Hunting For the Marijuana-Dopamine Connection

Why do heavy pot smokers show a blunted reaction to stimulants?

Most drugs of abuse increase dopamine transmission in the brain, and indeed, this is thought to be the basic neural mechanism underlying the rewarding effects of addictive drugs. But in the case of marijuana, the dopamine connection is not so clear-cut. Evidence has been found both for and against the notion of increases in dopamine signaling during marijuana intoxication.

Marijuana has always been the odd duck in the pond, research-wise. Partly this is due to longstanding federal intransigence toward cannabis research, and partly it is because cannabis, chemically speaking, is damnably complicated. The question of marijuana’s effect on dopamine transmission came under strong scrutiny a few years ago, when UK researchers began beating the drums for a theory that chronic consumption of strong cannabis can not only trigger episodes of psychosis, but can be viewed as the actual cause of schizophrenia in some cases.

It sounded like a new version of the old reefer madness, but this time around, the researchers raising their eyebrows had a new fact at hand: Modern marijuana is several times stronger than marijuana in use decades ago. Selective breeding for high THC content has produced some truly formidable strains of pot, even if cooler heads have slowly prevailed on the schizophrenia issue.

One of the reports helping to bank the fires on this notion appeared recently in the Proceedings of the National Academy of Sciences (PNAS). Joanna S. Fowler of the Biosciences Department at Brookhaven National Laboratory, Director Nora Volkow of the National Institute on Drug Abuse (NIDA), and other researchers compared brain dopamine reactivity in healthy controls and heavy marijuana users, using PET scans. For measuring dopamine reactivity, the researchers chose methylphenidate, better known as Ritalin, the psychostimulant frequently prescribed for attention-deficit hyperactivity disorder (ADHD). Ritalin basically functions as a dopamine reuptake inhibitor, meaning that the use of Ritalin leads to increased concentrations of synaptic dopamine.

In the study, heavy marijuana users showed a blunted reaction to the stimulant Ritalin due to reductions in brain dopamine release, according to the research. “The potency of methylphenidate (MP) was also reported to be stronger by the controls than by the marijuana abusers." And in marijuana abusers, Ritalin caused an increase in craving for marijuana and cigarettes.

 “We found that marijuana abusers display attenuated dopamine responses to MP including reduced decreases in striatal distribution volumes,” according to the study’s conclusion. “The significantly attenuated behavioral and striatal distribution volumes response to MP in marijuana abusers compared to controls, indicates reduced brain reactivity to dopamine stimulation that in the ventral striatum might contribute to negative emotionality and drug craving.”

Down-regulation from extended abuse is another complicated aspect of this: “Although, to our knowledge, this is the first clinical report of an attenuation of the effects of MP in marijuana abusers, a preclinical study had reported that rats treated chronically with THC exhibited attenuated locomotor responses to amphetamine. Such blunted responses to MP could reflect neuroadaptations from repeated marijuana abuse, such as downregulation of DA transporters.”

 Animal studies have suggested that these dopamine alterations are reversible over time.

Another recent study came to essentially the same conclusions. Writing in Biological Psychiatry, a group of British researchers led by Michael A.P. Bloomfield and Oliver D. Howes analyzed dope smokers who experienced psychotic symptoms when they were intoxicated. They looked for evidence of a link between cannabis use and psychosis and concluded: “These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia.” And again, the higher the level of current cannabis use, the lower the level of striatal dopamine synthesis capacity.  As for mechanisms, the investigators ran up against similar causation problems: “One explanation for our findings is that chronic cannabis use is associated with dopaminergic down-regulation. This might underlie amotivation and reduced reward sensitivity in chronic cannabis users. Alternatively, preclinical evidence suggests that low dopamine neurotransmission may predispose an individual to substance use.”

The findings of diminished responses to Ritalin in heavy marijuana users may have clinical implications, suggesting that marijuana abusers with ADHD may experience reduced benefits from stimulant medications.

Photo Credit: http://www.biologicalpsychiatryjournal.com/

Feeling a Need for Weed?

U.K. book on cannabis dependency.

For James Langton, author of "No Need for Weed: Understanding and Breaking Cannabis Dependency", it was no easy task to find information and support when he sought to rid himself of a 30-year marijuana relationship. Through his own efforts, and the early help of Marijuana Anonymous, Langton became abstinent. And in an effort to help others in the same boat, he published his own account, a combination of personal memoir, anecdotes from pot smokers drawn to his own Clearhead support website, and a thoughtful assessment of the nature of both active marijuana dependency and marijuana withdrawal.

Langton has written a valuable and insightful book, dedicated, he says, to those "who fell blindly in love with the drug, in all its forms, without a second thought. But this book is also for those who, just like me, found that ending this love affair was much more difficult than they could ever have imagined...."

The delights of pot are self-evident: "It didn't feel wrong, dangerous or difficult; I just enjoyed life more when my senses were heightened and when I allowed the reality of everyday life to become a little distorted. After a couple of tokes, I seemed to feel the disparate parts of my consciousness clicking into place."

So why quit at all? "For a start," writes Langton, "I wanted to be clearheaded again; to be able to remember things; to be aware of time passing at normal speed, not stretched or shrunk. I wanted more of a social life. I wanted to be more confident and not so self-obsessed. I wanted to be in control and less lazy." Finally, he felt ready to "turn away from a pleasure that had evolved into a routine, then into a habit, and finally into full-blown dependency."

Metabolically, Langton had reached a point of addiction: "I needed to smoke just to feel normal. My tolerance for dope had reached such a point that if the THC in my system fell below a certain level I would feel a deep lack, a terrible emptiness."

The author found that one aspect made quitting "harder and more demoralizing" than necessary --"the almost universal dismissal from the medical and drug treatment professions about the reality of cannabis withdrawal.... very little specialist help is available to anybody who has lost control over their dope smoking."

Langton's explanation of what had happened to him is simple and understandable: "Our dopamine levels aren't meant to be tuned to such a high pitch on an everyday basis. Maybe a few times a month or the occasional binge, but if you're smoking relentlessly day after day, particularly strong skunk, then is it any wonder you might find it hard to take pleasure in the ordinary things of life?"

Langton also offers vivid descriptions of common withdrawal effects, including "the feeling of being overwhelmed by even the simplest interactions with other people, or becoming frustrated by what you would normally consider straightforward tasks." He also noted that "night sweats are difficult because, combined with light sleeping, they can cause discomfort to your partner as well.... The sweating can last for anything up to 21 days, but usually you are over the worst after about 10." In addition, Langton suggests that if you are experiencing an extreme loss of appetite, "be reassured that this is a very common symptom. The important thing is to make sure you are taking some nutrients onboard, otherwise you will start to feel week, light-headed and slightly sick." He warns of vivid dreams, and episodes of outsized anger. (The author's salient advice on anger: You can take it back.) As for energy levels, the whole withdrawal experience can "feel like jet lag, and the best advice is to treat it as such; in other words, try not to go to bed as soon as you come home from work..."

How long does it take? "At Clearhead we have found that it takes, on average, around four to six weeks for most people to fully adjust to not using cannabis.... others will still hit upon lingering symptoms up to two months after smoking their last joint."

Overall, a good read, full of telling anecdotes, personal honesty, and practical advice.