Study finds link between marijuana abuse and blunted dopamine response

by Marcia Malory report
Credit: Rice University

(Medical Xpress)—People who use marijuana heavily experience a blunted response to dopamine, according to researchers at Brookhaven National Laboratory, New York University Langone Medical Center and the National Institute on Alcohol Abuse and Alcoholism. When marijuana abusers took methylphenidate, a drug that stimulates dopamine production, they did not experience the cardiovascular, behavioral and brain changes usually associated with an increase in dopamine levels. The research appears in the Proceedings of the National Academy of Sciences.

Scientists don't know much about how excessive use of marijuana affects the brain. Marijuana doesn't seem to affect the brain in the same way that other drugs of abuse do. Other drugs stimulate the release of , a neurotransmitter associated with feelings of pleasure, in a region of the forebrain known as the striatum. While some earlier studies have shown that marijuana does this as well, other studies have shown that marijuana does not have this effect. People who abuse alcohol, nicotine, cocaine, methamphetamine and heroin experience a decreased ability to produce dopamine. However, scientists have never found a link between marijuana use and reduced dopamine production.

Joanne Fowler of Brookhaven National Laboratory and her colleagues wanted to see if marijuana abusers have a different response to dopamine than other people do. To do this, they gave 24 marijuana abusers, who had been smoking a median of about five joints a day, five days a week for 10 years, the drug methylphenidate. This drug, also known as Ritalin, stimulates the production of dopamine. Fowler's team gave 24 control subjects methylphenidate as well.

When the researchers compared the two groups' reactions to methylphenidate, they found that members of the control group experienced greater increases in heart rate and than the marijuana abusers did. Members of the control group reported feeling more high, restless, anxious and affected by the drug than the marijuana abusers did.

PET scans showed that caused changes in the striatums and the cerebellums of the controls. These changes were significantly smaller in the marijuana abusers.

The research suggests that people who use marijuana excessively have problems with the reward circuitry in their brains. Even when their brains produce large amounts of dopamine, marijuana abusers don't respond to it normally. Personality tests showed that the marijuana abusers in the study were more likely to experience negative emotions, including depression, anxiety and irritability, than the controls were. This is a sign that marijuana abusers find it harder to experience pleasure than most people do.

It's not clear whether excessive marijuana use damages the brain's reward circuitry, or whether people who already have damaged reward circuitry use to make themselves feel better.

More information: Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity, PNAS, www.pnas.org/content/early/2014/07/10/1411228111

Abstract
Moves to legalize marijuana highlight the urgency to investigate effects of chronic marijuana in the human brain. Here, we challenged 48 participants (24 controls and 24 marijuana abusers) with methylphenidate (MP), a drug that elevates extracellular dopamine (DA) as a surrogate for probing the reactivity of the brain to DA stimulation. We compared the subjective, cardiovascular, and brain DA responses (measured with PET and [11C]raclopride) to MP between controls and marijuana abusers. Although baseline (placebo) measures of striatal DA D2 receptor availability did not differ between groups, the marijuana abusers showed markedly blunted responses when challenged with MP. Specifically, compared with controls, marijuana abusers had significantly attenuated behavioral ("self-reports" for high, drug effects, anxiety, and restlessness), cardiovascular (pulse rate and diastolic blood pressure), and brain DA [reduced decreases in distribution volumes (DVs) of [11C]raclopride, although normal reductions in striatal nondisplaceable binding potential (BPND)] responses to MP. In ventral striatum (key brain reward region), MP-induced reductions in DVs and BPND (reflecting DA increases) were inversely correlated with scores of negative emotionality, which were significantly higher for marijuana abusers than controls. In marijuana abusers, DA responses in ventral striatum were also inversely correlated with addiction severity and craving. The attenuated responses to MP, including reduced decreases in striatal DVs, are consistent with decreased brain reactivity to the DA stimulation in marijuana abusers that might contribute to their negative emotionality (increased stress reactivity and irritability) and addictive behaviors.

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kochevnik
2.2 / 5 (11) Jul 15, 2014
People who abuse food get fat. So the f*** what?

I smoked hash once and discovered a subconscious Morse code signal being broadcast in the neighborhood. I discovered this because my lady friend and I sang the beeps aloud in unison. Is this subversive broadcasting something the funders of these "studies" are really attempting to preserve?

Last time I smoked I say gnomes and pandas on neverending leaves growing inward into a vortex. Nice way to fall asleep
Scottingham
5 / 5 (5) Jul 15, 2014
Not sure if you helped the argument. Also not sure what point you're actually trying to make.
Scroofinator
3.3 / 5 (8) Jul 15, 2014
It's not clear whether excessive marijuana use damages the brain's reward circuitry, or whether people who already have damaged reward circuitry use marijuana to make themselves feel better.


