Opiates
Opium is distilled from the juice of the poppy and has been used medically
for thousands of years. It relieves pain and suffering, stops diarrhea and
dehydration from dysentery. It also produced pleasure and relief of anxiety.
This is why it is used recreationally. The opium seed pod oozes a white
substance that is collected in balls. Early users ate this substance, giving rise
to the description of drug addicts in China and in the 1800s as “Opium
eaters.” Raw opium is used to produce morphine and from that, heroin.
Opiates are all drugs derived from opium- morphine, codeine, or any
semisynthetic opium-based drug like heroin. Laudanum was a drug derived
from opium that many upstanding ladies used in the 17th, 18th centuries. It
was manufactured with a combination of other drugs in a wine base. Opium
seems to change the way the user perceives the world. Not only does it
relieve pain, but it sends the user into a phantasmagoria of dreams, waking
or sleeping. It lasts much longer than an alcoholic high and imposes a
serenity and calmness to the user. But it also removes motivation.
Morphine is the active narcotic agent in opium, names for the god of
dreams, Morpheus. Codeine (Greek for “poppy head”) is the secondary
active narcotic agent in opium. As the hypodermic syringe was perfected in
1853, morphine could be delivered directly into the bloodstream, acting
effectively more quickly. It was rapidly put into medical use during a variety
of wars in the mid-19th century. Unfortunately, many veterans came home
from these wars addicted to morphine.
Heroin was derived from morphine through a chemical transformation,
giving heroin about 3X the potency of morphine. The transformation
increases the lipid solubility of the heroin molecule to allow it to enter the
brain more rapidly. Heroin is more potent and acts faster than morphine. It
was introduced as a non-addicting substitute for codeine in 1898. Tolerance
and dependence were only considered minor problems. At low doses, this
was possible, but as it was used at higher doses, dependency was easily seen.
Harrison Act was passed in 1914 as a revenue measure. It did not make
addiction illegal and didn’t forbid doctors to prescribe drugs for addicts. It
simply required that drugs be received from doctors and those drugs should
be registered. Before the Harrison Act, drugs in all sorts of tonics could be
ordered OTC or even through the Sears catalog! Laudanum cost much less
than alcohol, so it was seen as a cure for alcoholism! Drug smuggling was
made illegal, and in 1920 – 22 it was made illegal to get drugs from the
doctor. It was placed on the list of Schedule I controlled substancesmeaning those with “no medical use.” Schedule II drugs are seen as having
medical use, but must be prescribed and controlled by a doctor. Later it was
made legal for doctors to prescribe outside the hospital, but most did not go
back to that practice, since they had been harassed for several years over
drug prescribing. Addicts were forced to go to illegal dealers for their
heroin. Cost went up 30-50X. So criminal activity associated with drug use.
The addict was no longer seen as a pathetic victim of his habit, but a scourge
of society, weak, self-indulgent, degenerate. There was a drop in middleclass, middle-aged users after the Harrison Act. Usage descended to people
in “the life”- meaning actors, musicians, show people, criminals, prostitutes.
After WWII, drug use was more associated with minority groups in city
slums, people with little hope of any successful life.
The 1960s changed everything- heroin became less available, the price of
heroin went up, it became adulterated and profits went through the roof. This
contributed to further deterioration of the ghettos, where most drug users
lived. College students, hippies were more likely to use LSD, but core cities
held more heroin users and crime skyrocketed in response to this increase.
Vietnam became a risk to many young soldiers trying to make sense of their
involvement in this foreign country, fighting a war most Americans didn’t
appreciate or honor. To deal with their increased frustration and
hopelessness, many servicemen were beginning to use pot and heroin.
Heroin in SE Asia was much more potent and cheaper than in the States.
Most troops believed that it was only addictive if injected, so most soldiers
sniffed it or smoked it. Now the service was urine-testing personnel ready to
come home. 5% of soldiers were testing positive. During follow-up studies it
was found that most vets did not continue to use once they came home. So it
was discovered that dependence was not inevitable, and that in
circumstances of wide availability and low cost, unhappiness, people will
use narcotics recreationally.
1970s and 1980s – estimates of heroin use came to 400K – 500,000. Heroin
was coming from opium grown in Turkey, process in Marseilles and shipped
to the US- the “French connection”. Turkey quit providing it when the US
offered $35 million to the growers to quit growing it in 1972 (the original
farm subsidy!) Once it was reduced by Turkey, Mexico took up the slack- it
was processed differently, producing a brown/black substance- black tar
heroin. In 1974 the US began drug eradication programs in Mexico and the
supply declined somewhat. In the 80s the supply was from Southwest AsiaAfghanistan, Pakistan, Iran, with Mexico next and Southeast Asia (Laos,
Thailand) third. By the 90s Southeast Asia was the biggest supplier.
