A Vaccine To Crack The Cocaine Bugs

Years ago I heard the song "Snowblind" by our one and only Ozzy Osbourne, from his album Speak of the Devil. The meaning of the song is two-fold. Firstly, people in a snowy landscape face such intense reflection of sunlight, that they might go blind. They wear special goggles to restrict sunlight, so that it doesn't burn the macular portion of the retina (the part where light rays are usually focussed.)

Another interpretation of this song could be this that someone gets blinded by the actions of cocaine (also known as snow or crack). That's precisely what Ozzy meant.

Cocaine, an alkaloid obtained from the leaves of Erythroxylum coca, produces euphoria (a feeling of elation) by increasing the amount of dopamine in the brain. Dopamine is normally liberated in brain structures such as the basal ganglia. After it has been liberated and it has finished its action, residual dopamine in the synapse is 'cleared' by dopamine transporters in a process called reuptake. These transporter proteins packs these chemicals back into where it came from (into the axon, as is shown in the picture), hence re-uptake. Cocaine binds with these transporters in such a tight embrace that these transporters fail to function: that is, cocaine functions as dopamine reuptake inhibitor. Dopamine, the pleasure (reward) chemical, which now accumulates in the synapse, gives the person a good kick. Frequent use of it through inhalation or injection (as these routes lead to faster absorption) gives them the feeling of an orgasm, which users refer to as 'rush'. Nucleus Accumbens, an area in the brain, supposedly 'reinforces' this addiction.

So isn't there a way out? Will they have to go on scratching their skin (cocaine produces a typical dermal itching sensation, Magnan sign or the cocaine bugs, where the patient feels as if insects are crawling under their skin)? Scientists are now on the verge of producing a vaccine (TA-CD Vaccine), which not only will cure their addiction but also decrease the severity of its 'withdrawal symptoms'. The human immune system can not recognize cocaine since it is a small molecule. Hence, they are combining parts of inactivated cocaine molecule with inactivated cholera proteins. After you give them a 'shot' of this vaccine, the immune system will now recognize the combine and produce antibodies against coke. Next time cocaine is consumed, the antibodies in the blood will combine with the cocaine molecule and prevent it from reaching the brain, its main seat of action. The vaccine is currently undergoing clinical trials.

Not only cocaine, vaccine is being developed against methamphetamine too (N-methyl amphetamine), another drug of abuse. The mechanism of action of the vaccine is the same. These drugs are still used in clinical practice: cocaine as an anesthetic; methamphetamine analogs, methyl phenidate (RITALIN) and pemoline are widely used in attention deficit hyperactivity disorder or ADHD. But keeping in mind their abuse potential, these drugs should be prescribed weighing the risk-benefit ratio. And when an addiction has already developed, we must cure it, may be by using a vaccine like this.

Last modified: 13 Jul 2009
Reference: hyper-links, unless specifically mentioned

Quitting Tobacco: An Easy Way For The Blind To Go!

Its really hard to quit smoking. So much so, that its quitting has been compared to that of cocaine or even heroin. First and foremost, a resolute and firm mental preparation is required. Once a decision has been made, it can be set forth into action. However, there are certain drugs which make quitting easier. For example, nicotine may be supplemented as a gum, nasal spray or as a dermal patch, so that a small amount of it will be released and weaning off may be easier (guess you remember, fight fire with fire).

Apart from that, clonidine, bupropion, varenicline (Chantix) and many other drugs have been tried. Bupropion (Wellbutrin, Zyban) is a dopamine and norepinephrine reuptake inhibitor (DNRI). Dopamine, the reward chemical, and norepinephrine are secreted by nerve terminals in the brain. They then exert their effects, till they are metabolized or they are recalled back (reuptake) to the originating cells. Thus, actions cease once they are uptaken by the secreting cells themselves. Bupropion, by preventing their (dopamine and nor-epinephrine) reuptake, lets them remain in the synapse for alonger time, thereby making the person feel the high, even while they are not on tobacco. Varenicline, on the other hand, acts as a partial agonist at nACh (nicotinic acetyl cholinergic) receptors. A partial agonist is one substance (ligand) that can bind with a receptor and can elicit an action, though milder. Thus when varenicline is given, it stimulates the same nACh receptor that nicotine of tobacco smoke used to bind and stimulate. Thus, the craze for the crazy puff is gone. But, no matter what therapy you are on, as long as you are resolute, you can win, and nothing else matters!!

Recently, a vaccine is being developed that would bind nicotine and thus will not allow nicotine to bind to the nicotinic receptors. This is expected to wean away smokers since they will no longer be able to get the 'kick'. Normally a vaccine is given to boost immunity to pathogens. Here however its properties will be exploited for another noble purpose.

N.B. Recently (July 1, 2009) the US Food and Drug Administration (FDA) has announced that bupropion and varenicline manufacturers must carry a 'boxed warning' in their labels, that use of these drugs has been associated with serious neuropsychiatric events. They can cause symptoms ranging from mood changes to suicidal tendencies, hostilities and agitation. Whether they were the effects of nicotine withdrwal or the effects of the drugs themselves were not clear.

However, the site concluded with the following advice: "Any adverse events associated with varenicline or bupropion should be communicated to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787."

Last updated: 2nd July 2009