December 12th, 2004

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Reducing Tolerance To Morphine Could Aid Pain Therapy

Morphine is one of the most commonly used drugs in the treatment of severe and chronic pain. A major complication with its use over the long term is that patients develop tolerance to it, as well as becoming addicted.

A way of reducing tolerance would be of great benefit, because it would allow doctors to use lower doses over longer periods and still control pain effectively.

A study published in this week's issue of Cell provides just that, by showing that giving a small level of a different drug at the same time as morphine can reduce the development of tolerance.


Utopian Pharmacology


Can safe, sustainable analogues of MDMA be developed? There is an urgent need for non-neurotoxic empathogens and entactogens suitable for lifelong use. Alas no single "magic bullet" yet exists that replicates the subjective effects of MDMA on a long-term basis. Hence most of us are doomed to display the quasi-psychopathic indifference to each other characteristic of the MDMA-naïve state.

A Brief History of MDMA

MDMA [3,4-methylenedioxy-methamphetamine: 'Ecstasy'] was first1 synthesized in 1912 by the German pharmaceutical company Merck. MDMA was patented in Darmstadt, Germany on May 16th 1914, issue number 274,350; and promptly forgotten. Merck's researchers had no idea of the significance of what they had done. Merck were searching for a good vasoconstrictor, a styptic to reduce bleeding. In 1912 two of their chemists, G. Mannish and W. Jacobsohn, created MDMA as a by-product while attempting to synthesise hydrastinin. MDMA is listed on Merck's patent-application merely as a chemical intermediate "for products of potential pharmaceutical value".

MDMA surfaced again briefly as one of a number of agents used in clandestine US military research during the 1950s. The CIA's Project MK-Ultra was investigating new techniques of brainwashing, espionage and mind-control. MDMA, code-named EA-1475, was tested at the US Army's Edgewood Arsenal in Maryland. However, unlike LSD or the ill-named "truth drug" scopolamine, MDMA was used only on animals: mice, rats, pigs, monkeys and dogs. Thankfully, MDMA's military potential was not realised. For although MDMA is no infallible truth-serum, its effects on the human user might indeed be abused for sinister purposes by skilled interrogators. The heightened emotional responsiveness, lowering of defensive barriers, openness and sense of closeness to others induced by MDMA can promote an honesty of self-disclosure that might be manipulated for malign ends. Fortunately, this hasn't yet happened on an organised scale.


Deadly Short Cuts

Heroin is named after the German word for hero, heroisch. According to popular legend, its substitute, methadone, was initially christened Dolophine in honour of Adolf Hitler. In reality, the name comes from the Latin dolor, meaning "pain", and fin, meaning "end": hence "end of pain".

The consumption of heroin is marked by a euphoric rush, a warm feeling of relaxation, a sense of security and protection, and a dissipation of pain, fear, hunger, tension and anxiety. When heroin is snorted or smoked, the rush is intense and orgasmic. Subjectively, time may slow down. Any sense of anger, frustration or aggression disappears. Users enjoy the feeling of "being wrapped in God's warmest blanket".

Heroin is the most fast-acting of all the opiates. When injected, it reaches the brain in 15-30 seconds; smoked heroin reaches the brain in around 7 seconds. The peak experience via this route lasts at most a few minutes. The surge of pleasure seems to start in the abdomen; a delicious warmth then spreads throughout the body. After the intense euphoria, a period of tranquillity ("on the nod") follows, lasting up to an hour. Experienced users will inject between 2-4 times per day. After taking heroin, some people feel cocooned and emotionally self-contained. Others feel stimulated and sociable. Either way, there is a profound sense of control and well-being. The euphoria gradually subsides into a dreamy and relaxed state of contentment. Higher doses of heroin normally make a person feel sleepy. At higher doses still, the user will nod off into a semi-conscious state. The effects usually wear off in 3-5 hours, depending on the dose. Heroin is not toxic to the organ systems of the body. But in prohibitionist society the mortality of street users is high.


