February 09, 2005
Dopamine D2 Receptor Blocker Cures Cocaine Addiction In Rats

Professor Malcolm Horne of the University of Melbourne's Howard Florey Institute has found that a drug which blocks the D2 receptor on dopamine neurons eliminates cocaine cravings in rats previously addicted to cocaine.

The Howard Florey Institute’s Prof Malcolm Horne and his team successfully cured cocaine addiction without withdrawal symptoms in rats - a discovery that could help develop drug addiction treatments for humans.

Cocaine increases dopamine, the body’s own ‘feel good’ drug produced by the brain. Repeated use causes tolerance for the drug so that withdrawal results in low levels of dopamine and continuous use is required to keep dopamine at normal levels, and even higher doses to get the ‘high’ levels of initial use. Cocaine withdrawal is often accompanied by mental and physical symptoms.

The Florey scientists cured cocaine addiction in rats by fooling their brain cells into thinking that there was a shortage of dopamine. As a result, their brain cells made more dopamine, which meant cocaine was not needed to increase dopamine levels and the addiction was cured.

Dopamine production and nerve cell endings capable of releasing dopamine were increased when the D2 receptor was blocked by the drug.

Dopamine is released by specialised nerve endings in the brain called terminals. The amount of dopamine is sensed by the D2 receptor, which regulates whether more or less dopamine needs to be released. Horne’s team discovered that the number of terminals increase or decrease according to the levels of dopamine and found that when dopamine levels are high, the D2 receptor not only shuts down dopamine synthesis, it also reduces the number of terminals. When dopamine is low, it gives the signal to produce dopamine and make more terminals.

Prof Horne’s team gave a drug that blocks the D2 receptor to cocaine addicted rats and found that they could increase the number of terminals even while the animals had free access to cocaine. With time, the rats stopped seeking cocaine, and even when re-exposed to the drug some weeks later, did not relapse in the way that would be expected. The rats’ normal dopamine levels had increased, curing the addiction and removing withdrawal symptoms such as anxiety.

The news release excerpted above and various Australian media reports on this study do not provide a name for the antipsychotic medication used by Professor Horne's team. However, many antipsychotics bind to D2 receptors including risperidone and olanzipine. Some of those drugs bind at serotonin receptors and other sites as well. So without more details from Horne's lab we can not be certain that the effect he saw was really due to the D2 receptor blocking effect. Still, if it works on humans the mechanism of operation is of secondary concern.

The paper that will provide the details is not out yet but you can watch for it in the journal Neurobiology of Disease.

D2 receptor blockers can cause the pituitary to make too much prolactin with all sorts of undesirable side effects.

Symptoms of hyperprolactinaemia include amenorrhoea, galactorrhoea, infertility, loss of libido and erectile dysfunction. Resulting hypogonadism may cause osteoporosis.

My guess is that many of those effects come from prolonged use of a D2 receptor blocker drug. This may not be a problem for cocaine addicts since Horne's work showed that the antipsychotic drug he used did not have to be taken indefinitely. The D2 receptor was blocked by the antipsychotic drug he used, more dopamine was produced by the brain, compulsion to use cocaine dropped, and then administration of the antipsychotic was halted.

The ability to cure drug addictions would reduce crime, child abuse, birth defects from pregnant moms on drugs, brain damage, and a whole host of other problems. Therefore we all stand to gain enormously from the development of effective treatments for curing drug addiction.

Share |      Randall Parker, 2005 February 09 01:16 PM  Brain Addiction

Name Withheld said at February 9, 2005 1:44 PM:

Ironically, my wife uses a D2 antagonist (domperidone) for control of gastroparesis. Yeah, it does blow your prolactin levels through the roof. Things can get a little milky sometimes. Libido does not seem to be affected in women ;)

The good news is that Domperidone has never been approved by the FDA, and the hundreds of people with severe gastroparesis who need it have to get it from outside the US. It passed FDA stage 1 trials, but not stage 2 trials for a technical reason. Maybe this will lead it to having type 2 trials for cocaine addiction, then it can be obtained by gastroparetics in the US. Ah yeah, my wife has a cocaine addiction, yeah, that's it!

Bob Badour said at February 9, 2005 9:39 PM:

The limitation I see with this as a treatment for addiction is it will only deal with physical withdrawal, and it will do nothing to overcome the psychological dependency caused by classical conditioning. Nor will it change the factors that led the individual to addiction in the first place.

While certainly physical withdrawal is a challenge for medical practitioners (withdrawal symptoms themselves can kill the patient after all), I suggest conditioned responses cause most recidivism.

In other words, while I think the discovery is important, I do not see a silver bullet that will end addiction.

Stormwind said at February 12, 2005 1:15 AM:

I agree that a "silver bullet" alone will not cure addiction. But removing the physical symptoms by increasing dopamine production might allow a person enough respite to gain control over and change the conditioned responses, especially with the help of a therapist who understands addiction and behavioral issues. One of the concerns I might have is what happens to the brain chemistry when the treatment drug is discontinued. Some addiction studies seem to show a longer term decreased ability to produce sufficient amounts of dopamine for a recovering addict (or an alternate theory is that some people produce lower levels in a pre-addiction state which prompted them to 'self-treat' and then become addicted). I look forward to reading the research.

