Addiction Treatment Blog

Schizophrenia can be dangerous to yourself and others around you if treated incorrectly.

In any consideration of the dopamine hypothesis of schizophrenia, one of the arguments invariably put forward is that psychostimulant drugs, in particular the amphetamines, lead to a mental disorder characterised by prominent paranoid feelings, or outright paranoid delusions. This many authorities have suggested, is a state that is very similar to some schizophrenic states. As the psychostimulants increase brain dopamine levels or neurotransmission, schizophrenia must therefore involve increased dopamine functioning and accordingly dopamine antagonists are its appropriate treatment.

However, the picture in real life is considerably more ambiguous. In the first place there has long been a substantial amount of evidence that up to a third of individuals with ‘schizophrenia‘ actually do well on psychostimulants. Read more…

Anticholinergics

The anticholinergics are a group of drugs, examples of which are given in the table below, which antagonise the action of the neurotransmitter acetylcholine (Ach) at one of its receptors – the muscarinic receptor.

These drugs were initially used to treat Parkinson’s disease. They have since largely been superseded by the use of L-dopa. As most neuroleptics commonly cause parkinsonian symptoms, the anticholinergics have been used routinely to alleviate side effects, where the effect of L-dopa would be blocked by the neuroleptics themselves.

It has been suggested that they have been used too routinely. In many instances it has been common practice to prescribe an anticholinergic agent along with a neuroleptic, when the neuroleptic is first given – that is even before side effects have appeared. The rationale for this has been that the emergence of side effects may compromise an individual’s willingness to continue with medication. The more cynical view is that an early prescription of an anticholinergic drug means that hospital staff or general practitioner will not be called out of hours by a distressed patient, who has just been paralysed by a dystonic reaction or had some other side effect. This of course ensures that they both get a night’s sleep. Read more…

As with most of the drugs, Neuroleptics may have some serious side effects.

Neuroleptics all bind to dopamine receptors. Almost all bind to at least one other receptor as well but not all of them bind to the same other receptor. People also differ. The combination of these two principles means that the side effects of a neuroleptic may differ from one individual to another.

The side effects listed seem fearsome. But most are readily reversible by reducing the dose, changing or halting the drug or using an antidote.

Treatment, however, may involve a trade-off. In practice, it seems that many individuals are prepared to tolerate the interference with daily living that some of the side effects listed may cause, in exchange for peace of mind. The reason for listing these side effects in full is not to deter prescribers from prescribing or takers from taking but rather to involve the taker in making the trade-off rather than having it imposed insensitively on them, and to give prescribers some feel for the nature of that trade-off. Read more…

History of the Neuroleptics

There is considerable controversy over who discovered the neuroleptics, one that is highly relevant to the question of just what these drugs do. Chlorpromazine was first synthesised in 1950, with the intention of producing centrally acting antihistamine for the control of cardiorespiratory sock or collapse. It was first used widely in humans in 1952, along with other agents, as part of an anaesthetic cocktail, when its effects were noted by a chlorpromazine – they were neither sedated in the usual way with anaesthetic agents or analgesic, but rather appeared to become indifferent. This he described as an ataractic effect. A notable point here is that the effect must have come on within an hour or so after having had the drug – and it came on in normal subjects.

In 1952, Jean Delay and Pierre Deniker reported that chlorpromazine was of benefit in controlling states of manic and psychotic agitation. Around the time of its launch in 1954, there was no suggestion that chlorpromazine was likely in any way to be specific to schizophrenia. That came later. In the mid-1950s, chlorpromazine was being reported as being useful for almost every psychiatric condition (hence its trade name Largactil – Large Action).

Laborit has always claimed priority in the discovery of chlorpromazine. Delay and Deniker and others have disputed this. To some extent taking sides in the dispute depends on whether you see the neuroleptics as being in some way curative of psychotic illness or as producing an anti-agitation effect – an effect that is produced equally in all takers who are agitated, whether or not they have a psychological problem. Laborit’s descriptions are in line with the approach that is adopted in this article, which is that neuroleptics act by inducing a state of psychic indifference – in everyone who has them, and that they do this within a short period of time. Delay and Deniker’s approach is the approach that later led to the notion that neuroleptics were anti-schizophrenic.