A Brief History of Opium

c.3400 B.C.

The opium poppy is cultivated in lower Mesopotamia. The Sumerians refer to it as Hul Gil, the 'joy plant.' The Sumerians would soon pass along the plant and its euphoric effects to the Assyrians. The art of opium poppy-culling would continue from the Assyrians to the Babylonians who in turn would pass their knowledge onto the Egyptians.

c.1300 B.C.

In the capital city of Thebes, Egyptians begin cultivation of opium thebaicum, grown in their famous poppy fields. The opium trade flourishes during the reign of Thutmose IV, Akhenaton and King Tutankhamen. The trade route included the Phoenicians and Minoans who move the profitable item across the Mediterranean Sea into Greece, Carthage, and Europe.

c.1100 B.C.

On the island of Cyprus, the "Peoples of the Sea" craft surgical-quality culling knives to harvest opium, which they would cultivate, trade and smoke before the fall of Troy.


Future Synthetic Drugs of Abuse


It seems likely that primitive man wished at times to escape his reality and most probably found some natural drug to facilitate this desire. In fact, abuse of the coca leaf and the opium poppy is thought to have been practiced for at least the last 3400 years (Lathrap 1976; Rosengarten 1969) and the use of peyote may have been known as early as 1000 BC (Schultes 1938; 1940). Perhaps due in part to the long history of opiate products, one of the first derivatives of a natural drug to be used pharmaceutically was heroin. The acceptance of heroin as a pharmaceutical was primal in establishing the concept that certain structural modifications of physiologically active compounds can result in new compounds which cause biological responses which are not only similar, but are enhanced as compared to those of the parent compounds. Other works such as the structural elucidation of mescaline and the preparation of N-methyl and N-acetyl derivatives of mescaline has served to strengthen this concept and to broaden the scope of permissible derivatives (Spath 1919). In the ensuing years much knowledge has been gained regarding biologically useful derivatives of the naturally occurring drugs but, most importantly, the structures of the alkaloids and the protoalkaloids have, one by one, been elucidated. This knowledge has then allowed researchers of recent times to deduce many of the structure relationships associated with specific biological responses. The sum of this hardwon knowledge allows one to produce pharmaceutically useful compounds, which have no counterpart in nature, from off the shelf chemicals. Unfortunately there are those people who would take this body of knowledge and, rather than use it for the enhancement of medical science, use it for their own financial gain. Individuals such as these have created the so-called designer drug phenomenon.

Henderson (1986) first described a synthetic drug as one which was designed by a clandestine chemist to produce a certain pharmacological response. However, today designer drugs are universally understood to belong to a group of clandestinely produced drugs which are structurally and pharmacologically very similar to a controlled substance but are not themselves controlled substances (Langston and Rosner 1986). The Drug Enforcement Administration (DEA) has noted that the designer drug terminology tends to cast a somewhat glamorous aura onto the concept, and as a result, the DEA feels that it would be wise to refer to these compounds in some other manner and suggests the use of the term Controlled Substance Analogs (CsA).

In October of 1987 the United States Government amended the Controlled Substance Act in an effort to curtail the illicit introduction of new CsA's. This amendment states that any new drug which is substantially similar to a controlled substance currently listed under the Code of Federal Regulations (CFR), Schedule I or II, and has either pharmacological properties similar to a Schedule I or II substance or is represented as having those properties, shall also be considered a controlled substance and will be placed in Schedule I. The amendment further contains provisions which exempt the legitimate researcher as well as compounds that are already being legally marketed from the provisions of the amendment.

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Medical Marijuana Facts

State Laws Protecting Patients

Effective medical marijuana laws have been enacted through ballot initiatives in Alaska, California, Colorado, Maine, Montana, Nevada, Oregon, and Washington. In Hawaii, an effective law was passed by the legislature and signed by the governor in June 2000. In Vermont, an effective law was passed by the legislature and allowed to become law without the governor's signature in May 2004.

