Introduction to Opiates

An opiate is any narcotic alkaloid found in opium (the latex released when immature seed-pods of the opium poppy, Papaver somniferum, are scored) or any semi-synthetic derivative thereof with narcotic properties. The main alkaloid are morphine, codeine, noscapine (also known as narcotine), thebaine and papaverine. There are also about 25 other minor alkaloids found in opium, which have unknown or negligible pharmacological value. Of these only morphine and codeine are truly opiates, although thebaine, due to its chemical similarity with codeine and morphine, is commonly classed as an opiate. It does not have narcotic effects, possessing rather stimulant properties, and is thus, by the above definition, not technically an opiate. It is a Schedule 2 controlled drug in America, as it can be used to manufacture hydrocodone and oxycodone and many other true opiates.

Some of the more well known semi-synthetics opiates, that is to say narcotic drugs, created from morphine, codeine and thebaine are heroin (diacetylmorphine / diamorphine), dihydrocodeine, hydrocodone, hydromorphone, oxycodone, oxymorphone, and there are many others.

An opioid is either a fully-synthetic or semi-synthetic alkaloid ("a naturally occurring organic nitrogenous molecule that has a pharmacological effect on humans or animals") made to mimic the action of a natural opiate alkaloid. These include all narcotic drugs which are made as derivatives of an alkaloid from an Opium Plant (Papaver Somniferum). A common example of this would be pain relieving drugs such as the Codone and Morphine group drugs. Morphemes are semi-synthetics usually derived from Morphine and the Codons are also semi-synthetics derived from Thebaine (An Opiate alkaloid found in P.Somniferum). However, there are both semi and fully synthetic alkaloids that are identical nitrogenous molecules which have a pharmacological effect on both humans and animals but are either fully or partly synthetic. These are opioids rather than opiates.

It is a common mistake to blanket define all of these narcotic substances as either "opiates" or "opioids." The two have become almost interchangeable but there is a very clear difference. Opiates are naturally occurring and organic nitrogenous molecules which posses a pharmaceutical value to humans and animals. Opioids are synthetic nitrogenous molecules which posses a pharmaceutical value to humans and animals.

Common parlance tends to use the term "opiate" to refer to all opiate/opioid drugs, and for the purposes of this article the term "opiate" shall be preferred except where differentiation is required.

Effects of Opiates/Opioids

The medical effects of most opiates/opioids are analgesia (pain relief), cough suppression, and reduced gut mobility that often leads to constipation. In some cases, respiratory depression is a desired effect; for example, tachypnoea causing respiratory fatigue and anxiety in patients with pulmonary oedema resulting from left sided heart failure may be given morphine to reduce work of breathing (National Heart Foundation, 2011).

Side Effects

Common side effects include sedation, euphoria, constipation, constricted pupils, nausea, itching, chest pain, difficulty breathing and sometimes even death. Some problems can also arise when mixed in sufficient quantity with other drugs that depress the central nervous system.

Opiate Addiction

Opiates are notorious for their addictive qualities. They are both physically and psychologically addictive. Physical addiction occurs when the body becomes dependent on opiates to achieve internal homeostasis, and when the cessation of such opiates would cause withdrawal symptoms. Opiate addicts typically develop a dosing routine which the body relies on, and shortly after missing a dose withdrawal symptoms will begin. Psychological addiction can be described as an overwhelming compulsion to use the drug. An extreme desire to use opiates of such a degree that it causes otherwise irrational thoughts and actions. One sign of addiction as opposed to legitimate medical use is attempting to use a different route of administration - snorting, smoking, or injecting the drug, instead of taking it by mouth as directed.

Intravenous (IV) use is common among opiate addicts. A number of opiates, such as heroin or hydromorphone, produce a "rush" effect when injected, a powerful wave of euphoria which hits quickly and dissipates with the same speed. This rush effect, and the ritual the addict goes through in preparing a shot, are often described as being equally or more addictive than the choice opiate itself. Thus intravenous abuse can greatly increase the severity of addiction and difficulty in achieving abstinence.

Withdrawal

Some symptoms of physical withdrawal from opiates/opioid are nausea, vomiting, diarrhea, dilated pupils, goose bumps, abdominal pain, insomnia, extreme anxiety, depression, painful joint aches, back pain, and intense drug craving. While the length of physical withdrawal depends on the opiate one is dependent on, the average length is 7 days. Longer acting opiates such as buprenorphine and methadone, however, have correspondingly longer withdrawal periods, and can last up to a month.

The psychological symptoms greatly out last the physical symptoms, and anxiety, depression, sleep disturbances, and drug cravings can last for months after cessation of use. These long lasting effects are commonly known as Post Acute Withdrawal Syndrome, and are a major reason for the prevalence of relapse among those struggling with opiate addiction.

Opiate Tolerance

Prolonged use of opiates can result in the development of tolerance. This means that, over time, the same amount of the opiate drug in question will have a diminishing effect. Or, contrarily, that an increased amount of the drug must be administered to achieve the original effect. The biological mechanisms of tolerance are not fully understood, however the down regulation and desensitization of the natural opioid receptors seems to play the greatest part in the development of tolerance. (1)

Decreasing Opiate Tolerance

There are a number of ways to decrease opiate tolerance. The first is cessation. For an "opiate naive" individual (someone having no built up tolerance to opiates), abstaining from opiate use for a time will result in tolerance returning to base levels. For an opiate addict, going through the withdrawal process will reset tolerance back to that of an opiate naive individual, with a marked decrease in tolerance beginning to occur around the second day. It is important to note that there is no such thing as a "permanent opiate tolerance" - a very large percent of overdoses occur when post-withdrawal addicts use the same dose that they were previously accustomed to, which, in their now opiate naive state, is fatal.

There are also drugs which can decrease opiate tolerance. First and foremost is Iboga. Iboga is a hallucinogenic plant which has been shown to almost completely reverse opiate tolerance and withdrawal symptoms - effectively "resetting" an individual back to a pre-physically addicted state.

Tolerance to opioids is attenuated by a number of substances, including:
-calcium channel blockers
-intrathecal magnesium and zinc
-NMDA antagonists, such as dextromethorphan, ketamine, and memantine.
-cholecystokinin antagonists, such as proglumide

NMDA receptor antagonists such as DXM and Ketamine have also been shown to have partial effects in decreasing opiate tolerance. Studies have shown Ketamine in particular to be effective in reversing opiate tolerance in humans and animals (2), and it is commonly reported among addicts that Ketamine gives an enormous amount of relief from the pain of opiate withdrawal. DXM appears to have a less pronounced effect than in reducing opiate tolerance, however it is also a common withdrawal aid for opiate addicts.

History of Opiate Use

The first known written reference to the poppy occurs in a Sumerian text from around 4,000 BC. The poppy was known as "hul gil", or the "plant of joy." This suggests that the effects of the poppy were known to prehistoric man. The medical use of the poppy plant was well known to the ancient Greeks and Egyptians, and appears in ancient texts regarding medical practice. (3) The famous ancient Greek physician Galen, for example, recommended opium for the treatment of melancholy.

References

1) Harrison, L. (1998). Opiate Tolerance and Dependence: receptors, G-proteins, and anti-opiates. Retrieved September 18, 2010 from http://opioids.com/tolerance/index.html
(2) Angst, M. (2010). Ketamine for Managing Perioperative Pain in Opioid-dependent Patients with Chronic Pain: A Unique Indication?. Retrieved September 18, 2010 from http://journals.lww.com/anesthesiolo...Pain_in.6.aspx
(3) Osler, W. (1999). A Brief History of Opium. Retrieved September 18, 2010 from http://opiates.net/