Current use of heroin - in the 90s the look of a heroin addict became
popular with models- Heroin chic.- sunken eyes, unhealthy thinness, loss of
any animation in the eyes. There was some increase in usage by high school
seniors in response to this celebrity attention. Smoking opiates became more
popular, along with smoking crack cocaine. Users would mix heroin with
crack or heat the heroin and inhale the vapors from a pipe. Smoking and
snorting allowed the user to get the effects they wanted without the use of
needle, with the risk of AIDS and hepatitis.
Chemical characteristics
Opioids are naturally occurring and synthetic drugs that stimulate or
block morphinelike receptors. Fentanyl is used mostly with surgical
anesthesia for pain relief. This was even produced in lollipop form for
children facing surgery, etc.
Narcotic antagonists are drugs that can block the actions of narcotics
such as morphine, heroin, or opioid agonists. Naloxone can reverse the
depressed respiration from narcotic overdose. Naltrexone is used for
addicted people to prevent them from getting a high if they do use heroin.
Mechanism of action
Opioid receptors in the brain were isolated in the 1970s, but
scientists couldn’t understand why we would have receptors in the brain for
such a bizarre drug. IN 1974 the enkephalins were isolated- morphinelike
neurotransmitters in the brain and adrenals. These substances, produced by
the brain acted like morphine and were many times more potent.
Endorphins were discovered next- endogenous morphinelike
substances that are found in the brain and pituitary gland. The enkephalins
and endorphins are stored in the neurons’ terminal vesicles and released to
modulate neural activity. These various endorphins operate in specific sites
in the brain, depending on what their functions are. The sites relate to pain
relief, as welll as response to stress, and producing a euphoric mood“runner’s high.”
Beneficial uses
Pain relief is the major therapeutic use for morphine. Narcotics
primarily reduce the users response to pain- the suffering. They say they are
still aware of the pain but it’s no longer very aversive. They tend to sleep
lightly when under a therapeutic dose.
Intestinal disorders – these drugs quiet the GI tract and were used for
babies’ colic early in the last century. They counteract diarrhea, so can save
lives when people suffer dysentery. Narcotics decrease peristaltic
contractions (so you can see why constipation can be a side effect for
recreational users.)
Cough suppressants- narcotics decrease activity in the cough control
center in the medulla. Codeine especially has antitussive properties.
Causes for concern
Dependence/ Tolerance develops to most of the effects of the
narcotics. For pain relief, the dosage usually will have to be increased to
maintain effect. This is true for the euphoria desired by recreational users.
There is also a tolerance built up as a conditioned reflex, triggered by the
environment usually associated with narcotic use. The reflex triggers
responses in the body to compensate and manage the drug more effectivelyproducing tolerance.
Physical dependence occurs as tolerance is established. Now as the
drug wears off, withdrawal signs begin. Symptoms are similar to a bad case
of flue- craving for the drug, of course, anxiety and agitation, running nose,
teary eyes, tremors, hot and cold flashes, aching, loss of appetite, insomnia,
higher blood pressure, temperature, nausea, vomiting, diarrhea. If the person
has been on a high dose, the symptoms will be more severe. Methadone
is a synthetic opiate designed to help users get off heroin, but it produces
withdrawal symptoms, too, but they are less severe.
Psychological dependence has to do with the reinforcement
properties of narcotics. Obviously the drug produces a euphoria after use
that is positively reinforcing, as well as sets up an expectation of this payoff
after every use. Once physical dependence has developed, however, and
withdrawal symptoms have been experienced, now the user will use as a
result of negative reinforcement- avoiding or removing the pain of
withdrawal. This contributes to establishing a powerful addiction.
The needle habit becomes associated with the pleasure- reward
expectation cycle due to classical conditioning. Like Pavlov’s dog salivating
at the expectation of food once hearing the bell, users develop a certain
enjoyment at simply preparing their injection, etc. They have developed a
positive conditioned response to the environment and ritual of drug use.
Even when users have had an antagonist designed to remove any high from
shooting up their drug, they will say they still experience pleasure from the
process of shooting up. It takes several experiences of shooting up without a
physiological reward before they experience the process as noxious.
Toxicity potential
Acute toxicity is depressing the respiration, which can be lethal, as
the respiratory centers become less responsive to carbon dioxide levels in the
blood. This is particularly risky when narcotics are combined with alcohol.
