The Principal Alkaloids in Opium

Alkaloid---Chemical Class---Amount in Opium

Morphine---Phenanthrene---10%–15%
Noscapine---Benzylisoquinoline---4%–8%
Codeine---Phenanthrene---1%–3%
Papaverine---Benzylisoquinoline---1%–3%
Thebaine---Phenanthrene---1%–2%

Adapted from Moraes, Francis, and Debra Moraes. Opium. Oakland, Calif.: Ronin Publishing, 2003, p. 58

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Opium Addiction Treatment

Opium has been used as a medicine for hundreds of years, inevitably creating countless addicts. Scientists have conducted a never-ending search for effective cures for opium addiction, morphine addiction (morphinism), and heroin addiction. For most of its history, opium addiction was treated as a disease with no cure, and doctors concerned themselves with treating the symptoms of addiction rather than the root cause. As a result, other opiates were used to lessen the effects of withdrawal. The addict is placed on a regimen of opiates that slowly decrease over time, weaning the addict from his or her addiction. This process of treatment is still used today.

Over the years, scores of seemingly counterintuitive methods have been tried to cure the addict. When morphine was first isolated and synthesized, it was considered to be, and utilized as, a cure for opium addiction. Later, heroin was created, and used as a treatment for morphinism. In the mid-twentieth century, lysergic acid diethylamide (LSD) likewise was tried as a therapy. The sad truth is that even today there is no real cure for any of the various forms of opiate addiction.

Modern therapy uses a drug called methadone.
Methadone, discovered in the 1940s, is similar to morphine and heroin as a powerful analgesic. When injected, methadone prevents heroin and morphine from working and lessens the withdrawal effects of both. While also an addictive drug, methadone is used to treat heroin and morphine addiction because it is supposedly easier to quit using. Essentially, an addict on the therapy is given a dose of methadone equivalent to that of their heroin or morphine use. The patient receives lower and lower dosages, until they eventually need no drug at all.

Many addicts, however, report that weaning themselves off of methadone is just as bad as coming off of heroin or morphine addiction. Ultimately, primary treatments for opiate addiction rely on replacing one drug for another and are essentially palliative treatments. The user is never “cured” and will always be tormented by the specter of addiction.

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ACTIVE INGREDIENTS IN OPIUM

Seventy-five percent of raw opium consists of ingredients that have no significant biological effects, such as water, sugars, and fatty acids. The remaining 25 percent contains numerous biologically active ingredients that interact with opioid receptors. These agents are termed the opiod alkaloids.

Alkaloids are complex organic molecules, many of which have been used in traditional medicine or as poisons.

Atropine from the deadly nightshade plant dilates the pupil of the eye, and curare is a skeletal muscle relaxant employed in anesthesia, but both agents have also been used as poisons.

Opium contains at least 20 alkaloids and by some claims as many as 50. However, five principal alkaloids are of major interest: these are morphine, codeine, noscapine, papaverine, and thebaine.

Morphine is the most abundant of the opium alkaloids. It constitutes as much as 15 percent of the plant extract.

Morphine has been used as a medicine and narcotic for thousands of years. Therapeutically, morphine has three principal uses: as an analgesic for the relief of acute and chronic pain, as a respiratory depressant, and as an antidiarrheal agent. The analgesic properties are morphine’s most important clinical use.

Codeine is a close chemical relative of morphine, differing in only one chemical group. Once administered, codeine is actually metabolized by enzymatic action, and its actions mimic those of morphine. Codeine is used primarily as a cough suppressant, although it certainly also possesses significant analgesic properties (approximately one tenth those of morphine) as in the relief of pain from toothache.

Noscapaine has only minimal therapeutic and narcotic properties. It can be used as a cough suppressant, but has no apparent advantage over other agents.

Papaverine also has minimal narcotic properties.However, it does have vasodilator (blood vessel relaxant) properties, and because of this property it has been employed for both cognition enhancement and erectile dysfunction.

Thebaine has, despite its chemical similarity to morphine, no narcotic or therapeutic uses. It does, however, cause convulsions at high doses. It is also a useful chemical intermediate in the laboratory for production of other opioid compounds.

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PHARMACOLOGICAL AND OPIOID RECEPTORS

It has been recognized for more than a century that the neurotransmitters of the nervous system produce their biological effects through interaction at specific drug binding sites or receptors. These receptors, many of which have been isolated and characterized in the past two decades, are typically specialized proteins on the cell surface. The function of these proteins is to recognize the neurotransmitter and to enable the molecule to bind to the receptor to trigger a biological response— muscle contraction, hormone or neurotransmitter secretion, or increased cardiac rate, for example. These interactions are typically quite specific and are often viewed in terms of a “lock and key”model. Despite this specificity it is usually found that a number of chemical variations around a particular structure can also be accommodated at the receptor site.

When these chemical variants can also trigger the biological response they
are termed “agonists.” However, some molecules can bind to the receptor and not trigger the response, but rather block the response: these drugs are termed “antagonists.”Thus, for example, the naturally occurring atropine from the Belladonna plant can block the actions of the neurotransmitter acetylcholine in the parasympathetic system by interacting with the same receptors that acetylcholine uses.

The alkaloids in opium, including morphine, also interact with specific receptors (opiate receptors) within the central and peripheral nervous systems. At these receptors, the alkaloids in opium mimic the effects of the body’s natural opiates.

