Opium Addiction Treatment
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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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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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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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
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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Contrary to what its name suggests, opium is not a single chemical compound. Its chemical make-up is more like a salad, consisting of various substances including sugars, proteins, acids, water, and many alkaloids, among others. The people who grow opium for its narcotic value are primarily interested in the alkaloids.
An alkaloid is a complex organic chemical substance found in plants, which characteristically combines nitrogen with other elements, has a bitter taste, and typically has some toxic, stimulant, analgesic effects. There are many different alkaloids, 30 of which are found in the opium plant. While morphine is the most important alkaloid in opium—for its natural narcotic qualities as well as providing the chemical structure for heroin—another alkaloid, codeine, is also sought after for its medicinal attributes. Other alkaloids include papaverine, narcotine, nicotine, atropine, cocaine, and mescaline. While the concentration of morphine in opium varies depending on where and how the plant is cultivated, it typically ranges from 3 percent to 20 percent.
The International Language of Poppy
Bengali Afing-gach, Posto
Burmese Bhainzi
Dutch Papaver
English Poppy
French Pavot somnifere
German Mohnblume
Hindi Post, Khas-khas, Post dana
Hungarian Mak, Kerti mak
Italian Papavero
Japanese Hinageshi
Polish Mak lekarski
Portuguese Popoula
Romanian Mac
Sanskrit Ahiphena
Spanish Adormidera, Amapola
Swedish Vallmo
Thai Ton fin
Turkish Hashhash tohuma
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Pronunciation: pay-OH-tih (also pronounced peh-YOH-teh)
Chemical Abstracts Service Registry Number: 11006-96-5
Formal Names: Lophophora williamsii
Informal Names: Bad Seed, Big Chief, Black Button, Britton, Buttons, Cactus, Cactus
Head, Challote, Devil’s Root, Dry Whiskey, Dumpling Cactus, Half Moon, Hikori, Hikuli, Hyatari, Mescal, Mescal Beans, Mescal Buttons, Mescalito, Mescy, Nubs, P, Pellote, Peyotl, Seni, Shaman, Tops
Type: Hallucinogen.
Federal Schedule Listing: Schedule I (DEA no. 7415)
USA Availability: Illegal to possess
Pregnancy Category: None
Uses.
Peyote is part of a cactus plant. Native American folk medicine has used peyote cactus root for doctoring scalp afflictions. In folk medicine peyote has also been used against snake bite, influenza, and arthritis. Scientists have determined that peyote contains substances that might fight infections. Some Native Americans are reported to use light doses of peyote as a stimulant to maintain endurance when engaged in relentless activity permitting little nourishment
or water, a practice sounding much like traditional use of coca. Spaniards observed such peyote usage in the Aztec empire.
Peyote’s main active component is the hallucinogen mescaline. Some other varieties of cactus also contain mescaline, although generally in much smaller amounts. Researchers suspect the peyote cactus may additionally contain chemicals similar to those appearing in the brain upon use of alcohol. In addition to causing hallucinations, peyote can change perception of time.
Psychic effects can include feeling more peaceful and connected with life; craziness of the everyday world can recede. People can use the experience to work through their concerns and may be more open to suggestions. Physical senses may seem enhanced, and barriers between them may melt, such as allowing sounds to be seen.
Normally a Schedule I substance is illegal to possess except under special permission to do research with it, but for many years members of the Native American Church were allowed to possess and use peyote (but not the pure drug mescaline) for religious purposes. During the 1990s their legal situation became confused, and the issue was a matter of controversy when this book was written.
The religion of Peyotism (of which the Native American Church is but one variety) is a topic beyond the scope of this book, but drug-induced visions are only one part of the practitioners’ way of life. Observers have noted that Peyotism can be an effective way of dealing with addiction to alcohol and opiates. Traditional peyote use occurs in a group context, a social gathering
of persons sharing and furthering the same beliefs and goals. A solitary user estranged from such a setting is likely to have a far different peyote experience.
For instance, one element of a peyote session can be nervousness and fear, emotions that may have different impacts depending on whether a user is alone or is with a group of reassuring and supportive persons. A researcher with the Indian Health Service of the U.S. Public Health Service estimated that traditional peyote usage produced bad psychological experiences once in
70,000 doses, a safety record that the researcher attributed to the social context of traditional use. Physical damage has not been noted from traditional use.
Drawbacks.