Overdose results in the narcotic triad: coma, depressed respiration, and
pinpoint pupils. ERs will dispense naloxone to antagonize the narcotic
effects in a few minutes. They slip into sleep- often having “pipe dreams”
along with a clouding of consciousness that makes mental work difficult, if
not impossible. There is loss of interest in sex, and men often suffer
impotence. Nausea and vomiting are also results of heroin injection.
Chronic toxicity does not show up in any organ system, but there are
often sores that develop at injection sites, blood-borne diseases like hepatitis
and HIV.
Patterns of abuse
As addiction is consolidated, the user will experience withdrawal
symptoms around 6 hours after dosage. That means they will shoot up 3-4
times a day and feel a definite urgency to meet the demands of the habit. A
habit of this depth will cost $30-100/day. Since the powder is mixed with
unsterile water and injected without cleansing the site, many infections
occur. So the common sites- left forearm become scarred and larger veins
often collapse. Some users start with skin-popping- subcutaneous injections.
As users lose their appetites, they can become very ill from malnutrition.
Other diseases can progress without the addict noticing, due to the pain
relieving properties of their drug. Many users who stay on the drug for years
may gradually mature out and lose interest in their drug. Most users use for
an average of 8-9 years. One of the biggest risks to users is getting a very
pure dosage, leading to inadvertent overdose.
Misconceptions and Preconceptions
The first high may be intensely pleasurable- described as a wholebody orgasm- but this experience declines quickly- and most users just
describe a feeling of pleasant effects- a brief rush and then longer tranquility.
Vomiting also happens in nontolerant users. But to keep getting these
pleasant effects, the amount of drug must be increased.
Withdrawal is not as awful, painful as depicted in movies. It may be if
the user has been on a very high dose, but those with a less extreme habit
can get naloxone, the antagonist, and feel no withdrawal symptoms at all.
After one shot, you are hooked for life- Becoming dependent takes
some time and persistence on the part of the beginner. It requires some
regular use to establish an addiction. There are occasional users.
New Users, New Drugs
As fentanyl was discovered, illicit chemists produced derivatives
called “China White.” These are known as designer drugs, since they are
synthesized in a lab, but they have a similar chemical structure as another
controlled substance.
MPPP is a derivative of meperidine (Demerol) but if it is impure, this
toxic substance can produce permanent brain damage through damage to
dopamine neurons, resulting in Parkinson’s disease.
Treatment
After the Harrison act of 1914, there were public narcotic clinics
established to help users get off the drugs. They gradually detoxified the
patients and recommended a lifestyle change such as work on a ranch, etc.
These centers were shut down in 1925.
Current approaches include narcotic antagonists. They begin
withdrawal immediately, but without the continued effectiveness of the drug.
It requires the patient to be motivated to continue the use of the antagonist.
There are some uncomfortable side effects of some of these drugs.
Naltrexone can antagonize the effects of heroin for 24 hours, but only works
for motivated users who will continue taking it.
Methadone maintenance- methadone is a synthetic narcotic
analgesic developed in WWII, taken orally it has a long duration of
effectiveness. It leaves the system slowly, so withdrawal symptoms are less
severe. It can be useful for heroin dependence, as it blocks the pleasurable
effects of opiates. It disrupts the states of being the addict experiences:
“straight” (normal), “high” or “sick”. Since he spends little time being
straight, it’s hard to maintain a functional life of work, etc.
Methadone clinics sprang up in the 60s to shift users to methadone,
since early studies showed 94% of criminal users ended their heroin
addiction in this way. The conflict here is- are we treating society for a
social problem, or actually helping an addict to become more functional? It
does require the user to show up at the clinic daily for the drug, and submit
to counseling and support as part of the requirements of the treatment.
LAAM is another synthetic opiate approved in 1993 for maintenance
treatment of narcotic-dependent patients. It has longer lasting effects than
methadone. Patients only need the drug 3X a week and feel less of a narcotic
effect from LAAM.
Buprenorphine is another semisynthetic opioid analgesic used for
treating opioid dependence. It lasts a long time and fills the opioid receptors
effectively.
There is still a controversy about how to manage individuals with a narcotic
habit- maintenance through a clinic, or repression of the supply and
prosecution of users. Our society seems to have more drug-related problems
because we hold such punitive views about narcotic use. The more we try to
control access to drugs, the greater number of addicts we have. In countries
that legally prescribe heroin for addicts, there have been drops in burglaries,
robberies and car thefts by users. The debate is whether harm reduction
(providing users methadone, clean needles, etc.) is more useful than a strict
moral stand against drug use.