Pharmacology

The hypoglycemic activity of alkaloids isolated from Catharanthus roseus have been studied pharmacologically and a natural remedy derived from the plant has been marketed under the proprietary name Vinculin® as a treatment for diabetes.
Alcoholic whole plant extracts at high dose (500 mg/kg) exhibited significant antihyperglycemic activity and has absence of acute toxicity. The extract effectively reverses the changes in the blood sugar level and the beta-cell population. The exact phytoconstituents responsible for the antidiabetic effect are not known yet.

Catharanthus  roseus
Don,  also known  as  Vinca,  which  is  used  by  the  population  in Madagascar  in  treating  diabetes.

Addictions, even as they resemble normal human yearnings, are more about desire than attainment. In the addicted mode, the emotional charge is in the pursuit and the acquisition of the desired object, not in the possession and enjoyment of it. The greatest pleasure is in the momentary satisfaction of yearning.
The fundamental addiction is to the fleeting experience of not being addicted. The addict craves the absence of the craving state. For a brief moment he’s liberated from emptiness, from boredom, from lack of meaning, from yearning, from being driven or from pain. He is free. His enslavement to the external-the substance, the object or the activity-consists of the impossibility, in his mind, of finding within himself the freedom from longing or irritability. "I want nothing and fear nothing," said Zorba the Greek. "I'm free." There are not many Zorbas amongst us.

In the cloudy swirl of misleading ideas surrounding public discussion of addiction, there's one that stands out: the misconception that drug taking by itself will lead to addiction – in other words, that the cause of addiction resides in the power of the drug over the human brain. It is one of the bedrock fables sustaining the so-called "War on Drugs." It also obscures the existence of a basic addiction process of which drugs are only one possible object, among many. Compulsive gambling, for example, is widely considered to be a form of addiction without anyone arguing that it’s caused by a deck of cards.

Heroin is considered to be a highly addictive drug--and it is, but only for a small minority of people, as the following example illustrates. It's well known that many American soldiers serving in the Vietnam War in the late 1960s and early 1970s were regular users. Along with heroin, most of these soldier addicts also used barbiturates or amphetamines or both. According to a study published in the Archives of General Psychiatry in 1975, 20 percent of the returning enlisted men met the criteria for the diagnosis of addiction while they were in Southeast Asia, whereas before they were shipped overseas fewer than 1 percent had been opiate addicts. The researchers were astonished to find that "after Vietnam, use of particular drugs and combinations of drugs decreased to near or below preservice levels." the remission (i.e., abatement or reduction of symptoms in illness or addiction) rate was 95 percent, "unheard of among narcotics addicts treated in the U.S."
"The high rates of narcotic use and addiction there were truly unlike anything prior in the American experience," the researchers concluded. "Equally dramatic was the surprisingly high remission rate after the return to the United States." These results suggested that the addiction did not arise from the heroin itself but from the needs of the men who used the drug. Otherwise most of them would have remained addicts.
The ones who persisted in heroin addiction back home were, for the most part, those with histories of unstable childhoods and previous drug use problems. What such statistics do show is that what-ever a drug's physical effects and powers, they cannot be the sole cause of addiction. Drugs, in short, do not make anyone into an addict, any more than food makes a person into a compulsive eater.

Opiates, in other words, are the chemical linchpins of the emotional apparatus in the brain that is responsible for protecting and nurturing infant life. Thus addiction to opiates like morphine and heroin arises in a brain system, that governs the most powerful emotional dynamic in human existence: the attachment instinct. Love.
Attachment is the drive for physical and emotional closeness with other people. It ensures infant survival by bonding infant to mother and mother to infant. Throughout life the attachment drive impels us to seek relationships and companionship, maintains family connections and helps build community. When endorphins lock onto opiate receptors, they trigger the chemistry of love and connection, helping us to be the social creatures we are.
It may seem puzzling that Nature would have given one class of chemicals the apparently very different tasks of alleviating physical pain, easing emotional pain, creating parent-infant bonds, maintaining social relationships and triggering feelings of intense pleasure.
In fact, the five roles are closely allied.

