Thursday, 28 March 2013

The Opiate Cure - Pain and the Bipolar Spectrum

The Opiate Cure tells the stories of people whose mental illness were relieved when they were given opioids for their chronic pain. 

This improbable outcome has occurred in those with bipolar depression and mania, attention deficit disorder, post-traumatic stress disorder (PTSD) obsessive-compulsive disorder (OCD), and narcolepsy. 

These several diseases are now linked together, constituting the bipolar spectrum. Linked also to bipolar spectrum is chronic pain in its many forms, including migraine. 

The Opiate Cure offers new insights and, more importantly, hope for those with acute and/or chronic pain.

This book clearly demonstrates bipolar spectrum is uniquely responsive to opiate therapy. 

The Truth About Heroin

The Truth About Heroin - UK documentary
(Actual title is "Drug Laws Don't Work: The Phoney War: (Dispatches)
by Nick Davies 2001

"Diamorphine (Heroin) is a very safe medicine to use, it is not unusually dangerous, I have prescribed it to hundreds of patients and the most common side effect is constipation which can be easily managed. In fact, Paracetemol is a more dangerous drug and is more likely to damage your body and kill you. The consequence of doubling a dose of Paracetemol could mean death whereas the consequence of doubling your dose of Diamporphine is that it may make you sleepy for a while, with no permanent damage as a result." 

- Dr. Theresa Tate, Medical Advisor to Marie Curie Cancer Care

"The available evidence indicates that heroin is a relatively safe drug when provided in pure form. Hence it is the illegal form of the drug (impure street Heroin), not Diamorphine itself, which leads to health and social problems associated with its use." 

- Ostini, Bammer Dance & Goodwin, 1993, 'Journal of Medical Ethics' 

"When Heroin-dependent persons have been provided with daily maintenance doses under medical supervision marked physiological deterioration or psychological impairment has not been observed." 
-Toronto Addiction Research Foundation

"To our surprise we have not been able to locate even one scientific study, on the proven harmful effects of (heroin) addiction." 
Dr. George Stevenson and a group of British Columbia researchers after exhaustively reviewing the medical literature on heroin addiction.

Opiate medicine crushes major depression

What could easily be the most important advance in the pharmacologic treatment of major depression and anxiety disorders is now unfolding. A new investigational drug, currently known as ALKS 5461, could deliver all the mood-enhancing and anxiety-lowering effects that lead people to use opiates like heroin and Oxycontin—without the potential for getting high or addicted. 
That’s right:  ALKS 5461 could be a non-abusable, non-addictive heroin-like compound. ALKS 5461 is actually a combination of two molecules. The first is buprenorphine, which is already used to provide some of the benefits of opiates, without many of the worst side effects, allowing people to get off of street drugs (as an alternative to methadone). The second molecule is now known as ALKS 33—and that’s the magic part. ALKS 33 interferes with the binding of buprenorphine to the receptors that are involved in making people feel euphoric. 
Those are the receptors also involved in getting people to crave opiates like alcoholics crave alcohol. In a double-blind, placebo controlled study (meaning, the participants had no idea whether they were getting ALKS 5461 or a sugar pill), ALKS 5461 was rapidly effective in relieving symptoms in 32 patients with major depression. 
 All 32 patients responded to the medicine—with results evident by seven days. What’s more, all of them had failed to respond adequately to traditional antidepressants like Prozac or Effexor. 
Ultimately, I believe ALKS 5461 could revolutionize the pharmacologic treatment of major depression and panic disorder and post-traumatic stress disorder and obsessive-compulsive disorder. 
It should come as no surprise that ALKS 5461 is the brainchild of scientists at Alkermes Pharmaceuticals, the same company, which invented and markets Vivitrol, a monthly injection that can take away the “high” of using alcohol and street drugs—and in my opinion, ought to be something that every family member of every addict clamors to get their loved one to take. 
If ALKS 5461 comes to market (and I believe it will), then that scourge we call major depression will be dealt a massive blow.  
It will still be imperative to use insight-oriented psychotherapy to get to the bottom of what unique psychological issues have fueled each person’s depression, but that should be easier—not harder—when folks aren’t struggling just to get out of bed and over to their psychiatrists’ offices. This is a really big deal.