Colin said at February 17, 2005 6:02 PM:

This doesn't sound right at all on many levels, especially if they are talking about risperidone, olanzapine or other atypical anti-psychotics. Sure the brain might be producing more dopamine in response to the antagonist but the anti-psychotics are also blocking the dopamine's action at the same time. People on anti-psychotics sleep a lot, have reduced libido's, weight gain, and generally don't get too exited about anything.

Because of this blocking action, people on anti-psychotics don't get as much of a rush off of cocaine/amphetamines. Additionally one of the mechanisms of (amphetamine-based) addiction is the pleasurable surge it gives you just thinking about the drug. The dopamine antagonist action of anti-psychotics most likely dampens this reaction as well.

My bet is that the rats didn't go of the cocaine as much not because they had more dopamine but because the anti-psychotics damped the rush of the drug and the rush part of the craving. This may still help some human addicts but it definately won't be so clear cut of a solution and most people won't be so thrilled with the side effects of anti-psychotics, which in many ways are just like withdrawal.

carrie said at March 16, 2005 6:14 PM:

having had a 19 year methamphetamine addiction i have to say that the physical withdrawal was, and still is, the absolute worst. i have yet to get my motivation back. i am grateful that i get up early and work full time; i do the domestic chores that have to be done (although i send my laundry out and have someone in every two weeks to clean) but i have no desire to do anything once i am off of work. and when at work, there are many many instances where i have to FORCE myself to initiate and complete a task. when i am not working, i do not do that at all. and my sexuality has gone to the wayside, big time. so, having a drug that would help with my dopamine system would be wonderful.

ilona said at April 8, 2005 12:10 PM:

funny thing is, i am looking for a treatment of depression-like fatigue because of shortage in dopamine. I should think that bupropion could be a better way to make dopamine levels increase. Bupropion inhibits reuptake of dopamine and also works on D2-recepotor. Anti-psychotics do have the tendency to supress a lot of functions which can lead to symptoms of fatigue, loss of libido etc. Might Bupropion be a way to help cocaine addicts, without the other symptoms occuring?

Laurie said at June 20, 2005 11:18 PM:

People/Carrie, You want a treatment that will bring dopamine to normal levels. GVG also called Vigabatrin STOPS ADDICTION, cravings, withdrawals. It stops addiction in a few ways. Research is at BNL.GOV. Also New York University. The two posts above that mentioned "psychological dependency caused by conditioned response." No, no, no! It seems and was thought psychological, but it totally biochemical, caused by high dopamine levels in brain. This response is called "environmental cue cravings." Months into recovery when no drugs of abuse in system, a simple thought, seeing or hearing something will cause brain dopamine to rise 25%, causing intense cravings. This rise is due to an increase in brain derived nerve cell growth hormone to mature junenile nerve cells (neurons) hatched daily. This is needed because of many destroyed neurons in drug addiction. Scientists/doctors are very excited about GVG for all drugs of abuse: Cocaine, methamphetamine, heroin, tobacco, alcohol, ectasy...any drug that increases dopamine. Two clinical trials for cocaine/methamphetamine have been successful. This is a 20 year journey of study, and FDA has given approval for trials in U.S. GVG is available outside the U.S. as Vigabatrin or Sabril.

Rita said at August 14, 2005 6:19 PM:

I have a sister whose boyfriend has a cocaine addiction. He came to her and asked her to help him. He is afraid she will leave him. Is there anything I could do to help her through this rough road ahead. Is there a drug that stops the withdrawals and make recovery easier on him and easier for my sister to cope. Is Rehab the only solution. Please Help!! I want my sister happy and not scared so she can stay stable for thier new born son they have together. They are a good couple and know it will work out if he stops using drugs. I know the best thing to is be there for them both But I don't know where to start nor How to.

Thank you respectfully,


Tony said at August 20, 2005 5:26 AM:

I have been taking the atypical antipsychotic Aripiprazole - Abilify (Dopamine sub-2 agonist) for a year and have quit smoking cigarettes and drinking alcohol except on a social basis since that time. The feeling is one of extreme nausea if I do cigarettes. I have a methamphetamine problem, but I don't get the Parkinsonian side-effects/withdrawl symptoms anymore. I do have a hard time finding direction (psyco-social addiction) in life, however. May Maximillian Kolbe be with us.

Zico said at August 25, 2005 7:12 PM:

I had problems with cocaine and 4 months latter I continue to have problems with dopamine,I have dysphoria,the cocaine anxiety, due to decreased receptors and dopamine release and some muscle tremors,low libido too.This happens cause cocaine is a dopamine indirect agonist by blocking its reuptake.These cause a low dopamine system,with a REDUCED number of receptors,to take L-DOPA,for example, would worst the problem.
Thats why this thing should really work,I didnt read the entire text,but I think thats the cure,cause is the same exact inverse of the damage done by cocaine.I hope the colateral effects wont be too strong.Sorry for english mistakes.