Medical Value

Doctors and patients have found that marijuana can ease the symptoms of a variety of diseases, including: relief from nausea and increase of appetite; reduction of intraocular ("within the eye") pressure; reduction of muscle spasms; and relief from chronic pain.

Many doctors recommend that their patients use marijuana as medicine when other prescriptions have failed. Indeed, access to medical marijuana is supported by: American Academy of Family Physicians; American Nurses Association; American Public Health Association; Lymphoma Foundation of America; National Nurses Society on Addictions; American Preventive Medical Association; New England Journal of Medicine; and National Association of People With AIDS.

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Administration Exploits Safety Concerns to Make Case Against Imports

The Bush administration has again found itself on the wrong side of a hot-button political issue. This time it's prescription drug importation, which a majority of Americans and members of Congress support. Without a compelling argument to support their case against drug importation, the administration has resorted to a familiar tactic in their political playbook: fear.

In hopes of swaying Americans from the truth, the administration and its allies in the drug industry are out making phony and scary claims. They warn that drug importation is inherently unsafe, that imported drugs aren't subject to the same rigorous safety standards as in the United States, and that allowing importation will flood the market with dangerous counterfeit drugs.

But the facts and just plain common sense belie their scare tactics.


Europe's Experience Shows Strong Safeguards are Needed

The U.S. presidential election saw re-importation of prescription drugs become one of the major dividing lines between Republicans and Democrats.

President Bush says the jury is still out on whether re-importation is safe, while most Democrats say there is no reason that Americans shouldn't import cheaper medicines from abroad if it lowers costs for patients.

Meanwhile, the Kaiser Family Foundation and the Harvard School of Public Health recently released results from a survey that found 80 percent of Medicare beneficiaries supported legalization of drug re-importation from Canada if it would lower costs.


More Than Half Of Police Chiefs Oppose Legalizing Medicinal Marijuana, Survey Says

Fewer than one in two police chiefs support the use of medicinal cannabis by authorized patients, according to the results of a survey of more than 300 police chiefs nationwide conducted by the Police Foundation and the think-tank Drug Strategies.

Fifty-one percent of respondents said that local laws permitting "medical marijuana to be used for seriously ill individuals" are a "step in the wrong direction." Only 38 percent of respondents favored such a policy.

The result sharply contrasts with national opinion polls, which demonstrate that 80 percent of Americans believe that it should be legal to dispense medical cannabis to qualified patients. However, the finding is similar to a previous 2004 survey conducted by the National Association of Chiefs of Police, in which 60 percent of respondents answered "no" to the question: "Should marijuana be legalized in the United States for those who have a legitimate medical need for the drug."


Federal Bill Introduced Calling For Meta-Analysis Of Marijuana Research

Federal legislation introduced last week seeks to require the US National Institutes on Drug Abuse (NIDA) to develop a "meta-analysis of the available scientific data regarding the safety and health risks of smoking marijuana and the clinically-proven effectiveness of smoking marijuana for medicinal purposes, and to require the Food and Drug Administration to promptly disseminate the meta-analysis." The bill, H.R. 5429, was introduced by longtime medical cannabis opponent Rep. Mark Souder (R-IN), along with Reps. Henry Bonilla (R-TX), Jack Kingston (R-GA), Pete Sessions (R-TX), and Christopher Smith (R-NJ).

NORML Foundation Executive Director Allen St. Pierre said that the scientific record shows definitively that cannabis has medical utility, and criticized Rep. Souder's "longstanding and willful ignorance" of the subject.

"NORML suggests that Rep. Souder and his colleagues begin their analysis by reviewing the National Academy of Sciences 1999 report, 'Marijuana and Medicine: Assessing the Science Base,' which verified that cannabis is efficacious in the treatment of a number of symptoms, including nausea, appetite loss, and chronic pain," St. Pierre said.