Wednesday, 27 March 2013

The Case for Legalizing Heroin

What group of currently illegal drugs did affluent, middle-age women in 19th century America widely favor? What drugs were also used in teething syrups for babies and as a cure for alcoholism? And what drugs were banned, not because of any demonstrated health hazard, but because of a congruence of special interests and anti-Chinese racism? And what drugs were first banned by the national government, not as a result of any conditions in this country, but in response to obscure international events occurring half way around the globe nearly a century ago?

The answer is the opiates: heroin, morphine, and opium.
Of all illicit drugs, heroin has the most vicious reputation. Even many of those favoring the legalization of marijuana and other "soft" drugs blanch at the prospect of a free market in heroin. The estimated half million heroin users presently within the United States are viewed, in the words of a 1962 Supreme Court decision, as a plague of "walking dead," driven into prostitution, if they are women, and into crime, if they are men, in order to finance their $100-a-day habits.

Heroin-related deaths number in the hundreds every year, while some analysts attribute as much as 70 percent of all property crimes to heroin. Despite the billions of tax dollars allocated by governments to deal with this drug problem - either through strict law enforcement or through various treatment panaceas - the problem persists at epidemic levels.

The drug problem is of particular concern to Californians. After New York, California has the largest and most expensive law enforcement system in the nation. The state ranks within the top ten for violent crime per capita and within the top five for property crime. During 1980, nearly 20 percent of all reported felony arrests in the state were for drug violations. That figure, 65,101, exceeds the number of arrests for any category of major offense except burglary. Within the last year, Los Angeles officials have reported a new surge in the use of heroin, especially among young people.
Contrast the current state of affairs with the 19th century, when there was no narcotic drug problem in this country and virtually no drug laws.

Heroin is a derivative of morphine, which in turn is derived from opium. Drug manufacturers did not synthesize heroin until 1898. But prior to that date, the other opiates were as freely available as aspirin is today. Drug stores and grocery stores sold products containing opium and morphine over the counter, and anyone could order these products through the mail. Opiates were the basic ingredients in many patent medicines and were used to treat everything from diarrhea to what was called "Women's troubles." Even teething syrups for babies contained opiates.

An 1880 medical text listed 54 diseases that could be treated with morphine. One wholesale drug house reportedly offered more than 600 medicines and other products with opiates. "Godfrey's Cordial," for instance, mixed opium, molasses for sweetening, and sassafras for flavoring.
"Godfrey's Cordial" was popular in England as well as the U.S. Residents of mid nineteenth-century Coventry bought ten gallons weekly - enough for 12,000 doses - and administered them to 3,000 infants under two years of age.

In the United States, regular users of opiates at the turn of the centtury numbered somewhere between 200,000 and 1 million, out of a population of 76 million, leading to a general recognition that excessive opiate use was peculiarly American. The majority of these users were white, middle or upper-class women, with an average age over forty. For them, opiates served the same function that alcohol, Valium, and other tranquilizers serve for housewives today. Although opium use was not socially respectable, it received less opprobrium than the use of alcohol, which was especially frowned upon forx women. Social reformers put a much higher priority on the flourishing crusade for alcohol prohibition, and the increasing number of state and local prohibition laws helped stimulate the demand for opiates. Indeed, both opium and morphine were widely recommended cures for alcoholism.
After heroin (diacetylmorphine) was introduced, it became as readily available as opium and morphine. Once in the body, heroin is converted back into morphine, which is also the primary active agent in opium.

Heroin differs from morphine only in that it is more potent and acts more rapidly. Interestingly enough, heroin was initially acclaimed as a non-addicting cure for morphine addiction. More recently, authorities have employed methadone, a synthetic narcotic resembling morphine and heroin, but not derived from opium, as a treatment for heroin addiction. Methadone, while not as pleasurable as heroin, turns out to be equally addictive. And ironically, the resulting use of alcohol to get off methandone has, within a century, brought the "treatment" cycle back to where it stated.