L.V. Morris said at November 14, 2005 8:28 AM:

I can't believe their may be a cure for this epidimic and you all are sitting on your behinds and not trying to save some of the men and women who would go as far as to volunteer in order to get out of the madness of addiction. I'm struggling with a cocaine addiction myself and if I could do anything to end this misery and pain I would; so if your organization needs a crash test dummy just seek out those like me who would do anything to overcome this addiction!

MYSTICLIVENOT said at March 6, 2007 3:06 AM:

"It only took one hit" as I looked back the day it happened.

...and I regret it so much that I wish I could reverse the time....Being in a "crack town" for 10 years operating a service-business is hard enough finding employees without any drug habits or addictions. Seeing all this young people in the streets, homeless and living a life based of getting high on crack.

I am so against those that gets out of control...doing everything just to get a rock to smoke, stealing from you and believing their own lies...stories, excuses and more lies...an addict not caring anymore and will find a way to rob you just to get high...This is what's happening in my town and I never "mingle" with those crack-addicts. I never understand why not just give it up...I rather stay smoking my herb that puffing on a crack pipe..

10 years in business,now 33 years old now...loosing more than $ 100,000 from a project that took 2 months and never got paid...$ 17,000 in lawyer cost and never made it to court...wiped 8 years of my life savings...now I'm broke and this was before I became an addict...this is why I puffed on that pipe and the reason was to put me in a state of mind not thinking about my lost...What a mistake to say Yes. WTF did I think?

"It only took one hit" and I will do anything to stop this habit; and a "12 step program" is just BS being in a crack town surrounded with bad energies, thinking you will be "drug-free" and re-covered. "That's my opinion"

Now I found this site and reading all this...I know it's out there but why so "hidden" helping this addiction?


--------------------------------PLEASE HELP AND LET US PUT IT TO THE TEST------------------------------------------

Being a crack smoker is not who I am, it's not ME... and loosing my family will be devastated!


Dave Peters said at March 11, 2007 5:23 AM:

The drug used was HALOPERIDOL

Richard Iles said at December 20, 2007 7:21 PM:

Addiction is an illness, no matter what the reason for the first puff or shot.... I don't believe it is about NOT caring. I believe it is about escape of a percieved reality or self-medicating. Once the addition has been born it is alive and is not easily put to death or controlled. The physical yearn is far less than the mental and emotional bond to the drug. I'm speaking from experience both as an addict and as a clean sober person today. I now am watching the people that I love still battling the roller coaster ride with the monster-gorilla riding on there back. Are any of the D2 receptor blocker approved for use today? Please HELP...

rcp said at February 22, 2008 8:33 PM:

wow, extremely enciteful and informative, I've been an addict for 20 years, if there was a pill that would cure addiction if you only took one pill, I would probably take two, and screw it up, i"m extremely intelligent, come from a strong family background, have had multiple years of clean time, good job, yet something always takes me back there, maybe something like this would help. Is there anything you can take that makes you deathly ill if you use cocaine? something similar to the effects of what they give alcoholics.its usually those last minute urges that get me, I'll tell myselg all day at work, don't want it,won;t use today, but then i get off work and can't make it home ww/out copping.

jake said at February 11, 2009 1:52 PM:

Little late on posting a comment, but for the record, haloperidol over TWO WEEKS causes up to 90% more dopamine receptors to grow. Now this is problematic as you get dyskinesias and such, but a slow, prolonged exposure to haloperidol THEN WITHDRAWAL will result in dopamine levels at least around 50% higher than normal people. If it is true that addicts have even less, then that number should possibly be higher. What they didn't mention in the article is when studies checked dopamine activity in humans, the hightened dopamine levels stayed that way - there was no evidence they down-regulated even after weeks/months of no haloperidol or even an antipsychotic.

FAROOQ AHMED said at February 10, 2010 12:39 AM:


Heather and Mike said at November 4, 2012 8:17 AM:

my husband is a good man ,does everything for his family ,hard working,and a wonderful father to his children. But he has a severe addiction problem with cocaine. He has clean time. But its like the drug wispers in his ears.He will not be thinking about it,and then all of a sudden he's shot out of a cannon. And he dont stop until all funds are exausted.The other day he came to me and said he's so tired of this addiction he's ready to end his life, because he's suffering! I cant bare to see him cry nor suffer anymore,he's my everything.Can someone please help us?my Email address is thisirishlassis2cute4u@yahoo.com. If theres something that can help he'll do it!

John said at March 19, 2013 8:34 AM:

Hey, it looks like there are a few people stumbling on this thread who are having trouble with cocaine addiction. One treatment that has been shown to be effective for cocaine addiction in smaller trials is n-acetylcysteine. Here's one of the studies related to this:


Here's somewhere you can buy n-acetylcysteine online:


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