The ACE researchers concluded that nearly two-thirds of injection drug use can be attributed to abusive and traumatic childhood events-and keep in mind that the population they surveyed was a relatively healthy and stable one. A third or more were college graduates, and most had at least some university education. With my patients, the childhood trauma percentages would run close to one hundred. Of course, not all addicts were subjected to childhood trauma-although most hardcore injection users were-just as not all severely abused children grow up to be addicts.

Some people may think that addicts invent or exaggerate their sad stories to earn sympathy or to excuse their habits. In my experience, the opposite is the case. As a rule, they tell their life histories reluctantly, only when asked and only after trust has been established-a process that may take months, even years. Often they see no link between childhood experiences and their self-harming habits. If they speak of the connection, they do so in a distanced manner that still insulates them against the full emotional impact of what happened.
Research shows that the vast majority of physical and sexual assault victims do not spontaneously reveal their histories to their doctors or therapists. If anything, there is a tendency to forget or to deny pain. One study followed up on young girls who had
been treated in an emergency ward for proven sexual abuse. When contacted seventeen years later as adult women, 40 percent of these abuse victims either did not recall or denied the
event outright. Yet their memory was found to be intact for other incidents in their lives.
Addicts who do remember often blame themselves. "I was hit a lot," says forty-year-old Wayne, "but I asked for it. Then I made some stupid decisions." (Wayne is the one who sometimes greets me with the bluesy chant "Doctor, doctor, gimme the news …" when I’m doing my rounds between the Hastings Street hotels.) And would he hit a child, I inquire, if that child "asked for it"? Would he blame that child for "stupid decisions"? Wayne looks away. 'I don’t want to talk about that crap,' says this tough man who has worked on oil rigs and construction sites and served fifteen years in jail for armed robbery. He looks away and wipes his eyes.

"The most important finding of research into a genetic role for alcoholism is that there is no such thing as a gene for alcoholism,' writes the addiction specialist Lance Dodes, "Nor can you directly inherit alcoholism."

Compulsive shoppers experience the same mental and emotional processes when engaged in their addiction. The thinking parts of the brain go on furlough. In a brain imaging study conducted at the University of Munster, Germany, scientists found "reduced activation in brain areas associated with working memory and reasoning and, on the other hand, increased activation in areas involved in processing of emotions," when even ordinary consumers were engaged in choosing between different brand names of a given product. Under logo capitalism, it turns out, the vaunted "market forces" are largely unconscious – a feature of addiction that advertising agencies well understand. In previous work the electrical discharges of the brain circuits governing pleasure were also found to be in overdrive during shopping, in contrast to the rationality circuits. Neurologist Michael Deppe, the lead researcher, said that "the more expensive the product, the crazier the shoppers get. And when buying really expensive products, the part of the brain dealing with rational thought has reduced its activity to almost zero … The stimulation of emotional centers shows that shopping is a stress relief."

These, then, are the traits that most often underlie the addiction process: poor self-regulation; lack of basic differentiation; lack of a healthy sense of self; a sense of deficient emptiness; and impaired impulse control. The development of these traits is not mysterious or, more correctly, there is no mystery about the circumstances under which the positive qualities of self-regulation, self-worth, differentiation and impulse control fail to develop. Any gardener knows that if a plant hasn't grown, most likely the conditions were lacking. The same goes for children. The addictive personality is a personality that hasn't matured. When we come to address healing, a key question will be how to promote maturity in ourselves or in others whose early environment sabotaged healthy emotional growth.

On the surface, the differences are obvious: they support wars I oppose and justify policies I dislike. I can tell myself that we're different. Moral judgments, however, are never about the obvious: they always speak to the underlying similarities between the judge and the condemned. My judgments of others are an accurate gauge of how, beneath the surface, I feel about myself. It's only the willful blindness in me that condemns others for deluding themselves; my own selfishness that excoriates others for being self-serving; my lack of authenticity that judges falsehood in others. It is the same, I believe, for all moral judgments people cast on each other and for all vehemently held communal judgments a society visits upon its members. So it is with the harsh social attitudes toward addicts, especially hard-core drug addicts.