Within a few years of their use, it became  clear that the new group of drugs produced extrapyramidal side effects. As further compounds came on stream, it seemed that only those that produced extrapyramidal effects brought about benefits in the psychoses. This led to two things. One was that the drugs as a group came to be called neuroleptics by Delay, a term which literally means ‘nerve seizing‘. The second effect was that, for 30 years, little effort was put into finding ‘antipsychotic‘ agents that would not produce extrapyramidal effects – atypical neuroleptics as such agents are now called. It is only in recent years with the rediscovery of clozapine – a drug almost devoid of extrapyramidal effects – that the picture is changing.

Are Neuroleptics Anti-Schizophrenic?

It is commonly believed that neuroleptics drugs are anti-schizophrenic.

The evidence that neuroleptics are anti-schizophrenic comes from a series of research projects which have shown that subjects who take them after discharge from hospital are much less likely to be readmitted than those who do not.

The dopamine hypothesis of schizophrenia has been developed based on this kind of evidence. Briefly, this hypothesis states that as all neuroleptics block the dopamine system in the brain, and as they are beneficial in schizophrenia, therefore there must be something wrong with the dopamine system in the brains of individuals with schizophrenia. A major research enterprise has developed around attempts to test this hypothesis. From a sociological point if view, there have been two consequences of this. One is that many current researchers have had a vested interest in believing that neuroleptics are anti-schizophrenic. Another has been given the ‘known’ abnormalities in the dopamine system in schizophrenia, the fact that the drugs work on the dopamine system means that they are anti-schizophrenic.

For those who take the approach that neuroleptics do reverse the core disturbance in schizophrenia, the usual response to patients not getting better has been to give more of the drugs, and the idea that an individual might not take their drugs is viewed very seriously. In addition, the idea of paying much heed to what the takers of the drugs have to say about whether they are helpful or not seemed irrelevant – after all, these drugs are curative of an illness, a cardinal manifestation of which is supposedly lack of judgement.

The view taken throughout this chapter is that neuroleptics are not specifically anti-schizophrenic but that they are useful for anyone who is agitated, rather than just for people who have schizophrenia. The evidence for this comes from daily practice. Anyone who is agitated will usually be prescribed neuroleptics, whether or not they have schizophrenia. They may have depression, mania or just be agitated. Read more…

GABA Receptor Agents

There are two reasons for using a medicine that turns on the GABA receptor. The first is to make withdrawal from sedatives and alcohol easier. The second is to get a special effect on the dopamine spike.

For withdrawal, we use the drugs that were originally designed to combat epileptic seizures. I’ll call them Anti-epilepsy Drugs (AEDs). There are several AEDs and most are equally as good in making sedative withdrawal better, but the one I like the best for that purpose is valproic acid, sometimes called valproate. Many of the newer medications have to have the dosage slowly built up over time, so it doesn’t do much good if you’re in withdrawal. With valproate we can start the full dose in the first day and get some relief. Another one that works fast is therefore good for withdrawal is a medicine called carbamazepine.

The other reason to use an agent that acts positively at the GABA receptor is to use one that specifically turns on a particular type of GABA receptor called GABAb. Under the influence of GABAb the dopamine spike from a drug is not as high and the resulting crash is not low. It can help someone who is trying to stop using from using as much as they had been. There’s no guarantee with it, but it’s a useful technique. The AEDs are good for this GABAb effect as well as an old muscle relaxant called baclofen. We don’t need to use this as much as we used to now that acamprosate is available in this country (see glutamate agents below).

Dopamine Agents

If the problem is that there is not enough dopamine tone and because of that normally rewarding things are not rewarding, we can raise the dopamine tone. Hopefully then the person can feel reward from normally rewarding events and not have to look for external rewards to get to a normal level. There are a few ways to do this. My favourite is to block the reuptake of dopamine with a drug called buproprion, but only the long acting version. Another is to stimulate the release of dopamine with a new drug called varenicline. Varenicline works at the nicotine receptor to release dopamine. It’s been approved by the FDA to help people stop smoking and it’s pretty new.