The first anti-morphine law appeared in Pennsylvania as early as 1860. For the rest of the century, however, those few state and local ordinances regulating opiates remained filled with loopholes, enforced laxly, and evaded easily. The most noteworthy exception to the general reign of laissez-faire in narcotics was San Francisco, where the smoking of opium in smoking houses or "dens" was prohibited in 1875. The motivation behind this San Francisco ordinance was not so much a moralistic disapproval of opium as it was a racist intolerance of the Chinese laborers pouring into the city. While white Americans preferred to ingest their opium orally, the Chinese, reflecting cultural differences, favored opium smoking.

U.S. labor unions, because of their fear of competition from Chinese laborers, contributed immensely to the spread of anti-Chinese racism. In response to this sentiment, Congress not only barred further Chinese immigration in 1889, but also, two years earlier, prohibited the importation of opium by Chinese and the importation of smoking opium altogether.
By 1914, 27 states and cities had passed laws against opium smoking. None of these laws, as could be expected, were very effective. Their main impact was to encourage opium users to shift to stronger substitutes: morphine and heroin.

At the same time that Chinese immigrants in the U.S. were suffering from increasing bigotry and brutality, American merchants in the Far East were attempting to penetrate Chinese markets. They faced very stiff competition from the British, who sold opium grown in India to the Chinese. The British government, in fact, had waged two opium wars in the mid-nineteenth century to protect and expand this opium traffic, and by 1894, opium accounted for 14 percent of China's total imports. Moreover, in 1905 Chinese merchants organized a voluntary embargo of American goods to protest the oppressive treatment of Chinese immigrants and travellers within the United States.
During the Progressive Era, the belief that a healthy domestic economy depended upon expanding foreign markets guided U.S. foreign policy. The U.S. government was embarked upon its first adventure with overseas imperialism, as epitomized by the seizure of the Phillipines from Spain in 1898. To open the British-dominated Chinese markets, the U.S. State Department began promoting international controls over the opium trade.

The U.S. further hoped that its advocacy of international controls would mollify both Chinese merchants and the Chinese government, which was engaged in a ruthless nationalistic effort to stamp out opium use among its own subjects. International controls would also please American missionaries in China, who felt that British opium was ruining the Chinese people. Finally, international controls would help the U.S. replace the Spanish government's narcotic monopoly in the Phillipines with total narcotic prohibition.

Two international opium conferences resulted, one in Shanghai in 1909 and one at The Hague in 1911. Out of the latter came the first international opium agreement, The Hague Convention of 1912, which called upon all participating nations to establish internal control over narcotics. Much to its embarrassment, the United States government, after sponsoring the opium agreement, had no such controls. In order to fulfill the U.S. obligation and to provide a model for other nations, Congress passed, virtually unnoticed, the Harrison Narcotics Act of 1914.

Federal control over narcotics also received endorsement from the American Medical Association and the American Pharmaceutical Association, both of which desired government regulation as an instrumental tool for dominating and cartelizing the medical and pharmaceutical professions. A diverse and weak system of state drug-prescription laws already existed as a result of the efforts of these two associations.

As originally written, the Harrison Act only regulated, and did not prohibit, opiates. Because of worries about the act's constitutionality, Congress explicitly framed it as a revenue measure and charged its enforcement to the Treasury Department. It licensed and taxed all importers, manufacturers, and distributors of narcotics, and required a doctor's prescription in order to acquire narcotics, except in small doses. The act, however, contained ambiguous language stating that a physician could prescribe drugs "in the course of his professional practice only." The Treasury Department, which was charged with enforcement of the Harrison Act because the act was ostensibly a revenue measure, interpreted this phrase as totally forbidding the prescription of narcotics to "addicts." The courts, after dissenting for five years, sustained the Treasury Department's interpretation.

The hard-line position of the Treasury Department, and the reversal of opinion by the courts, reflected the profound changes in public attitudes that resulted from the hysteria of World War I, the "Red Scare" of 1919, and the triumph of alcohol prohibition, all of which rapidly transpired after passage of the Harrison Act. Americans viewed narcotic addiction as undermining the war effort, and took seriously the frequent wild rumors of secret German plots to turn U.S. soldiers and citizens into dope fiends.
Suddenly, drugs were a major vice among young people. Fantasitc and unsubstantiated accounts of pushers giving candy loaded with narcotics to school children circulated widely. Once the war was over, narcotics became associated with Bolshevism and anarchism. New York City, for example, established a Committee on Public Safety in May of 1919 to investigate two supposedly related evils: bombings by revolutionaries and heroin use by youngsters.