Ya, let's go either or here... Stupid. It's the hippy effect: marijuana frees ones mind from the simplicity of a materialistic world to ponder grander things, so things that would typically make a non user happy just seem so plain to a user(I like how they found "abusers"). Why do you think it got on the schedule 1 drug list? Hippies don't fit into the capitalist picture, where materialism is king...
Tessellatedtessellations
4 / 5 (8) Jul 15, 2014
I am for marijuana legalization.

I also think users of it should read articles like this one and consider what they may be doing to themselves. I used to abuse it. I have no idea how anyone could smoke 5 joints a day, but I did use it every night for years. When I got bored with the high, I quit. It wasn't free of withdraw symptoms like pot advocates said it would be. And over a year later I am definitely less capable of feeling pleasure than I was before I ever used it. Believe it or not, numbness is a big deal. I gained a lot of valuable insights while high, not quite sure it was worth it though. In any case, I wish advocates would stop hyping it as a harmless drug and reflexively down voting articles like this one. Maybe it is less harmful than alcohol, but definitely harmful with lasting consequences that aren't fun.
Scottingham
4 / 5 (3) Jul 15, 2014
@Tessell Thank you for the insightful and level-headed comment!

Out of curiosity though, is your diminished pleasure/numbness constant or are there times when it subsides. For instance, your daily routine/life may feel that way but what about an exotic vacation?
jscroft
2.3 / 5 (6) Jul 15, 2014
Hmm, what are the odds THIS research was Federally funded?
Tessellatedtessellations
4 / 5 (4) Jul 15, 2014
@Scott when I tried two vacations it actually made me depressed because I couldn't experience any fun. Hanging out with friends, going places, anything that would normally be fun is kind of depressing to me. The closest I can come to bringing myself some pleasure is to bury myself in a book, focused work, or most especially computer programming. Those things distract me and give me a little buzz that feels somewhere between coffee and pleasure.

There is some variation, every now and then I feel almost normal, but I can't see a pattern to it except that it is perhaps very gradually trending toward better.
Scroofinator
4.3 / 5 (3) Jul 15, 2014
@ Tessell,
Not trying to dismiss how your feeling, but what you've described sounds like depression. What else happened during your period of smoking, followed by the year of not smoking? Lose a job, significant other, family? I find it hard to believe you quit and now your just not happy simply because of MJ and nothing else.

I agree with you though, MJ should be legal, and also that it isn't "risk free", although it is literally the only drug/substance that won't kill you based on consumption alone. People have to know how it affects them, and what their limits are, especially with the ever increasing potency that these kids are smoking these days.

wiyosaya
4 / 5 (3) Jul 15, 2014
I also abused it, too. I cannot quite quantify how much I used, but I did use quite a bit for many years. It has been almost 30-years since I quit; I had one toke off a joint, stayed high for three days and did not like that feeling, so I quit, cold turkey, and I cannot say that I experienced withdrawal symptoms.

I also cannot say that I have trouble feeling pleasure in many instances. I love taking vacations, I love getting outdoors and hiking, and I love learning new things. For me, pleasure comes down to an appreciation of the little things in life, and feeling grateful for my life.

I am not going to try and convince anyone that it is harmless, but my experience was nowhere near the "Reefer Madness" propaganda that is very likely part of what is behind the tough drug laws of the 1970's.
Stevepidge
3 / 5 (4) Jul 15, 2014
I am for marijuana legalization.

I also think users of it should read articles like this one and consider what they may be doing to themselves. I used to abuse it. I have no idea how anyone could smoke 5 joints a day, but I did use it every night for years. When I got bored with the high, I quit. It wasn't free of withdraw symptoms like pot advocates said it would be. And over a year later I am definitely less capable of feeling pleasure than I was before I ever used it. Believe it or not, numbness is a big deal. I gained a lot of valuable insights while high, not quite sure it was worth it though. In any case, I wish advocates would stop hyping it as a harmless drug and reflexively down voting articles like this one. Maybe it is less harmful than alcohol, but definitely harmful with lasting consequences that aren't fun.


Living life itself has lasting consequences. Walking down the railroad tracks, swimming across a river, riding a roller coaster, having sex and taking a dump
thingumbobesquire
1 / 5 (1) Jul 16, 2014
Who benefits from turning the American population into an even more desensitized state of consciousness?
Moebius
5 / 5 (2) Jul 16, 2014
Yes, smoking pot blunts (pun intended) the dopamine response. Luckily this effect can be moderated by smoking more pot blunts.
Shootist
5 / 5 (1) Jul 20, 2014
whosaya you did not stay high for three days off one puff, you lying sack.
kochevnik
5 / 5 (1) Jul 21, 2014
This finding illustrates why weed can be useful for methamphetamine addicts suffering the comedown from their euphoria