There are a couple of other medications that other doctors use that I have not found helpful in the long run in treating people with addiction. The first is amphetamines, and the second is a drug called modafinil. Amphetamines are dangerous because they don’t just block the reuptake of dopamine, they run the reuptake pump in reverse. At first it was thought that modafinil worked like buproprion, and only blocked the reuptake of dopamine. But I’ve had a couple of patients report it felt and acted more like an amphetamine, so I’ve stopped using it.

Glutamate Modulators

A new medication called acamprosate works to block the glutamate-triggered craving that comes in response to sensory cues that remind the person of previous drug use. The glutamate signal is normally released in the reward center and serves to get the compulsive use cycle spinning. Because each dopamine spike is followed by a crash, this spinning leads to the craving one normally feels during the dopamine crash. With acamprosate blocking the glutamate signal, the reward circuit doesn’t spin up as much, and there is less chance of craving.

I’ve also noticed that it helps with what we used to call “denial” and now call “pre-contemplation.” I think the denial is caused by an overflow of the brain’s opioids into the area that remembers emotions, and under the influence of this overflow the person cannot remember how bad it was to use. As the acamprosate emotions, and under the influence of this overflow the person cannot remember how bad it was to use. As the acamprosate tunes down the glutamate signal, the reward system doesn’t get spun up. So, instead of the brain’s opioids flooding the area and causing “denial,” acamprosate keeps the opioid flood from happening. It’s been very helpful and low in side effects.

Since using acamprosate, I have not had the need to use a GABAb agent much other than for withdrawal. The GABAb effect must have been lowering glutamate but maybe not as directly because acamprosate seems to work better than the AEDs on the issue of denial.

Opioid Receptor Agents

A lot of doctors block the opioid receptor, which makes sense if you want to stop drug use. It doesn’t make as much sense if you’re treating what was wrong with the person before they started using drugs to feel better. The medication to block the opiate receptor is called naltrexone, and it has recently been released as a once a month shot for people who have had trouble maintaining abstinence.

A new drug called buprenorphine has been approved by the DEA and the FDA to treat opioid addiction. It gets on the opioid receptor and turns it on just enough to feel normal and not high. My patients have had a great deal of success with it.

Buprenorphine can only be started once all the opioid the person has been using is out of his system, so it’s a difficult drug to get on, especially if the patient has been using methadone or another long acting opioid. But patients are on it they generally do very well.

The Causeway Retreat is an addiction treatment clinic, specialised in addictions, such as heroin addiction, cocain addiction, drug addiction. To talk about your condition and our help available to you, give us a call: +44 (0)207 100 7260.

Yes, I believe so. Let’s take a look at a recent article published in the prestigious Journal of Addiction Medicine. Han, Lee, et al published a study done on over 140 Korean male adolescents, about half of whom had what the authors called “Excessive Internet Game Play (EIGP).” What they found was that the boys with EIGP were more likely to have a mutation of one of their dopamine receptors that made it more difficult to see the dopamine signal. They also found that for kids with EIGP, the dopamine receptor mutation was associated with a measure of reward dependence that sort of corresponds with the Cloninger Type II I told you about. Well, that makes sense from what I’ve told you so far.

What’s surprising is that the EIGP kids were also more likely to have a mutation of their enzyme that breaks down dopamine (COMT), leading to a higher dopamine spike with a reward. Well, that doesn’t make sense at first, but let’s think about it. Say you have a low dopamine tone and you play a video game and get a normal person’s reward from it – well, no big deal. But if you got a better than normal reward from it because you also had the COMT mutation the game would be much more rewarding. In essence what the researchers found was that the dopamine receptor problem was the set up and the ability to have a bigger then normal release with such a little response was what made the kids respond to video games. Perhaps you don’t need that COMT mutation to respond to stronger stimulants, such as cocaine. This is an example where two problems pool together to make a specific reward more likely to be used.

What if your dopamine function is fine, but your enkephalin receptor is broken. You won’t feel normal levels of reward unless you have an opiate in your system. But maybe cocaine won’t work so well because your dopamine system is fine for now. Anything you can imagine that could go wrong in the diagram has probably been done in nature. In the future we’ll have the ability to look at the genes in this system so that we can more accurately pinpoint the treatment.