In this atmosphere of suspicion and intolerance, the governemnt campaign against narcotics encountered no restraints. The same agency, the Treasury Department, was initially responsible for administering both alcohol prohibition and the Harrison Act. Inevitably, enthusiasm for the prohibition experiment spilled over into the control of narcotics, with the same excessive enforcement techniques applied in both areas.

By 1925, the Treasury Department had tshut down 44 heroin-maintenance clinics around the country. One third of all persons in federal penitentiaries in mid-1928 were Harrison Act violators, more than the combined total for the next two categories of prisoners: violators of alcohol prohibition. By 1938, 25,000 doctors had been arraigned for supplying narcotics to users, and 3000 of them were serving prison sentences. The government also shut down 44 heroin-maintenance clinics around the country. A series of amendments that totaled 55 by 1970 steadily strengthened the Harrison Act; myriad state laws of increasing severity further supplemented the federal act.

As the government's war against narcotics was escalated, many of the notorious conditions associated with the modern drug problem made their first appearance. A black market in narcotics emerged, with its linkage to crime. And the health and status of identified opiate users began to decline. Heroin all but supplanted the other, milder opiates on the black market, because it packaged greater potency with the same risk of arrest and punishment.

One would expect that Congress and the state legislatures, as they stiffened the penalties for using and selling drugs, possessed overwhelming evidence about the harmful effects of opiates. Yet, on the contrary, they had no such evidence, and even today there is absolutely no scientific basis for the claim that the regular use of opium, morphine, or heroin has deleterious health effects.
In 1956, Dr. George Stevenson and a group of British Columbia researchers exhaustively reviewed the medical literature on narcotic addiction, and reported, "To our surprise we have not been able to locate even one scientific study, on the proved harmful effects of addiction."

Their findings are confirmed in such reputable pharmacology, texts as Goodman and Gilman's The Pharmacological Basis of Therapeutics, 6th ed. (1980), as well as such exhaustive surveys as Edward Breecher's Consumers Union Report, Licit and Illicit Drugs (197Z). Medical experts agree that the opiates are among the safest of all drugs, and undoubtedly far less dangerous than either alcohol or nicotine.

All of the alleged health consequences of heroin are actually the effects of the laws themselves. The prohibition of heroin results in an artificially and exorbitantly high price. Malnutrition, skin discoloration, rotted teeth, and the other "symptoms of addiction" result instead from users spending most of their money on drugs and very little on food, sanitary surroundings, and medical and dental care. Unsterile syringes cause hepatitis and spread other diseases. Without the laws, users could - with little difficulty - acquire either sterile syringes or heroin pure enough to sniff, smoke, or ingest orally.
Whenever users have been able to get opiates easily and cheaply, none of these effects have been noted. American soldiers in Vietnam had ready access to high-quality heroin, and it was impossible to tell who was using heroin by appearance or behavior. Only a urine test could make the distinction.
Throughout history, some very prominent and successful individuals have been regular opiate users. Dr. William Halsted, the father of American surgery and founder of Johns Hopkins Medical Center, was a morphine user all of his adult life, yet none but his closest friends knew. He died at the age of seventy, having performed some of his most brilliant operations while an addict.

Estimates of the number of doctors who regularly take opiates today run as high as one percent. Charles Winick, a New York public health official, discovered that exposed physician users were more successful than the average physician. Studies in Newark and Brooklyn indicate that heroin users, even in the ghetto may be better off economically and better educated than the average ghetto resident.
The popular impression of the addictiveness of heroin also requires some qualification. Regular users of heroin and other opiates can develop a very serious physical dependency that will lead to severe withdrawal symptoms if the drug is no longer administered, but the notion that after only one experience with heroin, an individual becomes hopelessly addicted, forever craving the drug, with only a slim chance of ever "kicking" the habit, is highly exaggerated. Even the Drug Enforcement Administration admits that 8O percent of the nation's half million heroin users are not hardcore addicts, but infrequent or light users who go on and off the drug with relative ease. It usually requires a couple of weeks of daily shooting to acquire any noticeable addiction. Heroin users, furthermore, can be remarkably flexible about the frequency and dosage of their drug use, and significant variations exist between different individual users.

