The Addicted Brain (21 page)

“Medical marijuana” is the use of the plant, its extracts, or its ingredients as a physician-recommended medicine. Its documented effects include reduction of nausea and vomiting, stimulation of appetite, and reduction of the symptoms of glaucoma. There are also recent studies of the use of THC in treating various cancers, opioid dependence, and even Alzheimer’s disease. The use of marijuana as medicine, or some aspects of it, is controversial in some circles.

Sigmund Freud, the founder of psychoanalysis, was one of the first scientists to experiment with cocaine, which comes from the leaves of the
Erythroxylon coca
plant. He was impressed with the stimulant properties of the drug, and because these properties were opposite to the depressant properties of alcohol and opiates, he reportedly proposed that cocaine be used as an antidote or cure for alcoholism or opiate addiction. He even suggested this to some friends who took his advice. Unfortunately, Freud realized his mistake when cocaine proved to be addicting. This highlights the fact that different addicting drugs can have different acute effects—even opposite ones—and yet, they share the same addicting property. Fortunately, today we have behavioral tests in animals that detect possible addicting substances before they are given to people.

Cocaine can be taken by chewing coca leaves where the drug is absorbed in the mouth, although this is hardly a concern in this country. When the pure form is available as a powder, it can be snorted into the nose, eaten, or dissolved and injected intravenously. The latter is the preferred route among experienced users because it more readily produces a rush of sensations. Crack cocaine, or the free base form of the drug, is smoked because heating readily vaporizes cocaine in this form. Smoking and intravenously injecting drugs are the most effective methods for producing high levels of drug in the brain quickly. Intravenous injections send the drugs effectively to the brain, and smoking results in an efficient transfer of drug from the lung to the blood and then to the brain.

Acute injection of cocaine produces arousal, a sense of well being and confidence, improved performance on tasks of alertness, and an increase in heart rate and blood pressure. Higher doses produce euphoria, which is often the goal of drug abusers. Repeated use can result in agitation, paranoia, psychosis, and addiction. Withdrawal, also referred to as the “crash,” includes fatigue, depression, anxiety, and craving for the drug. Other important toxicities include irregular
heart rhythms and other cardiac problems, oxygen deprivation because cocaine constricts blood vessels, and seizures. An elevation of blood pressure increases the risk of stroke. Other drugs are often taken together with cocaine. Users sometimes add alcohol to the mix to reduce irritability, which many cocaine users suffer. Similarly, cocaine is used with heroin.

In the brain, at the level of neurotransmission, cocaine blocks the transporters for dopamine, serotonin, and norepinephrine, which increase the amount of neurotransmitter in the synapse and increases the synaptic action of the neurotransmitters (see
Chapter 4
,
Figure 4-4
). But the addicting properties of cocaine are attributed to a blockade of only the dopamine transporter.
⁵
I discovered this along with Dr. Mary Ritz and others when it was shown that the most potent cocaine-like compounds in self-administration studies were also potent in blocking the transporter, and vice versa. This study was the culmination of the work of many including Drs. Roy Wise and Nick Goeders, whose studies pointed at dopamine as the key target for cocaine and other psychostimulants.
⁶
(see also
Chapter 4
, Endnote 2).

Methamphetamine (also known as crank or ice) has been around for many years and has been used to treat obesity, Attention Deficit Hyperactivity Disorder (ADHD), and sleepiness. Its trade names include Adipex, Desoxyn, and Methedrine. It is also a major drug of abuse and a dangerous one at that. There has been literally a torrent of meth abuse, partly because it is highly addicting and partly because it can be synthesized easily, even in your kitchen. Not only is the drug toxic, but the synthesis of it, or “cooking” as it is called, is dangerous. There are many cases of severe burns and injuries to those making the drug. This substance is most similar to amphetamine but its effects are somewhat different. Meth gets into the brain more easily than amphetamine, causes more dopamine to be released into the synapse than amphetamine, and has been associated with more
psychotic symptoms than cocaine. It has also been implicated in the development of Parkinson’s disease. Its psychostimulant-like effects are similar to those of the other psychostimulants like cocaine and amphetamine. They include increased alertness and wakefulness, elation, euphoria, and elevation of mood.
⁷