The Causeway Retreat is an addiction treatment and mental health clinic, specialised in addictions, such as heroin addiction, cocain addiction, drug addiction. To talk about your condition and our help available to you, give us a call: +44 (0)207 100 7260.

First, the basics of addiction are the inability to stop or moderate the reward when using, and not using, to be constantly thinking about the reward and highly prone to using. There are three parts of the brain that bear on these two characteristics:

1. the dopamine/enkephalin feedback loop in the MFB
2. the glutamine signal to the MFB that can trigger relapse
3. the Periaqueductal Gray that handles withdrawal.

In the MFB, dopamine is produced and the reward causes it to be released to act on the reward center. That dopamine release causes a release of enkephalins, which prompt a further dopamine release, and this goes around and around until the dopamine is exhausted. The reward center also sends a signal to the front part of the brain that instills positive self-esteem. If the enkephalin part or the dopamine part doesn’t work right, the reward center doesn’t send the signal as well as it should. Other things besides dopamine release can affect the dopamine signal. If the dopamine receptor isn’t up to par, the signal won’t get through as well. If the dopamine transporter recycles the dopamine too fast, it won’t be there long enough to produce a good signal. Other things can be wrong as well: don’t make enough dopamine, don’t get dopamine down to the end of the neuron, don’t release enough dopamine in each packet,don’t release enough packets with each rewards, don’t send the signal from the receptors, or don’t transmit the signal to the frontal cortex. And you can increase the list by thinking of everything that can go wrong in the enkephalin part of the cycle as well. Read more…

It’s kind of hard to come to terms with the words we need to use because all of the words already have a meaning to people. For instance, it makes no sense to call gambling a drug because it’s obviously a behaviour. To call taking cocaine a behaviour is confusing because it mixes up the drug with the action of taking it. So we need to come up with a word that means, in essence, stuff that releases dopamine. Science already has a term for that in behavioural psychology. The word is “reinforcer.” Reinforcer doesn’t really do it for me, but if you like that word for what we’re talking about, I can live with it. My problem is that for behavioural scientists it brings up the idea that the person is normal and that no illness exists. The word I like better is “reward.” A reward causes dopamine to be released in the reward center of the brain. It doesn’t tell us if the reward comes from outside or inside, and it doesn’t tell us if the person is ill or well. It’s just a reward.

Now, we can see that if people have normal reward systems and get normal reward from normal life, there is no need for other external reward inputs. However, if someone doesn’t have a normal reward system and needs a specific behaviour or drug to feel normal reward, then we will see their focus concentrate on that useful reward.

It might be helpful to know what sort of things give us a reward signal. For people with addiction these things can become compulsive. These include alcohol and drugs, of course, including nicotine. As well there is food and sex. Interestingly, novel stimuli also work and that would include 30 new images every second like TV or a video game. While I believe addiction is a single disease, people point out to me all the time the differences between addicts such as cocaine addicts and compulsive overeaters: “You don’t see people grinding up hamburger and injecting it,” they say with a smile to tell me how wrong I am. The difference is that different drugs and behaviours effect the reward system through different mechanisms. For instance, cocaine works directly in the MFB to block the reuptake of dopamine (it blocks the vacuum cleaner raising the dopamine level) while food works through several different sensory mechanisms to release dopamine.

The Causeway Retreat addiction treatment experts are ready for help to you and your loved ones 24 hours a day and 7 days a week. Please give us a call on +44 (0)207 100 7260 and talk to one of our doctors or nurses.

Dopamine

Yes, there is. Recent studies have been done where the gene for the dopamine receptor has been injected into the Medial Forebrain Bundle of a rodent that shows a preference for alcohol. The dopamine receptor gene turns out more dopamine receptors, the level rises, and the animal stops drinking as much alcohol.

So what’s the catch? The effect doesn’t last; it works for about 10 days. So if you’re looking for an easier softer way than being honest with yourself and going to AA meetings, all you have to do is brain injection every 10 days. And if that sounds like a good idea, then you can still hear your disease talking to you.