Chills, muscle tension, nausea, and vomiting are typical unwanted peyote effects.
Abuse factors.
A study published in the 1950s concluded that peyote tolerance, dependence, and craving did not occur from traditional usage—a finding supported by other authorities as well. A canine experiment showed that tolerance to the vomiting effect occurred if dogs received daily peyote for a year.
Drug interactions.
Not enough scientific information to report.
Cancer.
Not enough scientific information to report.
Pregnancy.
Peyote has caused birth defects in hamsters. A study comparing peyote users to nonusers from the same Indian group found no increase in chromosome damage among the users.
Additional information.
Peyote is sometimes called “mescal,” which is also the name of an alcoholic beverage. The two substances are different, and the beverage has no connection with peyote. Likewise “mescal beans” are an alternative peyote name and also the name of a nonhallucinogenic food.
Additional scientific information may be found in:
Bergman, R.L. “Navajo Peyote Use: Its Apparent Safety.” American Journal of Psychiatry
128 (1971): 695–99.
Boyer, L.B., R.M. Boyer, and H.W. Basehart. “Shamanism and Peyote Use among the
Apaches of the Mescalero Indian Reservation.” In Hallucinogens and Shamanism,
ed. M.J. Harner, 53–66. New York: Oxford University Press, 1973.
Bruhn, J.G. “Mescaline Use for 5700 Years.” Lancet 359 (2002): 1866.
Ellis, H. “Mescal: A New Artificial Paradise.” The Contemporary Review 71 (1897). Reprinted
in Smithsonian Institution’s Annual Report 1897. Washington, DC: Author,
1898. 537–48.
Huttlinger, K.W., and D. Tanner. “The Peyote Way: Implications for Culture Care Theory.”
Journal of Transcultural Nursing 5, no. 2 (1994): 5–11.
Kapadia, G.J., and M.B.E. Fayez. “Peyote Constituents: Chemistry, Biogenesis, and Biological
Effects.” Journal of Pharmaceutical Sciences 59 (1970): 1699–1727.
La Barre, W. “Peyotl and Mescaline.” Journal of Psychedelic Drugs 11 (1979): 33–39.
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Pronunciation: pen-toh-BAR-bi-tal
Chemical Abstracts Service Registry Number: 76-74-4
Formal Names: Cafergot, Nembutal, Pentobarbitone, Phenobarbitone
Informal Names: Nebbies, Nembies, Nemmies, Nimbies, Yellow Bullets, Yellow Dolls, Yellow Jackets, Yellows
Type: Depressant (barbiturate class).
Federal Schedule Listing: Schedule II (oral and parentral, DEA no. 2270), Schedule
III for suppositories (DEA no. 2271)
USA Availability: Prescription
Pregnancy Category: D
Uses.
This short-acting substance has sedative qualities but is considered ineffective in treating nervous apprehension. Because of the drug’s sleepinducing characteristics, it is used as a preliminary to administering anesthesia and as a short-term treatment for insomnia. Pentobarbital has been observed to lower blood pressure, body temperature, and muscle tone. The compound can be used as an emergency anticonvulsant when a person has seizures, and
has been used to treat alcohol addicts undergoing withdrawal. Pentobarbital has been found effective in reducing pressure that fluid creates in the brain after severe head injury. Pentobarbital reduces a type of nerve cell death called neuronal apoptosis, and this reduction may help prevent stroke. Animal studies indicate that pentobarbital can help protect brain tissue against radiation, which might have practical application during treatment of brain tumors. Veterinarians use the substance for euthanasia: An unusual demonstration of the drug’s strength occurred when a lion was poisoned by eating meat from a horse that had been killed with pentobarbital.
Drawbacks.
Although the drug is a sedative, it can cause hyperactivity in children. Sudden stoppage of combined pentobarbital and benzodiazepine therapy in an infant caused temporary chorea (involuntary jerking). A feline experiment showed that tremors reminiscent of Parkinson’s disease can occur when pentobarbital is administered with chlorpromazine (also called Thorazine, often used to treat psychotic behavior). Persons with porphyria, a body chemistry affliction that can provoke violence, are supposed to avoid pentobarbital. Examination of epileptic children receiving pentobarbital shows elevated readings for total cholesterol, though levels of high-density lipoprotein (so-called good cholesterol) and triglycerides (associated with heart attack and stroke) seem unaffected.