An outstanding feature of meth toxicity is its capability to severely impair and perhaps destroy dopamine- and serotonin-containing neurons in the brain. Drs. Jean Lud Cadet, Annette Fleckenstein, Syed Ali, Jerry Meyer, and others have carried out many studies on the way meth produces its toxic effects on neurons. Methamphetamine can also have serious implications related to pregnancy, including a shortened pregnancy and a lower birth weight. There might also be postnatal neurological symptoms in the offspring. In users, it can produce a psychosis characterized by grandiose and paranoid delusions, hallucinations, and disordered thoughts. The duration of these episodes can vary from hours to days. A tendency for the user to have rotten teeth is often associated with meth use. Withdrawal from methamphetamine can be serious. Symptoms include depression, anxiety, fatigue, craving, excessive sleep, loss of pleasure, and loss of concentration. The acute onset of withdrawal is sometimes called the “crash.”

A vivid description of what the author believed to be meth toxicity is described by Nick Reddy in
Methland
(reprinted by permission of International Creative Management, Inc. Copyright © 2009 by Nick Reding).

“Jarvis is just one of many local legends...staying high on crank for twenty-eight days....By the time I met him, he’d had four heart attacks...couldn’t sleep and rarely had an appetite. Almost all his teeth were gone, and those that remained were black and decaying. He was in almost constant pain; his muscles ached and his joints were stiff....One of (his children)...born at the peak of his parents’ intravenous meth use, was wearing a colostomy bag by the age of ten.
Unable to shoot up with the finger nubs left him by the lab explosion, Jarvis had taught himself to hold a pipe and lighter so that he could resume his meth habit...”

As already noted, meth produces its addicting effects by targeting the dopamine transporter. However, unlike cocaine, which blocks only the uptake of dopamine but does not promote its release, meth both blocks uptake and promotes the release of the neurotransmitter. Methamphetamine also blocks the transporters for serotonin and norepinephrine, which produces other effects. For example, blockade of the norepinephrine transporter increases the availability of norepinephrine and therefore increases blood pressure.

A separate section is not devoted to amphetamine because it is similar to both cocaine and methamphetamine. It affects nerve cells the way meth does.

An important class of drugs that are among the most widely prescribed in the world is the benzodiazepines. This is a general chemical name for drugs that share certain chemical structures and properties. Trade names of drugs in this class include Xanax, Klonopin, Valium, and Ativan. They are used as sedatives and as sleep inducers or hypnotics. As sedatives, they reduce anxiety and have a calming effect; as sleep inducers, they cause drowsiness that facilitates the onset of sleep. Each drug can be used as a sedative and as a sleep inducer, the only difference being the dose that is used. Sleep induction requires a higher dose than is required for calming. These drugs are relatively safe in overdose situations and have replaced older drugs such as the barbiturates. Sometimes these drugs are used before various diagnostic or surgical procedures to produce both calming and amnesia.

Important side effects are those expected of a sedating agent. They can cause increased reaction times, impairment of mental and
motor functions, amnesia, and accidents. When taken during the day for anxiety, the dose is important because the drugs can produce excessive sleepiness. Some drug users take these drugs to get high, and others take them to treat anxiety and irritability associated with use of other drugs. Chronic use, say over several months, can lead to addiction. Withdrawal symptoms include anxiety, agitation, sleep disturbance, muscle cramps, and dizziness. However, if the addict has been using high doses, seizures and delirium are also possible.

This class of drugs acts at the GABA-A receptors just like alcohol. By themselves, they do not stimulate the receptors, but they enhance the action of the naturally occurring neurotransmitter GABA. Patients who abuse alcohol are also more likely to abuse benzodiazepines.

Oxycontin is a popular drug of abuse that falls in the opiate class that also contains heroin and morphine. Opiate drugs are used legitimately in the treatment of pain and are mainstays in that area. But, the same neuronal systems that alter pain also produce feelings of euphoria and well being, which lead to abuse and addiction. Tolerance occurs, and there is a significant withdrawal syndrome when the drugs are not taken. Opiates produce some unpleasant effects including nausea, vomiting, and sedation, particularly in people not addicted or not being treated for pain.