The War on Drugs fails, and is doomed to perpetual failure, because it is directed not against the root causes of drug addiction and of the international black market in drugs, but only against
some drug producers, traffickers and users. More fundamentally, the War is doomed because neither the methods of war nor the war metaphor itself is appropriate to a complex social problem that calls for compassion, self-searching insight and factually researched scientific understanding.
The pertinent question is not why the War on Drugs is being lost, but why it continues to be waged in the face of all the evidence against it.

How much actual freedom to choose does anyone human being possess? There’s only one answer: We cannot know. We may have our particular beliefs, spiritual or otherwise, about this aspect of human nature-about how it is or how it should be. These beliefs may strengthen our commitment to helping others find freedom or they may become harmful dogma. Either way, in the end we all have to humble ourselves and admit to a degree of uncertainty. There is no way we can peer into a brain to measure a person’s capacity for awareness and rational choice or to estimate how the relative balance of these brain-mind systems will operate when that person is stressed. There is no gauging the burden of emotional suffering weighing down one person’s psyche against another's, and there is no way to know what hidden life-enhancing experiences one person may have enjoyed that another has been denied. That is why it’s facile to demand that anyone should be able to 'just say no' and to judge them as morally lacking if they can't.

"The War on Drugs is cultural schizophrenia," says Jaak Panksepp. I agree. The War on Drugs expresses a split mindset in two ways: we want to eradicate or limit addiction, yet our social policies are best suited to promote it, and we condemn the addict for qualities we dare not acknowledge in ourselves. Rather than exhort the addict to be other than the way she is, we need to find the strength to admit that we have greatly exacerbated her distress and perhaps our own. If we want to help people seek the possibility of transformation within themselves, we first have to transform our own view of our relationship to them.

To expect an addict to give up her drug is like asking the average person to imagine living without all her social skills, support networks, emotional stability and sense of physical and p psychological comfort. Those are the qualities that, in their illusory and evanescent way, drugs give the addict. People like Serena and Celia and the others whose portraits have appeared in this book perceive their drugs as their "rock and salvation." Thus, for all the valid reasons we have for wanting the addict to "just say no," we first need to offer her something to which she can say "yes." We must provide an island of relief. We have to demonstrate that esteem, acceptance, love and humane interaction are realities in this world, contrary to what she, the addict, has learned all her life. It is impossible to create that island for people unless they can feel secure that their substance dependency will be satisfied as long as they need it.

...These are the drugs for which animals and humans will develop craving and which they will seek compulsively.
But this is far from saying that the addiction is caused directly by access to the drug. We will later explore why these substances have addictive potential; the reasons are deeply rooted in the neurobiology and psychology of emotions.

Because almost all laboratory animals can be induced into compulsive self-administration of alcohol, stimulants, narcotics and other substances, research has appeared to reinforce the view that mere exposure to drugs will lead indiscriminately to drug addiction. The problem with this apparently reasonable assumption is that animal laboratory studies can prove no such thing. The experience of caged animals does not accurately represent the lives of free creatures, including human beings. There is much to be learned from animal studies, but only if we take into account the real circumstances. And, I should add, only if we accept the tremendous suffering imposed on these involuntary“subjects.”

Although there are anecdotes of animals in the wild becoming intoxicated, most of them are spurious, as is the case, for example, with stories of elephants getting “drunk”on fermenting marula fruit. There are no known examples of persistently addictive behaviors in the natural world. Of course, we cannot predict exactly what might happen if wild animals had free and easy access to addictive substances in the purified and potent forms administered in laboratories. What has been shown, however, is that conditions in the laboratory powerfully influence which animals will succumb to addiction. Among monkeys, for example, subordinate males who are stressed and relatively isolated are the ones more likely to self-administer cocaine. As I will later explain, being dominant leads to brain changes that give stronger monkeys some protection from an addictive response to cocaine.

Bruce Alexander, a psychologist at Simon Fraser University in British Columbia, points out the obvious: laboratory animals in particular can be induced into addiction because they live under unnatural circumstances of captivity and stress. Along with other astute researchers, Dr. Alexander has argued that drug self-administration by these creatures may be how the animals “cope with the stress of social and sensory isolation.” The animals may also be more prone to give themselves drugs because they are cooped up with the self-administration apparatus and cannot move freely.