There are actually three major structural classes of opiates that occur in the body: enkephalins, endorphins, and dynorphins. The existence of these endogenous molecules was initially theorized because morphine and related drugs had been shown to exert their pharmacological and therapeutic effects through interaction at specific receptors.Due to the specific locations of these interactions, scientists postulated that there must exist corresponding endogenous physiologically employed molecules. A similar argument was employed in the search for the endogenous equivalent of the cannabinoids found in marijuana and led to the recognition of the so-called “endocannabinoid” system.

There are three principal classes of opiate receptors, designated m, k, and d, and there exist a number of drugs that are specific for each of these receptor types. However, most of the clinically used opiates are quite selective for the mÙreceptor: the endogenous opiates enkephalin, endorphin and dynorphin are selective for the mÙand d, d and k receptors respectively.When activated by opioids these receptors produce biochemical signals that block neurotransmitter release from nerve terminals, a process that underlies their blockade of pain signaling pathways as well as other effects, such as constipation, diuresis, euphoria, and feeding.

Brief administration of opioids leads to the development of acute tolerance, whereby increased quantities of the opioid are required to produce the same end result, but this process is rapidly reversed once the administration is ceased.

However, more prolonged administration leads to classical or chronic tolerance from which state recovery to full sensitivity make take several days. These phenomena are not unique to opioid drugs, but rather are common to virtually all drug-receptor interactions and appear to be a common property of pharmacological receptors. Tolerance may also be associated with the state of physical dependence. The chronic administration of a drug, in this context an opioid, may result in a resetting of homeostatic mechanisms, and maintenance of this new state requires continued drug administration. Cessation of drug administration can then result in the phenomenon of withdrawal, during which the nervous system is excessively perturbed as it readapts to its original drug-free state. It should be emphasized that tolerance and physical dependence are physiological responses to continued administration of opioids and are not, contrary to some popular opinion, predictors of addiction. For example, patients with severe pain from bone cancer require very large amounts of opioids, yet these patients do not become addicted and will not even show withdrawal if the drug doses are reduced slowly over a period of days. Unfortunately, misinformation about opioids has led to patients with severe pain being undertreated.

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OPIUM AND THE NERVOUS SYSTEM

Although the nervous system is often discussed in terms of peripheral and central components, it should be regarded as a highly integrated whole in which the central nervous system (brain and spinal cord) plays a critical information gathering and processing role. The peripheral nervous system is often divided into the autonomic and somatic components. The somatic system controls the voluntary functions of the body, like those of the skeletal muscles. The autonomic system, in contrast, is often referred to as the “involuntary” system. It regulates parts of the body where we execute little or no conscious control, such as the heart, intestines, vasculature, and other internal organs.

The autonomic nervous system is divided into the sympathetic and parasympathetic components, which typically exert opposing effects. The sympathetic system is involved in the “fight or flight” reaction (increased blood pressure and heart rate, and accommodation for increased vision, for example) that prepares the organism for stressful situations. The parasympathetic system conversely establishes a more relaxed situation, for instance, the rest period after a meal. The autonomic nervous system that is responsible for the independent control of the mechanical and secretory functions of the gastrointestinal tract is sometimes called the enteric system.

Drugs that affect the central nervous system may also have a major action in the gut. Thus, the constipating effects of opium alkaloids are exerted through this system and a number of the important withdrawal symptoms reflect the actions of the enteric nervous system. The nervous system is often regarded as a command (efferent) system that sends instructions to be executed. However, there is also a sensory (afferent) component, that receives information from innervated systems and that is vital to the overall integrated nervous response.

Despite the anatomical and functional differences between the various components of the nervous system, they share a fundamental similarity in their use of chemicals (neurotransmitters) to convey information.

The individual unit of the nervous system is the neuron, a specialized cell that both receives and transmits information.

The nervous system contains more than 100 billion neurons and is a major user of metabolic energy in the human body. It is also a region particularly susceptible to injury from toxic chemicals, lack of oxygen, and other assaults. Depending on the nervous region in which they reside, neurons may have different anatomical features and may use different chemical transmitters. Neurons communicate with each other and with their end organs by these chemical signals, which are released from the nerve terminal and interact with specific receptors on adjacent neurons or cells.

The chemical transmitters may be small molecules—notably acetylcholine, norepinephrine, epinephrine, serotonin, dopamine, or histamine. Acetylcholine and norpeinephrine are the dominant neurotransmitters in the parasympathetic and sympathetic nervous systems, respectively.

Dopamine and serotonin are employed primarily in the central nervous system. Neurotransmitters may also be more complex peptides (small proteins) such as substance P, vasopressin, endorphins, and enkephalins. The latter agents are of particular importance to our considerations of opium since they represent the “endogenous” opiates—agents that exist within the body whose actions are mimicked by exogenous, or outside, agents such as morphine, heroin, codeine, and so on. These neurotransmitters serve to convey information between neurons across the synaptic cleft (the junction where two neurons meet) or at the neuroeffector junction (the site between neuron and an innervated organ such as muscle or secretory gland).

Each neuron has specific synthetic machinery that enables it to both synthesize and eliminate a specific neurotransmitter.

For example, neurons of the sympathetic nervous system employ norepinephrine and epinephrine as their transmitters. Other neurons, particularly in the central nervous system, employ dopamine as their transmitter. Dopamine is a particularly important transmitter for a variety of neuronal functions. Its loss is associated with Parkinson disease, and it is a critical agent in the mediation of pleasure and reward processes. Dopamine, due to its association
with pleasurable sensations, is widely implicated in the actions of a number of drugs of abuse, including cocaine, opiates, and methamphetamines.

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