Because of the medical importance of this group of compounds, there are many different opiates produced and made available for treating humans. Heroin is one of the most dangerous opiates. It is quickly converted to its active metabolite and gets into the brain rapidly. There is a period of intense euphoria followed by feelings of tranquility. Withdrawal produces a craving for the drug, anxiety, insomnia, irritability, cramps and muscle aches. Withdrawal can last five to ten days and is unpleasant, although it is usually not life threatening. Overdose is a danger and if death occurs, it is often due to
respiratory depression. The mortality rate for heroin addicts on the street is very high, as it is for users of other drugs as well. Opiates are often used in combination with other drugs. For example, it is often taken after or with cocaine (called a speedball) to quell the agitation and irritability produced by cocaine.

Drug users who inject opiates (and other drugs for that matter) can obtain serious infections associated with using contaminated and dirty needles. These include ugly skin abscesses, hepatitis, tuberculosis, and AIDS. They are also at higher risk for sexually transmitted diseases. Opiate drugs work by stimulating receptors for the opioid peptide neurotransmitters such as enkephalin and endorphin, which are chemicals that occur naturally in the brain.

Ecstasy, sometimes called X, is an interesting substance that has both stimulant effects like cocaine and amphetamine, but also has hallucinogenic or psychedelic effects like LSD. It is mainly popular among younger drug users, often at dances called raves. Ecstasy used to be considered useful in psychotherapy to promote compassion and insights, but hard data on this is lacking. Its laboratory name is methylenedioxymethamphetamine (MDMA).

Its effects are reported to include empathy, insight, and feelings of closeness to others. But it also produces, as psychological tests have shown, increased depression and anxiety, impulsiveness, and hostility. Its toxicity is serious in that it seems to deplete or destroy axons and nerve terminals that contain serotonin, perhaps forever, in animal studies. Drs. Perry Renshaw, Scott Lukas, and others have found a reduction in the size of the cerebral cortex in human MDMA abusers.
⁸
Paradoxically, some findings suggest that the behavior of human users does not seem to be a problem, but there is a concern about the future in that brain changes might presage significant, future problems. Although MDMA has not emerged as a significant addiction problem so far, there is concern that it might. It can result
in increased heart rate and blood pressure, and there have been reported overdoses that have resulted in death. MDMA has diverse effects in the brain. It can block serotonin transporters, resulting in changes in neurotransmission, and it can bind to a variety of neurotransmitter receptors. MDMA is basically an analogue of amphetamine and methamphetamine, and there are other analogues of amphetamine that are abused. For example, MDA has similar properties to MDMA.

Ecstasy is known as a club drug along with others substances that include GHB, Rohypnol, and ketamine. GHB and Rohypnol (roofies) are sedating, and Rohypnol can produce unconsciousness and amnesia. Ketamine distorts perceptions and feelings. They are called club drugs because they are sometimes used heavily at dance clubs, bars, parties, and other gatherings.

PCP (also known as angel dust or rocket fuel) is a synthetic substance that was originally made to be used as an anesthetic. But, it had negative psychological effects and was never approved for human use. It is called a dissociative drug because it produces feelings of detachment and disconnection from the environment. It also causes distortions of sights and sounds, and disordered thinking reminiscent of schizophrenia. For this reason, animals given PCP have been considered a model of that disease. At higher doses, it produces agitation, potentially life threatening seizures, and respiratory depression. There are press reports describing wildly aggressive behavior and bizarre acts of violence by those using the drug. For example, one anecdotal report describes a man on PCP who broke both of his wrists trying to get out of handcuffs. Another strange story involves a man on PCP who cut off parts of his face, including his nose, lips, and ears, and fed them to his dogs!
⁹
Although these behaviors might depend on a violence-prone personality or preexisting mental illness of the drug user just as much as on the drug itself, PCP can be a dangerous substance.
Microscopic signs of nerve toxicity are found in users that can lead to persistent brain damage. PCP works by blocking the NMDA subtype of the receptors for the neurotransmitter glutamate.