Of course heroin, like any other drug including caffeine, can cause death if taken in a large enough dose. Most of the reported heroin overdoses, however, are not genuine overdoses, but are another unintended ill consequence of the drug laws. Street-quality heroin is so diluted that a user would have to inject nearly 5O street "bags" at once in order to get a lethal quantity. This could hardly occur by accident, but even if it did, death from a true heroin overdose takes one to twelve hours, during which time death ean be easily forestalled with nalorphine, an effective antidote that is stocked in all pharmacies and hospitals and that brings the victim around in a few minutes.

Reported "overdoses" actually result from lethal combinations of heroin and other substances. Sometimes, these combinations result from taking heroin with another drug, like alcohol (as did Janis Joplin) or cocaine (as did John Belushi). More often, the other substances are those with which the heroin is cut, including quinine, strychnine, talc, battery acid, and sugar. Street-quality heroin contains these impurities only because it is illegal.

Finally, let us consider the connection between heroin and crime. Estimates of the proportion of property crimes committed by heroin users range from as high as 70 percent to as low as 10 percent. None of these estimates are very reliable, but the higher figures are particularly suspect. The Drug Abuse Council, in its report on The Facts About "Drug Abuse," reveals that the connection between heroin and crime "has been repeatedly overstated and even misrepresented to support tough enforcement policies." For instance, the Drug Enforcement Administration estimated that heroin users committed over 100,000 robberies, burglaries, larcenies, or auto thefts per day in 1974. That comes to 36.5 million crimes for the entire year, which according to the FBI Uniform Crime Report is almost four times the 9.7 million crimes reported in these categories for all persons. Even allowing for the Bureau of Justice Statistics' estimate that the number of unreported crimes approximately equals the number of reported crimes, the DEA is charging heroin users with 17 million crimes that never occurred.

Although we do not know the actual strength of the correlation between heroin and crime, one conclusion is certain: to the extent that heroin use does generate crime it has nothing to do with the physical characteristics of the drug, but rather results solely from the fact that heroin is illegal.
A Detroit study by the Public Research Institute of the Center for Naval Analyses found that whenever stricter law enforcement reduced the supply of illegal heroin, driving up its price, the rate of property crime would rise. Only because heroin is illegal does a user need approximately $100 a day to maintain a regular habit. Judging from the pharmacy price of morphine, the same amount of heroin - 50 mg. - would cost no more than $1.50 on the free market.

In short, all of the supposed evils of heroin are either (1) total fabrications or (2) consequences of the anti-heroin laws themselves. These laws did not originate from any sincere or legitimate health concerns, but were the product of blatant racism and special interest. Heroin on the free market would be cheap, as well as legal, leaving heroin users with no unique reason to commit crime. It would be available in unadulterated form, at precisely measured quantities, alleviating the "overdose" problem. And governments at all levels would no longer waste billions of tax dollars on a futile quest to suppress the trade in a substance that has no proven health hazards.

The solution to the heroin problem is complete legalization. Heroin should be openly available on the free market with no restrictions whatsoever on use, sale, or manufacture. Drug laws have not prevented heroin use, but instead have left a legacy of overcrowded prisons, clogged courts, increasing crime, wasted tax money, mounting "overdose" fatalities, and misallocated police resources that otherwise could have protected life and property.

Drug use in society is a function of many complicated cultural factors. Trying to stamp out drug use with laws is ineffective, and imposes additional intolerable costs.
Even restrictions upon the sale of heroin to minors are unnecessary and unjust. The current Draconian laws have not curtailed heroin's growing popularity with young people, since the power of the state can never substitute for parental guidance. And those young people effectively beyond parental guidance because they are out in the market supporting themselves deserve have the same freedom to run their own lives as adults.

