoquinone K3 is highly increased. These have been tested on human ovarian cancer, breast cancer, endometrial cancer and skin cancer cells. These vitamins can work even when given separately. When given separately they have an antigrowth effect on the tumors but must be highly concentrated. When both the vitamins were used as a single mixture, they demonstrated a synergistic inhibition of cell growth by up to 10 – 50 times in lower concentrations. The best part of this combination is that it does not affect the healthy body cells at all. The researchers also observed that when vitamin C and Vitamin K3 inhibited metastasis.

The mechanism by which vitamin C and vitamin K3 work in killing cancer is called autoschizic cell death. This is a novel type of cell death characterized by exaggerated cell membrane damage and progressive loss of cell contents. A process during which the nucleus becomes smaller, cell size decreases one-half to one-third of its original size. Co-administration of sodium ascorbate and K3 induces a cell cycle block on cancer cells making it harder for them to grow and divide. This is called a G1/S block. The intravenous vitamin cocktail containing sodium ascorbate and vitamin K3 diminishes cancer cell DNA synthesis, increases hydrogen peroxide production, and decreases cancer cell intracellular antioxidant defenses thereby killing them easily.

Dr. Dalal Akoury (MD) is an experienced integrative cancer doctor that has helped many cancer patients in their fight against the disease. She has worked hard not only in treating the disease but also in availing informational support to cancer patients at Awaremed which has become a place called home for many cancer patients. Call on her now and get help on cancer.