As we will see, emotional isolation, powerlessness and stress are exactly the conditions that promote the neurobiology of addiction in human beings, as well. Dr. Alexander has conducted elegant experiments to show that even lab rats, given reasonably normal living situations, will resist the addictive appeal of drugs:
 
My colleagues and I built the most natural environment for rats that we could contrive in the laboratory. “RatPark,” as it came to be called, was airy, spacious, with about 200 times the square footage of a standard laboratory cage. It was also scenic (with a peaceful British Columbia forest painted on the plywood walls),comfortable (with empty tins, wood scraps, and other desiderata strewn about on the floor), and sociable

 
(with 16–20 rats of both sexes in residence at once).…We built a short tunnel opening into Rat Park that was just large enough to accommodate one rat at a time. At the far end of the tunnel, the rats could release a fluid from either of two drop dispensers. One dispenser contained a morphine solution and the other an inert solution.
 
It turned out that for the Rat Park animals, morphine held little attraction, even when it was dissolved in a sickeningly sweet liquid usually irresistible to rodents and even after these rats were forced to consume morphine for weeks, to the point that they would develop distressing physical withdrawal symptoms if they didn't use it. In other words, in this “natural” environment a rat will stay away from the drug if given a choice in the matter—even if it’s already physically dependent on the narcotic. “Nothing that we tried,” reported Bruce Alexander, “instilled a strong appetite for morphine or produced anything that looked like addiction in rats that were housed in a reasonably normal environment.” By contrast, caged rats consumed up to twenty times more morphine than their relatively free living relatives. Dr. Alexander first published these findings in 1981.

In 1980 it had already been reported that social isolation increased animals' intake of morphine. Other scientists have since confirmed that some environmental conditions are likely to induce animals to use drugs; given different conditions, even captive creatures can resist the lure of addiction.

We see that substance addictions are only one specific form of blind attachment to harmful ways of being, yet we condemn the addict's stubborn refusal to give up something deleterious to his life or to the life of others. Why do we despise, ostracize and punish the drug addict, when as a social collective, we share the same blindness and engage in the same rationalizations?

Not every story has a happy ending, ... but the discoveries of science, the teachings of the heart, and the revelations of the soul all assure us that no human being is ever beyond redemption. The possibility of renewal exists so long as life exists. How to support that possibility in others and in ourselves is the ultimate question.

Anything can serve as the object of the addiction process, including religions that promise salvation and freedom. The physical entity called Jerusalem has itself become a fetish for many people of several faiths, with bloodshed and hatred being the consequence. It is no accident that in all major religions the most rigidly fundamentalist elements take the harshest, most punitive line against addicted people. Could it be that they see their own weakness and fear—and false attachments—reflected in the dark mirror addiction holds up to them?

The war mentality represents an unfortunate confluence of ignorance, fear, prejudice, and profit. ... The ignorance exists in its own right and is further perpetuated by government propaganda. The fear is that of ordinary people scared by misinformation but also that of leaders who may know better but are intimidated by the political costs of speaking out on such a heavily moralized and charged issue. The prejudice is evident in the contradiction that some harmful substances (alcohol, tobacco) are legal while others, less harmful in some ways, are contraband. This has less to do with the innate danger of the drugs than with which populations are publicly identified with using the drugs. The white and wealthier the population, the more acceptable is the substance. And profit. If you have fear, prejudice, and ignorance, there will be profit.

Coffee perks you up, lowers your risk of heart disease, and has antioxidants that ward off cancer. It's even a mild painkiller: Drinking a few cups before you exercise can prevent post-workout muscle aches and pains

For this study, the researchers took human cells that regulate acid secretion in the stomach and exposed them to different types of coffee: regular, dark-roast, mild, decaffeinated, and low-acid. They found that different compounds in the different roasts had compounds that do indeed cause stomach cells to produce more acid. The main culprits were caffeine and two different plant compounds, catechols and N-alkanoly-5-hydroxytryptamides. But they also found that another compound, N-methylpyridinium (NMP), had the opposite effect. NMP was generated as the coffee beans were roasted, and the longer they roasted, the higher the levels of NMP that were present.