If heroin were as dangerous as widely believed - or deadly - that still would not justify its prohibition or regulation. The best way to foster drug safety is through open competition on the market. Government laws, as we have repeatedly seen, artificially encourage the substitution of one drug for another. The substitute is either more powerful or more readily obtainable, but often more harmful.
The free market, in contrast, would permit individuals to seek out and indulge in the safest drug providing the desired sensation. Drug manufacturers would have a strong incentive to discover or synthesize such safe alternatives.

In the final analysis, the use, sale, or manufacture of an illegal drug, regardless of the drug's safety, are victimless crimes. The use of an illegal drug harms no one but possibly the drug user. The manufacture or sale of illegal drugs are capitalist acts, providing a service that customers value. Drug laws make criminals out of people for merely engaging in peaceful actions of which others disapprove.
Individuals should be free to produce, exchange, and put into their own bodies any chemicals or substances they choose, whatever the halth effects. Heroin laws are not merely counterproductive and costly; they are a fundamental violation of individual rights.

Treatment of Refractory Major Depression with Opiates

Source: American Journal of Psychiatry
Date: 156:2017, December 1999

Treatment Augmentation With Opiates in Severe and Refractory Major Depression
Belmont, Mass.

Letter to the Editor
To the Editor: Substantial evidence supports the antidepressant efficacy of opiates (1). This report summarizes our open-label experience using the µ-opiate agonists oxycodone or oxymorphone in patients with highly refractory and chronic major depression.

Mr. A was a 44-year-old man with severe and chronic depression. Numerous trials of antidepressants produced only limited benefit. Mr. A also had an extensive history of opiate abuse, and he noted that the only times he ever felt normal and not depressed was during opiate use. Because of the refractory nature of his depressive symptoms and his apparent self-medication with opiates, Mr. A was given a trial of oxycodone under strict supervision. After 18 months of oxycodone treatment (10 mg/day), Mr. A remained in his longest remission from depression without the emergence of opiate tolerance or abuse.

Ms. B was a 45-year-old woman with bipolar disorder and opiate abuse (in remission for 2 years). A trial with standard mood stabilizers had failed, and she had experienced mania with several standard antidepressant drugs. As with Mr. A, Ms. B reported feeling well only when taking opiates, particularly oxymorphone. Oxymorphone (8 mg/day) was thus cautiously added to ongoing lamotrigine therapy (as a mood stabilizer), and she remained well for a minimum of 20 months without drug tolerance or abuse.

Mr. C was a 43-year-old man with chronic major depression that was unresponsive to numerous antidepressants with and without augmentation. Detailed questioning revealed that he once experienced marked antidepressant effects from opiates that he received after a dental procedure. There was no history of opiate abuse, and a cautious trial of oxycodone was initiated. Mr. C experienced a dramatic and gratifying antidepressant response from oxycodone (10 mg t.i.d. for 9 months) without opiate tolerance or abuse.

This report describes three patients with chronic and refractory major depression who were treated with the µ-opiate agonists oxycodone or oxymorphone. All three patients experienced a sustained moderate to marked antidepressant effect from the opiates. The patients described a reduction in psychic pain and distress, much as they would describe the analgesic effects of opiates in treating nocioceptive pain (pain arising from the stimulation of nerve cells).

Two of the three patients described in this report were previous abusers of opiates. Although the clinical use of opiates in patients with a history of opiate addiction is usually contraindicated, in these cases there was a strong indication that they were self-medicating their mood disorders (2) with illicit opiates. None of the patients abused the opiates, developed tolerance, or started using other illicit substances.

We used oxycodone in three additional patients without histories of opiate abuse. In two of these three patients, oxycodone produced a similar sustained antidepressant effect. Two of these patients experienced mild-to-moderate constipation, and one experienced daytime drowsiness from the opiates. Opiates should be considered a reasonable option in carefully selected patients who are desperately ill with major depression that is refractory to standard therapies.

Bodkin JA, Zornberg GL, Lukas SE, Cole JO: Buprenorphine treatment of refractory depression. J Clin Psychopharmacol 1994; 15:49–57
Khantzian EJ: Self-regulation and self-medication factors in alcoholism and the addictions: similarities and differences. Recent Dev Alcohol 1990; 8:255–271