In a monkey experiment pentobarbital interfered with time perception, ability to learn, short-term memory, attention span, and interest in tasks. The substance impeded task performances in a human experiment, with performance getting worse as the amount of thinking necessary for a chore increased.
Such a drug is unlikely to be welcome in the workplace. Although children using the substance apparently have trouble with language skills, a study found language development to be normal two years after the medication ceased.
Abuse factors.
In a test, alcohol drinkers who were not alcoholics found pentobarbital less appealing than a placebo and experienced no euphoria from pentobarbital, a finding consistent with other studies of persons who do not abuse drugs. When given choices of assorted substances, monkeys chose pentobarbital less often than water, which indicates the compound has low addictive potential. In contrast, drug abusers participating in an experiment found effects of pentobarbital and diazepam to be similar. Those two drugs thus had comparable appeal even though scientists running the experiment found pentobarbital possessing only 10% of diazepam’s strength. A study testing various effects on former drug addicts found pentobarbital to be 15 times
stronger than meprobamate, but morphine acted 6 times stronger than pentobarbital.
Cross-tolerance among chlordiazepoxide, pentobarbital, and alcohol has been observed in rats. A study of sedative drug abusers found alcohol and pentobarbital to deliver similar effects, with pentobarbital possibly having more appeal. A monkey experiment indicates that alcohol increases the attractiveness of pentobarbital. Dependence can develop, and in humans the
pentobarbital withdrawal syndrome can duplicate the delirium tremens of alcohol withdrawal. A mice study found that tolerance to pentobarbital developed more rapidly if assorted drugs of abuse were also being administered (morphine, amphetamine, alcohol, or cocaine).
Drug interactions.
A case report notes that pentobarbital can almost double the speed with which theophylline (commonly used to treat asthma and other breathing difficulties) disappears from the bloodstream, requiring changes in normal theophylline dosage. In a mice experiment alcohol boosted pentobarbital’s potency. A human study found that chronic alcohol ingestion reduces
the effective length of a pentobarbital dose. Grapefruit juice extends the amount of sleep produced by pentobarbital in rats, and in mice the drug inhibits caffeine effects. At one time researchers suspected that taking pentobarbital along with MDMA would reduce organic brain damage caused by MDMA, but rat experiments indicate that any apparent benefit comes simply
from the lower body temperature produced by pentobarbital. Although cocaine is a stimulant, in a rat experiment it increased the sleep-inducing quality of pentobarbital.
Cancer.
In animal experimentation pentobarbital has caused cancer. In humans long-term usage is associated with cancer of the ovaries and bronchi, but that finding is weakened by the patients also smoking cigarettes. Pregnancy. A large survey of pregnancy outcomes found that pentobarbital does not appear to cause birth defects. Nonetheless pregnant women are supposed
to avoid the drug.
Additional information.
Some capsule formats of Nembutal (pentobarbital sodium CAS RN 57-33-0) contain FD&C Yellow No. 5 (tartrazine), which can cause asthma attacks or other allergic responses in sensitive persons, particularly if someone has adverse reactions to aspirin. Cafergot PB is a combination
of bellafoline, caffeine, and ergotamine tartrate. The combination was tested with and without pentobarbital sodium to determine effect on migraine headache. Presence of pentobarbital not only enhanced reduction of pain but also helped treat anxiety, nausea, vomiting, poor appetite, and low tolerance of light.
Additional scientific information may be found in:
Cole-Harding, S., and H. de Wit. “Self-Administration of Pentobarbital in Light and
Moderate Alcohol Drinkers.” Pharmacology, Biochemistry, and Behavior 43 (1992):
563–69.
Hambly, G., C. Frewin, and B. Dodd. “Effect of Anticonvulsant Medication in the Preschool
Years on Later Language Development.” Medical Journal of Australia 148
(1988): 658, 661–62.
Mintzer, M.Z., et al. “Ethanol and Pentobarbital: Comparison of Behavioral and Subjective
Effects in Sedative Drug Abusers.” Experimental and Clinical Psychopharmacology
5 (1997): 203–15.
Pickworth, W.B., M.S. Rohrer, and R.V. Fant. “Effects of Abused Drugs on Psychomotor
Performance.” Experimental and Clinical Psychopharmacology 5 (1997): 235–41.
Pierce, James I. “Drug-Withdrawal Psychoses.” American Journal of Psychiatry 119
(1963): 880–81.
